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Sample records for major unmet human

  1. Unmet needs among men with human immunodeficiency virus in community mental health care: a cross-sectional study.

    Durbin, Anna; Sirotich, Frank; Antoniou, Tony; Roesslein, Kay; Durbin, Janet; Lunsky, Yona

    2016-07-01

    While community-based mental health services play an important role in caring for persons with HIV (human immunodeficiency virus) and co-existing mental health disorders, the extent to which their support needs are addressed in this setting is unknown. Accordingly, we examined if HIV infection was associated with unmet support needs among men living with and without HIV receiving community mental health care. This cross-sectional study examined 215 men (135 living with HIV and 80 without HIV) receiving case management services in urban Ontario. Using the Camberwell Assessment of Need, we ascertained the prevalence of support needs in 13 domains grouped into three clusters: Basic needs (accommodation, food, benefits, and money management); self-care/functional needs (daytime activities, self-care, and looking after the home); and health/safety needs (physical, psychological distress, psychotic symptoms, safety to self, and safety to others). We used generalized estimating equations with a logit link to examine the association between HIV and unmet need in each domain. Compared to HIV-negative men, men with HIV were more likely to have mood and concurrent disorders, and intellectual and developmental disabilities. Following multivariable analyses, men with HIV had greater unmet needs related to food (odds ratio + 95% confidence interval: 9.36 (4.03, 21.75), p health and safety domains]. Despite living in a setting with universal health insurance, men with HIV receiving community mental health support had greater unmet need in basic and health domains than HIV-negative men receiving such support. Further research is required to develop and evaluate interventions to best support community-dwelling persons with HIV and mental health disorders.

  2. Comparing immediate-type food allergy in humans and companion animals-revealing unmet needs.

    Pali-Schöll, I; De Lucia, M; Jackson, H; Janda, J; Mueller, R S; Jensen-Jarolim, E

    2017-11-01

    Adverse food reactions occur in human as well as veterinary patients. Systematic comparison may lead to improved recommendations for prevention and treatment in both. In this position paper, we summarize the current knowledge on immediate-type food allergy vs other food adverse reactions in companion animals, and compare this to the human situation. While the prevalence of food allergy in humans has been well studied for some allergens, this remains to be investigated for animal patients, where owner-reported as well as veterinarian-diagnosed food adverse reactions are on the increase. The characteristics of the disease in humans vs dogs, cats, and horses are most often caused by similar, but sometimes species-dependent different pathophysiological mechanisms, prompting the specific clinical symptoms, diagnoses, and treatments. Furthermore, little is known about the allergen molecules causative for type I food allergy in animals, which, like in human patients, could represent predictive biomarkers for risk evaluation. The definite diagnosis of food allergy relies-as in humans-on elimination diet and provocation tests. Besides allergen avoidance in daily practice, novel treatment options and tolerization strategies are underway. Taken together, numerous knowledge gaps were identified in veterinary food allergy, which need to be filled by systematic comparative studies. © 2017 The Authors. Allergy Published by John Wiley & Sons Ltd.

  3. Prevalence and profiles of unmet healthcare need in Thailand

    Thammatacharee Noppakun

    2012-10-01

    Full Text Available Abstract Background In the light of the universal healthcare coverage that was achieved in Thailand in 2002, policy makers have raised concerns about whether there is still unmet need within the population. Our objectives were to assess the annual prevalence, characteristics and reasons for unmet healthcare need in the Thai population in 2010 and to compare our findings with relevant international literature. Methods A standard set of OECD unmet need questionnaires was used in a nationally-representative household survey conducted in 2010 by the National Statistical Office. The prevalence of unmet need among respondents with various socio-economic characteristics was estimated to determine an inequity in the unmet need and the reasons behind it. Results The annual prevalence of unmet need for outpatient and inpatient services in 2010 was 1.4% and 0.4%, respectively. Despite this low prevalence, there are inequities with relatively higher proportion of the unmet need among Universal Coverage Scheme members, and the poor and rural populations. There was less unmet need due to cost than there was due to geographical barriers. The prevalence of unmet need due to cost and geographical barriers among the richest and poorest quintiles were comparable to those of selected OECD countries. The geographical extension of healthcare infrastructure and of the distribution of health workers is a major contributing factor to the low prevalence of unmet need. Conclusions The low prevalence of unmet need for both outpatient and inpatient services is a result of the availability of well-functioning health services at the most peripheral level, and of the comprehensive benefit package offered free of charge by all health insurance schemes. This assessment prompts a need for regular monitoring of unmet need in nationally-representative household surveys.

  4. The human gut virome: a multifaceted majority

    Lesley Ann Ogilvie

    2015-09-01

    Full Text Available Here we outline our current understanding of the human gut virome, in particular the phage component of this ecosystem, highlighting progress and challenges in viral discovery in this arena. We reveal how developments in high-throughput sequencing technologies and associated data analysis methodologies are helping to illuminate this abundant ‘biological dark matter’. Current evidence suggests that the human gut virome is a highly individual but temporally stable collective, dominated by phage exhibiting a temperate lifestyle. This viral community also appears to encode a surprisingly rich functional repertoire that confers a range of attributes to their bacterial hosts, ranging from bacterial virulence and pathogenesis to maintaining host-microbiome stability and community resilience. Despite the significant advances in our understanding of the gut virome in recent years, it is clear that we remain in a period of discovery and revelation, as new methods and technologies begin to provide deeper understanding of the inherent ecological characteristics of this viral ecosystem. As our understanding increases, the nature of the multi-partite interactions occurring between host and microbiome will become clearer, helping us to more rationally define the concepts and principles that will underpin approaches to using human gut virome components for medical or biotechnological applications.

  5. The importance of measuring unmet healthcare needs.

    Gauld, Robin; Raymont, Antony; Bagshaw, Philip F; Nicholls, M Gary; Frampton, Christopher M

    2014-10-17

    Major restructuring of the health sector has been undertaken in many countries, including New Zealand and England, yet objective assessment of the outcomes has rarely been recorded. In the absence of comprehensive objective data, the success or otherwise of health reforms has been inferred from narrowly-focussed data or anecdotal accounts. A recent example relates to a buoyant King's Fund report on the quest for integrated health and social care in Canterbury, New Zealand which prompted an equally supportive editorial article in the British Medical Journal (BMJ) suggesting it may contain lessons for England's National Health Service. At the same time, a report published in the New Zealand Medical Journal expressed concerns at the level of unmet healthcare needs in Canterbury. Neither report provided objective information about changes over time in the level of unmet healthcare needs in Canterbury. We propose that the performance of healthcare systems should be measured regularly, objectively and comprehensively through documentation of unmet healthcare needs as perceived by representative segments of the population at formal interview. Thereby the success or otherwise of organisational changes to a health system and its adequacy as demographics of the population evolve, even in the absence of major restructuring of the health sector, can be better documented.

  6. Human oocyte chromosome analysis: complicated cases and major ...

    Human oocyte chromosome analysis: complicated cases and major ... dardized even after more than 20 years of research, making it difficult to draw .... (c) Part of a metaphase with a chromosome break in the centromeric region (arrows).

  7. Envisioning how new technologies can fulfill customers’ unmet needs

    Chuang, Y.; Chen, Y.; Chen, L.; Chen, Y.-H.

    2017-01-01

    Intended Contribution to Knowledge: Undeniably, home is the most important environment for human beings. This study investigates customers’ unmet needs, develops design concepts with new IoT technologies, envisions the values for family members, and reveals its impact on human life and interpersonal

  8. Unmet needs: relevance to medical technology innovation?

    McCarthy, Avril D; Sproson, Lise; Wells, Oliver; Tindale, Wendy

    2014-01-01

    This paper describes and discusses the role of unmet needs in the innovation of new medical technologies using the National Institute for Health Research Devices for Dignity (D4D) Healthcare Technology Co-operative as a case study. It defines an unmet need, providing a spectrum of classification and discusses the benefits and the challenges of identifying unmet need and its influence on the innovation process. The process by which D4D has captured and utilized unmet needs to drive technology innovation is discussed and examples given. It concludes by arguing that, despite the challenges, defining and reviewing unmet need is a fundamental factor in the success of medical technology innovation.

  9. Using the Humanities to Teach Neuroscience to Non-majors.

    McFarlane, Hewlet G; Richeimer, Joel

    2015-01-01

    We developed and offered a sequence of neuroscience courses geared toward changing the way non-science students interact with the sciences. Although we accepted students from all majors and at all class levels, our target population was first and second year students who were majoring in the fine arts or the humanities, or who had not yet declared a major. Our goal was to engage these students in science in general and neuroscience in particular by teaching science in a way that was accessible and relevant to their intellectual experiences. Our methodology was to teach scientific principles through the humanities by using course material that is at the intersection of the sciences and the humanities and by changing the classroom experience for both faculty and students. Examples of our course materials included the works of Oliver Sacks, V.S. Ramachandran, Martha Nussbaum, Virginia Woolf and Karl Popper, among others. To change the classroom experience we used a model of team-teaching, which required the simultaneous presence of two faculty members in the classroom for all classes. We changed the structure of the classroom experience from the traditional authority model to a model in which inquiry, debate, and intellectual responsibility were central. We wanted the students to have an appreciation of science not only as an endeavor guided by evidence and experimentation, but also a public discourse driven by creativity and controversy. The courses attracted a significant number of humanities and fine arts students, many of whom had already completed their basic science requirement.

  10. Anatomy and Histology of Rodent and Human Major Salivary Glands

    Amano, Osamu; Mizobe, Kenichi; Bando, Yasuhiko; Sakiyama, Koji

    2012-01-01

    Major salivary glands of both humans and rodents consist of three pairs of macroscopic glands: parotid, submandibular, and sublingual. These glands secrete serous, mucous or mixed saliva via the proper main excretory ducts connecting the glandular bodies with the oral cavity. A series of discoveries about the salivary ducts in the 17th century by Niels Stensen (1638–1686), Thomas Wharton (1614–1673), and Caspar Bartholin (1655–1738) established the concept of exocrine secretion as well as salivary glands. Recent investigations have revealed the endocrine functions of parotin and a variety of cell growth factors produced by salivary glands. The present review aims to describe macroscopic findings on the major salivary glands of rodents and the microscopic differences between those of humans and rodents, which review should be of interest to those researchers studying salivary glands. PMID:23209333

  11. Using the Humanities to Teach Neuroscience to Non-majors

    McFarlane, Hewlet G.; Richeimer, Joel

    2015-01-01

    We developed and offered a sequence of neuroscience courses geared toward changing the way non-science students interact with the sciences. Although we accepted students from all majors and at all class levels, our target population was first and second year students who were majoring in the fine arts or the humanities, or who had not yet declared a major. Our goal was to engage these students in science in general and neuroscience in particular by teaching science in a way that was accessible and relevant to their intellectual experiences. Our methodology was to teach scientific principles through the humanities by using course material that is at the intersection of the sciences and the humanities and by changing the classroom experience for both faculty and students. Examples of our course materials included the works of Oliver Sacks, V.S. Ramachandran, Martha Nussbaum, Virginia Woolf and Karl Popper, among others. To change the classroom experience we used a model of team-teaching, which required the simultaneous presence of two faculty members in the classroom for all classes. We changed the structure of the classroom experience from the traditional authority model to a model in which inquiry, debate, and intellectual responsibility were central. We wanted the students to have an appreciation of science not only as an endeavor guided by evidence and experimentation, but also a public discourse driven by creativity and controversy. The courses attracted a significant number of humanities and fine arts students, many of whom had already completed their basic science requirement. PMID:26240533

  12. Major genomic mitochondrial lineages delineate early human expansions

    Flores Carlos

    2001-08-01

    Full Text Available Abstract Background The phylogeographic distribution of human mitochondrial DNA variations allows a genetic approach to the study of modern Homo sapiens dispersals throughout the world from a female perspective. As a new contribution to this study we have phylogenetically analysed complete mitochondrial DNA(mtDNA sequences from 42 human lineages, representing major clades with known geographic assignation. Results We show the relative relationships among the 42 lineages and present more accurate temporal calibrations than have been previously possible to give new perspectives as how modern humans spread in the Old World. Conclusions The first detectable expansion occurred around 59,000–69,000 years ago from Africa, independently colonizing western Asia and India and, following this southern route, swiftly reaching east Asia. Within Africa, this expansion did not replace but mixed with older lineages detectable today only in Africa. Around 39,000–52,000 years ago, the western Asian branch spread radially, bringing Caucasians to North Africa and Europe, also reaching India, and expanding to north and east Asia. More recent migrations have entangled but not completely erased these primitive footprints of modern human expansions.

  13. Understanding unmet need: history, theory, and measurement.

    Bradley, Sarah E K; Casterline, John B

    2014-06-01

    During the past two decades, estimates of unmet need have become an influential measure for assessing population policies and programs. This article recounts the evolution of the concept of unmet need, describes how demographic survey data have been used to generate estimates of its prevalence, and tests the sensitivity of these estimates to various assumptions in the unmet need algorithm. The algorithm uses a complex set of assumptions to identify women: who are sexually active, who are infecund, whose most recent pregnancy was unwanted, who wish to postpone their next birth, and who are postpartum amenorrheic. The sensitivity tests suggest that defensible alternative criteria for identifying four out of five of these subgroups of women would increase the estimated prevalence of unmet need. The exception is identification of married women who are sexually active; more accurate measurement of this subgroup would reduce the estimated prevalence of unmet need in most settings. © 2013 The Population Council, Inc.

  14. UNMET NEED: KONSEP YANG MASIH PERLU DIPERDEBATKAN

    Umi Listyaningsih

    2017-04-01

    Full Text Available Unmet need or the unful lled need for contraception is often associated with two things, namely supply and demand. This research attempted to overview the concept of unmet need by giving the attention to the socio-economic background of the couples. Through analizing the result of family survey in Daerah Istimewa Yogyakarta (DIY and interviewing the eld surveyor of family planning (Petugas Lapangan Keluarga Berencana-PLKB and women that categorized as unmet need, this research found that the numet need concept still needed to be explored further, especially when unmet need was used as the performance indicator in DIY. It related to the evidance that unmet need did not always end up with pregnancy.

  15. Major national human biomonitoring programs in chemical exposure assessment

    Judy Choi

    2015-07-01

    Full Text Available Human biomonitoring (HBM programs have been established in several countries around the world in order to monitor the levels of chemical exposures in the general population and qualify health risk assessment of national and international interest. Study design, population, sample collection, and chemical analysis must be considered when comparing and interpreting the results. In this review, the objectives and brief descriptions of the major national HBM programs in North America, Europe, and Asia are provided. Similarities and differences observed from a comparative analysis among these programs, including the stratification of data according to age, sex, socioeconomic background, etc. as well as the identification of chemical exposure associated with food intake, are discussed. Overall, although there are some discrepancies in the study designs among the reviewed national HBM programs, results from the programs can provide useful information such as chemical levels found within the general population of a country that can be compared. Furthermore, the results can be used by regulatory authorities or the government to enforce legislations in order to reduce the exposure of chemicals into the human body.

  16. UNMET NEEDS FOR HEALTH CARE SERVICES IN BULGARIA

    Elka Atanasova

    2016-09-01

    Full Text Available Background: In all European countries, an important policy objective is the equity of access to health care. The factors that affect access to health care can differ as the demand- and supply-side factors. Moreover, there are many tools to assess the extent of inequity in access to services. One simple tool is the assessing reports of unmet needs for health care. Purpose: The study has two objectives: to examine the evidence of self-reported unmet needs and to analyze the relationship between foregone medical care and both type of residence and socioeconomic status. Materials and Methods: We use data from the European Union Statistics on Income and Living Conditions. The access to health care is measured using the concept of unmet need for medical examination or treatment during the last 12 months. The relationship between foregone medical care and both type of residence and socioeconomic status is examined through the representative survey conducted in 2014. Results: The Eurostat results show that treatment costs are the most common reason for foregone medical care in Bulgaria. We observe a gradual decrease in the share of people who reported having unmet needs due to being too expensive. According to the 2014 survey, significant differences between urban and rural areas as well as among the income groups are identified. The results show the problems in access to health care services mainly in small towns and villages. Conclusion: Although major essential changes were made in the Bulgarian health care system, the equity problems remain an important challenge to policy-makers.

  17. Human factors: A major issue in plant aging

    Widrig, R.D.

    1985-01-01

    Humans play a significant role in the effects of aging on safe and reliable operation of nuclear power plants. These human issues may be more important than the issues of materials and component degradation with age. Human actions can accelerate or decelerate physical aging of a plant. And an aging plant can have a significant negative impact on staff quality and performance. The purpose of this paper is to provide some insights into the nature of these human factors issues and their relationship to plant aging. An early awareness of these issues facilitates timely action to at least mitigate these problems before they become insurmountable

  18. Expressive Writing: Enhancing the Emotional Intelligence of Human Services Majors

    Castillo, Yuleinys; Fischer, Jerome M.

    2017-01-01

    The skills and tasks in the human services field are highly connected to emotional intelligence abilities. The purpose of the study was to investigate the effect of an expressive writing program involving human service students in an undergraduate rehabilitation services course. The program was developed to enhance their emotional intelligence.…

  19. The unmet need for philanthropic funding of early career cardiovascular investigators.

    Ahmad, Tariq; Becker, Richard C

    2014-05-01

    Philanthropic donations have funded scientific investigations of cardiovascular disease for much of human history, and the patrons who enabled them are indirectly responsible for major breakthroughs in the field. Today, however, the lion's share of funding for cardiovascular research in Western countries comes from the government, professional agencies, and industry. Rapid budget cuts at these traditional sources of financial support are having a devastating impact on the cardiovascular research infrastructure by slashing funding for investigators. A particularly unfortunate consequence is the discouraging effect this is having on early career investigators, who are the life-blood of future breakthroughs in the field, leading to the potential loss of an entire generation of researchers. Here, we summarize the challenges faced by emerging cardiovascular investigators, make a case for the unmet need for appropriately targeted philanthropic support for cardiovascular research, and provide a roadmap for solving the funding shortfall for these investigators.

  20. Human factors: a major issue in plant aging

    Widrig, R.D.

    1985-07-01

    Human factors issues will be of great significance in the safe and reliable operation of aging nuclear power plants, and they may be more important than materials/component-type issues. Human actions can accelerate or decelerate te physical aging process. And an aging plant can have significant negative implications on staff performance and actions. Some examples include difficulties in attracting and retaining good managers, financial decisions based on a short and uncertain remaining plant life, difficulties in replacing retiring staff, increased maintenance complexity, and increased burden on training. These problems can be dealt with more effectively by early recognition and a well conceived mitigation effort

  1. Overexpression of the human major vault protein in gangliogliomas.

    Aronica, E; Gorter, J.A.; Vliet, van EA; Spliet, WG; Veelen, van CW; Rijen, van PC; Leenstra, S.; Ramkema, MD; Scheffer, G.L.; Scheper, R.J.; Sisodiya, SM; Troost, D.

    2003-01-01

    PURPOSE: Recent evidence has been obtained that the major vault protein (MVP) may play a role in multidrug resistance (MDR). We investigated the expression and cellular localization of MVP in gangliogliomas (GGs), which are increasingly recognized causes of chronic pharmacoresistant epilepsy.

  2. Overexpression of the human major vault protein in gangliogliomas

    Aronica, Eleonora; Gorter, Jan A.; van Vliet, Erwin A.; Spliet, Wim G. M.; van Veelen, Cees W. M.; van Rijen, Peter C.; Leenstra, Sieger; Ramkema, Marja D.; Scheffer, George L.; Scheper, Rik J.; Sisodiya, Sanjay M.; Troost, Dirk

    2003-01-01

    Purpose: Recent evidence has been obtained that the major vault protein (MVP) may play a role in multidrug resistance (MDR). We investigated the expression and cellular localization of MVP in gangliogliomas (GGs), which are increasingly recognized causes of chronic pharmacoresistant epilepsy.

  3. Moral Disengagement in Business and Humanities Majors: An Exploratory Study

    Cory, Suzanne N.; Hernandez, Abigail R.

    2014-01-01

    This study measures moral disengagement of undergraduate business and humanities students with a focus on differences in moral disengagement between genders. Students completed a survey that consisted of 32 statements and were asked to determine the degree to which they agreed with each, using a 7-point Likert scale. The questions measured moral…

  4. Determinants of the unmet need for family planning among women of Jaipur, Rajasthan

    Rajaat Vohra

    2014-01-01

    Full Text Available Background: More than 100 million women in less developed countries or about 17% of all married women would prefer to avoid pregnancy, but are not using any form of family planning. Despite the government′s many efforts, the unmet need for family planning in India is still 12.8%. The present study is aimed to assess prevalence of the unmet need for family planning, its determinants, and the reasons for the unmet need for family planning. Materials and Methods: A sample size of 500 was divided equally among the rural and urban areas. A simple random technique was used to select the first household for the survey. A predesigned and pretested questionnaire was used to record the information. Data was entered on Microsoft Access and analyzed using the statistical software SPSS version 11.5 for Windows Vista. The chi square test was used for finding the association and trends. Results: In the present study, 35% of the population had an unmet need, of which 58.28% belonged to rural area, while 41.71% belonged to the urban area. The significant determinants associated with the unmet need for family planning were religion, type of family, husband′s education and occupation, socioeconomic class, women′s age, women′s education and occupation, exposure to mass media, and healthcare facility where services were provided. Overall, lack of motivation and obstacles were the major reasons for the unmet need. Conclusion: Improved access to family planning services, better education, improved standard of living, and higher exposure to mass media can significantly decrease the unmet need of family planning.

  5. The influence of family violence and child marriage on unmet need for family planning in Jordan.

    Clark, Cari Jo; Spencer, Rachael A; Khalaf, Inaam A; Gilbert, Louisa; El-Bassel, Nabila; Silverman, Jay G; Raj, Anita

    2017-04-01

    Risk for unmet need for contraception is associated with men's perpetration of intimate partner violence (IPV) against women and may be influenced by violence perpetrated by other family members (family violence, FV). Women who married as minors may be most vulnerable to the potential compounding effect of IPV and FV on unmet need. Using nationally representative data from the 2012 Jordan Population and Family Health Survey we examined unmet need by exposure to IPV and FV by women's age at marriage (<18, 18+ years). Logistic regression was used to test whether IPV and FV were independently associated with unmet need, by age at marriage. Interaction terms (IPV×FV) were tested in both models. Stratification by FV was employed to clarify the interpretation of significant interactions. IPV increased the odds of unmet need by 87% [adjusted odds ratio (AOR) 1.87; 95% confidence interval (95% CI) 1.13-3.10] and 76% (AOR 1.76; 95% CI 1.30-2.38) among women who married prior to and after the age of 18 years, respectively. Women married as minors who experienced IPV and FV had a four-fold higher likelihood of having an unmet need (AOR 6.75; 95% CI 1.95-23.29) compared to those experiencing only IPV (AOR 1.49; 95% CI 0.84-2.38). No interaction between IPV and FV was detected for women married at or above majority. Laws that prohibit child marriage should be strengthened and health sector screening for violence experience could help identify women at risk of unmet need and improve women's reproductive agency. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  6. Unmet patient needs in systemic sclerosis.

    Rubenzik, Tamara T; Derk, Chris T

    2009-04-01

    Assessment of systemic sclerosis patients has not directly addressed functioning from the patient's perspective. With this study, we aim to gain our patient's point of view by using a questionnaire to describe their unmet needs and understanding what demographic parameters influence these. A computer randomization program selected 50 patients, from 242 systemic sclerosis patients actively followed at our rheumatology clinic, to receive a survey about unmet needs. Twenty-five patients responded to the survey. Of 81 questions, 9 provided demographic data, whereas 72 questions addressed physical, daily living, psychologic, spiritual, existential, health services, health information, social support, and employment issues. A 4-point scale from no need to high need was used to rate all questions. Significant need was considered any issue for which more than 50% of patients reported a high need. The Fisher exact test was used to compare different demographic variables to unmet patient needs. The psychologic/spiritual/existential category had 9 questions reaching significance, the health services category had 5 significant questions, the physical category had 4 significant questions. Patients who had not attended college were more likely to have higher needs than patients who completed a college degree. Unmarried patients reported higher needs in 8 measures as compared with married patients, and patients in rural areas had higher needs in social support needs. The greatest prevalence of unmet needs in scleroderma patients were in the psychologic/spiritual/existential domain, such as being unable to do things they used to do, fear that the disease will worsen, anxiety and stress, feeling down or depressed, fears of physical disability, uncertainty about the future, change in appearance, keeping a positive outlook, and feeling in control. Significant differences were observed in unmet needs based on education, marital status, location, knowledge of disease, and age

  7. Unmet needs in automated cytogenetics

    Bender, M.A.

    1976-01-01

    Though some, at least, of the goals of automation systems for analysis of clinical cytogenetic material seem either at hand, like automatic metaphase finding, or at least likely to be met in the near future, like operator-assisted semi-automatic analysis of banded metaphase spreads, important areas of cytogenetic analsis, most importantly the determination of chromosomal aberration frequencies in populations of cells or in samples of cells from people exposed to environmental mutagens, await practical methods of automation. Important as are the clinical diagnostic applications, it is apparent that increasing concern over the clastogenic effects of the multitude of potentially clastogenic chemical and physical agents to which human populations are being increasingly exposed, and the resulting emergence of extensive cytogenetic testing protocols, makes the development of automation not only economically feasible but almost mandatory. The nature of the problems involved, and acutal of possible approaches to their solution, are discussed

  8. Family planning unmet need and access among iTaukei women in New Zealand and Fiji.

    Cammock, Radilaite; Herbison, Peter; Lovell, Sarah; Priest, Patricia

    2017-09-22

    The aim of the study was to identify unmet need and family planning access among indigenous Fijian or iTaukei women living in New Zealand and Fiji. A cross-sectional survey was undertaken between 2012-2013 in five major cities in New Zealand: Auckland, Hamilton, Wellington, Christchurch and Dunedin; and in three suburbs in Fiji. Women who did not want any (more) children but were not using any form of contraception were defined as having an unmet need. Access experiences involving cost and health provider interactions were assessed. Unmet need in New Zealand was 26% and similar to the unmet need found in Fiji (25%). Cost and concern over not being seen by a female provider were the most problematic access factors for women. There is a need for better monitoring and targeting of family planning services among minority Pacific groups, as the unmet need found in New Zealand was three times the national estimate overall and similar to the rate found in Fiji. Cost remains a problem among women trying to access family planning services. Gendered traditional roles in sexual and reproductive health maybe an area from which more understanding into cultural sensitivities and challenges may be achieved.

  9. Applying Technology to Unmet Needs. Technology and the American Economy, Appendix, Volume V.

    National Commission on Technology, Automation and Economic Progress, Washington, DC.

    Twelve studies dealing with the problems of applying technology to unmet human and community needs are presented. "Urban Planning and Metropolitan Development--The Role of Technology," examines the possibilities of the computer and other modern planning tools. "Technology, Automation, and Economic Progress in Housing and Urban Development"…

  10. Unmet need for family planning among married women of reproductive age group in urban Tamil Nadu

    Malini M Bhattathiry

    2014-01-01

    Full Text Available Context: Unmet need for family planning (FP, which refers to the condition in which there is the desire to avoid or post-pone child bearing, without the use of any means of contraception, has been a core concept in the field of international population for more than three decades. Objectives: The very objective of this study is to determine the prevalence of "unmet need for FP" and its socio-demographic determinants among married reproductive age group women in Chidambaram. Materials and Methods: The study was a community-based cross-sectional study of married women of the reproductive age group, between 15 and 49 years. The sample size required was 700. The cluster sampling method was adopted. Unmarried, separated, divorced and widows were excluded. Results: The prevalence of unmet need for FP was 39%, with spacing as 12% and limiting as 27%. The major reason for unmet need for FP among the married group was 18%, for low perceived risk of pregnancy, 9%, feared the side effects of contraception 5% lacked information on contraceptives, 4% had husbands who opposed it and 3% gave medical reasons. Higher education, late marriage, more than the desired family size, poor knowledge of FP, poor informed choice in FP and poor male participation were found to be associated with high unmet need for FP. Conclusion: Unmet need for younger women was spacing of births, whereas for older women, it was a limitation of births. Efforts should be made to identify the issues in a case by case approach. Male participation in reproductive issues should be addressed.

  11. Unmet needs in the management of schizophrenia

    Torres-González, Francisco; Ibanez-Casas, Inmaculada; Saldivia, Sandra; Ballester, Dinarte; Grandón, Pamela; Moreno-Küstner, Berta; Xavier, Miguel; Gómez-Beneyto, Manuel

    2014-01-01

    Studies on unmet needs during the last decades have played a significant role in the development and dissemination of evidence-based community practices for persistent schizophrenia and other severe mental disorders. This review has thoroughly considered several blocks of unmet needs, which are frequently related to schizophrenic disorders. Those related to health have been the first block to be considered, in which authors have examined the frequent complications and comorbidities found in schizophrenia, such as substance abuse and dual diagnosis. A second block has been devoted to psychosocial and economic needs, especially within the field of recovery of the persistently mentally ill. Within this block, the effects of the current economic difficulties shown in recent literature have been considered as well. Because no patient is static, a third block has reviewed evolving needs according to the clinical staging model. The fourth block has been dedicated to integrated evidence-based interventions to improve the quality of life of persons with schizophrenia. Consideration of community care for those reluctant to maintain contact with mental health services has constituted the fifth block. Finally, authors have aggregated their own reflections regarding future trends. The number of psychosocial unmet needs is extensive. Vast research efforts will be needed to find appropriate ways to meet them, particularly regarding so-called existential needs, but many needs could be met only by applying existing evidence-based interventions. Reinforcing research on the implementation strategies and capacity building of professionals working in community settings might address this problem. The final aim should be based on the collaborative model of care, which rests on the performance of a case manager responsible for monitoring patient progress, providing assertive follow-up, teaching self-help strategies, and facilitating communication among the patient, family doctor, mental

  12. The major surface glycoprotein (gp63) from Leishmania major and Leishmania donovani cleaves CD4 molecules on human T cells

    Hey, A S; Theander, T G; Hviid, L

    1994-01-01

    The effect of Leishmania major and L. donovani surface protease gp63 on surface markers on human T cells was studied using fluorescence-activated flow cytometry. Purified gp63 (63,000 m.w. glycoprotein) at concentrations above 10 micrograms/ml completely inhibited binding of six different anti-CD4......-expression of CD4, reaching 50% of the initial level after 72 h of incubation in medium. Preincubation of cells with live promastigotes showed an inhibitory effect on CD4 comparable to that seen with purified gp63. The binding of Abs directed against other surface markers present on human T-cells--CD2, CD3, CD5......, CD8, CD11A, CD25, CD45RO, CD45RA, CD58, TCR-alpha, TCR-gamma, and HLA DQ--was not inhibited by gp63. These data suggest that gp63, both in its purified form and in the form anchored to the parasite membrane, cleaves CD4 on human T cells. The cleavage of CD4 by the protease might play a role...

  13. Unmet health care needs for persons with environmental sensitivity

    Gibson, Pamela Reed; Kovach, Shannon; Lupfer, Alexis

    2015-01-01

    Pamela Reed Gibson, Shannon Kovach, Alexis LupferDepartment of Psychology, James Madison University, Harrisonburg, VA, USAAbstract: Studies of unmet health care needs have shown that women, people with poor health, and people with lower socioeconomic status are more likely to report having unmet health care needs. In this study, we examined the types of and reasons for unmet health care needs in 465 people with environmental sensitivities. A second area of inquiry involved negative reactions ...

  14. Th1-like human T-cell clones recognizing Leishmania gp63 inhibit Leishmania major in human macrophages

    Kemp, M; Hey, A S; Bendtzen, K

    1994-01-01

    The major surface protease of Leishmania major, gp63, has been suggested as a vaccine candidate for cutaneous leishmaniasis. In this study gp63 was purified from L. major promastigotes. A panel of human T-cell clones recognizing this protein were generated from individuals who had previously had...... resembling Th1 cells. Autologous mononuclear cells and Epstein-Barr virus-transformed B cell lines were equally efficient in presenting the antigen to the T cells. The gp63 reactive T cells induced resistance to infection in cultured human macrophages by L. major. The data confirm that human CD4+ T cells...... recognizing gp63 can take part in the host defence against L. major infections....

  15. Targeting the unmet medical need: the Abbott Laboratories oncology approach.

    Carlson, Dawn M; Steinberg, Joyce L; Gordon, Gary

    2005-09-01

    While significant advances in the treatment of cancer occured during the last half of the twentieth century, parallel decreases in overall cancer death rates were not observed. Cancer therapy remains an area of significant unmet medical need. Abbott's oncology research programs are focused on pioneering trageted, less toxic therapies, aimed at different aspects of tumor growth and development. Oncology drugs in development at Abbott target several mechanisms of cancer progression by interfering with multiple processes necessary for tumor growth: recruitment of a blood supply, cell proliferation, and the development of metastases. They include a selective endothelin A-receptor antagonist (atrasentan/Xinlay), 3 angiogenesis inhibitors (ABT 510, a thrombospondin mimetic: ABT-869, a multitargeted receptor tyrosine kinase inhibitor; and ABT 828, recombinant human plasminogen kringle 5), a cell proliferation inhibitor (ABT-751, an antimitotic agent), an apoptosis inducer (ABT 737, a Bcl-2 family inhibitor), and a poly(ADP-ribose)polymerase inhibitor.

  16. Unmet needs for cardiovascular care in Indonesia.

    Asri Maharani

    Full Text Available In the past twenty years the heaviest burden of cardiovascular diseases has begun to shift from developed to developing countries. However, little is known about the real needs for cardiovascular care in these countries and how well those needs are being met. This study aims to investigate the prevalence and determinants of unmet needs for cardiovascular care based on objective assessment.Multilevel analysis is used to analyse the determinants of met needs and multilevel multiple imputation is applied to manage missing data. The 2008 Indonesian Family Life Survey (IFLS4 survey is the source of the household data used in this study, while district data is sourced from the Ministry of Health and Ministry of Finance. The data shows that nearly 70% of respondents with moderate to high cardiovascular risk failed to receive cardiovascular care. Higher income, possession of health insurance and residence in urban areas are significantly associated with met needs for cardiovascular care, while health facility density and physician density show no association with them.The prevalence of unmet needs for cardiovascular care is considerable in Indonesia. Inequality persists as a factor in meeting needs for cardiovascular care as the needs of people with higher incomes and those living in urban areas are more likely to be met. Alleviation of poverty, provision of health care insurance for the poor, and improvement in the quality of healthcare providers are recommended in order to meet this ever-increasing need.

  17. Unmet needs for cardiovascular care in Indonesia.

    Maharani, Asri; Tampubolon, Gindo

    2014-01-01

    In the past twenty years the heaviest burden of cardiovascular diseases has begun to shift from developed to developing countries. However, little is known about the real needs for cardiovascular care in these countries and how well those needs are being met. This study aims to investigate the prevalence and determinants of unmet needs for cardiovascular care based on objective assessment. Multilevel analysis is used to analyse the determinants of met needs and multilevel multiple imputation is applied to manage missing data. The 2008 Indonesian Family Life Survey (IFLS4) survey is the source of the household data used in this study, while district data is sourced from the Ministry of Health and Ministry of Finance. The data shows that nearly 70% of respondents with moderate to high cardiovascular risk failed to receive cardiovascular care. Higher income, possession of health insurance and residence in urban areas are significantly associated with met needs for cardiovascular care, while health facility density and physician density show no association with them. The prevalence of unmet needs for cardiovascular care is considerable in Indonesia. Inequality persists as a factor in meeting needs for cardiovascular care as the needs of people with higher incomes and those living in urban areas are more likely to be met. Alleviation of poverty, provision of health care insurance for the poor, and improvement in the quality of healthcare providers are recommended in order to meet this ever-increasing need.

  18. Comparative genomics of the major agents of human and animal Sporotrichosis: Sporothrix schenckii and Sporothrix brasiliensis

    Teixeira, M.M.; de Almeida, L.G.P.; Kubitschek-Barreira, P.; Alves, F.L.; Kioshima, E.S.; Abadio, A.K.R.; Fernandes, L.; Derengowski, L.S.; Ferreira, K.S.; Souza, R.C.; Ruiz, J.C.; de Andrade, N.C.; Paes, H.C.; Nicola, A.M.; Albuquerque, P.; Gerber, A.L.; Martins, V.P.; Peconick, L.D.F.; Neto, A.V.; Chaucanez, C.B.; Silva, P.A.; cunha, O.L.; de Oliveira, F.F.M.; dos Santos, T.C.; Barros, A.L.N.; Soares, M.A.; de Oliveira, L.M.; Marini, M.M.; Villalobos-Duno, H.; Cunha, M.M.L.; de Hoog, S.; da Silveira, J.F.; Henrissat, B.; Niño-Vega, G.A.; Cisalpino, P.S.; Mora-Montes, H.M.; Almeida, S.R.; Stajich, J.E.; Lopes-Bezerra, L.M.; Vasconcelos, A.T.R.; Felipe, M.S.S.

    2014-01-01

    Background: The fungal genus Sporothrix includes at least four human pathogenic species. One of these species, S. brasiliensis, is the causal agent of a major ongoing zoonotic outbreak of sporotrichosis in Brazil. Elsewhere, sapronoses are caused by S. schenckii and S. globosa. The major aims on

  19. Human-accelerated weathering increases salinization, major ions, and alkalinization in fresh water across land use

    Human land use increases transport of dissolved inorganic carbon and major ions in watersheds due to the combination of easily weathered materials in watersheds and anthropogenic inputs. Here, we show that dissolved inorganic carbon (DIC), alkalinity, and major ions are significa...

  20. HUMAN CAPITAL: Major Human Capital Challenges at SEC and Key Trade Agencies

    Hillman, Richard

    2002-01-01

    .... The leadership provided by this subcommittee and the Senate Committee on Governmental Affairs has been especially important in focusing attention on the federal government s human capital challenges.

  1. Unmet needs in the management of schizophrenia

    Torres-González F

    2014-01-01

    Full Text Available Francisco Torres-González,1,8 Inmaculada Ibanez-Casas,1,8 Sandra Saldivia,2,8 Dinarte Ballester,3,8 Pamela Grandón,4,8 Berta Moreno-Küstner,5,8 Miguel Xavier,6,8 Manuel Gómez-Beneyto7,8 1Centro de Investigación Biomédica en Red de Salud Mental, University of Granada, Spain; 2Department of Psychiatry and Mental Health, Faculty of Medicine, University of Concepcion, Chile; 3Sistema de Saúde Mãe de Deus, Escola Superior de Saúde, Universidade do Vale do Rio dos Sinos, Brazil; 4Department of Psychology, Faculty of Social Sciences, University of Concepcion, Chile; 5Andalusian Psychosocial Research Group and Department of Personality, Assessment and Psychological Treatment, Faculty of Psychology, University of Malaga, Spain; 6Department of Mental Health, NOVA Medical School, Universidade Nova de Lisboa, Lisbon, Portugal; 7Centro de Investigación Biomédica en Red de Salud Mental, University of Valencia, Spain; 8Maristán Network, University of Granada, Granada, Spain Abstract: Studies on unmet needs during the last decades have played a significant role in the development and dissemination of evidence-based community practices for persistent schizophrenia and other severe mental disorders. This review has thoroughly considered several blocks of unmet needs, which are frequently related to schizophrenic disorders. Those related to health have been the first block to be considered, in which authors have examined the frequent complications and comorbidities found in schizophrenia, such as substance abuse and dual diagnosis. A second block has been devoted to psychosocial and economic needs, especially within the field of recovery of the persistently mentally ill. Within this block, the effects of the current economic difficulties shown in recent literature have been considered as well. Because no patient is static, a third block has reviewed evolving needs according to the clinical staging model. The fourth block has been dedicated to

  2. Borderline personality disorder and unmet needs.

    Grambal, Ales; Prasko, Jan; Ociskova, Marie; Slepecky, Milos; Kotianova, Antonia; Sedlackova, Zuzana; Zatkova, Marta; Kasalova, Petra; Kamaradova, Dana

    2017-08-01

    Borderline personality disorder (BPD) is a disabling psychiatric condition with a chronic and challenging course. BPD is reflected as a disorder of self-regulation" and is associated with both psychological vulnerabilities and social relations that fail to support basic emotional needs. The objective of the paper is to provide the up-to-date data on the unmet needs of BPD patients and their families. A computerized search of the literature printed between January 1990 and May 2017 was conducted in PubMed, and additional papers were extracted using keywords "borderline personality disorder,"needs," "pharmacotherapy," "psychotherapy," "CBT," and "family" in various combinations. According to the eligibility criteria, 57 articles were chosen. Secondary articles from the reference lists of primarily identified papers have been selected for the eligibility and added to the first list (N=151). The results were divided into three categories: the needs connected with (1) the symptom control; (2) the treatment; (3) the quality of life. The needs connected with symptoms were described issues such as emotional needs, social interactions, self-harm, parasuicide, suicidality, comorbidity, mentalization, identity disturbance, moreover, barriers to treatment. The needs connected with the treatment described are focused on needs for early diagnosis, early intervention, holding environment, therapeutic relation, assertive community treatment, destigmatization, hospitalization, and primary care. The needs connected with the quality of life involve family needs, physical health, spiritual needs, advocacy needs, and needs for the separation-individuation. The part focused on implications for the treatment presented several treatment approaches, focusing mostly on the their basics and efficacy. Observing the patients' needs may be essential to the treatment of the individuals suffering from BPD. However, many needs remain unmet in the areas linked to medical, personal, and social

  3. HUMAN CAPITAL: Major Human Capital Challenges at SEC and Key Trade Agencies

    Hillman, Richard

    2002-01-01

    We appreciate the opportunity to appear here today to discuss the human capital challenges facing the agencies that play key roles in monitoring publicly traded companies and enforcing our nation's trade laws...

  4. Genetic recombination as a major cause of mutagenesis in the human globin gene clusters.

    Borg, Joseph; Georgitsi, Marianthi; Aleporou-Marinou, Vassiliki; Kollia, Panagoula; Patrinos, George P

    2009-12-01

    Homologous recombination is a frequent phenomenon in multigene families and as such it occurs several times in both the alpha- and beta-like globin gene families. In numerous occasions, genetic recombination has been previously implicated as a major mechanism that drives mutagenesis in the human globin gene clusters, either in the form of unequal crossover or gene conversion. Unequal crossover results in the increase or decrease of the human globin gene copies, accompanied in the majority of cases with minor phenotypic consequences, while gene conversion contributes either to maintaining sequence homogeneity or generating sequence diversity. The role of genetic recombination, particularly gene conversion in the evolution of the human globin gene families has been discussed elsewhere. Here, we summarize our current knowledge and review existing experimental evidence outlining the role of genetic recombination in the mutagenic process in the human globin gene families.

  5. Enhancing the water management schemes of H08 global hydrological model to attribute human water use to six major water sources

    Hanasaki, N.; Yoshikawa, S.; Pokhrel, Y. N.; Kanae, S.

    2017-12-01

    Humans abstract water from various sources to sustain their livelihood and society. Some global hydrological models (GHMs) include explicit schemes of human water management, but the representation and performance of these schemes remain limited. We substantially enhanced the human water management schemes of the H08 GHM by incorporating the latest data and techniques. The model enables us to estimate water abstraction from six major water sources, namely, river flow regulated by global reservoirs (i.e., reservoirs regulating the flow of the world's major rivers), aqueduct water transfer, local reservoirs, seawater desalination, renewable groundwater, and nonrenewable groundwater. All the interactions were simulated in a single computer program and the water balance was always strictly closed at any place and time during the simulation period. Using this model, we first conducted a historical global hydrological simulation at a spatial resolution of 0.5 x 0.5 degree to specify the sources of water for humanity. The results indicated that, in 2000, of the 3628 km3yr-1 global freshwater requirement, 2839 km3yr-1 was taken from surface water and 789 km3yr-1 from groundwater. Streamflow, aqueduct water transfer, local reservoirs, and seawater desalination accounted for 1786, 199, 106, and 1.8 km3yr-1 of the surface water, respectively. The remaining 747 km3yr-1 freshwater requirement was unmet, or surface water was not available when and where it was needed in our simulation. Renewable and nonrenewable groundwater accounted for 607 and 182 km3yr-1 of the groundwater total, respectively. Second, we evaluated the water stress using our simulations and contrasted it with earlier global assessments based on empirical water scarcity indicators, namely, the Withdrawal to Availability ratio and the Falkenmark index (annual renewable water resources per capita). We found that inclusion of water infrastructures in our model diminished water stress in some parts of the world, on

  6. Health and Health Care From the Perspective of Intimate Partner Violence Adult Female Victims in Shelters: Impact of IPV, Unmet Needs, Barriers, Experiences, and Preferences.

    Wadsworth, Pamela; Kothari, Catherine; Lubwama, Grace; Brown, Cathy L; Frank Benton, Jennifer

    Intimate partner violence (IPV) predicts poor health for victims and their children, but little is known about the perspective of victims. This study reports the perspectives of adult female IPV victims about the impact of IPV on their health and barriers of health care access for themselves and their children. The majority rated their health as good to excellent (69%). However, 83.5% indicated that IPV negatively affected their health; 53.5% had unmet health care needs. Mental health care was the most common unmet need for women; children's unmet needs were immunizations and preventive care. Transportation difficulties posed the biggest barrier to health care access.

  7. What do multiple sclerosis patients and their caregivers perceive as unmet needs?

    Lorefice, Lorena; Mura, Gioia; Coni, Giulia; Fenu, Giuseppe; Sardu, Claudia; Frau, Jessica; Coghe, Giancarlo; Melis, Marta; Marrosu, Maria Giovanna; Cocco, Eleonora

    2013-01-01

    Background Multiple sclerosis (MS) has a major impact on the physical, psychological and social life of patients and their families. The aim of this study was to evaluate the different perceptions of patients and caregivers about management of MS, particularly about the same items, to gather information to ameliorate the care of patients. Methods We evaluated what MS patients and caregivers perceive as unmet needs and compared patients? opinions with caregivers? opinions using a multidimensio...

  8. Agrin is a major heparan sulfate proteoglycan in the human glomerular basement membrane

    Groffen, Alexander J.; Ruegg, Markus A.; Dijkman, Henri; Van De Velden, Thea J.; Buskens, Carin A.; Van Den Born, Jacob; Assmann, Karel J.; Monnens, Leo A.; Veerkamp, Jacques H.; Van Den Heuvel, Lambert P.

    Agrin is a heparan sulfate proteoglycan (HSPG) that is highly concentrated in the synaptic basal lamina at the neuromuscular junction (NMJ). Agrin-like immunoreactivity is also detected outside the NMJ. Here we show that agrin is a major HSPG component of the human glomerular basement membrane

  9. Service use and unmet service needs in grandparents raising grandchildren.

    Yancura, Loriena A

    2013-01-01

    Most in-depth studies of grandparents raising grandchildren use samples recruited from service providers, so little is known about those who do not use formal services. A sample of 200 grandparents registered with a public school district completed a survey on service use and unmet service needs. Of the 131 who did not use services, 82 reported unmet service needs, and 49 reported no needs. Those with unmet needs were younger, more likely to be Native Hawaiian, and less likely to receive public assistance. These findings indicate that some grandparents are falling through the cracks of the service provision network.

  10. Unmet medical needs in systemic lupus erythematosus

    2012-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease of diverse manifestations, with onset usually in young women in the third to fourth decade of life. The chronic nature of this relapsing remitting disease leads to organ damage accrual over time. Mortality and morbidity are increased in patients with SLE compared with the general population. Therapeutic advances over the last few decades have led to significant improvements in patient outcomes. Five-year survival has improved to over 90% from a low of 50% in the 1950s. However, multiple aspects of the management of SLE patients are still far from optimal. Early diagnosis remains a challenge; diagnostic delays leading to delay in definitive treatment are common. Monitoring treatment remains problematic due to the paucity of sensitive biomarkers. Current treatment regimens rely heavily on corticosteroids, even though corticosteroids are well known to cause organ damage. Treatment of refractory disease manifestations such as nephritis, recalcitrant cutaneous lesions and neurological involvement require new approaches with greater efficacy. Cognitive dysfunction is common in SLE patients, but early recognition and adequate treatment are yet to be established. Premature accelerated atherosclerosis remains a leading cause of morbidity and mortality. Fatigue is one of the most disabling symptoms, and contributes to the poor quality of life in patients with SLE. Ongoing research in SLE faces many challenges, including enrollment of homogeneous patient populations, use of reliable outcome measures and a standard control arm. The current review will highlight some of the outstanding unmet challenges in the management of this complex disease. PMID:23281889

  11. Magnetic measurements on human erythrocytes: Normal, beta thalassemia major, and sickle

    Sakhnini, Lama

    2003-05-01

    In this article magnetic measurements were made on human erythrocytes at different hemoglobin states (normal and reduced hemoglobin). Different blood samples: normal, beta thalassemia major, and sickle were studied. Beta thalassemia major and sickle samples were taken from patients receiving lifelong blood transfusion treatment. All samples examined exhibited diamagnetic behavior. Beta thalassemia major and sickle samples showed higher diamagnetic susceptibilities than that for the normal, which was attributed to the increase of membrane to hemoglobin volume ratio of the abnormal cells. Magnetic measurements showed that the erythrocytes in the reduced state showed less diamagnetic response in comparison with erythrocytes in the normal state. Analysis of the paramagnetic component of magnetization curves gave an effective magnetic moment of μeff=7.6 μB per reduced hemoglobin molecule. The same procedure was applied to sickle and beta thalassemia major samples and values for μeff were found to be comparable to that of the normal erythrocytes.

  12. Changing Patterns of Unmet Needs for Family Planning Among ...

    AJRH Managing Editor

    This study employed secondary data analysis of the National HIV/AIDS and. Reproductive Health ... Keywords: Unmet Need, Family Planning, Women of Reproductive Age group. Résumé ... The World Health Organization in 2012 highlighted ...

  13. Unmet needs for comprehensive services in outpatient addiction treatment.

    Pringle, Janice L; Emptage, Nicholas P; Hubbard, Robert L

    2006-04-01

    Many addiction treatment patients suffer from health and psychosocial problems in addition to substance misuse at the time of their treatment entry. Outpatient treatment programs have attempted to address these problems by providing or facilitating access to comprehensive health and social services. Nevertheless, previous research have suggested high levels of unmet needs for these services in the addiction treatment population. Using data from a large study on community-based outpatient addiction treatment, this article provides additional information on levels of unmet service needs and the relationship between need and receipt of services during treatment. Our results suggest extremely high levels of unmet needs for a wide variety of health and psychosocial services. Specifically, the data suggest that unmet service needs may be far more prevalent than previous estimates and that addiction treatment populations in rural areas may be particularly disadvantaged.

  14. Challenges Addressing Unmet Need for Contraception: Voices of ...

    AJRH Managing Editor

    Family Planning Service Providers in Rural Tanzania. Jitihada Baraka. 1 ... Keywords: Contraception, Unmet need for family planning, Provider perspectives, Tanzania, Quality of care. Résumé .... the Internal Review Board (IRB) of Columbia.

  15. Human parvovirus B19 in patients with beta thalassemia major from Tehran, Iran.

    Arabzadeh, Seyed Ali Mohammad; Alizadeh, Farideh; Tavakoli, Ahmad; Mollaei, Hamidreza; Bokharaei-Salim, Farah; Karimi, Gharib; Farahmand, Mohammad; Mortazavi, Helya Sadat; Monavari, Seyed Hamidreza

    2017-03-01

    Due to the tropism of human parvovirus B19 to erythroid progenitor cells, infection in patients with an underlying hemolytic disorder such as beta-thalassemia major leads to suppression of erythrocyte formation, referred to as transient aplasia crisis (TAC), which may be life-threatening. We investigated the prevalence of parvovirus B19 among patients with beta thalassemia major attending the Zafar Adult Thalassemia Clinic in Tehran, Iran. This cross-sectional study was performed to determine the presence of parvovirus B19 DNA in blood samples and parvovirus B19 genotypes in plasma samples of patients with thalassemia major. The population consisted of 150 patients with beta-thalassemia major who attended the Zafar clinic in Tehran. Specimens were studied using a real-time polymerase chain reaction assay. The prevalence of parvovirus B19 in our study population was 4%. Of 150 patients with thalassemia, six (4%) were positive for B19 DNA. There was no significant correlation between blood transfusion frequency and B19 DNA positivity. Finally, phylogenetic analysis of human parvovirus B19 revealed genotype I in these six patients. In this study, acute B19 infections were detected in patients with beta thalassemia major. Screening of such high-risk groups can considerably reduce the incidence and prevalence of B19 infection; thus, screening is required for epidemiologic surveillance and disease-prevention measures.

  16. mtDNA variation predicts population size in humans and reveals a major Southern Asian chapter in human prehistory.

    Atkinson, Quentin D; Gray, Russell D; Drummond, Alexei J

    2008-02-01

    The relative timing and size of regional human population growth following our expansion from Africa remain unknown. Human mitochondrial DNA (mtDNA) diversity carries a legacy of our population history. Given a set of sequences, we can use coalescent theory to estimate past population size through time and draw inferences about human population history. However, recent work has challenged the validity of using mtDNA diversity to infer species population sizes. Here we use Bayesian coalescent inference methods, together with a global data set of 357 human mtDNA coding-region sequences, to infer human population sizes through time across 8 major geographic regions. Our estimates of relative population sizes show remarkable concordance with the contemporary regional distribution of humans across Africa, Eurasia, and the Americas, indicating that mtDNA diversity is a good predictor of population size in humans. Plots of population size through time show slow growth in sub-Saharan Africa beginning 143-193 kya, followed by a rapid expansion into Eurasia after the emergence of the first non-African mtDNA lineages 50-70 kya. Outside Africa, the earliest and fastest growth is inferred in Southern Asia approximately 52 kya, followed by a succession of growth phases in Northern and Central Asia (approximately 49 kya), Australia (approximately 48 kya), Europe (approximately 42 kya), the Middle East and North Africa (approximately 40 kya), New Guinea (approximately 39 kya), the Americas (approximately 18 kya), and a second expansion in Europe (approximately 10-15 kya). Comparisons of relative regional population sizes through time suggest that between approximately 45 and 20 kya most of humanity lived in Southern Asia. These findings not only support the use of mtDNA data for estimating human population size but also provide a unique picture of human prehistory and demonstrate the importance of Southern Asia to our recent evolutionary past.

  17. EMPIRICAL REFLECTIONS ON MIGRATION PHENOMENON. MAJOR EFFECTS OF MIGRATION ON THE HUMAN CAPITAL

    Simona BUTA

    2013-12-01

    Full Text Available The paper Empirical reflections on migration phenomenon. Major effects of migration on the human capital analyzes the migration flows of the workforce (as part of the human capital globally/regionally, especially the highly qualified workforce migration. The qualified manpower processes of attracting on the work market have not been always well understood and, in some cases, have generated a series of difficulties. This is the reason why we will focus on the „waste of brains” phenomenon, which appears when highly qualified individuals are neither employed in the source-country nor in the target country; and, if they are, their job is below their qualifications.

  18. The major histocompatibility complex and perfumers' descriptions of human body odors

    Wedekind, C.; Escher, S.; Van de Waal, M.; Frei, E.

    2007-01-01

    The MHC (major histocompatibility complex) is a group of genes that play a crucial role in immune recognition and in tolerance of tissue grafting. The MHC has also been found to influence body odors, body odor preferences, and mate choice in mice and humans. Here we test whether verbal descriptions of human body odors can be linked to the MHC. We asked 45 male students to live as odor neutral as possible for two consecutive days and to wear a T-shirt during the nights. The odors of these T-sh...

  19. Oxidized Lipoprotein as a Major Vessel Cell Proliferator in Oxidized Human Serum.

    Yoshiro Saito

    Full Text Available Oxidative stress is correlated with the incidence of several diseases such as atherosclerosis and cancer, and oxidized biomolecules have been determined as biomarkers of oxidative stress; however, the detailed molecular relationship between generated oxidation products and the promotion of diseases has not been fully elucidated. In the present study, to clarify the role of serum oxidation products in vessel cell proliferation, which is related to the incidence of atherosclerosis and cancer, the major vessel cell proliferator in oxidized human serum was investigated. Oxidized human serum was prepared by free radical exposure, separated using gel chromatography, and then each fraction was added to several kinds of vessel cells including endothelial cells and smooth muscle cells. It was found that a high molecular weight fraction in oxidized human serum specifically induced vessel cell proliferation. Oxidized lipids were contained in this high molecular weight fraction, while cell proliferation activity was not observed in oxidized lipoprotein-deficient serum. Oxidized low-density lipoproteins induced vessel cell proliferation in a concentration-dependent manner. Taken together, these results indicate that oxidized lipoproteins containing lipid oxidation products function as a major vessel cell proliferator in oxidized human serum. These findings strongly indicate the relevance of determination of oxidized lipoproteins and lipid oxidation products in the diagnosis of vessel cell proliferation-related diseases such as atherosclerosis and cancer.

  20. Identification of Human Semiochemicals Attractive to the Major Vectors of Onchocerciasis

    Young, Ryan M.; Burkett-Cadena, Nathan D.; McGaha, Tommy W.; Rodriguez-Perez, Mario A.; Toé, Laurent D.; Adeleke, Monsuru A.; Sanfo, Moussa; Soungalo, Traore; Katholi, Charles R.; Noblet, Raymond; Fadamiro, Henry; Torres-Estrada, Jose L.; Salinas-Carmona, Mario C.; Baker, Bill; Unnasch, Thomas R.; Cupp, Eddie W.

    2015-01-01

    Background Entomological indicators are considered key metrics to document the interruption of transmission of Onchocerca volvulus, the etiological agent of human onchocerciasis. Human landing collection is the standard employed for collection of the vectors for this parasite. Recent studies reported the development of traps that have the potential for replacing humans for surveillance of O. volvulus in the vector population. However, the key chemical components of human odor that are attractive to vector black flies have not been identified. Methodology/Principal Findings Human sweat compounds were analyzed using GC-MS analysis and compounds common to three individuals identified. These common compounds, with others previously identified as attractive to other hematophagous arthropods were evaluated for their ability to stimulate and attract the major onchocerciasis vectors in Africa (Simulium damnosum sensu lato) and Latin America (Simulium ochraceum s. l.) using electroantennography and a Y tube binary choice assay. Medium chain length carboxylic acids and aldehydes were neurostimulatory for S. damnosum s.l. while S. ochraceum s.l. was stimulated by short chain aliphatic alcohols and aldehydes. Both species were attracted to ammonium bicarbonate and acetophenone. The compounds were shown to be attractive to the relevant vector species in field studies, when incorporated into a formulation that permitted a continuous release of the compound over time and used in concert with previously developed trap platforms. Conclusions/Significance The identification of compounds attractive to the major vectors of O. volvulus will permit the development of optimized traps. Such traps may replace the use of human vector collectors for monitoring the effectiveness of onchocerciasis elimination programs and could find use as a contributing component in an integrated vector control/drug program aimed at eliminating river blindness in Africa. PMID:25569240

  1. Identification of human semiochemicals attractive to the major vectors of onchocerciasis.

    Young, Ryan M; Burkett-Cadena, Nathan D; McGaha, Tommy W; Rodriguez-Perez, Mario A; Toé, Laurent D; Adeleke, Monsuru A; Sanfo, Moussa; Soungalo, Traore; Katholi, Charles R; Noblet, Raymond; Fadamiro, Henry; Torres-Estrada, Jose L; Salinas-Carmona, Mario C; Baker, Bill; Unnasch, Thomas R; Cupp, Eddie W

    2015-01-01

    Entomological indicators are considered key metrics to document the interruption of transmission of Onchocerca volvulus, the etiological agent of human onchocerciasis. Human landing collection is the standard employed for collection of the vectors for this parasite. Recent studies reported the development of traps that have the potential for replacing humans for surveillance of O. volvulus in the vector population. However, the key chemical components of human odor that are attractive to vector black flies have not been identified. Human sweat compounds were analyzed using GC-MS analysis and compounds common to three individuals identified. These common compounds, with others previously identified as attractive to other hematophagous arthropods were evaluated for their ability to stimulate and attract the major onchocerciasis vectors in Africa (Simulium damnosum sensu lato) and Latin America (Simulium ochraceum s. l.) using electroantennography and a Y tube binary choice assay. Medium chain length carboxylic acids and aldehydes were neurostimulatory for S. damnosum s.l. while S. ochraceum s.l. was stimulated by short chain aliphatic alcohols and aldehydes. Both species were attracted to ammonium bicarbonate and acetophenone. The compounds were shown to be attractive to the relevant vector species in field studies, when incorporated into a formulation that permitted a continuous release of the compound over time and used in concert with previously developed trap platforms. The identification of compounds attractive to the major vectors of O. volvulus will permit the development of optimized traps. Such traps may replace the use of human vector collectors for monitoring the effectiveness of onchocerciasis elimination programs and could find use as a contributing component in an integrated vector control/drug program aimed at eliminating river blindness in Africa.

  2. Communication Capacity Research in the Majority World: Supporting the human right to communication specialist services.

    Hopf, Suzanne C

    2018-02-01

    Receipt of accessible and appropriate specialist services and resources by all people with communication and/or swallowing disability is a human right; however, it is a right rarely achieved in either Minority or Majority World contexts. This paper considers communication specialists' efforts to provide sustainable services for people with communication difficulties living in Majority World countries. The commentary draws on human rights literature, particularly Article 19 of the Universal Declaration of Human Rights and the Communication Capacity Research program that includes: (1) gathering knowledge from policy and literature; (2) gathering knowledge from the community; (3) understanding speech, language and literacy use and proficiency; and (4) developing culturally and linguistically appropriate resources and assessments. To inform the development of resources and assessments that could be used by speech-language pathologists as well as other communication specialists in Fiji, the Communication Capacity Research program involved collection and analysis of data from multiple sources including 144 community members, 75 school students and their families, and 25 teachers. The Communication Capacity Research program may be applicable for achieving the development of evidence-based, culturally and linguistically sustainable SLP services in similar contexts.

  3. Unmet Health Care Needs among Children Exposed to Parental Incarceration.

    Turney, Kristin

    2017-05-01

    Objectives The incarceration rate in the United States has increased rapidly since the mid-1970s and, accordingly, a large number of children are exposed to parental incarceration. Research finds that parental incarceration is associated with deleterious physical and mental health outcomes among children, but little is known about these children's health care access. Methods I used data from the 2011-2012 National Survey of Children's Health (N = 95,531), a population-based and nationally representative survey of non-institutionalized children ages 0-17 in the United States, to estimate the association between exposure to parental incarceration and children's unmet health care needs. Results In logistic regression models that adjust for an array of demographic and socioeconomic characteristics, children exposed to parental incarceration, compared to their counterparts, have 1.26 (95% CI 1.02-1.54) times the odds of having any unmet health care need. Analyses that disaggregate by type of unmet health care need (mental, dental, vision, mental health, or other) suggest this association is driven by a greater likelihood of unmet mental health care needs (OR 1.60; 95% CI 1.04-2.46). Conclusions Children exposed to parental incarceration, a vulnerable group especially at risk of physical and mental health problems, face challenges to health care access, especially mental health care access. Given that parental incarceration is concentrated among those children most in need of health care, parental incarceration may exacerbate existing inequalities in unmet health care needs.

  4. Statistical evaluation of major human errors during the development of new technological systems

    Campbell, G; Ott, K.O.

    1979-01-01

    Statistical procedures are presented to evaluate major human errors during the development of a new system, errors that have led or can lead to accidents or major failures. The first procedure aims at estimating the average residual occurrence rate for s or major failures after several have occurred. The procedure is solely based on the historical record. Certain idealizations are introduced that allow the application of a sound statistical evaluation procedure. These idealizations are practically realized to a sufficient degree such that the proposed estimation procedure yields meaningful results, even for situations with a sparse data base, represented by very few accidents. Under the assumption that the possible human-error-related failure times have exponential distributions, the statistical technique of isotonic regression is proposed to estimate the failure rates due to human design error at the failure times of the system. The last value in the sequence of estimates gives the residual accident chance. In addition, theactual situation is tested against the hypothesis that the failure rate of the system remains constant over time. This test determines the chance for a decreasing failure rate being incidental, rather than an indication of an actual learning process. Both techniques can be applied not merely to a single system but to an entire series of similar systems that a technology would generate, enabling the assessment of technological improvement. For the purpose of illustration, the nuclear decay of isotopes was chosen as an example, since the assumptions of the model are rigorously satisfied in this case. This application shows satisfactory agreement of the estimated and actual failure rates (which are exactly known in this example), although the estimation was deliberately based on a sparse historical record

  5. Transcriptionally Driven DNA Replication Program of the Human Parasite Leishmania major

    Rodrigo Lombraña

    2016-08-01

    Full Text Available Faithful inheritance of eukaryotic genomes requires the orchestrated activation of multiple DNA replication origins (ORIs. Although origin firing is mechanistically conserved, how origins are specified and selected for activation varies across different model systems. Here, we provide a complete analysis of the nucleosomal landscape and replication program of the human parasite Leishmania major, building on a better evolutionary understanding of replication organization in Eukarya. We found that active transcription is a driving force for the nucleosomal organization of the L. major genome and that both the spatial and the temporal program of DNA replication can be explained as associated to RNA polymerase kinetics. This simple scenario likely provides flexibility and robustness to deal with the environmental changes that impose alterations in the genetic programs during parasitic life cycle stages. Our findings also suggest that coupling replication initiation to transcription elongation could be an ancient solution used by eukaryotic cells for origin maintenance.

  6. The Major Histocompatibility Complex and Perfumers' Descriptions of Human Body Odors

    Claus Wedekind

    2007-04-01

    Full Text Available The MHC (major histocompatibility complex is a group of genes that play a crucial role in immune recognition and in tolerance of tissue grafting. The MHC has also been found to influence body odors, body odor preferences, and mate choice in mice and humans. Here we test whether verbal descriptions of human body odors can be linked to the MHC. We asked 45 male students to live as odor neutral as possible for two consecutive days and to wear a T-shirt during the nights. The odors of these T-shirts were then described by five evaluators: two professional perfumers and three laymen. One of the perfumers was able to describe the T-shirt odors in such a way that some of the allelic specificity of the MHC was significantly revealed (after Bonferroni correction for multiple testing. This shows that, although difficult, some people are able to describe MHC-correlated body odor components.

  7. [SWOT Analysis of the National Survey on Current Status of Major Human Parasitic Diseases in China].

    ZHU, Hui-hui; ZHOU, Chang-hai; CHEN, Ying-dan; ZANG, Wei; XIAO, Ning; ZHOU, Xiao-nong

    2015-10-01

    The National Survey on Current Status of Major Human Parasitic Diseases in China has been carried out since 2014 under the organization of the National Health and Family Planning Commission of the People's Republic of China. The National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (NIPD, China CDC) provided technical support and was responsible for quality control in this survey. This study used SWOT method to analyze the strengths, weaknesses, opportunities and threats that were encountered by he NIPD, China CDC during the completion of the survey. Accordingly, working strategies were proposed to facilitate the future field work.

  8. Reduction in human Lyme neuroborreliosis associated with a major epidemic among roe deer

    Andersen, Nanna Skaarup; Skarphédinsson, Sigurdur; Knudtzen, Fredrikke C

    2018-01-01

    Lyme neuroborreliosis is the most severe clinical manifestation of Lyme borreliosis. In most of Denmark, and also Europe, the overall prevalence of Lyme borreliosis seems to be stabilising. This is not the case on the island of Funen, Denmark, where the number of human Lyme neuroborreliosis cases...... has markedly declined throughout the last decade. We propose the reason for the decline is a major epidemic among roe deer, killing almost half of their population, resulting in a reduction in the tick population which make it less likely to get a tick bite and therefore to contract Lyme...

  9. Molecular cloning of human protein 4.2: A major component of the erythrocyte membrane

    Sung, L.A.; Chien, Shu; Lambert, K.; Chang, Longsheng; Bliss, S.A.; Bouhassira, E.E.; Nagel, R.L.; Schwartz, R.S.; Rybicki, A.C.

    1990-01-01

    Protein 4.2 (P4.2) comprises ∼5% of the protein mass of human erythrocyte (RBC) membranes. Anemia occurs in patients with RBCs deficient in P4.2, suggesting a role for this protein in maintaining RBC stability and integrity. The authors now report the molecular cloning and characterization of human RBC P4.2 cDNAs. By immunoscreening a human reticulocyte cDNA library and by using the polymerase chain reaction, two cDNA sequences of 2.4 and 2.5 kilobases (kb) were obtained. These cDNAs differ only by a 90-base-air insert in the longer isoform located three codons downstream from the putative initiation site. The 2.4- and 2.5-kb cDNAs predict proteins of ∼77 and ∼80 kDa, respectively, and the authenticity was confirmed by sequence identity with 46 amino acids of three cyanogen bromide-cleaved peptides of P4.2. Northern blot analysis detected a major 2.4-kb RNA species in reticulocytes. Isolation of two P4.2 cDNAs implies existence of specific regulation of P4.2 expression in human RBCs. Human RBC P4.2 has significant homology with human factor XIII subunit a and guinea pig liver transglutaminase. Sequence alignment of P4.2 with these two transglutaminases, however, revealed that P4.2 lacks the critical cysteine residue required for the enzymatic crosslinking of substrates

  10. Muscle invasive bladder cancer: examining survivor burden and unmet needs.

    Mohamed, Nihal E; Chaoprang Herrera, Phapichaya; Hudson, Shawna; Revenson, Tracey A; Lee, Cheryl T; Quale, Diane Z; Zarcadoolas, Christina; Hall, Simon J; Diefenbach, Michael A

    2014-01-01

    Although improvements in perioperative care have decreased surgical morbidity after radical cystectomy for muscle invasive bladder cancer, treatment side effects still have a negative impact on patient quality of life. We examined unmet patient needs along the illness trajectory. A total of 30 patients (26.7% women) treated with cystectomy and urinary diversion for muscle invasive bladder cancer participated in the study. Patients were recruited from the Department of Urology at Mount Sinai and through advertisements on the Bladder Cancer Advocacy Network (BCAN) website between December 2011 and September 2012. Data were collected at individual interviews, which were audiotaped and transcribed. Transcribed data were quantitatively analyzed to explore key unmet needs. At diagnosis unmet informational needs were predominant, consisting of insufficient discussion of certain topics, including urinary diversion options and their side effects, self-care, the recovery process and medical insurance. Unmet psychological needs related to depression, and worries about changes in body image and sexual function were reported. Postoperative unmet needs revolved around medical needs (eg pain and bowel dysfunction) and instrumental needs (eg need of support for stomal appliances, catheters and incontinence). During survivorship (ie 6 to 72 months postoperatively) unmet needs centered around psychological support (ie depression, poor body image and sexual dysfunction) and instrumental support (eg difficulty adjusting to changes in daily living). Meeting patient needs is imperative to ensure adequate patient involvement in health care and enhance postoperative quality of life. An effective support provision plan should follow changes in patient needs. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  11. Dynamics of major histocompatibility complex class I association with the human peptide-loading complex.

    Panter, Michaela S; Jain, Ankur; Leonhardt, Ralf M; Ha, Taekjip; Cresswell, Peter

    2012-09-07

    Although the human peptide-loading complex (PLC) is required for optimal major histocompatibility complex class I (MHC I) antigen presentation, its composition is still incompletely understood. The ratio of the transporter associated with antigen processing (TAP) and MHC I to tapasin, which is responsible for MHC I recruitment and peptide binding optimization, is particularly critical for modeling of the PLC. Here, we characterized the stoichiometry of the human PLC using both biophysical and biochemical approaches. By means of single-molecule pulldown (SiMPull), we determined a TAP/tapasin ratio of 1:2, consistent with previous studies of insect-cell microsomes, rat-human chimeric cells, and HeLa cells expressing truncated TAP subunits. We also report that the tapasin/MHC I ratio varies, with the PLC population comprising both 2:1 and 2:2 complexes, based on mutational and co-precipitation studies. The MHC I-saturated PLC may be particularly prevalent among peptide-selective alleles, such as HLA-C4. Additionally, MHC I association with the PLC increases when its peptide supply is reduced by inhibiting the proteasome or by blocking TAP-mediated peptide transport using viral inhibitors. Taken together, our results indicate that the composition of the human PLC varies under normal conditions and dynamically adapts to alterations in peptide supply that may arise during viral infection. These findings improve our understanding of the quality control of MHC I peptide loading and may aid the structural and functional modeling of the human PLC.

  12. Unmet Needs in the Treatment of Gastroesophageal Reflux Disease

    Dickman, Ram; Maradey-Romero, Carla; Gingold-Belfer, Rachel; Fass, Ronnie

    2015-01-01

    Gastroesophageal reflux disease (GERD) is a highly prevalent gastrointestinal disorder. Proton pump inhibitors have profoundly revolutionized the treatment of GERD. However, several areas of unmet need persist despite marked improvements in the therapeutic management of GERD. These include the advanced grades of erosive esophagitis, nonerosive reflux disease, maintenance treatment of erosive esophagitis, refractory GERD, postprandial heartburn, atypical and extraesophageal manifestations of GERD, Barrett’s esophagus, chronic protein pump inhibitor treatment, and post-bariatric surgery GERD. Consequently, any future development of novel therapeutic modalities for GERD (medical, endoscopic, or surgical), would likely focus on the aforementioned areas of unmet need. PMID:26130628

  13. Nonproductive human immunodeficiency virus type 1 infection of human fetal astrocytes: independence from CD4 and major chemokine receptors.

    Sabri, F; Tresoldi, E; Di Stefano, M; Polo, S; Monaco, M C; Verani, A; Fiore, J R; Lusso, P; Major, E; Chiodi, F; Scarlatti, G

    1999-11-25

    Human immunodeficiency virus type 1 (HIV-1) infection of the brain is associated with neurological manifestations both in adults and in children. The primary target for HIV-1 infection in the brain is the microglia, but astrocytes can also be infected. We tested 26 primary HIV-1 isolates for their capacity to infect human fetal astrocytes in culture. Eight of these isolates, independent of their biological phenotype and chemokine receptor usage, were able to infect astrocytes. Although no sustained viral replication could be demonstrated, the virus was recovered by coculture with receptive cells such as macrophages or on stimulation with interleukin-1beta. To gain knowledge into the molecular events that regulate attachment and penetration of HIV-1 in astrocytes, we investigated the expression of several chemokine receptors. Fluorocytometry and calcium-mobilization assay did not provide evidence of expression of any of the major HIV-1 coreceptors, including CXCR4, CCR5, CCR3, and CCR2b, as well as the CD4 molecule on the cell surface of human fetal astrocytes. However, mRNA transcripts for CXCR4, CCR5, Bonzo/STRL33/TYMSTR, and APJ were detected by RT-PCR. Furthermore, infection of astrocytes by HIV-1 isolates with different chemokine receptor usage was not inhibited by the chemokines SDF-1beta, RANTES, MIP-1beta, or MCP-1 or by antibodies directed against the third variable region or the CD4 binding site of gp120. These data show that astrocytes can be infected by primary HIV-1 isolates via a mechanism independent of CD4 or major chemokine receptors. Furthermore, astrocytes are potential carriers of latent HIV-1 and on activation may be implicated in spreading the infection to other neighbouring cells, such as microglia or macrophages. Copyright 1999 Academic Press.

  14. Contemporary status of insecticide resistance in the major Aedes vectors of arboviruses infecting humans.

    Moyes, Catherine L; Vontas, John; Martins, Ademir J; Ng, Lee Ching; Koou, Sin Ying; Dusfour, Isabelle; Raghavendra, Kamaraju; Pinto, João; Corbel, Vincent; David, Jean-Philippe; Weetman, David

    2017-07-01

    Both Aedes aegytpi and Ae. albopictus are major vectors of 5 important arboviruses (namely chikungunya virus, dengue virus, Rift Valley fever virus, yellow fever virus, and Zika virus), making these mosquitoes an important factor in the worldwide burden of infectious disease. Vector control using insecticides coupled with larval source reduction is critical to control the transmission of these viruses to humans but is threatened by the emergence of insecticide resistance. Here, we review the available evidence for the geographical distribution of insecticide resistance in these 2 major vectors worldwide and map the data collated for the 4 main classes of neurotoxic insecticide (carbamates, organochlorines, organophosphates, and pyrethroids). Emerging resistance to all 4 of these insecticide classes has been detected in the Americas, Africa, and Asia. Target-site mutations and increased insecticide detoxification have both been linked to resistance in Ae. aegypti and Ae. albopictus but more work is required to further elucidate metabolic mechanisms and develop robust diagnostic assays. Geographical distributions are provided for the mechanisms that have been shown to be important to date. Estimating insecticide resistance in unsampled locations is hampered by a lack of standardisation in the diagnostic tools used and by a lack of data in a number of regions for both resistance phenotypes and genotypes. The need for increased sampling using standard methods is critical to tackle the issue of emerging insecticide resistance threatening human health. Specifically, diagnostic doses and well-characterised susceptible strains are needed for the full range of insecticides used to control Ae. aegypti and Ae. albopictus to standardise measurement of the resistant phenotype, and calibrated diagnostic assays are needed for the major mechanisms of resistance.

