WorldWideScience

Sample records for expanding clinical implications

  1. OCT Expanded Clinical Data Analysis

    Science.gov (United States)

    Van Baalen, Mary; Tafreshi, Ali; Patel, Nimesh; Young, Millennia; Mason, Sara; Otto, Christian; Samuels, Brian; Koslovsky, Matthew; Schaefer, Caroline; Taiym, Wafa; hide

    2017-01-01

    Vision changes identified in long duration space fliers has led to a more comprehensive clinical monitoring protocol. Optical Coherence Tomography (OCT) was recently implemented on board the International Space Station in 2013. NASA is collaborating with Heidelberg Engineering to expand our current OCT data analysis capability by implementing a volumetric approach. Volumetric maps will be created by combining the circle scan, the disc block scan, and the radial scan. This assessment may provide additional information about the optic nerve and further characterize changes related microgravity exposure. We will discuss challenges with collection and analysis of OCT data, present the results of this reanalysis and outline the potential benefits and limitations of the additional data.

  2. Japan: Implications of an Expanded Military Role,

    Science.gov (United States)

    1985-07-03

    served by diplomatic, economic and foreign assistance strategies. The Fukuda and Ohira " doctrines " emphasized the role of non-military policy in...encourage it to expand economic assistance under the comprehensive security doctrine . Weinstein is criticizing U.S. policy toward the Soviet Union; he...the United States. The second category of opinion which developed centered -~ on support for a policy line orginally set forth In the Yoshida Doctrine

  3. PROFAM expands Mexican family planning clinics.

    Science.gov (United States)

    1983-01-01

    Mexico's private, nonprofit social marketing company, known as PROFAM, intends to expand its family planning clinics to marginal urban areas. The clinics are part of PROFAM's push to diversify social marketing outlets for contraceptive products and other birth control methods. PROFAM expects to establish 3 new clinics, possibly including a pregnancy test laboratory, a small 1-doctor clinic, and a large clinic housing an operating room. 1 clinic will be located outside the Mexico City area, the program's traditional boundaries. The company currently runs 2 small clinics and a pregnancy testing laboratory in Ciudad Netzahualcoyti, a community of 3.5 million on Mexico City's outskirts. PROFAM recently obtaine d government approval to sell condoms in food stores, which should increase distribtuion and sales. Currently, the company sells over 1 million high quality, lubricated condoms each month, accounting for over half of the Mexican market. Distribution covers 85% of the country's drugstore. Program setbacks occurred in 1981, when the Mexican government cancelled PROFAM's sales permits for all contraceptive products except condoms. Cancelled products included an oral contraceptive and 3 vaginal spermicides. These 4 products had provided nearly 100,000 couple years of protection in 1979 and an estimated 120,000 CYP 1980. During 1979 and 1980, condoms provided about 27,000 and 60,000 CYP, respectively. PROFAM had relied heavily on the pill and spermicides because its early studies showed condoms had a negative image in Mexico, due largely to the product's association with extramarital affairs. To counter this, PROFAM launched a widespread, free product sampling program in 1979, along with a continuing educational and advertising drive. Subsequent consumer surveys revealed a marked increase in product acceptance, with PROFAM's condom becoming the most widely known brand available in Mexico.

  4. Lissencephaly: Expanded imaging and clinical classification.

    Science.gov (United States)

    Di Donato, Nataliya; Chiari, Sara; Mirzaa, Ghayda M; Aldinger, Kimberly; Parrini, Elena; Olds, Carissa; Barkovich, A James; Guerrini, Renzo; Dobyns, William B

    2017-06-01

    Lissencephaly ("smooth brain," LIS) is a malformation of cortical development associated with deficient neuronal migration and abnormal formation of cerebral convolutions or gyri. The LIS spectrum includes agyria, pachygyria, and subcortical band heterotopia. Our first classification of LIS and subcortical band heterotopia (SBH) was developed to distinguish between the first two genetic causes of LIS-LIS1 (PAFAH1B1) and DCX. However, progress in molecular genetics has led to identification of 19 LIS-associated genes, leaving the existing classification system insufficient to distinguish the increasingly diverse patterns of LIS. To address this challenge, we reviewed clinical, imaging and molecular data on 188 patients with LIS-SBH ascertained during the last 5 years, and reviewed selected archival data on another ∼1,400 patients. Using these data plus published reports, we constructed a new imaging based classification system with 21 recognizable patterns that reliably predict the most likely causative genes. These patterns do not correlate consistently with the clinical outcome, leading us to also develop a new scale useful for predicting clinical severity and outcome. Taken together, our work provides new tools that should prove useful for clinical management and genetic counselling of patients with LIS-SBH (imaging and severity based classifications), and guidance for prioritizing and interpreting genetic testing results (imaging based- classification). © 2017 Wiley Periodicals, Inc.