  15. Contemporary status of insecticide resistance in the major Aedes vectors of arboviruses infecting humans

    Vontas, John; Martins, Ademir J.; Ng, Lee Ching; Koou, Sin Ying; Dusfour, Isabelle; Raghavendra, Kamaraju; Pinto, João; Corbel, Vincent; David, Jean-Philippe; Weetman, David

    2017-01-01

    Both Aedes aegytpi and Ae. albopictus are major vectors of 5 important arboviruses (namely chikungunya virus, dengue virus, Rift Valley fever virus, yellow fever virus, and Zika virus), making these mosquitoes an important factor in the worldwide burden of infectious disease. Vector control using insecticides coupled with larval source reduction is critical to control the transmission of these viruses to humans but is threatened by the emergence of insecticide resistance. Here, we review the available evidence for the geographical distribution of insecticide resistance in these 2 major vectors worldwide and map the data collated for the 4 main classes of neurotoxic insecticide (carbamates, organochlorines, organophosphates, and pyrethroids). Emerging resistance to all 4 of these insecticide classes has been detected in the Americas, Africa, and Asia. Target-site mutations and increased insecticide detoxification have both been linked to resistance in Ae. aegypti and Ae. albopictus but more work is required to further elucidate metabolic mechanisms and develop robust diagnostic assays. Geographical distributions are provided for the mechanisms that have been shown to be important to date. Estimating insecticide resistance in unsampled locations is hampered by a lack of standardisation in the diagnostic tools used and by a lack of data in a number of regions for both resistance phenotypes and genotypes. The need for increased sampling using standard methods is critical to tackle the issue of emerging insecticide resistance threatening human health. Specifically, diagnostic doses and well-characterised susceptible strains are needed for the full range of insecticides used to control Ae. aegypti and Ae. albopictus to standardise measurement of the resistant phenotype, and calibrated diagnostic assays are needed for the major mechanisms of resistance. PMID:28727779

  16. Contemporary status of insecticide resistance in the major Aedes vectors of arboviruses infecting humans.

    Catherine L Moyes

    2017-07-01

    Full Text Available Both Aedes aegytpi and Ae. albopictus are major vectors of 5 important arboviruses (namely chikungunya virus, dengue virus, Rift Valley fever virus, yellow fever virus, and Zika virus, making these mosquitoes an important factor in the worldwide burden of infectious disease. Vector control using insecticides coupled with larval source reduction is critical to control the transmission of these viruses to humans but is threatened by the emergence of insecticide resistance. Here, we review the available evidence for the geographical distribution of insecticide resistance in these 2 major vectors worldwide and map the data collated for the 4 main classes of neurotoxic insecticide (carbamates, organochlorines, organophosphates, and pyrethroids. Emerging resistance to all 4 of these insecticide classes has been detected in the Americas, Africa, and Asia. Target-site mutations and increased insecticide detoxification have both been linked to resistance in Ae. aegypti and Ae. albopictus but more work is required to further elucidate metabolic mechanisms and develop robust diagnostic assays. Geographical distributions are provided for the mechanisms that have been shown to be important to date. Estimating insecticide resistance in unsampled locations is hampered by a lack of standardisation in the diagnostic tools used and by a lack of data in a number of regions for both resistance phenotypes and genotypes. The need for increased sampling using standard methods is critical to tackle the issue of emerging insecticide resistance threatening human health. Specifically, diagnostic doses and well-characterised susceptible strains are needed for the full range of insecticides used to control Ae. aegypti and Ae. albopictus to standardise measurement of the resistant phenotype, and calibrated diagnostic assays are needed for the major mechanisms of resistance.

  17. Transgender Veterans' Satisfaction With Care and Unmet Health Needs.

    Lehavot, Keren; Katon, Jodie G; Simpson, Tracy L; Shipherd, Jillian C

    2017-09-01

    Transgender individuals are overrepresented among Veterans. However, little is known regarding their satisfaction with Veterans Administration (VA) care and unmet health needs. This study examined transgender Veterans' satisfaction with VA medical and mental health care, prevalence of delaying care, and correlates of these outcomes. We used data from transgender Veterans collected in 2014 through an online, national survey. In total, 298 transgender Veterans living in the United States. We assessed patient satisfaction with VA medical and mental health care and self-reported delays in seeking medical and mental health care in the past year. Potential correlates associated with these 4 outcomes included demographic, health, and health care variables. Over half of the sample used VA (56%) since their military discharge. Among transgender Veterans who had used VA, 79% were satisfied with medical care and 69% with mental health care. Lower income was associated with dissatisfaction with VA medical care, and being a transgender man was associated with dissatisfaction with VA mental health care. A substantial proportion reported delays in seeking medical (46%) or mental (38%) health care in the past year (not specific to VA). Screening positive for depression and/or posttraumatic stress disorder was associated with delays in seeking both types of care. Although the majority of transgender Veterans are satisfied with VA health care, certain subgroups are less likely to be satisfied with care. Further, many report delaying accessing care, particularly those with depression and/or posttraumatic stress disorder symptoms. Adapting health care settings to better engage these vulnerable Veterans may be necessary.

  18. Unmet Needs and Unused Capacities: Time Banking as a Solution

    Neva Goodwin

    2018-02-01

    Full Text Available In market economies many human activities have little or no money value; these include, especially, the kinds of caring labor that are supplied, mostly by women, mostly in homes and communities. Nevertheless, there is, as ever, a great need for such activities. At the same time, wealthy societies are producing ever more people who suffer from feeling that they have little or nothing of value to offer to the world. Retired people, in their growing numbers, are the most obvious examples, but teenagers and other youth, who in other societies can contribute significantly to the well-being of a family or a community, are seldom seen as assets in modern economies. Market-dominated societies have had difficulty expressing the value of work that is not organized for profit. Such work is undertaken in the public purpose economy, consisting of governments and their agencies as well as non-profit organizations. Much of this kind of work is also undertaken in the core economy, where households and communities carry on their internal activities of resource management, production, distribution, and consumption. The core economy and the public purpose economy, together with the market economy, are a trio that are differentiated by their goals; by what kind of demand they respond to; by how they define and reward work; and by what kind of currency they use. TimeBanking is an innovation in currency that turns out to affect all of these areas by getting us out of the binary box that classifies all contributions in just two ways: work (defined in market terms, or volunteering (defined as uncompensated labor. Responding effectively to different values and goals than those recognized in the market, TimeBanking has been shown able to respond to a wide variety of unmet needs by creating relationships where everyone can get some of their needs met, and everyone is valued for what they can offer.  

  19. Identification of copy number variants defining genomic differences among major human groups.

    Lluís Armengol

    Full Text Available BACKGROUND: Understanding the genetic contribution to phenotype variation of human groups is necessary to elucidate differences in disease predisposition and response to pharmaceutical treatments in different human populations. METHODOLOGY/PRINCIPAL FINDINGS: We have investigated the genome-wide profile of structural variation on pooled samples from the three populations studied in the HapMap project by comparative genome hybridization (CGH in different array platforms. We have identified and experimentally validated 33 genomic loci that show significant copy number differences from one population to the other. Interestingly, we found an enrichment of genes related to environment adaptation (immune response, lipid metabolism and extracellular space within these regions and the study of expression data revealed that more than half of the copy number variants (CNVs translate into gene-expression differences among populations, suggesting that they could have functional consequences. In addition, the identification of single nucleotide polymorphisms (SNPs that are in linkage disequilibrium with the copy number alleles allowed us to detect evidences of population differentiation and recent selection at the nucleotide variation level. CONCLUSIONS: Overall, our results provide a comprehensive view of relevant copy number changes that might play a role in phenotypic differences among major human populations, and generate a list of interesting candidates for future studies.

  20. Assessment of Unmet Need for Contraception among eligible couples in Urban Slums of Raipur city of Chhattisgarh state

    Nirmal Verma

    2014-06-01

    Full Text Available Background: India was the first country to launch National Family Planning Program in 1952. Even though various measures have been taken to encourage the usage of contraception but the achievement in this field was not to the extent expected due to various social and cultural factors. Objective: This study was planned to assess the prevalence and its determinants of unmet need for contraception among eligible couples in urban slums of Raipur city. Methodology: A cross sectional community based study was conducted using cluster sampling in urban slums of Raipur city from November 2011 to October 2012. During the study, 711 fecund married women, age group 15-49 years were included and predesigned and pretested proforma was used as a study tool. The obtained data were analyzed using appropriate statistical test. Results: Among all eligible married women 45 % were concentrated in the prime reproductive age 20-29 yrs. Majority of women were not educated. The total unmet need for family planning comes out to 32.9%. Age, Education, literacy, Occupation, Type of Family, No of living children, Birth Order , No of male child, No of female child , Husband literacy were the most significant predictor of unmet need. Conclusion: Percentage of unmet need is higher as compared to national data, so there is urgently need to ensure the same.

  1. Frequency variations of discrete cranial traits in major human populations. III. Hyperostotic variations.

    Hanihara, T; Ishida, H

    2001-09-01

    Seven discrete cranial traits usually categorised as hyperostotic characters, the medial palatine canal, hypoglossal canal bridging, precondylar tubercle, condylus tertius, jugular foramen bridging, auditory exostosis, and mylohyoid bridging were investigated in 81 major human population samples from around the world. Significant asymmetric occurrences of the bilateral traits were detected in the medial palatine canal and jugular foramen bridging in several samples. Significant intertrait associations were found between some pairs of the traits, but not consistently across the large geographical samples. The auditory exostosis showed a predominant occurrence in males. With the exception of the auditory exostosis and mylohyoid bridging in a few samples, significant sex differences were slight. The frequency distributions of the traits (except for the auditory exostosis) showed some interregional clinality and intraregional discontinuity, suggesting that genetic drift could have contributed to the observed pattern of variation.

  2. Reduction in human Lyme neuroborreliosis associated with a major epidemic among roe deer.

    Andersen, Nanna Skaarup; Skarphédinsson, Sigurdur; Knudtzen, Fredrikke C; Olesen, Carsten Riis; Jensen, Thøger Gorm; Jensen, Per Moestrup

    2018-02-01

    Lyme neuroborreliosis is the most severe clinical manifestation of Lyme borreliosis. In most of Denmark, and also Europe, the overall prevalence of Lyme borreliosis seems to be stabilising. This is not the case on the island of Funen, Denmark, where the number of human Lyme neuroborreliosis cases has markedly declined throughout the last decade. We propose the reason for the decline is a major epidemic among roe deer, killing almost half of their population, resulting in a reduction in the tick population which make it less likely to get a tick bite and therefore to contract Lyme neuroborreliosis. This is the first time such a relationship is described as a naturally occurring phenomenon in Europe. Copyright © 2017 Elsevier GmbH. All rights reserved.

  3. Unmet health care needs for persons with environmental sensitivity

    Gibson PR

    2015-01-01

    Full Text Available Pamela Reed Gibson, Shannon Kovach, Alexis LupferDepartment of Psychology, James Madison University, Harrisonburg, VA, USAAbstract: Studies of unmet health care needs have shown that women, people with poor health, and people with lower socioeconomic status are more likely to report having unmet health care needs. In this study, we examined the types of and reasons for unmet health care needs in 465 people with environmental sensitivities. A second area of inquiry involved negative reactions to general anesthesia. Results showed that the most common barriers to receiving care were the inability to find a provider who understands environmental sensitivities and a lack of accessibility due to chemical and electromagnetic exposures in health care environments. Lower income and poorer health (longer illness, a worsening or fluctuating course of illness, and a higher level of disability were significantly correlated with the total number of reported unmet health care needs. Some people with environmental sensitivities reported having negative reactions to anesthesia of long duration; most common were nausea and vomiting, fatigue, and reduced cognitive ability.Keywords: environmental sensitivity, chemical sensitivity, electrohypersensitivity, chemical hypersensitivity, chemical intolerance, contested illness

  4. Assessing unmet anaesthesia need in Sierra Leone: a secondary ...

    Objectives: To determine the unmet anaesthesia need in a low resource region. Introduction: Surgery and anæsthesia services in low- and middle-income countries (LMICs) are under-equipped, under- staffed, and unable to meet current surgical need. There is little objective measure as to the true extent and nature of ...

  5. Variations in riboflavin binding by human plasma: identification of immunoglobulins as the major proteins responsible

    Innis, W.S.; McCormick, D.B.; Merrill, A.H. Jr.

    1985-01-01

    Riboflavin binding by plasma proteins from healthy human subjects was examined by equilibrium dialysis using a physiological concentration of [2-14C]riboflavin (0.04 microM). Binding ranged from 0.080 to 0.917 pmole of riboflavin/mg of protein (with a mean +/- SD of 0.274 +/- 0.206), which corresponded to 4.14 to 49.4 pmole/ml of plasma (15.5 +/- 11.0) (N = 34). Males and females yielded similar results. Upon fractionation of plasma by gel filtration, the major riboflavin-binding components eluted with albumin and gamma-globulins. Albumin was purified and found to bind riboflavin only very weakly (Kd = 3.8 to 10.4 mM), although FMN and photochemical degradation products (e.g., lumiflavine and lumichrome) were more tightly bound. Binding in the gamma-globulin fraction was attributed to IgG and IGA because the binding protein(s) and immunoglobulins copurified using various methods were removed by treatment of plasma with protein A-agarose, and were coincident upon immunoelectrophoresis followed by autoradiography to detect [2-14C]riboflavin. Differences among the plasma samples correlated with the binding recovered with the immunoglobulins. Binding was not directly related to the total IgG or IgA levels of subjects. Hence, it appears that the binding is due to a subfraction of these proteins. These findings suggest that riboflavin-binding immunoglobulins are a major cause of variations in riboflavin binding in human circulation, and may therefore affect the utilization of this micronutrient

  6. Human Rhinovirus Diversity and Evolution: How Strange the Change from Major to Minor.

    Lewis-Rogers, Nicole; Seger, Jon; Adler, Frederick R

    2017-04-01

    Rhinoviruses are the most common causes of the common cold. Their many distinct lineages fall into "major" and "minor" groups that use different cell surface receptors to enter host cells. Minor-group rhinoviruses are more immunogenic in laboratory studies, although their patterns of transmission and their cold symptoms are broadly similar to those of the major group. Here we present evolutionary evidence that minor-group viruses are also more immunogenic in humans. A key finding is that rates of amino acid substitutions at exposed sites in the capsid proteins VP2, VP3, and VP1 tend to be elevated in minor-group relative to major-group viruses, while rates at buried sites show no consistent differences. A reanalysis of historical virus watch data also indicates a higher immunogenicity of minor-group viruses, consistent with our findings about evolutionary rates at amino acid positions most directly exposed to immune surveillance. The increased immunogenicity and speed of evolution in minor-group lineages may contribute to the very large numbers of rhinovirus serotypes that coexist while differing in virulence. IMPORTANCE Most colds are caused by rhinoviruses (RVs). Those caused by a subset known as the minor-group members of rhinovirus species A (RV-A) are correlated with the inception and aggravation of asthma in at-risk populations. Genetically, minor-group viruses are similar to major-group RV-A, from which they were derived, although they tend to elicit stronger immune responses. Differences in their rates and patterns of molecular evolution should be highly relevant to their epidemiology. All RV-A strains show high rates of amino acid substitutions in the capsid proteins at exposed sites not previously identified as being immunogenic, and this increase is significantly greater in minor-group viruses. These findings will inform future studies of the recently discovered RV-C, which also appears to exacerbate asthma in adults and children. In addition, these

  7. Agrin is a major heparan sulfate proteoglycan in the human glomerular basement membrane.

    Groffen, A J; Ruegg, M A; Dijkman, H; van de Velden, T J; Buskens, C A; van den Born, J; Assmann, K J; Monnens, L A; Veerkamp, J H; van den Heuvel, L P

    1998-01-01

    Agrin is a heparan sulfate proteoglycan (HSPG) that is highly concentrated in the synaptic basal lamina at the neuromuscular junction (NMJ). Agrin-like immunoreactivity is also detected outside the NMJ. Here we show that agrin is a major HSPG component of the human glomerular basement membrane (GBM). This is in addition to perlecan, a previously characterized HSPG of basement membranes. Antibodies against agrin and against an unidentified GBM HSPG produced a strong staining of the GBM and the NMJ, different from that observed with anti-perlecan antibodies. In addition, anti-agrin antisera recognized purified GBM HSPG and competed with an anti-GBM HSPG monoclonal antibody in ELISA. Furthermore, both antibodies recognized a molecule that migrated in SDS-PAGE as a smear and had a molecular mass of approximately 200-210 kD after deglycosylation. In immunoelectron microscopy, agrin showed a linear distribution along the GBM and was present throughout the width of the GBM. This was again different from perlecan, which was exclusively present on the endothelial side of the GBM and was distributed in a nonlinear manner. Quantitative ELISA showed that, compared with perlecan, the agrin-like GBM HSPG showed a sixfold higher molarity in crude glomerular extract. These results show that agrin is a major component of the GBM, indicating that it may play a role in renal ultrafiltration and cell matrix interaction. (J Histochem Cytochem 46:19-27, 1998)

  8. Transcriptionally Driven DNA Replication Program of the Human Parasite Leishmania major.

    Lombraña, Rodrigo; Álvarez, Alba; Fernández-Justel, José Miguel; Almeida, Ricardo; Poza-Carrión, César; Gomes, Fábia; Calzada, Arturo; Requena, José María; Gómez, María

    2016-08-09

    Faithful inheritance of eukaryotic genomes requires the orchestrated activation of multiple DNA replication origins (ORIs). Although origin firing is mechanistically conserved, how origins are specified and selected for activation varies across different model systems. Here, we provide a complete analysis of the nucleosomal landscape and replication program of the human parasite Leishmania major, building on a better evolutionary understanding of replication organization in Eukarya. We found that active transcription is a driving force for the nucleosomal organization of the L. major genome and that both the spatial and the temporal program of DNA replication can be explained as associated to RNA polymerase kinetics. This simple scenario likely provides flexibility and robustness to deal with the environmental changes that impose alterations in the genetic programs during parasitic life cycle stages. Our findings also suggest that coupling replication initiation to transcription elongation could be an ancient solution used by eukaryotic cells for origin maintenance. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  9. Human space flight and future major space astrophysics missions: servicing and assembly

    Thronson, Harley; Peterson, Bradley M.; Greenhouse, Matthew; MacEwen, Howard; Mukherjee, Rudranarayan; Polidan, Ronald; Reed, Benjamin; Siegler, Nicholas; Smith, Hsiao

    2017-09-01

    Some concepts for candidate future "flagship" space observatories approach the payload limits of the largest launch vehicles planned for the next few decades, specifically in the available volume in the vehicle fairing. This indicates that an alternative to autonomous self-deployment similar to that of the James Webb Space Telescope will eventually be required. Moreover, even before this size limit is reached, there will be significant motivation to service, repair, and upgrade in-space missions of all sizes, whether to extend the life of expensive facilities or to replace outworn or obsolete onboard systems as was demonstrated so effectively by the Hubble Space Telescope program. In parallel with these challenges to future major space astronomy missions, the capabilities of in-space robotic systems and the goals for human space flight in the 2020s and 2030s offer opportunities for achieving the most exciting science goals of the early 21st Century. In this paper, we summarize the history of concepts for human operations beyond the immediate vicinity of the Earth, the importance of very large apertures for scientific discovery, and current capabilities and future developments in robot- and astronaut-enabled servicing and assembly.

  10. High-Resolution Patterns of Meiotic Recombination across the Human Major Histocompatibility Complex

    Cullen, Michael; Perfetto, Stephen P.; Klitz, William; Nelson, George; Carrington, Mary

    2002-01-01

    Definitive characteristics of meiotic recombination events over large (i.e., >1 Mb) segments of the human genome remain obscure, yet they are essential for establishing the haplotypic structure of the genome and for efficient mapping of complex traits. We present a high-resolution map of recombination at the kilobase level across a 3.3-Mb interval encompassing the major histocompatibility complex (MHC). Genotyping of 20,031 single sperm from 12 individuals resulted in the identification and fine mapping of 325 recombinant chromosomes within genomic intervals as small as 7 kb. Several principal characteristics of recombination in this region were observed: (1) rates of recombination can differ significantly between individuals; (2) intense hot spots of recombination occur at least every 0.8 Mb but are not necessarily evenly spaced; (3) distribution in the location of recombination events can differ significantly among individuals; (4) between hot spots, low levels of recombination occur fairly evenly across 100-kb segments, suggesting the presence of warm spots of recombination; and (5) specific sequence motifs associate significantly with recombination distribution. These data provide a plausible model for recombination patterns of the human genome overall. PMID:12297984

  11. Specificity of the trypanothione-dependent Leishmania major glyoxalase I: structure and biochemical comparison with the human enzyme.

    Ariza, Antonio; Vickers, Tim J; Greig, Neil; Armour, Kirsten A; Dixon, Mark J; Eggleston, Ian M; Fairlamb, Alan H; Bond, Charles S

    2006-02-01

    Trypanothione replaces glutathione in defence against cellular damage caused by oxidants, xenobiotics and methylglyoxal in the trypanosomatid parasites, which cause trypanosomiasis and leishmaniasis. In Leishmania major, the first step in methylglyoxal detoxification is performed by a trypanothione-dependent glyoxalase I (GLO1) containing a nickel cofactor; all other characterized eukaryotic glyoxalases use zinc. In kinetic studies L. major and human enzymes were active with methylglyoxal derivatives of several thiols, but showed opposite substrate selectivities: N1-glutathionylspermidine hemithioacetal is 40-fold better with L. major GLO1, whereas glutathione hemithioacetal is 300-fold better with human GLO1. Similarly, S-4-bromobenzylglutathionylspermidine is a 24-fold more potent linear competitive inhibitor of L. major than human GLO1 (Kis of 0.54 microM and 12.6 microM, respectively), whereas S-4-bromobenzylglutathione is >4000-fold more active against human than L. major GLO1 (Kis of 0.13 microM and >500 microM respectively). The crystal structure of L. major GLO1 reveals differences in active site architecture to both human GLO1 and the nickel-dependent Escherichia coli GLO1, including increased negative charge and hydrophobic character and truncation of a loop that may regulate catalysis in the human enzyme. These differences correlate with the differential binding of glutathione and trypanothione-based substrates, and thus offer a route to the rational design of L. major-specific GLO1 inhibitors.

  12. Screening for the synthetic cannabinoid JWH-018 and its major metabolites in human doping controls.

    Möller, Ines; Wintermeyer, Annette; Bender, Katja; Jübner, Martin; Thomas, Andreas; Krug, Oliver; Schänzer, Wilhelm; Thevis, Mario

    2011-09-01

    Referred to as 'spice', several new drugs, advertised as herbal blends, have appeared on the market in the last few years, in which the synthetic cannabinoids JWH-018 and a C(8) homologue of CP 47,497 were identified as major active ingredients. Due to their reported cannabis-like effects, many European countries have banned these substances. The World Anti-Doping Agency has also explicitly prohibited synthetic cannabinoids in elite sport in-competition. Since urine specimens have been the preferred doping control samples, the elucidation of the metabolic pathways of these substances is of particular importance to implement them in sports drug testing programmes. In a recent report, an in vitro phase-I metabolism study of JWH-018 was presented yielding mainly hydroxylated and N-dealkylated metabolites. Due to these findings, a urine sample of a healthy man declaring to have smoked a 'spice' product was screened for potential phase-I and -II metabolites by high-resolution/high-accuracy mass spectrometry in the present report. The majority of the phase-I metabolites observed in earlier in vitro studies of JWH-018 were detected in this urine specimen and furthermore most of their respective monoglucuronides. As no intact JWH-018 was detectable, the monohydroxylated metabolite being the most abundant one was chosen as a target analyte for sports drug testing purposes; a detection method was subsequently developed and validated in accordance to conventional screening protocols based on enzymatic hydrolysis, liquid-liquid extraction, and liquid chromatography/electrospray tandem mass spectrometry analysis. The method was applied to approximately 7500 urine doping control samples yielding two JWH-018 findings and demonstrated its capability for a sensitive and selective identification of JWH-018 and its metabolites in human urine. Copyright © 2010 John Wiley & Sons, Ltd.

  13. Observations on the expression of human papillomavirus major capsid protein in HeLa cells.

    Xiao, Chang-Yi; Fu, Bing-Bing; Li, Zhi-Ying; Mushtaq, Gohar; Kamal, Mohammad Amjad; Li, Jia-Hua; Tang, Gui-Cheng; Xiao, Shuo-Shuang

    2015-01-01

    The goal of this study was to identify the nature of the inclusion bodies that have been found in HeLa cells (cervical cancer immortal cell line) by electron microscope and to determine whether the major capsid protein (L1) of human papillomavirus (HPV) can be expressed in HPV-positive uterine cervix cancer cells. HPV L1 protein expression in HeLa cells was detected with anti-HPV L1 multivalent mice monoclonal antibody and rabbit polyclonal anti-HPV L1 antibody by ELISA, light microscope immunohistochemistry, electron microscope immunocytochemistry and Western blotting assays. Reverse transcriptional PCR (RT-PCR) was performed to detect the transcription of L1 mRNA in HeLa cells. The immortalized human keratinocyte HeCat was used as the negative control. HPV L1 proteins reacted positively in the lysate of HeLa cells by ELISA assays. HRP labeled light microscope immunohistochemistry assay showed that there was a strong HPV L1 positive reaction in HeLa cells. Under the electron microscope, irregular shaped inclusion bodies, assembled by many small and uniform granules, had been observed in the cytoplasm of some HeLa cells. These granules could be labeled by the colloidal gold carried by HPV L1 antibody. The Western blotting assay showed that there was a L1 reaction strap at 80-85 kDa in the HeLa cell lysates, hence demonstrating the existence of HPV18 L1 in HeLa cells. RT-PCR assay showed that the L1 mRNA was transcribed in HeLa cells. The inclusion bodies found in the cytoplasm of HeLa cells are composed of HPV18 L1 protein. Since HeLa cell line is a type of cervical cancer cells, this implies that HeLa cells have the ability to express HPV L1 proteins.

  14. Evolution of Gender Differences in Post-Secondary Human Capital Investments: College Majors. Working Paper #03-11

    Gemici, Ahu; Wiswall, Matthew

    2011-01-01

    Over the past 40 years, the level of human capital investments has changed substantially for men and women. Changes in the intensive margin of college major selection have been also been substantial, as the number of graduates in humanities, social science, and teaching has declined, and the number in science, engineering, and business has…

  15. Combining Human and Machine Learning to Map Cropland in the 21st Century's Major Agricultural Frontier

    Estes, L. D.; Debats, S. R.; Caylor, K. K.; Evans, T. P.; Gower, D.; McRitchie, D.; Searchinger, T.; Thompson, D. R.; Wood, E. F.; Zeng, L.

    2016-12-01

    In the coming decades, large areas of new cropland will be created to meet the world's rapidly growing food demands. Much of this new cropland will be in sub-Saharan Africa, where food needs will increase most and the area of remaining potential farmland is greatest. If we are to understand the impacts of global change, it is critical to accurately identify Africa's existing croplands and how they are changing. Yet the continent's smallholder-dominated agricultural systems are unusually challenging for remote sensing analyses, making accurate area estimates difficult to obtain, let alone important details related to field size and geometry. Fortunately, the rapidly growing archives of moderate to high-resolution satellite imagery hosted on open servers now offer an unprecedented opportunity to improve landcover maps. We present a system that integrates two critical components needed to capitalize on this opportunity: 1) human image interpretation and 2) machine learning (ML). Human judgment is needed to accurately delineate training sites within noisy imagery and a highly variable cover type, while ML provides the ability to scale and to interpret large feature spaces that defy human comprehension. Because large amounts of training data are needed (a major impediment for analysts), we use a crowdsourcing platform that connects amazon.com's Mechanical Turk service to satellite imagery hosted on open image servers. Workers map visible fields at pre-assigned sites, and are paid according to their mapping accuracy. Initial tests show overall high map accuracy and mapping rates >1800 km2/hour. The ML classifier uses random forests and randomized quasi-exhaustive feature selection, and is highly effective in classifying diverse agricultural types in southern Africa (AUC > 0.9). We connect the ML and crowdsourcing components to make an interactive learning framework. The ML algorithm performs an initial classification using a first batch of crowd-sourced maps, using

  16. Structures of the major capsid proteins of the human Karolinska Institutet and Washington University polyomaviruses.

    Neu, Ursula; Wang, Jianbo; Macejak, Dennis; Garcea, Robert L; Stehle, Thilo

    2011-07-01

    The Karolinska Institutet and Washington University polyomaviruses (KIPyV and WUPyV, respectively) are recently discovered human viruses that infect the respiratory tract. Although they have not yet been linked to disease, they are prevalent in populations worldwide, with initial infection occurring in early childhood. Polyomavirus capsids consist of 72 pentamers of the major capsid protein viral protein 1 (VP1), which determines antigenicity and receptor specificity. The WUPyV and KIPyV VP1 proteins are distant in evolution from VP1 proteins of known structure such as simian virus 40 or murine polyomavirus. We present here the crystal structures of unassembled recombinant WUPyV and KIPyV VP1 pentamers at resolutions of 2.9 and 2.55 Å, respectively. The WUPyV and KIPyV VP1 core structures fold into the same β-sandwich that is a hallmark of all polyomavirus VP1 proteins crystallized to date. However, differences in sequence translate into profoundly different surface loop structures in KIPyV and WUPyV VP1 proteins. Such loop structures have not been observed for other polyomaviruses, and they provide initial clues about the possible interactions of these viruses with cell surface receptors.

  17. Effective population sizes of a major vector of human diseases, Aedes aegypti.

    Saarman, Norah P; Gloria-Soria, Andrea; Anderson, Eric C; Evans, Benjamin R; Pless, Evlyn; Cosme, Luciano V; Gonzalez-Acosta, Cassandra; Kamgang, Basile; Wesson, Dawn M; Powell, Jeffrey R

    2017-12-01

    The effective population size ( N e ) is a fundamental parameter in population genetics that determines the relative strength of selection and random genetic drift, the effect of migration, levels of inbreeding, and linkage disequilibrium. In many cases where it has been estimated in animals, N e is on the order of 10%-20% of the census size. In this study, we use 12 microsatellite markers and 14,888 single nucleotide polymorphisms (SNPs) to empirically estimate N e in Aedes aegypti , the major vector of yellow fever, dengue, chikungunya, and Zika viruses. We used the method of temporal sampling to estimate N e on a global dataset made up of 46 samples of Ae. aegypti that included multiple time points from 17 widely distributed geographic localities. Our N e estimates for Ae. aegypti fell within a broad range (~25-3,000) and averaged between 400 and 600 across all localities and time points sampled. Adult census size (N c ) estimates for this species range between one and five thousand, so the N e / N c ratio is about the same as for most animals. These N e values are lower than estimates available for other insects and have important implications for the design of genetic control strategies to reduce the impact of this species of mosquito on human health.

  18. Modelling the regulation of thermal adaptation in Candida albicans, a major fungal pathogen of humans.

    Michelle D Leach

    Full Text Available Eukaryotic cells have evolved mechanisms to sense and adapt to dynamic environmental changes. Adaptation to thermal insults, in particular, is essential for their survival. The major fungal pathogen of humans, Candida albicans, is obligately associated with warm-blooded animals and hence occupies thermally buffered niches. Yet during its evolution in the host it has retained a bona fide heat shock response whilst other stress responses have diverged significantly. Furthermore the heat shock response is essential for the virulence of C. albicans. With a view to understanding the relevance of this response to infection we have explored the dynamic regulation of thermal adaptation using an integrative systems biology approach. Our mathematical model of thermal regulation, which has been validated experimentally in C. albicans, describes the dynamic autoregulation of the heat shock transcription factor Hsf1 and the essential chaperone protein Hsp90. We have used this model to show that the thermal adaptation system displays perfect adaptation, that it retains a transient molecular memory, and that Hsf1 is activated during thermal transitions that mimic fever. In addition to providing explanations for the evolutionary conservation of the heat shock response in this pathogen and the relevant of this response to infection, our model provides a platform for the analysis of thermal adaptation in other eukaryotic cells.

  19. Major Pesticides Are More Toxic to Human Cells Than Their Declared Active Principles

    Robin Mesnage

    2014-01-01

    Full Text Available Pesticides are used throughout the world as mixtures called formulations. They contain adjuvants, which are often kept confidential and are called inerts by the manufacturing companies, plus a declared active principle, which is usually tested alone. We tested the toxicity of 9 pesticides, comparing active principles and their formulations, on three human cell lines (HepG2, HEK293, and JEG3. Glyphosate, isoproturon, fluroxypyr, pirimicarb, imidacloprid, acetamiprid, tebuconazole, epoxiconazole, and prochloraz constitute, respectively, the active principles of 3 major herbicides, 3 insecticides, and 3 fungicides. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. Fungicides were the most toxic from concentrations 300–600 times lower than agricultural dilutions, followed by herbicides and then insecticides, with very similar profiles in all cell types. Despite its relatively benign reputation, Roundup was among the most toxic herbicides and insecticides tested. Most importantly, 8 formulations out of 9 were up to one thousand times more toxic than their active principles. Our results challenge the relevance of the acceptable daily intake for pesticides because this norm is calculated from the toxicity of the active principle alone. Chronic tests on pesticides may not reflect relevant environmental exposures if only one ingredient of these mixtures is tested alone.

  20. Hybridization of two major termite invaders as a consequence of human activity.

    Chouvenc, Thomas; Helmick, Ericka E; Su, Nan-Yao

    2015-01-01

    While hybridization of an invasive species with a native species is a common occurrence, hybridization between two invasive species is rare. Formosan subterranean termites (Coptotermes formosanus) and Asian subterranean termites (C. gestroi) are both ecologically successful and are the two most economically important termite pests in the world. Both species have spread throughout many areas of the world due to human activity; however, their distributions overlap in only three narrow areas because of distinct ecological requirements. In south Florida, where C. formosanus and C. gestroi are both invasive, the dispersal flight seasons of both species overlapped for the first time on record in 2013 and 2014. Pairings of heterospecific individuals were readily observed in the field and C. gestroi males preferentially engaged in mating behavior with C. formosanus females rather than females from their own species. In the laboratory, heterospecific and conspecific pairings had an equal colony establishment rate, but heterospecific incipient colonies had twice the growth rate of conspecific incipient colonies, suggesting a potential case of hybrid vigor. As all pre-zygotic barriers were lifted between the two species in the field, the apparent absence of post-zygotic barriers in the laboratory raises the possibility for introgressive hybridization in south Florida. While laboratory observations remain to be confirmed in the field, and the alate hybrid fertility is currently unknown, our results raise a tangible concern about the hybridization of two major destructive pest species. Such hybridization would likely be associated with a new economic impact.

  1. Hybridization of two major termite invaders as a consequence of human activity.

    Thomas Chouvenc

    Full Text Available While hybridization of an invasive species with a native species is a common occurrence, hybridization between two invasive species is rare. Formosan subterranean termites (Coptotermes formosanus and Asian subterranean termites (C. gestroi are both ecologically successful and are the two most economically important termite pests in the world. Both species have spread throughout many areas of the world due to human activity; however, their distributions overlap in only three narrow areas because of distinct ecological requirements. In south Florida, where C. formosanus and C. gestroi are both invasive, the dispersal flight seasons of both species overlapped for the first time on record in 2013 and 2014. Pairings of heterospecific individuals were readily observed in the field and C. gestroi males preferentially engaged in mating behavior with C. formosanus females rather than females from their own species. In the laboratory, heterospecific and conspecific pairings had an equal colony establishment rate, but heterospecific incipient colonies had twice the growth rate of conspecific incipient colonies, suggesting a potential case of hybrid vigor. As all pre-zygotic barriers were lifted between the two species in the field, the apparent absence of post-zygotic barriers in the laboratory raises the possibility for introgressive hybridization in south Florida. While laboratory observations remain to be confirmed in the field, and the alate hybrid fertility is currently unknown, our results raise a tangible concern about the hybridization of two major destructive pest species. Such hybridization would likely be associated with a new economic impact.

  2. Major Pesticides Are More Toxic to Human Cells Than Their Declared Active Principles

    Spiroux de Vendômois, Joël; Séralini, Gilles-Eric

    2014-01-01

    Pesticides are used throughout the world as mixtures called formulations. They contain adjuvants, which are often kept confidential and are called inerts by the manufacturing companies, plus a declared active principle, which is usually tested alone. We tested the toxicity of 9 pesticides, comparing active principles and their formulations, on three human cell lines (HepG2, HEK293, and JEG3). Glyphosate, isoproturon, fluroxypyr, pirimicarb, imidacloprid, acetamiprid, tebuconazole, epoxiconazole, and prochloraz constitute, respectively, the active principles of 3 major herbicides, 3 insecticides, and 3 fungicides. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. Fungicides were the most toxic from concentrations 300–600 times lower than agricultural dilutions, followed by herbicides and then insecticides, with very similar profiles in all cell types. Despite its relatively benign reputation, Roundup was among the most toxic herbicides and insecticides tested. Most importantly, 8 formulations out of 9 were up to one thousand times more toxic than their active principles. Our results challenge the relevance of the acceptable daily intake for pesticides because this norm is calculated from the toxicity of the active principle alone. Chronic tests on pesticides may not reflect relevant environmental exposures if only one ingredient of these mixtures is tested alone. PMID:24719846

  3. Regional differences in unmet need for contraception in Kenya: insights from survey data.

    Wafula, Sam W

    2015-10-14

    Women are described as experiencing unmet need for contraception if they are fecund, sexually active and wish to postpone or limit childbearing but fail to use contraception to do so. The consequences of unmet need include unwanted pregnancy, induced abortions, school dropout due to pregnancy and premature maternal deaths. Global efforts aimed at addressing the adverse effects of unmet need abound. In Kenya, one in every four married women in the reproductive age bracket (15-49 years) has unmet need for contraception. Regional differences exist but the reasons behind these differences remain poorly understood. The purpose of this study was to examine the extent to which regional differentials in unmet need for contraception exists and to explain the regional differences in unmet need for contraception in Kenya. The paper used the Kenya Demographic and Health Survey (2008/09) data. Unmet need for contraception was measured based on the revised estimates contained in the survey. Summary statistics were used to show the percentage differences in the values of selected covariates across the high and low unmet need zones. The dependent variable had three categories: no unmet need, unmet need for spacing and unmet need for limiting births. The categorical nature of this dependent variable which is not ordered in any way lends itself to the use of multinomial logistic regression. The paper applied the seemingly unrelated estimation (suest) test to ascertain whether the covariate coefficients between the high and low unmet need zones were different. Stata Version 13.0 was used for analysis. The percentage values of the selected covariates of unmet need for contraception were much higher in the high unmet need zone as compared to those observed in the low unmet need zones. On the overall, 15.4 % of women in the high unmet need zone had unmet need to space their next birth as compared to 8.6 % of their counterparts. Likewise, the percentage of women who wanted to limit

  4. A study of particulate emissions during 23 major industrial fires: Implications for human health.

    Griffiths, Simon D; Chappell, Philip; Entwistle, Jane A; Kelly, Frank J; Deary, Michael E

    2018-03-01

    Public exposure to significantly elevated levels of particulate matter (PM) as a result of major fires at industrial sites is a worldwide problem. Our paper describes how the United Kingdom developed its Air Quality in Major Incidents (AQinMI) service to provide fire emission plume concentration data for use by managers at the time of the incident and to allow an informed public health response. It is one of the first civilian services of its type anywhere in the world. Based on the involvement of several of the authors in the AQinMI service, we describe the service's function, detail the nature of fires covered by the service, and report for the first time on the concentration ranges of PM to which populations may be exposed in major incident fires. We also consider the human health impacts of short-term exposure to significantly elevated PM concentrations and reflect on the appropriateness of current short-term guideline values in providing public health advice. We have analysed monitoring data for airborne PM (≤10μm, PM 10 ;≤2.5μm, PM 2.5 and ≤1.0μm, PM 1 ) collected by AQinMI teams using an Osiris laser light scattering monitor, the UK Environment Agency's 'indicative standard' equipment, during deployment to 23 major incident industrial fires. In this context, 'indicative' is applied to monitoring equipment that provides confirmation of the presence of particulates and indicates a measured mass concentration value. Incident-averaged concentrations ranged from 38 to 1450μgm -3 for PM 10 and 7 to 258μgm -3 for PM 2.5 . Of concern was that, for several incidents, 15-min averaged concentrations reached >6500μgm -3 for PM 10 and 650μgm -3 for PM 2.5 , though such excursions tended to be of relatively short duration. In the absence of accepted very short-term (15-min to 1-h) guideline values for PM 10 and PM 2.5, we have analysed the relationship between the 1-h and 24-h threshold values and whether the former can be used as a predictor of longer

  5. Significant unmet oral health needs of homebound elderly adults.

    Ornstein, Katherine A; DeCherrie, Linda; Gluzman, Rima; Scott, Elizabeth S; Kansal, Jyoti; Shah, Tushin; Katz, Ralph; Soriano, Theresa A

    2015-01-01

    To assess the oral health status, use of dental care, and dental needs of homebound elderly adults and to determine whether medical diagnoses or demographic factors influenced perceived oral health. Cross-sectional analysis. Participants' homes in New York City. Homebound elderly adults (N = 125). A trained dental research team conducted a comprehensive clinical examination in participants' homes and completed a dental use and needs survey and the Geriatric Oral Health Assessment Index. Participants who reported a high level of unmet oral health needs were more likely to be nonwhite, although this effect was not significant in multivariate analysis. Individual medical diagnoses and the presence of multiple comorbidities were not associated with unmet oral health needs. The oral health status of homebound elderly adults was poor regardless of their medical diagnoses. High unmet oral health needs combined with strong desire to receive dental care suggests there is a need to improve access to dental care for this growing population. In addition to improving awareness of geriatricians and primary care providers who care for homebound individuals, the medical community must partner with the dental community to develop home-based programs for older adults. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

  6. Voluntary sterilization in Serbia: Unmet need?

    Rašević Mirjana M.

    2002-01-01

    Full Text Available Is voluntary sterilization as a birth control method accepted in Serbia? This is certainly a question that is being imposed for research, regardless of the fact that voluntary sterilization is neither accessible nor promoted. Most importantly because there is no understanding in the social nor political sphere for legalization of voluntary sterilization as a form of birth control, apart from the clear necessity for this, first, step. They are: the recognition that voluntary sterilization is an efficient and safe birth control method, respectability of basic human as well as sexual and reproductive rights, spreading of sterilization as a form of birth control among population of both developed and developing countries and an epidemic diffusion of repeated induced abortions in Serbia. Thus individual recognition of the advantages of relying on voluntary sterilization, in a non-encouraging atmosphere, certainly represents one more argument to enable couples to prevent conception by sterilization. Since it was impossible to carry out a representative research among the population of men and women who are at risk for conception, an attempt was made to obtain a reply to the set question among women who decided to induce abortion. It was done out of at least two reasons. The first being that women with induced abortion in their reproductive history were the target group for voluntary sterilization. The second reason was based on the assumption that bringing a decision on induced abortion is preceded by the reconsideration of an earlier adopted strategy regarding children, giving birth and contraception and thus its rational component is revealed more and therefore more easily measurable. The research was carried out in the University Clinic of Obstetrics and Gynecology 'Narodni front' in Belgrade from January 21st o March 1st 2002, and included 296 women. By comparing the social and demographic characteristics of the female respondents, as well as

  7. Determinants of unmet need for family planning among currently married women in Dangila town administration, Awi Zone, Amhara regional state; a cross sectional study.

    Genet, Ewnetu; Abeje, Gedefaw; Ejigu, Tadese

    2015-05-13

    Unmet need for family planning is a major problem of developing countries. Evidences about unmet need for family planning and associated factors are not enough in Dangila town. Therefore, this study was done to assess the magnitude and determinants of unmet need for family planning among currently married women in Dangila town. Community based cross sectional study design was used to collect data from a total of 551 currently married women from February to March 2014. Data were collected using pretested structured interviewer administered questionnaire after written consent was obtained from respondents. Collected data were edited, coded, and entered to SPSS version 16.0. Bivariate and multivariable logistic regression analyses were done to identify determinants of unmet need for family planning. This study revealed that 17.4 % of married women had unmet need for family planning. In this study, women who were housewife/farmers were about 7 [OR = 6.81 (1.91-24.29)] times more likely to have unmet need compared to employed women. Women who were not counseled about family planning by health workers [OR = 6.76 (3.17-14.42)], women whose partner had non-supportive attitude for family planning use [OR = 3.34 (1.26-8.90)] and rural women [OR = 17.65 (4.35-71.67)] were also more likely to have unmet need for family planning. About 33 %, 32 %, 23.5 % and 11.8 % of women mentioned less perceived risk of pregnancy due to breast feeding, fear of side effects, partner opposition and religious prohibition respectively as reasons for not using contraceptives at the time of interview. The level of unmet need for family planning in the study area is still high compared to the target set (10 %) in the national family planning guide plan of Ethiopia to be achieved by the end of 2015. Therefore, it is important to strengthen counseling and partner involvement in Dangila town to reduce unmet need for family planning.

  8. Sociodemographic disparities associated with perceived causes of unmet need for mental health care.

    Alang, Sirry M

    2015-12-01

    Mental disorders are among the leading causes of disability in the United States. In 2011, over 10 million adults felt that even though they needed treatment for mental health problems, they received insufficient or no mental health care and reported unmet need. This article assesses associations between sociodemographic characteristics and perceived causes of unmet needs for mental health care. A sample of 2,564 adults with unmet mental health need was obtained from the National Survey on Drug Use and Health. Outcome variables were 5 main reasons for unmet need: cost, stigma, minimization, low perceived treatment effectiveness, and structural barriers. Each cause of unmet need was regressed on sociodemographic, health, and service use characteristics. Women had higher odds of cost-related reasons for unmet need than men. Odds of stigma and structural barriers were greater among Blacks than Whites, and among rural than metropolitan residents. Compared with the uninsured, insured persons were less likely to report cost barriers. However, insured persons had higher odds of stigma and minimization of mental disorders. Insurance alone is unlikely to resolve the problem of unmet need. Understanding the social epidemiology of perceived unmet need will help identify populations at risk of not receiving mental health care or insufficient care. Focusing on specific programs and services that are designed to address the causes of perceived unmet need in particular populations is important. Future research should explore how intersecting social statuses affect the likelihood of perceived unmet need. (c) 2015 APA, all rights reserved).

  9. Leishmania major Infection Activates NF-κB and Interferon Regulatory Factors 1 and 8 in Human Dendritic Cells▿

    Jayakumar, Asha; Donovan, Michael J.; Tripathi, Vinita; Ramalho-Ortigao, Marcelo; McDowell, Mary Ann

    2008-01-01

    The salient feature of dendritic cells (DC) is the initiation of appropriate adaptive immune responses by discriminating between pathogens. Using a prototypic model of intracellular infection, we previously showed that Leishmania major parasites prime human DC for efficient interleukin-12 (IL-12) secretion. L. major infection is associated with self-limiting cutaneous disease and powerful immunity. In stark contrast, the causative agent of visceral leishmaniasis, Leishmania donovani, does not prime human DC for IL-12 production. Here, we report that DC priming by L. major infection results in the early activation of NF-κB transcription factors and the up-regulation and nuclear translocation of interferon regulatory factor 1 (IRF-1) and IRF-8. The inhibition of NF-κB activation by the pretreatment of DC with caffeic acid phenethyl ester blocks L. major-induced IRF-1 and IRF-8 activation and IL-12 expression. We further demonstrate that IRF-1 and IRF-8 obtained from L. major-infected human DC specifically bind to their consensus binding sites on the IL-12p35 promoter, indicating that L. major infection either directly stimulates a signaling cascade or induces an autocrine pathway that activates IRF-1 and IRF-8, ultimately resulting in IL-12 transcription. PMID:18316378

  10. Structural Analysis of Major Species Barriers between Humans and Palm Civets for Severe Acute Respiratory Syndrome Coronavirus Infections

    Li, Fang (UMM)

    2008-09-23

    It is believed that a novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV), was passed from palm civets to humans and caused the epidemic of SARS in 2002 to 2003. The major species barriers between humans and civets for SARS-CoV infections are the specific interactions between a defined receptor-binding domain (RBD) on a viral spike protein and its host receptor, angiotensin-converting enzyme 2 (ACE2). In this study a chimeric ACE2 bearing the critical N-terminal helix from civet and the remaining peptidase domain from human was constructed, and it was shown that this construct has the same receptor activity as civet ACE2. In addition, crystal structures of the chimeric ACE2 complexed with RBDs from various human and civet SARS-CoV strains were determined. These structures, combined with a previously determined structure of human ACE2 complexed with the RBD from a human SARS-CoV strain, have revealed a structural basis for understanding the major species barriers between humans and civets for SARS-CoV infections. They show that the major species barriers are determined by interactions between four ACE2 residues (residues 31, 35, 38, and 353) and two RBD residues (residues 479 and 487), that early civet SARS-CoV isolates were prevented from infecting human cells due to imbalanced salt bridges at the hydrophobic virus/receptor interface, and that SARS-CoV has evolved to gain sustained infectivity for human cells by eliminating unfavorable free charges at the interface through stepwise mutations at positions 479 and 487. These results enhance our understanding of host adaptations and cross-species infections of SARS-CoV and other emerging animal viruses.

  11. Major differences between human atopic dermatitis and murine models as determined by global transcriptomic profiling

    Ewald, David Adrian; Noda, Shinji; Oliva, Margeaux

    2017-01-01

    , and a comparison of these models with the human AD transcriptomic fingerprint is lacking. We sought to evaluate the transcriptomic profiles of six common murine models and determine how they relate to human AD skin. Transcriptomic profiling was performed using microarrays and qRT-PCR on biopsies from NC/Nga, flaky...

  12. Humans with chimpanzee-like major histocompatibility complex-specificities control HIV-1 infection

    Hoof, Ilka; Kesmir, Can; Lund, Ole

    2008-01-01

    and the progression rate to AIDS. Chimpanzees control HIV-1 viral replication and develop a chronic infection without progressing to AIDS. A similar course of disease is observed in human long-term non-progressors. Objective: To investigate if long-term non-progressors and chimpanzees have functional similarities...... in their MHC class I repertoire. Methods: We compared the specificity of groups of human MHC molecules associated with different levels of viremia in HIV-1 infected individuals with those of chimpanzee. Results and conclusion: We demonstrate that human MHC with control of HIV-1 viral load share binding motifs...... with chimpanzee MHC. Moreover, we find that chimpanzee and human MHC associated with low viral load are predicted to elicit broader Gag-specific immune responses than human MHC associated with high viral load, thus supporting earlier findings that Gag-specific immune responses are essential for HIV-1 control....

  13. Measuring unmet obstetric need at district level: how an epidemiological tool can affect health service organization and delivery.

    Guindo, Gabriel; Dubourg, Dominique; Marchal, Bruno; Blaise, Pierre; De Brouwere, Vincent

    2004-10-01

    A national retrospective survey on the unmet need for major obstetric surgery using the Unmet Obstetric Need Approach was carried out in Mali in 1999. In Koutiala, the district health team decided to carry on the monitoring of the met need for several years in order to assess their progress over time. The first prospective study, for 1999, estimated that more than 100 women in need of obstetric care never reached the hospital and probably died as a consequence. This surprising result shocked the district health team and the resulting increased awareness of service deficits triggered operational measures to tackle the problem. The Unmet Obstetric Need study in Koutiala district was implemented without financial support and only limited external technical back-up. The appropriation of the study by the district team for solving local problems of access to obstetric care may have contributed to the success of the experience. Used as a health service management tool, the study and its results started a dialogue between the hospital staff and both health centre staff and community representatives. This had not only the effect of triggering consideration of coverage, but also of quality of obstetric care. Copyright 2004 Oxford University Press

  14. Quality assurance of human error modelling in a major probabilistic risk assessment programme

    Rycraft, H.S.

    1990-01-01

    A method of incorporating the consideration of operator error within a major PRA exercise is described along with the quality assurance procedures employed to ensure a quality product. The exercise was undertaken at the Sellafield Reprocessing Plant. (author)

  15. Examining the evidence for major histocompatibility complex-dependent mate selection in humans and nonhuman primates

    Winternitz, Jamie Caroline; Abbate, J. L.

    2015-01-01

    Roč. 6, 13 May (2015), s. 73-88 ISSN 1179-7274 Institutional support: RVO:68081766 Keywords : major histocompatibility complex * sexual selection * olfaction * facial attraction * parasite resistance * inbreeding avoidance Subject RIV: EB - Genetics ; Molecular Biology

  16. Distribution of class ii major histocompatibility complex antigenexpressing cells in human dental pulp with carious lesions

    Tetiana Haniastuti

    2012-09-01

    Full Text Available Background: Dental caries is a bacterial infection which causes destruction of the hard tissues of the tooth. Exposure of the dentin to the oral environment as a result of caries inevitably results in a cellular response in the pulp. The major histocompatibility complex (MHC is a group of genes that code for cell-surface histocompatibility antigens. Cells expressing class II MHC molecules participate in the initial recognition and the processing of antigenic substances to serve as antigen-presenting cells. Purpose: The aim of the study was to elucidate the alteration in the distribution of class II MHC antigen-expressing cells in human dental pulp as carious lesions progressed toward the pulp. Methods: Fifteen third molars with caries at the occlusal site at various stages of decay and 5 intact third molars were extracted and used in this study. Before decalcifying with 10% EDTA solution (pH 7.4, all the samples were observed by micro-computed tomography to confirm the lesion condition three-dimensionally. The specimens were then processed for cryosection and immunohistochemistry using an anti-MHC class II monoclonal antibody. Results: Class II MHC antigen-expressing cells were found both in normal and carious specimens. In normal tooth, the class II MHC-immunopositive cells were observed mainly at the periphery of the pulp tissue. In teeth with caries, class II MHC-immunopositive cells were located predominantly subjacent to the carious lesions. As the caries progressed, the number of class II MHC antigen-expressing cells was increased. Conclusion: The depth of carious lesions affects the distribution of class II MHC antigen-expressing cells in the dental pulp.Latar belakang: Karies merupakan penyakit infeksi bakteri yang mengakibatkan destruksi jaringan keras gigi. Dentin yang terbuka akibat karies akan menginduksi respon imun seluler pada pulpa. Kompleks histokompatibilitas utama (MHC merupakan sekumpulan gen yang mengkode histokompatibilitas

  17. Indoor air and human health: major indoor air pollutants and their health implications

    1984-01-01

    This publication is a collection of abstracts of papers presented at the Indoor Air and Human Health symposium. Session titles include: Radon, Microorganisms, Passive Cigarette Smoke, Combustion Products, Organics, and Panel and Audience Discussion

  18. Indoor air and human health: major indoor air pollutants and their health implications

    1984-01-01

    This publication is a collection of abstracts of papers presented at the Indoor Air and Human Health symposium. Session titles include: Radon, Microorganisms, Passive Cigarette Smoke, Combustion Products, Organics, and Panel and Audience Discussion.

  19. Major Shifts in Glial Regional Identity Are a Transcriptional Hallmark of Human Brain Aging

    Soreq, Lilach; Rose, Jamie; Soreq, Eyal; Hardy, John; Trabzuni, Daniah; Cookson, Mark R.; Smith, Colin; Ryten, Mina; Patani, Rickie; Ule, Jernej

    2017-01-01

    Summary Gene expression studies suggest that aging of the human brain is determined by a complex interplay of molecular events, although both its region- and cell-type-specific consequences remain poorly understood. Here, we extensively characterized aging-altered gene expression changes across ten human brain regions from 480 individuals ranging in?age from 16 to 106 years. We show that astrocyte-?and oligodendrocyte-specific genes, but not neuron-specific genes, shift their regional express...

  20. Exploring patient experiences with prescription medicines to identify unmet patient needs: implications for research and practice.

    Kucukarslan, Suzan N; Lewis, Nancy J W; Shimp, Leslie A; Gaither, Caroline A; Lane, Daniel C; Baumer, Andrea L

    2012-01-01

    Pharmacy services are offered to patients, and often, they decline participation. Research is needed to better understand patients' unmet needs when taking prescribed medications. To identify and characterize patients' unmet needs related to using prescribed medication for chronic conditions. Focus groups of patients using prescription medication for chronic conditions discussed their experiences with medications, starting from initial diagnosis to ongoing management. Sessions involved 40 patients from 1 Midwestern U.S. state. Major themes were identified using content analysis. Three major themes emerged. First, patients seek information to understand their health condition and treatment rationale. Patients form an illness perception (its consequence, controllability, cause, and duration) that dictates their actions. Second, patients desire to be involved in treatment decisions, and they often feel that decisions are made for them without their understanding of the risk-to-benefit trade-off. Third, patients monitor the impact of treatment decisions to determine if anticipated outcomes are achieved. The results were consistent with Dowell's therapeutic alliance model (TAM) and Leventhal's common sense model (CSM). The TAM can be used to model the consultative services between pharmacists and patients. The impact of the new services (or interventions) can be evaluated using the CSM. Patients expressed a strong desire to be involved in their treatment decisions. The effectiveness of medication therapy management services may be enhanced if pharmacists build on patients' desire to be involved in their treatment decisions and assist them to understand the role of medications and their risks and expected outcomes within the context of the patients' perceptions of illness and desired coping strategies. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Murine but not human basophil undergoes cell-specific proteolysis of a major endoplasmic reticulum chaperone.

    Bei Liu

    Full Text Available Basophil has been implicated in anti-parasite defense, allergy and in polarizing T(H2 response. Mouse model has been commonly used to study basophil function although the difference between human and mouse basophils is underappreciated. As an essential chaperone for multiple Toll-like receptors and integrins in the endoplasmic reticulum, gp96 also participates in general protein homeostasis and in the ER unfolded protein response to ensure cell survival during stress. The roles of gp96 in basophil development are unknown.We genetically delete gp96 in mice and examined the expression of gp96 in basophils by Western blot and flow cytometry. We compared the expression pattern of gp96 between human and mouse basophils.We found that gp96 was dispensable for murine basophil development. Moreover, gp96 was cleaved by serine protease(s in murine but not human basophils leading to accumulation of a nun-functional N-terminal ∼50 kDa fragment and striking induction of the unfolded protein response. The alteration of gp96 was unique to basophils and was not observed in any other cell types including mast cells. We also demonstrated that the ectopic expression of a mouse-specific tryptase mMCP11 does not lead to gp96 cleavage in human basophils.Our study revealed a remarkable biochemical event of gp96 silencing in murine but not human basophils, highlighting the need for caution in using mouse models to infer the function of basophils in human immune response. Our study also reveals a novel mechanism of shutting down gp96 post-translationally in regulating its function.

  2. Murine but not human basophil undergoes cell-specific proteolysis of a major endoplasmic reticulum chaperone.

    Liu, Bei; Staron, Matthew; Li, Zihai

    2012-01-01

    Basophil has been implicated in anti-parasite defense, allergy and in polarizing T(H)2 response. Mouse model has been commonly used to study basophil function although the difference between human and mouse basophils is underappreciated. As an essential chaperone for multiple Toll-like receptors and integrins in the endoplasmic reticulum, gp96 also participates in general protein homeostasis and in the ER unfolded protein response to ensure cell survival during stress. The roles of gp96 in basophil development are unknown. We genetically delete gp96 in mice and examined the expression of gp96 in basophils by Western blot and flow cytometry. We compared the expression pattern of gp96 between human and mouse basophils. We found that gp96 was dispensable for murine basophil development. Moreover, gp96 was cleaved by serine protease(s) in murine but not human basophils leading to accumulation of a nun-functional N-terminal ∼50 kDa fragment and striking induction of the unfolded protein response. The alteration of gp96 was unique to basophils and was not observed in any other cell types including mast cells. We also demonstrated that the ectopic expression of a mouse-specific tryptase mMCP11 does not lead to gp96 cleavage in human basophils. Our study revealed a remarkable biochemical event of gp96 silencing in murine but not human basophils, highlighting the need for caution in using mouse models to infer the function of basophils in human immune response. Our study also reveals a novel mechanism of shutting down gp96 post-translationally in regulating its function.

  3. Vaginal biological and sexual health--the unmet needs.

    Graziottin, A

    2015-01-01

    The vagina is a most neglected organ. It is usually clinically considered with a minimalistic view, as a 'connecting tube' for a number of physiologic functions: passage of menstrual blood, intercourse, natural conception and delivery. Unmet needs include, but are not limited to, respect of vaginal physiologic biofilms; diagnosis and care of the optimal tone of the levator ani, which surrounds and partly support it; care of its anatomic integrity at and after delivery and at pelvic/vaginal surgery; care of long-term consequences of pelvic radiotherapy; long-term care of the atrophic changes it will undergo after the menopause, unless appropriate, at least local, estrogen therapy is used; appreciation and respect of its erotic meaning, as a loving, receptive, 'bonding' organ for the couple. The vaginal erotic value is key as a non-visible powerful center of femininity and sexuality, deeply and secretly attractive in terms of taste, scent (together with the vulva), touch and proprioception. The most welcoming when lubrication, softness and vaginal orgasm award the woman and the partner with the best of pleasures. Prevention of sexual/vaginal abuse is a very neglected unmet need, as well. Who cares?

  4. Examining the unmet need in adults with severe asthma

    M. R. Partridge

    2007-09-01

    Full Text Available Asthma currently affects an estimated 300 million people worldwide and the number is expected to rise to 400 million by 2025. Asthma morbidity remains high and the economic burden is significant. Approximately 20% of patients have severe persistent asthma. As patients with severe asthma often have a variety of conditions that may coexist with or be mistaken for asthma, careful diagnosis and management are essential, and adhering to a protocol for investigations is helpful. For patients with severe persistent asthma, the Global Initiative for Asthma 2005 guidelines recommend the use of high-dose inhaled corticosteroids in combination with a long-acting beta2-agonist, with one or more additional controller medications if required (step 4 therapy. However, recent studies have shown that asthma remains inadequately controlled in many patients with severe asthma, despite treatment in accordance with guidelines. Patients with severe asthma have the highest healthcare utilisation and mortality, and there is clearly an unmet need for the effective and safe treatment of patients with severe persistent allergic asthma who remain symptomatic despite optimised standard treatment. The latest guidelines suggest that omalizumab may address this unmet need.

  5. Heterogeneity in Human Capital Investments: High School Curriculum, College Major, and Careers

    Altonji, Joseph G.; Blom, Erica; Meghir, Costas

    2012-01-01

    Motivated by the large differences in labor market outcomes across college majors, we survey the literature on the demand for and return to high school and postsecondary education by field of study. We combine elements from several papers to provide a dynamic model of education and occupation choice that stresses the roles of the specificity of…

  6. Podocalyxin as a major pluripotent marker and novel keratan sulfate proteoglycan in human embryonic and induced pluripotent stem cells.

    Toyoda, Hidenao; Nagai, Yuko; Kojima, Aya; Kinoshita-Toyoda, Akiko

    2017-04-01

    Podocalyxin (PC) was first identified as a heavily sialylated transmembrane protein of glomerular podocytes. Recent studies suggest that PC is a remarkable glycoconjugate that acts as a universal glyco-carrier. The glycoforms of PC are responsible for multiple functions in normal tissue, human cancer cells, human embryonic stem cells (hESCs), and human induced pluripotent stem cells (hiPSCs). PC is employed as a major pluripotent marker of hESCs and hiPSCs. Among the general antibodies for human PC, TRA-1-60 and TRA-1-81 recognize the keratan sulfate (KS)-related structures. Therefore, It is worthwhile to summarize the outstanding chemical characteristic of PC, including the KS-related structures. Here, we review the glycoforms of PC and discuss the potential of PC as a novel KS proteoglycan in undifferentiated hESCs and hiPSCs.

  7. Identifying the Learning Styles and Instructional Tool Preferences of Beginning Food Science and Human Nutrition Majors

    Bohn, D. M.; Rasmussen, C. N.; Schmidt, S. J.

    2004-01-01

    Learning styles vary among individuals, and understanding which instructional tools certain learning styles prefer can be utilized to enhance student learning. Students in the introductory Food Science and Human Nutrition course (FSHN 101), taught at the Univ. of Illinois at Urbana-Champaign, were asked to complete Gregorc's Learning Style…

  8. Bipolar cell gap junctions serve major signaling pathways in the human retina.

    Kántor, Orsolya; Varga, Alexandra; Nitschke, Roland; Naumann, Angela; Énzsöly, Anna; Lukáts, Ákos; Szabó, Arnold; Németh, János; Völgyi, Béla

    2017-08-01

    Connexin36 (Cx36) constituent gap junctions (GJ) throughout the brain connect neurons into functional syncytia. In the retina they underlie the transmission, averaging and correlation of signals prior conveying visual information to the brain. This is the first study that describes retinal bipolar cell (BC) GJs in the human inner retina, whose function is enigmatic even in the examined animal models. Furthermore, a number of unique features (e.g. fovea, trichromacy, midget system) necessitate a reexamination of the animal model results in the human retina. Well-preserved postmortem human samples of this study are allowed to identify Cx36 expressing BCs neurochemically. Results reveal that both rod and cone pathway interneurons display strong Cx36 expression. Rod BC inputs to AII amacrine cells (AC) appear in juxtaposition to AII GJs, thus suggesting a strategic AII cell targeting by rod BCs. Cone BCs serving midget, parasol or koniocellular signaling pathways display a wealth of Cx36 expression to form homologously coupled arrays. In addition, they also establish heterologous GJ contacts to serve an exchange of information between parallel signaling streams. Interestingly, a prominent Cx36 expression was exhibited by midget system BCs that appear to maintain intimate contacts with bistratified BCs serving other pathways. These findings suggest that BC GJs in parallel signaling streams serve both an intra- and inter-pathway exchange of signals in the human retina.

  9. Epidemiology of Sepsis-like Illness in Young Infants Major Role of Enterovirus and Human Parechovirus

    de Jong, Eveline P.; van den Beuken, Monique G. A.; van Elzakker, Erika P. M.; Wolthers, Katja C.; Sprij, Arwen J.; Lopriore, Enrico; Walther, Frans J.; Brus, Frank

    2018-01-01

    Background: Sepsis-like illness is a main cause for hospital admission in young infants. Our aim was to investigate incidence, epidemiology and clinical characteristics of enterovirus (EV) and human parechovirus (HPeV) infections in young infants with sepsis-like illness. Methods: This is a

  10. Major differences between human atopic dermatitis and murine models, as determined by using global transcriptomic profiling

    Ewald, David A.; Noda, Shinji; Oliva, Margeaux

    2017-01-01

    , and a comparison of these models with the human AD transcriptomic fingerprint is lacking. Objective We sought to evaluate the transcriptomic profiles of 6 common murine models and determine how they relate to human AD skin. Methods Transcriptomic profiling was performed by using microarrays and quantitative RT......-PCR on biopsy specimens from NC/Nga, flaky tail, Flg-mutated, ovalbumin-challenged, oxazolone-challenged, and IL-23–injected mice. Gene expression data of patients with AD, psoriasis, and contact dermatitis were obtained from previous patient cohorts. Criteria of a fold change of 2 or greater and a false...... discovery rate of 0.05 or less were used for gene arrays. Results IL-23–injected, NC/Nga, and oxazolone-challenged mice show the largest homology with our human meta-analysis–derived AD transcriptome (37%, 18%, 17%, respectively). Similar to human AD, robust TH1, TH2, and also TH17 activation are seen in IL...

  11. Human disturbance is a major determinant of wildlife distribution in Himalayan midhill landscapes of Nepal

    Paudel, Prakash K.; Kindlmann, Pavel

    2012-01-01

    Roč. 15, č. 3 (2012), s. 283-293 ISSN 1367-9430 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0073 Institutional support: RVO:67179843 Keywords : human disturbance * midhills * wildlife conservation * mountain landscape * conservation challenges Subject RIV: EH - Ecology, Behaviour Impact factor: 2.692, year: 2012

  12. 5' diversity of human hepatic PXR (NR1I2) transcripts and identification of the major transcription initiation site.

    Kurose, Kouichi; Koyano, Satoru; Ikeda, Shinobu; Tohkin, Masahiro; Hasegawa, Ryuichi; Sawada, Jun-Ichi

    2005-05-01

    The human pregnane X receptor (PXR) is a crucial regulator of the genes encoding several major cytochrome P450 enzymes and transporters, such as CYP3A4 and MDR1, but its own transcriptional regulation remains unclear. To elucidate the transcriptional mechanisms of human PXR gene, we first endeavored to identify the transcription initiation site of human PXR using 5'-RACE. Five types of 5'-variable transcripts (a, b, c, d, and e) with common exon 2 sequence were found, and comparison of these sequences with the genomic sequence suggested that their 5' diversity is derived from initiation by alternative promoters and alternative splicing. None of the exons found in our study contain any new in-frame coding regions. Newly identified introns IVS-a and IVS-b were found to have CT-AC splice sites that do not follow the GT-AG rule of conventional donor and acceptor splice sites. Of the five types of 5' variable transcripts identified, RT-PCR showed that type-a was the major transcript type. Four transcription initiation sites (A-D) for type-a transcript were identified by 5'-RACE using GeneRacer RACE Ready cDNA (human liver) constructed by the oligo-capping method. Putative TATA boxes were located approximately 30 bp upstream from the transcriptional start sites of the major transcript (C) and the longest minor transcript (A) expressed in the human liver. These results indicate that the initiation of transcription of human PXR is more complex than previously reported.

  13. Condition-dependent clutch desertion in Great Tit (Parus major) females subjected to human disturbance

    2011-01-01

    Abstract Nest desertion behaviour in relation to body condition and timing of breeding was studied in Great Tit (Parus major) females during two breeding seasons. Desertion, most likely unintentionally provoked by catching females during the incubation period, occurred at a very high rate with 41.2 and 25.6% of deserted first clutches in the two study years. The association between desertion probability, body condition (index calculated as residuals from the regression of body mass...

  14. Bacteria associated with human saliva are major microbial components of Ecuadorian indigenous beers (chicha

    Ana L. Freire

    2016-04-01

    Full Text Available Indigenous beers (chicha are part of the indigenous culture in Ecuador. The fermentation process of these beers probably relies on microorganisms from fermented substrates, environment and human microbiota. We analyzed the microbiota of artisanal beers (including a type of beer produced after chewing boiled cassava using bacterial culture and 16S ribosomal RNA (rRNA gene-based tag-encoded FLX amplicon pyrosequencing (bTEFAP. Surprisingly, we found that Streptococcus salivarius and Streptococcus mutans (part of the human oral microbiota were among the most abundant bacteria in chewed cassava and in non-chewed cassava beers. We also demonstrated that S. salivarius and S. mutans (isolated from these beers could proliferate in cassava mush. Lactobacillus sp. was predominantly present in most types of Ecuadorian chicha.

  15. Operator error and emotions. Operator error and emotions - a major cause of human failure

    Patterson, B.K. [Human Factors Practical Incorporated (Canada); Bradley, M. [Univ. of New Brunswick, Saint John, New Brunswick (Canada); Artiss, W.G. [Human Factors Practical (Canada)

    2000-07-01

    This paper proposes the idea that a large proportion of the incidents attributed to operator and maintenance error in a nuclear or industrial plant are actually founded in our human emotions. Basic psychological theory of emotions is briefly presented and then the authors present situations and instances that can cause emotions to swell and lead to operator and maintenance error. Since emotional information is not recorded in industrial incident reports, the challenge is extended to industry, to review incident source documents for cases of emotional involvement and to develop means to collect emotion related information in future root cause analysis investigations. Training must then be provided to operators and maintainers to enable them to know one's emotions, manage emotions, motivate one's self, recognize emotions in others and handle relationships. Effective training will reduce the instances of human error based in emotions and enable a cooperative, productive environment in which to work. (author)

  16. Operator error and emotions. Operator error and emotions - a major cause of human failure

    Patterson, B.K.; Bradley, M.; Artiss, W.G.

    2000-01-01

    This paper proposes the idea that a large proportion of the incidents attributed to operator and maintenance error in a nuclear or industrial plant are actually founded in our human emotions. Basic psychological theory of emotions is briefly presented and then the authors present situations and instances that can cause emotions to swell and lead to operator and maintenance error. Since emotional information is not recorded in industrial incident reports, the challenge is extended to industry, to review incident source documents for cases of emotional involvement and to develop means to collect emotion related information in future root cause analysis investigations. Training must then be provided to operators and maintainers to enable them to know one's emotions, manage emotions, motivate one's self, recognize emotions in others and handle relationships. Effective training will reduce the instances of human error based in emotions and enable a cooperative, productive environment in which to work. (author)

  17. Evaluation of concentrations of major and trace elements in human lung using INAA and PIXE

    Altaf, W.J.; Spyrou, N.M.

    1997-01-01

    The elemental concentrations of Br, Ca, Ce, Cl, Co, Cr, Cs, F, Fe, Hf, K, Mg, Mn, Na, O, Rb, Sb, Sc, Se, V and Zn in 15 human lung autopsy samples, taken from subjects aged more than fifty years old, were determined by instrumental neutron activation analysis (INAA) using reactor neutrons in conjunction with a high resolution detection system. Two modes of irradiation and counting were applied; namely cyclic neutron activation analysis (CNAA) and conventional neutron activation analysis. Proton induced X-ray emission (PIXE) analysis, using a proton beam emerging from a 2 MV Van de Graaff accelerator, was additionally employed and Ge, Ni, P and Ti were also identified in the lung tissue. Detection of the X-ray spectra was performed using a high resolution Si(Li) semiconductor. The relevance of these results, including a comparison between the concentrations of elements measured in a pig's lung using CNAA and those found in the human lung is discussed. (author)

  18. Purification and characterization of a major human Pneumocystis carinii surface antigen

    Lundgren, B; Lipschik, G Y; Kovacs, J A

    1991-01-01

    . To evaluate humoral immune responses to the human P. carinii protein, an enzyme-linked immunosorbent assay using purified protein was developed. Some, but not all, patients who subsequently developed P. carinii pneumonia demonstrated a serum antibody response to the surface antigen. Nearly all subjects...... without a history of P. carinii pneumonia had no detectable antibodies. Purified P. carinii proteins will greatly facilitate the investigation of host-P. carinii interactions....

  19. Friends-enemies: endogenous retroviruses are major transcriptional regulators of human DNA

    Buzdin, Anton A.; Prassolov, Vladimir; Garazha, Andrew V.

    2017-06-01

    Endogenous retroviruses are mobile genetic elements hardly distinguishable from infectious, or “exogenous”, retroviruses at the time of insertion in the host DNA. Human endogenous retroviruses (HERVs) are not rare. They gave rise to multiple families of closely related mobile elements that occupy 8% of the human genome. Together, they shape genomic regulatory landscape by providing at least 320,000 human transcription factor binding sites (TFBS) located on 110,000 individual HERV elements. The HERVs host as many as 155,000 mapped DNaseI hypersensitivity sites, which denote loci active in the regulation of gene expression or chromatin structure. The contemporary view of the HERVs evolutionary dynamics suggests that at the early stages after insertion, the HERV is treated by the host cells as a foreign genetic element, and is likely to be suppressed by the targeted methylation and mutations. However, at the later stages, when significant number of mutations has been already accumulated and when the retroviral genes are broken, the regulatory potential of a HERV may be released and recruited to modify the genomic balance of transcription factor binding sites. This process goes together with further accumulation and selection of mutations, which reshape the regulatory landscape of the human DNA. However, developmental reprogramming, stress or pathological conditions like cancer, inflammation and infectious diseases, can remove the blocks limiting expression and HERV-mediated host gene regulation. This, in turn, can dramatically alter the gene expression equilibrium and shift it to a newer state, thus further amplifying instability and exacerbating the stressful situation.