  5. The expanding clinical spectrum of torpedo maculopathy.

    Science.gov (United States)

    Trevino, Richard; Kiani, Salma; Raveendranathan, Praneetha

    2014-04-01

    Torpedo maculopathy is an idiopathic, congenital, oval-shaped region of chorioretinal hypopigmentation located temporal to the macula. Torpedo lesions are typically unilateral, occasionally harbor an intraretinal cleft, and may be associated with varying degrees of hyperpigmentation. Visual acuity is usually normal, but the lesion may produce a scotoma in the visual field. There are no known associated systemic or ocular abnormalities. Diagnosis is based upon recognition of its characteristic shape and location. Because of its nonprogressive and generally benign nature, no treatment is required. Two cases of torpedo maculopathy associated with fundus excavation are presented. To the best of our knowledge, this is the first reported association of torpedo maculopathy with fundus excavation. In one case, the visual acuity remained unaffected and in the other case the visual acuity was reduced to 20/50. In both cases, optical coherence tomography clearly demonstrates the excavated nature of the torpedo lesions. In case 1, where the visual acuity was normal, the excavation is remote from the fovea but in case 2, where the visual acuity was 20/50, the excavation encroaches upon the fovea. In both cases, a scotoma corresponding to the excavated region could be demonstrated. Torpedo maculopathy is a usually benign condition associated with normal visual acuity and normal visual fields. Our cases demonstrate that torpedo maculopathy may be associated with excavation of the fundus and a corresponding scotoma in the visual field. Visual acuity may be compromised should the excavation encroach upon the central fovea. Knowledge of this previously unreported clinical manifestation of torpedo maculopathy may aid in advancing the understanding of this condition and the care of patients with the disorder.

  6. Glycemic variability: Clinical implications

    Directory of Open Access Journals (Sweden)

    Surabhi Venkata Satya Krishna

    2013-01-01

    Full Text Available Glycemic control and its benefits in preventing microvascular diabetic complications are convincingly proved by various prospective trials. Diabetes control and complications trial (DCCT had reported variable glycated hemoglobin (HbA1C as a cause of increased microvascular complications in conventional glycemic control group versus intensive one. However, in spite of several indirect evidences, its link with cardiovascular events or macrovascular complications is still not proved. Glycemic variability (GV is one more tool to explain relation between hyperglycemia and increased cardiovascular risk in diabetic patients. In fact GV along with fasting blood sugar, postprandial blood sugar, HbA1C, and quality of life has been proposed to form glycemic pentad, which needs to be considered in diabetes management. Postprandial spikes in blood glucose as well as hypoglycemic events, both are blamed for increased cardiovascular events in Type 2 diabetics. GV includes both these events and hence minimizing GV can prevent future cardiovascular events. Modern diabetes management modalities including improved sulfonylureas, glucagon like peptide-1 (GLP-1-based therapy, newer basal insulins, and modern insulin pumps address the issue of GV effectively. This article highlights mechanism, clinical implications, and measures to control GV in clinical practice.

  7. Expanded clinical spectrum of enhanced S-cone syndrome

    NARCIS (Netherlands)

    Yzer, Suzanne; Barbazetto, Irene; Allikmets, Rando; van Schooneveld, Mary J.; Bergen, Arthur; Tsang, Stephen H.; Jacobson, Samuel G.; Yannuzzi, Lawrence A.