  20. Perceived unmet need and barriers to care amongst street-involved people who use illicit drugs.

    Hyshka, Elaine; Anderson, Jalene Tayler; Wild, T Cameron

    2017-05-01

    Research on perceived unmet need for care for mental health and substance use problems focuses on general populations to the detriment of hidden populations. This study describes prevalence and correlates of perceived unmet need for care in a community-based sample of street-involved people who use illicit drugs and identifies barriers to care. A sample of 320 street-involved people who use drugs participated in a structured, interviewer-assisted survey in Edmonton, Canada. The survey included the Perceived Need for Care Questionnaire, which assessed unmet need for care for mental health and substance use problems across seven service types. Logistic regression examined the associations between perceived unmet need, extent of socioeconomic marginalisation and problem severity. Barriers underlying unmet service needs were also examined. Most (82%) participants reported unmet need for one or more services during the past year. Odds of reporting one or more unmet needs were elevated amongst participants reporting substantial housing instability (adjusted odds ratio = 2.37; 95% confidence interval 1.19-4.28) and amongst participants meeting criteria for drug dependence (adjusted odds ratio = 1.22; 95% confidence interval 1.03-1.50), even after adjustment for sociodemographic covariates. Structural, rather than motivational barriers were the most commonly reported reasons underlying unmet service needs. Street-involved people who use drugs experience very high rates of perceived unmet need for care for mental health and substance use problems. General population studies on perceived unmet need are insufficient for understanding needs and barriers to care in hidden populations.[Hyshka E, Anderson JT, Wild TC. Perceived unmet need and barriers to care amongst street-involved people who use illicit drugs. Drug Alcohol Rev 2017;36:295-304]. © 2016 Australasian Professional Society on Alcohol and other Drugs.

  1. Anatomy and histology of rodent and human major salivary glands: -overview of the Japan salivary gland society-sponsored workshop-.

    Amano, Osamu; Mizobe, Kenichi; Bando, Yasuhiko; Sakiyama, Koji

    2012-10-31

    MAJOR SALIVARY GLANDS OF BOTH HUMANS AND RODENTS CONSIST OF THREE PAIRS OF MACROSCOPIC GLANDS: parotid, submandibular, and sublingual. These glands secrete serous, mucous or mixed saliva via the proper main excretory ducts connecting the glandular bodies with the oral cavity. A series of discoveries about the salivary ducts in the 17th century by Niels Stensen (1638-1686), Thomas Wharton (1614-1673), and Caspar Bartholin (1655-1738) established the concept of exocrine secretion as well as salivary glands. Recent investigations have revealed the endocrine functions of parotin and a variety of cell growth factors produced by salivary glands.The present review aims to describe macroscopic findings on the major salivary glands of rodents and the microscopic differences between those of humans and rodents, which review should be of interest to those researchers studying salivary glands.

  2. Estimated Human and Economic Burden of Four Major Adult Vaccine-Preventable Diseases in the United States, 2013

    McLaughlin, John M.; McGinnis, Justin J.; Tan, Litjen; Mercatante, Annette; Fortuna, Joseph

    2015-01-01

    Low uptake of routinely recommended adult immunizations is a public health concern. Using data from the peer-reviewed literature, government disease-surveillance programs, and the US Census, we developed a customizable model to estimate human and economic burden caused by four major adult vaccine-preventable diseases (VPD) in 2013 in the United States, and for each US state individually. To estimate the number of cases for each adult VPD for a given population, we multiplied age-specific inci...

  3. Human skin wounds: A major and snowballing threat to public health and the economy

    Sen, C.K.; Gordillo, G.M.; Roy, S.

    2009-01-01

    . Forty million inpatient surgical procedures were performed in the United States in 2000, followed closely by 31.5 million outpatient surgeries. The need for post-surgical wound care is sharply on the rise. Emergency wound care in an acute setting has major significance not only in a war setting but also...... in homeland preparedness against natural disasters as well as against terrorism attacks. An additional burden of wound healing is the problem of skin scarring, a $12 billion annual market. The immense economic and social impact of wounds in our society calls for allocation of a higher level of attention...

  4. Major Shifts in Glial Regional Identity Are a Transcriptional Hallmark of Human Brain Aging

    Lilach Soreq

    2017-01-01

    Full Text Available Gene expression studies suggest that aging of the human brain is determined by a complex interplay of molecular events, although both its region- and cell-type-specific consequences remain poorly understood. Here, we extensively characterized aging-altered gene expression changes across ten human brain regions from 480 individuals ranging in age from 16 to 106 years. We show that astrocyte- and oligodendrocyte-specific genes, but not neuron-specific genes, shift their regional expression patterns upon aging, particularly in the hippocampus and substantia nigra, while the expression of microglia- and endothelial-specific genes increase in all brain regions. In line with these changes, high-resolution immunohistochemistry demonstrated decreased numbers of oligodendrocytes and of neuronal subpopulations in the aging brain cortex. Finally, glial-specific genes predict age with greater precision than neuron-specific genes, thus highlighting the need for greater mechanistic understanding of neuron-glia interactions in aging and late-life diseases.

  5. Major Shifts in Glial Regional Identity Are a Transcriptional Hallmark of Human Brain Aging.

    Soreq, Lilach; Rose, Jamie; Soreq, Eyal; Hardy, John; Trabzuni, Daniah; Cookson, Mark R; Smith, Colin; Ryten, Mina; Patani, Rickie; Ule, Jernej

    2017-01-10

    Gene expression studies suggest that aging of the human brain is determined by a complex interplay of molecular events, although both its region- and cell-type-specific consequences remain poorly understood. Here, we extensively characterized aging-altered gene expression changes across ten human brain regions from 480 individuals ranging in age from 16 to 106 years. We show that astrocyte- and oligodendrocyte-specific genes, but not neuron-specific genes, shift their regional expression patterns upon aging, particularly in the hippocampus and substantia nigra, while the expression of microglia- and endothelial-specific genes increase in all brain regions. In line with these changes, high-resolution immunohistochemistry demonstrated decreased numbers of oligodendrocytes and of neuronal subpopulations in the aging brain cortex. Finally, glial-specific genes predict age with greater precision than neuron-specific genes, thus highlighting the need for greater mechanistic understanding of neuron-glia interactions in aging and late-life diseases. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  6. Annotating DNA variants is the next major goal for human genetics.

    Cutting, Garry R

    2014-01-02

    Clinical genetic testing has undergone a dramatic transformation in the past two decades. Diagnostic laboratories that previously tested for well-established disease-causing DNA variants in a handful of genes have evolved into sequencing factories identifying thousands of variants of known and unknown medical consequence. Sorting out what does and does not cause disease in our genomes is the next great challenge in making genetics a central feature of healthcare. I propose that closing the gap in our ability to interpret variation responsible for Mendelian disorders provides a grand and unprecedented opportunity for geneticists. Human geneticists are well placed to coordinate a systematic evaluation of variants in collaboration with basic scientists and clinicians. Sharing of knowledge, data, methods, and tools will aid both researchers and healthcare workers in achieving their common goal of defining the pathogenic potential of variants. Generation of variant annotations will inform genetic testing and will deepen our understanding of gene and protein function, thereby aiding the search for molecular targeted therapies. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  7. [Distribution diversity of integrins and calcium channels on major human and mouse host cells of Leptospira species].

    Li, Cheng-xue; Zhao, Xin; Qian, Jing; Yan, Jie

    2012-07-01

    To determine the distribution of integrins and calcium channels on major human and mouse host cells of Leptospira species. The expression of β1, β2 and β3 integrins was detected with immunofluorescence assay on the surface of human monocyte line THP-1, mouse mononuclear-macrophage-like cell line J774A.1, human vascular endothelial cell line HUVEC, mouse vascular endothelial cell EOMA, human hepatocyte line L-02, mouse hepatocyte line Hepa1-6, human renal tubular epithelial cell line HEK-293, mouse glomerular membrane epithelial cell line SV40-MES13, mouse collagen blast line NIH/3T3, human and mouse platelets. The distribution of voltage gate control calcium channels Cav3.1, Cav3.2, Cav3.3 and Cav2.3, and receptor gate calcium channels P(2)X(1), P(2)2X(2), P(2)X(3), P(2)X(4), P(2)X(5), P(2)X(6) and P(2)X(7) were determined with Western blot assay. β1 integrin proteins were positively expressed on the membrane surface of J774A.1, THP-1, HUVEC, EOMA, L-02, Hepa1-6 and HEK-239 cells as well as human and mouse platelets. β2 integrin proteins were expressed on the membrane surface of J774A.1, THP-1, HUVEC, EOMA, and NIH/3T3 cells. β3 integrin proteins were expressed on the membrane surface of J774A.1, THP-1, HUVEC, EOMA, Hepa1-6, HEK-239 and NIH/3T3 cells as well as human and mouse platelets. P(2)X(1) receptor gate calcium channel was expressed on the membrane surface of human and mouse platelets, while P(2)X(5) receptor gate calcium channel was expressed on the membrane surface of J774A.1, THP-1, L-02, Hepa1-6, HEK-239 and HUVEC cells. However, the other calcium channels were not detected on the tested cell lines or platelets. There is a large distribution diversity of integrins and calcium channel proteins on the major human and mouse host cells of Leptospira species, which may be associated with the differences of leptospira-induced injury in different host cells.

  8. Unmet Student Financial Need in the State of Washington: A Study of the "Need Gap."

    Fenske, Robert; And Others

    A study of unmet student financial need in Washington State was conducted by the Washington Council for Postsecondary Education. "Unmet need" is the difference between need and the total amount of aid received by the student through federal, state, and institutional financial aid programs, privately funded scholarships, and nonsubsidized…

  9. Unmet Health Care Service Needs of Children With Disabilities in Penang, Malaysia.

    Tan, Seok Hong

    2015-11-01

    Information on unmet health care needs reveal problems that are related to unavailability and inaccessibility of services. The study objectives were to determine the prevalence, and the reasons for unmet service needs among children with disabilities in the state of Penang, Malaysia. Caregivers of children with disabilities aged 0 to 12 years registered with the Penang Social Welfare Department in 2012 answered a self-administered mailed questionnaire. A total of 305 questionnaires were available for analysis (response rate 37.9%). Services that were very much needed and yet highly unmet were dental services (49.6% needed, 59.9% unmet), dietary advice (30.9% needed, 63.3% unmet), speech therapy (56.9% needed, 56.8% unmet), psychology services (25.5% needed, 63.3% unmet), and communication aids (33.0% needed, 79.2% unmet). Access problems were mainly due to logistic issues and caregivers not knowing where to obtain services. Findings from this study can be used to inform strategies for service delivery and advocacy for children with disabilities in Penang, Malaysia. © 2015 APJPH.

  10. Unmet need for contraception among married women in an urban area of Puducherry, India.

    Sulthana, Bahiya; Shewade, Hemant Deepak; Sunderamurthy, Bhuvaneswary; Manoharan, Keerthana; Subramanian, Manimozhi

    2015-01-01

    Unmet need for contraception remains a national problem. The study was conducted in an urban area of Puducherry, India, among the eligible couples to assess the unmet need for contraception and to determine the awareness and pattern of use of contraceptives along with the socio-demographic factors associated with the unmet needs for contraception. This cross-sectional study included eligible couples with married women in age group of 15-45 yr as the study population (n=267). Probability proportional to size sampling followed by systematic random sampling was used. A pre-tested questionnaire was administered to collect data from the respondents. Double data entry and validation of data was done. Unmet need for contraception was 27.3 per cent (95% CI: 22.3-33); unmet need for spacing and limiting was 4.9 and 22.5 per cent, respectively. Among those with unmet need (n=73), 50 per cent reported client related factors (lack of knowledge, shyness, etc.); and 37 per cent reported contraception related factors (availability, accessibility, affordability, side effects) as a cause for unmet need. Our study showed a high unmet need for contraception in the study area indicating towards a necessity to address user perspective to meet the contraception needs.

  11. Unmet need for contraception among married women in an urban area of Puducherry, India

    Bahiya Sulthana

    2015-01-01

    Full Text Available Background & objectives: Unmet need for contraception remains a national problem. The study was conducted in an urban area of Puducherry, India, among the eligible couples to assess the unmet need for contraception and to determine the awareness and pattern of use of contraceptives along with the socio-demographic factors associated with the unmet needs for contraception. Methods: This cross-sectional study included eligible couples with married women in age group of 15-45 yr as the study population (n=267. Probability proportional to size sampling followed by systematic random sampling was used. A pre-tested questionnaire was administered to collect data from the respondents. Double data entry and validation of data was done. Results: Unmet need for contraception was 27.3 per cent (95% CI: 22.3-33; unmet need for spacing and limiting was 4.9 and 22.5 per cent, respectively. Among those with unmet need (n=73, 50 per cent reported client related factors (lack of knowledge, shyness, etc.; and 37 per cent reported contraception related factors (availability, accessibility, affordability, side effects as a cause for unmet need. Interpretation & conclusions: Our study showed a high unmet need for contraception in the study area indicating towards a necessity to address user perspective to meet the contraception needs.

  12. Unmet needs in obesity management: From guidelines to clinic.

    Ritten, Angela; LaManna, Jacqueline

    2017-10-01

    Despite the rather slow acceptance of obesity as a disease state, several obesity staging systems and weight-management guidelines have been developed and are in use, along with an ever-growing number of treatment options. Many primary care clinicians, including nurse practitioners (NPs), are at the forefront of clinical efforts to assist individuals with obesity, but face challenges due to lack of alignment and consensus among the various staging systems and guidelines. This is further complicated by shortfalls in clinical training related to obesity management and increasing complexities in reimbursement for obesity-related services. Unmet needs in the management of obesity thus stretch from guidelines to clinic. This article examines the principal barriers to effective management of individuals with obesity and considers how concerns might be overcome, with particular emphasis on the role of the NP. ©2017 American Association of Nurse Practitioners.

  13. Lateral gene transfer of an ABC transporter complex between major constituents of the human gut microbiome

    Meehan Conor J

    2012-11-01

    Full Text Available Abstract Background Several links have been established between the human gut microbiome and conditions such as obesity and inflammatory bowel syndrome. This highlights the importance of understanding what properties of the gut microbiome can affect the health of the human host. Studies have been undertaken to determine the species composition of this microbiome and infer functional profiles associated with such host properties. However, lateral gene transfer (LGT between community members may result in misleading taxonomic attributions for the recipient organisms, thus making species-function links difficult to establish. Results We identified a peptides/nickel transport complex whose components differed in abundance based upon levels of host obesity, and assigned the encoded proteins to members of the microbial community. Each protein was assigned to several distinct taxonomic groups, with moderate levels of agreement observed among different proteins in the complex. Phylogenetic trees of these proteins produced clusters that differed greatly from taxonomic attributions and indicated that habitat-directed LGT of this complex is likely to have occurred, though not always between the same partners. Conclusions These findings demonstrate that certain membrane transport systems may be an important factor within an obese-associated gut microbiome and that such complexes may be acquired several times by different strains of the same species. Additionally, an example of individual proteins from different organisms being transferred into one operon was observed, potentially demonstrating a functional complex despite the donors of the subunits being taxonomically disparate. Our results also highlight the potential impact of habitat-directed LGT on the resident microbiota.

  14. Developing and Evaluating Medical Humanities Problem-Based Learning Classes Facilitated by the Teaching Assistants Majored in the Liberal Arts

    Tseng, Fen-Yu; Shieh, Jeng-Yi; Kao, Tze-Wah; Wu, Chau-Chung; Chu, Tzong-Shinn; Chen, Yen-Yuan

    2016-01-01

    Abstract Although medical humanities courses taught by teachers from nonmedical backgrounds are not unusual now, few studies have compared the outcome of medical humanities courses facilitated by physicians to that by teaching assistants majored in the liberal arts. The objectives of this study were to (1) analyze the satisfaction of medical students with medical humanities problem-based learning (PBL) classes facilitated by nonmedical teaching assistants (TAF) majored in the liberal arts, and those facilitated by the attending physicians (APF) and (2) examine the satisfaction of medical students with clinical medicine-related and clinical medicine-unrelated medical humanities PBL classes. A total of 123 medical students, randomly assigned to 16 groups, participated in this study. There were 16 classes in the course: 8 of them were TAF classes; and the others were APF classes. Each week, each group rotated from 1 subject of the 16 subjects of PBL to another subject. All of the 16 groups went through all the 16 subjects in the 2013 spring semester. We examined the medical students’ satisfaction with each class, based on a rating score collected after each class was completed, using a scale from 0 (the lowest satisfaction) to 100 (the highest satisfaction). We also conducted multivariate linear regression analysis to examine the association between the independent variables and the students’ satisfaction. Medical students were more satisfied with the TAF (91.35 ± 7.75) medical humanities PBL classes than APF (90.40 ± 8.42) medical humanities PBL classes (P = 0.01). Moreover, medical students were more satisfied with the clinical medicine-unrelated topics (92.00 ± 7.10) than the clinical medicine-related topics (90.36 ± 7.99) in the medical humanities PBL course (P = 0.01). This medical humanities PBL course, including nonmedical subjects and topics, and nonmedical teaching assistants from the liberal arts as class facilitators, was

  15. Frequency variations of discrete cranial traits in major human populations. I. Supernumerary ossicle variations.

    Hanihara, T; Ishida, H

    2001-06-01

    Four supernumerary ossicle variations-the ossicle at the lambda, the parietal notch bone, the asterionic bone, and the occipitomastoid bone-were examined for laterality differences, intertrait correlations, sex differences, and between group variations in the samples from around the world. Significant laterality differences were not detected in almost all samples. In some pairs of traits, significant association of occurrence were found. Several geographic samples were sexually dimorphic with respect to the asterionic bone and to a lesser extent for the parietal notch bone. East/Northeast Asians including the Arctic populations in general had lower frequencies of the 4 accessory ossicles. Australians, Melanesians and the majority of the New World peoples, on the other hand, generally had high frequencies. In the western hemisphere of the Old World, Subsaharan Africans had relatively high frequencies. Except for the ossicle at the lambda, the distribution pattern in incidence showed clinal variation from south to north. Any identifiable adaptive value related to environmental or subsistence factors may be expressed in such clinal variation. This may allow us to hypothesise that not only mechanical factors but a founder effect, genetic drift, and population structure could have been the underlying causes for interregional variation and possible clines in the incidences of the accessory ossicles.

  16. A practical guide for the identification of major sulcogyral structures of the human cortex.

    Destrieux, Christophe; Terrier, Louis Marie; Andersson, Frédéric; Love, Scott A; Cottier, Jean-Philippe; Duvernoy, Henri; Velut, Stéphane; Janot, Kevin; Zemmoura, Ilyess

    2017-05-01

    The precise sulcogyral localization of cortical lesions is mandatory to improve communication between practitioners and to predict and prevent post-operative deficits. This process, which assumes a good knowledge of the cortex anatomy and a systematic analysis of images, is, nevertheless, sometimes neglected in the neurological and neurosurgical training. This didactic paper proposes a brief overview of the sulcogyral anatomy, using conventional MR-slices, and also reconstructions of the cortical surface after a more or less extended inflation process. This method simplifies the cortical anatomy by removing part of the cortical complexity induced by the folding process, and makes it more understandable. We then reviewed several methods for localizing cortical structures, and proposed a three-step identification: after localizing the lateral, medial or ventro-basal aspect of the hemisphere (step 1), the main interlobar sulci were located to limit the lobes (step 2). Finally, intralobar sulci and gyri were identified (step 3) thanks to the same set of rules. This paper does not propose any new identification method but should be regarded as a set of practical guidelines, useful in daily clinical practice, for detecting the main sulci and gyri of the human cortex.

  17. In vitro assessment of human airway toxicity from major aldehydes in automotive emissions

    Grafstroem, R.C. [Karolinska Inst., Stockholm (Sweden). Inst. of Environmental Medicine

    1997-09-01

    Automotive exhausts can significantly contribute to the levels of reactive aldehydes, including formaldehyde, acetaldehyde and acrolein, in urban air. The use of alcohols as an alternative fuel for gasoline or diesel may further increase these emissions. Since it is unclear if aldehyde inhalation may induce pathological states, including cancer, in human airways, the toxic properties of the above-mentioned aldehydes were studied in cultured target cell types. Each aldehyde modified vital cellular functions in a dose-dependent manner, and invariably inhibited growth and induced abnormal terminal differentiation. Decreases of cellular thiols and increases of intracellular Ca{sup 2+} were observed, and moreover, variable types and amounts of short-lived or persistent genetic damage were induced. The concentrations required for specified levels of a particular type of injury varied up to 10000-fold among the aldehydes. Overall, distinctive patterns of cytopathological activity were observed, which differed both qualitatively and quantitatively among the aldehydes. Finally, aldehydes inhibited DNA repair processes and increased cytotoxicity and mutagenesis in synergy with other known toxicants, indicating that aldehydes may also enhance damage by other constituents in automotive exhausts. In summary, the aldehydes, notably {sup m}u{sup M}-mM formaldehyde, caused pathological effects and induced mechanisms that relate to acute toxicity and cancer development in airway epithelial cells. Since `no-effect` levels may not exist for carcinogenic agents, the overall results support a need for elimination of aldehydes in automotive exhausts. 41 refs

  18. Controlling major cellular processes of human mesenchymal stem cells using microwell structures.

    Xu, Xun; Wang, Weiwei; Kratz, Karl; Fang, Liang; Li, Zhengdong; Kurtz, Andreas; Ma, Nan; Lendlein, Andreas

    2014-12-01

    Directing stem cells towards a desired location and function by utilizing the structural cues of biomaterials is a promising approach for inducing effective tissue regeneration. Here, the cellular response of human adipose-derived mesenchymal stem cells (hADSCs) to structural signals from microstructured substrates comprising arrays of square-shaped or round-shaped microwells is explored as a transitional model between 2D and 3D systems. Microwells with a side length/diameter of 50 μm show advantages over 10 μm and 25 μm microwells for accommodating hADSCs within single microwells rather than in the inter-microwell area. The cell morphologies are three-dimensionally modulated by the microwell structure due to differences in focal adhesion and consequent alterations of the cytoskeleton. In contrast to the substrate with 50 μm round-shaped microwells, the substrate with 50 μm square-shaped microwells promotes the proliferation and osteogenic differentiation potential of hADSCs but reduces the cell migration velocity and distance. Such microwell shape-dependent modulatory effects are highly associated with Rho/ROCK signaling. Following ROCK inhibition, the differences in migration, proliferation, and osteogenesis between cells on different substrates are diminished. These results highlight the possibility to control stem cell functions through the use of structured microwells combined with the manipulation of Rho/ROCK signaling. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Genetic Variation among Major Human Geographic Groups Supports a Peculiar Evolutionary Trend in PAX9

    Paixão-Côrtes, Vanessa R.; Meyer, Diogo; Pereira, Tiago V.; Mazières, Stéphane; Elion, Jacques; Krishnamoorthy, Rajagopal; Zago, Marco A.; Silva, Wilson A.; Salzano, Francisco M.; Bortolini, Maria Cátira

    2011-01-01

    A total of 172 persons from nine South Amerindian, three African and one Eskimo populations were studied in relation to the Paired box gene 9 (PAX9) exon 3 (138 base pairs) as well as its 5′and 3′flanking intronic segments (232 bp and 220 bp, respectively) and integrated with the information available for the same genetic region from individuals of different geographical origins. Nine mutations were scored in exon 3 and six in its flanking regions; four of them are new South American tribe-specific singletons. Exon3 nucleotide diversity is several orders of magnitude higher than its intronic regions. Additionally, a set of variants in the PAX9 and 101 other genes related with dentition can define at least some dental morphological differences between Sub-Saharan Africans and non-Africans, probably associated with adaptations after the modern human exodus from Africa. Exon 3 of PAX9 could be a good molecular example of how evolvability works. PMID:21298044

  20. Genetic variation among major human geographic groups supports a peculiar evolutionary trend in PAX9.

    Vanessa R Paixão-Côrtes

    Full Text Available A total of 172 persons from nine South Amerindian, three African and one Eskimo populations were studied in relation to the Paired box gene 9 (PAX9 exon 3 (138 base pairs as well as its 5'and 3'flanking intronic segments (232 bp and 220 bp, respectively and integrated with the information available for the same genetic region from individuals of different geographical origins. Nine mutations were scored in exon 3 and six in its flanking regions; four of them are new South American tribe-specific singletons. Exon3 nucleotide diversity is several orders of magnitude higher than its intronic regions. Additionally, a set of variants in the PAX9 and 101 other genes related with dentition can define at least some dental morphological differences between Sub-Saharan Africans and non-Africans, probably associated with adaptations after the modern human exodus from Africa. Exon 3 of PAX9 could be a good molecular example of how evolvability works.

  1. Alteration of major vault protein in human glioblastoma and its relation with EGFR and PTEN status.

    Navarro, L; Gil-Benso, R; Megías, J; Muñoz-Hidalgo, L; San-Miguel, T; Callaghan, R C; González-Darder, J M; López-Ginés, C; Cerdá-Nicolás, M J

    2015-06-25

    Glioblastoma (GBM) is the most frequent and malignant primary brain tumor. Conventional therapy of surgical removal, radiation and chemotherapy is largely palliative. Major vault protein (MVP), the main component of the vault organelle has been associated with multidrug resistance by reducing cellular accumulation of chemotherapeutic agents. With regard to cancer, MVP has been shown to be overexpressed in drug resistance development and malignant progression. The aim of the present study was to evaluate the MVP gene dosage levels in 113 archival samples from GBM and its correlation with patients' survival and epidermal growth factor receptor (EGFR) and phosphatase and tensin homolog (PTEN) gene dosages. Fluorescent in situ hybridization revealed polysomy of chromosome 7 in 76.1% of the GBMs and EGFR amplification in a 64.6% of the tumors. Genetic status of EGFR, PTEN and MVP copies was determined by multiplex ligation-dependent probe amplification (MLPA) technique. 31% of the tumors showed the EGFR is variant III mutation (EGFRvIII) mutation and 74.3% of them presented amplification of MVP gene. Amplification of EGFR and MVP was found in a 63.7% and 56.6% of the GBM, respectively. An inverse correlation between MVP and PTEN dosage values was observed. Besides, an inverse relationship between the survival of the patients treated with chemotherapy and the levels of MVP copies was determined. In conclusion, our study reveals an important role of MVP, together with EGFRvIII and PTEN, in the progression of GBM and proposes it as a novel and interesting target for new treatment approaches. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Characterization of the human RAB38 and RAB7 genes: exclusion of new major pathological loci for Japanese OCA.

    Suzuki, Tamio; Miyamura, Yoshinori; Inagaki, Katsuhiko; Tomita, Yasushi

    2003-08-01

    Oculocutaneous albinisms (OCAs) are due to various gene mutations that cause a disruption of melanogenesis in the melanocyte. Four different genes associated with human OCA have been reported, however, not all of OCA patients can be classified according to these four genes. We have sought to find a new major locus for Japanese OCA. Recently two genes, RAB38 and RAB7, were reported to play an important role in melanogenesis in the melanocyte, suggesting that these two genes could be good candidates for new OCA loci. To determine the structures of the human RAB38 and RAB7 genes, and examine if the two genes are new major loci for Japanese OCA. We screened mutations in these genes of 25 Japanese OCA patients who lacked mutations in the OCA1 and OCA2 genes with SSCP/heteroduplexes method. We determined the both genes, and their genomic organizations to design the primers for SSCP/heteroduplexes method. And then we screened mutations, but no mutation was detected. Neither of the genes is a new major locus for Japanese OCA.

  3. Current progress in the development and use of artemether for chemoprophylaxis of major human schistosome parasites.

    Utzinger, J; Xiao, S; Keiser, J; Chen, M; Zheng, J; Tanner, M

    2001-12-01

    Human schistosomiasis, a chronic and debilitating parasitic disease of the tropics, is ranked second after malaria in terms of public health importance. At present, there is no vaccine available, and chemotherapy is the cornerstone of schistosomiasis control. Praziquantel is the drug of choice. Oxamniquine has become difficult to obtain and metrifonate has recently been withdrawn from the market. Rapid re-infection following treatment and concern about praziquantel resistance called for the search of novel drugs for prevention and cure of schistosomiasis. Significant progress has been made with artemether, the methyl ether of dihydroartemisinin, already widely used for the treatment of malaria. The present article reviews the literature that led to the development of artemether for chemoprophylaxis in schistosomiasis, and it summarises the experiences so far obtained with its use to control schistosomiasis in different endemic settings. Topics covered include an overview of the global burden of schistosomiasis and approaches for its control; the nature and features of artemisinin and related derivatives, initially discovered as antimalarials, other bioactivities, and their recent discovery of antischistosomal properties; a historic account disclosing the antischistosomal activity of artemether; in vivo assessment of drug susceptibility of different developmental stages of schistosome parasites; artemether-induced pathology evidenced by scanning and transmission electron microscopy; the possible mechanism of action; in vivo studies with combination therapy of artemether and praziquantel; results of randomised controlled clinical trials of oral artemether for the prevention of patent infection and morbidity; and, ultimately the translation of this knowledge into public health action in different endemic settings towards a more integrated approach of schistosomiasis control.

  4. Differences in behavioral health disorders and unmet treatment needs between medical marijuana users and recreational marijuana users: Results from a national adult sample.

    Park, Ji-Yeun; Wu, Li-Tzy

    2017-11-01

    Available data suggest that medical marijuana users may have more mental health problems than recreational marijuana users. There is limited information about differences in behavioral health disorders and unmet treatment needs between medical and recreational marijuana users. We compared past-year prevalence of behavioral health disorders and unmet treatment needs across three marijuana subgroups (recreational use only, medical use only, and both). Sex-stratified logistic regression was performed to determine their associations with marijuana use status. We analyzed data from adults (≥18 years) who used marijuana in the past year (N=15,440) from 2013 to 2014 National Surveys on Drug Use and Health. Among 15,440 past-year marijuana users, 90.2% used recreational marijuana only, 6.2% used medical marijuana only, and 3.6% used both. Both users had the highest prevalence of behavioral health disorders and unmet treatment needs overall, with no significant sex differences. In the sex-specific logistic regression analysis, medical only users and both users showed somewhat different patterns of associations (reference group=recreational only users). Medical only users had decreased odds of alcohol or drug use disorders, and unmet need for alcohol or drug treatment among males and females. Additionally, female medical only users had decreased odds of opioid use disorder. Both users had increased odds of major depressive episode, hallucinogen use disorder, and unmet need for mental health services among males, and cocaine use disorder among females. Different approaches tailored to individuals' sex and motives for marijuana use is needed for the prevention and treatment of behavioral health problems. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Effect of caffeine on the expression of a major X-ray induced protein in human tumor cells

    Hughes, E.N.; Boothman, D.A. (Univ. of Pennsylvania School of Medicine, Philadelphia (USA))

    1991-03-01

    We have examined the effect of caffeine on the concomitant processes of the repair of potentially lethal damage (PLD) and the synthesis of X-ray-induced proteins in the human malignant melanoma cell line, Ul-Mel. Caffeine administered at a dose of 5mM after X radiation not only inhibited PLD repair but also markedly reduced the level of XIP269, a major X-ray-induced protein whose expression has been shown to correlate with the capacity to repair PLD. The expression of the vast majority of other cellular proteins, including seven other X-ray-induced proteins, remained unchanged following caffeine treatment. A possible role for XIP269 in cell cycle delay following DNA damage by X irradiation is discussed.

  6. RNA of Enterococcus faecalis Strain EC-12 Is a Major Component Inducing Interleukin-12 Production from Human Monocytic Cells.

    Ryoichiro Nishibayashi

    Full Text Available Interleukin-12 (IL-12 is an important cytokine for the immunomodulatory effects of lactic acid bacteria (LAB. Using murine immune cells, we previously reported that the RNA of Enterococcus faecalis EC-12, a LAB strain exerting probiotic-like beneficial effects, is the major IL-12-inducing immunogenic component. However, it was recently revealed that bacterial RNA can be a ligand for Toll-like receptor (TLR 13, which is only expressed in mice. Because TLR13 is not expressed in humans, the immuno-stimulatory and -modulatory effects of LAB RNA in human cells should be augmented excluding TLR13 contribution. In experiment 1 of this study, the role of LAB RNA in IL-12 induction in human immune cells was studied using three LAB strains, E.faecalis EC-12, Lactobacillus gasseri JCM5344, and Bifidobacterium breve JCM1192. RNase A treatment of heat-killed LAB significantly decreased the IL-12 production of human peripheral blood mononuclear cells on stimulation, while RNase III treatment revealed virtually no effects. Further, IL-12 production against heat-killed E. faecalis EC-12 was abolished by depleting monocytes. These results demonstrated that single stranded RNA (ssRNA of LAB is a strong inducer of IL-12 production from human monocytes. In experiment 2, major receptor for ssRNA of E. faecalis EC-12 was identified using THP-1 cells, a human monocytic cell line. The type of RNA molecules of E. faecalis EC-12 responsible for IL-12 induction was also identified. IL-12 production induced by the total RNA of E. faecalis EC-12 was significantly reduced by the treatment of siRNA for TLR8 but not for TLR7. Furthermore, both 23S and 16S rRNA, but not mRNA, of E. faecalis EC-12 markedly induced IL-12 production from THP-1 cells. These results suggested that the recognition of ssRNA of E. faecalis EC-12 was mediated by TLR8 and that rRNA was the RNA molecule that exhibited IL-12-inducing ability in human cells.

  7. Low vascularization of the nephrogenic zone of the fetal kidney suggests a major role for hypoxia in human nephrogenesis.

    Gerosa, C; Fanni, D; Faa, A; Van Eyken, P; Ravarino, A; Fanos, V; Faa, G

    2017-09-01

    CD31 reactivity is generally utilized as a marker of endothelial cells. CD31 immunoreactivity in the developing human kidney revealed that fetal glomerular capillary endothelial cells change their immunohistochemical phenotype during maturation. The aim of this study was to analyze CD31 reactivity in the fetal human kidney in the different stages of intrauterine development: We observed different distribution of CD31-reactive vascular progenitors in the different areas of the developing kidney. In particular, the nephrogenic zone and the renal capsule were characterized by a scarcity of CD31-reactive cells at all gestational ages. These data suggest the hypothesis that nephrogenesis does not need high oxygen levels and confirms a major role of hypoxia in nephrogenesis.

  8. Major histocompatibility complex-unrestricted cytolytic activity of human T cells: analysis of precursor frequency and effector phenotype

    Patel, S.S.; Thiele, D.L.; Lipsky, P.E.

    1987-01-01

    The frequency and phenotype of human T cells that mediate major histocompatibility complex (MHC)-unrestricted cytolysis were analyzed. T cell clones were generated by culturing adherent cell-depleted peripheral blood mononuclear cells at a density of 0.3 cell/well with phytohemagglutinin, recombinant interleukin 2 (rIL-2), and irradiated autologous peripheral blood mononuclear cells and/or Epstein-Barr virus-transformed lymphoblastoid cell lines. All of the 198 clones generated by this method were T cells (CD2 + , CD3 + , CD4 + or CD2 + , CD3 + , CD8 + ) that possessed potent lytic activity against K562, an erythroleukemia line sensitive to lysis by human natural killer cells, and Cur, a renal carcinoma cell line resistant to human natural killer activity. Cytolysis, measured by 51 Cr release, was MHC-unrestricted, since the clones were able to lyse MHC class I or class II negative targets, as well as MHC class I and class II negative targets. Although the clones produced tissue necrosis factor/lymphotoxin-like molecules, lysis of Cur of K562 was not mediated by a soluble factor secreted by the clones. These data indicate that the capacity for MHC-unrestricted tumoricidal activity and expression of NKH1 and CD11b, but not CD 16, are properties common to all or nearly all human peripheral blood-derived T cell clones regardless of CD4 or CD8 phenotype

  9. Unmet need and fertility decline: a comparative perspective on prospects in sub-Saharan Africa.

    Casterline, John B; El-Zeini, Laila O

    2014-06-01

    This study assesses how changes in unmet need for family planning have contributed to contemporary fertility declines, and the implications of this historical record for further fertility decline, especially in sub-Saharan Africa. We examine joint trends at the national level in fertility, unintended fertility, and unmet need. We bring unintended fertility into the analysis because the underlying rationale for reducing unmet need is to avert unintended pregnancies and births. The association over time between unmet need and fertility is investigated using survey data from 45 countries in Africa, Asia, and Latin America and the Caribbean from the mid-1970s to the present. The empirical analysis finds that reduction in unmet need, especially unmet need for limiting, is strongly associated with fertility decline in Latin America and the Caribbean and in Asia and North Africa. Fertility decline in sub-Saharan Africa is weakly associated with trends in unmet need (and satisfaction of demand). We propose that the stark regional difference is due to measurement problems and to the fundamentally different character of fertility decline in sub-Saharan Africa, itself reflective of basic differences in pretransition reproductive regimes. © 2013 The Population Council, Inc.

  10. Associations between neighbourhood support and financial burden with unmet needs of head and neck cancer survivors.

    O'Brien, Katie M; Timmons, Aileen; Butow, Phyllis; Gooberman-Hill, Rachael; O'Sullivan, Eleanor; Balfe, Myles; Sharp, Linda

    2017-02-01

    To assess the unmet needs of head and neck cancer survivors and investigate associated factors. In particular, to explore whether social support (family/friends and neighbours) and financial burden are associated with unmet needs of head and neck cancer (HNC) survivors. This was a cross-sectional study of HNC survivors, with 583 respondents included in the analysis. Information was collected on unmet supportive care needs as measured by the Supportive Care Needs Survey (SCNS-SF34). Poisson regression with robust standard errors was used to examine factors associated with having one or more needs in each of the five domains (physical; psychological; sexuality; patient care and support; and health system and information). The mean age of respondents was 62.9years (standard deviation 11.3years) and one third of respondents were female. The top ten unmet needs was composed exclusively of items from the physical and psychological domains. Financial strain due to cancer and finding it difficult to obtain practical help from a neighbour were both associated with unmet needs in each of the five domains, in the adjusted analyses. Whilst in each domain, a minority of respondents have unmet needs, approximately half of respondents reported at least one unmet need, with the commonest unmet needs in the psychological domain. Providing services to people with these needs should be a priority for healthcare providers. We suggest that studies, which identify risk factors for unmet needs, could be used to develop screening tools or aid in the targeting of support. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Unmet need for healthcare services in adolescents and young adults with cancer and their parent carers.

    Sawyer, Susan M; McNeil, Robyn; McCarthy, Maria; Orme, Lisa; Thompson, Kate; Drew, Sarah; Dunt, David

    2017-07-01

    Cancer in adolescents in and young adults (AYA) has the potential to disrupt health, well-being and developmental trajectories. This study aimed to describe the healthcare support service needs of AYAs with cancer and parent carers and to explore the association of unmet need and emotional distress. As part of a national Australian survey of 15-25 year olds with cancer and a nominated parent carer, 196 AYAs reported total and unmet need for 10 clinical services and 204 parents reported on their child's and their own healthcare service needs. Proportions of total and unmet need for specific clinical services are reported. The association of unmet service needs and distress (measured using the Posttraumatic Stress Disorder Checklist) was also examined. AYAs and parent carers expressed high total need for clinical services during treatment. Leading AYA unmet needs were for an exercise therapist (37%), genetic counsellor (30%), dietitian (26%), peer support group (26%) and educational and vocational advisor (24%). After treatment, AYAs and parents had fewer total needs. However, 60% of AYA and 38% of parents had two or more unmet needs, similar to during treatment. Female gender and receiving treatment in an adult setting were significantly associated with unmet need for clinical services. After treatment, higher distress levels in AYAs and parents were associated with two or more unmet service needs. AYAs and parents had high levels of total and unmet service need, which were associated with greater emotional distress. These results highlight opportunities to re-orientate services to better meet AYA and parent needs.

  12. Unmet healthcare need among women who use methamphetamine in San Francisco.

    Powelson, Elisabeth; Lorvick, Jennifer; Lutnick, Alexandra; Wenger, Lynn; Klausner, Jeffery; Kral, Alex H

    2014-02-01

    Methamphetamine use has increased substantially in the United States since the 1990s. Few studies have examined the healthcare service needs of women who use methamphetamine. This study describes unmet medical needs in a community-based sample of women who use methamphetamine in San Francisco, CA. Women who use methamphetamine were recruited in San Francisco and participated in a computer-assisted survey (N = 298 HIV-negative women). Multivariate analysis was performed to explore associations among sociodemographic variables, drug use, use of health and social services, and unmet healthcare need across three domains: chronic health problems, dermatologic problems, and women's preventive healthcare. Sixty-nine percent of participants reported a need for care for a chronic health condition, and 31% of them had an unmet need for care, in the last six months. Thirty-five percent of participants reported a need for dermatologic healthcare, and 66% had an unmet need for care in the last 6 months. Ninety-two percent of participants reported a need for women's preventive healthcare and 46% had an unmet need for care in the last year. Women who reported having a healthcare provider had lower odds of reporting an unmet need for a chronic health condition or women's preventive healthcare. Women who used a case manager had lower odds of having an unmet need for dermatologic care. A significant proportion of women who use methamphetamine in this sample had an unmet need for women's preventive healthcare, and overall these women had a significant unmet need for healthcare. These findings suggest that contact with a healthcare provider or a caseworker could help to expand access to healthcare for this vulnerable population.

  13. Unmet need for contraception and its association with unintended pregnancy in Bangladesh.

    Bishwajit, Ghose; Tang, Shangfeng; Yaya, Sanni; Feng, Zhanchun

    2017-06-12

    Unmet need for contraception and unintended pregnancy are important public health concerns both in developing and developed countries. Previous researches have attempted to study the factors that influence unintended pregnancy. However, the association between unmet need for contraception and unwanted pregnancy is not studied adequately. The aim of the present study was to measure the prevalence of unmet need for contraception and unwanted pregnancy, and to explore the association between these two in a nationally representative sample in Bangladesh. Data for the present study were collected from Bangladesh demographic and health survey conducted in 2011. Participants were 7338 mothers ageing between 13 and 49 years selected from both rural and urban residencies. Planning status of last pregnancy was the main outcome variable and unmet need for contraception was the explanatory variable of primary interest. Cross tabulation, chi-square tests and logistic regression (Generalised estimating equations) methods were used for data analysis. Mean age of the sample population was 25.6 years (SD 6.4). Prevalence of unmet need for contraception was 13.5%, and about 30% of the women described their last pregnancy as unintended. In the adjusted model, the odds of unintended pregnancy were about 16 fold among women who reported facing unmet need for contraception compared to those who did not (95% CI = 11.63-23.79). National rates of unintended pregnancy and of unmet need for contraception remain considerably high and warrant increased policy attention. Findings suggests that programs targeting to reduce unmet need for contraception could contribute to a lower rate of unintended pregnancy in Bangladesh. More in-depth and qualitative studies on the underlying sociocultural causes of unmet need can help develop context specific solutions to unintended pregnancies.

  14. Foodstuff analyses show that seafood and water are major perfluoroalkyl acids (PFAAs) sources to humans in Korea

    Heo, Jin-Ju; Lee, Ji-Woo [Department of Civil and Environmental Engineering, Pusan National University, Busan, 609-735 (Korea, Republic of); Kim, Seung-Kyu [Department of Marine Science, College of Natural Sciences, Incheon National University, Incheon, 406-772 (Korea, Republic of); Oh, Jeong-Eun, E-mail: jeoh@pusan.ac.kr [Department of Civil and Environmental Engineering, Pusan National University, Busan, 609-735 (Korea, Republic of)

    2014-08-30

    Graphical abstract: - Highlights: • 16 PFAAs in 397 samples of 66 food types and 34 tap water samples were analyzed. • Dietary exposure to PFAAs was estimated by using the PFAAs measured concentrations. • The major contributors of PFAAs dietary exposure were confirmed. - Abstract: We measured concentrations of PFAAs in 397 foods, of 66 types, in Korea, and determined the daily human dietary PFAAs intake and the contribution of each foodstuff to that intake. The PFAAs concentration in the 66 different food types ranged from below the detection limit to 48.3 ng/g. Perfluorooctane sulfonate (PFOS) and long-chain perfluorocarboxylic acids (PFCAs) were the dominant PFAAs in fish, shellfish, and processed foods, while perfluorooctanoic acid (PFOA) and short-chain PFCAs dominated dairy foodstuffs and beverages. The Korean adult dietary intake ranges, estimated for a range of scenarios, were 0.60–3.03 and 0.17–1.68 ng kg{sup −1} bw d{sup −1} for PFOS and PFOA, respectively, which were lower than the total daily intake limits suggested by European Food Safety Authority (PFOS: 150 ng kg{sup −1} bw d{sup −1}; PFOA: 1500 ng kg{sup −1} bw d{sup −1}). The major contributors to PFAAs dietary exposure varied with subject age and PFAAs. For example, fish was a major contributor of PFOS but dairy foods were major contributors of PFOA. However, tap water was a major contributor to PFOA intake when it was the main source of drinking water (rather than bottled water)

  15. Differential Impact of LPG-and PG-Deficient Leishmania major Mutants on the Immune Response of Human Dendritic Cells.

    Michelle A Favila

    2015-12-01

    Full Text Available Leishmania major infection induces robust interleukin-12 (IL12 production in human dendritic cells (hDC, ultimately resulting in Th1-mediated immunity and clinical resolution. The surface of Leishmania parasites is covered in a dense glycocalyx consisting of primarily lipophosphoglycan (LPG and other phosphoglycan-containing molecules (PGs, making these glycoconjugates the likely pathogen-associated molecular patterns (PAMPS responsible for IL12 induction.Here we explored the role of parasite glycoconjugates on the hDC IL12 response by generating L. major Friedlin V1 mutants defective in LPG alone, (FV1 lpg1-, or generally deficient for all PGs, (FV1 lpg2-. Infection with metacyclic, infective stage, L. major or purified LPG induced high levels of IL12B subunit gene transcripts in hDCs, which was abrogated with FV1 lpg1- infections. In contrast, hDC infections with FV1 lpg2- displayed increased IL12B expression, suggesting other PG-related/LPG2 dependent molecules may act to dampen the immune response. Global transcriptional profiling comparing WT, FV1 lpg1-, FV1 lpg2- infections revealed that FV1 lpg1- mutants entered hDCs in a silent fashion as indicated by repression of gene expression. Transcription factor binding site analysis suggests that LPG recognition by hDCs induces IL-12 in a signaling cascade resulting in Nuclear Factor κ B (NFκB and Interferon Regulatory Factor (IRF mediated transcription.These data suggest that L. major LPG is a major PAMP recognized by hDC to induce IL12-mediated protective immunity and that there is a complex interplay between PG-baring Leishmania surface glycoconjugates that result in modulation of host cellular IL12.

  16. Foodstuff analyses show that seafood and water are major perfluoroalkyl acids (PFAAs) sources to humans in Korea

    Heo, Jin-Ju; Lee, Ji-Woo; Kim, Seung-Kyu; Oh, Jeong-Eun

    2014-01-01

    Graphical abstract: - Highlights: • 16 PFAAs in 397 samples of 66 food types and 34 tap water samples were analyzed. • Dietary exposure to PFAAs was estimated by using the PFAAs measured concentrations. • The major contributors of PFAAs dietary exposure were confirmed. - Abstract: We measured concentrations of PFAAs in 397 foods, of 66 types, in Korea, and determined the daily human dietary PFAAs intake and the contribution of each foodstuff to that intake. The PFAAs concentration in the 66 different food types ranged from below the detection limit to 48.3 ng/g. Perfluorooctane sulfonate (PFOS) and long-chain perfluorocarboxylic acids (PFCAs) were the dominant PFAAs in fish, shellfish, and processed foods, while perfluorooctanoic acid (PFOA) and short-chain PFCAs dominated dairy foodstuffs and beverages. The Korean adult dietary intake ranges, estimated for a range of scenarios, were 0.60–3.03 and 0.17–1.68 ng kg −1 bw d −1 for PFOS and PFOA, respectively, which were lower than the total daily intake limits suggested by European Food Safety Authority (PFOS: 150 ng kg −1 bw d −1 ; PFOA: 1500 ng kg −1 bw d −1 ). The major contributors to PFAAs dietary exposure varied with subject age and PFAAs. For example, fish was a major contributor of PFOS but dairy foods were major contributors of PFOA. However, tap water was a major contributor to PFOA intake when it was the main source of drinking water (rather than bottled water)

  17. Human major histocompatibility complex contains a minimum of 19 genes between the complement cluster and HLA-B

    Spies, T.; Bresnahan, M.; Strominger, J.L.

    1989-01-01

    A 600-kilobase (kb) DNA segment from the human major histocompatibility complex (MHC) class III region was isolated by extension of a previous 435-kb chromosome walk. The contiguous series of cloned overlapping cosmids contains the entire 555-kb interval between C2 in the complement gene cluster and HLA-B. This region is known to encode the tumor necrosis factors (TNFs) α and β, B144, and the major heat shock protein HSP70. Moreover, a cluster of genes, BAT1-BAT5 (HLA-B-associated transcripts) have been localized in the vicinity of the genes for TNFα and TNFβ. An additional four genes were identified by isolation of corresponding cDNA clones with cosmid DNA probes. These genes for BAT6-BAT9 were mapped near the gene for C2 within a 120-kb region that includes a HSP70 gene pair. These results, together with complementary data from a similar recent study, indicated the presence of a minimum of 19 genes within the C2-HLA-B interval of the MHC class III region. Although the functional properties of most of these genes are yet unknown, they may be involved in some aspects of immunity. This idea is supported by the genetic mapping of the hematopoietic histocompatibility locus-1 (Hh-1) in recombinant mice between TNFα and H-2S, which is homologous to the complement gene cluster in humans

  18. What do multiple sclerosis patients and their caregivers perceive as unmet needs?

    Lorefice, Lorena; Mura, Gioia; Coni, Giulia; Fenu, Giuseppe; Sardu, Claudia; Frau, Jessica; Coghe, Giancarlo; Melis, Marta; Marrosu, Maria Giovanna; Cocco, Eleonora

    2013-11-15

    Multiple sclerosis (MS) has a major impact on the physical, psychological and social life of patients and their families. The aim of this study was to evaluate the different perceptions of patients and caregivers about management of MS, particularly about the same items, to gather information to ameliorate the care of patients. We evaluated what MS patients and caregivers perceive as unmet needs and compared patients' opinions with caregivers' opinions using a multidimensional questionnaire. The questionnaire was specifically designed for the study, taking into account different aspects of the global care perceived by patients and care givers, such as information about MS, medical treatment and rehabilitation, patients' relationships with medical staff and their psychological and social life. We administered the questionnaire to 497 patients and 206 caregivers. Results showed that the majority of participants were satisfied with medical staff but expressed a desire that staff be more forthcoming with information about MS. As for medical treatment concerns, more patients found there to be useful a multidisciplinary approach than caregivers did. Both required psychological support for patients but patients felt a greater need for it at the time of diagnosis, whereas caregivers felt it was required post-diagnosis. Both reported significant strains on patient relationships at work but no effect on other social interactions. A better understanding of MS patient needs, starting from the point of view of patients and caregivers, could have a great impact on quality of life and on management of the disease.

  19. Clinical roundtable monograph: unmet needs in the treatment of chronic lymphocytic leukemia: integrating a targeted approach.

    O'Brien, Susan M; Furman, Richard R; Byrd, John C; Smith, Ashbel

    2014-01-01

    Chronic lymphocytic leukemia (CLL) is the most frequently diagnosed hematologic malignancy in the United States. Although several features can be useful in the diagnosis of CLL, the most important is the immunophenotype.Two staging systems--the Binet system and the Rai classification--are used to assess risk. After diagnosis, the first major therapeutic decision is when to initiate therapy, as a watchful waiting approach is often appropriate for patients with asymptomatic disease. Once a patient has met the criteria for treatment, the choice of therapy is the next major decision. Younger patients (<65 years) often receive more aggressive treatment that typically consists of cytotoxic chemotherapy. There is a great unmet need concerning treatment of older patients with CLL, who often present with more comorbid conditions that can decrease their ability to tolerate particular regimens. The current standard of care for older patients with CLL is rituximab plus chlorambucil. The concept of targeted agents is currently an area of intense interest in CLL. The Bruton’s tyrosine kinase inhibitor ibrutinib is the targeted agent that is furthest along in clinical development. It is associated with an overall survival rate of 83%. Idelalisib targets the phosphatidyl inositol 3-kinase and is under evaluation in pivotal trials. Targeted agents offer much promise in terms of efficacy, toxicity, and oral availability. They will change the management of patients with CLL.

  20. Methodology for and the determination of the major constituents and metabolites of the Amazonian botanical medicine ayahuasca in human urine.

    McIlhenny, Ethan H; Riba, Jordi; Barbanoj, Manel J; Strassman, Rick; Barker, Steven A

    2011-09-01

    Ayahuasca, also known as caapi or yage among various South American groups, holds a highly esteemed and millennia-old position in these cultures' medical and religious pharmacopeia. There is now an increasing interest in the potential for modern medical applications of ayahuasca, as well as concerns regarding its increasing potential for abuse. Toxicological and clinical research to address these issues will require information regarding its metabolism and clearance. Thus, a rapid, sensitive and specific method for characterization and quantitation of the major constituents and of the metabolites of ayahuasca in urine is needed. The present research provides a protocol for conducting such analyses. The characteristics of the method, conducted by sample dilution and using HPLC-electrospray ionization (ESI)-selected reaction monitoring (SRM)-tandem mass spectrometry, are presented. The application of the analytical protocol to urine samples collected from three individuals that were administered ayahuasca has also been demonstrated. The data show that the major metabolite of the hallucinogenic component of ayahuasca, N,N-dimethyltryptamine (DMT), is the corresponding N-oxide, the first time this metabolite has been described in in vivo studies in humans. Further, very little DMT was detected in urine, despite the inhibition of monoamine oxidase afforded by the presence of the harmala alkaloids in ayahuasca. The major harmala alkaloid excreted was tetrahydroharmine. Other excretion products and metabolites were also identified and quantified. The method described would be suitable for use in further toxicological and clinical research on ayahuasca. Copyright © 2010 John Wiley & Sons, Ltd.

  1. Slaughterhouse pigs are a major reservoir of Streptococcus suis serotype 2 capable of causing human infection in southern Vietnam.

    Thi Hoa Ngo

    2011-03-01

    Full Text Available Streptococcus suis is a pathogen of major economic significance to the swine industry and is increasingly recognized as an emerging zoonotic agent in Asia. In Vietnam, S. suis is the leading cause of bacterial meningitis in adult humans. Zoonotic transmission is most frequently associated with serotype 2 strains and occupational exposure to pigs or consumption of infected pork. To gain insight into the role of pigs for human consumption as a reservoir for zoonotic infection in southern Vietnam, we determined the prevalence and diversity of S. suis carriage in healthy slaughterhouse pigs. Nasopharyngeal tonsils were sampled from pigs at slaughterhouses serving six provinces in southern Vietnam and Ho Chi Minh City area from September 2006 to November 2007. Samples were screened by bacterial culture. Isolates of S. suis were serotyped and characterized by multi locus sequence typing (MLST and pulse field gel electrophoresis (PFGE. Antibiotic susceptibility profiles and associated genetic resistance determinants, and the presence of putative virulence factors were determined. 41% (222/542 of pigs carried S. suis of one or multiple serotypes. 8% (45/542 carried S. suis serotype 2 which was the most common serotype found (45/317 strains, 14%. 80% of serotype 2 strains belonged to the MLST clonal complex 1,which was previously associated with meningitis cases in Vietnam and outbreaks of severe disease in China in 1998 and 2005. These strains clustered with representative strains isolated from patients with meningitis in PFGE analysis, and showed similar antimicrobial resistance and virulence factor profiles. Slaughterhouse pigs are a major reservoir of S. suis serotype 2 capable of causing human infection in southern Vietnam. Strict hygiene at processing facilities, and health education programs addressing food safety and proper handling of pork should be encouraged.

  2. Irritable bowel syndrome: the burden and unmet needs in Europe.

    Quigley, E M M

    2012-02-03

    Irritable bowel syndrome affects approximately 10-15% of the European population, although prevalence rates vary depending on the classification used and the country surveyed. This may be due to differences in patterns of medical care and diagnosis of the condition. Up to 70% of individuals with irritable bowel syndrome may not have been formally diagnosed. The disorder affects 1.5-3 times as many women as men and poses a significant economic burden in Europe, estimated at euro 700-euro 1600 per person per year. It also reduces quality of life and is associated with psychological distress, disturbed work and sleep, and sexual dysfunction. It is a chronic disorder, which affects many individuals for more than 10 years. Most patients are managed in primary care, although some are referred to gastroenterologists and other specialists. Patients with irritable bowel syndrome undergo more abdomino-pelvic surgery than the general population. We propose that a positive diagnosis of the condition may avoid the delay in diagnosis many patients experience. We conclude that, in Europe, there are significant unmet needs including lack of familiarity with irritable bowel syndrome, difficulties in diagnosis and lack of effective treatments for the multiple symptoms of the disorder. The development of pan-European guidelines for irritable bowel syndrome will benefit patients with this condition in Europe.

  3. Mucoadhesive oral films: The potential for unmet needs.

    Silva, Branca M A; Borges, Ana Filipa; Silva, Cláudia; Coelho, Jorge F J; Simões, Sérgio

    2015-10-15

    Oral drug delivery is the most common route of drug administration. Nevertheless, there are some important limitations that reinforce the need for developing new drug delivery systems. Mucoadhesive oral films (MOF) are promising dosage forms that adhere to the oral mucosa and deliver the drug through it, which present several advantages. These include: bypassing the hepatic first pass effect, fast onset of action, ease of transportation and handling. The use of such dosage form is beneficial for drugs that have poor oral bioavailability and also for drugs that need to be rapidly absorbed. In spite of the known benefits, the number of marketed MOF is still quite small. This review explores the products under development and corresponding clinical trials in respect to their status, therapeutic indication, companies involved and technologies. In this way, it was possible to identify the preferred therapeutic indications, new research and market trends as well as future prospects of MOF. Moreover, it is reasonable to expect an increase in the number of products on the market due to their great potential to satisfy unmet medical needs. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Merkel cell carcinoma: Epidemiology, prognosis, therapy and unmet medical needs.

    Schadendorf, Dirk; Lebbé, Céleste; Zur Hausen, Axel; Avril, Marie-Françoise; Hariharan, Subramanian; Bharmal, Murtuza; Becker, Jürgen C

    2017-01-01

    Merkel cell carcinoma (MCC) is a rare skin cancer that is associated with Merkel cell polyomavirus infection in most cases. Incidence rates of MCC have increased in past decades. Risk factors for MCC include ultraviolet light exposure, immunosuppression and advanced age. MCC is an aggressive malignancy with frequent recurrences and a high mortality rate, although patient outcomes are generally more favourable if the patient is referred for treatment at an early stage. Although advances have been made recently in the MCC field, large gaps remain with regard to definitive biomarkers and prognostic indicators. Although MCC is chemosensitive, responses in advanced stages are mostly of short duration, and the associated clinical benefit on overall survival is unclear. Recent nonrandomised phase 2 clinical trials with anti-PD-L1/PD-1 antibodies have demonstrated safety and efficacy; however, there are still no approved treatments for patients with metastatic MCC. Patients with advanced disease are encouraged to participate in clinical trials for treatment, indicating the largely unmet need for durable, safe treatment within this population. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Identifying unmet clinical need in hypertrophic cardiomyopathy using national electronic health records.

    Mar Pujades-Rodriguez

    Full Text Available To evaluate unmet clinical need in unselected hypertrophic cardiomyopathy (HCM patients to determine the risk of a wide range of subsequent cardiovascular disease endpoints and safety endpoints relevant for trial design.Population based cohort (CALIBER, linked primary care, hospital and mortality records in England, period 1997-2010, all people diagnosed with HCM were identified and matched by age, sex and general practice with ten randomly selected people without HCM. Random-effects Poisson models were used to assess the associations between HCM and cardiovascular diseases and bleeding.Among 3,290,455 eligible people a diagnosis of hypertrophic cardiomyopathy was found in 4 per 10,000. Forty-one percent of the 1,160 individuals with hypertrophic cardiomyopathy were women and the median age was 57 years. The median follow-up was 4.0 years. Compared to general population controls, people with HCM had higher risk of ventricular arrhythmia (incidence rate ratio = 23.53, [95% confidence interval 12.67-43.72], cardiac arrest or sudden cardiac death (6.33 [3.69-10.85], heart failure (4.31, [3.30-5.62], and atrial fibrillation (3.80 [3.04-4.75]. HCM was also associated with a higher incidence of myocardial infarction ([MI] 1.90 [1.27-2.84] and coronary revascularisation (2.32 [1.46-3.69].The absolute Kaplan-Meier risks at 3 years were 8.8% for the composite endpoint of cardiovascular death or heart failure, 8.4% for the composite of cardiovascular death, stroke or myocardial infarction, and 1.5% for major bleeding.Our study identified major unmet need in HCM and highlighted the importance of implementing improved cardiovascular prevention strategies to increase life-expectancy of the contemporary HCM population. They also show that national electronic health records provide an effective method for identifying outcomes and clinically relevant estimates of composite efficacy and safety endpoints essential for trial design in rare diseases.

  6. Identifying unmet clinical need in hypertrophic cardiomyopathy using national electronic health records.

    Pujades-Rodriguez, Mar; Guttmann, Oliver P; Gonzalez-Izquierdo, Arturo; Duyx, Bram; O'Mahony, Constantinos; Elliott, Perry; Hemingway, Harry

    2018-01-01

    To evaluate unmet clinical need in unselected hypertrophic cardiomyopathy (HCM) patients to determine the risk of a wide range of subsequent cardiovascular disease endpoints and safety endpoints relevant for trial design. Population based cohort (CALIBER, linked primary care, hospital and mortality records in England, period 1997-2010), all people diagnosed with HCM were identified and matched by age, sex and general practice with ten randomly selected people without HCM. Random-effects Poisson models were used to assess the associations between HCM and cardiovascular diseases and bleeding. Among 3,290,455 eligible people a diagnosis of hypertrophic cardiomyopathy was found in 4 per 10,000. Forty-one percent of the 1,160 individuals with hypertrophic cardiomyopathy were women and the median age was 57 years. The median follow-up was 4.0 years. Compared to general population controls, people with HCM had higher risk of ventricular arrhythmia (incidence rate ratio = 23.53, [95% confidence interval 12.67-43.72]), cardiac arrest or sudden cardiac death (6.33 [3.69-10.85]), heart failure (4.31, [3.30-5.62]), and atrial fibrillation (3.80 [3.04-4.75]). HCM was also associated with a higher incidence of myocardial infarction ([MI] 1.90 [1.27-2.84]) and coronary revascularisation (2.32 [1.46-3.69]).The absolute Kaplan-Meier risks at 3 years were 8.8% for the composite endpoint of cardiovascular death or heart failure, 8.4% for the composite of cardiovascular death, stroke or myocardial infarction, and 1.5% for major bleeding. Our study identified major unmet need in HCM and highlighted the importance of implementing improved cardiovascular prevention strategies to increase life-expectancy of the contemporary HCM population. They also show that national electronic health records provide an effective method for identifying outcomes and clinically relevant estimates of composite efficacy and safety endpoints essential for trial design in rare diseases.

  7. YB-1 facilitates basal and 5-fluorouracil-inducible expression of the human major vault protein (MVP) gene.

    Stein, Ulrike; Bergmann, Stephan; Scheffer, George L; Scheper, Rik J; Royer, Hans-Dieter; Schlag, Peter M; Walther, Wolfgang

    2005-05-19

    Vaults have been suggested to play a direct role in multidrug resistance (MDR) to anticancer drugs. The human major vault protein (MVP) also known as lung resistance-related protein (LRP) represents the predominant component of vaults that may be involved in the defense against xenobiotics. Here, we demonstrate that besides MDR-related cytostatics, also the non-MDR-related drug 5-fluorouracil (5-FU) was able to induce MVP mRNA and protein expression. Treatment with 5-FU amplified the binding activity and interaction of the transcription factor Y-box binding protein-1 (YB-1) with the Y-box of the human MVP gene promoter in a time-dependent manner. 5-FU also induced reporter expressions driven by a panel of newly generated MVP promoter deletion mutants. Interestingly, stably YB-1 overexpressing cell clones showed enhanced binding of YB-1 to the Y-box motif, associated with enhanced basal as well as 5-FU-inducible MVP promoter-driven reporter expressions. Moreover, transduction of YB-1 cDNA led to increased expression of endogenous MVP protein. Under physiological conditions, we observed a strong coexpression of MVP and YB-1 in human colon carcinoma specimen. In summary, our data demonstrate a direct involvement of YB-1 in controlling basal and 5-FU-induced MVP promoter activity. Therefore, YB-1 is directly linked to MVP-mediated drug resistance.

  8. Medical Undergraduate Survey on Headache Education in Singapore: Knowledge, Perceptions, and Assessment of Unmet Needs.

    Ong, Jonathan Jia Yuan; Chan, Yee Cheun

    2017-06-01

    There have been no prior studies assessing the status of undergraduate headache training and education in Singapore. Unmet needs of undergraduate medical students in terms of knowledge-practice gaps pertaining to diagnosis and management of headache disorders are unknown. The possible underemphasis of this aspect of the curriculum as compared to other chronic conditions such as diabetes mellitus has also not been ascertained. The aim of this article is to assess the knowledge base and perceptions, thereby identifying the unmet needs of headache disorder education in undergraduate medical students. Students reported their perceived time that was devoted to the subject matter and this was recorded and reported. In order to provide a comparative indication on the level of prioritization, the total duration within the syllabus dedicated to headache education vs other chronic diseases (using diabetes mellitus as a surrogate) was sought. A comprehensive survey consisting of questions assessing the headache curriculum, knowledge, and perceptions was developed. The questionnaire was distributed to final year medical students attending a full-day Neurology review course in their last semester. Attendees were given the duration of the course to complete the questionnaire, and forms were collected at the end of the day. About 127 final year medical students completed our survey. More than half (55.1%) did not receive formal teaching on how to take a complete headache history. The majority (90.6%) have not attended a headache sub-specialty clinic. The mean total number of hours exposed to headache disorders was 5.69h (SD ± 5.19). The vast majority (96.1%) were unfamiliar with locally published clinical practice guidelines, and a significant proportion (74.0%) were unfamiliar with the third edition (beta) of the International Classification of Headache Disorders. Nearly half (47.2%) were unfamiliar with 'medication overuse headache' as a disease entity. Only one (0

  9. Donor-recipient human leukocyte antigen matching practices in vascularized composite tissue allotransplantation: a survey of major transplantation centers.

    Ashvetiya, Tamara; Mundinger, Gerhard S; Kukuruga, Debra; Bojovic, Branko; Christy, Michael R; Dorafshar, Amir H; Rodriguez, Eduardo D

    2014-07-01

    Vascularized composite tissue allotransplant recipients are often highly sensitized to human leukocyte antigens because of multiple prior blood transfusions and other reconstructive operations. The use of peripheral blood obtained from dead donors for crossmatching may be insufficient because of life support measures taken for the donor before donation. No study has been published investigating human leukocyte antigen matching practices in this field. A survey addressing human leukocyte antigen crossmatching methods was generated and sent to 22 vascularized composite tissue allotransplantation centers with active protocols worldwide. Results were compiled by center and compared using two-tailed t tests. Twenty of 22 centers (91 percent) responded to the survey. Peripheral blood was the most commonly reported donor sample for vascularized composite tissue allotransplant crossmatching [78 percent of centers (n=14)], with only 22 percent (n=4) using lymph nodes. However, 56 percent of the 18 centers (n=10) that had performed vascularized composite tissue allotransplantation reported that they harvested lymph nodes for crossmatching. Of responding individuals, 62.5 percent (10 of 16 individuals) felt that lymph nodes were the best donor sample for crossmatching. A slight majority of vascularized composite tissue allotransplant centers that have performed clinical transplants have used lymph nodes for human leukocyte antigen matching, and centers appear to be divided on the utility of lymph node harvest. The use of lymph nodes may offer a number of potential benefits. This study highlights the need for institutional review board-approved crossmatching protocols specific to vascularized composite tissue allotransplantation, and the need for global databases for sharing of vascularized composite tissue allotransplantation experiences.

  10. Apamin does not inhibit human cardiac Na+ current, L-type Ca2+ current or other major K+ currents.

    Chih-Chieh Yu

    Full Text Available Apamin is commonly used as a small-conductance Ca2+-activated K+ (SK current inhibitor. However, the specificity of apamin in cardiac tissues remains unclear.To test the hypothesis that apamin does not inhibit any major cardiac ion currents.We studied human embryonic kidney (HEK 293 cells that expressed human voltage-gated Na+, K+ and Ca2+ currents and isolated rabbit ventricular myocytes. Whole-cell patch clamp techniques were used to determine ionic current densities before and after apamin administration.Ca2+ currents (CACNA1c+CACNB2b were not affected by apamin (500 nM (data are presented as median [25th percentile;75th percentile] (from -16 [-20;-10] to -17 [-19;-13] pA/pF, P = NS, but were reduced by nifedipine to -1.6 [-3.2;-1.3] pA/pF (p = 0.008. Na+ currents (SCN5A were not affected by apamin (from -261 [-282;-145] to -268 [-379;-132] pA/pF, P = NS, but were reduced by flecainide to -57 [-70;-47] pA/pF (p = 0.018. None of the major K+ currents (IKs, IKr, IK1 and Ito were inhibited by 500 nM of apamin (KCNQ1+KCNE1, from 28 [20]; [37] to 23 [18]; [32] pA/pF; KCNH2+KCNE2, from 28 [24]; [30] to 27 [24]; [29] pA/pF; KCNJ2, from -46 [-48;-40] to -46 [-51;-35] pA/pF; KCND3, from 608 [505;748] to 606 [454;684]. Apamin did not inhibit the INa or ICaL in isolated rabbit ventricular myocytes (INa, from -67 [-75;-59] to -68 [-71;-59] pA/pF; ICaL, from -16 [-17;-14] to -14 [-15;-13] pA/pF, P = NS for both.Apamin does not inhibit human cardiac Na+ currents, L-type Ca2+ currents or other major K+ currents. These findings indicate that apamin is a specific SK current inhibitor in hearts as well as in other organs.

  11. Association between unmet needs and quality of life of cancer patients

    Hansen, Dorte Gilså; Larsen, Pia Veldt; Holm, Lise Vilstrup

    2013-01-01

    patients diagnosed between 1 October 2007 and 30 September 2008 was established. At 14 months following diagnosis participants completed a questionnaire including health-related quality of life (EORTC QLQ C-30), psychological distress (POMS-SF), and unmet needs with regard to physical, emotional, family......Abstract Background. Two conceptually different morbidity outcomes unmet needs and health-related quality of life are used to identify cancer patients in need of clinical attention and to evaluate rehabilitation programmes. The knowledge on the interrelation between unmet needs and health-related...... quality of life is scarce. This paper studies the hypothesis that patient-perceived unmet needs of rehabilitation during the cancer trajectory are associated with decreased quality of life. Material and methods. Based on registers, a Danish population-based cohort of adult, incident, mixed-site cancer...

  12. Comparative genomics of the major fungal agents of human and animal Sporotrichosis: Sporothrix schenckii and Sporothrix brasiliensis.

    Teixeira, Marcus M; de Almeida, Luiz G P; Kubitschek-Barreira, Paula; Alves, Fernanda L; Kioshima, Erika S; Abadio, Ana K R; Fernandes, Larissa; Derengowski, Lorena S; Ferreira, Karen S; Souza, Rangel C; Ruiz, Jeronimo C; de Andrade, Nathalia C; Paes, Hugo C; Nicola, André M; Albuquerque, Patrícia; Gerber, Alexandra L; Martins, Vicente P; Peconick, Luisa D F; Neto, Alan Viggiano; Chaucanez, Claudia B; Silva, Patrícia A; Cunha, Oberdan L; de Oliveira, Fabiana F M; dos Santos, Tayná C; Barros, Amanda L N; Soares, Marco A; de Oliveira, Luciana M; Marini, Marjorie M; Villalobos-Duno, Héctor; Cunha, Marcel M L; de Hoog, Sybren; da Silveira, José F; Henrissat, Bernard; Niño-Vega, Gustavo A; Cisalpino, Patrícia S; Mora-Montes, Héctor M; Almeida, Sandro R; Stajich, Jason E; Lopes-Bezerra, Leila M; Vasconcelos, Ana T R; Felipe, Maria S S

    2014-10-29

    The fungal genus Sporothrix includes at least four human pathogenic species. One of these species, S. brasiliensis, is the causal agent of a major ongoing zoonotic outbreak of sporotrichosis in Brazil. Elsewhere, sapronoses are caused by S. schenckii and S. globosa. The major aims on this comparative genomic study are: 1) to explore the presence of virulence factors in S. schenckii and S. brasiliensis; 2) to compare S. brasiliensis, which is cat-transmitted and infects both humans and cats with S. schenckii, mainly a human pathogen; 3) to compare these two species to other human pathogens (Onygenales) with similar thermo-dimorphic behavior and to other plant-associated Sordariomycetes. The genomes of S. schenckii and S. brasiliensis were pyrosequenced to 17x and 20x coverage comprising a total of 32.3 Mb and 33.2 Mb, respectively. Pair-wise genome alignments revealed that the two species are highly syntenic showing 97.5% average sequence identity. Phylogenomic analysis reveals that both species diverged about 3.8-4.9 MYA suggesting a recent event of speciation. Transposable elements comprise respectively 0.34% and 0.62% of the S. schenckii and S. brasiliensis genomes and expansions of Gypsy-like elements was observed reflecting the accumulation of repetitive elements in the S. brasiliensis genome. Mitochondrial genomic comparisons showed the presence of group-I intron encoding homing endonucleases (HE's) exclusively in S. brasiliensis. Analysis of protein family expansions and contractions in the Sporothrix lineage revealed expansion of LysM domain-containing proteins, small GTPases, PKS type1 and leucin-rich proteins. In contrast, a lack of polysaccharide lyase genes that are associated with decay of plants was observed when compared to other Sordariomycetes and dimorphic fungal pathogens, suggesting evolutionary adaptations from a plant pathogenic or saprobic to an animal pathogenic life style. Comparative genomic data suggest a unique ecological shift in the

  13. Using the unmet obstetric needs indicator to map inequities in life-saving obstetric interventions at the local health care system in Kenya

    Echoka, Elizabeth; Dubourg, Dominique; Makokha, Anselimo

    2014-01-01

    BackgroundDeveloping countries with high maternal mortality need to invest in indicators that not only provide information about how many women are dying, but also where, and what can be done to prevent these deaths. The unmet Obstetric Needs (UONs) concept provides this information. This concept...... was applied at district level in Kenya to assess how many women had UONs and where the women with unmet needs were located.MethodsA facility based retrospective study was conducted in 2010 in Malindi District, Kenya. Data on pregnant women who underwent a major obstetric intervention (MOI) or died...... in facilities that provide comprehensive Emergency Obstetric Care (EmOC) services in 2008 and 2009 were collected. The difference between the number of women who experienced life threatening obstetric complications and those who received care was quantified. The main outcome measures in the study were...

  14. Distribution and Determinants of Unmet Need for Supportive Care Among Women with Breast Cancer in China.

    Wang, Shouhua; Li, Yanqing; Li, Chaozhuo; Qiao, Yijun; He, Shuling

    2018-03-21

    BACKGROUND The aim of this study was to determine the need for supportive care among women suffering from breast cancer in China and to identify its potential determinants to inform the development of effective and efficient healthcare services across different settings. MATERIAL AND METHODS In a tertiary-care hospital in Weifang, China, between July 2015 and January 2016, all women attending the Breast Cancer Clinic for regular physical examinations after treatment for breast cancer were consecutively recruited. The 34-item Supportive Care Needs Survey tool (Chinese version) (SCNS-SF34-C) was used to assess the unmet needs among participants. RESULTS Among 264 recruited patients, based on at least single-item endorsement, 60.2% had moderate to high level of need for supportive care, while only 13.3% expressed no need. Lack of information regarding health systems was the most common domain with moderate to high unmet needs, more so among rural patients (8 vs. 5 out of 10). In each information-related domain, huge unmet need was observed among all patients irrespective of urban or rural residence. Both overall and individual information-related domain-specific unmet needs were significantly higher among rural patients as opposed to their urban counterparts. Multiple regression analyses revealed a significant rural-urban variation of unmet needs. Moreover, education and post-diagnosis time duration were negatively associated with unmet needs while stage of cancer was positively associated with these unmet needs. CONCLUSIONS There is a huge burden of unmet needs for information on the healthcare system among breast cancer survivors in China. Rural residence, less education, advanced stage of cancer, and shorter duration since diagnosis were the identified determinants requiring targeted intervention.

  15. Examining Sexual Orientation Disparities in Unmet Medical Needs among Men and Women

    Everett, Bethany G.; Mollborn, Stefanie

    2013-01-01

    Using the National Longitudinal Study of Adolescent Health (N = 13,810), this study examines disparities in unmet medical needs by sexual orientation identity during young adulthood. We use binary logistic regression and expand Andersen’s health care utilization framework to identify factors that shape disparities in unmet medical needs by sexual orientation. We also investigate whether the well-established gender disparity in health-seeking behaviors among heterosexual persons holds for sexu...

  16. Determinants of unmet need for family planning in rural Burkina Faso: a multilevel logistic regression analysis.

    Wulifan, Joseph K; Jahn, Albrecht; Hien, Hervé; Ilboudo, Patrick Christian; Meda, Nicolas; Robyn, Paul Jacob; Saidou Hamadou, T; Haidara, Ousmane; De Allegri, Manuela

    2017-12-19

    Unmet need for family planning has implications for women and their families, such as unsafe abortion, physical abuse, and poor maternal health. Contraceptive knowledge has increased across low-income settings, yet unmet need remains high with little information on the factors explaining it. This study assessed factors associated with unmet need among pregnant women in rural Burkina Faso. We collected data on pregnant women through a population-based survey conducted in 24 rural districts between October 2013 and March 2014. Multivariate multilevel logistic regression was used to assess the association between unmet need for family planning and a selection of relevant demand- and supply-side factors. Of the 1309 pregnant women covered in the survey, 239 (18.26%) reported experiencing unmet need for family planning. Pregnant women with more than three living children [OR = 1.80; 95% CI (1.11-2.91)], those with a child younger than 1 year [OR = 1.75; 95% CI (1.04-2.97)], pregnant women whose partners disapproves contraceptive use [OR = 1.51; 95% CI (1.03-2.21)] and women who desired fewer children compared to their partners preferred number of children [OR = 1.907; 95% CI (1.361-2.672)] were significantly more likely to experience unmet need for family planning, while health staff training in family planning logistics management (OR = 0.46; 95% CI (0.24-0.73)] was associated with a lower probability of experiencing unmet need for family planning. Findings suggest the need to strengthen family planning interventions in Burkina Faso to ensure greater uptake of contraceptive use and thus reduce unmet need for family planning.

  17. Prevalence and determinants of unmet need for family planning in Kishanganj district, Bihar, India

    Kanchan Lata

    2012-01-01

    Full Text Available Background: Unmet need is a valuable indicator for assessing the achievements of national family planning programs. The present study was undertaken with the objectives to determine the magnitude of unmet need for family planning among the married women of reproductive age group (15-49 years, to evaluate the various factors that influence the unmet need and to explore the common reasons for unmet need for family planning. Methods: A community based, cross-sectional study was conducted from February to April 2012 in Laucha village in Kishanganj, Bihar through multistage sampling. Married women aged 15-49 years, who were permanent residents of the village, were selected by complete enumeration (330 in total and interviewed through house to house survey with the help of a pre-designed, pre-tested and semi-structured questionnaire. Results: The total unmet need for family planning was 23.9%; 9.4% for spacing births and 14.5% for limiting births. The unmet need varied significantly with age (p < 0.05 and was highest in ≤ 19 years age group (33.7%. It was also significantly higher among illiterates, those with low monthly per capita income, among Muslims and among those having more than two living issues (p < 0.05. Husband’s disapproval (34.2%, lack of awareness (27.8% and fear of side effects (24.1% were common reasons behind the unmet need. Conclusion: the unmet need for family planning was quite high among the respondents and associated with various bio-social determinants that should be considered while planning for scaling-up the program.

  18. Prevalence and determinants of unmet need for family planning in Kishanganj district, Bihar, India

    Kanchan Lata

    2012-07-01

    Full Text Available Background: Unmet need is a valuable indicator for assessing the achievements of national family planning programs. The present study was undertaken with the objectives to determine the magnitude of unmet need for family planning among the married women of reproductive age group (15-49 years, to evaluate the various factors that influence the unmet need and to explore the common reasons for unmet need for family planning. Methods: A community based, cross-sectional study was conducted from February to April 2012 in Laucha village in Kishanganj, Bihar through multistage sampling. Married women aged 15-49 years, who were permanent residents of the village, were selected by complete enumeration (330 in total and interviewed through house to house survey with the help of a pre-designed, pre-tested and semi-structured questionnaire. Results: The total unmet need for family planning was 23.9%; 9.4% for spacing births and 14.5% for limiting births. The unmet need varied significantly with age (p < 0.05 and was highest in ≤ 19 years age group (33.7%. It was also significantly higher among illiterates, those with low monthly per capita income, among Muslims and among those having more than two living issues (p < 0.05. Husband’s disapproval (34.2%, lack of awareness (27.8% and fear of side effects (24.1% were common reasons behind the unmet need. Conclusion: the unmet need for family planning was quite high among the respondents and associated with various bio-social determinants that should be considered while planning for scaling-up the program.

  19. Unmet/met need for contraception and self-reported abortion in Ghana.

    Amo-Adjei, Joshua; Darteh, Eugene K M

    2017-10-01

    Unmet need for contraception in several sub-Saharan African countries, including Ghana, remains high, with implications for unintended pregnancies and unsafe abortion, associated maternal morbidity and mortality. In this paper, we analysed for any associations between unmet/met need for contraception and the prevalence of abortion. The paper utilizes the 2014 Ghana Demographic Health Survey dataset. Applying descriptive statistics initially, and later, a binary logistic regression, we estimate two different models, taking into account, unmet/met need for contraception (Model 1) and a multivariable one comprising socioeconomic, spatial, cultural and demographic behaviour variables (Model 2) to test the associations between unmet/met need for contraception in Ghana. One-fourth (25%) of sampled women in 2014 had ever had an abortion. The bivariate results showed that women who reported "no unmet" considerably tended to report abortion more than the reference category - not married and no sex in the last 30days. The elevated odds among respondents who indicated "no unmet need" persisted even after controlling for all the relevant confounders. Relatedly, unlike women with an unmet need for spacing, women who desired to limit childbearing had a slightly higher tendency to report an abortion. The linkage between unmet need for contraception appears more complex, particularly when the connections are explored post-abortion. Thus, while an abortion episode is most likely due to unintended pregnancy, contraception may still not be used, after an abortion, probably because of failure, side effects or simply, a dislike for any method. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Economic crisis, austerity and unmet healthcare needs: the case of Greece.

    Zavras, Dimitris; Zavras, Athanasios I; Kyriopoulos, Ilias-Ioannis; Kyriopoulos, John

    2016-07-27

    The programme for fiscal consolidation in Greece has led to income decrease and several changes in health policy. In this context, this study aims to assess how economic crisis affected unmet healthcare needs in Greece. Time series analysis was performed for the years 2004 through 2011 using the EU-SILC database. The dependent variable was the percentage of people who had medical needs but did not use healthcare services. Median income, unemployment and time period were used as independent variables. We also compared self-reported unmet healthcare needs drawn from a national survey conducted in pre-crisis 2006 with a similar survey from 2011 (after the onset of the crisis). A common questionnaire was used in both years to assess unmet healthcare needs, including year of survey, gender, age, health status, chronic disease, educational level, income, employment, health insurance status, and prefecture. The outcome of interest was unmet healthcare needs due to financial reasons. Ordinary least squares, as well as logistic regression analysis were conducted to analyze the results. Unmet healthcare needs increased after the enactment of austerity measures, while the year of participation in the survey was significantly associated with unmet healthcare needs. Income, educational level, employment status, and having insurance, private or public, were also significant determinants of unmet healthcare needs due to financial reasons. The adverse economic environment has significantly affected unmet health needs. Therefore health policy actions and social policy measures are essential in order to mitigate the negative impact on access to healthcare services and health status.

  1. The Human Cytomegalovirus Major Immediate-Early Proteins as Antagonists of Intrinsic and Innate Antiviral Host Responses

    Michael Nevels

    2009-11-01

    Full Text Available The major immediate-early (IE gene of human cytomegalovirus (CMV is believed to have a decisive role in acute infection and its activity is an important indicator of viral reactivation from latency. Although a variety of gene products are expressed from this region, the 72-kDa IE1 and the 86-kDa IE2 nuclear phosphoproteins are the most abundant and important. Both proteins have long been recognized as promiscuous transcriptional regulators. More recently, a critical role of the IE1 and IE2 proteins in counteracting nonadaptive host cell defense mechanisms has been revealed. In this review we will briefly summarize the available literature on IE1- and IE2-dependent mechanisms contributing to CMV evasion from intrinsic and innate immune responses.

  2. Leishmania major surface protease Gp63 interferes with the function of human monocytes and neutrophils in vitro

    Sørensen, A L; Hey, A S; Kharazmi, A

    1994-01-01

    In the present study the effect of Leishmania major surface protease Gp63 on the chemotaxis and oxidative burst response of human peripheral blood monocytes and neutrophils was investigated. It was shown that prior incubation of cells with Gp63 inhibited chemotaxis of neutrophils but not monocytes...... towards the chemotactic peptide f-met-leu-phe. On the other hand, chemotaxis of both neutrophils and monocytes towards zymosan-activated serum containing C5a was inhibited by Gp63. Monocyte and neutrophil chemiluminescence response to opsonized zymosan was reduced by preincubation of the cells with Gp63...... in a concentration-dependent manner. Notably, monocytes were inhibited to a much greater degree than neutrophils by a given concentration of Gp63, and they were also inhibited at much lower concentrations of the protease. The inhibitory effect of Gp63 on chemotaxis and chemiluminescence was completely abolished...

  3. Managing the unmet psychosocial and information needs of patients with cancer

    Kathleen Abrahamson

    2010-11-01

    Full Text Available Kathleen Abrahamson1, Morgan Durham1, Rebekah Fox21Department of Public Health, Western Kentucky University, Bowling Green, KY, USA; 2Department of Communication, Texas State University, San Marcos, TX, USAAbstract: In this article, we synthesize current literature regarding the unmet needs of cancer patients, with a specific focus on interventions that address psychosocial distress, social support, and information deficits. Research indicates many patients diagnosed with cancer express unmet needs in terms of emotional distress, decision-making support, and practical concerns such as childcare, transportation, and financial assistance. Four types of system-level barriers to the meeting of patient psychosocial and information-based needs emerge from the literature: underidentification of needs due to inadequate assessment, time constraints on cancer care providers, lack of adequate reimbursement for psychosocial and information services, and barriers related to communication of disease-related information. There is also evidence that unmet need, especially unmet information need, is related to the level of patient health literacy. Patient empowerment through the resolution of unmet needs increases patient participation in care, and is especially crucial in regards to understanding risks and benefits of treatment. There is evidence that some interventions are effective for some patients, and that even relatively simple interventions can reduce psychosocial and information-based needs. The challenge is therefore to discover which intervention will be effective for each individual patient, and to attain the skills and resources necessary to intervene appropriately.Keywords: cancer, unmet need, health literacy, intervention

  4. Examining Sexual Orientation Disparities in Unmet Medical Needs among Men and Women.

    Everett, Bethany G; Mollborn, Stefanie

    2014-08-01

    Using the National Longitudinal Study of Adolescent Health (N = 13,810), this study examines disparities in unmet medical needs by sexual orientation identity during young adulthood. We use binary logistic regression and expand Andersen's health care utilization framework to identify factors that shape disparities in unmet medical needs by sexual orientation. We also investigate whether the well-established gender disparity in health-seeking behaviors among heterosexual persons holds for sexual minorities. The results show that sexual minority women are more likely to report unmet medical needs than heterosexual women, but no differences are found between sexual minority and heterosexual men. Moreover, we find a reversal in the gender disparity between heterosexual and sexual minority populations: heterosexual women are less likely to report unmet medical needs than heterosexual men, whereas sexual minority women are more likely to report unmet medical needs compared to sexual minority men. Finally, this work advances Andersen's model by articulating the importance of including social psychological factors for reducing disparities in unmet medical needs by sexual orientation for women.

  5. Do unmet needs differ geographically for children with special health care needs?

    Fulda, Kimberly G; Johnson, Katandria L; Hahn, Kristen; Lykens, Kristine

    2013-04-01

    The purpose of this study was to identify geographic differences in health indicators for children with special health care needs (CSHCN). It was hypothesized that geographic differences in unmet health care needs exist among CSHCN by region in the United States. Data were obtained from the National Survey of Children with Special Health Care Needs, 2005-2006. Nine variables representing unmet needs were analyzed by geographic region. The region with the highest percent of unmet needs was identified for each service. Logistic regression was utilized to determine differences by region after controlling for age, gender, ethnicity, race, federal poverty level, relationship of responder to child, insurance status, severity of condition, and size of household. A total of 40,723 CSHCN were represented. Crude analysis demonstrated that the greatest unmet need for routine preventive care, specialist care, prescription medications, physical/occupational/speech therapy, mental health care, and genetic counseling occurred in the West. The greatest unmet need for preventive dental care, respite care, and vision care occurred in the South. Significant differences between regions remained for six of the nine services after controlling for potential confounders. Geographic differences in unmet health care needs exist for CSHCN. Further delving into these differences provides valuable information for program and policy planning and development. Meeting the needs of CSHCN is important to reduce cost burden and improve quality of life for the affected child and care providers.

  6. Examining Sexual Orientation Disparities in Unmet Medical Needs among Men and Women

    Everett, Bethany G.; Mollborn, Stefanie

    2013-01-01

    Using the National Longitudinal Study of Adolescent Health (N = 13,810), this study examines disparities in unmet medical needs by sexual orientation identity during young adulthood. We use binary logistic regression and expand Andersen’s health care utilization framework to identify factors that shape disparities in unmet medical needs by sexual orientation. We also investigate whether the well-established gender disparity in health-seeking behaviors among heterosexual persons holds for sexual minorities. The results show that sexual minority women are more likely to report unmet medical needs than heterosexual women, but no differences are found between sexual minority and heterosexual men. Moreover, we find a reversal in the gender disparity between heterosexual and sexual minority populations: heterosexual women are less likely to report unmet medical needs than heterosexual men, whereas sexual minority women are more likely to report unmet medical needs compared to sexual minority men. Finally, this work advances Andersen’s model by articulating the importance of including social psychological factors for reducing disparities in unmet medical needs by sexual orientation for women. PMID:25382887

  7. MAJOR AND LYMPHOCYTE POPULATIONS OF HUMAN PERIPHERAL BLOOD LYMPHOCYTES AND THEIR REFERENCE VALUES, AS ASSAYED BY MULTI-COLOUR CYTOMETRY

    S. V. Khaidukov

    2009-01-01

    Full Text Available Abstract. Determination of lymphocyte subpopulations and their phenotypes is an important diagnostic feature, in order to elucidate some disturbances connected with immune system functioning. However, insufficient data are obtained when analyzing only major populations of peripheral lymphocytes. In order to perform clinical diagnostics, the data about minor lymphocytic populations and activated cellular pools seem to be more pertinent.Studies of peripheral blood cell subpopulations of healthy donors performed in different Russian regions allowed to assess quantitative distribution intervals for both major and minor immune cell subpopulations in humans. The results obtained, as compared with data from literature, provide an evidence for similar reference intervals for main immune cell subpopulations in healthy donors, independent on their habitation area.Present work has resulted into development of algorithms for cytometric studies and generation of certain panels of monoclonal antibodies enabling evaluation of all main lymphocyte subpopulations, as well as their minor subsets participating in emerging immune response. The distribution intervals have been estimated for such minor subpopulations, as B1- and B2-lymphocytes, memory B-cells, γδ- and αβT-cells, regulatory and naїve T-cells, cytotoxic and secretory NK-cell polupations.The results of present study, while been performed with peripheral blood of healthy donors, may provide a basis of reference values when studying subpopulation profile of immune cells.

  8. Ashwagandha leaf derived withanone protects normal human cells against the toxicity of methoxyacetic acid, a major industrial metabolite.

    Priyandoko, Didik; Ishii, Tetsuro; Kaul, Sunil C; Wadhwa, Renu

    2011-05-04

    The present day lifestyle heavily depends on industrial chemicals in the form of agriculture, cosmetics, textiles and medical products. Since the toxicity of the industrial chemicals has been a concern to human health, the need for alternative non-toxic natural products or adjuvants that serve as antidotes are in high demand. We have investigated the effects of Ayurvedic herb Ashwagandha (Withania somnifera) leaf extract on methoxyacetic acid (MAA) induced toxicity. MAA is a major metabolite of ester phthalates that are commonly used in industry as gelling, viscosity and stabilizer reagents. We report that the MAA cause premature senescence of normal human cells by mechanisms that involve ROS generation, DNA and mitochondrial damage. Withanone protects cells from MAA-induced toxicity by suppressing the ROS levels, DNA and mitochondrial damage, and induction of cell defense signaling pathways including Nrf2 and proteasomal degradation. These findings warrant further basic and clinical studies that may promote the use of withanone as a health adjuvant in a variety of consumer products where the toxicity has been a concern because of the use of ester phthalates.

  9. Ashwagandha leaf derived withanone protects normal human cells against the toxicity of methoxyacetic acid, a major industrial metabolite.

    Didik Priyandoko

    Full Text Available The present day lifestyle heavily depends on industrial chemicals in the form of agriculture, cosmetics, textiles and medical products. Since the toxicity of the industrial chemicals has been a concern to human health, the need for alternative non-toxic natural products or adjuvants that serve as antidotes are in high demand. We have investigated the effects of Ayurvedic herb Ashwagandha (Withania somnifera leaf extract on methoxyacetic acid (MAA induced toxicity. MAA is a major metabolite of ester phthalates that are commonly used in industry as gelling, viscosity and stabilizer reagents. We report that the MAA cause premature senescence of normal human cells by mechanisms that involve ROS generation, DNA and mitochondrial damage. Withanone protects cells from MAA-induced toxicity by suppressing the ROS levels, DNA and mitochondrial damage, and induction of cell defense signaling pathways including Nrf2 and proteasomal degradation. These findings warrant further basic and clinical studies that may promote the use of withanone as a health adjuvant in a variety of consumer products where the toxicity has been a concern because of the use of ester phthalates.

  10. Brain-derived neurotrophic factor--a major player in stimulation-induced homeostatic metaplasticity of human motor cortex?

    Claudia Mastroeni

    Full Text Available Repetitive transcranial magnetic stimulation (rTMS of the human motor hand area (M1HAND can induce lasting changes in corticospinal excitability as indexed by a change in amplitude of the motor-evoked potential. The plasticity-inducing effects of rTMS in M1HAND show substantial inter-individual variability which has been partially attributed to the val(66met polymorphism in the brain-derived neurotrophic factor (BDNF gene. Here we used theta burst stimulation (TBS to examine whether the BDNF val(66met genotype can be used to predict the expression of TBS-induced homeostatic metaplasticity in human M1HAND. TBS is a patterned rTMS protocol with intermittent TBS (iTBS usually inducing a lasting increase and continuous TBS (cTBS a lasting decrease in corticospinal excitability. In three separate sessions, healthy val(66met (n = 12 and val(66val (n = 17 carriers received neuronavigated cTBS followed by cTBS (n = 27, cTBS followed by iTBS (n = 29, and iTBS followed by iTBS (n = 28. Participants and examiner were blinded to the genotype at the time of examination. As expected, the first TBS intervention induced a decrease (cTBS and increase (iTBS in corticospinal excitability, respectively, at the same time priming the after effects caused by the second TBS intervention in a homeostatic fashion. Critically, val(66met carriers and val(66val carriers showed very similar response patterns to cTBS and iTBS regardless of the order of TBS interventions. Since none of the observed TBS effects was modulated by the BDNF val(66met polymorphism, our results do not support the notion that the BDNF val(66met genotype is a major player with regard to TBS-induced plasticity and metaplasticity in the human M1HAND.

  11. Brain-Derived Neurotrophic Factor – A Major Player in Stimulation-Induced Homeostatic Metaplasticity of Human Motor Cortex?

    Rizzo, Vincenzo; Ritter, Christoph; Klein, Christine; Pohlmann, Ines; Brueggemann, Norbert; Quartarone, Angelo; Siebner, Hartwig Roman

    2013-01-01

    Repetitive transcranial magnetic stimulation (rTMS) of the human motor hand area (M1HAND) can induce lasting changes in corticospinal excitability as indexed by a change in amplitude of the motor-evoked potential. The plasticity-inducing effects of rTMS in M1HAND show substantial inter-individual variability which has been partially attributed to the val66met polymorphism in the brain-derived neurotrophic factor (BDNF) gene. Here we used theta burst stimulation (TBS) to examine whether the BDNF val66met genotype can be used to predict the expression of TBS-induced homeostatic metaplasticity in human M1HAND. TBS is a patterned rTMS protocol with intermittent TBS (iTBS) usually inducing a lasting increase and continuous TBS (cTBS) a lasting decrease in corticospinal excitability. In three separate sessions, healthy val66met (n = 12) and val66val (n = 17) carriers received neuronavigated cTBS followed by cTBS (n = 27), cTBS followed by iTBS (n = 29), and iTBS followed by iTBS (n = 28). Participants and examiner were blinded to the genotype at the time of examination. As expected, the first TBS intervention induced a decrease (cTBS) and increase (iTBS) in corticospinal excitability, respectively, at the same time priming the after effects caused by the second TBS intervention in a homeostatic fashion. Critically, val66met carriers and val66val carriers showed very similar response patterns to cTBS and iTBS regardless of the order of TBS interventions. Since none of the observed TBS effects was modulated by the BDNF val66met polymorphism, our results do not support the notion that the BDNF val66met genotype is a major player with regard to TBS-induced plasticity and metaplasticity in the human M1HAND. PMID:23469118

  12. Brain-derived neurotrophic factor--a major player in stimulation-induced homeostatic metaplasticity of human motor cortex?

    Mastroeni, Claudia; Bergmann, Til Ole; Rizzo, Vincenzo; Ritter, Christoph; Klein, Christine; Pohlmann, Ines; Brueggemann, Norbert; Quartarone, Angelo; Siebner, Hartwig Roman

    2013-01-01

    Repetitive transcranial magnetic stimulation (rTMS) of the human motor hand area (M1HAND) can induce lasting changes in corticospinal excitability as indexed by a change in amplitude of the motor-evoked potential. The plasticity-inducing effects of rTMS in M1HAND show substantial inter-individual variability which has been partially attributed to the val(66)met polymorphism in the brain-derived neurotrophic factor (BDNF) gene. Here we used theta burst stimulation (TBS) to examine whether the BDNF val(66)met genotype can be used to predict the expression of TBS-induced homeostatic metaplasticity in human M1HAND. TBS is a patterned rTMS protocol with intermittent TBS (iTBS) usually inducing a lasting increase and continuous TBS (cTBS) a lasting decrease in corticospinal excitability. In three separate sessions, healthy val(66)met (n = 12) and val(66)val (n = 17) carriers received neuronavigated cTBS followed by cTBS (n = 27), cTBS followed by iTBS (n = 29), and iTBS followed by iTBS (n = 28). Participants and examiner were blinded to the genotype at the time of examination. As expected, the first TBS intervention induced a decrease (cTBS) and increase (iTBS) in corticospinal excitability, respectively, at the same time priming the after effects caused by the second TBS intervention in a homeostatic fashion. Critically, val(66)met carriers and val(66)val carriers showed very similar response patterns to cTBS and iTBS regardless of the order of TBS interventions. Since none of the observed TBS effects was modulated by the BDNF val(66)met polymorphism, our results do not support the notion that the BDNF val(66)met genotype is a major player with regard to TBS-induced plasticity and metaplasticity in the human M1HAND.

  13. Anti-apoptotic BFL-1 is the major effector in activation-induced human mast cell survival.

    Maria Ekoff

    Full Text Available Mast cells are best known for their role in allergic reactions, where aggregation of FcεRI leads to the release of mast cell mediators causing allergic symptoms. The activation also induces a survival program in the cells, i.e., activation-induced mast cell survival. The aim of the present study was to investigate how the activation-induced survival is mediated. Cord blood-derived mast cells and the mast cell line LAD-2 were activated through FcεRI crosslinking, with or without addition of chemicals that inhibit the activity or expression of selected Bcl-2 family members (ABT-737; roscovitine. Cell viability was assessed using staining and flow cytometry. The expression and function of Bcl-2 family members BFL-1 and MCL-1 were investigated using real-time quantitative PCR and siRNA treatment. The mast cell expression of Bfl-1 was investigated in skin biopsies. FcεRI crosslinking promotes activation-induced survival of human mast cells and this is associated with an upregulation of the anti-apoptotic Bcl-2 family member Bfl-1. ABT-737 alone or in combination with roscovitine decreases viability of human mast cells although activation-induced survival is sustained, indicating a minor role for Bcl-X(L, Bcl-2, Bcl-w and Mcl-1. Reducing BFL-1 but not MCL-1 levels by siRNA inhibited activation-induced mast cell survival. We also demonstrate that mast cell expression of Bfl-1 is elevated in birch-pollen-provocated skin and in lesions of atopic dermatitis and psoriasis patients. Taken together, our results highlight Bfl-1 as a major effector in activation-induced human mast cell survival.

  14. Developing a European research network to address unmet needs in anxiety disorders.

    Baldwin, David S; Pallanti, Stefano; Zwanzger, Peter

    2013-12-01

    Anxiety disorders are common, typically have an early onset, run a chronic or relapsing course, cause substantial personal distress, impair social and occupational function, reduce quality of life, and impose a substantial economic burden: they are often comorbid with major depression, bipolar disorder, schizophrenia, substance misuse and physical illness, and are associated with increased risks of suicidal behaviour. As such, anxiety disorders should be regarded as a significant public health problem. However the causes of anxiety disorders remain largely unknown, which hinders accurate diagnosis, the prediction of prognosis, and the development of refined treatment approaches. In clinical practice, many patients with anxiety disorders do not present or are not recognised, the standard of care they receive is often sub-optimal, and the effectiveness of pharmacological and psychological treatment interventions in real-world clinical practice can be disappointing. The current substantial unmet public health, clinical and research needs in anxiety disorders could be addressed in part by developing independent collaborative European networks. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Agomelatine, an innovative pharmacological response to unmet needs.

    Le Strat, Y; Gorwood, P

    2008-09-01

    Most of the available antidepressants, with different pharmacological profiles, such as inhibitors of serotonin reuptake (SSRIs) or norepinephrine reuptake (NRIs) or both (SNRIs), have limitations leading some patients to drop out of treatment. Another direction of research has therefore been undertaken, based initially on the fact that affective disorders are most often characterized by abnormal patterns of circadian rhythms. This consideration has led to the synthesis of agomelatine, a novel antidepressant combining melatonergic MT(1) and MT(2) agonism and serotonergic 5-HT(2C) antagonism. The antidepressant effects of agomelatine have been investigated in different animal models, including chronic mild stress, forced swimming, learned helplessness and psychosocial stress. All studies reported an antidepressant-like effect of agomelatine. A resynchronizing activity of agomelatine was seen in animal models for delayed sleep phase syndrome and in several original models of circadian disturbance, such as rodents infected by trypanosome or old hamsters. This activity of agomelatine on circadian rhythms was further confirmed in humans. Furthermore, several randomized, double-blind, placebo-controlled and comparator-controlled studies of agomelatine in the treatment of major depressive disorder indicate that agomelatine is effective and well tolerated.

  16. Perceptions of unmet healthcare needs: what do Punjabi and Chinese-speaking immigrants think? A qualitative study.

    Marshall, Emily G; Wong, Sabrina T; Haggerty, Jeannie L; Levesque, Jean-Fréderic

    2010-02-22

    Unmet healthcare needs - the difference between healthcare services deemed necessary to deal with a particular health problem and the actual services received - is commonly measured by the question, "During the past 12 months, was there ever a time when you felt that you needed healthcare, but you didn't receive it?" In 2003, unmet needs were reported by 10% of immigrants in Canada, yet, little is known specifically about Chinese- or Punjabi-speaking immigrants' perceptions and reporting of unmet needs. Our study examined: 1) How are unmet healthcare needs conceptualized among Chinese- and Punjabi-speaking immigrants? 2) Are their primary healthcare experiences related to their unmet healthcare needs? Twelve focus groups (6 Chinese, 6 Punjabi; n = 78) were conducted in Chinese or Punjabi and socio-demographic and health data were collected. Thematic analysis of focus group data examined the perceptions of unmet needs and any relationship to primary healthcare experiences. Our analysis revealed two overarching themes: 1) defining an unmet healthcare need and 2) identifying an unmet need. Participants had unmet healthcare needs in relation to barriers to accessing care, their lack of health system literacy, and when the health system was less responsive than their expectations. Asking whether someone ever had a time when they needed healthcare but did not receive it can either underestimate or overestimate unmet need. Measuring unmet need using single items is likely insufficient since more detail in a revised set of questions could begin to clarify whether the reporting of an unmet need was based on an expectation or a clinical need. Who defines what an unmet healthcare need is depends on the context (insured versus uninsured health services, experience in two or more healthcare systems versus experience in one healthcare system) and who is defining it (provider, patient, insurer).

  17. Can profiles of poly- and Perfluoroalkyl substances (PFASs) in human serum provide information on major exposure sources?

    Hu, Xindi C; Dassuncao, Clifton; Zhang, Xianming; Grandjean, Philippe; Weihe, Pál; Webster, Glenys M; Nielsen, Flemming; Sunderland, Elsie M

    2018-02-01

    Humans are exposed to poly- and perfluoroalkyl substances (PFASs) from diverse sources and this has been associated with negative health impacts. Advances in analytical methods have enabled routine detection of more than 15 PFASs in human sera, allowing better profiling of PFAS exposures. The composition of PFASs in human sera reflects the complexity of exposure sources but source identification can be confounded by differences in toxicokinetics affecting uptake, distribution, and elimination. Common PFASs, such as perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS) and their precursors are ubiquitous in multiple exposure sources. However, their composition varies among sources, which may impact associated adverse health effects. We use available PFAS concentrations from several demographic groups in a North Atlantic seafood consuming population (Faroe Islands) to explore whether chemical fingerprints in human sera provide insights into predominant exposure sources. We compare serum PFAS profiles from Faroese individuals to other North American populations to investigate commonalities in potential exposure sources. We compare individuals with similar demographic and physiological characteristics and samples from the same years to reduce confounding by toxicokinetic differences and changing environmental releases. Using principal components analysis (PCA) confirmed by hierarchical clustering, we assess variability in serum PFAS concentrations across three Faroese groups. The first principal component (PC)/cluster consists of C9-C12 perfluoroalkyl carboxylates (PFCAs) and is consistent with measured PFAS profiles in consumed seafood. The second PC/cluster includes perfluorohexanesulfonic acid (PFHxS) and the PFOS precursor N-ethyl perfluorooctane sulfonamidoacetate (N-EtFOSAA), which are directly used or metabolized from fluorochemicals in consumer products such as carpet and food packaging. We find that the same compounds are associated with the same

  18. Quantitative Profiling of Major Neutral Lipid Classes in Human Meibum by Direct Infusion Electrospray Ionization Mass Spectrometry

    Chen, Jianzhong; Green, Kari B.; Nichols, Kelly K.

    2013-01-01

    Purpose. The purpose of this investigation was to better understand lipid composition in human meibum. Methods. Intact lipids in meibum samples were detected by direct infusion electrospray ionization mass spectrometry (ESI-MS) analysis in positive detection mode using sodium iodide (NaI) as an additive. The peak intensities of all major types of lipid species, that is, wax esters (WEs), cholesteryl esters (CEs), and diesters (DEs) were corrected for peak overlapping and isotopic distribution; an additional ionization efficiency correction was performed for WEs and CEs, which was simplified by the observation that the corresponding ionization efficiency was primarily dependent on the specific lipid class and saturation degree of the lipids while independent of the carbon chain length. A set of WE and CE standards was spiked in meibum samples for ionization efficiency determination and absolute quantitation. Results. The absolute amount (μmol/mg) for each of 51 WEs and 31 CEs in meibum samples was determined. The summed masses for 51 WEs and 31 CEs accounted for 48 ± 4% and 40 ± 2%, respectively, of the total meibum lipids. The mass percentages of saturated and unsaturated species were determined to be 75 ± 2% and 25 ± 1% for CEs and 14 ± 1% and 86 ± 1% for WEs. The profiles for two types of DEs were also obtained, which include 42 α,ω Type II DEs, and 21 ω Type I-St DEs. Conclusions. Major neutral lipid classes in meibum samples were quantitatively profiled by ESI-MS analysis with NaI additive. PMID:23847307

  19. Special needs children with speech and hearing difficulties: prevalence and unmet needs.

    Kenney, Mary Kay; Kogan, Michael D

    2011-01-01

    The purpose of this study was to establish prevalences and sociodemographic characteristics associated with parent-reported speech and hearing difficulties among children with special health care needs (CSHCN); determine unmet needs for therapy, hearing aids, and communication devices; and examine the association between unmet needs and resources such as health insurance, early intervention/special education, and a medical home. Data were analyzed for 300,910 children without special health care needs and 40,723 CSHCN from the 2005-2006 National Survey of Children with Special Health Care Needs. Prevalence, sociodemographic characteristics, and unmet needs for 7132 CSHCN with speech difficulties and 1982 CSHCN with hearing difficulties were assessed. Logistic regression was used to determine the associations between unmet needs for therapy or hearing/communication devices and resources for addressing needs for therapy, hearing, and communication aids. The parent-reported prevalence of speech difficulty among CSHCN in the general population was 2.9% and approximately 20% among all CSHCN, in contrast to the lower prevalence of hearing difficulty (0.7% and 5%, respectively). Relative unmet need was greatest for communication devices and least for hearing aids. The strongest association with reducing unmet needs was having a medical home, and the most significant aspect of medical home was having effective care coordination. Having a medical home is significantly associated with fewer unmet needs for therapy and hearing/communication devices among CSHCN with speech and hearing difficulties. Care coordination may constitute an important factor that allows the primary care provider to link with services that CSHCN with communication problems require. Published by Elsevier Inc.

  20. Care coordination and unmet specialty care among children with special health care needs.

    Boudreau, Alexy Arauz; Perrin, James M; Goodman, Elizabeth; Kurowski, Daniel; Cooley, W Carl; Kuhlthau, Karen

    2014-06-01

    Care coordination and the medical home may ensure access to specialty care. Children with special health care needs (CSHCN) have higher rates of specialty care use and unmet need compared with the general pediatric population. We hypothesized that care coordination, regardless of whether it was provided in a medical home, would decrease unmet specialty care needs among CSHCN and that the effect of care coordination would be greater among low-income families. Secondary data analysis of participants in the 2009–2010 National Survey of CSHCN who reported unmet specialty care needs and for whom care coordination and medical home status could be determined (n = 18 905). Logistic regression models explored the association of unmet need with care coordination and medical home status adjusting for household income. Approximately 9% of CSHCN reported having unmet specialty care needs. Care coordination was associated with reduced odds of unmet specialty care need (without a medical home, odds ratio: 0.63, 95% confidence interval: 0.47–0.86; within a medical home, odds ratio: 0.22, 95% confidence interval: 0.16–0.29) with a greater reduction among those receiving care coordination within a medical home versus those receiving care coordination without a medical home. We did not find differences in the impact of care coordination by percentage of the federal poverty level. Care coordination is associated with family report of decreased unmet specialty care needs among CSHCN independent of household income. The effect of care coordination is greater when care is received in a medical home.

  1. The Expression of MTUS1/ATIP and Its Major Isoforms, ATIP1 and ATIP3, in Human Prostate Cancer

    Louis, Simon N.S., E-mail: simonnsl@unimelb.edu.au; Chow, Laurie T.C.; Varghayee, Naghmeh; Rezmann, Linda A.; Frauman, Albert G.; Louis, William J. [Clinical Pharmacology and Therapeutics Unit, Department of Medicine, University of Melbourne, Austin Health, Heidelberg 3084, Victoria (Australia)

    2011-10-11

    Angiotensin II (Ang II), the main effector of the renin angiotensin system, acts upon two distinct transmembrane receptors, the Ang II type 1 and the type 2 (AT{sub 2}-) receptor, to induce promotion and inhibition of ERK2 phosphorylation. The AT{sub 2}-receptor, through an interaction with its putative signaling partner MTUS1/ATIP (AT{sub 2}-receptor interacting protein), inhibits the mitogenic effects of EGF in prostate cancer cell lines representing both early and late stage disease. This is the first report on the expression of ATIP in normal and malignant human prostatic biopsies. The expression of ATIP and its major isoforms, ATIP1 and ATIP3, in normal prostatic cells and three prostate cancer cell lines was examined using QPCR and immunohistochemistry. Human biopsies containing benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN) and well, moderately and poorly differentiated prostate cancer were also examined. Overall, ATIP1 and ATIP3 mRNA expression was increased in malignant compared to normal tissues and cell lines. ATIP immunostaining was low or absent in both the basal and columnar epithelial cell layers surrounding BPH acini; however, it was observed in high concentration in neoplastic epithelial cells of HGPIN and was clearly evident in cytoplasms of malignant cells in all prostate cancer grades. ATIP immunostaining was also identified in the cytoplasms of LNCaP and PC3 prostate cancer cells. As the AT{sub 2}-receptor/ATIP inhibitory signaling pathway exists in malignant cells in all grades of prostate cancer, enhancement of this pathway may be a therapeutic target even after the development of androgen-independence.

  2. The Expression of MTUS1/ATIP and Its Major Isoforms, ATIP1 and ATIP3, in Human Prostate Cancer

    Louis, Simon N.S.; Chow, Laurie T.C.; Varghayee, Naghmeh; Rezmann, Linda A.; Frauman, Albert G.; Louis, William J.

    2011-01-01

    Angiotensin II (Ang II), the main effector of the renin angiotensin system, acts upon two distinct transmembrane receptors, the Ang II type 1 and the type 2 (AT 2 -) receptor, to induce promotion and inhibition of ERK2 phosphorylation. The AT 2 -receptor, through an interaction with its putative signaling partner MTUS1/ATIP (AT 2 -receptor interacting protein), inhibits the mitogenic effects of EGF in prostate cancer cell lines representing both early and late stage disease. This is the first report on the expression of ATIP in normal and malignant human prostatic biopsies. The expression of ATIP and its major isoforms, ATIP1 and ATIP3, in normal prostatic cells and three prostate cancer cell lines was examined using QPCR and immunohistochemistry. Human biopsies containing benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN) and well, moderately and poorly differentiated prostate cancer were also examined. Overall, ATIP1 and ATIP3 mRNA expression was increased in malignant compared to normal tissues and cell lines. ATIP immunostaining was low or absent in both the basal and columnar epithelial cell layers surrounding BPH acini; however, it was observed in high concentration in neoplastic epithelial cells of HGPIN and was clearly evident in cytoplasms of malignant cells in all prostate cancer grades. ATIP immunostaining was also identified in the cytoplasms of LNCaP and PC3 prostate cancer cells. As the AT 2 -receptor/ATIP inhibitory signaling pathway exists in malignant cells in all grades of prostate cancer, enhancement of this pathway may be a therapeutic target even after the development of androgen-independence

  3. Inhibitory Effects of Trapping Agents of Sulfur Drug Reactive Intermediates against Major Human Cytochrome P450 Isoforms

    Jasleen K. Sodhi

    2017-07-01

    Full Text Available In some cases, the formation of reactive species from the metabolism of xenobiotics has been linked to toxicity and therefore it is imperative to detect potential bioactivation for candidate drugs during drug discovery. Reactive species can covalently bind to trapping agents in in vitro incubations of compound with human liver microsomes (HLM fortified with β-nicotinamide adenine dinucleotide phosphate (NADPH, resulting in a stable conjugate of trapping agent and reactive species, thereby facilitating analytical detection and providing evidence of short-lived reactive metabolites. Since reactive metabolites are typically generated by cytochrome P450 (CYP oxidation, it is important to ensure high concentrations of trapping agents are not inhibiting the activities of CYP isoforms. Here we assessed the inhibitory properties of fourteen trapping agents against the major human CYP isoforms (CYP1A2, 2C9, 2C19, 2D6 and 3A. Based on our findings, eleven trapping agents displayed inhibition, three of which had IC50 values less than 1 mM (2-mercaptoethanol, N-methylmaleimide and N-ethylmaleimide (NEM. Three trapping agents (dimedone, N-acetyl-lysine and arsenite did not inhibit CYP isoforms at concentrations tested. To illustrate effects of CYP inhibition by trapping agents on reactive intermediate trapping, an example drug (ticlopidine and trapping agent (NEM were chosen for further studies. For the same amount of ticlopidine (1 μM, increasing concentrations of the trapping agent NEM (0.007–40 mM resulted in a bell-shaped response curve of NEM-trapped ticlopidine S-oxide (TSO-NEM, due to CYP inhibition by NEM. Thus, trapping studies should be designed to include several concentrations of trapping agent to ensure optimal trapping of reactive metabolites.

  4. Contribution of the major and minor subunits to fimbria-mediated adherence of Haemophilus influenzae to human epithelial cells and erythrocytes

    van Ham, S. M.; van Alphen, L.; Mooi, F. R.; van Putten, J. P.

    1995-01-01

    Fimbriae are colonization factors of the human pathogen Haemophilus influenzae in that they mediate bacterial adherence to human eukaryotic cells. The contribution of the major (HifA) and putative minor (HifD and HifE) subunits of H. influenzae fimbriae to fimbria-specific adherence was studied by

  5. A Cross-Reactive Human Single-Chain Antibody for Detection of Major Fish Allergens, Parvalbumins, and Identification of a Major IgE-Binding Epitope.

    Merima Bublin

    Full Text Available Fish allergy is associated with moderate to severe IgE-mediated reactions to the calcium binding parvalbumins present in fish muscle. Allergy to multiple fish species is caused by parvalbumin-specific cross-reactive IgE recognizing conserved epitopes. In this study, we aimed to produce cross-reactive single chain variable fragment (scFv antibodies for the detection of parvalbumins in fish extracts and the identification of IgE epitopes. Parvalbumin-specific phage clones were isolated from the human ETH-2 phage display library by three rounds of biopanning either against cod parvalbumin or by sequential biopanning against cod (Gad m 1, carp (Cyp c 1 and rainbow trout (Onc m 1 parvalbumins. While biopanning against Gad m 1 resulted in the selection of clones specific exclusively for Gad m 1, the second approach resulted in the selection of clones cross-reacting with all three parvalbumins. Two clones, scFv-gco9 recognizing all three parvalbumins, and scFv-goo8 recognizing only Gad m 1 were expressed in the E. coli non-suppressor strain HB2151 and purified from the periplasm. scFv-gco9 showed highly selective binding to parvalbumins in processed fish products such as breaded cod sticks, fried carp and smoked trout in Western blots. In addition, the scFv-gco9-AP produced as alkaline phosphatase fusion protein, allowed a single-step detection of the parvalbumins. In competitive ELISA, scFv-gco9 was able to inhibit binding of IgE from fish allergic patients' sera to all three β-parvalbumins by up to 80%, whereas inhibition by scFv-goo8 was up to 20%. 1H/15N HSQC NMR analysis of the rGad m 1:scFv-gco9 complex showed participation of amino acid residues conserved among these three parvalbumins explaining their cross-reactivity on a molecular level. In this study, we have demonstrated an approach for the selection of cross-reactive parvalbumin-specific antibodies that can be used for allergen detection and for mapping of conserved epitopes.

  6. A Cross-Reactive Human Single-Chain Antibody for Detection of Major Fish Allergens, Parvalbumins, and Identification of a Major IgE-Binding Epitope.

    Bublin, Merima; Kostadinova, Maria; Fuchs, Julian E; Ackerbauer, Daniela; Moraes, Adolfo H; Almeida, Fabio C L; Lengger, Nina; Hafner, Christine; Ebner, Christof; Radauer, Christian; Liedl, Klaus R; Valente, Ana Paula; Breiteneder, Heimo

    2015-01-01

    Fish allergy is associated with moderate to severe IgE-mediated reactions to the calcium binding parvalbumins present in fish muscle. Allergy to multiple fish species is caused by parvalbumin-specific cross-reactive IgE recognizing conserved epitopes. In this study, we aimed to produce cross-reactive single chain variable fragment (scFv) antibodies for the detection of parvalbumins in fish extracts and the identification of IgE epitopes. Parvalbumin-specific phage clones were isolated from the human ETH-2 phage display library by three rounds of biopanning either against cod parvalbumin or by sequential biopanning against cod (Gad m 1), carp (Cyp c 1) and rainbow trout (Onc m 1) parvalbumins. While biopanning against Gad m 1 resulted in the selection of clones specific exclusively for Gad m 1, the second approach resulted in the selection of clones cross-reacting with all three parvalbumins. Two clones, scFv-gco9 recognizing all three parvalbumins, and scFv-goo8 recognizing only Gad m 1 were expressed in the E. coli non-suppressor strain HB2151 and purified from the periplasm. scFv-gco9 showed highly selective binding to parvalbumins in processed fish products such as breaded cod sticks, fried carp and smoked trout in Western blots. In addition, the scFv-gco9-AP produced as alkaline phosphatase fusion protein, allowed a single-step detection of the parvalbumins. In competitive ELISA, scFv-gco9 was able to inhibit binding of IgE from fish allergic patients' sera to all three β-parvalbumins by up to 80%, whereas inhibition by scFv-goo8 was up to 20%. 1H/15N HSQC NMR analysis of the rGad m 1:scFv-gco9 complex showed participation of amino acid residues conserved among these three parvalbumins explaining their cross-reactivity on a molecular level. In this study, we have demonstrated an approach for the selection of cross-reactive parvalbumin-specific antibodies that can be used for allergen detection and for mapping of conserved epitopes.

  7. Two putative subunits of a peptide pump encoded in the human major histocompatability complex class 2 region

    Bahram, S.; Arnold, D.; Bresnahan, M.; Strominger, J.L.; Spies, T.

    1991-01-01

    The class 2 region of the human major histocompatibility complex (MHC) may encode several genes controlling the processing of endogenous antigen and the presentation of peptide epitopes by MHC class 1 molecules to cytotoxic T lymphocytes. A previously described peptide supply factor (PSF1) is a member of the multidrug-resistance family of transporters and may pump cytosolic peptides into the membrane-bound compartment where class 1 molecules assemble. A second transporter gene, PSF2, was identified 10 kilobases (kb) from PSF1, near the class 2 DOB gene. The complete sequences of PSF1 and PSF2 were determined from cDNA clones. The translation products are closely related in sequence and predicted secondary structure. Both contain a highly conserved ATP-binding fold and share 25% homology in a hydrophobic domain with a tentative number of eight membrane-spanning segments. Based on the principle dimeric organization of these two domains in other transporters, PSF1 and PSF2 may function as complementary subunits, independently as homodimers, or both. Taken together with previous genetic evidence, the coregulation of PSF1 and PSF2 by γ interferon and the to-some-degree coordinate transcription of these genes suggest a common role in peptide-loading of class 1 molecules, although a distinct function of PSF2 cannot be ruled out

  8. Generation of a genomic tiling array of the human Major Histocompatibility Complex (MHC and its application for DNA methylation analysis

    Ottaviani Diego

    2008-05-01

    Full Text Available Abstract Background The major histocompatibility complex (MHC is essential for human immunity and is highly associated with common diseases, including cancer. While the genetics of the MHC has been studied intensively for many decades, very little is known about the epigenetics of this most polymorphic and disease-associated region of the genome. Methods To facilitate comprehensive epigenetic analyses of this region, we have generated a genomic tiling array of 2 Kb resolution covering the entire 4 Mb MHC region. The array has been designed to be compatible with chromatin immunoprecipitation (ChIP, methylated DNA immunoprecipitation (MeDIP, array comparative genomic hybridization (aCGH and expression profiling, including of non-coding RNAs. The array comprises 7832 features, consisting of two replicates of both forward and reverse strands of MHC amplicons and appropriate controls. Results Using MeDIP, we demonstrate the application of the MHC array for DNA methylation profiling and the identification of tissue-specific differentially methylated regions (tDMRs. Based on the analysis of two tissues and two cell types, we identified 90 tDMRs within the MHC and describe their characterisation. Conclusion A tiling array covering the MHC region was developed and validated. Its successful application for DNA methylation profiling indicates that this array represents a useful tool for molecular analyses of the MHC in the context of medical genomics.

  9. Beta-lipotropin is the major component of the plasma opioid response to surgical stress in humans

    Porro, C.A.; Facchinetti, F.; Bertellini, E.; Petraglia, F.; Stacca, R.; Barbieri, G.C.; Genazzani, A.R.

    1987-12-07

    There is growing experimental evidence that beta-endorphin immunoreactivity is raised by surgical stress in patients undergoing general anesthesia. As the assay methods employed to date did not allow to fully discriminate between beta-endorphin and its immediate precursor, beta-lipotropin, the authors have investigated in the present study plasma levels of these two peptides by separating them by chromatography on plasma extracts prior to radioimmunoassay. Beta-lipotropin, but not beta-endorphin, plasma levels were found to be significantly elevated during surgery in the general anesthesia group, while no change was found in either peptide concentration in the spinal one. Cortisol plasma levels also increased significantly 90 minutes after the beginning of surgery. Although the sampling time they adopted may have prevented them from detecting an early peak of beta-endorphin during the first 30 minutes of surgery, the major component of the pituitary opioid response to surgical stress appears to be related to beta-lipotropin. This is in agreement with results of experimental work on various kinds of stress in animals and humans and seems to rule out a role for plasma beta-endorphin in post-operative analgesia. 38 references, 1 figure, 1 table.

  10. Genomic polymorphism, recombination, and linkage disequilibrium in human major histocompatibility complex-encoded antigen-processing genes.

    van Endert, P M; Lopez, M T; Patel, S D; Monaco, J J; McDevitt, H O

    1992-01-01

    Recently, two subunits of a large cytosolic protease and two putative peptide transporter proteins were found to be encoded by genes within the class II region of the major histocompatibility complex (MHC). These genes have been suggested to be involved in the processing of antigenic proteins for presentation by MHC class I molecules. Because of the high degree of polymorphism in MHC genes, and previous evidence for both functional and polypeptide sequence polymorphism in the proteins encoded by the antigen-processing genes, we tested DNA from 27 consanguineous human cell lines for genomic polymorphism by restriction fragment length polymorphism (RFLP) analysis. These studies demonstrate a strong linkage disequilibrium between TAP1 and LMP2 RFLPs. Moreover, RFLPs, as well as a polymorphic stop codon in the telomeric TAP2 gene, appear to be in linkage disequilibrium with HLA-DR alleles and RFLPs in the HLA-DO gene. A high rate of recombination, however, seems to occur in the center of the complex, between the TAP1 and TAP2 genes. Images PMID:1360671

  11. UNMET NEED OF SEX EDUCATION AMONG ADOLESCENTS IN URBAN SLUM AREA: AN INTERVENTIONAL STUDY

    Tamboli Kshitij S, Avachat Subhada S, Tamboli Suchit S

    2015-07-01

    Full Text Available Context: Adolescents comprise one-fifth of India’s total population. There is widespread ignorance associated with unprotected sex, contraceptives, among young people. As majority adolescents in slum areas have illiterate and ignorant family backgrounds; they are misguided by the myths. Hence providing sex education for them is the need of the hour. Aims: 1 To assess the knowledge and awareness of adolescents in an urban slum area regarding some aspects of reproductive health. 2 To assess the need of sex education among them. 3 To study the impact of sex education on their knowledge Material and Methods: An interventional study was done on 132 adolescents of urban slum area, selected by simple random sampling. Informed consent was obtained from the participants. Data was collected with the help of structured questionnaire prepared by literature search. Response of adolescents was recorded through questionnaires. A sensitization workshop was organized as intervention. The same questionnaire was given to them and the effect of intervention was assessed. Statistical analysis of data was done using percentage, proportion and appropriate tests of significance. Result and Conclusions: Only 31.06% adolescents had discussed the topic of reproductive health with some or other person and out of them friends were the major sources (39.2% of information. Only 38.63% knew the hazards of teenage pregnancy which significantly rose to 89.4% after intervention workshop. The study concludes that the slum adolescents profoundly lack adequate knowledge of sexuality related matters. Even before intervention workshop, unmet need of reproductive health education was 59.1% and 93.93% was the felt need in the post test.

  12. Unmet service needs evaluated by case managers among disabled patients on hemodialysis in Japan

    Sugisawa H

    2018-03-01

    Full Text Available Hidehiro Sugisawa,1 Toshio Shinoda,2 Yumiko Shimizu,3 Tamaki Kumagai,4 Hiroaki Sugisaki,5 Seiji Ohira6,† 1Department of Gerontology, Graduate School of Gerontology, J. F. Oberlin University, Tokyo, 2Department of Medical Care Technology, Faculty of Medical and Health Science, Tsukuba International University, Tsuchiura, 3Department of Community Health Nursing, The Jikei University School of Nursing, Chofu, 4Department of Fundamental Nursing, Graduate School of Nursing, Osaka City University, Osaka, 5Hachioji Azumacho Clinic, Hachioji, Tokyo, 6Sapporo Kita Clinic, Sapporo, Hokkai-do, Japan †Professor Dr. Seiji Ohira passed away on September 5, 2017 Background: This study aimed to investigate the levels of unmet needs for home and ­community-based services (HCBS evaluated by case managers (CMs among disabled patients on hemodialysis (DPHD and to examine factors related to unmet needs. Unmet needs for HCBS were defined as situations in which patients do not use or underuse HCBS despite needing them. Candidates for the factors relating to unmet needs for HCBS included three dimensions: predisposing, enabling, and need factors.Methods: Self-administrated questionnaires were collected from 391 CMs of DPHD certified with long-term care insurance. These were introduced by the dialysis facilities that a member of the Japanese Association of Dialysis Physicians belonged to. CMs were asked questions about their management of each individual case. HCBS included home help, visiting nursing, daycare, and short stay.Results: The prevalence of unmet needs for each HCBS ranged from 32% for home help to 48% for short stay. Barriers to service usage in the patients were associated with unmet needs for all four services. The patients with more severe cognitive malfunction were more likely to have unmet needs for visiting nursing and short stay. Heavier burden with caregiving was associated with more likelihood of unmet needs for home help and short stay

  13. Effect of Family Wealth and Attitudes toward Unmet Need for Family Planning Among Fertile Couples in Makassar, South Sulawesi, Indonesia

    Rahmawati Azis; Muhammad Syafar; Andi Zulkifli; Arifin Seweng

    2016-01-01

    One of the problems generated by unmet need for family planning is the occurrence of unwanted pregnancies, that could impact on abortion. Unmet need for family planning affected by various factors, both from within and from outside the woman. This study aimed to analyze the influence of socio-demographic characteristics, knowledge and attitudes towards family planning unmet need in women of childbearing age couple in Makassar, South Sulawesi. This study is analytic observational research. Cro...

  14. Patterns of unmet needs in adolescent and young adult (AYA) cancer survivors: in their own words.

    Wong, Alex W K; Chang, Ting-Ting; Christopher, Katrina; Lau, Stephen C L; Beaupin, Lynda K; Love, Brad; Lipsey, Kim L; Feuerstein, Michael

    2017-12-01

    Categorization of the needs of AYA cancer survivors is primarily based on quantitative analyses of epidemiological and observational research. The present study classified the phenomenological experiences of AYA survivors based on their own language. A systematic approach for selecting qualitative studies of unmet needs in AYA cancer survivors was used. Following selection based on quality, survivor statements were entered verbatim and thematic analysis was conducted using NVivo qualitative research software. A total of 1993 AYA cancer survivors (post-treatment) were included in 58 studies (78% individual interviews). Mean age was 27.6 with an average of 8.6 years post-primary treatment. The organizational framework reported in this study was based on a heterogeneous group of cancer types. Thirteen themes including symptoms, function, reproductive health, emotional well-being, health management, health care system, social interaction, romantic relationships, cancer disclosure, normalcy, career development and employment, and school and fiscal concerns were identified. Forty-eight subthemes were also identified covering such areas as fertility, integrative health services, advice for cancer disclosure, family interaction, and insurance challenges. Direct analysis of text identified many common unmet needs similarly reported in the quantitative literature. The phenomenological data also provided a breakdown of unmet needs into subthemes or elements of unmet needs. This information can help form the basis for a personalized, valid, and reliable evaluation tool of the range of unmet needs in AYA survivors.

  15. Family perception of unmet support needs following a diagnosis of congenital coronary anomaly in children: Results of a survey.

    Agrawal, Hitesh; Wright, Oriana K; Carberry, Kathleen E; Sexson Tejtel, S Kristen; Mery, Carlos M; Molossi, Silvana

    2017-12-01

    Long-term outcome data on patients with anomalous aortic origin of coronary arteries (AAOCA) is sparse and they are often managed in a nonuniform manner. There is subjective perception of anxiety and unmet needs in these patients and families. An online survey of 13 questions was sent to 74 families of patients with AAOCA between May and October 2015. Descriptive statistics were performed. A total of 31 (47%) families responded. Of these, 27 expressed the need to interact with other patients/families with AAOCA. The majority were interested in either face-to-face meetings (77%) or online support groups (71%). Regarding content of the meeting, 74% were interested in brief talks by medical personnel/families, 58% suggested informal interactions with families, 55% proposed a structured discussion with a moderator and 39% mentioned fun activities/games. Regarding participants in these meetings, 90% would like to include healthcare providers, 61% suggested including family friends, 58% wished to include psychologists and 16% mentioned including social workers. The families currently use various social media including Facebook (87%), YouTube (39%), Google+ (36%), and LinkedIn (32%). For future online resources, 77% of families would like a Facebook site, an informative website (58%), a blog (52%), or an open forum (29%). The majority of the families (77%) were interested in attending a dedicated AAOCA meeting. There appears to be an unmet need for family support in those affected by AAOCA, a substantial life changing diagnosis for patients and families. Further research is needed to assess quality of life in this population. © 2017 Wiley Periodicals, Inc.

  16. Roles of Polypyrimidine Tract Binding Proteins in Major Immediate-Early Gene Expression and Viral Replication of Human Cytomegalovirus▿

    Cosme, Ruth S. Cruz; Yamamura, Yasuhiro; Tang, Qiyi

    2009-01-01

    Human cytomegalovirus (HCMV), a member of the β subgroup of the family Herpesviridae, causes serious health problems worldwide. HCMV gene expression in host cells is a well-defined sequential process: immediate-early (IE) gene expression, early-gene expression, DNA replication, and late-gene expression. The most abundant IE gene, major IE (MIE) gene pre-mRNA, needs to be spliced before being exported to the cytoplasm for translation. In this study, the regulation of MIE gene splicing was investigated; in so doing, we found that polypyrimidine tract binding proteins (PTBs) strongly repressed MIE gene production in cotransfection assays. In addition, we discovered that the repressive effects of PTB could be rescued by splicing factor U2AF. Taken together, the results suggest that PTBs inhibit MIE gene splicing by competing with U2AF65 for binding to the polypyrimidine tract in pre-mRNA. In intron deletion mutation assays and RNA detection experiments (reverse transcription [RT]-PCR and real-time RT-PCR), we further observed that PTBs target all the introns of the MIE gene, especially intron 2, and affect gene splicing, which was reflected in the variation in the ratio of pre-mRNA to mRNA. Using transfection assays, we demonstrated that PTB knockdown cells induce a higher degree of MIE gene splicing/expression. Consistently, HCMV can produce more viral proteins and viral particles in PTB knockdown cells after infection. We conclude that PTB inhibits HCMV replication by interfering with MIE gene splicing through competition with U2AF for binding to the polypyrimidine tract in MIE gene introns. PMID:19144709

  17. Roles of polypyrimidine tract binding proteins in major immediate-early gene expression and viral replication of human cytomegalovirus.

    Cosme, Ruth S Cruz; Yamamura, Yasuhiro; Tang, Qiyi

    2009-04-01

    Human cytomegalovirus (HCMV), a member of the beta subgroup of the family Herpesviridae, causes serious health problems worldwide. HCMV gene expression in host cells is a well-defined sequential process: immediate-early (IE) gene expression, early-gene expression, DNA replication, and late-gene expression. The most abundant IE gene, major IE (MIE) gene pre-mRNA, needs to be spliced before being exported to the cytoplasm for translation. In this study, the regulation of MIE gene splicing was investigated; in so doing, we found that polypyrimidine tract binding proteins (PTBs) strongly repressed MIE gene production in cotransfection assays. In addition, we discovered that the repressive effects of PTB could be rescued by splicing factor U2AF. Taken together, the results suggest that PTBs inhibit MIE gene splicing by competing with U2AF65 for binding to the polypyrimidine tract in pre-mRNA. In intron deletion mutation assays and RNA detection experiments (reverse transcription [RT]-PCR and real-time RT-PCR), we further observed that PTBs target all the introns of the MIE gene, especially intron 2, and affect gene splicing, which was reflected in the variation in the ratio of pre-mRNA to mRNA. Using transfection assays, we demonstrated that PTB knockdown cells induce a higher degree of MIE gene splicing/expression. Consistently, HCMV can produce more viral proteins and viral particles in PTB knockdown cells after infection. We conclude that PTB inhibits HCMV replication by interfering with MIE gene splicing through competition with U2AF for binding to the polypyrimidine tract in MIE gene introns.

  18. Transcriptome association analysis identifies miR-375 as a major determinant of variable acetaminophen glucuronidation by human liver.

    Papageorgiou, Ioannis; Freytsis, Marina; Court, Michael H

    2016-10-01

    Acetaminophen is the leading cause of acute liver failure (ALF) in many countries including the United States. Hepatic glucuronidation by UDP-glucuronosyltransferase (UGT) 1A subfamily enzymes is the major route of acetaminophen elimination. Reduced glucuronidation may predispose some individuals to acetaminophen-induced ALF, but mechanisms underlying reduced glucuronidation are poorly understood. We hypothesized that specific microRNAs (miRNAs) may reduce UGT1A activity by direct effects on the UGT1A 3'-UTR shared by all UGT1A enzyme transcripts, or by indirect effects on transcription factors regulating UGT1A expression. We performed an unbiased miRNA whole transcriptome association analysis using a bank of human livers with known acetaminophen glucuronidation activities. Of 754 miRNAs evaluated, 9 miRNAs were identified that were significantly overexpressed (p2-fold) in livers with low acetaminophen glucuronidation activities compared with those with high activities. miR-375 showed the highest difference (>10-fold), and was chosen for further mechanistic validation. We demonstrated using in silico analysis and luciferase reporter assays that miR-375 has a unique functional binding site in the 3'-UTR of the aryl hydrocarbon receptor (AhR) gene. Furthermore overexpression of miR-375 in LS180 cells demonstrated significant repression of endogenous AhR protein (by 40%) and mRNA (by 10%), as well as enzyme activity and/or mRNA of AhR regulated enzymes including UGT1A1, UGT1A6, and CYP1A2, without affecting UGT2B7, which is not regulated by AhR. Thus miR-375 is identified as a novel repressor of UGT1A-mediated hepatic acetaminophen glucuronidation through reduced AhR expression, which could predispose some individuals to increased risk for acetaminophen-induced ALF. Published by Elsevier Inc.

  19. Semi-Metric Topology of the Human Connectome: Sensitivity and Specificity to Autism and Major Depressive Disorder.

    Tiago Simas

    Full Text Available The human functional connectome is a graphical representation, consisting of nodes connected by edges, of the inter-relationships of blood oxygenation-level dependent (BOLD time-series measured by MRI from regions encompassing the cerebral cortices and, often, the cerebellum. Semi-metric analysis of the weighted, undirected connectome distinguishes an edge as either direct (metric, such that there is no alternative path that is accumulatively stronger, or indirect (semi-metric, where one or more alternative paths exist that have greater strength than the direct edge. The sensitivity and specificity of this method of analysis is illustrated by two case-control analyses with independent, matched groups of adolescents with autism spectrum conditions (ASC and major depressive disorder (MDD.Significance differences in the global percentage of semi-metric edges was observed in both groups, with increases in ASC and decreases in MDD relative to controls. Furthermore, MDD was associated with regional differences in left frontal and temporal lobes, the right limbic system and cerebellum. In contrast, ASC had a broadly increased percentage of semi-metric edges with a more generalised distribution of effects and some areas of reduction. In summary, MDD was characterised by localised, large reductions in the percentage of semi-metric edges, whilst ASC is characterised by more generalised, subtle increases. These differences were corroborated in greater detail by inspection of the semi-metric backbone for each group; that is, the sub-graph of semi-metric edges present in >90% of participants, and by nodal degree differences in the semi-metric connectome.These encouraging results, in what we believe is the first application of semi-metric analysis to neuroimaging data, raise confidence in the methodology as potentially capable of detection and characterisation of a range of neurodevelopmental and psychiatric disorders.

  20. The impact of family planning programs on unmet need and demand for contraception.

    Bongaarts, John

    2014-06-01

    Much of the existing literature on the demographic impact of family planning programs focuses on their role in increasing contraceptive use, which, in turn, accelerates fertility decline. What is not clear, however, is whether this effect operates solely through a reduction in unmet need brought about by eliminating obstacles to use or whether and to what extent the programs also affect demand for contraception through messages concerning the benefits of family planning. This article aims to shed additional light on this issue by analyzing data drawn from recent Demographic and Health Surveys conducted in 63 developing countries. The first section reviews general levels and trends in unmet need, demand, and use over the course of the fertility transition. The second section presents different types of evidence of program effects, including results from a controlled experiment and from country case studies. The evidence indicates a program impact on both unmet need and demand. © 2013 The Population Council, Inc.

  1. Human CD4+ T cell responses to the dog major allergen Can f 1 and its human homologue tear lipocalin resemble each other.

    Aino L K Liukko

    Full Text Available Lipocalin allergens form a notable group of proteins, as they contain most of the significant respiratory allergens from mammals. The basis for the allergenic capacity of allergens in the lipocalin family, that is, the development of T-helper type 2 immunity against them, is still unresolved. As immunogenicity has been proposed to be a decisive feature of allergens, the purpose of this work was to examine human CD4+ T cell responses to the major dog allergen Can f 1 and to compare them with those to its human homologue, tear lipocalin (TL. For this, specific T cell lines were induced in vitro from the peripheral blood mononuclear cells of Can f 1-allergic and healthy dog dust-exposed subjects with peptides containing the immunodominant T cell epitopes of Can f 1 and the corresponding TL peptides. We found that the frequency of Can f 1 and TL-specific T cells in both subject groups was low and close to each other, the difference being about two-fold. Importantly, we found that the proliferative responses of both Can f 1 and TL-specific T cell lines from allergic subjects were stronger than those from healthy subjects, but that the strength of the responses within the subject groups did not differ between these two antigens. Moreover, the phenotype of the Can f 1 and TL-specific T cell lines, determined by cytokine production and expression of cell surface markers, resembled each other. The HLA system appeared to have a minimal role in explaining the allergenicity of Can f 1, as the allergic and healthy subjects' HLA background did not differ, and HLA binding was very similar between Can f 1 and TL peptides. Along with existing data on lipocalin allergens, we conclude that strong antigenicity is not decisive for the allergenicity of Can f 1.

  2. Cancer survivors and their partners: the assessment of unmet supportive care needs

    Smith, K.; Pendlebury, S.; Butow, P.; Hobbs, K.; Wain, G.

    2003-01-01

    Our understanding of unmet supportive care needs of cancer survivors and their partners is limited. Most studies have focused on needs of patients undergoing treatment and on Quality of life or patient satisfaction. For the purpose of this research, cancer survivors are defined as persons who received a cancer diagnosis at least one year previously and are disease free. The aim of this study is to develop measures to assess unmet needs in survivors and their partners. After developing the questionnaire items it was piloted for validity in a wide sample of cancer patients from the radiation oncology department. 105 patients, all women, 101 with breast cancer and 40 partners participated. Psychological morbidity of depression and anxiety was recorded and was low. Quality of life for both survivors and partners was close to the US population mean. For patients top 4 unmet needs was 1. Anxiety about cancer returning (35%), current information (21%), understandable information (28%), ongoing case manager (25%). Unmet needs for partners were 1. Need to know all the doctors were communication (3.2%), need for local health services (2.8%), current information (2.1%) and help with managing concerns about the cancer returning (2.1%). 73% of partners reported at least one positive outcome from their partner's experience, significantly more than the survivors. In conclusion, interim analysis of the questionnaire reveals validity. Survivors report ongoing high levels of unmet needs 3-9 years after cancer diagnosis ( 30%). Less than 4% of partners report such unmet needs. There is significant correlation between needs of partners and survivors, many of which relate to issues of ongoing support and information delivery

  3. Unmet healthcare needs in homeless women with children in the Greater Paris area in France.

    Cécile Vuillermoz

    Full Text Available Despite their poor health status, homeless women encounter many barriers to care. The objectives of our study were to estimate the prevalence of unmet healthcare needs in homeless women and to analyse associated relationships with the following factors: financial and spatial access to care, housing history, migration status, healthcare utilisation, victimization history, caring for children, social network and self-perceived health status.We used data from 656 homeless women interviewed during the ENFAMS representative survey of sheltered homeless families, conducted in the Paris region in 2013. Structural equation models (SEM were used to estimate the impact of various factors on homeless women's unmet healthcare needs.Among those interviewed, 25.1% (95%CI[21.3-29.0] had at least one unmet healthcare need over the previous year. Most had given up on visiting general practitioners and medical specialists. No association with factors related to financial access or to health insurance status was found. However, food insecurity, poor spatial health access and poor self-perceived health were associated with unmet healthcare needs. Self-perceived health appeared to be affected by victimization and depression.The lower prevalence of unmet healthcare needs in homeless women compared with women in stable housing situations suggests that homeless women have lower needs perceptions and/or lower expectations of the healthcare system. This hypothesis is supported by the results from SEM. Strategies to provide better access to care for this population should not only focus on financial interventions but also more broadly on spatial healthcare access, cultural norms, and perceptions of health. Reducing their unmet needs and improving their access to healthcare and prevention must include an improvement in their living, financial and housing conditions.

  4. Habitual Sleep Duration, Unmet Sleep Need, and Excessive Daytime Sleepiness in Korean Adults.

    Hwangbo, Young; Kim, Won Joo; Chu, Min Kyung; Yun, Chang Ho; Yang, Kwang Ik

    2016-04-01

    Sleep need differs between individuals, and so the same duration of sleep will lead to sleep insufficiency in some individuals but not others. The aim of this study was to determine the separate and combined associations of both sleep duration and unmet sleep need with excessive daytime sleepiness (EDS) in Korean adults. The participants comprised 2,769 Korean adults aged 19 years or older. They completed questionnaires about their sleep habits over the previous month. The question regarding sleep need was "How much sleep do you need to be at your best during the day?" Unmet sleep need was calculated as sleep need minus habitual sleep duration. Participants with a score of >10 on the Epworth Sleepiness Scale were considered to have EDS. The overall prevalence of EDS was 11.9%. Approximately one-third of the participants (31.9%) reported not getting at least 7 hours of sleep. An unmet sleep need of >0 hours was present in 30.2% of the participants. An adjusted multivariate logistic regression analysis revealed a significant excess risk of EDS in the groups with unmet sleep needs of ≥2 hours [odds ratio (OR), 1.80; 95% confidence interval (CI), 1.27-2.54] and 0.01-2 hours (OR, 1.42; 95% CI, 1.02-1.98). However, habitual sleep duration was not significantly related to EDS. EDS was found to be associated with unmet sleep need but not with habitual sleep duration when both factors were examined together. We suggest that individual unmet sleep need is more important than habitual sleep duration in terms of the relation to EDS.

  5. DETERMINANTS OF UNMET NEED FOR FAMILY PLANNING IN SLUMS OF LUCKNOW

    Mukesh

    2015-06-01

    Full Text Available INTRODUCTION: Understanding of family planning scenario among different societies and communities, which by and large reside in urban slum areas, might prove useful in increasing family planning acceptance by them and decreasing population growth. Unmet need is a valuable indicator for assessing the achievements of national family planning programs. OBJECTIVES: The present study was undertaken with the objectives to estimate unmet need for family planning among the married women of reproductive age group (15 - 49 years in urban slums of Lucknow and to determine the various factors that influence the unmet need. METHODS: A community based cross - sectional study was conducted in slums of Lucknow City from February 2014 to September 2014. A total 452 married women in reproductive age group were interviewed through house to house survey with the help of a pre - designed, pre - tested and semi - structured questionnaire. RESULTS: The total unmet need for family planning was 69.0%. Multivariate logistic regression revealed socioeconomic status upper lower and below (OR 2.7; 95% CI 1.5 - 5.1; p = 0.00; duration of marriage less than 1 year (OR 1.8; 95% CI 1.1 - 2.9; p = 0.01; less number of live issues (OR 1.6; 95% CI 1.1 - 2.5; p = 0.00; working status of women (OR 1.9; 95% CI 1.1 - 2.9; p = 0.03; social class i.e. OBC and SC/ST (OR 2.3; 95% CI 1.1 - 4.6; p = 0.02 were found to be independent predictors of unmet need of family planning. CONCLUSION: The present study revealed that unmet need for family planning was quite high among women belonging to social class i.e. OBC and SC/ST, with low socioeconomic status, duration of marriage less than one year less number of live issues and working status of the women.

  6. Family Caregiver Factors Associated with Unmet Needs for Care of Older Adults.

    Beach, Scott R; Schulz, Richard

    2017-03-01

    To examine caregiver factors associated with unmet needs for care of older adults. Population-based surveys of caregivers and older adult care recipients in the United States in 2011. 2011 National Health and Aging Trends Study and National Study of Caregiving. Family caregivers (n = 1,996) of community-dwelling older adults with disabilities (n = 1,366). Disabled care recipient reports of unmet needs for care in the past month with activities of daily living (ADLs; e.g., wet or soiled clothing), mobility (e.g., have to stay inside), or instrumental activities of daily living (IADLs; e.g., medication errors). Caregiver reported sociodemographic characteristics, caregiving intensity and tasks performed, health, and psychosocial effects. Of the care recipients, 44.3% reported at least one unmet need for care in the past month (38.2% ADL related, 14.6% IADL related). Younger caregivers, caregiving sons, caregivers not living with care recipients, and having supplemental paid caregivers were associated with more unmet needs. Caregivers with recipients reporting two or more unmet needs were more likely to spend more than 100 hours per month caregiving, help with skin care and wounds, report caregiving as emotionally and physically difficult, and report restricted participation in valued activities (all P family caregivers. Caregivers experiencing high levels of burden, stress, and negative physical and psychosocial impacts may provide substandard or poor care to older adults, which may be a risk factor for neglect. Clinicians caring for disabled older adults should assess their unmet needs and the capacity of caregivers to address them. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

  7. Nurse's Desk: food bank-based outreach and screening to decrease unmet referral needs.

    Larsson, Laura S; Kuster, Emilie

    2013-01-01

    The Nurse's Desk health screening project used the Intervention Wheel model to conduct outreach, screening, education, and referral for food bank clients (n = 506). Blood glucose, blood pressure, health care utilization, and unmet referral needs were assessed. Screening results identified 318 clients (62.8%) with 1 or more unmet referral needs, including 6 clients (3.16%) with capillary blood glucose more than 199 mg/dL and 132 (31.9%) with hypertension. Clients had higher-than-average systolic and diastolic blood pressures and undiagnosed diabetes than in the general population. A client-approved method for tracking completed referrals is needed for this potentially high-risk population.