    2013-01-01

    New funduscopic findings in patients with enhanced S-cone syndrome (ESCS) may help clinicians in diagnosing this rare autosomal recessive retinal dystrophy. To expand the clinical spectrum of ESCS due to mutations in the NR2E3 gene. Retrospective, noncomparative case series of 31 patients examined

  8. Reshaping the Sword and Chrysanthemum: Regional Implications of Expanding the Mission of the Japan Self Defense Forces

    Science.gov (United States)

    2005-03-01

    NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS RESHAPING THE SWORD AND CHRYSANTHEMUM : REGIONAL IMPLICATIONS OF EXPANDING THE...Sword and Chrysanthemum : Regional Implications of Expanding the Mission of the Japan Self Defense Forces 6. AUTHOR(S) Robert F. Hight Jr. 5. FUNDING...SWORD AND CHRYSANTHEMUM : REGIONAL IMPLICATIONS OF EXPANDING THE MISSION OF THE JAPAN SELF DEFENSE FORCES Robert F. Hight Jr. Lieutenant

  9. Long-term implications of observing an expanding cosmological civilization

    Science.gov (United States)

    Olson, S. Jay

    2018-01-01

    Suppose that advanced civilizations, separated by a cosmological distance and time, wish to maximize their access to cosmic resources by rapidly expanding into the universe. How does the presence of one limit the expansionistic ambitions of another, and what sort of boundary forms between their expanding domains? We describe a general scenario for any expansion speed, separation distance and time. We then specialize to a question of particular interest: What are the future prospects for a young and ambitious civilization if they can observe the presence of another at a cosmological distance? We treat cases involving the observation of one or two expanding domains. In the single-observation case, we find that almost any plausible detection will limit one's future cosmic expansion to some extent. Also, practical technological limits to expansion speed (well below the speed of light) play an interesting role. If a domain is visible at the time one embarks on cosmic expansion, higher practical limits to expansion speed are beneficial only up to a certain point. Beyond this point, a higher speed limit means that gains in the ability to expand are more than offset by the first-mover advantage of the observed domain. In the case of two visible domains, it is possible to be `trapped' by them if the practical speed limit is high enough and their angular separation in the sky is large enough, i.e. one's expansion in any direction will terminate at a boundary with the two visible civilizations. Detection at an extreme cosmological distance has surprisingly little mitigating effect on our conclusions.

  10. Expanding the mutation and clinical spectrum of Roberts syndrome.

    Science.gov (United States)

    Afifi, Hanan H; Abdel-Salam, Ghada M H; Eid, Maha M; Tosson, Angie M S; Shousha, Wafaa Gh; Abdel Azeem, Amira A; Farag, Mona K; Mehrez, Mennat I; Gaber, Khaled R

    2016-07-01

    Roberts syndrome and SC phocomelia syndrome are rare autosomal recessive genetic disorders representing the extremes of the spectrum of severity of the same condition, caused by mutations in ESCO2 gene. We report three new patients with Roberts syndrome from three unrelated consanguineous Egyptian families. All patients presented with growth retardation, mesomelic shortening of the limbs more in the upper than in the lower limbs and microcephaly. Patients were subjected to clinical, cytogenetic and radiologic examinations. Cytogenetic analysis showed the characteristic premature separation of centromeres and puffing of heterochromatic regions. Further, sequencing of the ESCO2 gene identified a novel mutation c.244_245dupCT (p.T83Pfs*20) in one family besides two previously reported mutations c.760_761insA (p.T254Nfs*27) and c.764_765delTT (p.F255Cfs*25). All mutations were in homozygous state, in exon 3. The severity of the mesomelic shortening of the limbs and craniofacial anomalies showed variability among patients. Interestingly, patient 1 had abnormal skin hypopigmentation. Serial fetal ultrasound examinations and measurements of long bones diagnosed two affected fetuses in two of the studied families. A literature review and case comparison was performed. In conclusion, we report a novel ESCO2 mutation and expand the clinical spectrum of Roberts syndrome. © 2015 Japanese Teratology Society.

  11. Venous chest anatomy: clinical implications.

    Science.gov (United States)

    Chasen, M H; Charnsangavej, C

    1998-03-01

    This article provides a practical approach to the clinical implications and importance of understanding the collateral venous anatomy of the thorax. Routine radiography, conventional venography, computed tomography (CT), and magnetic resonance (MR) imaging studies provide correlative anatomic models for the demonstration of how interconnecting collateral vascular networks within the thorax maintain venous stability at all times. Five major systems comprise the collateral venous network of the thorax (Fig. 1). These include the paravertebral, azygos-hemiazygos, internal mammary, lateral thoracic, and anterior jugular venous systems (AJVS). The five systems are presented in the following sequence: (a) a brief introduction to the importance of catheter position and malposition in understanding access to the thoracic venous system, (b) the anatomy of the azygos-hemiazygos systems and their relationship with the paravertebral plexus, (c) the importance of the AJVS, (d) 'loop' concepts interconnecting the internal mammary and azygos-hemiazygos systems by means of the lateral thoracic and intercostal veins, and (e) the interconnecting venous networks on the thoracic side of the thoracoabdominal junction. Certain aspects of the venous anatomy of the thorax will not be discussed in this chapter and include (a) the intra-abdominal anastomoses between the superior and inferior vena cavae (IVC) via the internal mammary, lateral thoracic, and azygos-hemiazygos systems (beyond the scope of this article), (b) potential collateral vessels involving vertebral, parascapular, thyroidal, thymic, and other smaller veins that might anastomose with the major systems, and (c) anatomic variants and pitfalls that may mimic pathologic conditions (space limitations).

  12. Venous chest anatomy: clinical implications

    Energy Technology Data Exchange (ETDEWEB)

    Chasen, M.H.; Charnsangavej, C. [Department of Diagnostic Imaging, The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030 (United States)

    1998-03-01

    This article provides a practical approach to the clinical implications and importance of understanding the collateral venous anatomy of the thorax. Routine radiography, conventional venography, computed tomography (CT), and magnetic resonance (MR) imaging studies provide correlative anatomic models for the demonstration of how interconnecting collateral vascular networks within the thorax maintain venous stability at all times. Five major systems comprise the collateral venous network of the thorax ( Fig. 1 ). These include the paravertebral, azygos-hemiazygos, internal mammary, lateral thoracic, and anterior jugular venous systems (AJVS). The five systems are presented in the following sequence: (a) a brief introduction to the importance of catheter position and malposition in understanding access to the thoracic venous system, (b) the anatomy of the azygos-hemiazygos systems and their relationship with the paravertebral plexus, (c) the importance of the AJVS, (d) 'loop' concepts interconnecting the internal mammary and azygos-hemiazygos systems by means of the lateral thoracic and intercostal veins, and (e) the interconnecting venous networks on the thoracic side of the thoracoabdominal junction. Certain aspects of the venous anatomy of the thorax will not be discussed in this chapter and include (a) the intra-abdominal anastomoses between the superior and inferior vena cavae (IVC) via the internal mammary, lateral thoracic, and azygos-hemiazygos systems (beyond the scope of this article), (b) potential collateral vessels involving vertebral, parascapular, thyroidal, thymic, and other smaller veins that might anastomose with the major systems, and (c) anatomic variants and pitfalls that may mimic pathologic conditions (space limitations). (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  13. Cockayne syndrome: the expanding clinical and mutational spectrum.

    Science.gov (United States)

    Laugel, Vincent

    2013-01-01

    Cockayne syndrome is a progressive multisystem disorder characterized by a specific cellular defect in transcription-coupled repair. Typical features include developmental delay, failure to thrive, microcephaly, cutaneous photosensitivity, dental anomalies, progressive hearing loss, pigmentary retinopathy, cataracts and enophthalmia. Various levels of severity have been described including the "classical" or moderate type I CS, the early-onset or severe type II and the mild or late-onset type III. Adult-onset cases with prolonged survival and normal initial development have also been identified. At the opposite end of the scale, the most severely affected patients, showing a prenatal onset of the symptoms, are overlapping with the cerebro-oculo-facio-skeletal (COFS) syndrome. These overlapping subtypes build a continuous spectrum without clear thresholds. Revised diagnostic criteria are proposed to improve the recognition of the disease. Two thirds of the patients are linked to mutations in the CSB (ERCC6) gene, one third to mutations in the CSA (ERCC8) gene. At least 78 different mutations are known in the CSB gene and 30 in the CSA gene to date, in more than 120 genetically confirmed patients. Large clinical and molecular databases are needed to unravel genotype-phenotype correlations and to gain more insight into the underlying molecular mechanisms. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Pyridoxine-Dependent Epilepsy: An Expanding Clinical Spectrum.