  8. Comprehensive care and pregnancy: The unmet care needs of pregnant women with a history of rape

    Munro, Michelle L.; Rietz, Melissa Foster

    2013-01-01

    This paper proposes a framework for assessing the unmet needs of rape survivors during pregnancy based on the Sexual Assault Nurse Examiner (SANE) practice level theory and an empirical exploration of rape survivors’ health status in pregnancy via a secondary analysis. Our findings indicate that there may be unmet needs in pregnancy related to all five post-assault comprehensive care components: (1) physical care, (2) pregnancy prevention, (3) sexually transmitted infection screening, (4) psychological care, and (5) legal care. Rape history and its current impact on the survivor predicted somatic disorders, substance use, unwanted pregnancy, infections, posttraumatic stress disorder, and recent abuse. PMID:23215990

  9. Test-Retest Reliability of the Short-Form Survivor Unmet Needs Survey.

    Taylor, Karen; Bulsara, Max; Monterosso, Leanne

    2018-01-01

    Reliable and valid needs assessment measures are important assessment tools in cancer survivorship care. A new 30-item short-form version of the Survivor Unmet Needs Survey (SF-SUNS) was developed and validated with cancer survivors, including hematology cancer survivors; however, test-retest reliability has not been established. The objective of this study was to assess the test-retest reliability of the SF-SUNS with a cohort of lymphoma survivors ( n = 40). Test-retest reliability of the SF-SUNS was conducted at two time points: baseline (time 1) and 5 days later (time 2). Test-retest data were collected from lymphoma cancer survivors ( n = 40) in a large tertiary cancer center in Western Australia. Intraclass correlation analyses compared data at time 1 (baseline) and time 2 (5 days later). Cronbach's alpha analyses were performed to assess the internal consistency at both time points. The majority (23/30, 77%) of items achieved test-retest reliability scores 0.45-0.74 (fair to good). A high degree of overall internal consistency was demonstrated (time 1 = 0.92, time 2 = 0.95), with scores 0.65-0.94 across subscales for both time points. Mixed test-retest reliability of the SF-SUNS was established. Our results indicate the SF-SUNS is responsive to the changing needs of lymphoma cancer survivors. Routine use of cancer survivorship specific needs-based assessments is required in oncology care today. Nurses are well placed to administer these assessments and provide tailored information and resources. Further assessment of test-retest reliability in hematology and other cancer cohorts is warranted.

  10. Methodological approaches and magnitude of the clinical unmet need associated with amotivation in mood disorders.

    Calabrese, Joseph R; Fava, Maurizio; Garibaldi, George; Grunze, Heinz; Krystal, Andrew D; Laughren, Thomas; Macfadden, Wayne; Marin, Robert; Nierenberg, Andrew A; Tohen, Mauricio

    2014-10-01

    There is growing research interest in studying motivational deficits in different neuropsychiatric disorders because these symptoms appear to be more common than originally reported and negatively impact long-term functional outcomes. However, there is considerable ambiguity in the terminology used to describe motivational deficits in the scientific literature. For the purposes of this manuscript, the term "amotivation" will be utilised in the context of mood disorders, since this is considered a more inclusive/appropriate term for this patient population. Other challenges impacting the study of amotivation in mood disorders, include: appropriate patient population selection; managing or controlling for potential confounding factors; the lack of gold-standard diagnostic criteria and assessment scales; and determination of the most appropriate study duration. This paper summarises the search for a consensus by a group of experts in the optimal approach to studying amotivation in mood disorders. The consensus of this group is that amotivation in mood disorders is a legitimate therapeutic target, given the magnitude of the associated unmet needs, and that proof-of-concept studies should be conducted in order to facilitate subsequent larger investigations. The focus of this manuscript is to consider the study of amotivation, as a residual symptom of major depressive disorder (MDD) or bipolar depression (BD), following adequate treatment with a typical antidepressant or mood stabiliser/antipsychotic, respectively. There is a paucity of data studying amotivation in mood disorders. This manuscript provides general guidance on the most appropriate study design(s) and methodology to assess potential therapeutic options for the management of residual amotivation in mood disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Pleiotropic Associations of Allelic Variants in a 2q22 Region with Risks of Major Human Diseases and Mortality.

    Alexander M Kulminski

    2016-11-01

    Full Text Available Gaining insights into genetic predisposition to age-related diseases and lifespan is a challenging task complicated by the elusive role of evolution in these phenotypes. To gain more insights, we combined methods of genome-wide and candidate-gene studies. Genome-wide scan in the Atherosclerosis Risk in Communities (ARIC Study (N = 9,573 was used to pre-select promising loci. Candidate-gene methods were used to comprehensively analyze associations of novel uncommon variants in Caucasians (minor allele frequency~2.5% located in band 2q22.3 with risks of coronary heart disease (CHD, heart failure (HF, stroke, diabetes, cancer, neurodegenerative diseases (ND, and mortality in the ARIC study, the Framingham Heart Study (N = 4,434, and the Health and Retirement Study (N = 9,676. We leveraged the analyses of pleiotropy, age-related heterogeneity, and causal inferences. Meta-analysis of the results from these comprehensive analyses shows that the minor allele increases risks of death by about 50% (p = 4.6×10-9, CHD by 35% (p = 8.9×10-6, HF by 55% (p = 9.7×10-5, stroke by 25% (p = 4.0×10-2, and ND by 100% (p = 1.3×10-3. This allele also significantly influences each of two diseases, diabetes and cancer, in antagonistic fashion in different populations. Combined significance of the pleiotropic effects was p = 6.6×10-21. Causal mediation analyses show that endophenotypes explained only small fractions of these effects. This locus harbors an evolutionary conserved gene-desert region with non-coding intergenic sequences likely involved in regulation of protein-coding flanking genes ZEB2 and ACVR2A. This region is intensively studied for mutations causing severe developmental/genetic disorders. Our analyses indicate a promising target region for interventions aimed to reduce risks of many major human diseases and mortality.

  12. Estimated Human and Economic Burden of Four Major Adult Vaccine-Preventable Diseases in the United States, 2013.

    McLaughlin, John M; McGinnis, Justin J; Tan, Litjen; Mercatante, Annette; Fortuna, Joseph

    2015-08-01

    Low uptake of routinely recommended adult immunizations is a public health concern. Using data from the peer-reviewed literature, government disease-surveillance programs, and the US Census, we developed a customizable model to estimate human and economic burden caused by four major adult vaccine-preventable diseases (VPD) in 2013 in the United States, and for each US state individually. To estimate the number of cases for each adult VPD for a given population, we multiplied age-specific incidence rates obtained from the literature by age-specific 2013 Census population data. We then multiplied the estimated number of cases for a given population by age-specific, estimated medical and indirect (non-medical) costs per case. Adult VPDs examined were: (1) influenza, (2) pneumococcal disease (both invasive disease and pneumonia), (3) herpes zoster (shingles), and (4) pertussis (whooping cough). Sensitivity analyses simulated the impact of various epidemiological scenarios on the total estimated economic burden. Estimated US annual cost for the four adult VPDs was $26.5 billion (B) among adults aged 50 years and older, $15.3B (58 %) of which was attributable to those 65 and older. Among adults 50 and older, influenza, pneumococcal disease, herpes zoster, and pertussis made up $16.0B (60 %), $5.1B (19 %), $5.0B (19 %), and $0.4B (2 %) of the cost, respectively. Among those 65 and older, they made up $8.3B (54 %), $3.8B (25 %), $3.0B (20 %), and 0.2B (1 %) of the cost, respectively. Most (80-85 %) pneumococcal costs stemmed from nonbacteremic pneumococcal pneumonia (NPP). Cost attributable to adult VPD in the United States is substantial. Broadening adult immunization efforts beyond influenza only may help reduce the economic burden of adult VPD, and a pneumococcal vaccination effort, primarily focused on reducing NPP, may constitute a logical starting place. Sensitivity analyses revealed that a pandemic influenza season or change in size of the US elderly population

  13. Psychological distress, quality of life, symptoms and unmet needs of colorectal cancer survivors near the end of treatment.

    Russell, Lahiru; Gough, Karla; Drosdowsky, Allison; Schofield, Penelope; Aranda, Sanchia; Butow, Phyllis N; Westwood, Jennifer A; Krishnasamy, Mei; Young, Jane M; Phipps-Nelson, Jo; King, Dorothy; Jefford, Michael

    2015-09-01

    This study investigated psychological morbidity, quality of life (QoL), colorectal cancer (CRC)-specific symptoms and supportive care needs in a CRC population at the end of treatment (EOT). CRC survivors (n = 152) completed a post-treatment baseline questionnaire as part of a multisite supportive care randomised controlled trial (SurvivorCare). CRC survivors had completed treatment with curative intent within 0 to 6 months. Measures are as follows: Brief Symptom Inventory 18 (BSI-18) (psychological morbidity), EORTC QLQ-C30 and QLQ-CR29 (QoL and CRC-specific symptoms and problems) and Cancer Survivors' Unmet Needs (CaSUN) measure with a simplified response format (unmet needs). Linear regression models were used to compare participants' QoL with a general population sample. Correlation analysis examined associations between psychological morbidity, QoL and CRC-specific symptoms and problems. Average participant age was 64 years, and 51% were male. The majority (68%) had stage 3 disease. In comparison to population norms, CRC survivors had lower depression and anxiety scores (47.4 and 45.6, respectively) but higher somatisation, and lower role, cognitive and social functioning (p < 0.001). CRC survivors had higher fatigue, nausea/vomiting, appetite loss, diarrhoea and financial problems (all p < 0.001), as well as pain (p = 0.002) and constipation (p = 0.019). CRC-specific psychological scores were positively correlated with all three BSI domain scores, and pain and fatigue symptom scores on the QLQ-C30 while negatively correlated with all five functional scales of the QLQ-C30. CRC survivors reported good mental health at EOT. Role and social functioning were impaired compared to population norms, possibly related to physical symptoms. Findings may help guide consultations with patients and inform the design of more tailored supportive care interventions. ACTRN12610000207011.

  14. Unmet needs of people with severe multiple sclerosis and their carers: qualitative findings for a home-based intervention.

    Claudia Borreani

    Full Text Available Few data on services for people with severe multiple sclerosis (MS are available. The Palliative Network for Severely Affected Adults with MS in Italy (PeNSAMI developed a home palliative care program for MS patients and carers, preceded by a literature review and qualitative study (here reported.To identify unmet needs of people with severe MS living at home by qualitative research involving key stakeholders, and theorize broad areas of intervention to meet those needs.Data were collected from: at least 10 personal interviews with adults with severe MS (primary/secondary progressive, EDSS≥8.0; three focus group meetings (FGs of carers of people with severe MS; and two FGs of health professionals (HPs. Grounded theory guided the analysis of interview and FG transcripts, from which the areas of intervention were theorized.Between October 2012 and May 2013, 22 MS patients, 30 carers and 18 HPs participated. Forty-eight needs themes were identified, grouped into 14 categories and four domains. Seven, highly interdependent intervention areas were theorized. Patients had difficulties expressing needs; experiences of burden and loneliness were prominent, chiefly in dysfunctional, less affluent families, and among parent carers. Needs differed across Italy with requirements for information and access to services highest in the South. All participants voiced a strong need for qualified personnel and care coordination in day-to-day home care. Personal hygiene emerged as crucial, as did the need for a supportive network and preservation of patient/carer roles within family and community.Unmet needs transcended medical issues and embraced organizational and psychosocial themes, as well as health policies. The high interdependence of the seven intervention areas theorized is in line with the multifaceted approach of palliative care. At variance with typical palliative contexts, coping with disability rather than end-of-life was a major concern of patients

  15. Children--The Effect of Rural Residence on Dental Unmet Need for Children with Special Health Care Needs

    Skinner, Asheley Cockrell; Slifkin, Rebecca T.; Mayer, Michelle L.

    2006-01-01

    Background: Unmet need for dental care is the most prevalent unmet health care need among children with special health care needs (CSHCN), even though these children are at a greater risk for dental problems. The combination of rural residence and special health care needs may leave rural CSHCN particularly vulnerable to high levels of unmet…

  16. Comparison of problems and unmet needs of patients with advanced cancer in a European country and an asian country

    Effendy, C.; Vissers, K.; Osse, B.H.; Tejawinata, S.; Vernooij-Dassen, M.J.F.J.; Engels, Y.M.

    2015-01-01

    BACKGROUND: Patients with advanced cancer experience problems and unmet needs. However, we assume that patients with advanced cancer will have more problems and unmet needs in a country with a lower economic status than in an economically stronger country. We studied whether patients with advanced

  17. Drug costs and benefits of medical treatments in high-unmet need solid tumours in the Nordic countries

    Osterlund, P; Sorbye, H; Pfeiffer, P.

    2016-01-01

    -unmet need solid tumour indications in Nordic countries (Sweden, Denmark, Finland, Norway and Sweden). Methods: For a selected number of cancer dugs, approved for metastatic cancer or non-curable treatment intention patients by the European Medicine Agency (EMA) after 2000, and indicated in high-unmet need...

  18. "Being an English Major, Being a Humanities Student": Connecting Academic Subject Identity in Literary Studies to Other Social Domains

    Chan, Evelyn T. Y.

    2016-01-01

    This study examined students' construction of academic subject identity in a university humanities discipline, English literary studies. In so doing, the study aimed to provide an empirically grounded intervention in current debates on the value of the humanities in higher education. Eight students participated in interviews lasting 15-20 minutes…

  19. Unmet Needs of Families of School-Aged Children with an Autism Spectrum Disorder

    Brown, Hilary K.; Ouellette-Kuntz, Helene; Hunter, Duncan; Kelley, Elizabeth; Cobigo, Virginie

    2012-01-01

    Background: To aid decision making regarding the allocation of limited resources, information is needed on the perceived unmet needs of parents of school-aged children with an autism spectrum disorder. Materials and Methods: A cross-sectional survey was conducted of 101 Canadian families of school-aged children with an autism spectrum disorder.…

  20. Disparities in unmet dental need and dental care received by pregnant women in Maryland.

    Singhal, Astha; Chattopadhyay, Amit; Garcia, A Isabel; Adams, Amy B; Cheng, Diana

    2014-09-01

    To examine prenatal dental care needs, utilization and oral health counseling among Maryland women who delivered a live infant during 2001-2003 and identify the factors associated with having a dental visit and having an unmet dental need during pregnancy. Pregnancy Risk Assessment Monitoring System is an ongoing population based surveillance system that collects information of women's attitudes and experiences before, during, and shortly after pregnancy. Logistic regression was used to model dental visits and unmet dental need using predictor variables for Maryland 2001-2003 births. Less than half of all women reported having a dental visit and receiving oral health advice during pregnancy. Twenty-five percent of women reported a need for dental care, of which 33 % did not receive dental care despite their perceived need. Multivariate modeling revealed that racial minorities, women who were not married and those with annual income dental visit. Women who were not married, had low annual income, were older than 40 years of age, had an unintended pregnancy and received prenatal care later than desired were most likely to have an unmet dental need during pregnancy. Despite reported needs and existing recommendations to include oral health as a component of prenatal care, less than half of pregnant women have a dental visit during their pregnancy. One-third of women with a dental problem did not have a dental visit highlighting the unmet need for dental care during pregnancy.

  1. Hospital Readmission among Older Adults Who Return Home with Unmet Need for ADL Disability

    DePalma, Glen; Xu, Huiping; Covinsky, Kenneth E.; Craig, Bruce A.; Stallard, Eric; Thomas, Joseph, III.; Sands, Laura P.

    2013-01-01

    Purpose: This study determined whether returning to the community from a recent hospitalization with unmet activities of daily living (ADL) need was associated with probability of readmission. Methods: A total of 584 respondents to the 1994, 1999, and/or 2004 National Long-Term Care Surveys (NLTCS) who were hospitalized within 90 days prior to the…

  2. Unmet Dental Needs and Barriers to Dental Care among Children with Autism Spectrum Disorders

    Lai, Bien; Milano, Michael; Roberts, Michael W.; Hooper, Stephen R.

    2012-01-01

    Mail-in pilot-tested questionnaires were sent to a stratified random sample of 1,500 families from the North Carolina Autism Registry. Multivariate logistic regression analysis was used to determine the significance of unmet dental needs and other predictors. Of 568 surveys returned (Response Rate = 38%), 555 were complete and usable. Sixty-five…

  3. Faktor yang Berhubungan dengan Terjadinya Unmet Need KB pada Pasangan Usia Subur (PUS di Kota Yogyakarta

    Susiana Sariyati

    2015-11-01

    Full Text Available The problem of population is important big issues and urgent, primarily related with aspects of the quality of population control, improving the quality of population and mobility of population, if its associated with the potential threat of explosion of population. The purpose of this study was to know factors associated with unmet need family planning among reproductive age couples in Yogyakarta. This study used descriptive method. The populations of this study were all of reproductive age couples in Yogyakarta. The sampling technique was done by probability proportional to size resulted on 779 respondents of reproductive age couples from 30 sub village in 30 village in Yogyakarta. The results of study showed that there was no significant relationship between respondent ages and unmet need, no significant relationship between wife education and unmet need, and no significant relationship between the number of children still live and unmet need.

  4. Self-perceived met and unmet care needs of frail older adults in primary care

    Hoogendijk, Emiel O; Muntinga, Maaike E; van Leeuwen, Karen M; van der Horst, Henriëtte E; Deeg, Dorly J H; Frijters, Dinnus H M; Hermsen, Lotte A H; Jansen, Aaltje P D; Nijpels, Giel; van Hout, Hein P J

    2013-01-01

    In order to provide adequate care for frail older adults in primary care it is essential to have insight into their care needs. Our aim was to describe the met and unmet care needs as perceived by frail older adults using a multi-dimensional needs assessment, and to explore their associations with

  5. Unmet dental needs and barriers to care for children with significant special health care needs.

    Nelson, Linda P; Getzin, Anne; Graham, Dionne; Zhou, Jing; Wagle, Elke M; McQuiston, Jessie; McLaughlin, Suzanne; Govind, Akshay; Sadof, Matthew; Huntington, Noelle L

    2011-01-01

    The purpose of this study was to conduct the first known large scale survey of parents of children with special health care needs (CSHCN) to determine their child's: oral health status; access to dental care; perceived barriers (environmental/system and nonenvironmental/family); and oral health quality of life, accounting for each child's medical diagnosis and severity of diagnosis. A 72-item survey was sent to 3760 families of CSHCN throughout urban and rural Massachusetts. The study yielded 1,128 completed surveys. More than 90% of the children had seen a dentist within the past year; 66% saw a pediatric dentist, and 21% needed intense behavioral interventions. Although most families had high education levels, private dental insurance, and above average incomes, 20% of CSHCN had an unmet dental need. Children with craniofacial anomalies had twice as many unmet needs and children with cystic fibrosis had fewer unmet needs. Children with cerebral palsy, autism, developmental delay, and Down syndrome had more aversions to dental treatment, more treatment complications posed by their medical conditions, and more difficulty finding a dentist willing to provide care. Children with cystic fibrosis, metabolic disorders, or hemophilia encountered fewer barriers to care. The data paint a picture of high unmet dental needs with subpopulations of children with special health care needs who are more at risk for system barriers and internal family barriers to care based on their medical diagnoses.

  6. Unmet Needs of Family Planning Among Women: A Cross-Sectional Study in a Rural Area of Kanchipuram District, Tamil Nadu, South India.

    Vishnu Prasad, R; Venkatachalam, J; Singh, Zile

    2016-10-01

    Global contraceptive usage was 63.3 % in 2010 which was 9 % more than that in 1990. NFHS-III 2005-2006 revealed that the contraceptive prevalence rate was 56 % while in the past decade it was 48 %. In India, female sterilization is the most commonly preferred method of contraception accounting for 76 %, while in Tamil Nadu it was 90 %. Thus, this study aims at measuring the prevalence of unmet needs of family planning and its determinants in a rural area of Kancheepuram district, Tamil Nadu. The study was carried out as a community-based cross-sectional study in Chunambed panchayat, a rural area in Kanchipuram District, Tamil Nadu, India, among 505 women of age group 15-49 years. Cluster random sampling was done to select the households to include in the study. In every household, all the available and eligible women were explained about the study and recruited after obtaining informed consent. Chi-square test was applied for finding the difference in proportion, and p value <0.05 was considered statistically significant. The prevalence of unmet need for family planning in our study population was nearly 31 %; it was even more for younger age groups and for the women whose family size was less. 51.7 % of the participants were currently using a contraceptive measure and very few of their partners used contraception. Government health facilities were the major source of contraceptive service and majority of our participants were well aware about the various contraceptive methods. Unmet needs of family planning were high in our study population, and the knowledge about the contraceptive use and family planning was found to be fairly adequate.

  7. Macroeconomic costs of the unmet burden of surgical disease in Sierra Leone: a retrospective economic analysis.

    Grimes, Caris E; Quaife, Matthew; Kamara, Thaim B; Lavy, Christopher B D; Leather, Andy J M; Bolkan, Håkon A

    2018-03-14

    The Lancet Commission on Global Surgery estimated that low/middle-income countries will lose an estimated cumulative loss of US$12.3 trillion from gross domestic product (GDP) due to the unmet burden of surgical disease. However, no country-specific data currently exist. We aimed to estimate the costs to the Sierra Leone economy from death and disability which may have been averted by surgical care. We used estimates of total, met and unmet need from two main sources-a cluster randomised, cross-sectional, countrywide survey and a retrospective, nationwide study on surgery in Sierra Leone. We calculated estimated disability-adjusted life years from morbidity and mortality for the estimated unmet burden and modelled the likely economic impact using three different methods-gross national income per capita, lifetime earnings foregone and value of a statistical life. In 2012, estimated, discounted lifetime losses to the Sierra Leone economy from the unmet burden of surgical disease was between US$1.1 and US$3.8 billion, depending on the economic method used. These lifetime losses equate to between 23% and 100% of the annual GDP for Sierra Leone. 80% of economic losses were due to mortality. The incremental losses averted by scale up of surgical provision to the Lancet Commission target of 80% were calculated to be between US$360 million and US$2.9 billion. There is a large economic loss from the unmet need for surgical care in Sierra Leone. There is an immediate need for massive investment to counteract ongoing economic losses. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  8. Unmet needs in immigrant cancer survivors: a cross-sectional population-based study.

    Butow, P N; Bell, M L; Aldridge, L J; Sze, M; Eisenbruch, M; Jefford, M; Schofield, P; Girgis, A; King, M; Duggal, P S; McGrane, J; Goldstein, D

    2013-09-01

    Social suffering, language difficulties, and cultural factors may all make the cancer experience more difficult for immigrants. This study aimed to document unmet needs, and variables associated with these, in a population-based sample of first-generation immigrants and Anglo-Australians who had survived cancer. Participants were recruited via Australian cancer registries. Eligible cancer survivors had a new diagnosis 1-6 years earlier and were aged between 18 and 80 years at diagnosis. Eligible immigrant participants and parents were born in a country where Arabic, Chinese (Mandarin, Cantonese, and other dialects), or Greek is spoken, and they spoke one of these languages. A random sample of English-speaking Anglo-Australian-born controls was recruited. Five hundred ninety-six patients (277 immigrants) were recruited to the study (response rate, 26%). Compared to Anglo-Australians, the adjusted odds ratio of Chinese immigrants for at least one unmet information/support need was 5.1 (95% CI 3.1, 8.3) and for any unmet physical need was 3.1 (95% CI 1.9, 5.1). For Greek, these were 2.0 (95% CI 1.1, 4.0) and 2.7 (95% CI 1.4, 5.2). Arabic patients had elevated, but not statistically significant, odds ratios compared to Anglo-Australians. Written information and having a specialist, support services, and other health professionals who spoke their language were in the top ten unmet needs amongst immigrants. Immigrant cancer survivors, several years after initial diagnosis, are more likely to have an unmet need for information or for help with a physical problem than Anglo-Australians. They strongly desire information and support in their own language.

  9. Computational sequence analysis of predicted long dsRNA transcriptomes of major crops reveals sequence complementarity with human genes.

    Jensen, Peter D; Zhang, Yuanji; Wiggins, B Elizabeth; Petrick, Jay S; Zhu, Jin; Kerstetter, Randall A; Heck, Gregory R; Ivashuta, Sergey I

    2013-01-01

    Long double-stranded RNAs (long dsRNAs) are precursors for the effector molecules of sequence-specific RNA-based gene silencing in eukaryotes. Plant cells can contain numerous endogenous long dsRNAs. This study demonstrates that such endogenous long dsRNAs in plants have sequence complementarity to human genes. Many of these complementary long dsRNAs have perfect sequence complementarity of at least 21 nucleotides to human genes; enough complementarity to potentially trigger gene silencing in targeted human cells if delivered in functional form. However, the number and diversity of long dsRNA molecules in plant tissue from crops such as lettuce, tomato, corn, soy and rice with complementarity to human genes that have a long history of safe consumption supports a conclusion that long dsRNAs do not present a significant dietary risk.

  10. Major Findings from The Changing Body: Health, Nutrition, and Human Development in the Western World since 1700.

    Fogel, Robert W; Grotte, Nathaniel

    2011-12-01

    This paper discusses findings from The Changing Body: Health, Nutrition, and Human Development in the Western World since 1700 (Cambridge University Press) The book is built on the authors' work with 300 years of height and nutrition data and discusses their findings in the context of technophysio evolution, a uniquely modern form of rapid physiological development, the result of humanity's ability to control its environment and create technological innovations to adapt to it.

  11. Beyond symptom management: Family relations, unmet needs of persons living with severe mental illnesses, and potential implications for social work in South Africa

    Tomita, Andrew; Burns, Jonathan K.; King, Howard; Baumgartner, Joy Noel; Davis, Glen P.; Mtshemla, Sisanda; Nene, Siphumelele; Susser, Ezra

    2016-01-01

    This study examined the quality of family relationships and its associations with the severity of unmet needs of individuals admitted to a tertiary psychiatric hospital in South Africa. The quality of family relations and perceived unmet needs were assessed using the Lehman Quality of Life Interview and Camberwell Assessment of Needs, respectively. The results show that higher total unmet needs were associated with lower quality of family relations. The main areas of serious unmet needs inclu...

  12. Dichotomy of the human T cell response to Leishmania antigens. I. Th1-like response to Leishmania major promastigote antigens in individuals recovered from cutaneous leishmaniasis

    Kemp, M; Hey, A S; Kurtzhals, J A

    1994-01-01

    of skin lesions, and in Danes without known exposure to Leishmania parasites. Proliferation and production of interferon-gamma (IFN-gamma) and IL-4 in antigen-stimulated cultures was measured. Lymphocytes from individuals with a history of CL proliferated vigorously and produced IFN-gamma after...... the unexposed Danes were not activated by gp63. The cells from Danish donors produced either IFN-gamma or IL-4, but not both cytokines after incubation with the crude preparation of L. major antigens. The data show that the T cell response to Leishmania antigens in humans who have had uncomplicated CL...... stimulation with either a crude preparation of L. major antigens or the major surface protease gp63. These cultures produced no or only little IL-4. Also cells from leishmanin skin test-positive donors with no history of CL produced IFN-gamma and no IL-4 in response to L. major antigens. Cells from...

  13. Identification of human cytochrome P450 and UGT enzymes involved in the metabolism of ferulic acid, a major bioactive component in traditional Chinese medicines.

    Zhuang, Xiao-Mei; Chen, Lin; Tan, Yan; Yang, Hai-Ying; Lu, Chuang; Gao, Yue; Li, Hua

    2017-09-01

    Ferulic acid (FA) is an active component of herbal medicines. One of the best documented activities of FA is its antioxidant property. Moreover, FA exerts antiallergic, anti-inflammatory, and hepatoprotective effects. However, the metabolic pathways of FA in humans remain unclear. To identify whether human CYP or UGT enzymes are involved in the metabolism of FA, reaction phenotyping of FA was conducted using major CYP-selective chemical inhibitors together with individual CYP and UGT Supersomes. The CYP- and/or UGT-mediated metabolism kinetics were examined simultaneously or individually. Relative activity factor and total normalized rate approaches were used to assess the relative contributions of each major human CYPs towards the FA metabolism. Incubations of FA with human liver microsomes (HLM) displayed NADPH- and UDPGA-dependent metabolism with multiple CYP and UGT isoforms involved. CYPs and UGTs contributed equally to the metabolism of FA in HLM. Although CYP1A2 and CYP3A4 appeared to be the major contributors in the CYP-mediated clearance, their contributions to the overall clearance are still minor (medicines because multiple phase I and phase II enzymes are involved in its metabolism. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  14. Identification of neurotensin-related peptides in human thymic epithelial cell membranes and relationship with major histocompatibility complex class I molecules.

    Vanneste, Y; Thome, A N; Vandersmissen, E; Charlet, C; Franchimont, D; Martens, H; Lhiaubet, A M; Schimpff, R M; Rostène, W; Geenen, V

    1997-06-01

    This study shows the expression at the cell surface of human thymic epithelial cells (TEC) of a neurotensin (NT)-like immunoreactivity. NT radio-immunoassay (RIA) revealed that cultured human TEC contain +/-5 ng immunoreactive (ir) NT/10(6) cells, of which 5% is associated with plasma cell membranes. HPLC analysis of NT-ir present in human TEC showed a major peak of NT-ir corresponding to NT1-13. NT-ir was not detected in the supernatant of human TEC cultures. Using an affinity column prepared with a anti-MHC class I monoclonal antibody, NT-ir-related peptides were retained on the column and eluted together with MHC class I-related proteins. According to the elution time on HPLC of these peptides, they correspond to intact NT1-13, as well as to smaller fragments of NT1-13.

  15. Using Survey Data to Identify Opportunities to Reach Women with An Unmet Need for Family Planning: The Example of Madagascar.

    Meekers, Dominique; Ratovonanahary, Raseliarison; Andrianantoandro, Tokinirina; Randrianarisoa, Hiangotiana

    2016-01-01

    In several African countries fertility levels have stagnated or increased slightly. However, many women still report an unmet need for family planning. Therefore achieving further fertility declines requires programs that increase demand for family planning, but that also address the existing unmet need. One way to improve contraceptive access in a cost-effective manner might be to integrate family planning services into other existing health services. This paper analyzes secondary data from the 2012-2013 Millennium Development Goals (MDG) survey in Madagascar to estimate the number of women with an unmet need for family planning that might benefit from integrating family planning services into other health services. In Madagascar, one third of the demand for family planning is not met; an estimated 820,000 women have an unmet need for family planning. A substantial portion of these women can be reached by integrating family planning services into existing maternal and child health services. Health providers are uniquely positioned to help address method-related reasons for non-use of family planning, such as concerns about health problems and side-effects. Given the large unmet need for family planning, programs should not exclusively focus on increasing the demand for family planning, but also seek new ways to address the existing unmet need. Our study illustrates that simple analyses of existing health survey data can be an important tool for informing the design of programs to tackle this unmet need.

  16. Public Housing Relocations and Relationships of Changes in Neighborhood Disadvantage and Transportation Access to Unmet Need for Medical Care.

    Haley, Danielle F; Linton, Sabriya; Luo, Ruiyan; Hunter-Jones, Josalin; Adimora, Adaora A; Wingood, Gina M; Bonney, Loida; Ross, Zev; Cooper, Hannah L

    2017-01-01

    Cross-sectional research suggests that neighborhood characteristics and transportation access shape unmet need for medical care. This longitudinal analysis explores relationships of changes in neighborhood socioeconomic disadvantage and trans- portation access to unmet need for medical care. We analyzed seven waves of data from African American adults (N = 172) relocating from severely distressed public housing complexes in Atlanta, Georgia. Surveys yielded individual-level data and admin- istrative data characterized census tracts. We used hierarchical generalized linear models to explore relationships. Unmet need declined from 25% pre-relocation to 12% at Wave 7. Post-relocation reductions in neighborhood disadvantage were inversely associated with reductions in unmet need over time (OR = 0.71, 95% CI = 0.51-0.99). More frequent transportation barriers predicted unmet need (OR = 1.16, 95% CI = 1.02-1.31). These longitudinal findings support the importance of neighborhood environments and transportation access in shaping unmet need and suggest that improvements in these exposures reduce unmet need for medical care in this vulnerable population.

  17. Humans as major geological and geomorphological agents in the Anthropocene: the significance of artificial ground in Great Britain.

    Price, Simon J; Ford, Jonathan R; Cooper, Anthony H; Neal, Catherine

    2011-03-13

    Since the first prehistoric people started to dig for stone to make implements, rather than pick up loose material, humans have modified the landscape through excavation of rock and soil, generation of waste and creation of artificial ground. In Great Britain over the past 200 years, people have excavated, moved and built up the equivalent of at least six times the volume of Ben Nevis. It is estimated that the worldwide deliberate annual shift of sediment by human activity is 57,000 Mt (million tonnes) and exceeds that of transport by rivers to the oceans (22,000 Mt) almost by a factor of three. Humans sculpt and transform the landscape through the physical modification of the shape and properties of the ground. As such, humans are geological and geomorphological agents and the dominant factor in landscape evolution through settlement and widespread industrialization and urbanization. The most significant impact of this has been since the onset of the Industrial Revolution in the eighteenth century, coincident with increased release of greenhouse gases to the atmosphere. The anthropogenic sedimentological record, therefore, provides a marker on which to characterize the Anthropocene.

  18. Wide Variability in Caloric Density of Expressed Human Milk Can Lead to Major Underestimation or Overestimation of Nutrient Content.

    Sauer, Charles W; Boutin, Mallory A; Kim, Jae H

    2017-05-01

    Very-low-birth-weight infants continue to face significant difficulties with postnatal growth. Human milk is the optimal form of nutrition for infants but may exhibit variation in nutrient content. This study aimed to perform macronutrient analysis on expressed human milk from mothers whose babies are hospitalized in the neonatal intensive care unit. Up to five human milk samples per participant were analyzed for protein, carbohydrate, and fat content using reference chemical analyses (Kjeldahl for protein, high pressure liquid chromatography for carbohydrates, and Mojonnier for fat). Calorie content was calculated. A total of 64 samples from 24 participants was analyzed. Wide variability was found in calorie, protein, carbohydrate, and fat composition. The authors found an average of 17.9 kcal/ounce, with only 34% of samples falling within 10% of the expected caloric density. The assumption that human milk contains 20 kcal/ounce is no longer supported based on this study. This supports promoting an individualized nutrition strategy as a crucial aspect to optimal nutrition.

  19. Omega-oxidation is the major pathway for the catabolism of leukotriene B4 in human polymorphonuclear leukocytes.

    Shak, S; Goldstein, I M

    1984-08-25

    Leukotriene B4 (LTB4), formed by the 5-lipoxygenase pathway in human polymorphonuclear leukocytes (PMN), may be an important mediator of inflammation. Recent studies suggest that human leukocytes can convert LTB4 to products that are less biologically active. To examine the catabolism of LTB4, we developed (using high performance liquid chromatography) a sensitive, reproducible assay for this mediator and its omega-oxidation products (20-OH- and 20-COOH-LTB4). With this assay, we have found that human PMN (but not human monocytes, lymphocytes, or platelets) convert exogenous LTB4 almost exclusively to 20-OH- and 20-COOH-LTB4 (identified by gas chromatography-mass spectrometry). Catabolism of exogenous LTB4 by omega-oxidation is rapid (t1/2 approximately 4 min at 37 degrees C in reaction mixtures containing 1.0 microM LTB4 and 20 X 10(6) PMN/ml), temperature-dependent (negligible at 0 degrees C), and varies with cell number as well as with initial substrate concentration. The pathway for omega-oxidation in PMN is specific for LTB4 and 5(S),12(S)-dihydroxy-6,8,10,14-eicosatetraenoic acid (only small amounts of other dihydroxylated-derivatives of arachidonic acid are converted to omega-oxidation products). Even PMN that are stimulated by phorbol myristate acetate to produce large amounts of superoxide anion radicals catabolize exogenous leukotriene B4 primarily by omega-oxidation. Finally, LTB4 that is generated when PMN are stimulated with the calcium ionophore, A23187, is rapidly catabolized by omega-oxidation. Thus, human PMN not only generate and respond to LTB4, but also rapidly and specifically catabolize this mediator by omega-oxidation.

  20. Protocol for Isolation of Primary Human Hepatocytes and Corresponding Major Populations of Non-parenchymal Liver Cells

    Pfeiffer, Elisa; Zeilinger, Katrin; Seehofer, Daniel; Damm, Georg

    2016-01-01

    Beside parenchymal hepatocytes, the liver consists of non-parenchymal cells (NPC) namely Kupffer cells (KC), liver endothelial cells (LEC) and hepatic Stellate cells (HSC). Two-dimensional (2D) culture of primary human hepatocyte (PHH) is still considered as the "gold standard" for in vitro testing of drug metabolism and hepatotoxicity. It is well-known that the 2D monoculture of PHH suffers from dedifferentiation and loss of function. Recently it was shown that hepatic NPC play a central role in liver (patho-) physiology and the maintenance of PHH functions. Current research focuses on the reconstruction of in vivo tissue architecture by 3D- and co-culture models to overcome the limitations of 2D monocultures. Previously we published a method to isolate human liver cells and investigated the suitability of these cells for their use in cell cultures in Experimental Biology and Medicine1. Based on the broad interest in this technique the aim of this article was to provide a more detailed protocol for the liver cell isolation process including a video, which will allow an easy reproduction of this technique. Human liver cells were isolated from human liver tissue samples of surgical interventions by a two-step EGTA/collagenase P perfusion technique. PHH were separated from the NPC by an initial centrifugation at 50 x g. Density gradient centrifugation steps were used for removal of dead cells. Individual liver cell populations were isolated from the enriched NPC fraction using specific cell properties and cell sorting procedures. Beside the PHH isolation we were able to separate KC, LEC and HSC for further cultivation. Taken together, the presented protocol allows the isolation of PHH and NPC in high quality and quantity from one donor tissue sample. The access to purified liver cell populations could allow the creation of in vivo like human liver models. PMID:27077489

  1. Levels, trends and reasons for unmet need for family planning among married women in Botswana: a cross-sectional study.

    Letamo, Gobopamang; Navaneetham, Kannan

    2015-03-31

    The objectives of this study are: (1) to estimate the prevalence of unmet need for family planning among married women using Botswana Family Health Survey 2007 data and (2) to identify risk factors for unmet need for family planning among married women. This study used secondary data from a cross-sectional survey that was conducted to provide a snapshot of health issues in Botswana. Nationally representative population survey data. 2601 married or in union women aged 15-49 years who participated in the 2007 Botswana Family Health Survey were included in the analysis. Unmet need for family planning, which was defined as the percentage of all fecund married women who are not using a method of contraception even though they do not want to get pregnant. Married women who had unmet need for family planning were 9.6% in 2007. Most of the unmet need was for limiting (6.7%) compared to spacing (2.9%). Unmet need for family planning was more likely to be among women whose partners disapproved of family planning, non-Christians, had one partner and had never discussed family planning with their partner. Women of low parity, aged 25-34 years, and greater exposure to mass media, were less likely to have experienced unmet need. The patterns and magnitude of covariates differed between unmet need for limiting and for spacing. The prevalence of unmet need for family planning was low in Botswana compared to other sub-Saharan African countries. The findings from this study reemphasise the importance of women's empowerment and men's involvement in women's sexual and reproductive healthcare needs and services. Different approaches are needed to satisfy the demand for family planning for spacing and limiting. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  2. Simultaneous assessments of occurrence, ecological, human health, and organoleptic hazards for 77 VOCs in typical drinking water sources from 5 major river basins, China

    Chen, Xichao; Luo, Qian; Wang, Donghong; Gao, Jijun; Wei, Zi; Wang, Zijian; Zhou, Huaidong; Mazumder, Asit

    2015-01-01

    Owing to the growing public awareness on the safety and aesthetics in water sources, more attention has been given to the adverse effects of volatile organic compounds (VOCs) on aquatic organisms and human beings. In this study, 77 target VOCs (including 54 common VOCs, 13 carbonyl compounds, and 10 taste and odor compounds) were detected in typical drinking water sources from 5 major river basins (the Yangtze, the Huaihe, the Yellow, the Haihe and the Liaohe River basins) and their occurrences were characterized. The ecological, human health, and olfactory assessments were performed to assess the major hazards in source water. The investigation showed that there existed potential ecological risks (1.30 × 10 ≤ RQ_t_o_t_a_ls ≤ 8.99 × 10) but little human health risks (6.84 × 10"−"7 ≤ RQ_t_o_t_a_ls ≤ 4.24 × 10"−"4) by VOCs, while that odor problems occurred extensively. The priority contaminants in drinking water sources of China were also listed based on the present assessment criteria. - Highlights: • VOCs with various polarities were screened in typical water sources of China. • Ecological, human health and olfactory assessments were simultaneously performed. • The risk assessments were used to identify the major hazards by VOCs. • The detected VOCs posed potential ecological risks but little human health risks. • Odor problems occurred extensively in source water of China. - Detected VOCs with various polarities caused odor problems and posed potential ecological risks but little human health risks in drinking water sources in China.

  3. Podiatry services for patients with arthritis: an unmet need.

    Rome, Keith; Chapman, Jonathan; Williams, Anita E; Gow, Peter; Dalbeth, Nicola

    2010-03-05

    Foot problems are extremely common in patients with rheumatoid arthritis (RA). There is ample evidence that foot pain, either alone or as a comorbidity, contributes significantly to disability. Despite the high prevalence of foot disease in RA, this problem is often trivialised or underappreciated. The inequity in foot health provision for patients with rheumatic disorders in New Zealand has recently been highlighted. Expertise in dealing with foot problems is often limited among healthcare professionals, and it has been argued that better integration of podiatric services into rheumatology services would be beneficial. The aim of this paper is to highlight the major issues related to foot care for patients with arthritis and provide key recommendations that should implemented to improve access to podiatric services in New Zealand.

  4. Major depression

    Depression - major; Depression - clinical; Clinical depression; Unipolar depression; Major depressive disorder ... providers do not know the exact causes of depression. It is believed that chemical changes in the ...

  5. Restoring function in major depressive disorder: A systematic review.

    Sheehan, David V; Nakagome, Kazuyuki; Asami, Yuko; Pappadopulos, Elizabeth A; Boucher, Matthieu

    2017-06-01

    Functional impairment contributes to significant disability and economic burden in major depressive disorder (MDD). Treatment response is measured by improvement in depressive symptoms, but functional improvement often lags behind symptomatic improvement. Residual deficits are associated with relapse of depressive symptoms. A literature search was conducted using the following terms: "major depressive disorder," "functional impairment," "functional outcomes," "recovery of function," "treatment outcome," "outcome assessment," "social functioning," "presenteeism," "absenteeism," "psychiatric status rating scales," and "quality of life." Search limits included publication date (January 1, 1995 to August 31, 2016), English language, and human clinical trials. Controlled, acute-phase, nonrecurrent MDD treatment studies in adults were included if a functional outcome was measured at baseline and endpoint. The qualitative analysis included 35 controlled studies. The Sheehan Disability Scale was the most commonly used functional assessment. Antidepressant treatments significantly improved functional outcomes. Early treatment response predicted functional improvement, while baseline disease severity did not. Clinical studies utilized various methodologies and assessments for functional impairment, and were not standardized or adequately powered. The lack of synchronicity between symptomatic and functional improvement highlights an unmet need for MDD. Treatment guided by routine monitoring of symptoms and functionality may minimize residual functional impairments. Copyright © 2017. Published by Elsevier B.V.

  6. Can profiles of poly- and Perfluoroalkyl substances (PFASs) in human serum provide information on major exposure sources?

    Hu, Xindi C; Dassuncao, Clifton; Zhang, Xianming

    2018-01-01

    BACKGROUND: Humans are exposed to poly- and perfluoroalkyl substances (PFASs) from diverse sources and this has been associated with negative health impacts. Advances in analytical methods have enabled routine detection of more than 15 PFASs in human sera, allowing better profiling of PFAS......) and their precursors are ubiquitous in multiple exposure sources. However, their composition varies among sources, which may impact associated adverse health effects. METHODS: We use available PFAS concentrations from several demographic groups in a North Atlantic seafood consuming population (Faroe Islands...... sulfonamidoacetate (N-EtFOSAA), which are directly used or metabolized from fluorochemicals in consumer products such as carpet and food packaging. We find that the same compounds are associated with the same exposure sources in two North American populations, suggesting generalizability of results from the Faroese...

  7. The Global Acetylome of the Human Pathogen Vibrio cholerae V52 Reveals Lysine Acetylation of Major Transcriptional Regulators

    Jers, Carsten; Ravikumar, Vaishnavi; Lezyk, Mateusz Jakub

    2018-01-01

    Protein lysine acetylation is recognized as an important reversible post translational modification in all domains of life. While its primary roles appear to reside in metabolic processes, lysine acetylation has also been implicated in regulating pathogenesis in bacteria. Several global lysine...... acetylome analyses have been carried out in various bacteria, but thus far there have been no reports of lysine acetylation taking place in the important human pathogen Vibrio cholerae. In this study, we analyzed the lysine acetylproteome of the human pathogen V. cholerae V52. By applying a combination...... in direct regulation of virulence in V. cholerae were acetylated. In conclusion, this is the first global protein lysine acetylome analysis of V. cholerae and should constitute a valuable resource for in-depth studies of the impact of lysine acetylation in pathogenesis and other cellular processes....

  8. A new splice variant of the major subunit of human asialoglycoprotein receptor encodes a secreted form in hepatocytes.

    Jia Liu

    Full Text Available BACKGROUND: The human asialoglycoprotein receptor (ASGPR is composed of two polypeptides, designated H1 and H2. While variants of H2 have been known for decades, the existence of H1 variants has never been reported. PRINCIPAL FINDINGS: We identified two splice variants of ASGPR H1 transcripts, designated H1a and H1b, in human liver tissues and hepatoma cells. Molecular cloning of ASGPR H1 variants revealed that they differ by a 117 nucleotide segment corresponding to exon 2 in the ASGPR genomic sequence. Thus, ASGPR variant H1b transcript encodes a protein lacking the transmembrane domain. Using an H1b-specific antibody, H1b protein and a functional soluble ASGPR (sASGPR composed of H1b and H2 in human sera and in hepatoma cell culture supernatant were identified. The expression of ASGPR H1a and H1b in Hela cells demonstrated the different cellular loctions of H1a and H1b proteins at cellular membranes and in intracellular compartments, respectively. In vitro binding assays using fluorescence-labeled sASGPR or the substract ASOR revealed that the presence of sASGPR reduced the binding of ASOR to cells. However, ASOR itself was able to enhance the binding of sASGPR to cells expressing membrane-bound ASGPR. Further, H1b expression is reduced in liver tissues from patients with viral hepatitis. CONCLUSIONS: We conclude that two naturally occurring ASGPR H1 splice variants are produced in human hepatocytes. A hetero-oligomeric complex sASGPR consists of the secreted form of H1 and H2 and may bind to free substrates in circulation and carry them to liver tissue for uptake by ASGPR-expressing hepatocytes.

  9. Recombinant human thyrotropin-stimulated radioiodine therapy of nodular goiter allows major reduction of the radiation burden with retained efficacy

    Fast, Søren; Hegedüs, Laszlo; Grupe, Peter

    2010-01-01

    Context and Objective: Stimulation with recombinant human TSH (rhTSH) before radioiodine ((131)I) therapy augments goiter volume reduction (GVR). Observations indicate that rhTSH has a preconditioning effect beyond increasing thyroid (131)I uptake. We test the hypothesis that an equivalent GVR mi....... This approach is attractive in terms of minimizing posttherapeutic restrictions and in reducing the potential risk of radiation-induced malignancy....

  10. The simultaneous identification of metoprolol and its major acidic and basic metabolites in human urine by gas chromatography-mass spectrometry

    Li, Feng; Cooper, S.F. [Universite du Quebec, Pointe-Claire (Canada)

    1996-12-31

    A novel gas chromatography-mass spectrometric (GC-MS) method was developed to confirm and identify metoprolol and its metabolites by double derivatization with S-(-)menthyl chloroformate [(-)-MCF] and N-methyl(trimethylsilyl-trifluoroacetamide) (MSTFA). This is the first report, which describes the simultaneous identification of metoprolol, its one major acidc and other basic metabolites in human urine based on solid-phase extraction with C{sub 18} reversed-phase cartridges. 12 refs., 4 figs.

  11. Specific interactions between transcription factors and the promoter-regulatory region of the human cytomegalovirus major immediate-early gene

    Ghazal, P.; Lubon, H.; Hennighausen, L.

    1988-01-01

    Repeat sequence motifs as well as unique sequences between nucleotides -150 and -22 of the human cytomegalovirus immediate-early 1 gene interact in vitro with nuclear proteins. The authors show that a transcriptional element between nucleotides -91 and -65 stimulated promoter activity in vivo and in vitro by binding specific cellular transcription factors. Finally, a common sequence motif, (T)TGG/AC, present in 15 of the determined binding sites suggests a particular class of nuclear factors associated with the immediate-early 1 gene

  12. Unmet need of contraceptives among eligible couples of urban slum dwellers in Dhaka

    Shamsun Nahar

    2009-01-01

    Full Text Available This cross-sectional study was conducted on married women residing in urban slums of Kamrangirchar in Dhaka to determine the magnitude of unmet need for family planning. A total of 265 married women of reproductive age who were fecund and living with husband were the sample of the study. The mean age of the respondents was 26.8±6.7 years. A little above 14% of the women were in the age group of 15–19 years. Almost equal proportion of respondents and their husbands were found to be illiterate. Nearly one-tenth of the respondents have not had ever experienced pregnancy, while 23% experienced pregnancy once, 18.1% twice and 33.6% three-four times, 17% more than four times. Among the respondents, 51.3% were currently using a contraceptive method. Around 5% were pregnant, which was intended. Another 3% wanted to conceive. The rest 41.1% wanted to use a contraceptive but certain barriers did not allow them to use the same suggesting that their family planning need was unmet. This need included limiting (21.5% and spacing (19.6%. Lactational amenorrhea, no specific reasons, side effect of past contraceptive use, lack of support from husband or other family members, lack of proper knowledge of contraceptive and difficulties in obtaining contraceptive supplies were the cited reasons. Unmet need of contraceptive is high despite an extensive family planning programme in Bangladesh. Mean age at marriage is still below the legal age and gender discrimination plays a vital role in this unmet need. Ibrahim Med. Coll. J. 2009; 3(1: 24-28

  13. A Systematic Review of Unmet Information and Psychosocial Support Needs of Adults Diagnosed with Thyroid Cancer.

    Hyun, Yong Gyu; Alhashemi, Ahmad; Fazelzad, Rouhi; Goldberg, Alyse S; Goldstein, David P; Sawka, Anna M

    2016-09-01

    Patient education and psychosocial support to patients are important elements of comprehensive cancer care, but the needs of thyroid cancer survivors are not well understood. The published English-language quantitative literature on (i) unmet medical information and (ii) psychosocial support needs of thyroid cancer survivors was systematically reviewed. A librarian information specialist searched seven electronic databases and a hand search was conducted. Two reviewers independently screened citations from the electronic search and reviewed relevant full-text papers. There was consensus between reviewers on the included papers, and duplicate independent abstraction was performed. The results were summarized descriptively. A total of 1984 unique electronic citations were screened, and 51 full-text studies were reviewed (three from the hand search). Seven cross-sectional, single-arm, survey studies were included, containing data from 6215 thyroid cancer survivor respondents. The respective study sizes ranged from 57 to 2398 subjects. All of the studies had some methodological limitations. Unmet information needs were variable relating to the disease, diagnostic tests, treatments, and co-ordination of medical care. There were relatively high unmet information needs related to aftercare (especially long-term effects of the disease or its treatment and its management) and psychosocial concerns (including practical and financial matters). Psychosocial support needs were incompletely met. Patient information on complementary and alternative medicine was very limited. In conclusion, thyroid cancer survivors perceive many unmet information needs, and these needs extend to aftercare. Psychosocial information and supportive care needs may be insufficiently met in this population. More work is needed to improve knowledge translation and psychosocial support for thyroid cancer survivors.

  14. Perceived Unmet Rehabilitation Needs 1 Year After Stroke: An Observational Study From the Swedish Stroke Register.

    Ullberg, Teresa; Zia, Elisabet; Petersson, Jesper; Norrving, Bo

    2016-02-01

    Met care demands are key aspects in poststroke quality of care. This study aimed to identify baseline predictors and 12-month factors that were associated with perceived unmet rehabilitation needs 1 year poststroke. Data on patients who were independent in activities of daily living, hospitalized for acute stroke during 2008 to 2010, and followed up 1 year poststroke through a postal questionnaire were obtained from the Swedish stroke register. Patients reporting fulfilled rehabilitation needs were compared with those with unmet needs (Chi square test). The study included 37 383 patients, 46% female. At 12 months, 8019 (21.5%) patients reported unmet rehabilitation needs. Compared with those with met rehabilitation needs, patients reporting unmet rehabilitation needs were older (75.4 versus 72.4 years; Prehabilitation needs at 12 months in an age-adjusted model were severe stroke (odds ratio [OR]=3.04; confidence interval [CI]: 2.39-3.87), prior stroke (OR=1.63; CI: 1.53-1.75), female sex (OR=1.14; CI: 1.07-1.20), diabetes mellitus (OR=1.24; CI: 1.15-1.32), stroke other than ischemic (OR=1.26; CI: 1.20-1.32), and atrial fibrillation (OR=1.19; CI: 1.12-1.27). Unfulfilled rehabilitation needs 1 year poststroke are common and associated with high age, dependency, pain, and depression. Long-term follow-up systems should, therefore, be comprehensive and address multiple domains of poststroke problems, rather than having a single-domain focus. © 2016 American Heart Association, Inc.

  15. Unmet dental and orthodontic need of children with special healthcare needs in West Virginia.

    Wiener, R C; Wiener, M A

    2012-01-01

    Of children aged 0-17 years in the USA, an estimated 11 203 616 (15.1%; 95% CI: 14.8, 15.3) are Children with Special Health Care Needs (CSHCN). The state of West Virginia, the heart of Appalachia, has a land mass which is 97.65% rural with previously identified high overall dental need and oral health disparities. It is home to an estimated 70 609 CSHCN, or 18.5% (95% CI: 17.0, 19.9) of the state's children in 2009-2010. The purpose of this study was to determine the parent/guardian's perceived unmet dental care need of CSHCN in West Virginia. Data from the National Survey of Children with Special Health Care Needs was used to determine prevalence. A telephone survey of 59 941 parents/guardians of CSHCN (1149 from West Virginia) for the dental interview was conducted in 2009-2010. Nationwide, 26.7% (25.9, 27.5) of parents/guardians reported their CSHCN had dental care or orthodontia needs other than preventive care. In West Virginia, the perceived dental care or orthodontia needs other than preventive dental care need was 26.5% (22.2, 30.0). Unmet national dental care need other than preventive dental care was 5.4% (5.0, 5.9) and in West Virginia 5.0% (2.4, 7.5). CSHCN have significant unmet dental needs. Parents/guardians in West Virginia reported similar unmet need compared with national reporting. Policies to address the health care of CSHCN should include dental needs. The clinical implications are that CSHCN have a variety of needs, including orthodontia. The benefits of orthodontic referrals should be considered in treatment planning options for CSHCN.

  16. Habitual Sleep Duration, Unmet Sleep Need, and Excessive Daytime Sleepiness in Korean Adults

    Hwangbo, Young; Kim, Won-Joo; Chu, Min Kyung; Yun, Chang-Ho; Yang, Kwang Ik

    2016-01-01

    Background and Purpose Sleep need differs between individuals, and so the same duration of sleep will lead to sleep insufficiency in some individuals but not others. The aim of this study was to determine the separate and combined associations of both sleep duration and unmet sleep need with excessive daytime sleepiness (EDS) in Korean adults. Methods The participants comprised 2,769 Korean adults aged 19 years or older. They completed questionnaires about their sleep habits over the previous...

  17. The Northridge earthquake: community-based approaches to unmet recovery needs.

    Bolin, R; Stanford, L

    1998-03-01

    The 1994 Northridge, California earthquake has proven to be one of the most costly disasters in United States history. Federal and state assistance programmes received some 681,000 applications from victims for various forms of relief. In spite of the flow of US$11 billion in federal assistance into Los Angeles and Ventura counties, many victims have failed to obtain adequate relief. These unmet needs relate to the vulnerability of particular class and ethnic groups. In response to unmet needs, a number of non-governmental organisations (NGOs) have become involved in the recovery process. This paper, based on evidence collected from hundreds of in-depth interviews with the people involved, examines the activities of several community-based organisations (CBOs) and other NGOs as they have attempted to assist vulnerable people with unmet post-disaster needs. We discuss two small ethnically diverse communities in Ventura County, on the periphery of the Los Angeles metropolitan region. The earthquake and resultant disaster declaration provided an opportunity for local government and NGOs to acquire federal resources not normally available for economic development. At the same time the earthquake created political openings in which longer-term issues of community development could be addressed by various local stakeholders. A key issue in recovery has been the availability of affordable housing for those on low incomes, particularly Latinos, the elderly and farm workers. We discuss the successes and limitations of CBOs and NGOs as mechanisms for dealing with vulnerable populations, unmet needs and recovery issues in the two communities.

  18. The Leishmania promastigote surface antigen-2 (PSA-2) is specifically recognised by Th1 cells in humans with naturally acquired immunity to L. major

    Kemp, M; Handman, E; Kemp, K

    1998-01-01

    The promastigote surface antigen-2 (PSA-2) is a Leishmania parasite antigen, which can induce Th1-mediated protection against murine leishmaniasis when used as a vaccine. To evaluate PSA-2 as a human vaccine candidate the specific T-cell response to PSA-2 was characterised in individuals immune...... to cutaneous leishmaniasis. Peripheral blood mononuclear cells from Sudanese individuals with a past history of self-healing cutaneous leishmaniasis proliferated vigorously in response to PSA-2 isolated from Leishmania major, whereas the antigen did not activate cells from presumably unexposed Danes....... Peripheral blood mononuclear cells from individuals with previous L. major infection had varying proliferative responses to PSA-2 derived from L. donovani promastigotes. Peripheral blood mononuclear cells activated by PSA-2 from L. major produced high amounts of interferon-gamma and tumour necrosis factor...

  19. Human colon cancers as a major problem in poland and in the world – medical and environmental issues

    Sylwia Katarzyna Król

    2011-12-01

    Full Text Available Many epidemiological data have shown an increasing incidence and mortality of colon cancer cases in the past several years, not only in Poland but all over the world as well. Each year, approximately a million new cases of colon cancer are diagnosed and that is the cause of death of almost half a million patients in the world. The aim of this article is to present the epidemiology and the current state of scientific knowledge concerning etiology and pathogenesis of neoplastic diseases in human large intestine. Furthermore, this short review describes the essential risk factors and suggests the simple and effective ways of colon cancer prevention.Colorectal cancer is one of the most frequently diagnosed cancers in EU countries. Scientific studies have proved that genetic and hereditary factors have a strong influence on carcinogenesis in human colon. Moreover, environmental factors, such as dietary contribute to the development of colon neoplasm. The most useful tool to reduce high morbidity and mortality is a prevention. Screening tests in nonsymptomatic people from high-risk groups or populations enable diagnosis in the early stage of colorectal cancer. Many publications have reported that modification of lifestyle and daily diet also play a significant role in prevention.

  20. The Virome and Its Major Component, Anellovirus, a Convoluted System Molding Human Immune Defenses and Possibly Affecting the Development of Asthma and Respiratory Diseases in Childhood

    Giulia Freer

    2018-04-01

    Full Text Available The microbiome, a thriving and complex microbial community colonizing the human body, has a broad impact on human health. Colonization is a continuous process that starts very early in life and occurs thanks to shrewd strategies microbes have evolved to tackle a convoluted array of anatomical, physiological, and functional barriers of the human body. Cumulative evidence shows that viruses are part of the microbiome. This part, called virome, has a dynamic composition that reflects what we eat, how and where we live, what we do, our genetic background, and other unpredictable variables. Thus, the virome plays a chief role in shaping innate and adaptive host immune defenses. Imbalance of normal microbial flora is thought to trigger or exacerbate many acute and chronic disorders. A compelling example can be found in the respiratory apparatus, where early-life viral infections are major determinants for the development of allergic diseases, like asthma, and other non-transmissible diseases. In this review, we focus on the virome and, particularly, on Anelloviridae, a recently discovered virus family. Anelloviruses are major components of the virome, present in most, if not all, human beings, where they are acquired early in life and replicate persistently without causing apparent disease. We will discuss how modulation of innate and adaptive immune systems by Anelloviruses can influence the development of respiratory diseases in childhood and provide evidence for the use of Anelloviruses as useful and practical molecular markers to monitor inflammatory processes and immune system competence.

  1. Unmet social needs and teenage pregnancy in Ogbomosho, South-western Nigeria.

    Salami, Kabiru K; Ayegboyin, Matthew; Adedeji, Isaac A

    2014-12-01

    Consistent high teenage pregnancy rates in South-western Nigeria are characteristically underpinned by the unmet social needs of the teenagers. To elicit intergenerational views on the influence of unmet social needs on teenage pregnancy. Through a descriptive and cross-sectional design, a total of 174 respondents who were either pregnant teenagers, teenage mothers during the survey or had been pregnant as teenagers, were interviewed, using questionnaire supplemented with 12 key informant interviews. With the mean age of 16.5 years, and educational status range of between primary and below (25.8%) and tertiary (9.8%) levels, only 39.7% respondents were married, about half (47.7%) remained single while others were separated (12.6%). Less than half (44.9%) of the respondents were engaged in occupational activities. The unmet material and financial supports expected from parents (43.1%), the lack of free education from government up till secondary school level (51.2%), the lack of sex education and knowledge needs for signs of maturity (53.4%) and discouragement from friends not to have boyfriend (66.1%) prone teenagers to unplanned pregnancy. Promotion of sexual education and parental care is encouraged as strategy against unplanned pregnancy among teenagers.

  2. Financial hardship, unmet medical need, and health self-efficacy among African American men.

    Tucker-Seeley, Reginald D; Mitchell, Jamie A; Shires, Deirdre A; Modlin, Charles S

    2015-06-01

    Health self-efficacy (the confidence to take care of one's health) is a key component in ensuring that individuals are active partners in their health and health care. The purpose of this study was to determine the association between financial hardship and health self-efficacy among African American men and to determine if unmet medical need due to cost potentially mediates this association. Cross-sectional analysis was conducted using data from a convenience sample of African American men who attended a 1-day annual community health fair in Northeast Ohio (N = 279). Modified Poisson regression models were estimated to obtain the relative risk of reporting low health self-efficacy. After adjusting for sociodemographic characteristics, those reporting financial hardship were 2.91 times, RR = 2.91 (confidence interval [1.24, 6.83]; p financial hardship and low health self-efficacy was no longer statistically significant. Our results suggest that the association between financial hardship and health self-efficacy can be explained by unmet medical need due to cost. Possible intervention efforts among African American men with low financial resources should consider expanding clinical and community-based health assessments to capture financial hardship and unmet medical need due to cost as potential contributors to low health self-efficacy. © 2014 Society for Public Health Education.

  3. Challenges Addressing Unmet Need for Contraception: Voices of Family Planning Service Providers in Rural Tanzania.

    Baraka, Jitihada; Rusibamayila, Asinath; Kalolella, Admirabilis; Baynes, Colin

    2015-12-01

    Provider perspectives have been overlooked in efforts to address the challenges of unmet need for family planning (FP). This qualitative study was undertaken in Tanzania, using 22 key informant interviews and 4 focus group discussions. The research documents perceptions of healthcare managers and providers in a rural district on the barriers to meeting latent demand for contraception. Social-ecological theory is used to interpret the findings, illustrating how service capability is determined by the social, structural and organizational environment. Providers' efforts to address unmet need for FP services are constrained by unstable reproductive preferences, low educational attainment, and misconceptions about contraceptive side effects. Societal and organizational factors--such as gender dynamics, economic conditions, religious and cultural norms, and supply chain bottlenecks, respectively--also contribute to an adverse environment for meeting needs for care. Challenges that healthcare providers face interact and produce an effect which hinders efforts to address unmet need. Interventions to address this are not sufficient unless the supply of services is combined with systems strengthening and social engagement strategies in a way that reflects the multi-layered, social institutional problems.

  4. Socioeconomic Inequalities in Health and Perceived Unmet Needs for Healthcare among the Elderly in Germany

    Jens Hoebel

    2017-09-01

    Full Text Available Research into health inequalities in the elderly population of Germany is relatively scarce. This study examines socioeconomic inequalities in health and perceived unmet needs for healthcare and explores the dynamics of health inequalities with age among elderly people in Germany. Data were derived from the Robert Koch Institute’s cross-sectional German Health Update study. The sample was restricted to participants aged 50–85 years (n = 11,811. Socioeconomic status (SES was measured based on education, (former occupation, and income. Odds ratios and prevalence differences were estimated using logistic regression and linear probability models, respectively. Our results show that self-reported health problems were more prevalent among men and women with lower SES. The extent of SES-related health inequalities decreased at older ages, predominantly among men. Although the prevalence of perceived unmet needs for healthcare was low overall, low SES was associated with higher perceptions of unmet needs in both sexes and for several kinds of health services. In conclusion, socioeconomic inequalities in health exist in a late working age and early retirement but may narrow at older ages, particularly among men. Socially disadvantaged elderly people perceive greater barriers to accessing healthcare services than those who are better off.

  5. Measuring Nutrition-Related Unmet Needs in Recently Hospital-Discharged Homebound Older Adults.

    Vaudin, Anna; Song, Hee-Jung; Mehta, Mira; Sahyoun, Nadine

    2018-01-01

    Functional limitations in homebound older adults may cause difficulties with obtaining and preparing adequate healthy food. Services exist to help with these difficulties, however, not all individuals who could benefit receive them. This secondary analysis of observational data, obtained via questionnaires from homebound, recently hospital discharged older adults (n = 566), aimed to identify the prevalence and correlates of unmet need for such services, and to examine the disagreement between self-reported need for a service and functional limitation that could be addressed by that service. One-fifth of respondents reported unmet need for vision services and oral health services, and one-tenth reported unmet need for transportation services and physical therapy. There was a significant association between reported need and functional limitation (p < 0.001) for all services, except mental health and grocery delivery. However, for each service there were participants who under-reported need, compared with functional ability indicators. More research is required to determine the best methods for measuring these needs to ensure that nutritional vulnerability is detected and addressed in those returning from hospital.

  6. In normal human fibroblasts variation in DSB repair capacity cannot be ascribed to radiation-induced changes in the localisation, expression or activity of major NHEJ proteins

    Kasten-Pisula, Ulla; Vronskaja, Svetlana; Overgaard, Jens

    2008-01-01

    in the activity of the DNA-PK complex induced upon irradiation. CONCLUSIONS: For normal human fibroblasts, the level or activity of NHEJ proteins measured prior to or after irradiation cannot be used to predict the DSB repair capacity or cellular radiosensitivity. Udgivelsesdato: 2008-Mar......BACKGROUND AND PURPOSE: The aim of the present study was to test whether for normal human fibroblasts the variation in double-strand break (DSB) repair capacity results from radiation-induced differences in localisation, expression or activity of major non-homologous end-joining (NHEJ) proteins....... MATERIALS AND METHODS: Experiments were performed with 11 normal human fibroblast strains AF01-11. NHEJ proteins were determined by Western blot and DNA-PK activity by pulldown-assay. RESULTS: The four NHEJ proteins tested (Ku70, Ku80, XRCC4 and DNA-PKcs) were found to be localised almost exclusively...

  7. Unmet needs of women with breast cancer during and after primary treatment: A prospective study in Denmark

    von Heymann-Horan, A.B; Dalton, Susanne Oksbjerg; Dziekanska, Angelika

    2013-01-01

    their diagnosis and throughout the disease trajectory. Material and methods. Consecutive women with newly diagnosed breast cancer, undergoing surgery at the Breast Surgery Clinic, Rigshospitalet, Denmark, between 2008 and 2009 (N = 261), completed questionnaires on their unmet needs, anxiety, physical functioning....... A total of 53% of women with breast cancer had unmet needs at some time between diagnosis and the end of primary treatment (eight months after diagnosis). A contextual understanding of unmet needs is necessary for planning cancer rehabilitation, as not only factors such as anxiety, physical functioning......Abstract Integrated plans will be required to ensure care and rehabilitation for the growing number of cancer survivors. Information is lacking, however, about the extent to which patients' rehabilitation needs are being met, and characteristics of patients who experience unmet needs after...

  8. A Comparative Analyses of Granulometry, Mineral Composition and Major and Trace Element Concentrations in Soils Commonly Ingested by Humans

    Veronica M. Ngole-Jeme

    2015-07-01

    Full Text Available This study compared the granulometric properties, mineralogical composition and concentrations of major and trace element oxides of commonly ingested soils (geophagic soil collected from different countries with a view of understanding how varied they may be in these properties and to understand the possible health implications of ingesting them. Soil samples were collected from three different countries (South Africa, Swaziland and Democratic Republic of Congo (DRC and their granulometric properties, concentrations of major and trace element oxides as well as mineralogical composition determined. Differences were observed in the granulometric properties of geophagic soil from the three different countries with most of them having <20% clay content. The soils also showed varied degrees of weathering with values of Chemical Index of Alteration (CIA and Chemical Index of Weathering (CIW being between 60% and 99.9% respectively. The mineral assemblages of the soils from South Africa and Swaziland were dominated by the primary minerals quartz and feldspar whereas soils from DRC had more of kaolinite, a secondary mineral than primary minerals. Soils from DRC were associated with silt, clay, Al2O3, and CIA unlike most samples from South Africa which were associated with SiO2, sand, K2O, CaO, and MgO. The soils from Swaziland were closely associated with silt, H2O and Fe2O3(t. These associations reflect the mineralogy of the samples. These soils are not likely to serve as nutrient supplements because of the low concentrations of the nutrient elements contained. The coarse texture of the samples may also result in dental destruction during mastication. Sieving of the soils before ingestion to remove coarse particles is recommended to reduce the potential health threat associated with the ingestion of coarse-textured soils.

  9. A Comparative Analyses of Granulometry, Mineral Composition and Major and Trace Element Concentrations in Soils Commonly Ingested by Humans

    Ngole-Jeme, Veronica M.; Ekosse, Georges-Ivo E.

    2015-01-01

    This study compared the granulometric properties, mineralogical composition and concentrations of major and trace element oxides of commonly ingested soils (geophagic soil) collected from different countries with a view of understanding how varied they may be in these properties and to understand the possible health implications of ingesting them. Soil samples were collected from three different countries (South Africa, Swaziland and Democratic Republic of Congo (DRC)) and their granulometric properties, concentrations of major and trace element oxides as well as mineralogical composition determined. Differences were observed in the granulometric properties of geophagic soil from the three different countries with most of them having soils also showed varied degrees of weathering with values of Chemical Index of Alteration (CIA) and Chemical Index of Weathering (CIW) being between 60% and 99.9% respectively. The mineral assemblages of the soils from South Africa and Swaziland were dominated by the primary minerals quartz and feldspar whereas soils from DRC had more of kaolinite, a secondary mineral than primary minerals. Soils from DRC were associated with silt, clay, Al2O3, and CIA unlike most samples from South Africa which were associated with SiO2, sand, K2O, CaO, and MgO. The soils from Swaziland were closely associated with silt, H2O and Fe2O3(t). These associations reflect the mineralogy of the samples. These soils are not likely to serve as nutrient supplements because of the low concentrations of the nutrient elements contained. The coarse texture of the samples may also result in dental destruction during mastication. Sieving of the soils before ingestion to remove coarse particles is recommended to reduce the potential health threat associated with the ingestion of coarse-textured soils. PMID:26264010

  10. Expression and characterization of recombinant human factor V and a mutant lacking a major portion of the connecting region

    Kane, W.H.; Devore-Carter, D.; Ortel, T.L.

    1990-01-01

    Human coagulation factor V is a protein cofactor that is an essential component of the prothrombinase complex. A full-length factor V cDNA has been subcloned into the mammalian expression vector pDX and used to transfect COS cells. Approximately 95 ± 4% of the recombinant human factor V (rHFV) synthesized in COS cells is secreted into the culture medium. Factor V activity determined by fibrometer assay increased approximately 5-fold from 0.027 ± 0.012 to 0.124 ± 0.044 unit/mL following activation by the factor V activating enzyme from Russell's viper venom (RVV-V). A chromogenic assay specific for factor Va indicated that recombinant factor V had 3.8 ± 1.3% of the activity of the activated protein. The estimated specific activity of the recombinant factor Va was approximately 1,800 ± 500 units/mg, which is similar to the specific activity of purified plasma factor Va of 1,700-2,000 units/mg. Immunoprecipitation of [ 35 S]methionine-labeled rHFV revealed a single high molecular mass component. Treatment of rHFV with thrombin or RVV-V resulted in the formation of proteolytic products that were similar to those seen with plasma factor V. The authors have also expressed a mutant, rHFV-des-B 811-1441 , that lacks a large portion of the highly glycosylated connecting region that is present in factor V. This mutant constitutively expressed 38 ± 7% of the activity of the RVV-V-activated protein. These results suggest that one of the functions of the large connecting region in factor V is to inhibit constitutive procoagulant activity

  11. RhoA/ROCK pathway is the major molecular determinant of basal tone in intact human internal anal sphincter.

    Rattan, Satish; Singh, Jagmohan

    2012-04-01

    The knowledge of molecular control mechanisms underlying the basal tone in the intact human internal anal sphincter (IAS) is critical for the pathophysiology and rational therapy for a number of debilitating rectoanal motility disorders. We determined the role of RhoA/ROCK and PKC pathways by comparing the effects of ROCK- and PKC-selective inhibitors Y 27632 and Gö 6850 (10(-8) to 10(-4) M), respectively, on the basal tone in the IAS vs. the rectal smooth muscle (RSM). Western blot studies were performed to determine the levels of RhoA/ROCK II, PKC-α, MYPT1, CPI-17, and MLC(20) in the unphosphorylated and phosphorylated forms, in the IAS vs. RSM. Confocal microscopic studies validated the membrane distribution of ROCK II. Finally, to confirm a direct relationship, we examined the enzymatic activities and changes in the basal IAS tone and p-MYPT1, p-CPI-17, and p-MLC(20), before and after Y 27632 and Gö 6850. Data show higher levels of RhoA/ROCK II and related downstream signal transduction proteins in the IAS vs. RSM. In addition, data show a significant correlation between the active RhoA/ROCK levels, ROCK enzymatic activity, downstream proteins, and basal IAS tone, before and after ROCK inhibitor. From these data we conclude 1) RhoA/ROCK and downstream signaling are constitutively active in the IAS, and this pathway (in contrast with PKC) is the critical determinant of the basal tone in intact human IAS; and 2) RhoA and ROCK are potential therapeutic targets for a number of rectoanal motility disorders for which currently there is no satisfactory treatment.

  12. Fear, opposition, ambivalence, and omission: Results from a follow-up study on unmet need for family planning in Ghana.

    Staveteig, Sarah

    2017-01-01

    Despite a relatively strong family planning program and regionally modest levels of fertility, Ghana recorded one of the highest levels of unmet need for family planning on the African continent in 2008. Unmet need for family planning is a composite measure based on apparent contradictions between women's reproductive preferences and practices. Women who want to space or limit births but are not using contraception are considered to have an unmet need for family planning. The study sought to understand the reasons behind high levels of unmet need for family planning in Ghana. A mixed methods follow-up study was embedded within the stratified, two-stage cluster sample of the 2014 Ghana Demographic and Health Survey (GDHS). Women in 13 survey clusters who were identified as having unmet need, along with a reference group of current family planning users, were approached to be reinterviewed within an average of three weeks from their GDHS interview. Follow-up respondents were asked a combination of closed- and open-ended questions about fertility preferences and contraceptive use. Closed-ended responses were compared against the original survey; transcripts were thematically coded and analyzed using qualitative analysis software. Among fecund women identified by the 2014 GDHS as having unmet need, follow-up interviews revealed substantial underreporting of method use, particularly traditional methods. Complete postpartum abstinence was sometimes the intended method of family planning but was overlooked during questions about method use. Other respondents classified as having unmet need had ambivalent fertility preferences. In several cases, respondents expressed revised fertility preferences upon follow-up that would have made them ineligible for inclusion in the unmet need category. The reference group of family planning users also expressed unstable fertility preferences. Aversion to modern method use was generally more substantial than reported in the GDHS

  13. Beyond using composite measures to analyze the effect of unmet supportive care needs on caregivers' anxiety and depression.