    Science.gov (United States)

    van Karnebeek, Clara D M; Tiebout, Sylvia A; Niermeijer, Jikkemien; Poll-The, Bwee Tien; Ghani, Aisha; Coughlin, Curtis R; Van Hove, Johan L K; Richter, Jost Wigand; Christen, Hans Juergen; Gallagher, Renata; Hartmann, Hans; Stockler-Ipsiroglu, Sylvia

    2016-06-01

    Pyridoxine-dependent epilepsy is a rare autosomal recessive epileptic encephalopathy caused by antiquitin (ALDH7A1) deficiency. In spite of adequate seizure control, 75% of patients suffer intellectual developmental disability. Antiquitin deficiency affects lysine catabolism resulting in accumulation of α-aminoadipic semialdehyde/pyrroline 6' carboxylate and pipecolic acid. Beside neonatal refractory epileptic encephalopathy, numerous neurological manifestations and metabolic/biochemical findings have been reported. We present a phenotypic spectrum of antiquitin deficiency based on a literature review (2006 to 2015) of reports (n = 49) describing the clinical presentation of confirmed patients (n > 200) and a further six patient vignettes. Possible presentations include perinatal asphyxia; neonatal withdrawal syndrome; sepsis; enterocolitis; hypoglycemia; neuroimaging abnormalities (corpus callosum and cerebellar abnormalities, hemorrhage, white matter lesions); biochemical abnormalities (lactic acidosis, electrolyte disturbances, neurotransmitter abnormalities); and seizure response to pyridoxine, pyridoxal-phosphate, and folinic acid dietary interventions. The phenotypic spectrum of pyridoxine-dependent epilepsy is wide, including a myriad of neurological and systemic symptoms. Its hallmark feature is refractory seizures during the first year of life. Given its amenability to treatment with lysine-lowering strategies in addition to pyridoxine supplementation for optimal seizure control and developmental outcomes, early diagnosis of pyridoxine-dependent epilepsy is essential. All infants presenting with unexplained seizures should be screened for antiquitin deficiency by determination of α-aminoadipic semialdehyde/pyrroline 6' carboxylate (in urine, plasma or cerebrospinal fluid) and ALDH7A1 molecular analysis. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. THE EXPANDING CLINICAL SPECTRUM OF CHOROIDAL EXCAVATION IN MACULAR DYSTROPHIES.

    Science.gov (United States)

    Battaglia Parodi, Maurizio; Casalino, Giuseppe; Iacono, Pierluigi; Introini, Ugo; Adamyan, Tatevik; Bandello, Francesco

    2017-08-09

    To assess the prevalence and the clinical course of focal choroidal excavation (FCE) in patients affected by macular dystrophies. Prospective case series. All the patients underwent a complete ophthalmologic examination, including best-corrected visual acuity and spectral domain optical coherence tomography. The presence of choroidal neovascularization (CNV) was assessed on the basis of the leakage detected on fluorescein angiography. A total of 162 eyes from 81 patients with macular dystrophy were included in the study. FCE was diagnosed in seven eyes (4.3% of the eyes), including four eyes with Best vitelliform dystrophy, two eyes with pattern dystrophy associated with pseudoxanthoma elasticum, and one case of Stargardt disease. In eyes with FCE and macular dystrophy, the mean best-corrected visual acuity was 0.4 ± 0.1 logarithm of the minimum angle of resolution (approximately corresponding to 20/50 Snellen equivalent) at baseline and was stable to 0.41 ± 0.1 logarithm of the minimum angle of resolution (approximately corresponding to 20/50 Snellen equivalent) at the final visit. In four of these seven eyes, FCE was associated with a subfoveal CNV. The CNV was managed with one intravitreal anti-vascular endothelial growth factor injection, achieving the complete anatomical stabilization of the CNV and recovery of the best-corrected visual acuity. Focal choroidal excavation can be infrequently encountered in patients with macular dystrophies. The presence of CNV may complicate FCE in these patients, and anti-vascular endothelial growth factor seems to be an effective treatment with no progression of FCE over time.

  16. Clinical Implications Of Childhood Bilingualism | Southwood ...

    African Journals Online (AJOL)

    Stellenbosch Papers in Linguistics Plus. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 32 (2003) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Clinical Implications Of Childhood Bilingualism.