    Lambert, Sylvie D; Hulbert-Williams, Nicholas; Belzile, Eric; Ciampi, Antonio; Girgis, Afaf

    2018-06-01

    Caregiver research has relied on composite measures (eg, count) of unmet supportive care needs to determine relationships with anxiety and depression. Such composite measures assume that all unmet needs have a similar impact on outcomes. The purpose of this study is to identify individual unmet needs most associated with caregivers' anxiety and depression. Two hundred nineteen caregivers completed the 44-item Supportive Care Needs Survey and the Hospital Anxiety and Depression Scale (minimal clinically important difference = 1.5) at 6 to 8 months and 1, 2, 3.5, and 5 years following the patients' cancer diagnosis. The list of needs was reduced using partial least square regression, and those with a variance importance in projection >1 were analyzed using Bayesian model averaging. Across time, 8 items remained in the top 10 based on prevalence and were labelled "core." Three additional ones were labelled "frequent," as they remained in the top 10 from 1 year onwards. Bayesian model averaging identified a maximum of 3 significant unmet needs per time point-all leading to a difference greater than the minimal clinically important difference. For depression, none of the core unmet needs were significant, rather significance was noted for frequent needs and needs that were not prevalent. For anxiety, 3/8 core and 3/3 frequent unmet needs were significant. Those unmet needs that are most prevalent are not necessarily the most significant ones, and findings provide an evidence-based framework to guide the development of caregiver interventions. A broader contribution is proposing a different approach to identify significant unmet needs. Copyright © 2018 John Wiley & Sons, Ltd.

  14. Factors associated with unmet dental care needs in Canadian immigrants: an analysis of the longitudinal survey of immigrants to Canada

    Calvasina, Paola; Muntaner, Carles; Quiñonez, Carlos

    2014-01-01

    Background Immigrants are often considered to have poorer oral health than native born-populations. One possible explanation for immigrants’ poor oral health is lack of access to dental care. There is very little information on Canadian immigrants’ access to dental care, and unmet dental care needs. This study examines predictors of unmet dental care needs among a sample of adult immigrants to Canada over a three-point-five-year post-migration period. Methods A secondary data analysis was con...

  15. Fear, opposition, ambivalence, and omission: Results from a follow-up study on unmet need for family planning in Ghana.

    Sarah Staveteig

    Full Text Available Despite a relatively strong family planning program and regionally modest levels of fertility, Ghana recorded one of the highest levels of unmet need for family planning on the African continent in 2008. Unmet need for family planning is a composite measure based on apparent contradictions between women's reproductive preferences and practices. Women who want to space or limit births but are not using contraception are considered to have an unmet need for family planning. The study sought to understand the reasons behind high levels of unmet need for family planning in Ghana.A mixed methods follow-up study was embedded within the stratified, two-stage cluster sample of the 2014 Ghana Demographic and Health Survey (GDHS. Women in 13 survey clusters who were identified as having unmet need, along with a reference group of current family planning users, were approached to be reinterviewed within an average of three weeks from their GDHS interview. Follow-up respondents were asked a combination of closed- and open-ended questions about fertility preferences and contraceptive use. Closed-ended responses were compared against the original survey; transcripts were thematically coded and analyzed using qualitative analysis software.Among fecund women identified by the 2014 GDHS as having unmet need, follow-up interviews revealed substantial underreporting of method use, particularly traditional methods. Complete postpartum abstinence was sometimes the intended method of family planning but was overlooked during questions about method use. Other respondents classified as having unmet need had ambivalent fertility preferences. In several cases, respondents expressed revised fertility preferences upon follow-up that would have made them ineligible for inclusion in the unmet need category. The reference group of family planning users also expressed unstable fertility preferences. Aversion to modern method use was generally more substantial than reported in

  16. Fear, opposition, ambivalence, and omission: Results from a follow-up study on unmet need for family planning in Ghana

    2017-01-01

    Introduction Despite a relatively strong family planning program and regionally modest levels of fertility, Ghana recorded one of the highest levels of unmet need for family planning on the African continent in 2008. Unmet need for family planning is a composite measure based on apparent contradictions between women’s reproductive preferences and practices. Women who want to space or limit births but are not using contraception are considered to have an unmet need for family planning. The study sought to understand the reasons behind high levels of unmet need for family planning in Ghana. Methods A mixed methods follow-up study was embedded within the stratified, two-stage cluster sample of the 2014 Ghana Demographic and Health Survey (GDHS). Women in 13 survey clusters who were identified as having unmet need, along with a reference group of current family planning users, were approached to be reinterviewed within an average of three weeks from their GDHS interview. Follow-up respondents were asked a combination of closed- and open-ended questions about fertility preferences and contraceptive use. Closed-ended responses were compared against the original survey; transcripts were thematically coded and analyzed using qualitative analysis software. Results Among fecund women identified by the 2014 GDHS as having unmet need, follow-up interviews revealed substantial underreporting of method use, particularly traditional methods. Complete postpartum abstinence was sometimes the intended method of family planning but was overlooked during questions about method use. Other respondents classified as having unmet need had ambivalent fertility preferences. In several cases, respondents expressed revised fertility preferences upon follow-up that would have made them ineligible for inclusion in the unmet need category. The reference group of family planning users also expressed unstable fertility preferences. Aversion to modern method use was generally more substantial

  17. Developing and Evaluating Medical Humanities Problem-Based Learning Classes Facilitated by the Teaching Assistants Majored in the Liberal Arts: A Longitudinal Crossover Study.

    Tseng, Fen-Yu; Shieh, Jeng-Yi; Kao, Tze-Wah; Wu, Chau-Chung; Chu, Tzong-Shinn; Chen, Yen-Yuan

    2016-02-01

    Although medical humanities courses taught by teachers from nonmedical backgrounds are not unusual now, few studies have compared the outcome of medical humanities courses facilitated by physicians to that by teaching assistants majored in the liberal arts. The objectives of this study were to (1) analyze the satisfaction of medical students with medical humanities problem-based learning (PBL) classes facilitated by nonmedical teaching assistants (TAF) majored in the liberal arts, and those facilitated by the attending physicians (APF) and (2) examine the satisfaction of medical students with clinical medicine-related and clinical medicine-unrelated medical humanities PBL classes.A total of 123 medical students, randomly assigned to 16 groups, participated in this study. There were 16 classes in the course: 8 of them were TAF classes; and the others were APF classes. Each week, each group rotated from 1 subject of the 16 subjects of PBL to another subject. All of the 16 groups went through all the 16 subjects in the 2013 spring semester. We examined the medical students' satisfaction with each class, based on a rating score collected after each class was completed, using a scale from 0 (the lowest satisfaction) to 100 (the highest satisfaction). We also conducted multivariate linear regression analysis to examine the association between the independent variables and the students' satisfaction.Medical students were more satisfied with the TAF (91.35 ± 7.75) medical humanities PBL classes than APF (90.40 ± 8.42) medical humanities PBL classes (P = 0.01). Moreover, medical students were more satisfied with the clinical medicine-unrelated topics (92.00 ± 7.10) than the clinical medicine-related topics (90.36 ± 7.99) in the medical humanities PBL course (P = 0.01).This medical humanities PBL course, including nonmedical subjects and topics, and nonmedical teaching assistants from the liberal arts as class facilitators, was satisfactory. This

  18. Health-related quality of life and unmet healthcare needs in Huntington's disease.

    van Walsem, Marleen R; Howe, Emilie I; Ruud, Gunvor A; Frich, Jan C; Andelic, Nada

    2017-01-07

    Huntington's disease (HD) is a rare neurodegenerative disorder with a prevalence of 6 per 100.000. Despite increasing research activity on HD, evidence on healthcare utilization, patients' needs for healthcare services and Health-Related Quality of Life (HRQoL) is still sparse. The present study describes HRQoL in a Norwegian cohort of HD patients, and assesses associations between unmet healthcare and social support service needs and HRQoL. In this cross-sectional population-based study, 84 patients with a clinical diagnosis of HD living in the South-East of Norway completed the HRQoL questionnaire EuroQol, EQ-5D-3L. Unmet needs for healthcare and social support services were assessed by the Needs and Provision Complexity Scale (NPCS). Furthermore, functional ability was determined using the Unified Huntington's Disease Rating Scale (UHDRS) Functional assessment scales. Socio-demographics (age, gender, marital status, occupation, residence, housing situation) and clinical characteristics (disease duration, total functional capacity, comorbidity) were also recorded. Descriptive statistics were used to describe the patients' HRQoL. Regression analyses were conducted in order to investigate the relationship between unmet healthcare needs and self-reported HRQoL. The patients were divided across five disease stages as follows: Stage I: n = 12 (14%), Stage II: n = 22 (27%), Stage III: n = 19 (23%), Stage IV: n = 14 (16%), and Stage V: n = 17 (20%). Overall HRQoL was lowest in patients with advanced disease (Stages IV and V), while patients in the middle phase (Stage III) showed the most varied health profile for the five EQ-5D-3L dimensions. The regression model including level of unmet needs, clinical characteristics and demographics (age and education) accounted for 42% of variance in HRQoL. A higher level of unmet needs was associated with lower HRQoL (β value - 0.228; p = 0.018) whereas a better total functional capacity corresponded to

  19. A single point in protein trafficking by Plasmodium falciparum determines the expression of major antigens on the surface of infected erythrocytes targeted by human antibodies.

    Chan, Jo-Anne; Howell, Katherine B; Langer, Christine; Maier, Alexander G; Hasang, Wina; Rogerson, Stephen J; Petter, Michaela; Chesson, Joanne; Stanisic, Danielle I; Duffy, Michael F; Cooke, Brian M; Siba, Peter M; Mueller, Ivo; Bull, Peter C; Marsh, Kevin; Fowkes, Freya J I; Beeson, James G

    2016-11-01

    Antibodies to blood-stage antigens of Plasmodium falciparum play a pivotal role in human immunity to malaria. During parasite development, multiple proteins are trafficked from the intracellular parasite to the surface of P. falciparum-infected erythrocytes (IEs). However, the relative importance of different proteins as targets of acquired antibodies, and key pathways involved in trafficking major antigens remain to be clearly defined. We quantified antibodies to surface antigens among children, adults, and pregnant women from different malaria-exposed regions. We quantified the importance of antigens as antibody targets using genetically engineered P. falciparum with modified surface antigen expression. Genetic deletion of the trafficking protein skeleton-binding protein-1 (SBP1), which is involved in trafficking the surface antigen PfEMP1, led to a dramatic reduction in antibody recognition of IEs and the ability of human antibodies to promote opsonic phagocytosis of IEs, a key mechanism of parasite clearance. The great majority of antibody epitopes on the IE surface were SBP1-dependent. This was demonstrated using parasite isolates with different genetic or phenotypic backgrounds, and among antibodies from children, adults, and pregnant women in different populations. Comparisons of antibody reactivity to parasite isolates with SBP1 deletion or inhibited PfEMP1 expression suggest that PfEMP1 is the dominant target of acquired human antibodies, and that other P. falciparum IE surface proteins are minor targets. These results establish SBP1 as part of a critical pathway for the trafficking of major surface antigens targeted by human immunity, and have key implications for vaccine development, and quantifying immunity in populations.

  20. Unmet information needs and limited health literacy in newly diagnosed breast cancer patients over the course of cancer treatment.

    Halbach, Sarah Maria; Ernstmann, Nicole; Kowalski, Christoph; Pfaff, Holger; Pförtner, Timo-Kolja; Wesselmann, Simone; Enders, Anna

    2016-09-01

    To investigate unmet information needs in newly diagnosed breast cancer patients over the course of cancer treatment and its association with health literacy. We present results from a prospective, multicenter cohort study (PIAT). Newly diagnosed breast cancer patients (N=1060) were surveyed directly after breast cancer surgery, 10 and 40 weeks later. Pooled linear regression modeling was employed analyzing changes in unmet information needs over time and its association with health literacy. Unmet information needs on side effects and medication and medical examination results and treatment options were high and increased during the first 10 weeks after breast cancer surgery. Considering health promotion and social issues, unmet information needs started high and decreased during post-treatment. Patients with limited health literacy had higher unmet information needs. Our results indicate a mismatch in information provision and breast cancer patients' information needs. Patients with limited health literacy may be at a distinct disadvantage in having their information needs met over the course of breast cancer treatment. Strategies are needed to reduce unmet information needs in breast cancer patients considering treatment-phase and health literacy and thereby enable them to better cope with their diseases. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Targeting allergenic fungi in agricultural environments aids the identification of major sources and potential risks for human health.

    Weikl, F; Radl, V; Munch, J C; Pritsch, K

    2015-10-01

    Fungi are, after pollen, the second most important producers of outdoor airborne allergens. To identify sources of airborne fungal allergens, a workflow for qPCR quantification from environmental samples was developed, thoroughly tested, and finally applied. We concentrated on determining the levels of allergenic fungi belonging to Alternaria, Cladosporium, Fusarium, and Trichoderma in plant and soil samples from agricultural fields in which cereals were grown. Our aims were to identify the major sources of allergenic fungi and factors potentially influencing their occurrence. Plant materials were the main source of the tested fungi at and after harvest. Amounts of A. alternata and C. cladosporioides varied significantly in fields under different management conditions, but absolute levels were very high in all cases. This finding suggests that high numbers of allergenic fungi may be an inevitable side effect of farming in several crops. Applied in large-scale studies, the concept described here may help to explain the high number of sensitization to airborne fungal allergens. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. 5-Hydroxytryptophan, a major product of tryptophan degradation, is essential for optimal replication of human parainfluenza virus.

    Rabbani, M A G; Barik, Sailen

    2017-03-01

    Interferon (IFN) exerts its antiviral effect by inducing a large family of cellular genes, named interferon (IFN)-stimulated genes (ISGs). An intriguing member of this family is indoleamine 2,3-dioxygenase (IDO), which catalyzes the first and rate-limiting step of the main branch of tryptophan (Trp) degradation, the kynurenine pathway. We recently showed that IDO strongly inhibits human parainfluenza virus type 3 (PIV3), a significant respiratory pathogen. Here, we show that 5-hydoxytryptophan (5-HTP), the first product of an alternative branch of Trp degradation and a serotonin precursor, is essential to protect virus growth against IDO in cell culture. We also show that the apparent antiviral effect of IDO on PIV3 is not due to the generation of the kynurenine pathway metabolites, but rather due to the depletion of intracellular Trp by IDO, as a result of which this rare amino acid becomes unavailable for the alternative, proviral 5-HTP pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Aberrant Free Radical Biology Is a Unifying Theme in the Etiology and Pathogenesis of Major Human Diseases

    Frederick E. Domann

    2013-04-01

    Full Text Available The seemingly disparate areas of oxygen toxicity, radiation exposure, and aging are now recognized to share a common feature—the aberrant production and/or removal of biologically derived free radicals and other reactive oxygen and nitrogen species (ROS/RNS. Advances in our understanding of the effects of free radicals in biology and medicine have been, and continue to be, actively translated into clinically tractable diagnostic and therapeutic applications. This issue is dedicated to recent advances, both basic discoveries and clinical applications, in the field of free radicals in biology and medicine. As more is understood about the proximal biological targets of aberrantly produced or removed reactive species, their sensors, and effectors of compensatory response, a great deal more will be learned about the commonalities in mechanisms underlying seemingly disparate disease states. Together with this deeper understanding, opportunities will arise to devise rational therapeutic interventions to decrease the incidence and severity of these diseases and positively impact the human healthspan.

  4. Brain-derived neurotrophic factor--a major player in stimulation-induced homeostatic metaplasticity of human motor cortex?

    Mastroeni, Claudia; Bergmann, Til Ole; Rizzo, Vincenzo

    2013-01-01

    in human M1HAND. TBS is a patterned rTMS protocol with intermittent TBS (iTBS) usually inducing a lasting increase and continuous TBS (cTBS) a lasting decrease in corticospinal excitability. In three separate sessions, healthy val(66)met (n = 12) and val(66)val (n = 17) carriers received neuronavigated c......TBS followed by cTBS (n = 27), cTBS followed by iTBS (n = 29), and iTBS followed by iTBS (n = 28). Participants and examiner were blinded to the genotype at the time of examination. As expected, the first TBS intervention induced a decrease (cTBS) and increase (iTBS) in corticospinal excitability, respectively......, at the same time priming the after effects caused by the second TBS intervention in a homeostatic fashion. Critically, val(66)met carriers and val(66)val carriers showed very similar response patterns to cTBS and iTBS regardless of the order of TBS interventions. Since none of the observed TBS effects...

  5. Large Isoform of Mammalian Relative of DnaJ is a Major Determinant of Human Susceptibility to HIV-1 Infection

    Yu-Ping Chiang

    2014-12-01

    Full Text Available Individual differences in susceptibility to human immunodeficiency virus type 1 (HIV-1 infection have been of interest for decades. We aimed to determine the contribution of large isoform of Mammalian DnaJ (MRJ-L, a HIV-1 Vpr-interacting cellular protein, to this natural variation. Expression of MRJ-L in monocyte-derived macrophages was significantly higher in HIV-infected individuals (n = 31 than their uninfected counterparts (n = 27 (p = 0.009. Fifty male homosexual subjects (20 of them are HIV-1 positive were further recruited to examine the association between MRJ-L levels and occurrence of HIV infection. Bayesian multiple logistic regression revealed that playing a receptive role and increased levels of MRJ-L in macrophages were two risk factors for HIV-1 infection. A 1% rise in MRJ-L expression was associated with a 1.13 fold (95% CrI 1.06–1.29 increase in odds of contracting HIV-1 infection. Ex vivo experiments revealed that MRJ-L facilitated Vpr-dependent nuclear localization of virus. Infection of macrophage-tropic strain is a critical step in HIV-1 transmission. MRJ-L is a critical factor in this process; hence, subjects with higher macrophage MRJ-L levels are more vulnerable to HIV-1 infection.

  6. Polymorphic Human Sulfotransferase 2A1 Mediates the Formation of 25-Hydroxyvitamin D3-3-O-Sulfate, a Major Circulating Vitamin D Metabolite in Humans.

    Wong, Timothy; Wang, Zhican; Chapron, Brian D; Suzuki, Mizuki; Claw, Katrina G; Gao, Chunying; Foti, Robert S; Prasad, Bhagwat; Chapron, Alenka; Calamia, Justina; Chaudhry, Amarjit; Schuetz, Erin G; Horst, Ronald L; Mao, Qingcheng; de Boer, Ian H; Thornton, Timothy A; Thummel, Kenneth E

    2018-04-01

    Metabolism of 25-hydroxyvitamin D 3 (25OHD 3 ) plays a central role in regulating the biologic effects of vitamin D in the body. Although cytochrome P450-dependent hydroxylation of 25OHD 3 has been extensively investigated, limited information is available on the conjugation of 25OHD 3 In this study, we report that 25OHD 3 is selectively conjugated to 25OHD 3 -3- O -sulfate by human sulfotransferase 2A1 (SULT2A1) and that the liver is a primary site of metabolite formation. At a low (50 nM) concentration of 25OHD 3 , 25OHD 3 -3- O -sulfate was the most abundant metabolite, with an intrinsic clearance approximately 8-fold higher than the next most efficient metabolic route. In addition, 25OHD 3 sulfonation was not inducible by the potent human pregnane X receptor agonist, rifampicin. The 25OHD 3 sulfonation rates in a bank of 258 different human liver cytosols were highly variable but correlated with the rates of dehydroepiandrosterone sulfonation. Further analysis revealed a significant association between a common single nucleotide variant within intron 1 of SULT2A1 (rs296361; minor allele frequency = 15% in whites) and liver cytosolic SULT2A1 content as well as 25OHD 3 -3- O -sulfate formation rate, suggesting that variation in the SULT2A1 gene contributes importantly to interindividual differences in vitamin D homeostasis. Finally, 25OHD 3 -3- O -sulfate exhibited high affinity for the vitamin D binding protein and was detectable in human plasma and bile but not in urine samples. Thus, circulating concentrations of 25OHD 3 -3- O -sulfate appear to be protected from rapid renal elimination, raising the possibility that the sulfate metabolite may serve as a reservoir of 25OHD 3 in vivo, and contribute indirectly to the biologic effects of vitamin D. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

  7. Cellular homeoproteins, SATB1 and CDP, bind to the unique region between the human cytomegalovirus UL127 and major immediate-early genes

    Lee Jialing; Klase, Zachary; Gao Xiaoqi; Caldwell, Jeremy S.; Stinski, Mark F.; Kashanchi, Fatah; Chao, S.-H.

    2007-01-01

    An AT-rich region of the human cytomegalovirus (CMV) genome between the UL127 open reading frame and the major immediate-early (MIE) enhancer is referred to as the unique region (UR). It has been shown that the UR represses activation of transcription from the UL127 promoter and functions as a boundary between the divergent UL127 and MIE genes during human CMV infection [Angulo, A., Kerry, D., Huang, H., Borst, E.M., Razinsky, A., Wu, J., Hobom, U., Messerle, M., Ghazal, P., 2000. Identification of a boundary domain adjacent to the potent human cytomegalovirus enhancer that represses transcription of the divergent UL127 promoter. J. Virol. 74 (6), 2826-2839; Lundquist, C.A., Meier, J.L., Stinski, M.F., 1999. A strong negative transcriptional regulatory region between the human cytomegalovirus UL127 gene and the major immediate-early enhancer. J. Virol. 73 (11), 9039-9052]. A putative forkhead box-like (FOX-like) site, AAATCAATATT, was identified in the UR and found to play a key role in repression of the UL127 promoter in recombinant virus-infected cells [Lashmit, P.E., Lundquist, C.A., Meier, J.L., Stinski, M.F., 2004. Cellular repressor inhibits human cytomegalovirus transcription from the UL127 promoter. J. Virol. 78 (10), 5113-5123]. However, the cellular factors which associate with the UR and FOX-like region remain to be determined. We reported previously that pancreatic-duodenal homeobox factor-1 (PDX1) bound to a 45-bp element located within the UR [Chao, S.H., Harada, J.N., Hyndman, F., Gao, X., Nelson, C.G., Chanda, S.K., Caldwell, J.S., 2004. PDX1, a Cellular Homeoprotein, Binds to and Regulates the Activity of Human Cytomegalovirus Immediate Early Promoter. J. Biol. Chem. 279 (16), 16111-16120]. Here we demonstrate that two additional cellular homeoproteins, special AT-rich sequence binding protein 1 (SATB1) and CCAAT displacement protein (CDP), bind to the human CMV UR in vitro and in vivo. Furthermore, CDP is identified as a FOX-like binding protein

  8. Oxidation of cholesterol moiety of low density lipoprotein in the presence of human endothelial cells or Cu+2 ions: identification of major products and their effects.

    Bhadra, S; Arshad, M A; Rymaszewski, Z; Norman, E; Wherley, R; Subbiah, M T

    1991-04-15

    Oxidation of lipoproteins is believed to play a key role in atherogenesis. In this study, low density lipoproteins (LDL) was subjected to oxidation in the presence of either human umbilical vein endothelial cells or with Cu+2 ions and the major oxides formed were identified. While cholesterol-alpha-epoxide (C-alpha EP) was the major product of cholesterol peroxidation in the presence of endothelial cells, cholest-3,5-dien-7-one (CD) predominated in the presence of Cu+2 ion. Both steroids were identified by gas chromatography/mass spectrometry. HDL cholesterol was resistant to oxidation. When tested on human skin fibroblasts in culture C-alpha EP (10 micrograms/ml) caused marked stimulation of 14C-oleate incorporation into cholesterol esters, while CD stimulated cholesterol esterification only mildly. These studies show that a) C-alpha EP is the major peroxidation product of LDL cholesterol moiety in the presence of endothelial cells and b) it causes marked stimulation of cholesterol esterification in cells. C-alpha EP may play a key role in increasing cholesterol esterification noted in atherogenesis.

  9. EAACI Food Allergy and Anaphylaxis Guidelines. Protecting consumers with food allergies: understanding food consumption, meeting regulations and identifying unmet needs.

    Muraro, A; Hoffmann-Sommergruber, K; Holzhauser, T; Poulsen, L K; Gowland, M H; Akdis, C A; Mills, E N C; Papadopoulos, N; Roberts, G; Schnadt, S; van Ree, R; Sheikh, A; Vieths, S

    2014-11-01

    Individuals suffering from IgE-mediated food allergy usually have to practise life-long food allergen avoidance. This document aims to provide an overview of recent evidence-based recommendations for allergen risk assessment and management in the food industry and discusses unmet needs and expectations of the food allergic consumer in that context. There is a general duty of care on the food industry and obligations in European Union legislation to reduce and manage the presence of allergens alongside other food hazards. Current evidence enables quantification of allergen reference doses used to set-up reliable food safety management plans for some foods. However, further work is required to include a wider variety of foods and to understand the impact of the food matrix as well as additional factors which affect the progression and severity of symptoms as a function of dose. Major concerns have been raised by patients, carers and patient groups about the use of precautionary 'may contain' labelling to address the issue of unintended presence of allergens; these therefore need to be reconsidered. New and improved allergen detection methods should be evaluated for their application in food production. There is an urgent requirement for effective communication between healthcare professionals, patient organizations, food industry representatives and regulators to develop a better approach to protecting consumers with food allergies. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Human factors aspects of the major upgrade to control systems at the Los Alamos National Laboratory Plutonium Facility

    Higgins, J.; Pope, N.

    1997-01-01

    The Plutonium Facility (TA-55) at Los Alamos National Laboratory (LANL) has been in operation for over 15 years. It handles projects such as: stockpile maintenance, surveillance, and dismantlement; pit rebuild; plutonium power source fabrication for long duration spacecraft missions (e.g., Cassini); nuclear materials technology research; nuclear materials storage; and remediation of nuclear waste. The Operations Center of TA-55 is the nerve center of the facility where operators are on duty around the clock and monitor several thousand data points using the Facility Control System (FCS). The FCS monitors, displays, alarms, and provides some limited control of the following systems; HVAC, fire detection and suppression, radiation detection, electrical, and other miscellaneous systems. The FCS was originally based on late 1970s digital technology, which is not longer supported by the vendors. Additionally, the equipment failure rates increased notably in the 1990s. Thus, plans were put into place to upgrade and replace the FCS hardware, software, and display components with modernized equipment. The process was complicated by the facts that: the facility was operational and could not be totally closed for the modifications; complete documentation was not available for the existing system; the Safety Analyses for the facility were in the process of being upgraded at the same time; and of course limited time and budgets. This paper will discuss the human factors aspects of the design, installation, and testing of the new FCS within the above noted constraints. Particular items to be discussed include the functional requirements definition, operating experience review, screen designs, test program, operator training, and phased activation of the new circuits in an operational facility

  11. Simultaneous assessments of occurrence, ecological, human health, and organoleptic hazards for 77 VOCs in typical drinking water sources from 5 major river basins, China.

    Chen, Xichao; Luo, Qian; Wang, Donghong; Gao, Jijun; Wei, Zi; Wang, Zijian; Zhou, Huaidong; Mazumder, Asit

    2015-11-01

    Owing to the growing public awareness on the safety and aesthetics in water sources, more attention has been given to the adverse effects of volatile organic compounds (VOCs) on aquatic organisms and human beings. In this study, 77 target VOCs (including 54 common VOCs, 13 carbonyl compounds, and 10 taste and odor compounds) were detected in typical drinking water sources from 5 major river basins (the Yangtze, the Huaihe, the Yellow, the Haihe and the Liaohe River basins) and their occurrences were characterized. The ecological, human health, and olfactory assessments were performed to assess the major hazards in source water. The investigation showed that there existed potential ecological risks (1.30 × 10 ≤ RQtotals ≤ 8.99 × 10) but little human health risks (6.84 × 10(-7) ≤ RQtotals ≤ 4.24 × 10(-4)) by VOCs, while that odor problems occurred extensively. The priority contaminants in drinking water sources of China were also listed based on the present assessment criteria. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. The Climate and Human Impacts of Major Explosive Volcanism AD670-730, A Multi-proxy Assessment

    Gao, C.; Ludlow, F.

    2013-12-01

    Chronologically secure volcanic events can provide an important tool to improve ice core dating as well as our understanding of volcano-climate responses. However, there is a substantial lack of reference horizons for ice-core dating during the first millennium, excepting the Taupo (New Zealand, AD186×10) and Vesuvius (Italy, AD 79) eruptions. In this exploratory case-study, we use a total of 20 ice core records, 9 from the Arctic and 11 from the Antarctic, together with historical records to examine the occurrence and climatic impact of explosive volcanism, AD 670-730. Sulfate signals comparable in magnitude to the sizeable 1815 Tambora eruption are detected in all of the ice-core time series, with different cores attributing the timing of eruptions to AD 676×2, 688×2, or 700×2, respectively. Historical records of widespread frost damage, anomalously warm winters, drought, famine and mortality from Chinese, European and Middle Eastern chronicles suggest substantial climate and social perturbations during AD 677-685 and AD 699-709. The distinctive double-peak feature seen in the majority of the volcanic signals from both poles at AD 676×2 and AD 688×2 suggests that these signals may belong to the same eruption, with those cores dating the signals to c.AD 676 generally considered to have a more precise chronology. Combining the evidence from natural and historical anthropogenic records and taking into account uncertainties (e.g. resolution, dating accuracy) associated with individual ice cores, we propose that a (most-likely) low-latitude eruption took place around AD676, followed by another possible eruption around AD700, identifiable by the significant acidity in polar ice-caps and historical documents. Unique historical observations of 'blood rain' in Ireland (often associated with Saharan sand deposition, but also plausibly with iron and manganese-rich tephra falls) also suggest a high-latitude eruption (possibly Icelandic) at AD693, corresponding to a

  13. Biological assessment of neonicotinoids imidacloprid and its major metabolites for potentially human health using globular proteins as a model.

    Ding, Fei; Peng, Wei

    2015-06-01

    The assessment of biological activities of imidacloprid and its two major metabolites, namely 6-chloronicotinic acid and 2-imidazolidone for nontarget organism, by employing essentially functional biomacromolecules, albumin and hemoglobin as a potentially model with the use of circular dichroism (CD), fluorescence, extrinsic 8-anilino-1-naphthalenesulfonic acid (ANS) fluorescence as well as molecular modeling is the theme of this work. By dint of CD spectra and synchronous fluorescence, it was clear that the orderly weak interactions between amino acid residues within globular proteins were disturbed by imidacloprid, and this event led to marginally alterations or self-regulations of protein conformation so as to lodge imidacloprid more tightly. Both steady state and time-resolved fluorescence suggested that the fluorescence of Trp residues in proteins was quenched after the presence of imidacloprid, corresponding to noncovalent protein-imidacloprid complexes formation and, the reaction belongs to moderate association (K=1.888/1.614×10(4)M(-1) for albumin/hemoglobin-imidacloprid, respectively), hydrogen bonds and π stacking performed a vital role in stabilizing the complexes, as derived from thermodynamic analysis and molecular modeling. With the aid of hydrophobic ANS experiments, subdomain IIA and α1β2 interface of albumin and hemoglobin, respectively, were found to be preserved high-affinity for imidacloprid. These results ties in with the subsequently molecular modeling laying imidacloprid in the Sudlow's site I and close to Trp-213 residue on albumin, while settling down B/Trp-37 residue nearby in hemoglobin, and these conclusions further confirmed by site-directed mutagenesis and molecular dynamics simulation. But, at the same time, several crucial noncovalent bonds came from other amino acid residues, e.g. Arg-194 and Arg-198 (albumin) and B/Arg-40, B/Asp-99 and B/Asn-102 (hemoglobin) cannot be ignored completely. Based on the comparative studies of

  14. Major losses of fat, carbohydrates and energy content of preterm human milk frozen at -80°C.

    Lev, H M; Ovental, A; Mandel, D; Mimouni, F B; Marom, R; Lubetzky, R

    2014-05-01

    Long-term storage of human milk (HM) requires freezing at low temperatures, the consequences of which upon macronutrients are unclear. To test the null hypothesis that HM freezing and storage for a range of 1 to 10 weeks at -80 °C does not affect HM fat, protein, lactose and energy contents. Samples of HM were obtained from 20 mothers (60 samples) of preterm infants (25 to 35 weeks gestation), who routinely expressed their milk, every 3 h, using an electric pump, from the second to the seventh week after delivery. All samples were frozen at -80 °C for 8 to 83 days (43.8 days average). After thawing and homogenization, energy and macronutrient contents were measured using an HM analyzer. Fat, carbohydrates and energy contents were significantly lower in thawed HM than in fresh HM (fat, fresh vs thawed: 3.72±1.17 vs 3.36±1.19 g/100 ml, Pcarbohydrates, fresh vs thawed: 5.86±0.71 vs 4.09±0.96 g/100 ml, Pvs thawed: 64.93±12.97 vs 56.63±16.82 kcal/100 ml, Pvs thawed: 1.14±0.36 vs 1.15±0.37 g/100 ml, P=0.7). The decline in carbohydrates content but not in fat and energy correlated significantly with freezing duration. Freezing at -80 °C significantly decreases the energy content of HM, both from fat and carbohydrates. Since quantitatively the decrease in macronutrients was much higher than that published for HM storage at -20 °C, our results do not support freezing HM at -80 °C as the gold standard for long-term storage. We suggest that caloric intake calculations in preterm infants cannot be established based upon fresh HM data.

  15. Antibody responses to a major Pneumocystis carinii antigen in human immunodeficiency virus-infected patients with and without P. carinii pneumonia

    Lundgren, Bettina; Lundgren, Jens Dilling; Nielsen, T

    1992-01-01

    of pulmonary symptoms. Significantly more patients with P. carinii pneumonia (PCP) had detectable antibodies compared with HIV-infected patients without PCP and with HIV-negative controls (50 [66%] of 76 vs. 18 [34%] of 53 and 7 [35%] of 20, respectively; P less than .001), and the level of antibody response......Antibody responses to a major purified human Pneumocystis carinii surface antigen (gp95) were determined by ELISA in human immunodeficiency virus (HIV)-infected patients. Serum IgG directed against gp95 was measured in 129 consecutive HIV-infected patients who underwent bronchoscopy for evaluation...... response, compared with only 1 (3%) of 31 patients without PCP (P less than .001). This patient had PCP on the basis of clinical criteria, including response to therapy. Thus, despite severe immunosuppression, a proportion of HIV-infected patients with PCP can mount a specific IgG-mediated antibody...

  16. Major proteins in normal human lymphocyte subpopulations separated by fluorescence-activated cell sorting and analyzed by two-dimensional gel electrophoresis

    Madsen, P S; Hokland, M; Ellegaard, J

    1988-01-01

    markers were observed in all cell types. All the putative protein markers have been identified in the protein database of human peripheral blood mononuclear cells (PBMCs) (see accompanying article by Celis et al.). Comparison of the overall patterns of protein synthesis of the unsorted PBMCs with those...... of the four subpopulations showed that the synthesis of some major PBMC proteins decreased substantially in the sorted subsets. These proteins are most likely not of monocyte origin, as these cells constituted only about 15% of the total PBMCs. Also, the inhibition does not seem to be due to the addition...

  17. Engineering chimeric human and mouse major histocompatibility complex (MHC) class I tetramers for the production of T-cell receptor (TCR) mimic antibodies

    Bentley, Carol; Yates, Jenna; Salimi, Maryam; Greig, Jenny; Wiblin, Sarah; Hassanali, Tasneem; Banham, Alison H.

    2017-01-01

    Therapeutic monoclonal antibodies targeting cell surface or secreted antigens are among the most effective classes of novel immunotherapies. However, the majority of human proteins and established cancer biomarkers are intracellular. Peptides derived from these intracellular proteins are presented on the cell surface by major histocompatibility complex class I (MHC-I) and can be targeted by a novel class of T-cell receptor mimic (TCRm) antibodies that recognise similar epitopes to T-cell receptors. Humoural immune responses to MHC-I tetramers rarely generate TCRm antibodies and many antibodies recognise the α3 domain of MHC-I and β2 microglobulin (β2m) that are not directly involved in presenting the target peptide. Here we describe the production of functional chimeric human-murine HLA-A2-H2Dd tetramers and modifications that increase their bacterial expression and refolding efficiency. These chimeric tetramers were successfully used to generate TCRm antibodies against two epitopes derived from wild type tumour suppressor p53 (RMPEAAPPV and GLAPPQHLIRV) that have been used in vaccination studies. Immunisation with chimeric tetramers yielded no antibodies recognising the human α3 domain and β2m and generated TCRm antibodies capable of specifically recognising the target peptide/MHC-I complex in fully human tetramers and on the cell surface of peptide pulsed T2 cells. Chimeric tetramers represent novel immunogens for TCRm antibody production and may also improve the yield of tetramers for groups using these reagents to monitor CD8 T-cell immune responses in HLA-A2 transgenic mouse models of immunotherapy. PMID:28448627

  18. Impact of caregivers' unmet needs for supportive care on quality of terminal cancer care delivered and caregiver's workforce performance.

    Park, Sang Min; Kim, Young Jin; Kim, Samyong; Choi, Jong Soo; Lim, Ho-Yeong; Choi, Youn Seon; Hong, Young Seon; Kim, Si-Young; Heo, Dae Seog; Kang, Ki Moon; Jeong, Hyun Sik; Lee, Chang Geol; Moon, Do Ho; Choi, Jin-Young; Kong, In Sik; Yun, Young Ho

    2010-06-01

    Family caregivers play an important role in caring for cancer patients, but the impact of caregivers' unmet needs on the quality of end-of-life (EOL) care they deliver and on their workplace performance are less understood. We identified 1,662 family caregivers of cancer patients who had died at any of 17 hospitals in Korea during 2004. The caregivers answered a telephone questionnaire about needs that were not met when they delivered terminal cancer care and how those unmet their needs affected their workplace performance; they also answered the Quality Care Questionnaire-End of Life (QCQ-EOL). Compared with caregivers who did not have unmet needs, caregivers who had unmet needs for symptom management, financial support, or community support showed poorer QCQ-EOL scores (P < 0.01). Caregivers who had unmet needs for financial support (adjusted odds ratio (aOR) = 7.55; 95% confidential interval (CI) 3.80-15.00), psychosocial support (aOR = 6.24; 95% CI 2.95-13.05), symptom management (aOR = 3.21; 95% CI 2.26-4.54), community support (aOR = 3.82; 95% CI 2.38-6.11), or religious support (aOR = 4.55; 95% CI 1.84-11.26) were more likely to experience work limitations. Caregivers of patients receiving conventional hospital care were more likely to have unmet needs for symptom management (aOR = 1.21; 95% CI 1.00-1.47), psychosocial support (aOR = 1.99; 95% CI 1.37-2.88), and religious support (aOR = 1.73; 95% CI 1.08-2.78) than those of patients receiving palliative hospice care. Caregivers' unmet needs negatively affected both the quality of EOL care they delivered and their workplace performance. More investment in caregiver support and public policies that meet caregiver needs are needed, and hospice use should be encouraged.

  19. Unmet supportive care needs: a cross-cultural comparison between Hong Kong Chinese and German Caucasian women with breast cancer.

    Lam, Wendy W T; Au, Angel H Y; Wong, Jennifer H F; Lehmann, Claudia; Koch, Uwe; Fielding, Richard; Mehnert, Anja

    2011-11-01

    The comparison of psychosocial needs across different cultural settings can identify cultural and service impacts on psychosocial outcomes. We compare psychosocial needs in Hong Kong Chinese and German Caucasian women with breast cancer. Completed questionnaires were collected from 348 Chinese and 292 German women with breast cancer for assessing unmet psychosocial needs (Supportive Care Needs Survey Short Form), psychological distress (the Hospital Anxiety and Depression scale), and listed physical and psychological symptoms. Only 11% of the participants reported not needing help for any of the 34 items. More German (14%) than Chinese women (8%) reported no unmet needs (χ(2) = 6.16, P = .013). With both samples combined, the Health System and Information domain unmet needs were the most prevalent, apart from one Psychological need domain item, "Fear about the cancer spreading." Chinese and German samples differed significantly in prevalence and patterns of unmet psychosocial needs. Multivariate adjustment for demographic, clinical, and sample characteristics, psychological distress, and symptoms showed that significantly greater unmet Health system and Information, and Patient care and support domain needs, associated with the presence of symptoms (β = .232, P German group membership, among others. German women reported more anxiety (t = 10.45, P German, but not Chinese women reporting greater anxiety and depression had greater unmet Psychological and Sexuality domain needs (P culture-specific differences in supportive care needs exist. Hong Kong Chinese women prioritize needs for information about their disease and treatment, whereas German Caucasian women prioritize physical and psychological support. Planning for cancer supportive care services or interventions to reduce unmet needs must consider cultural and/or health service contexts.

  20. Care coordination, medical complexity, and unmet need for prescription medications among children with special health care needs.

    Aboneh, Ephrem A; Chui, Michelle A

    Children with special health care needs (CSHCN) have multiple unmet health care needs including that of prescription medications. The objectives of this study were twofold: 1) to quantify and compare unmet needs for prescription medications for subgroups of CSHCN without and with medical complexity (CMC)-those who have multiple, chronic, and complex medical conditions associated with severe functional limitations and high utilization of health care resources, and 2) to describe its association with receipt of effective care coordination services and level of medical complexity. A secondary data analysis of the 2009/2010 National Survey of CSHCN, a nationally representative telephone survey of parents of CSHCN, was conducted. Logistic regression models were constructed to determine associations between unmet need for prescription medications and medical complexity and care coordination for families of CSHCN, while controlling for demographic variables such as race, insurance, education level, and household income. Analyses accounted for the complex survey design and sampling weights. CMC represented about 3% of CSHCN. CMC parents reported significantly more unmet need for prescription medications and care coordination (4%, 68%), compared to Non-CMC parents (2%, 40%). Greater unmet need for prescription medications was associated with unmet care coordination (adjusted OR 3.81; 95% CI: 2.70-5.40) and greater medical complexity (adjusted OR 2.01; 95% CI: 1.00-4.03). Traditional care coordination is primarily facilitated by nurses and nurse practitioners with little formal training in medication management. However, pharmacists are rarely part of the CSHCN care coordination model. As care delivery models for these children evolve, and given the complexity of and numerous transitions of care for these patients, pharmacists can play an integral role to improve unmet needs for prescription medications. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Does a medical home mediate racial disparities in unmet healthcare needs among children with special healthcare needs?

    Bennett, Amanda C; Rankin, Kristin M; Rosenberg, Deborah

    2012-12-01

    This study extends mediation analysis techniques to explore whether and to what extent differential access to a medical home explains the black/white disparity in unmet healthcare needs among children with special healthcare needs (CSHCN). Data were obtained from the 2007 National Survey of Children's Health, with analyses limited to non-Hispanic white and black CSHCN (n = 14,677). The counterfactual approach to mediation analysis was used to estimate odds ratios for the natural direct and indirect effects of race on unmet healthcare needs. Overall, 43.0 % of white CSHCN and 60.4 % of black CSHCN did not have a medical home. Additionally, 8.8 % of white CSHCN and 15.3 % of black CSHCN had unmet healthcare needs. The natural indirect effect indicates that the odds of unmet needs among black CSHCN are elevated by approximately 20 % as a result of their current level of access to the medical home rather than access at a level equal to white CSHCN (OR(NIE) = 1.2, 95 % CI = 1.1, 1.3). The natural direct effect indicates that even if black CSHCN had the same level of access to a medical home as white CSHCN, blacks would still have 60 % higher odds of unmet healthcare needs than whites (OR(NDE) = 1.6, 95 % CI = 1.1, 2.4). The racial disparity in unmet healthcare needs among CSHCN is only partially explained by disparities in having a medical home. Ensuring all CSHCN have equal access to a medical home may reduce the racial disparity in unmet needs, but will not completely eliminate it.

  2. Trends in Unmet Need for Genetic Counseling Among Children With Special Health Care Needs, 2001-2010.

    Smith, Anna Jo; Oswald, Donald; Bodurtha, Joann

    2015-01-01

    Access to genetic counseling is increasingly important to guide families' and clinicians' decision making, yet there is limited research on accessibility and affordability of counseling for families with children with special health care needs (CSHCN). Our study's objectives were to measure changes in unmet need for genetic counseling for CSHCN from 2001 to 2010 and to characterize child, family, and health system factors associated with unmet need. We used parent-reported data from the 2001, 2005-2006, and 2009-2010 National Survey of Children With Special Health Care Needs. We used a logistic regression model to measure the impact of survey year, child (sex, age, severity of health condition), family (primary language, household income, insurance, financial problems related to cost of CSHCN's health care), and health system factors (region, genetic counselors per capita, having a usual source of care) on access to genetic counseling. Unmet need for genetic counseling increased significantly in 2009-2010 compared to 2001 (odds ratio 1.89; 95% confidence interval [CI] 1.44-2.47). Being older (adjusted odds ratio [aOR] 1.04; 95% CI 1.02-1.06), having severe health limitations (aOR 1.72; 95% CI 1.16-2.58), being uninsured (aOR 3.56; 95% CI 2.16-5.87), and having family financial problems due to health care costs (aOR 1.90; 95% CI 1.52-2.38) were significantly associated with greater unmet need for genetic counseling. Having a usual source of care was associated with decreased unmet need (aOR 0.55; 95% CI 0.37-0.83). Unmet need for genetic counseling has increased over the past 12 years. Uninsurance and financial problems related to health care costs were the largest drivers of unmet need over time. Copyright © 2015 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

  3. Public pensions and unmet medical need among older people: cross-national analysis of 16 European countries, 2004–2010

    Reeves, Aaron; McKee, Martin; Mackenbach, Johan; Whitehead, Margaret; Stuckler, David

    2017-01-01

    Background Since the onset of the Great Recession in Europe, unmet need for medical care has been increasing, especially in persons aged 65 or older. It is possible that public pensions buffer access to healthcare in older persons during times of economic crisis, but to our knowledge, this has not been tested empirically in Europe. Methods We integrated panel data on 16 European countries for years 2004–2010 with indicators of public pension, unemployment insurance and sickness insurance entitlement from the Comparative Welfare Entitlements Dataset and unmet need (due to cost) prevalence rates from EuroStat 2014 edition. Using country-level fixed-effects regression models, we evaluate whether greater public pension entitlement, which helps reduce old-age poverty, reduces the prevalence of unmet medical need in older persons and whether it reduces inequalities in unmet medical need across the income distribution. Results We found that each 1-unit increase in public pension entitlement is associated with a 1.11 percentage-point decline in unmet medical need due to cost among over 65s (95% CI −0.55 to −1.66). This association is strongest for the lowest income quintile (1.65 percentage points, 95% CI −1.19 to −2.10). Importantly, we found consistent evidence that out-of-pocket payments were linked with greater unmet needs, but that this association was mitigated by greater public pension entitlement (β=−1.21 percentage points, 95% CI −0.37 to −2.06). Conclusions Greater public pension entitlement plays a crucial role in reducing inequalities in unmet medical need among older persons, especially in healthcare systems which rely heavily on out-of-pocket payments. PMID:27965315

  4. Factors associated with unmet dental care needs in Canadian immigrants: an analysis of the longitudinal survey of immigrants to Canada.

    Calvasina, Paola; Muntaner, Carles; Quiñonez, Carlos

    2014-12-03

    Immigrants are often considered to have poorer oral health than native born-populations. One possible explanation for immigrants' poor oral health is lack of access to dental care. There is very little information on Canadian immigrants' access to dental care, and unmet dental care needs. This study examines predictors of unmet dental care needs among a sample of adult immigrants to Canada over a three-point-five-year post-migration period. A secondary data analysis was conducted on the Longitudinal Survey of Immigrants to Canada (LSIC). Sampling and bootstrap weights were applied to make the data nationally representative. Simple descriptive analyses were conducted to describe the demographic characteristics of the sample. Bivariate and multiple logistic regression analyses were applied to identify factors associated with immigrants' unmet dental care needs over a three-point-five-year period. Approximately 32% of immigrants reported unmet dental care needs. Immigrants lacking dental insurance (OR = 2.63; 95% CI: 2.05-3.37), and those with an average household income of $20,000 to $40,000 per year (OR = 1.62; 95% CI: 1.01-2.61), and lower than $20,000 (OR = 2.25; 95% CI: 1.31-3.86), were more likely to report unmet dental care needs than those earning more than $60,000 per year. In addition, South Asian (OR = 1.85; CI: 1.25-2.73) and Chinese (OR = 2.17; CI: 1.47-3.21) immigrants had significantly higher odds of reporting unmet dental care needs than Europeans. Lack of dental insurance, low income and ethnicity predicted unmet dental care needs over a three-point-five-year period in a sample of immigrants to Canada.

  5. Public pensions and unmet medical need among older people: cross-national analysis of 16 European countries, 2004-2010.

    Reeves, Aaron; McKee, Martin; Mackenbach, Johan; Whitehead, Margaret; Stuckler, David

    2017-02-01

    Since the onset of the Great Recession in Europe, unmet need for medical care has been increasing, especially in persons aged 65 or older. It is possible that public pensions buffer access to healthcare in older persons during times of economic crisis, but to our knowledge, this has not been tested empirically in Europe. We integrated panel data on 16 European countries for years 2004-2010 with indicators of public pension, unemployment insurance and sickness insurance entitlement from the Comparative Welfare Entitlements Dataset and unmet need (due to cost) prevalence rates from EuroStat 2014 edition. Using country-level fixed-effects regression models, we evaluate whether greater public pension entitlement, which helps reduce old-age poverty, reduces the prevalence of unmet medical need in older persons and whether it reduces inequalities in unmet medical need across the income distribution. We found that each 1-unit increase in public pension entitlement is associated with a 1.11 percentage-point decline in unmet medical need due to cost among over 65s (95% CI -0.55 to -1.66). This association is strongest for the lowest income quintile (1.65 percentage points, 95% CI -1.19 to -2.10). Importantly, we found consistent evidence that out-of-pocket payments were linked with greater unmet needs, but that this association was mitigated by greater public pension entitlement (β=-1.21 percentage points, 95% CI -0.37 to -2.06). Greater public pension entitlement plays a crucial role in reducing inequalities in unmet medical need among older persons, especially in healthcare systems which rely heavily on out-of-pocket payments. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  6. A dose-response relationship between long working hours and unmet need for access to hospital facilities.

    Soek, Hongdeok; Won, Jong-Uk; Lee, Tae Il; Kim, Yeong-Kwang; Lee, Wanhyung; Lee, June-Hee; Roh, Jaehoon; Yoon, Jin-Ha

    2016-03-01

    Lack of access to hospital facilities, indicating unmet healthcare need, plays an important role in health inequity in the workplace. We aimed to investigate the association between long working hours and unmet healthcare need. We used data from the Korea National Health and Nutrition Examination Surveys collected during 2007-2012, which included 8369 participants (4765 males, 3604 females) aged 20-54 years, who were paid workers. We used a logistic regression model with gender stratification to investigate the association between working hours and unmet healthcare need. Of the 8369 participants, 855 males (17.94%) and 981 females (27.22%) experienced unmet healthcare need. After adjusting for covariates, and compared to 30-39 working hours per week, the odds ratios (OR) of unmet healthcare need were 1.07 [(95% confidence interval (95% CI) 0.76-1.51], 1.46 (95% CI 1.03-2.07), and 1.57 (95% CI 1.11-2.23) in males, and 1.13 (95% CI 0.92-1.40), 1.30 (95% CI 0.99-1.69), and 1.60 (95% CI 1.21-2.10) in females, for 40-49, 50-59, and ≥ 60 work hours per week, respectively. There was a dose-response relationship between working hours per week and unmet healthcare need in both genders. Those who work long hours are more likely to have unmet healthcare needs, the cause of which seems to be lack of time.

  7. Assessing met and unmet needs in the oldest-old and psychometric properties of the German version of the Camberwell assessment of need for the elderly (CANE)--a pilot study.

    Stein, Janine; Luppa, Melanie; König, Hans-Helmut; Riedel-Heller, Steffi G

    2014-02-01

    The current demographic and social developments in our society will lead to a significant increase in treatment and healthcare needs in the future, particularly in the elderly population. The Camberwell Assessment of Need for the Elderly (CANE) was developed in the United Kingdom to measure physical-, psychological-, and environment-related treatment as well as healthcare needs of older people in order to identify their unmet needs. So far, the German version of the CANE has not been established in health services research. Major reasons for this are a lack of publications of CANE's German version and the missing validation of the instrument. The aims of the present study were to evaluate the currently available German version of the CANE in a sample of older primary care patients. Descriptive statistics and inference-statistical analyses were calculated. Patients reported unmet needs mostly in CANE's following sections: mobility/falls, physical health, continence, company, and intimate relationships. Agreement level between patients' and relatives' ratings in CANE was moderate to low. Evidence for the construct validity of CANE was found in terms of significant associations between CANE and other instruments or scores. The study results provide an important basis for studies aiming at the assessment of met and unmet needs in the elderly population. Using the German version of the CANE may substantially contribute to an effective and good-quality health and social care as well as an appropriate allocation of healthcare resources in the elderly population.

  8. The relationship between unmet needs and distress amongst young people with cancer.

    Dyson, Gavin J; Thompson, Kate; Palmer, Susan; Thomas, David M; Schofield, Penelope

    2012-01-01

    Most psychosocial research in cancer has been restricted to paediatric or older adult populations. This study aimed to explore psychological distress and unmet needs in adolescents and young adults (AYA) with cancer and identify predictors of distress among demographic and illness characteristics and supportive care needs. Fifty-three patients between 16 and 30 years completed a cross-sectional survey, administered shortly after presentation to an AYA oncology service and within 4 months of diagnosis. Measures included the Beck Depression Inventory-Fast Screen (BDI-FS), State-Trait Anxiety Inventory-State Form (STAI-S) and the Supportive Care Needs Survey. Level of distress-related sypmtomatology in this population was based on previous work, whereby a cut-off score of 4 or greater was used for the BDI-FS, and one standard deviation above the sample population mean was used for the STAI-S. Prevalence of distress (25%) was lower than that found previously in AYA with cancer. Physical and daily living needs were the most frequently unmet needs overall, followed by psychological needs, health system and information needs and care and support needs. Lastly, being pre-treatment predicted increased depression and state anxiety, while having treatment post-surgery predicted reduced state anxiety. After controlling for treatment status, however, the main predictors of depression and state anxiety were physical and daily living needs and health system and information needs, respectively. Lower levels of distress and unmet psychological needs were related to the few participants (17%) in this study who were pre-treatment, when distress was most likely. However, physical needs and information needs, which are almost inevitable throughout treatment and beyond, were more important predictors of distress. Further exploration must consider the psychosocial difficulties underlying this association and the needs of AYA at transitions between critical periods in their cancer journey

  9. Burden of mental disorders and unmet needs among street homeless people in Addis Ababa, Ethiopia.

    Fekadu, Abebaw; Hanlon, Charlotte; Gebre-Eyesus, Emebet; Agedew, Melkamu; Solomon, Haddis; Teferra, Solomon; Gebre-Eyesus, Tsehaysina; Baheretibeb, Yonas; Medhin, Girmay; Shibre, Teshome; Workneh, Abraham; Tegegn, Teketel; Ketema, Alehegn; Timms, Philip; Thornicroft, Graham; Prince, Martin

    2014-08-20

    The impact of mental disorders among homeless people is likely to be substantial in low income countries because of underdeveloped social welfare and health systems. As a first step towards advocacy and provision of care, we conducted a study to determine the burden of psychotic disorders and associated unmet needs, as well as the prevalence of mental distress, suicidality, and alcohol use disorder among homeless people in Addis Ababa, the capital of Ethiopia. A cross-sectional survey was conducted among street homeless adults. Trained community nurses screened for potential psychosis and administered standardized measures of mental distress, alcohol use disorder and suicidality. Psychiatric nurses then carried out confirmatory diagnostic interviews of psychosis and administered a locally adapted version of the Camberwell Assessment of Needs Short Appraisal Schedule. We assessed 217 street homeless adults, about 90% of whom had experienced some form of mental or alcohol use disorder: 41.0% had psychosis, 60.0% had hazardous or dependent alcohol use, and 14.8% reported attempting suicide in the previous month. Homeless people with psychosis had extensive unmet needs with 80% to 100% reporting unmet needs across 26 domains. Nearly 30% had physical disability (visual and sensory impairment and impaired mobility). Only 10.0% of those with psychosis had ever received treatment for their illness. Most had lived on the streets for over 2 years, and alcohol use disorder was positively associated with chronicity of homelessness. Psychoses and other mental and behavioural disorders affect most people who are street homeless in Addis Ababa. Any programme to improve the condition of homeless people should include treatment for mental and alcohol use disorders. The findings have significant implications for advocacy and intervention programmes, particularly in similar low income settings.

  10. Do ambivalent women have an unmet need for family planning? A longitudinal study from Bali, Indonesia.

    Withers, Mellissa H; Tavrow, Paula; Adinata, N Ardika

    2011-01-01

    Fertility intentions often can predict contraceptive demand and fertility outcomes. Little is known about women reporting ambivalent fertility intentions, who are usually classified as having an unmet need for contraception. This study's objectives were to determine 1) which fertility intention group ambivalent women more closely resemble and 2) whether ambivalent women seem to have an unmet contraceptive need. We analyzed longitudinal data from 1,018 married Balinese women aged 15 to 45, of whom 33% desired more children, 52% wanted no more, and 14% were ambivalent. Ambivalent women were compared with those with definitive intentions using bivariate analyses. Regression analysis was used to determine the predictors of birth avoidance. Although ambivalent women were significantly older, and had less education and more children than women who wanted more children, ambivalent women were more similar in their contraceptive use to those who wanted more children than those who wanted no more. However, in terms of birth outcomes, ambivalent women resembled more the women who intended to avoid childbearing: After 4 years, 33% of ambivalent women had another birth compared with 29% of women who wanted no more and 57% of women who desired more children. Contraceptive use at baseline did not predict ambivalent women's fertility outcomes, unlike the other groups. Despite their relatively low rates of contraceptive use at baseline, ambivalent women generally avoided giving birth during the study period. This suggests that ambivalent women may not have a high unmet need for family planning. Copyright © 2011 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

  11. Major involvement of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) in uptake of biotin and pantothenic acid by human brain capillary endothelial cells.

    Uchida, Yasuo; Ito, Katsuaki; Ohtsuki, Sumio; Kubo, Yoshiyuki; Suzuki, Takashi; Terasaki, Tetsuya

    2015-07-01

    The purpose of this study was to clarify the expression of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) and its contribution to the supply of biotin and pantothenic acid to the human brain via the blood-brain barrier. DNA microarray and immunohistochemical analyses confirmed that SLC5A6 is expressed in microvessels of human brain. The absolute expression levels of SLC5A6 protein in isolated human and monkey brain microvessels were 1.19 and 0.597 fmol/μg protein, respectively, as determined by a quantitative targeted absolute proteomics technique. Using an antibody-free method established by Kubo et al. (2015), we found that SLC5A6 was preferentially localized at the luminal membrane of brain capillary endothelium. Knock-down analysis using SLC5A6 siRNA showed that SLC5A6 accounts for 88.7% and 98.6% of total [(3) H]biotin and [(3) H]pantothenic acid uptakes, respectively, by human cerebral microvascular endothelial cell line hCMEC/D3. SLC5A6-mediated transport in hCMEC/D3 was markedly inhibited not only by biotin and pantothenic acid, but also by prostaglandin E2, lipoic acid, docosahexaenoic acid, indomethacin, ketoprofen, diclofenac, ibuprofen, phenylbutazone, and flurbiprofen. This study is the first to confirm expression of SLC5A6 in human brain microvessels and to provide evidence that SLC5A6 is a major contributor to luminal uptake of biotin and pantothenic acid at the human blood-brain barrier. In humans, it was unclear (not concluded) about what transport system at the blood-brain barrier (BBB) is responsible for the brain uptakes of two vitamins, biotin and pantothenic acid, which are necessary for brain proper function. This study clarified for the first time that the solute carrier 5A6/Na(+) -dependent multivitamin transporter SLC5A6/SMVT is responsible for the supplies of biotin and pantothenic acid into brain across the BBB in humans. DHA, docosahexaenoic acid; NSAID, non-steroidal anti-inflammatory drug; PGE2, prostaglandin E2. © 2015

  12. Seniors’ unmet mobility needs – how important is a driving licence?

    Haustein, Sonja; Siren, Anu Kristiina

    2014-01-01

    Previous studies have come to different conclusions regarding how important a driving licence is for seniors to fulfil their mobility needs. We investigated this question based on three groups of Danish seniors: persons who were licensed as drivers (‘‘drivers’’); persons who have never been...... it became insignificant for unmet shopping needs. The effect of never having had a licence was hardly affected by the inclusion of control variables. The results emphasise the importance of a driving licence in fulfilling seniors’ mobility needs. Contrary to our hypotheses, more experience with, and better...

  13. Determinants of low family planning use and high unmet need in Butajira District, South Central Ethiopia

    Mekonnen Wubegzier

    2011-12-01

    Full Text Available Abstract Background The rapid population growth does not match with available resource in Ethiopia. Though household level family planning delivery has been put in place, the impact of such programs in densely populated rural areas was not studied. The study aims at measuring contraception and unmet need and identifying its determinants among married women. Methods A total of 5746 married women are interviewed from October to December 2009 in the Butajira Demographic Surveillance Area. Contraceptive prevalence rate and unmet need with their 95% confidence interval is measured among married women in the Butajira district. The association of background characteristics and family planning use is ascertained using crude and adjusted Odds ratio in logistic regression model. Results Current contraceptive prevalence rate among married women is 25.4% (95% CI: 24.2, 26.5. Unmet need of contraception is 52.4% of which 74.8% was attributed to spacing and the rest for limiting. Reasons for the high unmet need include commodities' insecurity, religion, and complaints related to providers, methods, diet and work load. Contraception is 2.3 (95% CI: 1.7, 3.2 times higher in urbanites compared to rural highlanders. Married women who attained primary and secondary plus level of education have about 1.3 (95% CI: 1.1, 1.6 and 2 (95% CI: 1.4, 2.9 times more risk to contraception; those with no child death are 1.3 (95% CI: 1.1, 1.5 times more likely to use contraceptives compared to counterparts. Besides, the odds of contraception is 1.3 (95% CI: 1.1, 1.6 and 1.5 (1.1, 2.0 times more likely among women whose partners completed primary and secondary plus level of education. Women discussing about contraception with partners were 2.2 (95% CI: 1.8, 2.7 times more likely to use family planning. Nevertheless, contraception was about 2.6 (95% CI: 2.1, 3.2 more likely among married women whose partners supported the use of family planning. Conclusions The local government

  14. Participation in cancer rehabilitation and unmet needs: a population-based cohort study

    Holm, L.V.; Hansen, D.G.; Johansen, C.

    2012-01-01

    sex, age, and diagnosis, and the outcome variables for rehabilitation. RESULTS: A total of 3,439 patients participated, yielding an overall response rate of 70%. One third of the cancer patients reported a need for physical rehabilitation and one third for psychological rehabilitation. Half...... of the patients participated in at least one activity. Unmet needs were most often reported in psychological, sexual, and financial areas. Women expressed more needs, participated more often in rehabilitation activities, and had, to a higher extent, their emotional needs fulfilled. Breast cancer patients...

  15. Influenza human monoclonal antibody 1F1 interacts with three major antigenic sites and residues mediating human receptor specificity in H1N1 viruses.

    Tshidi Tsibane

    Full Text Available Most monoclonal antibodies (mAbs to the influenza A virus hemagglutinin (HA head domain exhibit very limited breadth of inhibitory activity due to antigenic drift in field strains. However, mAb 1F1, isolated from a 1918 influenza pandemic survivor, inhibits select human H1 viruses (1918, 1943, 1947, and 1977 isolates. The crystal structure of 1F1 in complex with the 1918 HA shows that 1F1 contacts residues that are classically defined as belonging to three distinct antigenic sites, Sa, Sb and Ca(2. The 1F1 heavy chain also reaches into the receptor binding site (RBS and interacts with residues that contact sialoglycan receptors and determine HA receptor specificity. The 1F1 epitope is remarkably similar to the previously described murine HC63 H3 epitope, despite significant sequence differences between H1 and H3 HAs. Both antibodies potently inhibit receptor binding, but only HC63 can block the pH-induced conformational changes in HA that drive membrane fusion. Contacts within the RBS suggested that 1F1 may be sensitive to changes that alter HA receptor binding activity. Affinity assays confirmed that sequence changes that switch the HA to avian receptor specificity affect binding of 1F1 and a mAb possessing a closely related heavy chain, 1I20. To characterize 1F1 cross-reactivity, additional escape mutant selection and site-directed mutagenesis were performed. Residues 190 and 227 in the 1F1 epitope were found to be critical for 1F1 reactivity towards 1918, 1943 and 1977 HAs, as well as for 1I20 reactivity towards the 1918 HA. Therefore, 1F1 heavy-chain interactions with conserved RBS residues likely contribute to its ability to inhibit divergent HAs.

  16. Major Links.

    Henderson, Tona

    1995-01-01

    Provides electronic mail addresses for resources and discussion groups related to the following academic majors: art, biology, business, chemistry, computer science, economics, health sciences, history, literature, math, music, philosophy, political science, psychology, sociology, and theater. (AEF)

  17. Major Roads

    Minnesota Department of Natural Resources — This data set contains roadway centerlines for major roads (interstates and trunk highways) found on the USGS 1:24,000 mapping series. These roadways are current...

  18. Evaluation of molecular brain changes associated with environmental stress in rodent models compared to human major depressive disorder: A proteomic systems approach.

    Cox, David Alan; Gottschalk, Michael Gerd; Stelzhammer, Viktoria; Wesseling, Hendrik; Cooper, Jason David; Bahn, Sabine

    2016-11-25

    Rodent models of major depressive disorder (MDD) are indispensable when screening for novel treatments, but assessing their translational relevance with human brain pathology has proved difficult. Using a novel systems approach, proteomics data obtained from post-mortem MDD anterior prefrontal cortex tissue (n = 12) and matched controls (n = 23) were compared with equivalent data from three commonly used preclinical models exposed to environmental stressors (chronic mild stress, prenatal stress and social defeat). Functional pathophysiological features associated with depression-like behaviour were identified in these models through enrichment of protein-protein interaction networks. A cross-species comparison evaluated which model(s) represent human MDD pathology most closely. Seven functional domains associated with MDD and represented across at least two models such as "carbohydrate metabolism and cellular respiration" were identified. Through statistical evaluation using kernel-based machine learning techniques, the social defeat model was found to represent MDD brain changes most closely for four of the seven domains. This is the first study to apply a method for directly evaluating the relevance of the molecular pathology of multiple animal models to human MDD on the functional level. The methodology and findings outlined here could help to overcome translational obstacles of preclinical psychiatric research.

  19. Estimating demand and unmet need for allogeneic hematopoietic cell transplantation in the United States using geographic information systems.

    Besse, Kelsey L; Preussler, Jaime M; Murphy, Elizabeth A; Denzen, Ellen M; Lill, Michael C; Chell, Jeffrey W; Senneka, Mary K; Majhail, Navneet S; Williams, Eric P

    2015-03-01

    Allogeneic hematopoietic cell transplantation (HCT) is an increasingly used therapy for many patients with hematologic malignancies and other marrow failure or immune system disorders. The purpose of this study was to quantify and visualize both the demand and unmet need for HCT. HCT use for 2012 was described using the Center for International Blood and Marrow Transplant Research registry. Potential demand for HCT was calculated using 2012 SEER data and published literature for HCT-treatable conditions. Point locations of transplant centers were geocoded using geographic information system (GIS) software; Thiessen polygons were created to establish adult (age 20 to 74 years) and pediatric (age 0 to 19 years) market areas. Market-area population estimates were calculated using 2012 population estimates by age aggregated by census block. US market areas for HCTs were identified separately for transplant centers treating adult (n = 62) and pediatric patients (n = 52). Overall HCT demand among adults was 16,096, with an unmet need for HCTs of 10,276 patients. For pediatric patients, the total demand was 4,561, with an unmet need of 3,213 potential recipients. Evaluation of adult and pediatric market areas indicated that the largest unmet needs tended to be in areas with large populations. Market-area maps and statistics developed using GIS will help communicate the unmet need for HCT, inform policy, and assist transplant centers in planning for the anticipated growth in HCT use. Copyright © 2015 by American Society of Clinical Oncology.

  20. Is Team-Based Primary Care Associated with Less Access Problems and Self-Reported Unmet Need in Canada?

    Zygmunt, Austin; Asada, Yukiko; Burge, Frederick

    2017-10-01

    As in many jurisdictions, the delivery of primary care in Canada is being transformed from solo practice to team-based care. In Canada, team-based primary care involves general practitioners working with nurses or other health care providers, and it is expected to improve equity in access to care. This study examined whether team-based care is associated with fewer access problems and less unmet need and whether socioeconomic gradients in access problems and unmet need are smaller in team-based care than in non-team-based care. Data came from the 2008 Canadian Survey of Experiences with Primary Health Care (sample size: 10,858). We measured primary care type as team-based or non-team-based and socioeconomic status by income and education. We created four access problem variables and four unmet need variables (overall and three specific components). For each, we ran separate logistic regression models to examine their associations with primary care type. We examined socioeconomic gradients in access problems and unmet need stratified by primary care type. Primary care type had no statistically significant, independent associations with access problems or unmet need. Among those with non-team-based care, a statistically significant education gradient for overall access problems existed, whereas among those with team-based care, no statistically significant socioeconomic gradients existed.

  1. Beyond symptom management: Family relations, unmet needs of persons living with severe mental illnesses, and potential implications for social work in South Africa.

    Tomita, Andrew; Burns, Jonathan K; King, Howard; Baumgartner, Joy Noel; Davis, Glen P; Mtshemla, Sisanda; Nene, Siphumelele; Susser, Ezra

    2016-01-01

    This study examined the quality of family relationships and its associations with the severity of unmet needs of individuals admitted to a tertiary psychiatric hospital in South Africa. The quality of family relations and perceived unmet needs were assessed using the Lehman Quality of Life Interview and Camberwell Assessment of Needs, respectively. The results show that higher total unmet needs were associated with lower quality of family relations. The main areas of serious unmet needs included accessing government benefits and information, and establishing social relations. The results have implications for hospital-based social workers beyond managing psychiatric symptoms in South Africa.

  2. Breast cancer patients receiving postoperative radiotherapy: Distress, depressive symptoms and unmet needs of psychosocial support

    Luutonen, Sinikka; Vahlberg, Tero; Eloranta, Sini; Hyvaeri, Heidi; Salminen, Eeva

    2011-01-01

    Background and purpose: The diagnosis and treatment of breast cancer can cause considerable psychological consequences, which may remain unrecognized and untreated. In this study, the prevalence of depressive symptoms and distress, and unmet needs for psychosocial support were assessed among breast cancer patients receiving postoperative radiotherapy. Material and methods: Out of 389 consecutive patients, 276 responded and comprised the final study group. Depressive symptoms were assessed with the Beck Depression Inventory. Distress was measured with the Distress Thermometer. Hospital records of the patients were examined for additional information. Results: Nearly one third of patients (32.1%) displayed depressive symptoms, and more than a quarter of patients (28.4%) experienced distress. Younger age (p = 0.001) and negative hormone receptor status (p = 0.008) were independent factors associated with distress. One quarter of the patients expressed an unmet need for psychosocial support, which was independently associated with depressive symptoms and/or distress (p = 0.001) and younger age (p = 0.006). Conclusions: During radiotherapy for breast cancer, the staff should have awareness of the higher risk of depression and distress in their patients and should consider screening tools to recognise distress and depressive symptoms. Special attention should be paid to younger patients.

  3. Unmet clinical needs and burden in Angelman syndrome: a review of the literature.

    Wheeler, Anne C; Sacco, Patricia; Cabo, Raquel

    2017-10-16

    Angelman syndrome (AS) is a rare disorder with a relatively well-defined phenotype. Despite this, very little is known regarding the unmet clinical needs and burden of this condition, especially with regard to some of the most prevalent clinical features-movement disorders, communication impairments, behavior, and sleep. A targeted literature review using electronic medical databases (e.g., PubMed) was conducted to identify recent studies focused on specific areas of the AS phenotype (motor, communication, behavior, sleep) as well as epidemiology, diagnostic processes, treatment, and burden. 142 articles were reviewed and summarized. Findings suggest significant impairment across the life span in all areas of function. While some issues may resolve as individuals get older (e.g., hyperactivity), others become worse (e.g., movement disorders, aggression, anxiety). There are no treatments focused on the underlying etiology, and the symptom-based therapies currently prescribed do not have much, if any, empirical support. The lack of standardized treatment protocols or approved therapies, combined with the severity of the condition, results in high unmet clinical needs in the areas of motor functioning, communication, behavior, and sleep for individuals with AS and their families.

  4. Predictors of unmet needs and psychological distress in adolescent and young adult siblings of people diagnosed with cancer.

    McDonald, F E J; Patterson, P; White, K J; Butow, P; Bell, M L

    2015-03-01

    Predictors of psychological distress and unmet needs amongst adolescents and young adults (AYAs) who have a brother or sister diagnosed with cancer were examined. There were 106 AYAs (12-24 years old) who completed questionnaires covering demographics, psychological distress (Kessler 10), unmet needs (Sibling Cancer Needs Instrument) and family relationships (Family Relationship Index; Adult Sibling Relationship Questionnaire; Sibling Perception Questionnaire (SPQ)). Three models were analysed (demographic variables, cancer-specific variables and family functioning variables) using multiple linear regression to determine the role of the variables in predicting psychological distress and unmet needs. Unmet needs were higher for AYA siblings when treatment was current or a relapse had occurred. Higher scores on the SPQ-Interpersonal subscale indicating a perceived decrease in the quality of relationships with parents and others were associated with higher levels of distress and unmet needs. The age and gender of the AYA sibling, whether it was their brother or sister who was diagnosed with cancer, the age difference between them, the number of parents living with the AYA sibling, parental birth country, time since diagnosis, Family Relationship Index, Adult Sibling Relationship Questionnaire and the SPQ-Communication subscale did not significantly impact outcome variables. These results highlight the variables that can assist in identifying AYA siblings of cancer patients who are at risk and have a greater need for psychosocial assistance. Variables that may be associated with increased distress and unmet needs are reported to assist with future research. The results are also useful in informing the development of targeted psychosocial support for AYA siblings of cancer patients. Copyright © 2014 John Wiley & Sons, Ltd.

  5. Unmet need for modern contraceptives and associated factors among women in the extended postpartum period in Dessie town, Ethiopia.

    Tegegn, Masresha; Arefaynie, Mastewal; Tiruye, Tenaw Yimer

    2017-01-01

    The contraceptive use of women in the extended postpartum period is usually different from other times in a woman's life cycle due to the additional roles and presence of emotional changes. However, there is lack of evidence regarding women contraceptive need during this period and the extent they met their need. Therefore, the objective of this study was to assess unmet need for modern contraceptives and associated factors among women during the extended postpartum period in Dessie Town, North east Ethiopia in December 2014. A community-based cross-sectional study was conducted among women who gave birth one year before the study period. Systematic random sampling technique was employed to recruit a total of 383 study participants. For data collection, a structured and pretested standard questionnaire was used. Descriptive statistics were done to characterize the study population using different variables. Bivariate and multiple logistic regression models were fitted to control confounding factors. Odds ratios with 95% confidence intervals were computed to identify factors associated with unmet need. This study revealed that 44% of the extended post-partum women had unmet need of modern contraceptives of which 57% unmet need for spacing and 43% for limiting. Education of women (being illiterate) (AOR (adjusted odds ratio) =3.37, 95% CI (confidence interval) 1.22-7.57), antenatal care service (no) (AOR = 2.41, 95% CI 1.11-5.79), Post-natal care service (no) (AOR = 3.63, CI 2.13-6.19) and knowledge of lactational amenorrhea method (AOR = 7.84 95% CI 4.10-15.02) were the factors positively associated with unmet need modern contraceptives in the extended postpartum period. The unmet need for modern contraception is high in the study area. There is need to improve the quality of maternal health service, girls education, information on postpartum risk of pregnancy on the recommended postpartum contraceptives to enable mothers make informed choices of

  6. Factors affecting unmet need for family planning in married women of reproductive age group in urban slums of Lucknow

    Anjali Pal

    2014-03-01

    Full Text Available Background: Unmet need for family planning signifies the gap between the reproductive intentions of couples and their actual contraceptive behaviour. The National Family Health Surveys carried out in India in 1992-93, 1998-99 and 2004-2005 have revealed that for a sizable proportion of the population in the reproductive age group, the need for contraceptive services are not met with despite the existence of a National Policy on family planning since 1983. This study was carried out to assess the extent of unmet need for family planning among married women of reproductive age group in urban slums of Lucknow and identify the various factors affecting it. Study design: Cross sectional Setting: four urban slums of Lucknow Participants: 414 married women in the age group of 15- 44 years Study variables: age, education, occupation, religion, parity Statistical analysis: chi- square test, logistic regression analysis, fisher’s exact test Results: the extent of unmet need among married women of reproductive age group was 53.1%. The unmet need was found to be significantly associated with age, number of living sons, discussion of family planning with husband, perception of husband’s view on family planning and husbands’ behaviour towards use of family planning method. Logistic regression analysis of unmet need showed that the lower age of the woman, lesser number of living sons and husband’s discouragement towards the use of FP method were correlated with the unmet need for Family Planning.

  7. Stigma, explanatory models and unmet needs of caregivers of children with developmental disorders in a low-income African country: a cross-sectional facility-based survey.

    Tilahun, Dejene; Hanlon, Charlotte; Fekadu, Abebaw; Tekola, Bethlehem; Baheretibeb, Yonas; Hoekstra, Rosa A

    2016-04-27

    Understanding the perspectives of caregivers of children with developmental disorders living in low-income countries is important to inform intervention programmes. The purpose of this study was to examine the stigma experiences, explanatory models, unmet needs, preferred interventions and coping mechanisms of caregivers of children with developmental disorders in Ethiopia. Participants comprised caregivers (n = 102) of children with developmental disorders attending two child mental health clinics in Addis Ababa. The majority (66.7%; n = 68) had a diagnosis of intellectual disability (ID); 34 children (33.3%) had autism spectrum disorder (ASD) as their primary diagnosis. All caregivers were administered a structured questionnaire via a face-to-face interview, which included an adaptation of the Family Interview Schedule, closed questions about socio-demographic characteristics, explanatory models of illness, type of interventions used or desired and coping strategies, and an open ended question regarding the family's unmet needs. Most caregivers reported experience of stigma: 43.1% worried about being treated differently, 45.1% felt ashamed about their child's condition and 26.7% made an effort to keep their child's condition secret. Stigma did not depend on the type of developmental disorder, the child's age or gender, or on the age or level of education of the caregiver (all p > 0.05). Reported stigma was significantly higher in caregivers who had sought traditional help (p child's condition (p = .02) and in caregivers of Orthodox Christian faith (p = .03). Caregivers gave a mixture of biomedical explanations (e.g. head injury (30.4%) or birth complications (25.5%)) and supernatural explanations (e.g. spirit possession (40.2%) or sinful act (27.5%)) for their child's condition. The biggest reported unmet need was educational provision for their child (74.5%), followed by treatment by a health professional (47.1%), financial support (30.4%) and expert help to

  8. A STUDY TO ASSESS THE FACTORS DETERMINING THE UNMET NEED FOR CONTRACEPTIVE USAGE IN AN URBAN AREA RAJAPUR

    Mohammad Waseem Faraz

    2015-08-01

    Full Text Available INTRODUCTI ON: Family planning is a “way of thinking and living that is adopted voluntarily, upon the basis of knowledge, attitudes, and responsible decisions by individuals and couples, in order to promote the health and welfare of the family group and thus contribute effectively to the social development of a country”. 1 The concept of unmet need for contraception has been central to international family planning programs and research for more than forty years, but it has perhaps never been more salient to research and practice than it is now. Over the past decade, the rising rates of contraceptive use have reduced the unmet need for family planning in most countries. However the unmet need remains persistently high or is increasing in developing countries like India, indicating that greater efforts are needed to understand and address the causes of unm et need. OBJECTIVES: 1 To assess the Unmet need for family planning among married women of reproductive age group (15 – 44 years. 2 To identify certain socio - demographic factors associated with unmet need for family planning. 3 To determine the reasons for non - usage of contraceptive use. MATERIALS AND METHODS: A cross - sectional study was carried out in the Urban health training Centre of Department of Community Medicine. The study population included 924 married women aged 15 - 44 years. The data was collected u sing pre te st ed profor m a and was analyzed using percentages and Chi - Square test. RESULTS : The unmet need for family planning was 28.9% in the study population. The overall unmet need is low at the beginning of reproductive age, but it increased and reached a peak in the mid - twenties & then declined. The literacy status among women with unmet needs is plays a vital role. Want of child in future was quoted as the main reason for non - use of contraceptives. CONCLUSION: Despite a fair knowledge about the family planning methods, various socio - cultural and problems

  9. Codon and amino acid usage in two major human pathogens of genus Bartonella--optimization between replicational-transcriptional selection, translational control and cost minimization.

    Das, Sabyasachi; Paul, Sandip; Chatterjee, Sanjib; Dutta, Chitra

    2005-01-01

    Intra-genomic variation in synonymous codon and amino acid usage in two human pathogens Bartonella henselae and B. quintana has been carried out through multivariate analysis. Asymmetric mutational bias, coupled with replicational-transcriptional selection, has been identified as the prime selection force behind synonymous codon selection--a characteristic of the genus Bartonella, not exhibited by any other alpha-proteobacterial genome. Distinct codon usage patterns and low synonymous divergence values between orthologous sequences of highly expressed genes from the two Bartonella species indicate that there exists a residual intra-strand synonymous codon bias in the highly expressed genes, possibly operating at the level of translation. In the case of amino acid usage, the mean hydropathy level and aromaticity are the major sources of variation, both having nearly equal impact, while strand-specific mutational pressure and gene expressivity strongly influence the inter-strand variations. In both species under study, the highly expressed gene products tend not to contain heavy and/or aromatic residues, following the cost-minimization hypothesis in spite of their intracellular lifestyle. The codon and amino acid usage in these two human pathogens are, therefore, consequences of a complex balance between replicational-transcriptional selection, translational control, protein hydropathy and cost minimization.

  10. A binary logistic regression model with complex sampling design of unmet need for family planning among all women aged (15-49) in Ethiopia.

    Workie, Demeke Lakew; Zike, Dereje Tesfaye; Fenta, Haile Mekonnen; Mekonnen, Mulusew Admasu

    2017-09-01

    Unintended pregnancy related to unmet need is a worldwide problem that affects societies. The main objective of this study was to identify the prevalence and determinants of unmet need for family planning among women aged (15-49) in Ethiopia. The Performance Monitoring and Accountability2020/Ethiopia was conducted in April 2016 at round-4 from 7494 women with two-stage-stratified sampling. Bi-variable and multi-variable binary logistic regression model with complex sampling design was fitted. The prevalence of unmet-need for family planning was 16.2% in Ethiopia. Women between the age range of 15-24 years were 2.266 times more likely to have unmet need family planning compared to above 35 years. Women who were currently married were about 8 times more likely to have unmet need family planning compared to never married women. Women who had no under-five child were 0.125 times less likely to have unmet need family planning compared to those who had more than two-under-5. The key determinants of unmet need family planning in Ethiopia were residence, age, marital-status, education, household members, birth-events and number of under-5 children. Thus the Government of Ethiopia would take immediate steps to address the causes of high unmet need for family planning among women.

  11. Unmet demand for training among mature age Australians: Prevalence, differentials and perceived causes.

    Adair, Tim; Lourey, Emma; Taylor, Philip

    2016-03-01

    To explore the prevalence of unmet demand for training by mature age Australians and to identify the main barriers to accessing training. A total of 3007 Australians aged 45-74 years were surveyed using Computer Assisted Telephone Interviewing. The sample frame was randomly selected and stratified based on the capital city and the rest of the state, and data were weighted to be nationally representative. Over one-third (37%) of respondents who had worked in the past five years reported wanting to attend some form of training but were unable to; these were most likely women and those aged 45-54 year. Commonly cited reasons for not being able to attend training included not being able to fit it in with work commitments, affordability and employer reluctance. Reduction of these barriers to workplace training can improve mature age people's ability to remain engaged in the workforce. © 2015 AJA Inc.

  12. Exploring the Unmet Needs of the Patient in the Outpatient Respiratory Medical Clinic

    Jensen, Lone Birgitte; Brinkkjær, Ulf; Larsen, Kristian

    2015-01-01

    Aim. Developing a theoretical framework explaining patients’ behaviour and actions related to unmet needs during interactions with health care professionals in hospital-based outpatient respiratory medical clinics. Background. The outpatient respiratory medical clinic plays a prominent role in many...... patients’ lives regarding treatment and counselling increasing the need for a better understanding of patients’ perspective to the counselling of the health care professionals. Design. The study is exploratory and based on Charmaz’s interpretation of grounded theory. Methods. The study included 65 field...... observations with a sample of 43 patients, 11 doctors, and 11 nurses, as well as 30 interviews with patients, conducted through theoretical sampling from three outpatient respiratory medical clinics in Denmark. Findings. The patients’ efforts to share their significant stories triggered predominantly...

  13. Traumatic brain injury: unmet support needs of caregivers and families in Florida.

    Christina Dillahunt-Aspillaga

    Full Text Available Sustaining a Traumatic Brain Injury results in familial strain due to the significant impact the injury has upon the role and function of individuals and their families at home and in the community. Using the Stress Process Model of Caregiving, a caregiver needs assessment survey was developed and conducted to better understand the needs of individuals with a Traumatic Brain Injury and their caregivers. Survey results indicate that caregivers experience many challenges including unmet needs in areas of relational supports such as maintaining relationships, long-term emotional and financial support for themselves and the survivor, and the need for a patient or caregiver advocate. Implications for future practice are presented.

  14. The Challenge of Controlling the COPD Epidemic Chronic Obstructive Pulmonary Disease: Unmet Needs.

    Polverino, Francesca; Celli, Bartolome

    2018-05-17

    Many unmet needs still remain in the assessment and treatment of patients with chronic obstructive pulmonary disease (COPD), particularly in relation to its under- and misdiagnosis, which lead to under- and mistreatment. This paucity of knowledge about the importance and presence of COPD, as well as its treatment, is seen with patients and carers as well as healthcare providers. This review considers the areas of key educational need, including the clinical characteristics of COPD, factors contributing to the disease, effective diagnosis, and clinical management of patients, and the implementation of treatment guidelines. As COPD remains the third most frequent cause of death in the world, we must continue to expand the scope and reach of our efforts to improve outcomes in this debilitating disease. Copyright © 2018. Published by Elsevier Inc.

  15. Unmet needs for analyzing biological big data: A survey of 704 NSF principal investigators.

    Lindsay Barone

    2017-10-01

    Full Text Available In a 2016 survey of 704 National Science Foundation (NSF Biological Sciences Directorate principal investigators (BIO PIs, nearly 90% indicated they are currently or will soon be analyzing large data sets. BIO PIs considered a range of computational needs important to their work, including high performance computing (HPC, bioinformatics support, multistep workflows, updated analysis software, and the ability to store, share, and publish data. Previous studies in the United States and Canada emphasized infrastructure needs. However, BIO PIs said the most pressing unmet needs are training in data integration, data management, and scaling analyses for HPC-acknowledging that data science skills will be required to build a deeper understanding of life. This portends a growing data knowledge gap in biology and challenges institutions and funding agencies to redouble their support for computational training in biology.

  16. Unmet needs for analyzing biological big data: A survey of 704 NSF principal investigators.

    Barone, Lindsay; Williams, Jason; Micklos, David

    2017-10-01

    In a 2016 survey of 704 National Science Foundation (NSF) Biological Sciences Directorate principal investigators (BIO PIs), nearly 90% indicated they are currently or will soon be analyzing large data sets. BIO PIs considered a range of computational needs important to their work, including high performance computing (HPC), bioinformatics support, multistep workflows, updated analysis software, and the ability to store, share, and publish data. Previous studies in the United States and Canada emphasized infrastructure needs. However, BIO PIs said the most pressing unmet needs are training in data integration, data management, and scaling analyses for HPC-acknowledging that data science skills will be required to build a deeper understanding of life. This portends a growing data knowledge gap in biology and challenges institutions and funding agencies to redouble their support for computational training in biology.

  17. Unmet need for contraception among sex workers in Madagascar☆,☆☆

    Khan, Maria R.; Turner, Abigail Norris; Pettifor, Audrey; Van Damme, Kathleen; Rabenja, Ny Lovaniaina; Ravelomanana, Noro; Swezey, Teresa; Williams, D’Nyce; Jamieson, Denise; Behets, Frieda

    2018-01-01

    Background The study was conducted to investigate past and future pregnancy preferences and contraceptive need among Malagasy sex workers. Study Design We analyzed data on pregnancy and contraceptive use collected during the baseline visit of a randomized, prospective formative trial which assessed diaphragm and microbicide acceptability among sex workers. To be eligible, women could not be pregnant or planning pregnancy for the next 2 months. Results Women (N=192) from four cities (Antananarivo, Antsiranana, Mahajanga and Toamasina) reported a median of 10 sex acts per week. Fifty-two percent reported a prior unwanted pregnancy, 45% at least one induced abortion and 86% that preventing future pregnancy was moderately to very important. During the last sex act, 24% used a hormonal method, 36% used a male condom, 2% used a traditional method and 38% used no method. Nearly 30% of participants reported that pregnancy prevention was moderately or very important but used no contraception at last sex; these women were categorized as having “unmet need” for contraception. In multivariable binomial regression analyses, factors associated with unmet need included low knowledge of contraceptive effectiveness [age- and site-adjusted prevalence ratio (PR): 2.1; 95% confidence interval (CI): 1.4–3.0] and low self-efficacy to negotiate condom use (age- and site-adjusted PR: 2.0; 95% CI: 1.4–3.0). Conclusions Among these women, prior unwanted pregnancy and induced abortion were common and preventing future pregnancy was important, yet gaps in contraceptive use were substantial. Contraceptive knowledge and self-efficacy should be improved to promote contraceptive use by sex workers. PMID:19185677

  18. Geospatial Analysis of Unmet Surgical Need in Uganda: An Analysis of SOSAS Survey Data.

    Farber, S Harrison; Vissoci, Joao Ricardo Nickenig; Tran, Tu M; Fuller, Anthony T; Butler, Elissa K; Andrade, Luciano; Staton, Catherine; Makumbi, Fredrick; Luboga, Samuel; Muhumuza, Christine; Namanya, Didacus B; Chipman, Jeffrey G; Galukande, Moses; Haglund, Michael M

    2017-02-01

    Globally, a staggering five billion people lack access to adequate surgical care. Sub-Saharan Africa represents one of the regions of greatest need. We sought to understand how geographic factors related to unmet surgical need (USN) in Uganda. We performed a geographic information system analysis of a nationwide survey on surgical conditions performed in 105 enumeration areas (EAs) representing the national population. At the district level, we determined the spatial autocorrelation of the following study variables: prevalence of USN, hub distance (distance from EA to the nearest surgical center), area of coverage (geographic catchment area of each center), tertiary facility transport time (average respondent-reported travel time), and care availability (rate of hospital beds by population and by district). We then used local indicators of spatial association (LISA) and spatial regression to identify any significant clustering of these study variables among the districts. The survey enumerated 4248 individuals. The prevalence of USN varied from 2.0-45 %. The USN prevalence was highest in the Northern and Western Regions. Moran's I bivariate analysis indicated a positive correlation between USN and hub distance (p = 0.03), area of coverage (p = 0.02), and facility transport time (p = 0.03). These associations were consistent nationally. The LISA analysis showed a high degree of clustering among sets of districts in the Northern Sub-Region. This study demonstrates a statistically significant association between USN and the geographic variables examined. We have identified the Northern Sub-Region as the highest priority areas for financial investment to reduce this unmet surgical disease burden.

  19. Rationing of hip and knee referrals in the public hospital: the true unmet need.

    Inglis, Tom; Armour, Paul; Inglis, Grahame; Hooper, Gary

    2017-03-24

    The aim of this paper is to outline the development of a triage system for elective hip and knee referrals to the Orthopaedic Department of the Canterbury District Health Board (CDHB), and to determine the unmet need within this population for accessing first specialist assessment (FSA). Between 1 August 2015 and 31 March 2016 data was collected from all elective hip and knee referrals that underwent triage for a FSA. The number of outpatient appointments available according to the government four-month waiting time is set by the CDHB. Patients were triaged by two consultant surgeons on the basis of their referral letter and radiological imaging into one of five categories: accepted for FSA, insufficient information, no capacity, low priority or direct entry to waiting list (if already seen by a specialist). Those not accepted for an FSA were returned to general practitioner (GP) care. During the study period there were 1,733 referrals (838 hip related referrals and 895 knee related referrals) to the orthopaedic department with a request for FSA. All patients had failed conservative management. Of these referrals 43% of hip and 54% of knee related referrals could not be offered an FSA and were returned, following triage, to general practitioner care unseen. Only 8% and 9% respectively were declined for insufficient information in the referral letter or lack of need. This study details the implementation of a triage system for elective hip and knee referrals to the CDHB and with accurate data we have been able to determine the large number of patients unable to access a specialist opinion. These patients represent the unmet need within our community and highlights the degree of rationing taking place within the public hospital.

  20. Unmet belongingness needs but not high belongingness needs alone predict adverse well-being; A response surface modeling approach

    Verhagen, M.; Lodder, G.M.A.; Baumeister, R.F.

    2018-01-01

    Objective: Previous work has linked high levels of belongingness needs to low well-being, suggesting that high desire for social connection causes problems. Against that view, we hypothesized that problems stem especially from unmet belongingness needs. To examine this, discrepancies between

  1. Public pensions and unmet medical need among older people: Cross-national analysis of 16 European countries, 2004-2010

    A. Reeves (Aaron); M. McKee (Martin); J.P. Mackenbach (Johan); M. Whitehead (Margaret); D. Stuckler (David)

    2016-01-01

    textabstractBackground Since the onset of the Great Recession in Europe, unmet need for medical care has been increasing, especially in persons aged 65 or older. It is possible that public pensions buffer access to healthcare in older persons during times of economic crisis, but to our knowledge,

  2. Great expectations - and what comes of it: The effects of unmet expectations on work motivation and outcomes among newcomers

    Taris, T.W.; Feij, J.A.; Capel, S.

    2006-01-01

    Purpose - Examines how the socialization of new employees affects their future work performance, studying the impact of unmet expectations on their later motivation for learning, effort and turnover. Design/methodology/approach - Uses data from the Work Socialization of Youth study, which studied

  3. Unmet need and demand for family planning among married women of Abha, Aseer Region in Saudi Arabia

    Shamsun Nahar Khalil

    2018-03-01

    Conclusion: Around one third of the women in the present study have an unmet need for family planning and demand for Contraception for this population has been found to be high. All these findings point out the need of action in this regards.

  4. 78 FR 3005 - Creating an Alternative Approval Pathway for Certain Drugs Intended to Address Unmet Medical Need...

    2013-01-15

    ... approaches that can facilitate development of treatment for unmet needs. Traditional drug development... considerations need to be taken into account before and after marketing and how should they be addressed? 6..., subject to certain limitations, to videotape, film, or otherwise record FDA's public administrative...

  5. Great expectations and what comes of it: the effects of unmet expectations on work motivation and outcomes among newcomers

    Taris, T.W.; Feij, J.A.; Capel, S.

    2006-01-01

    The present research focused on newcomers' socialization process in a three-wave study among 1477 newcomers from seven Western (mainly European) countries. Based on previous research, we expected that unmet expectations regarding selected intrinsic work aspects would have adverse effects on work

  6. EAACI Food Allergy and Anaphylaxis Guidelines. Protecting consumers with food allergies: understanding food consumption, meeting regulations and identifying unmet needs

    Muraro, A.; Hoffmann-Sommergruber, K.; Holzhauser, T.; Poulsen, L. K.; Gowland, M. H.; Akdis, C. A.; Mills, E. N. C.; Papadopoulos, N.; Roberts, G.; Schnadt, S.; van Ree, R.; Sheikh, A.; Vieths, S.

    2014-01-01

    Individuals suffering from IgE-mediated food allergy usually have to practise life-long food allergen avoidance. This document aims to provide an overview of recent evidence-based recommendations for allergen risk assessment and management in the food industry and discusses unmet needs and

  7. Phenol-Explorer 2.0: a major update of the Phenol-Explorer database integrating data on polyphenol metabolism and pharmacokinetics in humans and experimental animals

    Rothwell, Joseph A.; Urpi-Sarda, Mireia; Boto-Ordoñez, Maria; Knox, Craig; Llorach, Rafael; Eisner, Roman; Cruz, Joseph; Neveu, Vanessa; Wishart, David; Manach, Claudine; Andres-Lacueva, Cristina; Scalbert, Augustin

    2012-01-01

    Phenol-Explorer, launched in 2009, is the only comprehensive web-based database on the content in foods of polyphenols, a major class of food bioactives that receive considerable attention due to their role in the prevention of diseases. Polyphenols are rarely absorbed and excreted in their ingested forms, but extensively metabolized in the body, and until now, no database has allowed the recall of identities and concentrations of polyphenol metabolites in biofluids after the consumption of polyphenol-rich sources. Knowledge of these metabolites is essential in the planning of experiments whose aim is to elucidate the effects of polyphenols on health. Release 2.0 is the first major update of the database, allowing the rapid retrieval of data on the biotransformations and pharmacokinetics of dietary polyphenols. Data on 375 polyphenol metabolites identified in urine and plasma were collected from 236 peer-reviewed publications on polyphenol metabolism in humans and experimental animals and added to the database by means of an extended relational design. Pharmacokinetic parameters have been collected and can be retrieved in both tabular and graphical form. The web interface has been enhanced and now allows the filtering of information according to various criteria. Phenol-Explorer 2.0, which will be periodically updated, should prove to be an even more useful and capable resource for polyphenol scientists because bioactivities and health effects of polyphenols are dependent on the nature and concentrations of metabolites reaching the target tissues. The Phenol-Explorer database is publicly available and can be found online at http://www.phenol-explorer.eu. Database URL: http://www.phenol-explorer.eu PMID:22879444

  8. Assessment of inhibitory effects on major human cytochrome P450 enzymes by spasmolytics used in the treatment of overactive bladder syndrome.

    Dahlinger, Dominik; Aslan, Sevinc; Pietsch, Markus; Frechen, Sebastian; Fuhr, Uwe

    2017-07-01

    The objective of this study was to examine the inhibitory potential of darifenacin, fesoterodine, oxybutynin, propiverine, solifenacin, tolterodine and trospium chloride on the seven major human cytochrome P450 enzymes (CYP) by using a standardized and validated seven-in-one cytochrome P450 cocktail inhibition assay. An in vitro cocktail of seven highly selective probe substrates was incubated with human liver microsomes and varying concentrations of the seven test compounds. The major metabolites of the probe substrates were simultaneously analysed using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Enzyme kinetics were estimated by determining IC 50 and K i values via nonlinear regression. Obtained K i values were used for predictions of potential clinical impact of the inhibition using a static mechanistic prediction model. In this study, 49 IC 50 experiments were conducted. In six cases, IC 50 values lower than the calculated threshold for drug-drug interactions (DDIs) in the gut wall were observed. In these cases, no increase in inhibition was determined after a 30 min preincubation. Considering a typical dosing regimen and applying the obtained K i values of 0.72 µM (darifenacin, 15 mg daily) and 7.2 µM [propiverine, 30 mg daily, immediate release (IR)] for the inhibition of CYP2D6 yielded a predicted 1.9-fold and 1.4-fold increase in the area under the curve (AUC) of debrisoquine (CYP2D6 substrate), respectively. Due to the inhibition of the particular intestinal CYP3A4, the obtained K i values of 14 µM of propiverine (30 mg daily, IR) resulted in a predicted doubling of the AUC for midazolam (CYP3A4 substrate). In vitro / in vivo extrapolation based on pharmacokinetic data and the conducted screening experiments yielded similar effects of darifenacin on CYP2D6 and propiverine on CYP3A4 as obtained in separately conducted in vivo DDI studies. As a novel finding, propiverine was identified to potentially inhibit CYP2D6 at

  9. Evidence of dengue virus transmission and factors associated with the presence of anti-dengue virus antibodies in humans in three major towns in Cameroon.

    Demanou, Maurice; Pouillot, Régis; Grandadam, Marc; Boisier, Pascal; Kamgang, Basile; Hervé, Jean Pierre; Rogier, Christophe; Rousset, Dominique; Paupy, Christophe

    2014-07-01

    Dengue is not well documented in Africa. In Cameroon, data are scarce, but dengue infection has been confirmed in humans. We conducted a study to document risk factors associated with anti-dengue virus Immunoglobulin G seropositivity in humans in three major towns in Cameroon. A cross sectional survey was conducted in Douala, Garoua and Yaounde, using a random cluster sampling design. Participants underwent a standardized interview and were blood sampled. Environmental and housing characteristics were recorded. Randomized houses were prospected to record all water containers, and immature stages of Aedes mosquitoes were collected. Sera were screened for anti-dengue virus IgG and IgM antibodies. Risk factors of seropositivity were tested using logistic regression methods with random effects. Anti-dengue IgG were found from 61.4% of sera in Douala (n = 699), 24.2% in Garoua (n = 728) and 9.8% in Yaounde (n = 603). IgM were found from 0.3% of Douala samples, 0.1% of Garoua samples and 0.0% of Yaounde samples. Seroneutralization on randomly selected IgG positive sera showed that 72% (n = 100) in Douala, 80% (n = 94) in Garoua and 77% (n = 66) in Yaounde had antibodies specific for dengue virus serotype 2 (DENV-2). Age, temporary house walls materials, having water-storage containers, old tires or toilets in the yard, having no TV, having no air conditioning and having travelled at least once outside the city were independently associated with anti-dengue IgG positivity in Douala. Age, having uncovered water containers, having no TV, not being born in Garoua and not breeding pigs were significant risk factors in Garoua. Recent history of malaria, having banana trees and stagnant water in the yard were independent risk factors in Yaounde. In this survey, most identified risk factors of dengue were related to housing conditions. Poverty and underdevelopment are central to the dengue epidemiology in Cameroon.

  10. Involvement of the major histocompatibility complex region in the genetic regulation of circulating CD8 T-cell numbers in humans.

    Cruz, E; Vieira, J; Gonçalves, R; Alves, H; Almeida, S; Rodrigues, P; Lacerda, R; Porto, G

    2004-07-01

    Variability in T-lymphocyte numbers is partially explained by a genetic regulation. From studies in animal models, it is known that the Major Histocompatibility Complex (MHC) is involved in this regulation. In humans, this has not been shown yet. The objective of the present study was to test the hypothesis that genes in the MHC region influence the regulation of T-lymphocyte numbers. Two approaches were used. Association studies between T-cell counts (CD4(+) and CD8(+)) or total lymphocyte counts and HLA class I alleles (A and B) or mutations in the HFE (C282Y and H63D), the hemochromatosis gene, in an unrelated population (n = 264). A second approach was a sibpair correlation analysis of the same T-cell counts in relation to HLA-HFE haplotypes in subjects belonging to 48 hemochromatosis families (n = 456 sibpairs). In the normal population, results showed a strong statistically significant association of the HLA-A*01 with high numbers of CD8(+) T cells and a less powerful association with the HLA-A*24 with low numbers of CD8(+) T cells. Sibpair correlations revealed the most significant correlation for CD8(+) T-cell numbers for sibpairs with HLA-HFE-identical haplotypes. This was not observed for CD4(+) T cells. These results show that the MHC region is involved in the genetic regulation of CD8(+) T-cell numbers in humans. Identification of genes responsible for this control may have important biological and clinical implications.

  11. Age-related changes in the proteoglycans of human skin. Specific cleavage of decorin to yield a major catabolic fragment in adult skin.

    Carrino, David A; Onnerfjord, Patrik; Sandy, John D; Cs-Szabo, Gabriella; Scott, Paul G; Sorrell, J Michael; Heinegård, Dick; Caplan, Arnold I

    2003-05-09

    Dramatic changes occur in skin as a function of age, including changes in morphology, physiology, and mechanical properties. Changes in extracellular matrix molecules also occur, and these changes likely contribute to the overall age-related changes in the physical properties of skin. The major proteoglycans detected in extracts of human skin are decorin and versican. In addition, adult human skin contains a truncated form of decorin, whereas fetal skin contains virtually undetectable levels of this truncated decorin. Analysis of this molecule, herein referred to as decorunt, indicates that it is a catabolic fragment of decorin rather than a splice variant. With antibody probes to the core protein, decorunt is found to lack the carboxyl-terminal portion of decorin. Further analysis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry shows that the carboxyl terminus of decorunt is at Phe(170) of decorin. This result indicates that decorunt represents the amino-terminal 43% of the mature decorin molecule. Such a structure is inconsistent with alternative splicing of decorin and suggests that decorunt is a catabolic fragment of decorin. A neoepitope antiserum, anti-VRKVTF, was generated against the carboxyl terminus of decorunt. This antiserum does not recognize intact decorin in any skin proteoglycan sample tested on immunoblots but recognizes every sample of decorunt tested. The results with anti-VRKVTF confirm the identification of the carboxyl terminus of decorunt. Analysis of collagen binding by surface plasmon resonance indicates that the affinity of decorunt for type I collagen is 100-fold less than that of decorin. This observation correlates with the structural analysis of decorunt, in that it lacks regions of decorin previously shown to be important for interaction with type I collagen. The detection of a catabolic fragment of decorin suggests the existence of a specific catabolic pathway for this proteoglycan. Because of the

  12. Levels, trends and correlates of unmet need for family planning among postpartum women in Indonesia: 2007-2015.

    Wilopo, Siswanto Agus; Setyawan, Althaf; Pinandari, Anggriyani Wahyu; Prihyugiarto, Titut; Juliaan, Flourisa; Magnani, Robert J

    2017-11-28

    Although Indonesia has relatively high contraceptive prevalence, postpartum family planning (PP-FP) has not been a particular point of emphasis. This article reports the results of analyses undertaken in order to (1) better understand levels and trends in unmet need for family planning among postpartum women, (2) assess the extent to which unmet need is concentrated among particular population sub-groups, and (3) assess the policy priority that PP-FP should have in relation to other interventions. The analyses were based on data from the 2007 and 2012 Indonesia Demographic and Health Surveys (IDHS) and the 2015 PMA2020 survey. Postpartum contraceptive use and unmet need were analyzed for fecund women who had given birth in the 3-5 years of preceding the respective surveys who were in the extended postpartum period at the time of the respective surveys. Factors associated with contraceptive use and unmet were assessed via multivariable logistic regressions using merged data from all three surveys. A wide range of biologic, demographic, socio-economic, geographic and programmatic factors were considered. Contraceptive use during the extended postpartum period is high in Indonesia, with more than 74% of post-partum women reporting currently using a family planning method in the 2015 PMA2020 survey. This is up from 68% in 2007 and 70% in 2012. Total unmet need was 28% in 2007, falling slightly to 23% in 2012 and 24% in 2015. However, the timing of contraceptive initiation is less than optimal. By six months postpartum, only 50% of mothers had begun contraceptive use. Unmet need was highest among older women, women with 4+ children, with limited knowledge of contraceptive methods, making fewer ANC visits, from poor families and residents of islands other than Java and Bali. Unmet need for family planning among postpartum women in Indonesia is low in comparison with other low- and middle-income countries. However, because of limited durations of exclusive breastfeeding

  13. The endogenous and reactive depression subtypes revisited: integrative animal and human studies implicate multiple distinct molecular mechanisms underlying major depressive disorder.

    Malki, Karim; Keers, Robert; Tosto, Maria Grazia; Lourdusamy, Anbarasu; Carboni, Lucia; Domenici, Enrico; Uher, Rudolf; McGuffin, Peter; Schalkwyk, Leonard C

    2014-05-07

    Traditional diagnoses of major depressive disorder (MDD) suggested that the presence or absence of stress prior to onset results in either 'reactive' or 'endogenous' subtypes of the disorder, respectively. Several lines of research suggest that the biological underpinnings of 'reactive' or 'endogenous' subtypes may also differ, resulting in differential response to treatment. We investigated this hypothesis by comparing the gene-expression profiles of three animal models of 'reactive' and 'endogenous' depression. We then translated these findings to clinical samples using a human post-mortem mRNA study. Affymetrix mouse whole-genome oligonucleotide arrays were used to measure gene expression from hippocampal tissues of 144 mice from the Genome-based Therapeutic Drugs for Depression (GENDEP) project. The study used four inbred mouse strains and two depressogenic 'stress' protocols (maternal separation and Unpredictable Chronic Mild Stress) to model 'reactive' depression. Stress-related mRNA differences in mouse were compared with a parallel mRNA study using Flinders Sensitive and Resistant rat lines as a model of 'endogenous' depression. Convergent genes differentially expressed across the animal studies were used to inform candidate gene selection in a human mRNA post-mortem case control study from the Stanley Brain Consortium. In the mouse 'reactive' model, the expression of 350 genes changed in response to early stresses and 370 in response to late stresses. A minimal genetic overlap (less than 8.8%) was detected in response to both stress protocols, but 30% of these genes (21) were also differentially regulated in the 'endogenous' rat study. This overlap is significantly greater than expected by chance. The VAMP-2 gene, differentially expressed across the rodent studies, was also significantly altered in the human study after correcting for multiple testing. Our results suggest that 'endogenous' and 'reactive' subtypes of depression are associated with largely

  14. The association between perceived unmet medical need and mental health among the Republic of Korea Armed Forces.

    Kim, Tae Kyung; Lee, S G; Han, K-T; Choi, Y; Lee, S Y; Park, E-C

    2017-06-01

    We investigated the effect of unmet medical need on the mental health of Republic of Korea (ROK) Armed Forces personnel, as most of the service members work in remote areas and often experience such unmet needs. This study used secondary data from the 2014 Military Health Survey (MHS), conducted by the ROK School of Military Medicine and designed to collect military health determinants. Descriptive statistics showed the general characteristics of the study populations by variable. We specifically compared the population after stratifying participants by suicide ideation. An analysis of variance was also carried out to compare Kessler Psychological Distress Scale 10 Scores. Additionally, dependent spouses and children of both active-duty service members and retirees are included among those entitled to Military Health System healthcare. Among the 4967 military personnel, 681 (13.7%) individuals reported an experience of unmet medical need within the past 12 months and gave reasons of 'no time (5.15%)', 'long office wait (2.6%)', 'no money (0.22%)', 'long distance from base (1.19%)', 'illness but not very serious (1.65%)', 'mistrust in doctors (1.95%)' and 'pressure due to performance appraisal (0.95%)'. Regression analysis revealed that unmet medical need was significantly associated with negative mental health (β=1.753, pmental health effects. Our study indicates that unmet medical need is significantly associated with soldiers' mental health decline and suicide ideation, highlighting the importance of providing military personnel with timely, affordable and sufficient medical care. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  15. Use, non-use and perceived unmet needs of assistive technology among Swedish people in the third age.

    Löfqvist, Charlotte; Slaug, Björn; Ekström, Henrik; Kylberg, Marianne; Haak, Maria

    2016-01-01

    To describe the most prominent use of or perceived unmet need of assistive technology (AT) and to compare the characteristics of users, non-users and those expressing perceived unmet need with respect to overall health, independence in everyday life, environmental barriers and socio-demographic features. The study is based on data collected in the "Home and Health in the Third Age Project". In all, 371 individuals participated and data were collected during home visits in southern Sweden by interviewers trained specifically for this project. The data collection comprised well-proven self-report scales and observational formats on the home environment and health indicators as well as questions about basic demographics and socio-structural data. The proportion of users constituted almost half of the total sample. The most common types of AT used were for furnishing/adaptation (35%) and the highest perceived unmet need concerned AT for communication, in total 8%. Those cohabiting were to a higher extent users of AT for furnishing/adaptation, compared to those who lived alone. A higher perceived unmet need was seen among those who lived alone compared with cohabiting people. These findings are of importance for future planning and development of policy to improve health services for the new generation of elderly. Implications for Rehabilitation In order to support the ageing process, the need for assistive technology has to be monitored in the third age. Assistive technology for furnishings and adaptation are frequently used by individuals in their third age and are important to support ageing in the home. Not only do health aspects impact the use of assistive technology, but gender, living conditions and social situation also matter - older men especially need to be monitored thoroughly according to their perceived unmet needs as well as do older persons living alone.

  16. Association of family-centered care with improved anticipatory guidance delivery and reduced unmet needs in child health care.

    Kuo, Dennis Z; Frick, Kevin D; Minkovitz, Cynthia S

    2011-11-01

    Little is known about the association of family-centered care (FCC) with the quality of pediatric primary care. The objectives were to assess (1) associations between family-centered care (FCC), receipt of anticipatory guidance, and unmet need for health care; and (2) whether these associations vary for children with special health care needs (CSHCN). The study, a secondary data analysis of the 2004 Medical Expenditure Panel Survey, used a nationally representative sample of family members of children 0-17 years. We measured receipt of FCC in the last 12 months with a composite score average>3.5 on a 4 point Likert scale from 4 Consumer Assessment of Healthcare Providers and Systems questions. Outcome measures were six anticipatory guidance and six unmet health care service needs items. FCC was reported by 69.6% of family members. One-fifth (22.1%) were CSHCN. Thirty percent of parents reported≥4 of 6 anticipatory guidance topics discussed and 32.5% reported≥1 unmet need. FCC was positively associated with anticipatory guidance for all children (OR=1.45; 95% CI 1.19, 1.76), but no relation was found for CSHCN in stratified analyses (OR=1.01; 95% CI .75, 1.37). FCC was associated with reduced unmet needs (OR=.38; 95% CI .31, .46), with consistent findings for both non-CSHCN and CSHCN subgroups. Family-centered care is associated with greater receipt of anticipatory guidance and reduced unmet needs. The association between FCC and anticipatory guidance did not persist for CSHCN, suggesting the need for enhanced understanding of appropriate anticipatory guidance for this population.

  17. A half-century ago physicists missed a major public service opportunity, costing the human race widespread chronic illness and many deaths!

    Lundquist, Marjorie

    2005-03-01

    Radar-pulsed microwave (MW) radiation-helped the Allies win World War II but health concerns soon arose. Alerted to a syndrome resembling mild radiation poisoning,^1 a worried M.D. surveyed radar-exposed workers, finding a high incidence of internal bleeding, 2 leukemia cases in 600 radar operators, 2 brain tumor cases in a 5-man MW research team and many complaints of headache. He sent his report^2 to the Pentagon in 1953. Alarmed Navy officers convened a meeting^3 [mostly of electrical engineers (EEs)] to identify a safe level of MW exposure for servicemen. Biophysicist Herman Schwan attended, playing a major role in establishing 10 mW/cm^2 as a thermally safe MW exposure limit. The IEEE became sole sponsor of ANSI C95 [an early health standard for radiofrequency (RF) exposure] with negative long-term consequences for human health! I review RF health standards development since 1953, comparing what physicists might have done, had they-not EEs-had this responsibility! [See also my technical abstract.] ^1 N.H. Steneck, The Microwave Debate, Cambridge, MA: MIT Press, 1984; p. 33. ^2 J.T. McLaughlin, A Study of Possible Health Hazards from Exposure to Microwave Radiation (Hughes Aircraft, Culver City CA, Feb. 9, 1953). ^3 Biological Effects of Microwaves, meeting minutes (Navy Dept. Conference, Naval Medical Research Institute, Bethesda MD, Apr. 29, 1953).

  18. Correlation Between Expression of Recombinant Proteins and Abundance of H3K4Me3 on the Enhancer of Human Cytomegalovirus Major Immediate-Early Promoter.

    Soo, Benjamin P C; Tay, Julian; Ng, Shirelle; Ho, Steven C L; Yang, Yuansheng; Chao, Sheng-Hao

    2017-08-01

    Role of epigenetic regulation in the control of gene expression is well established. The impact of several epigenetic mechanisms, such as DNA methylation and histone acetylation, on recombinant protein production in mammalian cells has been investigated recently. Here we investigate the correlation between the selected epigenetic markers and five trastuzumab biosimilar-producing Chinese hamster ovary (CHO) cell lines in which the expression of trastuzumab is driven by human cytomegalovirus (HCMV) major immediate-early (MIE) promoter. We chose the producing clones in which transcription was the determinative step for the production of recombinant trastuzumab. We found that the abundance of trimethylation of histone 3 at lysine 4 (H3K4Me3) on the enhancer of HCMV MIE promoter correlated well with the relative titers of recombinant trastuzumab among the clones. Such close correlation was not observed between the recombinant protein and other epigenetic markers examined in our study. Our results demonstrate that the HCMV MIE enhancer-bound H3K4Me3 epigenetic marker may be used as the epigenetic indicator to predict the relative production of recombinant proteins between the producing CHO cell lines.

  19. Liquid Chromatography/Tandem Mass Spectrometry for the Simultaneous Determination of Ursodiol and its Major Metabolites, Tauroursodeoxycholic Acid and Glycoursodeoxycholic Acid in Human Plasma

    M. Ganesan

    2012-01-01

    Full Text Available A rapid and sensitive method is described for the quantification of ursodiol and its major metabolites glycoursodeoxycholic acid (GUDCA and tauroursodeoxycholic acid (TUDCA in human plasma using single internal standard (Ursodeoxycholic Acid d4. Solid phase extraction was performed and chromatographic separation of 5µL injected sample was achieved using Waters Xterra, 5µm column with a mobile phase comprised of methanol and 5 mM ammonium formate with 0.1 % acetic acid ( 70 : 30, v/v . The mass spectrometer was used in negative ion mode and multiple reactions monitoring using electro spray ionization mode as an interface. The method was fully validated and the calibration curves were linear over the concentration range of 25.9 to 15300.1 ng/mL for ursodiol, 2.7 to 1587.5ng/mLfor tauroursodeoxycholicacid and 25.4 to 15040.9 ng/mL for glycoursodeoxycholic acid. The method was sensitive and specific, with the lower limit of quantification of 25.9, 2.7 and 25.4 ng/ml for ursodiol, tauroursodeoxycholic acid and glycoursodeoxycholic acid respectively. The present method includes a simple and rapid sample preparation with shorter analysis run time and less flow rate compared to previously reported methods. The method was applied successfully for a bioequivalence study in healthy subjects.

  20. Overview of the taxonomy and of the major secondary metabolites and their biological activities related to human health of the Laurencia complex (Ceramiales, Rhodophyta from Brazil

    Mutue T. Fujii

    2011-04-01

    Full Text Available In Brazil, the Laurencia complex is represented by twenty taxa: Laurencia s.s. with twelve species, Palisada with four species (including Chondrophycus furcatus now that the proposal of its transference to Palisada is in process, and Osmundea and Yuzurua with two species each. The majority of the Brazilian species of the Laurencia complex have been phylogenetically analyzed by 54 rbcL sequences, including five other Rhodomelacean species as outgroups. The analysis showed that the Laurencia complex is monophyletic with high posterior probability value. The complex was separated into five clades, corresponding to the genera: Chondrophycus, Laurencia, Osmundea, Palisada, and Yuzurua. A bibliographical survey of the terpenoids produced by Brazilian species showed that only six species of Laurencia and five of Palisada (including C. furcatcus have been submitted to chemical analysis with 48 terpenoids (47 sesquiterpenes and one triterpene isolated. No diterpenes were found. Of the total, 23 sesquiterpenes belong to the bisabolane class and eighteen to the chamigrene type, whose biochemical precursor is bisabolane, two are derived from lauranes and four are triquinols. Despite the considerable number of known terpenes and their ecological and pharmacological importance, few experimental biological studies have been performed. In this review, only bioactivities related to human health were considered.

  1. The Isolation of Novel Phage Display-Derived Human Recombinant Antibodies Against CCR5, the Major Co-Receptor of HIV

    Shimoni, Moria; Herschhorn, Alon; Britan-Rosich, Yelena; Kotler, Moshe; Benhar, Itai

    2013-01-01

    Abstract Selecting for antibodies against specific cell-surface proteins is a difficult task due to many unrelated proteins that are expressed on the cell surface. Here, we describe a method to screen antibody-presenting phage libraries against native cell-surface proteins. We applied this method to isolate antibodies that selectively recognize CCR5, which is the major co-receptor for HIV entry (consequently, playing a pivotal role in HIV transmission and pathogenesis). We employed a phage screening strategy by using cells that co-express GFP and CCR5, along with an excess of control cells that do not express these proteins (and are otherwise identical to the CCR5-expressing cells). These control cells are intended to remove most of the phages that bind the cells nonspecifically; thus leading to an enrichment of the phages presenting anti-CCR5-specific antibodies. Subsequently, the CCR5-presenting cells were quantitatively sorted by flow cytometry, and the bound phages were eluted, amplified, and used for further successive selection rounds. Several different clones of human single-chain Fv antibodies that interact with CCR5-expressing cells were identified. The most specific monoclonal antibody was converted to a full-length IgG and bound the second extracellular loop of CCR5. The experimental approach presented herein for screening for CCR5-specific antibodies can be applicable to screen antibody-presenting phage libraries against any cell-surface expressed protein of interest. PMID:23941674

  2. 10-Hydroxy-2-decenoic Acid, a Major Fatty Acid from Royal Jelly, Inhibits VEGF-Induced Angiogenesis in Human Umbilical Vein Endothelial Cells

    Hiroshi Izuta

    2009-01-01

    Full Text Available Vascular endothelial growth factor (VEGF is reported to be a potent pro-angiogenic factor that plays a pivotal role in both physiological and pathological angiogenesis. Royal jelly (RJ is a honeybee product containing various proteins, sugars, lipids, vitamins and free amino acids. 10-Hydroxy-2-decenoic acid (10HDA, a major fatty acid component of RJ, is known to have various pharmacological effects; its antitumor activity being especially noteworthy. However, the mechanism underlying this effect is unclear. We examined the effect of 10HDA on VEGF-induced proliferation, migration and tube formation in human umbilical vein endothelial cells (HUVECs. Our findings showed that, 10HDA at 20 µM or more significantly inhibited such proliferation, migration and tube formation. Similarly, 10 µM GM6001, a matrix metalloprotease inhibitor, prevented VEGF-induced migration and tube formation. These findings indicate that 10HDA exerts an inhibitory effect on VEGF-induced angiogenesis, partly by inhibiting both cell proliferation and migration. Further experiments will be needed to clarify the detailed mechanism.

  3. Glucocorticoids facilitate the transcription from the human cytomegalovirus major immediate early promoter in glucocorticoid receptor- and nuclear factor-I-like protein-dependent manner

    Inoue-Toyoda, Maki; Kato, Kohsuke; Nagata, Kyosuke; Yoshikawa, Hiroyuki

    2015-01-01

    Human cytomegalovirus (HCMV) is a common and usually asymptomatic virus agent in healthy individuals. Initiation of HCMV productive infection depends on expression of the major immediate early (MIE) genes. The transcription of HCMV MIE genes is regulated by a diverse set of transcription factors. It was previously reported that productive HCMV infection is triggered probably by elevation of the plasma hydroxycorticoid level. However, it is poorly understood whether the transcription of MIE genes is directly regulated by glucocorticoid. Here, we found that the dexamethasone (DEX), a synthetic glucocorticoid, facilitates the transcription of HCMV MIE genes through the MIE promoter and enhancer in a glucocorticoid receptor (GR)-dependent manner. By competitive EMSA and reporter assays, we revealed that an NF-I like protein is involved in DEX-mediated transcriptional activation of the MIE promoter. Thus, this study supports a notion that the increased level of hydroxycorticoid in the third trimester of pregnancy reactivates HCMV virus production from the latent state. - Highlights: • DEX facilitates the transcription from the HCMV MIE promoter. • GR is involved in DEX-dependent transcription from the HCMV MIE promoter. • A 17 bp repeat is responsible for the HCMV MIE promoter activation by DEX. • An NF-I-like protein is involved in the HCMV MIE promoter activation by DEX

  4. Expression of bovine non-classical major histocompatibility complex class I proteins in mouse P815 and human K562 cells.

    Parasar, Parveen; Wilhelm, Amanda; Rutigliano, Heloisa M; Thomas, Aaron J; Teng, Lihong; Shi, Bi; Davis, William C; Suarez, Carlos E; New, Daniel D; White, Kenneth L; Davies, Christopher J

    2016-08-01

    Major histocompatibility complex class I (MHC-I) proteins can be expressed as cell surface or secreted proteins. To investigate whether bovine non-classical MHC-I proteins are expressed as cell surface or secreted proteins, and to assess the reactivity pattern of monoclonal antibodies with non-classical MHC-I isoforms, we expressed the MHC proteins in murine P815 and human K562 (MHC-I deficient) cells. Following antibiotic selection, stably transfected cell lines were stained with H1A or W6/32 antibodies to detect expression of the MHC-I proteins by flow cytometry. Two non-classical proteins (BoLA-NC1*00501 and BoLA-NC3*00101) were expressed on the cell surface in both cell lines. Surprisingly, the BoLA-NC4*00201 protein was expressed on the cell membrane of human K562 but not mouse P815 cells. Two non-classical proteins (BoLA-NC1*00401, which lacks a transmembrane domain, and BoLA-NC2*00102) did not exhibit cell surface expression. Nevertheless, Western blot analyses demonstrated expression of the MHC-I heavy chain in all transfected cell lines. Ammonium-sulfate precipitation of proteins from culture supernatants showed that BoLA-NC1*00401 was secreted and that all surface expressed proteins where shed from the cell membrane by the transfected cells. Interestingly, the surface expressed MHC-I proteins were present in culture supernatants at a much higher concentration than BoLA-NC1*00401. This comprehensive study shows that bovine non-classical MHC-I proteins BoLA-NC1*00501, BoLA-NC3*00101, and BoLA-NC4*00201 are expressed as surface isoforms with the latter reaching the cell membrane only in K562 cells. Furthermore, it demonstrated that BoLA-NC1*00401 is a secreted isoform and that significant quantities of membrane associated MHC-I proteins can be shed from the cell membrane. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Evidence of dengue virus transmission and factors associated with the presence of anti-dengue virus antibodies in humans in three major towns in Cameroon.

    Maurice Demanou

    2014-07-01

    Full Text Available Dengue is not well documented in Africa. In Cameroon, data are scarce, but dengue infection has been confirmed in humans. We conducted a study to document risk factors associated with anti-dengue virus Immunoglobulin G seropositivity in humans in three major towns in Cameroon.A cross sectional survey was conducted in Douala, Garoua and Yaounde, using a random cluster sampling design. Participants underwent a standardized interview and were blood sampled. Environmental and housing characteristics were recorded. Randomized houses were prospected to record all water containers, and immature stages of Aedes mosquitoes were collected. Sera were screened for anti-dengue virus IgG and IgM antibodies. Risk factors of seropositivity were tested using logistic regression methods with random effects. Anti-dengue IgG were found from 61.4% of sera in Douala (n = 699, 24.2% in Garoua (n = 728 and 9.8% in Yaounde (n = 603. IgM were found from 0.3% of Douala samples, 0.1% of Garoua samples and 0.0% of Yaounde samples. Seroneutralization on randomly selected IgG positive sera showed that 72% (n = 100 in Douala, 80% (n = 94 in Garoua and 77% (n = 66 in Yaounde had antibodies specific for dengue virus serotype 2 (DENV-2. Age, temporary house walls materials, having water-storage containers, old tires or toilets in the yard, having no TV, having no air conditioning and having travelled at least once outside the city were independently associated with anti-dengue IgG positivity in Douala. Age, having uncovered water containers, having no TV, not being born in Garoua and not breeding pigs were significant risk factors in Garoua. Recent history of malaria, having banana trees and stagnant water in the yard were independent risk factors in Yaounde.In this survey, most identified risk factors of dengue were related to housing conditions. Poverty and underdevelopment are central to the dengue epidemiology in Cameroon.

  6. Roles of different IRES-dependent FGF2 isoforms in the acquisition of the major aggressive features of human metastatic melanoma.

    Andreucci, Elena; Bianchini, Francesca; Biagioni, Alessio; Del Rosso, Mario; Papucci, Laura; Schiavone, Nicola; Magnelli, Lucia

    2017-01-01

    Fibroblast growth factor 2 (FGF2) is involved in many physiological and pathological processes. Fgf2 deregulation contributes to the acquisition of malignant features of melanoma and other cancers. FGF2 is an alternative translation product expressed as five isoforms, a low-molecular-weight (18 KDa) and four high-molecular-weight (22, 22.5, 24, 34 KDa) isoforms, with different subcellular distributions. An internal ribosomal entry site (IRES) in its mRNA controls the translation of all the isoforms with the exception for the cap-dependent 34 KDa. The 18-KDa isoform has been extensively studied, while very few is known about the roles of high molecular weight isoforms. FGF2 is known to promote melanoma development and progression. To disclose the differential contribution of FGF2 isoforms in melanoma, we forced the expression of IRES-dependent low-molecular-weight (LMW, 18 KDa) and high-molecular-weight (HMW, 22, 22.5, 24 KDa) isoforms in a human metastatic melanoma cell line. This comparative study highlights that, while LMW isoform confers stem-like features to melanoma cells and promotes angiogenesis, HMW isoforms induce higher migratory ability and contribute to tumor perfusion by promoting vasculogenic mimicry (VM) when endothelial cell-driven angiogenesis is lacking. To conclude, FGF2 isoforms mainly behave in specific, antithetical manners, but can cooperate in different steps of tumor progression, providing melanoma cells with major malignant features. FGF2 is an alternative translation product expressed as different isoforms termed LMW and HMW. FGF2 is involved in melanoma development and progression. HMW FGF2 isoforms enhance in vitro motility of melanoma cells. LMW FGF2 confers stem-like features and increases in vivo metastasization. LMW FGF2 promotes angiogenesis while HMW FGF2 induces vasculogenic mimicry.

  7. Impaired control of body cooling during heterothermia represents the major energetic constraint in an aging non-human primate exposed to cold.

    Jeremy Terrien

    2009-10-01

    Full Text Available Daily heterothermia is used by small mammals for energy and water savings, and seems to be preferentially exhibited during winter rather than during summer. This feature induces a trade-off between the energy saved during daily heterothermia and the energy cost of arousal, which can impact energy balance and survival under harsh environmental conditions. Especially, aging may significantly affect such trade off during cold-induced energy stress, but direct evidences are still lacking. We hypothesized that aging could alter the energetics of daily heterothermia, and that the effects could differ according to season. In the gray mouse lemur (Microcebus murinus, a non-human primate species which exhibits daily heterothermia, we investigated the effects of exposures to 25 and 12 degrees C on body composition, energy balance, patterns of heterothermia and water turnover in adult (N = 8 and aged animals (N = 7 acclimated to winter-like or summer-like photoperiods. Acclimation to summer prevented animals from deep heterothermia, even during aging. During winter, adult animals at 12 degrees C and aged animals at 25 degrees C exhibited low levels of energy expenditure with minor modulations of heterothermia. The major effects of cold were observed during winter, and were particularly pronounced in aged mouse lemurs which exhibited deep heterothermia phases. Body composition was not significantly affected by age and could not explain the age-related differences in heterothermia patterns. However, aging was associated with increased levels of energy expenditure during cold exposure, in concomitance with impaired energy balance. Interestingly, increased energy expenditure and depth of heterothermia phases were strongly correlated. In conclusion, it appeared that the exhibition of shallow heterothermia allowed energy savings during winter in adult animals only. Aged animals exhibited deep heterothermia and increased levels of energy expenditure, impairing

  8. Determination of growth hormone releasing peptides (GHRP) and their major metabolites in human urine for doping controls by means of liquid chromatography mass spectrometry.

    Thomas, Andreas; Höppner, Sebastian; Geyer, Hans; Schänzer, Wilhelm; Petrou, Michael; Kwiatkowska, Dorota; Pokrywka, Andrzej; Thevis, Mario

    2011-08-01

    A family of small peptides has reached the focus of doping controls representing a comparably new strategy for cheating sportsmen. These growth hormone releasing peptides (GHRP) are orally active and induce an increased production of endogenous growth hormone (GH). While the established test for exogenous GH fails, the misuse of these prohibited substances remains unrecognized. The present study provides data for the efficient extraction of a variety of known drug candidates (GHRP-1, GHRP-2, GHRP-4, GHRP-5, GHRP-6, alexamorelin, ipamorelin, and hexarelin) from human urine with subsequent mass spectrometric detection after liquid chromatographic separation. The used method potentially enables the retrospective evaluation of the acquired data for unknown metabolites by means of a non-targeted approach with high-resolution/high-accuracy full-scan mass spectrometry with additional higher collision energy dissociation experiments. This is of great importance due to the currently unknown metabolism of most of the targets and, thus, the method is focused on the intact peptidic drugs. Only the already characterised major metabolite of GHRP-2 (D-Ala-D-2-naphthylAla-L-Ala, as well as its stable isotope-labelled analogue) was synthesised and implemented in the detection assay. Method validation for qualitative purpose was performed with respect to specificity, precision (<20%), intermediate precision (<20%), recovery (47-95%), limit of detection (0.2-1 ng/mL), linearity, ion suppression and stability. Two stable isotope-labelled internal standards were used (deuterium-labelled GHRP-4 and GHRP-2 metabolite). The proof-of-principle was obtained by the analysis of excretion study urine samples obtained from a single oral administration of 10 mg of GHRP-2. Here, the known metabolite was detectable over 20 h after administration while the intact drug was not observed.

  9. The catalytic chain of human complement subcomponent C1r. Purification and N-terminal amino acid sequences of the major cyanogen bromide-cleavage fragments.

    Arlaud, G J; Gagnon, J; Porter, R R

    1982-01-01

    1. The a- and b-chains of reduced and alkylated human complement subcomponent C1r were separated by high-pressure gel-permeation chromatography and isolated in good yield and in pure form. 2. CNBr cleavage of C1r b-chain yielded eight major peptides, which were purified by gel filtration and high-pressure reversed-phase chromatography. As determined from the sum of their amino acid compositions, these peptides accounted for a minimum molecular weight of 28 000, close to the value 29 100 calculated from the whole b-chain. 3. N-Terminal sequence determinations of C1r b-chain and its CNBr-cleavage peptides allowed the identification of about two-thirds of the amino acids of C1r b-chain. From our results, and on the basis of homology with other serine proteinases, an alignment of the eight CNBr-cleavage peptides from C1r b-chain is proposed. 4. The residues forming the 'charge-relay' system of the active site of serine proteinases (His-57, Asp-102 and Ser-195 in the chymotrypsinogen numbering) are found in the corresponding regions of C1r b-chain, and the amino acid sequence around these residues has been determined. 5. The N-terminal sequence of C1r b-chain has been extended to residue 60 and reveals that C1r b-chain lacks the 'histidine loop', a disulphide bond that is present in all other known serine proteinases.

  10. Emerging organisational models of primary healthcare and unmet needs for care: insights from a population-based survey in Quebec province

    Levesque Jean-Frédéric

    2012-07-01

    Full Text Available Abstract Background Reform of primary healthcare (PHC organisations is underway in Canada. The capacity of various types of PHC organizations to respond to populations’ needs remains to be assessed. The main objective of this study was to evaluate the association of PHC affiliation with unmet needs for care. Methods Population-based survey of 9205 randomly selected adults in two regions of Quebec, Canada. Outcomes Self-reported unmet needs for care and identification of the usual source of PHC. Results Among eligible adults, 18 % reported unmet needs for care in the last six months. Reasons reported for unmet needs were: waiting times (59 % of cases; unavailability of usual doctor (42 %; impossibility to obtain an appointment (36 %; doctors not accepting new patients (31 %. Regression models showed that unmet needs were decreasing with age and was lower among males, the least educated, and unemployed or retired. Controlling for other factors, unmet needs were higher among the poor and those with worse health status. Having a family doctor was associated with fewer unmet needs. People reporting a usual source of care in the last two-years were more likely to report unmet need for care. There were no differences in unmet needs for care across types of PHC organisations when controlling for affiliation with a family physician. Conclusion Reform models of primary healthcare consistent with the medical home concept did not differ from other types of organisations in our study. Further research looking at primary healthcare reform models at other levels of implementation should be done.

  11. Determinants of unmet needs for healthcare and sexual health counselling among Ugandan university students with same-sex sexuality experience.

    Larsson, Markus; Ross, Michael W; Tumwine, Gilbert; Agardh, Anette

    2016-01-01

    Research from sub-Saharan Africa has shown that persons with same-sex sexuality experience are at elevated risk for ill health due to sexual risk taking, stigma, and discrimination. However, studies of healthcare seeking among young people in this region with same-sex sexuality experience are limited. To identify determinants of unmet healthcare and sexual health counselling needs, respectively, among Ugandan university students with experience of same-sex sexuality. In 2010, 1,954 Ugandan university students completed a questionnaire assessing socio-demographic factors, mental health, alcohol usage, sexual behaviours, and healthcare seeking. The study population consisted of those 570 who reported ever being in love with, sexually attracted to, sexually fantasised about, or sexually engaged with someone of the same sex. Findings showed that 56% and 30% reported unmet healthcare and sexual health counselling needs, respectively. Unmet healthcare needs were associated with poor mental health and exposure to sexual coercion (OR 3.9, 95% confidence intervals [CI]: 2.7-5.7; OR 2.0, 95% CI: 1.3-3.0, respectively). Unmet sexual health counselling needs were significantly associated with poor mental health (OR 3.2, 95% CI: 2.1-4.8), exposure to sexual coercion (OR 2.6, 95% CI: 1.7-3.9), frequent heavy episodic drinking (OR 3.3, 95% CI: 1.9-5.8), and number of sexual partners (OR 1.9, 95% CI: 1.04-3.3). The associations between poor mental health, sexual coercion, and unmet healthcare needs (AOR 4.2, 95% CI: 2.1-8.5; AOR 2.8, 95% CI: 1.3-5.8) and unmet needs for sexual health counselling (AOR 3.3, 95% CI: 1.6-7.1; AOR 2.7, 95% CI: 1.4-5.4) persisted after adjustment for socio-demographic factors, number of sexual partners, and frequent heavy episodic drinking. These findings indicate that exposure to sexual coercion and poor mental health may influence healthcare seeking behaviours of same-sex sexuality experienced students. Targeted interventions that integrate mental

  12. Determinants of unmet needs for healthcare and sexual health counselling among Ugandan university students with same-sex sexuality experience

    Markus Larsson

    2016-03-01

    Full Text Available Background: Research from sub-Saharan Africa has shown that persons with same-sex sexuality experience are at elevated risk for ill health due to sexual risk taking, stigma, and discrimination. However, studies of healthcare seeking among young people in this region with same-sex sexuality experience are limited. Objective: To identify determinants of unmet healthcare and sexual health counselling needs, respectively, among Ugandan university students with experience of same-sex sexuality. Design: In 2010, 1,954 Ugandan university students completed a questionnaire assessing socio-demographic factors, mental health, alcohol usage, sexual behaviours, and healthcare seeking. The study population consisted of those 570 who reported ever being in love with, sexually attracted to, sexually fantasised about, or sexually engaged with someone of the same sex. Results: Findings showed that 56% and 30% reported unmet healthcare and sexual health counselling needs, respectively. Unmet healthcare needs were associated with poor mental health and exposure to sexual coercion (OR 3.9, 95% confidence intervals [CI]: 2.7–5.7; OR 2.0, 95% CI: 1.3–3.0, respectively. Unmet sexual health counselling needs were significantly associated with poor mental health (OR 3.2, 95% CI: 2.1–4.8, exposure to sexual coercion (OR 2.6, 95% CI: 1.7–3.9, frequent heavy episodic drinking (OR 3.3, 95% CI: 1.9–5.8, and number of sexual partners (OR 1.9, 95% CI: 1.04–3.3. The associations between poor mental health, sexual coercion, and unmet healthcare needs (AOR 4.2, 95% CI: 2.1–8.5; AOR 2.8, 95% CI: 1.3–5.8 and unmet needs for sexual health counselling (AOR 3.3, 95% CI: 1.6–7.1; AOR 2.7, 95% CI: 1.4–5.4 persisted after adjustment for socio-demographic factors, number of sexual partners, and frequent heavy episodic drinking. Conclusions: These findings indicate that exposure to sexual coercion and poor mental health may influence healthcare seeking behaviours of

  13. Metabolism of aflatoxin B1 and identification of the major aflatoxin B1-DNA adducts formed in cultured human bronchus and colon

    Autrup, Herman; Essigmann, John M.; Croy, Robert G.

    1979-01-01

    Aflatoxin B1 and benzo(a)pyrene were activated by both cultured human bronchus and human colon as measured by binding to cellular DNA and protein. The binding of aflatoxin B1 to DNA was dose dependent, and the level of binding was higher in cultured human bronchus than it was in the colon. When c...

  14. Clinical roundtable monograph: Unmet needs in the management of chronic myelogenous leukemia.

    Jabbour, Elias J; Bixby, Dale; Akard, Luke P

    2012-12-01

    Approximately 5,000 cases of chronic myelogenous leukemia (CML) are diagnosed each year in the United States. The introduction of tyrosine kinase inhibitors (TKIs) has dramatically improved survival time for many CML patients. Current first-line treatment options include imatinib and the second-generation agents nilotinib and dasatinib. Second- and third-line agents include nilotinib, dasatinib, bosutinib, and the new agent ponatinib. Despite the effectiveness of TKIs, some patients develop resistance or intolerance to these agents. A number of mutations of the BCR-ABL gene have been identified and are associated with TKI resistance. Patients may benefit from switching to a second-line TKI, undergoing hematopoietic stem cell transplant, or receiving newly emerging agents. Although early response is associated with improved patient outcome, clinicians lack tests that can determine which patients will benefit from which therapies. To ensure adequate response, patients should be monitored by both polymerase chain reaction and cytogenetic analysis of the bone marrow. This roundtable monograph reviews key unmet needs in patients with CML related to disease management and treatment options.

  15. Nurses' burnout and unmet nursing care needs of patients' relatives in a Turkish State Hospital.

    Tekindal, Benian; Tekindal, Mustafa Agah; Pinar, Gul; Ozturk, Filiz; Alan, Sumeyra

    2012-02-01

    One of the biggest problems of work life today is burnout. With burnout, satisfaction of clients and service givers reduces. In this study, burnout levels of nurses working in the internal, surgical and intensive care units of a university hospital and the unmet needs of the patients' relatives related to nursing care were investigated. In the study, 225 nurses and 222 relatives of patients constituted the sample group of this study. Three separate forms were used in the study, namely, Nurse and Patient Relative Identification Form, the Maslach Burnout Inventory and the Nursing Services Satisfaction Inventory. In the study, burnout levels of the nurses were found to be high. Conditions like younger ages, scarcity of experience in the profession, lower levels of education, having chosen the profession and the unit they work in not willingly and working in environments like intensive care increase the burnout and as a result, expectations of the relatives of patients from nursing care are not fully met. Some suggestions have been made to make some regulations to prevent the burnout of nurses and to increase the satisfaction of relatives. © 2012 Blackwell Publishing Asia Pty Ltd.

  16. Measuring household consumption and waste in unmetered, intermittent piped water systems

    Kumpel, Emily; Woelfle-Erskine, Cleo; Ray, Isha; Nelson, Kara L.

    2017-01-01

    Measurements of household water consumption are extremely difficult in intermittent water supply (IWS) regimes in low- and middle-income countries, where water is delivered for short durations, taps are shared, metering is limited, and household storage infrastructure varies widely. Nonetheless, consumption estimates are necessary for utilities to improve water delivery. We estimated household water use in Hubli-Dharwad, India, with a mixed-methods approach combining (limited) metered data, storage container inventories, and structured observations. We developed a typology of household water access according to infrastructure conditions based on the presence of an overhead storage tank and a shared tap. For households with overhead tanks, container measurements and metered data produced statistically similar consumption volumes; for households without overhead tanks, stored volumes underestimated consumption because of significant water use directly from the tap during delivery periods. Households that shared taps consumed much less water than those that did not. We used our water use calculations to estimate waste at the household level and in the distribution system. Very few households used 135 L/person/d, the Government of India design standard for urban systems. Most wasted little water even when unmetered, however, unaccounted-for water in the neighborhood distribution systems was around 50%. Thus, conservation efforts should target loss reduction in the network rather than at households.

  17. Pricing Unmetered Irrigation Water under Asymmetric Information and Full Cost Recovery

    Alban Lika

    2016-12-01

    Full Text Available The objective of this study is to define an efficient pricing scheme for irrigation water in conditions of unmetered water use. The study is based on a principal-agent model and identifies a menu of contracts, defined as a set of payments and share of irrigated area, able to provide incentives for an efficient use of the resource by maximizing social welfare. The model is applied in the case study of the Çukas region (Albania where irrigation water is not metered. The results demonstrate that using a menu of contracts makes it possible to define a second best solution that may improve the overall social welfare derived from irrigation water use compared with the existing pricing structure, though, in the specific case study, the improvement is small. Furthermore, the results also suggest that irrigation water pricing policy needs to take into account different farm types, and that appropriate contract-type pricing schemes have a potential role in providing incentives to farmers to make irrigation choices to the social optimum.

  18. Allergy in Hong Kong: an unmet need in service provision and training.

    Chan, Y T; Ho, H K; Lai, Christopher K W; Lau, C S; Lau, Y L; Lee, T H; Leung, T F; Wong, Gary W K; Wu, Y Y

    2015-02-01

    Many children in Hong Kong have allergic diseases and epidemiological data support a rising trend. Only a minority of children will grow out of their allergic diseases, so the heavy clinical burden will persist into adulthood. In an otherwise high-quality health care landscape in Hong Kong, allergy services and training are a seriously unmet need. There is one allergy specialist for 1.5 million people, which is low not only compared with international figures, but also compared with most other specialties in Hong Kong. The ratio of paediatric and adult allergists per person is around 1:460 000 and 1:2.8 million, respectively, so there is a severe lack of adult allergists, while the paediatric allergists only spend a fraction of their time working with allergy. There are no allergists and no dedicated allergy services in adult medicine in public hospitals. Laboratory support for allergy and immunology is not comprehensive and there is only one laboratory in the public sector supervised by accredited immunologists. These findings clearly have profound implications for the profession and the community of Hong Kong and should be remedied without delay. Key recommendations are proposed that could help bridge the gaps, including the creation of two new pilot allergy centres in a hub-and-spoke model in the public sector. This could require recruitment of specialists from overseas to develop the process if there are no accredited allergy specialists in Hong Kong who could fulfil this role.

  19. Mentorship Programs in Radiation Oncology Residency Training Programs: A Critical Unmet Need

    Dhami, Gurleen; Gao, Wendy; Gensheimer, Michael F. [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States); Trister, Andrew D. [Sage Bionetworks, Seattle, Washington (United States); Kane, Gabrielle [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States); Zeng, Jing, E-mail: jzeng13@uw.edu [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States)

    2016-01-01

    Purpose: To conduct a nationwide survey to evaluate the current status of resident mentorship in radiation oncology. Methods and Materials: An anonymous electronic questionnaire was sent to all residents and recent graduates at US Accreditation Council for Graduate Medical Education–accredited radiation oncology residency programs, identified in the member directory of the Association of Residents in Radiation Oncology. Factors predictive of having a mentor and satisfaction with the mentorship experience were identified using univariate and multivariate analyses. Results: The survey response rate was 25%, with 85% of respondents reporting that mentorship plays a critical role in residency training, whereas only 53% had a current mentor. Larger programs (≥10 faculty, P=.004; and ≥10 residents, P<.001) were more likely to offer a formal mentorship program, which makes it more likely for residents to have an active mentor (88% vs 44%). Residents in a formal mentoring program reported being more satisfied with the overall mentorship experience (univariate odds ratio 8.77, P<.001; multivariate odds ratio 5, P<.001). On multivariate analysis, women were less likely to be satisfied with the mentorship experience. Conclusions: This is the first survey focusing on the status of residency mentorship in radiation oncology. Our survey highlights the unmet need for mentorship in residency programs.

  20. County-level poverty is equally associated with unmet health care needs in rural and urban settings.

    Peterson, Lars E; Litaker, David G

    2010-01-01

    Regional poverty is associated with reduced access to health care. Whether this relationship is equally strong in both rural and urban settings or is affected by the contextual and individual-level characteristics that distinguish these areas, is unclear. Compare the association between regional poverty with self-reported unmet need, a marker of health care access, by rural/urban setting. Multilevel, cross-sectional analysis of a state-representative sample of 39,953 adults stratified by rural/urban status, linked at the county level to data describing contextual characteristics. Weighted random intercept models examined the independent association of regional poverty with unmet needs, controlling for a range of contextual and individual-level characteristics. The unadjusted association between regional poverty levels and unmet needs was similar in both rural (OR = 1.06 [95% CI, 1.04-1.08]) and urban (OR = 1.03 [1.02-1.05]) settings. Adjusting for other contextual characteristics increased the size of the association in both rural (OR = 1.11 [1.04-1.19]) and urban (OR = 1.11 [1.05-1.18]) settings. Further adjustment for individual characteristics had little additional effect in rural (OR = 1.10 [1.00-1.20]) or urban (OR = 1.11 [1.01-1.22]) settings. To better meet the health care needs of all Americans, health care systems in areas with high regional poverty should acknowledge the relationship between poverty and unmet health care needs. Investments, or other interventions, that reduce regional poverty may be useful strategies for improving health through better access to health care. © 2010 National Rural Health Association.

  1. Unmet need for modern contraceptives and associated factors among women in the extended postpartum period in Dessie town, Ethiopia

    Tegegn, Masresha; Arefaynie, Mastewal; Tiruye, Tenaw Yimer

    2017-01-01

    Background The contraceptive use of women in the extended postpartum period is usually different from other times in a woman’s life cycle due to the additional roles and presence of emotional changes. However, there is lack of evidence regarding women contraceptive need during this period and the extent they met their need. Therefore, the objective of this study was to assess unmet need for modern contraceptives and associated factors among women during the extended postpartum period in Dessi...

  2. Functional characterization of the 1,5-benzodiazepine clobazam and its major active metabolite N-desmethylclobazam at human GABA(A receptors expressed in Xenopus laevis oocytes.

    Harriet Hammer

    Full Text Available The 1,5-benzodiazepine clobazam is indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in patients 2 years of age or older in the United States, and for treatment of anxiety and various forms of epilepsy elsewhere. Clobazam has been reported to exhibit different in vivo adverse effects and addiction liability profile than the classic 1,4-benzodiazepines. In this study, it was investigated whether the in vitro pharmacological properties of clobazam and its major active metabolite N-desmethylclobazam could explain some of these clinical differences. The functional properties of the two 1,5-benzodiazepines were characterized at the human γ-aminobutyric acid type A receptor (GABA(AR subtypes α1β2γ(2S, α2β2γ(2S, α3β2γ(2S, α5β2γ(2S and α6β2δ expressed in Xenopus laevis oocytes by use of two-electrode voltage-clamp electrophysiology and compared to those exhibited by the 1,4-benzodiazepine clonazepam. All three compounds potentiated GABA EC20-evoked responses through the α(1,2,3,5β2γ(2S GABA(ARs in a reversible and concentration-dependent manner, with each displaying similar EC50 values at the four subtypes. Furthermore, the degrees of potentiation of the GABA EC20 currents through the four receptors mediated by saturating modulator concentrations did not differ substantially for any of the three benzodiazepines. The three compounds were substantially less potent (200-3900 fold as positive allosteric modulators at the α6β2δ GABA(AR than at the α(1,2,3,5β2γ(2S receptors. Interestingly, however, clobazam and especially N-desmethylclobazam were highly efficacious potentiators of α6β2δ receptor signaling. Although this activity component is unlikely to contribute to the in vivo effects of clobazam/N-desmethylclobazam, the 1,5-benzodiazepine could constitute an interesting lead for novel modulators targeting this low-affinity binding site in GABAARs. In conclusion, the non

  3. Relationship between health-related quality of life, perceived family support and unmet health needs in adult patients with multimorbidity attending primary care in Portugal: a multicentre cross-sectional study.

    Prazeres, Filipe; Santiago, Luiz

    2016-11-11

    Multimorbidity has a high prevalence in the primary care context and it is frequently associated with worse health-related quality of life (HRQoL). Few studies evaluated the variables that could have a potential effect on HRQoL of primary care patients with multimorbidity. The purpose of this study, the first of its kind ever undertaken in Portugal, is to analyse the relationship between multimorbidity, health-related quality of life, perceived family support and unmet health needs in adult patients attending primary care. Multicentre, cross-sectional survey conducted among primary care patients with multimorbidity. It included 521 participants (64.1 % females) who met the inclusion criteria. HRQoL was evaluated using the Portuguese Short Form-12 Health Status Questionnaire. The Portuguese Family APGAR was used to measure the perceived family support. A patients' unmet health needs questionnaire was used. The unmet needs for medical, surgical and dental care; prescription medications; mental healthcare or counselling; and eyeglasses or other technical aid was assessed. Descriptive and multivariate analyses were performed. The sample had an overall average of 4.5 chronic health problems. Increased multimorbidity levels were linked to worse health-related quality of life, particularly the physical health. Some variables were confirmed as playing a role on health-related quality of life. Male patients with high monthly incomes and highly functional families had better physical and mental health. High levels of education and the presence of asthma were also associated with better physical health. Contrariwise, elderly patients with high levels of multimorbidity and with osteoarthritis had lower physical health. The majority of the patients did not have unmet health needs. When health needs were stated they were mostly for generalist medical care, dental care, and eyeglasses/other technical aid. Financial insufficiency was the primary reason for not fulfilling their

  4. A cross-sectional study of parental awareness of and reasons for lack of health insurance among minority children, and the impact on health, access to care, and unmet needs.