  17. [Orexin: clinical and therapeutic implications].

    Science.gov (United States)

    Mediavilla, Cristina; Risco, Severiano

    2014-02-01

    INTRODUCTION. Recent research has reported the existence of a new class of neuropeptides, called orexins or hypocretins, which are produced by a small group of neurons in the hypothalamus and whose actions are mediated by two types of receptors: OX1R and OX2R. More specifically, the orexinergic neurons have been located exclusively in cells in the lateral, dorsomedial and perifornical areas of the hypothalamus. Despite this highly specific anatomical origin, the orexinergic neurons are projected widely into a number of brainstem, cortical and limbic regions. DEVELOPMENT. This fuzzy pattern of distribution of the orexinergic fibres would be indicating the involvement of this peptidic system in a wide range of functions; indeed, it has been related with the mechanisms that enable regulation of the sleep-wake cycle, the ingestion of food and drink, and some particular types of learning, such as learning certain preferences regarding tastes. It has also been suggested that upsets in the functioning of the orexinergic system would explain the appearance of certain clinical disorders like narcolepsy, obesity or addiction to drug of abuse. CONCLUSIONS. Further research will help to determine the functioning of orexinergic neurons and the interaction between the systems that regulate emotion, energetic homeostasis and the reward mechanisms, on the one hand, and the systems that regulate the sleep-wake cycle on the other. That knowledge would almost certainly make it possible to develop new drugs that, by acting upon the orexinergic system, would be effective in the treatment of sleep disorders such as insomnia or narcolepsy, eating disorders or drug addiction.

  18. Clinical implications of contemporary gender theory.

    Science.gov (United States)

    Kulish, Nancy

    2010-04-01

    The current intellectual scene in psychoanalysis is marked by vigorous theoretical controversies about gender. The ideas being debated have important implications for clinical work, which have not been thoroughly explicated or integrated into common practice. These implications include the following: gender can accrue idiosyncratic meanings; gender identity is considered fluid and rigidity of gender identity deemed problematic; gender-related conflicts are typically described as divergent; analysis of superego conflicts related to gender becomes particularly important; and, finally, gender-related biases are seen as inevitable and must be taken into account in the clinical situation. A detailed clinical example illustrates the application of these ideas. While the more dramatic cases related to gender have been more frequent subjects of study, conflicts about gender are everyday occurrences for our patients and deserve further attention.

  19. Clinical Implications of Sarcopenic Obesity in Cancer.

    Science.gov (United States)

    Carneiro, Isabella P; Mazurak, Vera C; Prado, Carla M

    2016-10-01

    Sarcopenia has been associated with several negative clinical outcomes in cancer. However, the consequences of sarcopenic obesity, a condition of combined sarcopenia and obesity burden, have been less extensively investigated. The aim of this paper was to review the current evidence on the prevalence and clinical implications of sarcopenic obesity in cancer. A total of 14 studies linking sarcopenic obesity to a clinical outcome in cancer were included. There is considerable inconsistency in methods used to evaluate body composition as well as in the criteria used to define sarcopenic obesity, which limits comparison among studies. Therefore, the prevalence of sarcopenic obesity varied substantially: between 1 and 29 % in studies including individuals from all body mass index categories and between 15 and 36 % for those including obese individuals only. Negative clinical outcomes reported to be associated with sarcopenic obesity included higher risk of dose-limiting toxicity, surgical complications, physical disability, and shorter survival.

  20. Clinical implications of angiogenesis in cancers

    Directory of Open Access Journals (Sweden)