    Flores, Glenn; Lin, Hua; Walker, Candy; Lee, Michael; Portillo, Alberto; Henry, Monica; Fierro, Marco; Massey, Kenneth

    2016-03-22

    of uninsured minority children are unaware that their children are Medicaid/CHIP-eligible. These uninsured children have suboptimal health, impaired access to care, and major unmet needs. The child's health causes considerable family financial burden, and one in 10 parents ceased work. The study findings indicate urgent needs for better parental education about Medicaid/CHIP, and for improved Medicaid/CHIP outreach and enrollment.

  5. Unmet Supportive Care Needs among Breast Cancer Survivors of Community-Based Support Group in Kuching, Sarawak

    Emmanuel Joseph Fong

    2016-01-01

    Full Text Available Background. Recognizing the needs of cancer survivors is one of the important aspects in healthcare delivery. This study aimed to determine the prevalence of unmet supportive care needs and its associated factors among the breast cancer survivors of community-based support group in Kuching, Sarawak. Materials and Methods. This was a cross-sectional study using Supportive Care Needs Survey (SCNS-SF34. All the members of community-based breast cancer support groups in Kuching were invited. A total of 101 respondents were face-to-face interviewed after the consent was obtained. Data was entered and analyzed using SPSS version 20. Results. The respondents endorsed health system and information domain with the highest mean score (2.48; 95% CI: 2.32–2.64. Top 10 items with “moderate to high” level unmet needs had a prevalence of 14.9% to 34.7% of respondents indicating need. Significantly higher level of unmet needs was associated with survivors who were younger (less than 60 years old, had higher education attainment, were unemployed, had survival duration of up to 5 years, and were undergoing active treatment. Conclusion. Systematic delivery of health information which is targeted, culturally sensitive, and linguistically appropriate for addressing younger age, education level, employment status, length of survivorship, and treatment stage should be considered not only at hospital-based setting but also at the community-based support groups.

  6. Association between unmet needs and quality of life in hospitalised cancer patients no longer receiving anti-cancer treatment.

    Bužgová, R; Hajnová, E; Sikorová, L; Jarošová, D

    2014-09-01

    Assessing the quality of life and unmet needs of cancer patients is an integral part of palliative care. This cross-sectional study sought to determine whether there is an association between quality of life and unmet needs, anxiety and depression in cancer patients who are no longer receiving anti-cancer treatment. The sample consisted of 93 patients from the oncology department at the University Hospital in Ostrava for whom further cancer treatment had been terminated as ineffective in halting the progression of their cancer. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the Patient Needs Assessment in Palliative Care (PNAP) questionnaire, and the Hospital Anxiety and Depression Scale (HADS) were used to collect data. The overall quality of life score was quite low at 46. Most unmet needs were defined in terms of physical, psychological or spiritual needs. Correlations were found between impaired quality of life and lower Karnofsky scores (r = 0.50); increased physical (r = 0.52), psychological (r = 0.44) and spiritual (r = 0.36) needs; and higher levels of anxiety (r = -0.30) and depression (r = -0.68). Effective management of patients' physical (pain, fatigue and depression), psychological and spiritual needs may improve their quality of life. © 2014 John Wiley & Sons Ltd.

  7. Poverty in the midst of plenty: unmet needs and distribution of health care resources in South Korea.

    Jongho Heo

    Full Text Available BACKGROUND: The unmet needs for health care have been used as an alternative measurement to monitor equity in health services. We sought to examine contextual influences on unmet needs for health care whereas precedent studies have been focused on individual characteristics on them. METHODS AND FINDINGS: The current study conducted multilevel logistic regression analysis to assess the effects of individual- and contextual-level predictors in meeting individual health care needs in South Korea. We sampled 7,200 individuals over the age of 19 in the Fourth Korea National Health and Nutrition Examination Survey in 2009. Included in the regression model were individual predictors such as demographic variables, socio-economic status, and self-rated health; the density of beds and physicians in public and private sectors within different regions were used as contextual-level predictors. This study showed the inverse association between unmet needs and regional resources in private sectors after controlling for the effects of individual-level predictors. CONCLUSION: Our findings suggest that increasing regional resources in private sectors might produce inefficiency in the health care system and inequity in access to health services, particularly where the competition in private health care sectors was highly stimulated under the fee-for-service reimbursement scheme. Policies for the reallocation of health care resources and for reduction of individual health care costs are needed in Korea.

  8. Mental health care services for children with special health care needs and their family members: prevalence and correlates of unmet needs.

    Ganz, Michael L; Tendulkar, Shalini A

    2006-06-01

    To estimate the prevalence and correlates of unmet needs for mental health care services for children with special health care needs and their families. We use the National Survey of Children With Special Health Care Needs to estimate the prevalence of unmet mental health care needs among children with special health care needs (1-17 years old) and their families. Using logistic-regression models, we also assess the independent impact of child and family factors on unmet needs. Substantial numbers of children with special health care needs and members of their families have unmet needs for mental health care services. Children with special health care needs who were poor, uninsured, and were without a usual source of care were statistically significantly more likely to report that their mental health care needs were unmet. More severely affected children and those with emotional, developmental, or behavioral conditions were also statistically significantly more likely to report that their mental health care needs went unmet. Families of severely affected children or of children with emotional, developmental, or behavioral conditions were also statistically significantly more likely to report that their mental health care needs went unmet. Our results indicate that children with special health care needs and their families are at risk for not receiving needed mental health care services. Furthermore, we find that children in families of lower socioeconomic status are disproportionately reporting higher rates of unmet needs. These data suggest that broader policies to identify and connect families with needed services are warranted but that child- and family-centered approaches alone will not meet the needs of these children and their families. Other interventions such as anti-poverty and insurance expansion efforts may be needed as well.

  9. Professional health care use and subjective unmet need for social or emotional problems: a cross-sectional survey of the married and divorced population of Flanders.

    Colman, Elien; Symoens, Sara; Bracke, Piet

    2012-11-22

    The high mental health care consumption rates of divorced singles may constitute a heavy burden on the public health care system. This raises the question of whether their higher health care use stems from a greater need, or whether there are other factors contributing to these high consumption rates. We examine both health care use and subjective unmet need (perceiving a need for care without seeking it) because of social or emotional problems of the divorced singles, the repartnered divorcees, and the married. Moreover, we investigate how health care use and subjective unmet need relate to each other. We conduct several gender specific logistic regressions employing data from the Divorce in Flanders Survey (N men = 2884; N women = 3317). Results show that the divorced singles have more contact with professional health care providers (general practitioners, psychiatrists, and psychologists) because of social or emotional problems, and more often perceive unmet needs. The higher health care use rates and greater subjective unmet needs can largely be attributed to higher levels of depressive symptoms. Surprisingly, we find that non-frequent health care users more often perceive a subjective unmet need than frequent health care users and those who have not contacted any health care provider. The single divorced consult health care providers more often because of social or emotional problems and they also perceive unmet needs more often.

  10. Professional health care use and subjective unmet need for social or emotional problems: a cross-sectional survey of the married and divorced population of Flanders

    Colman Elien

    2012-11-01

    Full Text Available Abstract Background The high mental health care consumption rates of divorced singles may constitute a heavy burden on the public health care system. This raises the question of whether their higher health care use stems from a greater need, or whether there are other factors contributing to these high consumption rates. We examine both health care use and subjective unmet need (perceiving a need for care without seeking it because of social or emotional problems of the divorced singles, the repartnered divorcees, and the married. Moreover, we investigate how health care use and subjective unmet need relate to each other. Methods We conduct several gender specific logistic regressions employing data from the Divorce in Flanders Survey (N men = 2884; N women = 3317. Results Results show that the divorced singles have more contact with professional health care providers (general practitioners, psychiatrists, and psychologists because of social or emotional problems, and more often perceive unmet needs. The higher health care use rates and greater subjective unmet needs can largely be attributed to higher levels of depressive symptoms. Surprisingly, we find that non-frequent health care users more often perceive a subjective unmet need than frequent health care users and those who have not contacted any health care provider. Conclusion The single divorced consult health care providers more often because of social or emotional problems and they also perceive unmet needs more often.

  11. Beyond Stroke Prevention in Atrial Fibrillation: Exploring Further Unmet Needs with Rivaroxaban.

    Gibson, C M; Hankey, G J; Nafee, T; Welsh, R C

    2018-03-22

    With improved life expectancy and the aging population, the global burden of atrial fibrillation (AF) continues to increase, and with AF comes an estimated fivefold increased risk of ischaemic stroke. Prophylactic anticoagulant therapy is more effective in reducing the risk of ischaemic stroke in AF patients than acetylsalicylic acid or dual-antiplatelet therapy combining ASA with clopidogrel. Non-vitamin K antagonist oral anticoagulants are the standard of care for stroke prevention in patients with non-valvular AF. The optimal anticoagulant strategy to prevent thromboembolism in AF patients who are undergoing percutaneous coronary intervention and stenting, those who have undergone successful transcatheter aortic valve replacement and those with embolic stroke of undetermined source are areas of ongoing research. This article provides an update on three randomized controlled trials of rivaroxaban, a direct, oral factor Xa inhibitor, that are complete or are ongoing, in these unmet areas of stroke prevention: oPen-label, randomized, controlled, multicentre study explorIng twO treatmeNt stratEgiEs of Rivaroxaban and a dose-adjusted oral vitamin K antagonist treatment strategy in patients with Atrial Fibrillation who undergo Percutaneous Coronary Intervention (PIONEER AF-PCI) trial; the New Approach riVaroxaban Inhibition of factor Xa in a Global trial vs Aspirin to prevenT Embolism in Embolic Stroke of Undetermined Source (NAVIGATE ESUS) trial and the Global study comparing a rivAroxaban-based antithrombotic strategy to an antipLatelet-based strategy after transcatheter aortIc vaLve rEplacement to Optimize clinical outcomes (GALILEO) trial. The data from these studies are anticipated to help address continuing challenges for a range of patients at risk of stroke. Schattauer.

  12. Family planning services for incarcerated women: models for filling an unmet need.

    Sufrin, Carolyn; Baird, Sara; Clarke, Jennifer; Feldman, Elizabeth

    2017-03-13

    Purpose Incarcerated women around the globe are predominantly of reproductive age. Most of these women have been pregnant before, and many want to be sexually active and avoid pregnancy upon release. Yet few of these women are on a regular method of contraception. Providing contraceptive services for women in custody benefits individual and public health goals of reducing unintended pregnancy. This policy briefing reviews evidence for an unmet need for family planning in the correctional setting, and policy implications for expanding services. The paper aims to discuss these issues. Design/methodology/approach The authors describe four model programs in the USA with established contraceptive services on site, highlighting practical steps other facilities can implement. Findings Correctional facilities health administrators, providers, advocates, and legislators should advance policies which should counsel women on family planning and should make a range of contraceptive methods available before release, while remaining sensitive to the potential pressure these women may feel to use birth control in this unique environment. Practical implications Family planning services for incarcerated women benefits individuals, facilities, and the community. Social implications Policies which enable correctional facilities to provide comprehensive family planning to incarcerated women - including reproductive life goals counseling and contraceptive method provision - promote equity in access to critical reproductive health services and also provide broad scale population level benefits in preventing unintended pregnancy or enabling counseling for healthy pregnancies for a group of women who often have limited access to such services. Originality/value This policy briefing highlights an area of health care in prisons and jails which gets little attention in research and in policy circles: family planning services for incarcerated women. In addition to reviewing the importance of

  13. Rabbit IgG directed to a synthetic C-terminal peptide of the major grass pollen allergen Lol p I inhibits human basophil histamine release induced by natural Lol p I

    van Ree, R.; Aalberse, R. C.

    1995-01-01

    The potential role of allergen-specific IgG antibodies as 'blocking' antibodies in allergen-induced human basophil histamine release was investigated. This was studied in a model with the major grass pollen allergen Lol p I and polyclonal rabbit antisera directed against this allergen and against a

  14. Cultured Representatives of Two Major Phylogroups of Human Colonic Faecalibacterium prausnitzii Can Utilize Pectin, Uronic Acids, and Host-Derived Substrates for Growth

    Lopez-Siles, Mireia; Khan, Tanweer M.; Duncan, Sylvia H.; Harmsen, Hermie J. M.; Garcia-Gil, L. Jesus; Flint, Harry J.

    Faecalibacterium prausnitzii is one of the most abundant commensal bacteria in the healthy human large intestine, but information on genetic diversity and substrate utilization is limited. Here, we examine the phylogeny, phenotypic characteristics, and influence of gut environmental factors on

  15. β-lipotropin is the major opioid-like peptide of human pituitary and rat pars distalis: lack of significant β-endorphin

    Liotta, A.S.; Suda, T.; Krieger, D.T.

    1978-01-01

    β-Lipotropin is the predominant opioid peptide of the human pituitary and rat pars distalis and is present in concentrations essentially equimolar with corticotropin. When freshly obtained nonfrozen rat anterior pituitaries were homogenized with 0.2 M HCl, approximately 98% of the immunoreactivity detected utilizing an antiserum that crossreacts equally with β-lipotropin and β-endorphin coeluted with 125 I-labeled human β-lipotropin upon molecular sieve chromatography. The remainder of the activity eluted with synthetic human β-endorphin. Similar results were obtained for human pituitary. HCl homogenization of thawed tissue or homogenization of fresh tissue with acetic acid yielded substantially greater concentrations of β-endorphin and decreased concentrations of β-lipotropin. In human subjects, acute anterior pituitary stimulation using either insulin-induced hypoglycemia or vasopressin administration was associated with increased plasma β-lipotropin and corticotropin levels. At the time of peak concentrations, no significant levels of β-endorphin were detectable. These data indicate the lack of significant amounts of β-endorphin in human pituitary. Additionally, there appears to be no specific intrapituitary conversion of β-lipotropin to β-endorphin

  16. High prevalence of human anti-bovine IgG antibodies as the major cause of false positive reactions in two-site immunoassays based on monoclonal antibodies

    Andersen, Ditte C; Koch, Claus; Jensen, Charlotte H

    2004-01-01

    were purified by protein G affinity chromatography from culture supernatant containing 10% (v/v) fetal calf serum (FCS). Human anti-animal IgG (bovine, mouse, horse, and swine) antibodies and human anti-bovine serum albumin antibodies were measured using an ELISA design, with direct bridging...... of the solid phase and biotinylated antigens. The false positive reactions were abolished by addition of 1% (v/v) bovine serum to the dilution buffer (DB). Human anti-bovine IgG antibodies (HABIA) were detected in 99 out of 104 sera from blood donors (50 females; 54 males). HABIA levels in male sera (n = 54......) were positively correlated to the false positive signals in the PP14 ELISA (r = 0.923; p detected in the donor sera, but levels and frequencies were lower compared to that of HABIA. Furthermore, HABIA were...

  17. Ileal Digesta Nondietary Substrates from Cannulated Pigs Are Major Contributors to In Vitro Human Hindgut Short-Chain Fatty Acid Production.

    Montoya, Carlos A; Rutherfurd, Shane M; Moughan, Paul J

    2017-02-01

    It has been assumed that short-chain fatty acids (SCFAs) in the colon originate mainly from dietary fiber fermentation. However, SCFAs in the colon are also produced from the fermentation of nondietary material. We aimed to predict the relative contributions of dietary and nondietary substrates in the production of SCFAs with the use of a human fecal inoculum for diets containing kiwifruit as a model fiber. Terminal ileal digesta were collected from ileal-cannulated male pigs [n = 7; mean ± SD: 41.4 ± 2.98 kg body weight] adapted (44-d feeding) to diets containing either 25 g/kg dry matter (DM) of kiwifruit fiber (KFf) (25 KFf) or 50 g/kg DM of KFf (50 KFf) and then again after receiving a fiber-free diet (n = 14) for a further 7 d. Pigs were used as a model for adult humans for digestion in the upper digestive tract (mouth to the terminal ileum). The ileal digesta (either unfractionated or fractionated into crude mucin and microbial fractions) were fermented in vitro for 24 h with the use of a fresh human fecal inoculum to predict SCFA production in the human hindgut. SCFAs of nondietary origin were the main source (65%) of total SCFAs predicted to be produced in the human hindgut. The contribution of SCFAs from KFf was only 26% of the total SCFAs, and that from total dietary material was 35%. The higher contribution of nondietary material to total predicted SCFA production was observed at both dietary fiber concentrations. Predicted SCFA intake from dietary fiber was 76 and 105 mmol/kg diet DM intake for the diets containing 25 KFf and 50 KFf, respectively, and from the nondietary substrates it was 178 and 280 mmol/kg diet DM intake, respectively. A considerable proportion of the SCFAs produced in the human hindgut seems to be derived from the fermentation of nondietary substrates. © 2017 American Society for Nutrition.

  18. Separation, purification and identification of the major selenium metabolite from human urine by multi-dimensional HPLC-ICP-MS and APCI-MS

    Gammelgaard, Bente; Madsen, K.G.; Bjerrum, J.

    2003-01-01

    volunteers were collected and analysed by ion-pair chromatography with ICP-MS detection for this major selenium metabolite. Samples containing the metabolite were pooled and solid phase extracted to remove ionic substances. The extracted pool was purified and preconcentrated twice by preparative reversed...

  19. Foot problems in a group of patients with rheumatoid arthritis: an unmet need for foot care.

    Borman, Pinar; Ayhan, Figen; Tuncay, Figen; Sahin, Mehtap

    2012-01-01

    found to be correlated with Larsen scores (pfoot involvement and foot symptoms were seen frequently in RA but there is an unmet need for provision and monitoring of foot care in patients suffering from this chronic disease.

  20. Review of ICT-Based Services for Identified Unmet Needs in People with Dementia

    Lauriks, Steve; Reinersmann, Annika; van der Roest, Henriëtte Geralde; Meiland, Franka; Davies, Richard; Moelaert, Ferial; Mulvenna, Maurice D.; Nugent, Chris D.; Dröes, Rose-Marie

    Some of the needs that people with dementia and their informal carers currently perceive as insufficiently met by regular care and support services might be alleviated, or even be met, using modern Information and Communication Technology (ICT). The study described in this chapter was designed to provide an insight into the state of the art in ICT solutions that could contribute to meet the most frequently mentioned unmet needs by people with dementia and their informal carers. These needs can be summarized as (1) the need for general and personalized information; (2) the need for support with regard to symptoms of dementia; (3) the need for social contact and company; and (4) the need for health monitoring and perceived safety. Databases that were searched include PubMed, Cinahl, Psychinfo, Google (Scholar), INSPEC and IEEE. In total 22 websites and 46 publications were included that satisfied the following criteria: the article reports on people with dementia and/or their informal carers and discusses an ICT device that has been tested within the target group and has proven to be helpful. Within the first need area 18 relevant websites and three studies were included; within the second need area 4 websites and 20 publications were included. Within the third and fourth need area 11 and 12 publications were included, respectively. Most articles reported on uncontrolled studies. It is concluded that the informational websites offer helpful information for carers but seem less attuned to the person with dementia and do not offer personalized information. ICT solutions aimed at compensating for disabilities, such as memory problems and daily activities, demonstrate that people with mild to moderate dementia are capable of handling simple electronic equipment and can benefit from it in terms of more confidence and enhanced positive affect. Instrumental ICT support for coping with behavioural and psychological changes in dementia is relatively disregarded as yet, while

  1. Patch-occupancy models indicate human activity as major determinant of forest elephant Loxodonta cyclotis seasonal distribution in an industrial corridor in Gabon

    Buij, R.; McShea, W.J.; Campbell, P.; Lee, M.E.; Dallmeier, F.; Guimondou, S.; Mackaga, L.; Guisseougou, N.; Mboumba, S.; Hines, J.E.; Nichols, J.D.; Alonso, A.

    2007-01-01

    The importance of human activity and ecological features in influencing African forest elephant ranging behaviour was investigated in the Rabi-Ndogo corridor of the Gamba Complex of Protected Areas in southwest Gabon. Locations in a wide geographical area with a range of environmental variables were selected for patch-occupancy surveys using elephant dung to assess seasonal presence and absence of elephants. Patch-occupancy procedures allowed for covariate modelling evaluating hypotheses for both occupancy in relation to human activity and ecological features, and detection probability in relation to vegetation density. The best fitting models for old and fresh dung data sets indicate that (1) detection probability for elephant dung is negatively related to the relative density of the vegetation, and (2) human activity, such as presence and infrastructure, are more closely associated with elephant distribution patterns than are ecological features, such as the presence of wetlands and preferred fresh fruit. Our findings emphasize the sensitivity of elephants to human disturbance, in this case infrastructure development associated with gas and oil production. Patch-occupancy methodology offers a viable alternative to current transect protocols for monitoring programs with multiple covariates.

  2. Generation and epitope analysis of human monoclonal antibody isotypes with specificity for the timothy grass major allergen Phl p 5a

    Hecker, J.; Diethers, A.; Seismann, H.

    2011-01-01

    The scarcity of monoclonal human IgE antibodies with specificity for defined allergens is a bottleneck for the molecular characterisation of allergens and their epitopes. Insights into the characteristics of such antibodies may allow for analyses of the molecular basis underlying allergenicity an...

  3. Positive selection pressure introduces secondary mutations at Gag cleavage sites in human immunodeficiency virus type 1 harboring major protease resistance mutations

    Banke, S.; Lillemark, M.R.; Gerstoft, J.

    2009-01-01

    Human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs) specifically target the HIV-1 protease enzyme. Mutations in the enzyme can result in PI resistance (termed PI mutations); however, mutations in the HIV-1 gag region, the substrate for the protease enzyme, might also lead to PI ...

  4. Metabolism of benzo(a)pyrene and identification of the major benzo(a)pyrene-DNA adducts in cultured human colon

    Autrup, Herman; Harris, Curtis C.; Trump, Benjamin F.

    1978-01-01

    The metabolism of benzo(a)pyrene in cultured human colon has been investigated. Nontumorous colonie tissue was collected at the time of either surgery or "immediate autopsy" from patients with or without colonic cancer. After 24 hr in culture the expiants were exposed to [3H]benzo(a)pyrene for an...

  5. Long-term trends of daily maximum and minimum temperatures for the major cities of South Korea and their implications on human health

    Choi, B. C.; Kim, J.; Lee, D. G.; Kyselý, Jan

    2007-01-01

    Roč. 17, č. 2 (2007), s. 171-183 ISSN N R&D Projects: GA ČR GC205/07/J044 Institutional research plan: CEZ:AV0Z30420517 Keywords : Temperature trends * Biometeorology * Climate change * Global warming * Human health * Temperature extremes * Urbanization Subject RIV: DG - Athmosphere Sciences, Meteorology

  6. Unmet Support Service Needs and Health-Related Quality of Life among Adolescents and Young Adults with Cancer: The AYA HOPE Study

    Ashley Wilder Smith

    2013-04-01

    Full Text Available Introduction: Cancer for adolescents and young adults (AYA differs from younger and older patients; AYA face medical challenges while navigating social and developmental transitions. Research suggests that these patients are under- or inadequately served by current support services, which may affect health-related quality of life (HRQOL.Methods: We examined unmet service needs and HRQOL in the National Cancer Institute’s Adolescent and Young Adult Health Outcomes and Patient Experience (AYA HOPE study, a population-based cohort (n=484, age 15-39, diagnosed with cancer 6-14 months prior, in 2007-2009. Unmet service needs were psychosocial, physical, spiritual, and financial services where respondents endorsed that they needed, but did not receive, a listed service. Linear regression models tested associations between any or specific unmet service needs and HRQOL, adjusting for demographic, medical and health insurance variables.Results: Over one-third of respondents reported at least one unmet service need. The most common were financial (16%, mental health (15%, and support group (14% services. Adjusted models showed that having any unmet service need was associated with worse overall HRQOL, fatigue, physical, emotional, social, and school/work functioning, and mental health (p’s<0.0001. Specific unmet services were related to particular outcomes (e.g., needing pain management was associated with worse overall HRQOL, physical and social functioning (p’s<0.001. Needing mental health services had the strongest associations with worse HRQOL outcomes; needing physical/occupational therapy was most consistently associated with poorer functioning across domains.Discussion: Unmet service needs in AYAs recently diagnosed with cancer are associated with worse HRQOL. Research should examine developmentally appropriate, relevant practices to improve access to services demonstrated to adversely impact HRQOL, particularly physical therapy and mental

  7. Fracture liaison services for osteoporosis in the Asia-Pacific region: current unmet needs and systematic literature review.

    Chang, Y -F; Huang, C -F; Hwang, J -S; Kuo, J -F; Lin, K -M; Huang, H -C; Bagga, S; Kumar, A; Chen, F -P; Wu, C -H

    2018-04-01

    The analysis aimed to identify the treatment gaps in current fracture liaison services (FLS) and to provide recommendations for best practice establishment of future FLS across the Asia-Pacific region. The findings emphasize the unmet need for the implementation of new programs and provide recommendations for the refinement of existing ones. The study's objectives were to evaluate fracture liaison service (FLS) programs in the Asia-Pacific region and provide recommendations for establishment of future FLS programs. A systematic literature review (SLR) of Medline, PubMed, EMBASE, and Cochrane Library (2000-2017 inclusive) was performed using the following keywords: osteoporosis, fractures, liaison, and service. Inclusion criteria included the following: patients ≥ 50 years with osteoporosis-related fractures; randomized controlled trials or observational studies with control groups (prospective or retrospective), pre-post, cross-sectional and economic evaluation studies. Success of direct or indirect interventions was assessed based on patients' understanding of risk, bone mineral density assessment, calcium intake, osteoporosis treatment, re-fracture rates, adherence, and mortality, in addition to cost-effectiveness. Overall, 5663 unique citations were identified and the SLR identified 159 publications, reporting 37 studies in Asia-Pacific. These studies revealed the unmet need for public health education, adequate funding, and staff resourcing, along with greater cooperation between departments and physicians. These actions can help to overcome therapeutic inertia with sufficient follow-up to ensure adherence to recommendations and compliance with treatment. The findings also emphasize the importance of primary care physicians continuing to prescribe treatment and ensure service remains convenient. These findings highlight the limited evidence supporting FLS across the Asia-Pacific region, emphasizing the unmet need for new programs and/or refinement of

  8. Challenges, coping strategies, and unmet needs of families with a child with autism spectrum disorder in Goa, India.

    Divan, Gauri; Vajaratkar, Vivek; Desai, Miraj U; Strik-Lievers, Luisa; Patel, Vikram

    2012-06-01

    Autism Spectrum Disorders (ASD) are increasingly recognized in developing countries like India. However, little is known about the experiences of parents raising a child with ASD. This study aimed to describe the experiences of families in Goa, India with a view to understanding the unmet needs of families raising a child with ASD. Twenty in-depth interviews and nine focus group discussions were carried out with families of children with ASD and key community stakeholders such as special educators, teachers, and parents of typically developing children. This qualitative data was triangulated to explore the experiences, life impact, and unmet needs of raising a child with ASD. Key findings suggest that raising a child with ASD puts a tremendous strain on families due to competing commitments, often leading to initial social withdrawal with later reintegration into social networks. Second, the impact is multidimensional, involving the personal sphere but also extending into the wider community with negative experiences of discrimination. Third, parents actively respond to these challenges through a range of approaches with help from existing and new social support networks and health care providers. Fourth, professionals from the health, education, and religious sectors have a low awareness of the unique needs of families living with ASD which leads to a considerable economic and emotional burden on families. Finally, as a consequence of these experiences, several unmet needs can be identified, notably for supporting increasingly isolated families and the limited access to multidisciplinary evidence-based services for ASD. Autism Res 2012, 5: 190-200. © 2012 International Society for Autism Research, Wiley Periodicals, Inc. © 2012 International Society for Autism Research, Wiley Periodicals, Inc.

  9. The Isolation of Novel Phage Display-Derived Human Recombinant Antibodies Against CCR5, the Major Co-Receptor of HIV

    Shimoni, Moria; Herschhorn, Alon; Britan-Rosich, Yelena; Kotler, Moshe; Benhar, Itai; Hizi, Amnon

    2013-01-01

    Selecting for antibodies against specific cell-surface proteins is a difficult task due to many unrelated proteins that are expressed on the cell surface. Here, we describe a method to screen antibody-presenting phage libraries against native cell-surface proteins. We applied this method to isolate antibodies that selectively recognize CCR5, which is the major co-receptor for HIV entry (consequently, playing a pivotal role in HIV transmission and pathogenesis). We employed a phage screening s...

  10. Expert Nordic perspectives on the potential of novel inhalers to overcome unmet needs in the management of obstructive lung disease

    Løkke, Anders; Ahlbeck, Lars; Bjermer, Leif

    2015-01-01

    fails to achieve adequate lung deposition and therapeutic effect. In this report, the potential of novel inhaler devices to overcome unmet needs in the management of obstructive lung disease is considered by a panel of Nordic experts. The panel concludes that innovative inhalers can contribute to good......The effective self-management of obstructive lung disease is dependent upon the patient achieving good inhaler technique. However, many current inhalers are complicated to use, which may lead to handling difficulties. These difficulties can cause clinically relevant errors, whereby pharmacotherapy...... disease management and better use of healthcare resources....

  11. Gallic Acid Is the Major Active Component of Cortex Moutan in Inhibiting Immune Maturation of Human Monocyte-Derived Dendritic Cells

    Ben Chung Lap Chan

    2015-09-01

    Full Text Available Atopic dermatitis (AD is a widely prevalent and chronically relapsing inflammatory skin disease. Penta Herbs Formula (PHF is efficacious in improving the quality of life and reducing topical corticosteroid used in children with AD and one of the active herbs it contains is Cortex Moutan. Recent studies showed that altered functions of dendritic cells (DC were observed in atopic individuals, suggesting that DC might play a major role in the generation and maintenance of inflammation by their production of pro-inflammatory cytokines. Hence, the aims of the present study were to identify the major active component(s of Cortex Moutan, which might inhibit DC functions and to investigate their possible interactions with conventional corticosteroid on inhibiting the development of DC from monocytes. Monocyte-derived dendritic cells (moDC culture model coupled with the high-speed counter-current chromatography (HSCCC, high pressure liquid chromatography (HPLC and Liquid Chromatography-Mass Spectrometry (LCMS analyses were used. Gallic acid was the major active component from Cortex Moutan which could dose dependently inhibit interleukin (IL-12 p40 and the functional cluster of differentiation (CD surface markers CD40, CD80, CD83 and CD86 expression from cytokine cocktail-activated moDC. Gallic acid could also lower the concentration of hydrocortisone required to inhibit the activation of DC.

  12. Public Spending On Human Capital In Major Industrialized Countries = Endüstrileşmenin En Yüksek Olduğu Ülkelerde Beşeri Sermayeye Yönelik Kamu Harcamalari

    Meriç Subaşı ERTEKİN

    2005-06-01

    Full Text Available Human capital is important for firms and nations in the knowledge based economy that needs skills. Thus, investment in education is a public policy to support human capital formation and offset the magnitude of capital looses. Policies and reforms designed to foster early learning which are determined as a high quality of education, early intervention and job training programs and promote skill formation. The public sector plays an important role in the funding of all education in major industrialized countries. Public spending on primary, secondary, post-secondary and tertiary educational institutions is higher than private spending.

  13. Heme oxygenase is the major 32-kDa stress protein induced in human skin fibroblasts by UVA radiation, hydrogen peroxide, and sodium arsenite

    Keyse, S.M.; Tyrrell, R.M.

    1989-01-01

    We have shown that UVA (320-380 nm) radiation, hydrogen peroxide, and sodium arsenite induce a stress protein of approximately 32 kDa in human skin fibroblasts. The synthesis and cloning of cDNA from arsenite-induced mRNA populations have now allowed us to unequivocally identify the 32-kDa protein as heme oxygenase. By mRNA analysis we have shown that the heme oxygenase gene is also induced in cultured human skin fibroblasts by UVA radiation, hydrogen peroxide, cadmium chloride, iodoacetamide, and menadione. The known antioxidant properties of heme catabolites taken together with the observation of a high level of induction of the enzyme in cells from an organ not involved in hemoglobin breakdown strongly supports the proposal that the induction of heme oxygenase may be a general response to oxidant stress and constitutes an important cellular defense mechanism against oxidative damage

  14. Detecting Site-Specific Physicochemical Selective Pressures: Applications to the Class I HLA of the Human Major Histocompatibility Complex and the SRK of the Plant Sporophytic Self-Incompatibility System

    Sainudiin, Raazesh; Wong, Wendy Shuk Wan; Yogeeswaran, Krithika

    2005-01-01

    :transversion biases. Here, we apply this method to two positively selected receptors involved in ligand-recognition: the class I alleles of the human major histocompatibility complex (MHC) of known structure and the S-locus receptor kinase (SRK) of the sporophytic self-incompatibility system (SSI) in cruciferous...... Bayes approach is used to identify sites that may be important for ligand recognition in these proteins....

  15. Residential Stability Reduces Unmet Health Care Needs and Emergency Department Utilization among a Cohort of Homeless and Vulnerably Housed Persons in Canada.

    Jaworsky, Denise; Gadermann, Anne; Duhoux, Arnaud; Naismith, Trudy E; Norena, Monica; To, Matthew J; Hwang, Stephen W; Palepu, Anita

    2016-08-01

    This study examined the association of housing status over time with unmet physical health care needs and emergency department utilization among homeless and vulnerably housed persons in Canada. Homeless and vulnerably housed individuals completed interviewer-administered surveys on housing, unmet physical health care needs, health care utilization, sociodemographic characteristics, substance use, and health conditions at baseline and annually for 4 years. Generalized logistic mixed effects regression models examined the association of residential stability with unmet physical health care needs and emergency department utilization, adjusting for potential confounders. Participants were from Vancouver (n = 387), Toronto (n = 390), and Ottawa (n = 396). Residential stability was associated with lower odds of having unmet physical health needs (adjusted odds ratio (AOR), 0.82; 95 % confidence interval (CI), 0.67, 0.98) and emergency department utilization (AOR, 0.74; 95 % CI, 0.62, 0.88) over the 4-year follow-up period, after adjusting for potential confounders. Residential stability is associated with fewer unmet physical health care needs and lower emergency department utilization among homeless and vulnerably housed individuals. These findings highlight the need to address access to stable housing as a significant determinant of health disparities.

  16. Functional characterization of the 1,5-benzodiazepine clobazam and its major active metabolite N-desmethylclobazam at human GABAA receptors expressed in Xenopus laevis oocytes

    Hammer, Harriet; Ebert, Bjarke; Jensen, Henrik S.

    2015-01-01

    different in vivo adverse effects and addiction liability profile than the classic 1,4-benzodiazepines. In this study, it was investigated whether the in vitro pharmacological properties of clobazam and its major active metabolite N-desmethylclobazam could explain some of these clinical differences...... by the 1,4-benzodiazepine clonazepam. All three compounds potentiated GABA EC20-evoked responses through the α1,2,3,5β2γ2S GABAARs in a reversible and concentration-dependent manner, with each displaying similar EC50 values at the four subtypes. Furthermore, the degrees of potentiation of the GABA EC20...

  17. The GluN2B subunit represents a major functional determinant of NMDA receptors in human induced pluripotent stem cell-derived cortical neurons

    Ioana Neagoe

    2018-04-01

    Full Text Available Abnormal signaling pathways mediated by N-methyl-d-aspartate receptors (NMDARs have been implicated in the pathogenesis of various CNS disorders and have been long considered as promising points of therapeutic intervention. However, few efforts have been previously described concerning evaluation of therapeutic modulators of NMDARs and their downstream pathways in human neurons with endogenous expression of NMDARs. In the present study, we assessed expression, functionality, and subunit composition of endogenous NMDARs in human induced pluripotent stem cell (hiPSC-derived cortical neurons (iCell Neurons and iCell GlutaNeurons. We initially confirmed the expected pharmacological response of iCell Neurons and iCell GlutaNeurons to NMDA by patch-clamp recordings. Subsequent pharmacological interrogation using GluN2 subunit-selective antagonists revealed the predominance of GluN2B in both iCell Neurons and iCell GlutaNeurons. This observation was also supported by qRT-PCR and Western blot analyses of GluN2 subunit expression as well as pharmacological experiments using positive allosteric modulators with distinct GluN2 subunit selectivity. We conclude that iCell Neurons and iCell GlutaNeurons express functional GluN2B-containing NMDARs and could serve as a valuable system for development and validation of GluN2B-modulating pharmaceutical agents. Keywords: Human induced pluripotent stem cell-derived neurons, iCell Neurons, iCell GlutaNeurons, NMDA receptors, GluN2B, Positive allosteric modulators

  18. Metabolism of benzo(a)pyrene, N-nitrosomethylamine, and N-nitrosopyrrolidine and identification of the major carcinogen-DNA adducts formed in cultured human esophagus

    Harris, Curtis C.; Autrup, Herman; Stoner, Gary D.

    1979-01-01

    The wide variation in the world-wide incidence of esophageal carcinoma suggests that environmental agents including chemicals cause this cancer. Since the interaction between chemical procarcinogens and human esophagus has not been studied previously, we examined the metabolic fate of benzo......(a)pyrene (BP), N-nitrosodimethylamine (DMN), and A/-nitrosopyrrolidine in cultured nontumorous esophagus from two patients with and six patients without esophageal carcinoma. Esophageal explants were cultured in a chemically defined medium for 7 days prior to adding [3H]BP (1.5 JUM),[14C]DMN (100 /IM), or [14C...

  19. Study of the safety, immunogenicity and efficacy of attenuated and killed Leishmania (Leishmania major vaccines in a rhesus monkey (Macaca mulatta model of the human disease

    VF Amaral

    2002-10-01

    Full Text Available We have compared the efficacy of two Leishmania (Leishmania major vaccines, one genetically attenuated (DHFR-TS deficient organisms, the other inactivated [autoclaved promastigotes (ALM with bacillus Calmete-Guérin (BCG], in protecting rhesus macaques (Macaca mulatta against infection with virulent L. (L. major. Positive antigen-specific recall proliferative response was observed in vaccinees (79% in attenuated parasite-vaccinated monkeys, versus 75% in ALM-plus-BCG-vaccinated animals, although none of these animals exhibited either augmented in vitro gamma interferon (IFN-g production or positive delayed-type hypersensitivity (DTH response to the leishmanin skin test prior to the challenge. Following challenge, there were significant differences in blastogenic responses (p < 0.05 between attenuated-vaccinated monkeys and naïve controls. In both vaccinated groups very low levels of antibody were found before challenge, which increased after infective challenge. Protective immunity did not follow vaccination, in that monkeys exhibited skin lesion at the site of challenge in all the groups. The most striking result was the lack of pathogenicity of the attenuated parasite, which persisted in infected animals for up to three months, but were incapable of causing disease under the conditions employed. We concluded that both vaccine protocols used in this study are safe in primates, but require further improvement for vaccine application.

  20. Cultured representatives of two major phylogroups of human colonic Faecalibacterium prausnitzii can utilize pectin, uronic acids, and host-derived substrates for growth.

    Lopez-Siles, Mireia; Khan, Tanweer M; Duncan, Sylvia H; Harmsen, Hermie J M; Garcia-Gil, L Jesús; Flint, Harry J

    2012-01-01

    Faecalibacterium prausnitzii is one of the most abundant commensal bacteria in the healthy human large intestine, but information on genetic diversity and substrate utilization is limited. Here, we examine the phylogeny, phenotypic characteristics, and influence of gut environmental factors on growth of F. prausnitzii strains isolated from healthy subjects. Phylogenetic analysis based on the 16S rRNA sequences indicated that the cultured strains were representative of F. prausnitzii sequences detected by direct analysis of fecal DNA and separated the available isolates into two phylogroups. Most F. prausnitzii strains tested grew well under anaerobic conditions on apple pectin. Furthermore, F. prausnitzii strains competed successfully in coculture with two other abundant pectin-utilizing species, Bacteroides thetaiotaomicron and Eubacterium eligens, with apple pectin as substrate, suggesting that this species makes a contribution to pectin fermentation in the colon. Many F. prausnitzii isolates were able to utilize uronic acids for growth, an ability previously thought to be confined to Bacteroides spp. among human colonic anaerobes. Most strains grew on N-acetylglucosamine, demonstrating an ability to utilize host-derived substrates. All strains tested were bile sensitive, showing at least 80% growth inhibition in the presence of 0.5 μg/ml bile salts, while inhibition at mildly acidic pH was strain dependent. These attributes help to explain the abundance of F. prausnitzii in the colonic community but also suggest factors in the gut environment that may limit its distribution.

  1. Results from an online survey of patient and caregiver perspectives on unmet needs in the treatment of bipolar disorder.

    Masand, Prakash S; Tracy, Natasha

    2014-01-01

    To look at the manner in which patients and caregivers perceive the treatment of bipolar disorder compared with the evidence base for bipolar treatment. Between April 2013 and March 2014, 469 respondents took a 14-question online survey on demographics, medications taken, and perspectives on bipolar treatment and medications. Participants were recruited through social media outlets (Facebook and Twitter accounts) of Global Medical Education (New York, New York) and the blog Bipolar Burble, which has a primary audience of people with bipolar disorder. There were no exclusion criteria to participation, and both patients and health care professionals were encouraged to participate. Most respondents were taking ≥ 3 medications, and the greatest unmet need in treatment was for bipolar depression. In general, respondent perspectives on the effectiveness of individual medication treatments did not align with the available literature. Weight gain was the greatest side effect concern for both antipsychotics and mood stabilizers. Our survey demonstrates that there are still many unmet needs in the treatment of bipolar disorder. There is also a mismatch between the evidence base for treatments in bipolar disorder and patient perception of the relative efficacy of different medications. In order to achieve better outcomes, there is a need to provide patients and clinicians greater quality education with regard to the best evidence-based treatments for bipolar disorder.

  2. Beliefs about unmet interpersonal needs mediate the relation between conflictual family relations and borderline personality features in young adult females.

    Kalpakci, Allison; Venta, Amanda; Sharp, Carla

    2014-01-01

    Central to most theories of borderline personality disorder (BPD) is the notion that the family environment interacts with genetically-based vulnerabilities to influence the development of BPD, with particular attention given to risk conferred by conflictual familial relations. However, the extent to which family conflict may relate to the development of BPD via related interpersonal beliefs is currently unknown. This study sought to test the hypothesis that the concurrent relation between conflictual family relations and borderline features in female college students is explained by beliefs associated with real or perceived unmet interpersonal needs (captured by Joiner's [2005] Interpersonal Psychological Theory, specifically thwarted belongingness and perceived burdensomeness). The sample included 267 female undergraduates ages 18-25 years (M = 20.86; SD = 1.80). Level of borderline personality features, unmet interpersonal needs, and family conflict were assessed. Bivariate analyses revealed significant relations between both thwarted belongingness and perceived burdensomeness, conflictual family relations, and borderline features. Multivariate analyses revealed that thwarted belongingness and perceived burdensomeness both mediated the relation between family conflict and borderline personality features, thus supporting a multiple mediation model. This cross-sectional study is a preliminary step towards confirming the broad theoretical hypothesis that conflictual family relations relate to beliefs about thwarted belongingness and perceived burdensomeness, which, in turn, relate to borderline personality pathology. Limitations and areas of future research are discussed.

  3. Desire for more children, contraceptive use and unmet need for family planning in a remote area of Bali, Indonesia.

    Withers, Mellissa; Kano, Megumi; Pinatih, Gde Ngurah Indraguna

    2010-07-01

    Exploring fertility preferences in relation to contraceptive use can increase the understanding of future reproductive behaviour and unmet family planning needs. This knowledge can help assist women in meeting their reproductive goals. The influences on the desire for more children and current contraceptive use were examined among 1528 married women of reproductive age in an isolated community in Bali, Indonesia, using multivariate logistic regression analysis. Women who were younger, had fewer living children, had given birth in the past year and had regular access to health services were more likely to desire children. Being older, having fewer living children, not having regular access to health services, having given birth in the past year and having the desire for more children were associated with a lower likelihood of using contraception. Women with regular access to health care are more likely to desire more children, probably because they are confident in their ability to have successful birth outcomes. However, specialized clinics or family planning outreach workers may be required to reduce barriers to service utilization among some groups. The findings of this study identify key target populations for family planning, including older women and postpartum women--groups that may not perceive themselves to be at risk for unintended pregnancy. Meeting unmet need for family planning among these groups could help women meet their fertility goals, as well as reduce maternal morbidity and mortality.

  4. LGBT Identity, Untreated Depression, and Unmet Need for Mental Health Services by Sexual Minority Women and Trans-Identified People.

    Steele, Leah S; Daley, Andrea; Curling, Deone; Gibson, Margaret F; Green, Datejie C; Williams, Charmaine C; Ross, Lori E

    2017-02-01

    Previous studies have found that transgender, lesbian, and bisexual people report poorer mental health relative to heterosexuals. However, available research provides little information about mental health service access among the highest need groups within these communities: bisexual women and transgender people. This study compared past year unmet need for mental health care and untreated depression between four groups: heterosexual cisgender (i.e., not transgender) women, cisgender lesbians, cisgender bisexual women, and transgender people. This was a cross-sectional Internet survey. We used targeted sampling to recruit 704 sexual and gender minority people and heterosexual cisgendered adult women across Ontario, Canada. To ensure adequate representation of vulnerable groups, we oversampled racialized and low socioeconomic status (SES) women. Trans participants were 2.4 times (95% confidence intervals [CI] = 1.6-3.8, p mental healthcare as cisgender heterosexual women. Trans participants were also 1.6 times (95% CI = 1.0-27, p = 0.04) more likely to report untreated depression. These differences were not seen after adjustment for social context factors such as discrimination and social support. We conclude that there are higher rates of unmet need and untreated depression in trans and bisexual participants that are partly explained by differences in social factors, including experiences of discrimination, lower levels of social support, and systemic exclusion from healthcare. Our findings suggest that the mental health system in Ontario is not currently meeting the needs of many sexual and gender minority people.

  5. Major groove binding track residues of the connection subdomain of human immunodeficiency virus type 1 reverse transcriptase enhance cDNA synthesis at high temperatures.

    Matamoros, Tania; Barrioluengo, Verónica; Abia, David; Menéndez-Arias, Luis

    2013-12-23

    At high temperatures, RNA denaturation can improve the efficiency and specificity of reverse transcription. Refined structures and molecular models of HIV-1 reverse transcriptases (RTs) from phylogenetically distant clades (i.e., group M subtype B and group O) revealed a major interaction between the template-primer and the Arg³⁵⁸-Gly³⁵⁹-Ala³⁶⁰ triad in the large subunit of HIV-1M/B RT. However, fewer contacts were predicted for the equivalent Lys³⁵⁸-Ala³⁵⁹-Ser³⁶⁰ triad of HIV-1O RT and the nucleic acid. An engineered HIV-1O K358R/A359G/S360A RT showed increased cDNA synthesis efficiency above 68 °C, as determined by qualitative and quantitative reverse transcription polymerase chain reactions. In comparison with wild-type HIV-1O RT, the mutant enzyme showed higher thermal stability but retained wild-type RNase H activity. Mutations that increased the accuracy of HIV-1M/B RTs were tested in combination with the K358R/A359G/S360A triple mutation. Some of them (e.g., F61A, K65R, K65R/V75I, and V148I) had a negative effect on reverse transcription efficiency above 65 °C. RTs with improved DNA binding affinities also showed higher cDNA synthesis efficiencies at elevated temperatures. Two of the most thermostable RTs (i.e., mutants T69SSG/K358R/A359G/S360A and K358R/A359G/S360A/E478Q) showed moderately increased fidelity in forward mutation assays. Our results demonstrate that the triad of Arg³⁵⁸, Gly³⁵⁹, and Ala³⁶⁰ in the major groove binding track of HIV-1 RT is a major target for RT stabilization, and most relevant for improving reverse transcription efficiency at high temperatures.

  6. Activation of Stat-3 is involved in the induction of apoptosis after ligation of major histocompatibility complex class I molecules on human Jurkat T cells

    Skov, S; Nielsen, M; Bregenholt, S

    1998-01-01

    Activation of Janus tyrosine kinases (Jak) and Signal transducers and activators of transcription (Stat) after ligation of major histocompatibility complex class I (MHC-I) was explored in Jurkat T cells. Cross-linking of MHC-I mediated tyrosine phosphorylation of Tyk2, but not Jak1, Jak2, and Jak3......-probe derived from the interferon-gamma activated site (GAS) in the c-fos promoter, a common DNA sequence for Stat protein binding. An association between hSIE and Stat-3 after MHC-I ligation was directly demonstrated by precipitating Stat-3 from nuclear extracts with biotinylated hSIE probe and avidin......-coupled agarose. To investigate the function of the activated Stat-3, Jurkat T cells were transiently transfected with a Stat-3 isoform lacking the transactivating domain. This dominant-negative acting Stat-3 isoform significantly inhibited apoptosis induced by ligation of MHC-I. In conclusion, our data suggest...

  7. Fetzima (levomilnacipran), a drug for major depressive disorder as a dual inhibitor for human serotonin transporters and beta-site amyloid precursor protein cleaving enzyme-1.

    Rizvi, Syed Mohd Danish; Shaikh, Sibhghatulla; Khan, Mahiuddin; Biswas, Deboshree; Hameed, Nida; Shakil, Shazi

    2014-01-01

    Pharmacological management of Major Depressive Disorder includes the use of serotonin reuptake inhibitors which targets serotonin transporters (SERT) to increase the synaptic concentrations of serotonin. Beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1) is responsible for amyloid β plaque formation. Hence it is an interesting target for Alzheimer's disease (AD) therapy. This study describes molecular interactions of a new Food and Drug Administration approved antidepressant drug named 'Fetzima' with BACE-1 and SERT. Fetzima is chemically known as levomilnacipran. The study has explored a possible link between the treatment of Depression and AD. 'Autodock 4.2' was used for docking study. The free energy of binding (ΔG) values for 'levomilnacipran-SERT' interaction and 'levomilnacipran-BACE1' interaction were found to be -7.47 and -8.25 kcal/mol, respectively. Levomilnacipran was found to interact with S438, known to be the most important amino acid residue of serotonin binding site of SERT during 'levomilnacipran-SERT' interaction. In the case of 'levomilnacipran-BACE1' interaction, levomilnacipran interacted with two very crucial aspartic acid residues of BACE-1, namely, D32 and D228. These residues are accountable for the cleavage of amyloid precursor protein and the subsequent formation of amyloid β plaques in AD brain. Hence, Fetzima (levomilnacipran) might act as a potent dual inhibitor of SERT and BACE-1 and expected to form the basis of a future dual therapy against depression and AD. It is an established fact that development of AD is associated with Major Depressive Disorder. Therefore, the design of new BACE-1 inhibitors based on antidepressant drug scaffolds would be particularly beneficial.

  8. Risk assessment of PCDD/Fs levels in human tissues related to major food items based on chemical analyses and micro-EROD assay.

    Tsang, H L; Wu, S C; Wong, C K C; Leung, C K M; Tao, S; Wong, M H

    2009-10-01

    Nine groups of food items (freshwater fish, marine fish, pork, chicken, chicken eggs, leafy, non-leafy vegetables, rice and flour) and three types of human samples (human milk, maternal serum and cord serum) were collected for the analysis of PCDD/Fs. Results of chemical analysis revealed PCDD/Fs concentrations (pg g(-1) fat) in the following ascending order: pork (0.289 pg g(-1) fat), grass carp (Ctenopharyngodon idellus) (freshwater fish) (0.407), golden thread (Nemipterus virgatus) (marine fish) (0.511), chicken (0.529), mandarin fish (Siniperca kneri) (marine fish) (0.535), chicken egg (0.552), and snubnose pompano (Trachinotus blochii) (marine fish) (1.219). The results of micro-EROD assay showed relatively higher PCDD/Fs levels in fish (2.65 pg g(-1) fat) when compared with pork (0.47), eggs (0.33), chicken (0.13), flour (0.07), vegetables (0.05 pg g(-1) wet wt) and rice (0.05). The estimated average daily intake of PCDD/Fs of 3.51 pg EROD-TEQ/kg bw/day was within the range of WHO Tolerable Daily Intake (1-4 pg WHO-TEQ/kg bw/day) and was higher than the Provisional Tolerable Daily Intake (PMTL) (70 pg for dioxins and dioxin-like PCBs) recommended by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) [Joint FAO/WHO Expert Committee on Food Additives (JECFA), Summary and conclusions of the fifty-seventh meeting, JECFA, 2001.]. Nevertheless, the current findings were significantly lower than the TDI (14 pg WHO-TEQ/kg/bw/day) recommended by the Scientific Committee on Food of the Europe Commission [European Scientific Committee on Food (EU SCF), Opinions on the SCF on the risk assessment of dioxins and dioxin-like PCBs in food, 2000.]. However, it should be noted that micro-EROD assay overestimates the PCDD/Fs levels by 2 to 7 folds which may also amplify the PCDD/Fs levels accordingly. Although the levels of PCDD/Fs obtained from micro-EROD assay were much higher than those obtained by chemical analysis by 2 to 7 folds, it provides a cost-effective and

  9. Construction of synthetic nucleoli in human cells reveals how a major functional nuclear domain is formed and propagated through cell division.

    Grob, Alice; Colleran, Christine; McStay, Brian

    2014-02-01

    Human cell nuclei are functionally organized into structurally stable yet dynamic bodies whose cell cycle inheritance is poorly understood. Here, we investigate the biogenesis and propagation of nucleoli, sites of ribosome biogenesis and key regulators of cellular growth. Nucleolar and cell cycles are intimately connected. Nucleoli disappear during mitosis, reforming around prominent uncharacterized chromosomal features, nucleolar organizer regions (NORs). By examining the effects of UBF depletion on both endogenous NORs and synthetic pseudo-NORs, we reveal its essential role in maintaining competency and establishing a bookmark on mitotic NORs. Furthermore, we demonstrate that neo-NORs, UBF-binding site arrays coupled with rDNA transcription units, direct the de novo biogenesis of functional compartmentalized neonucleoli irrespective of their site of chromosomal integration. For the first time, we establish the sequence requirements for nucleolar biogenesis and provide proof that this is a staged process where UBF-dependent mitotic bookmarking precedes function-dependent nucleolar assembly.

  10. Long-chain perfluoroalkyl carboxylic acids in Pacific cods from coastal areas in northern Japan: A major source of human dietary exposure

    Fujii, Yukiko; Sakurada, Tsukasa; Harada, Kouji H.; Koizumi, Akio; Kimura, Osamu; Endo, Tetsuya; Haraguchi, Koichi

    2015-01-01

    This study investigates perfluoroalkyl carboxylic acids (PFCAs) contamination of edible fish muscle from Japanese coastal waters. The concentrations of PFCAs with 8–14 carbon atoms (C8–C14) in Pacific cods in Hokkaido, Japan were 51 (median: pg/g-wet weight) for C8, 93 for C9, 99 for C10, 746 for C11, 416 for C12, 404 for C13, and 93 for C14. The levels of C9–C14 PFCAs in fish were strongly correlated to each other, but not to C8 and the other chlorinated persistent organic pollutants, indicating that C9–C14 PFCAs have a different emission source and/or bioaccumulation mechanism. The relative ratios between estimated PFCAs intake through fish consumption and the reported total dietary exposure of PFCAs were less than 1 for C8 to C9, but were more than 1 for C10 to C14. This result strongly suggests that fish consumption is a significant source of human dietary exposure to C10–C14 PFCAs. - Highlights: • Perfluoroalkyl carboxylic acids were detected in edible cod fish from Japanese coastal waters. • The levels of long-chain PFCAs in fish were independent from those of C8 and other POPs. • Long chain PFCAs intake through fish and the reported total dietary exposure were comparable. • Sea fish such as Pacific cod may be a significant human dietary source of long-chain PFCAs. - Sea fish are a significant source of long-chain perfluoroalkyl carboxylic acids for the Japanese population

  11. Identification and quantification of major maillard cross-links in human serum albumin and lens protein. Evidence for glucosepane as the dominant compound.

    Biemel, Klaus M; Friedl, D Alexander; Lederer, Markus O

    2002-07-12

    Glycation reactions leading to protein modifications (advanced glycation end products) contribute to various pathologies associated with the general aging process and long term complications of diabetes. However, only few relevant compounds have so far been detected in vivo. We now report on the first unequivocal identification of the lysine-arginine cross-links glucosepane 5, DOGDIC 6, MODIC 7, and GODIC 8 in human material. For their accurate quantification by coupled liquid chromatography-electrospray ionization mass spectrometry, (13)C-labeled reference compounds were synthesized independently. Compounds 5-8 are formed via the alpha-dicarbonyl compounds N(6)-(2,3-dihydroxy-5,6-dioxohexyl)-l-lysinate (1a,b), 3-deoxyglucosone (), methylglyoxal (), and glyoxal (), respectively. The protein-bound dideoxyosone 1a,b seems to be of prime significance for cross-linking because it presumably is not detoxified by mammalian enzymes as readily as 2-4. Hence, the follow-up product glucosepane 5 was found to be the dominant compound. Up to 42.3 pmol of 5/mg of protein was identified in human serum albumin of diabetics; the level of 5 correlates markedly with the glycated hemoglobin HbA(1c). In the water-insoluble fraction of lens proteins from normoglycemics, concentration of 5 ranges between 132.3 and 241.7 pmol/mg. The advanced glycoxidation end product GODIC 8 is elevated significantly in brunescent lenses, indicating enhanced oxidative stress in this material. Compounds 5-8 thus appear predestined as markers for pathophysiological processes.

  12. Clusters of ancestrally related genes that show paralogy in whole or in part are a major feature of the genomes of humans and other species.

    Michael B Walker

    Full Text Available Arrangements of genes along chromosomes are a product of evolutionary processes, and we can expect that preferable arrangements will prevail over the span of evolutionary time, often being reflected in the non-random clustering of structurally and/or functionally related genes. Such non-random arrangements can arise by two distinct evolutionary processes: duplications of DNA sequences that give rise to clusters of genes sharing both sequence similarity and common sequence features and the migration together of genes related by function, but not by common descent. To provide a background for distinguishing between the two, which is important for future efforts to unravel the evolutionary processes involved, we here provide a description of the extent to which ancestrally related genes are found in proximity.Towards this purpose, we combined information from five genomic datasets, InterPro, SCOP, PANTHER, Ensembl protein families, and Ensembl gene paralogs. The results are provided in publicly available datasets (http://cgd.jax.org/datasets/clustering/paraclustering.shtml describing the extent to which ancestrally related genes are in proximity beyond what is expected by chance (i.e. form paraclusters in the human and nine other vertebrate genomes, as well as the D. melanogaster, C. elegans, A. thaliana, and S. cerevisiae genomes. With the exception of Saccharomyces, paraclusters are a common feature of the genomes we examined. In the human genome they are estimated to include at least 22% of all protein coding genes. Paraclusters are far more prevalent among some gene families than others, are highly species or clade specific and can evolve rapidly, sometimes in response to environmental cues. Altogether, they account for a large portion of the functional clustering previously reported in several genomes.

  13. Breast cancer patients treated with chemotherapy reports more unmet supportive care needs in the early treatment phase, than patients treated only with radiotherapy

    Jensen-Johansen, Mikael Birkelund; Meldgaard, Anette; Henriksen, Jette

    2016-01-01

    of a large battery of selfadministered questionnaires, the women filled out at home, the Supportive Care Needs Survey (SCNS-SF34) together with demographic items (socioeconomic status, working hours, marital status etc.). The SCNS-SF34 includes 5 different domains of needs: Psychological-, Health system...... Aims: The purpose was to identify unmet supportive care needs in the early treatment phase of women treated for breast cancer and to investigate differences in needs between groups treated with chemo-therapy and radiationtherapy. If it is possible to identify early unmet needs, it may be possible...... to predict levels of unmet needs in the post-treatment phase and target an early rehabilitation to specific groups and with specific interventions. Population: Over a six-month period, 123 Danish women treated with mastectomy or lumpectomy, were assessed for eligibility in the midst of their primary...

  14. The mediating role of self-stigma and unmet needs on the recovery of people with schizophrenia living in the community.

    Chan, Kevin K S; Mak, Winnie W S

    2014-11-01

    For people with schizophrenia living in the community and receiving outpatient care, the issues of stigma and discrimination and dearth of recovery-oriented services remain barriers to recovery and community integration. The experience of self-stigma and unmet recovery needs can occur regardless of symptom status or disease process, reducing life satisfaction and disrupting overall well-being. The present study examined the mediating role of self-stigma and unmet needs in the relationship between psychiatric symptom severity and subjective quality of life. Structural equation modeling and mediation analyses were conducted based on a community sample of 400 mental health consumers with schizophrenia spectrum disorders in Hong Kong. The model of self-stigma and unmet needs as mediators between symptom severity and subjective quality of life had good fit to the data (GFI = .93, CFI = .93, NNFI = .92, RMSEA = .06, χ(2)/df ratio = 2.62). A higher level of symptom severity was significantly associated with increased self-stigma (R (2) = .24) and a greater number of unmet needs (R (2) = .53). Self-stigma and unmet needs were in turn negatively related to subjective quality of life (R (2) = .45). It is essential that service providers and administrators make greater efforts to eliminate or reduce self-stigma and unmet recovery needs, which are associated with the betterment of the overall quality of life and long-term recovery. Both incorporating empowerment and advocacy-based interventions into recovery-oriented services and providing community-based, person-centered services to people based on personally defined needs are important directions for future recovery-oriented efforts.

  15. Do We Reap What We Sow? Exploring the Association between the Strength of European Primary Healthcare Systems and Inequity in Unmet Need.

    Jens Detollenaere

    Full Text Available Access to healthcare is inequitably distributed across different socioeconomic groups. Several vulnerable groups experience barriers in accessing healthcare, compared to their more wealthier counterparts. In response to this, many countries use resources to strengthen their primary care (PC system, because in many European countries PC is the first entry-point to the healthcare system and plays a central role in the coordination of patients through the healthcare system. However it is unclear whether this strengthening of PC leads to less inequity in access to the whole healthcare system. This study investigates the association between strength indicators of PC and inequity in unmet need by merging data from the European Union Statistics on Income and Living Conditions database (2013 and the Primary Healthcare Activity Monitor for Europe (2010. The analyses reveal a significant association between the Gini coefficient for income inequality and inequity in unmet need. When the Gini coefficient of a country is one SD higher, the social inequity in unmet need in that particular country will be 4.960 higher. Furthermore, the accessibility and the workforce development of a country's PC system is inverse associated with the social inequity of unmet need. More specifically, when the access- and workforce development indicator of a country PC system are one standard deviation higher, the inequity in unmet healthcare needs are respectively 2.200 and 4.951 lower. Therefore, policymakers should focus on reducing income inequality to tackle inequity in access, and strengthen PC (by increasing accessibility and better-developing its workforce as this can influence inequity in unmet need.

  16. Racial/ethnic differences in unmet needs for mental health and substance use treatment in a community-based sample of sexual minority women.

    Jeong, Yoo Mi; Veldhuis, Cindy B; Aranda, Frances; Hughes, Tonda L

    2016-12-01

    To examine the unmet needs for mental health and substance use treatment among a diverse sample of sexual minority women (lesbian, bisexual). Sexual minority women are more likely than heterosexual women to report depression and hazardous drinking. However, relatively little is known about sexual minority women's use of mental health or substance use treatment services, particularly about whether use varies by race/ethnicity. Cross-sectional analysis of existing data. Analyses included data from 699 Latina, African American and white sexual minority women interviewed in wave 3 of the 17-year Chicago Health and Life Experiences of Women study. Using logistic regression, we examined the associations among sexual identity, race/ethnicity, use of mental health and substance use treatment, as well as potential unmet need for treatment. Overall, women in the study reported high levels of depression and alcohol dependence, and these varied by sexual identity and race/ethnicity. Use of mental health and substance use treatment also varied by race/ethnicity, as did potential unmet need for both mental health and substance use treatment. Our findings that suggest although use of treatment among sexual minority women is high overall, there is a potentially sizable unmet need for mental health and substance use treatment that varies by race/ethnicity, with Latina women showing the greatest unmet need for treatment. Nurses and other healthcare providers should be aware of the high rates of depression and hazardous drinking among sexual minority women, understand the factors that may increase the risk of these conditions among sexual minority women, the potentially high unmet need for mental health and substance use treatment - perhaps particularly among Latina women and be equipped to provide culturally sensitive care or refer to appropriate treatment services as needed. © 2016 John Wiley & Sons Ltd.

  17. Fertility desires and unmet need for family planning among HIV infected individuals in two HIV clinics with differing models of family planning service delivery.

    Wanyenze, Rhoda K; Matovu, Joseph K B; Kamya, Moses R; Tumwesigye, Nazarius M; Nannyonga, Maria; Wagner, Glenn J

    2015-01-28

    Eliminating family planning (FP) unmet need among HIV-infected individuals (PLHIV) is critical to elimination of mother-to-child HIV transmission. We assessed FP unmet need among PLHIV attending two clinics with differing models of FP services. Nsambya Home Care provided only FP information while Mulago HIV clinic provided information and contraceptives onsite. In a cross-sectional study conducted between February-June 2011, we documented pregnancies, fertility desires, and contraceptive use among 797 HIV-infected men and women (408 in Mulago and 389 in Nsambya). FP unmet need was calculated among women who were married, unmarried but had sex within the past month, did not desire the last or future pregnancy at all or wished to postpone for ≥ two years and were not using contraceptives. Multivariable analyses for correlates of FP unmet need were computed for each clinic. Overall, 40% (315) had been pregnant since HIV diagnosis; 58% desired the pregnancies. Of those who were not pregnant, 49% (366) did not desire more children at all; 15.7% wanted children then and 35.3% later. The unmet need for FP in Nsambya (45.1%) was significantly higher than that in Mulago at 30.9% (p = 0.008). Age 40+ compared to 18-29 years (OR = 6.05; 95% CI: 1.69, 21.62 in Mulago and OR = 0.21; 95% CI: 0.05, 0.90 in Nsambya), other Christian denominations (Pentecostal and Seventh Day Adventists) compared to Catholics (OR = 7.18; 95% CI: 2.14, 24.13 in Mulago and OR = 0.23; 95% CI: 0.06, 0.80 in Nsambya), and monthly expenditure > USD 200 compared to fertility support and elimination of FP unmet need among PLHIV, even with integration of FP information and supplies into HIV clinics.

  18. Characterization of the Major Purine and Pyrimidine Adducts Formed after Incubations of 1-Chloro-3-buten-2-one with Single-/Double-Stranded DNA and Human Cells.

    Liu, Ling-Yan; Zheng, Jin; Kong, Cong; An, Jing; Yu, Ying-Xin; Zhang, Xin-Yu; Elfarra, Adnan A

    2017-02-20

    We have previously shown that 1-chloro-3-buten-2-one (CBO), a potential reactive metabolite of 1,3-butadiene (BD), exhibits potent cytotoxicity and genotoxicity that have been attributed in part to its reactivity toward DNA. In an effort to identify the DNA adducts of CBO, we characterized the CBO reactions with 2'-deoxyguanosine (dG), 2'-deoxycytidine (dC), and 2'-deoxyadenosine (dA) under in vitro physiological conditions (pH 7.4, 37 °C). In the present study, we investigated the CBO reaction with 2'-deoxythymidine (dT) and compared the rate constants of the reactions of CBO with dA, dC, dG, and dT at both individual- and mixed-nucleosides levels. We also investigated the reactions of CBO with single- and double-stranded DNA using HPLC with UV detection after adducts were released by either acid or enzymatic hydrolysis of DNA. Consistent with the results from the nucleoside reactions and the rate constant experiments, 1,N 6 -(1-hydroxy-1-chloromethylpropan-1,3-diyl)adenine (A-2D) was identified as the major DNA adduct detected after acid hydrolysis, followed by N7-(4-chloro-3-oxobutyl)guanine (CG-2H) and a small amount of 1,N 6 -(1-hydroxy-1-hydroxymethylpropan-1,3-diyl)adenine (A-1D). After enzymatic hydrolysis, 1,N 6 -(1-hydroxy-1-hydroxymethylpropan-1,3-diyl)-2'-dexoyadenosine (dA-1), 3,N 4 -(1-hydroxy-1-hydroxymethylpropan-1,3-diyl)-2'-deoxycytidine (dC-1/2), and 1,N 2 -(3-hydroxy-3-hydroxymethylpropan-1,3-diyl)-2'-dexoyguanosine (CG-1) were detected, with dA-1 being the major product, followed by dC-1/2. When a nontoxic concentration of CBO (1 μM) was incubated with HepG2 cells, no adducts could be detected by LC-MS. However, pretreatment of cells with l-buthionine sulfoximine to deplete GSH levels allowed A-2D to be consistently detected in cellular DNA. These results may contribute to a better understanding of the role of the DNA adducts in CBO genotoxicity and mutagenicity. It also suggests that A-2D could be developed as a biomarker of CBO formation

  19. House dust mite major allergens Der p 1 and Der p 5 activate human airway-derived epithelial cells by protease-dependent and protease-independent mechanisms

    Timmerman J André B

    2006-03-01

    Full Text Available Abstract House dust mite allergens (HDM cause bronchoconstriction in asthma patients and induce an inflammatory response in the lungs due to the release of cytokines, chemokines and additional mediators. The mechanism how HDM components achieve this is largely unknown. The objective of this study was to assess whether HDM components of Dermatophagoides pteronissinus with protease activity (Der p 1 and unknown enzymatic activity (Der p 2, Der p 5 induce biological responses in a human airway-derived epithelial cell line (A549, and if so, to elucidate the underlying mechanism(s of action. A549 cells were incubated with HDM extract, Der p 1, recombinant Der p 2 and recombinant Der p 5. Cell desquamation was assessed by microscopy. The proinflammatory cytokines, IL-6 and IL-8, were measured by ELISA. Intracellular Ca2+ levels were assessed in A549 cells and in mouse fibroblasts expressing the human protease activated receptor (PAR1, PAR2 or PAR4. HDM extract, Der p 1 and Der p 5 dose-dependently increased the production of IL-6 and IL-8. Added simultaneously, Der p 1 and Der p 5 further increased the production of IL-6 and IL-8. The action of Der p 1 was blocked by cysteine-protease inhibitors, while that of Der p 5 couldn't be blocked by either serine- or cysteine protease inhibitors. Der p 5 only induced cell shrinking, whereas HDM extract and Der p1 also induced cell desquamation. Der p 2 had no effect on A549 cells. Der p 1's protease activity causes desquamation and induced the release of IL6 and IL-8 by a mechanism independent of Ca2+ mobilisation and PAR activation. Der p 5 exerts a protease-independent activation of A549 that involves Ca2+ mobilisation and also leads to the production of these cytokines. Together, our data indicate that allergens present in HDM extracts can trigger protease-dependent and protease-independent signalling pathways in A549 cells.

  20. Human cellular and humoral immune responses to Phlebotomus papatasi salivary gland antigens in endemic areas differing in prevalence of Leishmania major infection.

    Wafa Kammoun-Rebai

    2017-10-01

    Full Text Available Sand fly saliva compounds are able to elicit specific immune responses that have a significant role in Leishmania parasite establishment and disease outcome. Characterizing anti-saliva immune responses in individuals living in well defined leishmaniasis endemic areas would provide valuable insights regarding their effect on parasite transmission and establishment in humans.We explored the cellular and humoral immune responses to Phlebotomus (P. papatasi salivary gland extracts (SGE in individuals living in cutaneous leishmaniasis (CL old or emerging foci (OF, EF. OF was characterized by a higher infection prevalence as assessed by higher proportions of leishmanin skin test (LST positive individuals compared to EF. Subjects were further subdivided into healed, asymptomatic or naïve groups. We showed anti-SGE proliferation in less than 30% of the individuals, regardless of the immune status, in both foci. IFN-γ production was higher in OF and only observed in immune individuals from OF and naïve subjects from EF. Although IL-10 was not detected, addition of anti-human IL-10 antibodies revealed an increase in proliferation and IFN-γ production only in individuals from OF. The percentage of seropositive individuals was similar in immune and naïves groups but was significantly higher in OF. No correlation was observed between anti-saliva immune responses and LST response. High anti-SGE-IgG responses were associated with an increased risk of developing ZCL. No differences were observed for anti-SGE humoral or cellular responses among naïve individuals who converted or not their LST response or developed or not ZCL after the transmission season.These data suggest that individuals living in an old focus characterized by a frequent exposure to sand fly bites and a high prevalence of infection, develop higher anti-saliva IgG responses and IFN-γ levels and a skew towards a Th2-type cellular response, probably in favor of parasite establishment

  1. Human health and wellbeing in environmental impact assessment in New South Wales, Australia: Auditing health impacts within environmental assessments of major projects

    Harris, Patrick J.; Harris, Elizabeth; Thompson, Susan; Harris-Roxas, Ben; Kemp, Lynn

    2009-01-01

    Internationally the inclusion of health within environmental impact assessment (EIA) has been shown to be limited. While Australian EIA documentation has not been studied empirically to date, deficiencies in practice have been documented. This research developed an audit tool to undertake a qualitative descriptive analysis of 22 Major Project EAs in New South Wales, Australia. Results showed that health and wellbeing impacts were not considered explicitly. They were, however, included indirectly in the identification of traditional public health exposures associated with the physical environment and to a lesser extent the inclusion of social and economic impacts. However, no health data was used to inform any of the assessments, there was no reference to causal pathways between exposures or determinants and physical or mental health effects, and there was no inclusion of the differential distribution of exposures or health impacts on different populations. The results add conceptually and practically to the long standing integration debate, showing that health is in a position to add value to the EIA process as an explicit part of standard environmental, social and economic considerations. However, to overcome the consistently documented barriers to integrating health in EIA, capacity must be developed amongst EIA professionals, led by the health sector, to progress health related knowledge and tools.

  2. Low prevalence of human immunodeficiency virus type-1 (HIV-1) infection in population attending a major hospital in New Delhi, India.

    Aggarwal, R K; Chattopadhya, D; Kumari, S

    1996-03-01

    During 4 year period between April 1990 and March 1994, 4120 specimens from the patients attending out patient departments of Medical, Surgical and Antenatal units of a major city hospital were tested for HIV infection as a part of an on-going sentinel surveillance programme. In addition, 1440 specimens from the patients attending STD clinic of the same hospital and 862 females seeking termination of pregnancy from a near by hospital were included for comparison. It was found that only 3 individuals with high risk behaviours out of 2002 females attending antenatal clinic showed evidence of HIV infection (rate 1.49 per 1000). The corresponding rate for the group of patients attending STD clinic and seeking termination of pregnancy were 3 out of 1440 (rate 2.15 per 1000) and 1 out of 862 (rate 1.16 per 1000) respectively. It was noted that prevalence of HIV infection in the hospital attending population with unspecified risk factor (medical, surgical and antenatal clinics) was not a matter of serious concern. The importance of finding out risk factors in females attending antenatal clinic is evident from the study.

  3. Quantitative determination of regorafenib and its two major metabolites in human plasma with high-performance liquid chromatography and ultraviolet detection.

    Fujita, Kazuma; Miura, Masatomo; Shibata, Hiroyuki

    2016-10-01

    A simple, highly sensitive and specific high-performance liquid chromatography (HPLC) method was developed for the simultaneous quantitation of regorafenib, N-oxidemetabolite (M-2) and the desmethyl N-oxide metabolite (M-5) in human plasma. Regorafenib, M-2, M-5 and the internal standard sorafenib were separated using a mobile phase of 0.5% KH2 PO4 (pH 3.5)-acetonitrile (30:70, v/v), on a Capcell PAK MG II column at a flow rate of 0.5 mL/min and measurement at UV 260 nm. The lower limits of quantification for regorafenib, M-2 and M-5 were 10 ng/mL for each analyte. A procedure using solid-phase extraction required only a small amount of plasma (100 μL) for one analysis while providing high extraction recovery (>81% for all compounds) and good selectivity. Coefficients of variation for intra- and inter-day assays were HPLC assay is suitable for clinical pharmacokinetic studies of regorafenib. Th