    Roberta WC Pang

    2006-06-01

    Full Text Available Roberta WC Pang1, Ronnie TP Poon2 Departments of 1Medicine and 2Surgery, The University of Hong Kong, Pokfulam, Hong Kong, ChinaAbstract: Angiogenesis plays an important role in the growth and progression of cancer. The regulation of tumor angiogenesis depends on a net balance of angiogenic factors and antiangiogenic factors, which are secreted by both tumor cells and host-infiltrating cells. Numerous studies have indicated that assessment of angiogenic activity by either microvessel density or expression of angiogenic factors in cancer can provide prognostic information independent of conventional clinicopathological factors such as tumor staging. Some studies also suggested that assessment of tumor angiogenesis may predict cancer response to chemotherapy or radiotherapy. However, the most important clinical implication of tumor angiogenesis is the development of a novel strategy of anticancer therapy targeting tumor vessels instead of cancer cells. Antiangiogenic therapy aims to inhibit the growth of tumor, and current evidence suggests that it works best in combination with conventional cytotoxic chemotherapy. Recently, a monoclonal antibody against vascular endothelial growth factor, which is one of the most potent angiogenic factors, has been approved for clinical use in colorectal cancer patients after a clinical trial confirmed that combining the antibody with standard chemotherapy regimen could prolong patient survival. The clinical implications of angiogenesis in cancer are reviewed in this article.Keywords: angiogenesis, antiangiogenic therapy, cancer, prognosis

  1. Clinical Implications of Antiviral Resistance in Influenza

    Directory of Open Access Journals (Sweden)

    Timothy C. M. Li

    2015-09-01

    Full Text Available Influenza is a major cause of severe respiratory infections leading to excessive hospitalizations and deaths globally; annual epidemics, pandemics, and sporadic/endemic avian virus infections occur as a result of rapid, continuous evolution of influenza viruses. Emergence of antiviral resistance is of great clinical and public health concern. Currently available antiviral treatments include four neuraminidase inhibitors (oseltamivir, zanamivir, peramivir, laninamivir, M2-inibitors (amantadine, rimantadine, and a polymerase inhibitor (favipiravir. In this review, we focus on resistance issues related to the use of neuraminidase inhibitors (NAIs. Data on primary resistance, as well as secondary resistance related to NAI exposure will be presented. Their clinical implications, detection, and novel therapeutic options undergoing clinical trials are discussed.

  2. Honesty, candour, and transparency: clinical implications.

    Science.gov (United States)

    Papanikitas, Andrew

    2016-01-01

    In advance of a medical conference on the duty of candour for medical ethics educators, this paper discusses the duty of candour as a significant development in the culture of medicine. Those who teach medical ethics need to assess its implications for their own practice. It is also a duty that needs to be critically examined in light of both patients' interests and clinical work environments if it is to be practical and not meaningless rhetoric. Two examples of ways in which that critical examination might take place are outlined.

  3. When are nursing students on clinical placements ready to expand their learning repertoire?

    DEFF Research Database (Denmark)

    Holmberg, Marlene; Stisen, Bente Kjærgaard; Grau, Sarah M.

    2018-01-01

    . What is unknown is when baccalaureate nursing students are ready to develop the other learning styles, and what facilitates such an expansion in their learning style repertoire? This is important, because students need to develop the abilities to learn both by acting and by deepen their knowledge...... of theory to meet the requirements of the nursing profession. An American study found that operating room students felt confident to adopt new learning styles by the third week of clinical placements. No studies to date have retrieved a similar pattern of readiness to expand learning style repertoire among...... nursing students. Therefore, the aim of our study was to investigate when students are ready to expand their learning style repertoire in a Baccalaureate Nursing Programme and to investigate the factors that influence such an expansion. Data were generated through participant observations and interviews...

  4. Sclerostin: recent advances and clinical implications.

    Science.gov (United States)

    Honasoge, Mahalakshmi; Rao, Ajay D; Rao, Sudhaker D

    2014-12-01

    Discovery of the Wnt signaling pathway and understanding the central role of osteocyte in skeletal homeostasis have been the major advances in skeletal biology over the past decade. Sclerostin, secreted mainly (but not exclusively) by osteocytes, has emerged as a key player in skeletal homeostasis. This review highlights the most relevant recent advances. Sclerostin by inhibiting Wnt signaling pathway decreases bone formation and osteoblast differentiation and promotes osteoblast apoptosis. Ability to measure serum sclerostin levels better clarified the role of sclerostin in various physiologic and pathologic states. Early clinical trials with antibodies to sclerostin have produced robust increases in bone mineral density, and fracture prevention trials are underway. Since the discovery of Wnt signaling pathway and sclerostin's association with high bone mass, there has been a remarkable progress. Clinical trials with fracture endpoints, already underway, should expand osteoanabolic therapeutic horizon in the very near future. Measurement of sclerostin levels in a number of conditions has advanced our knowledge about pathophysiology of skeletal and nonskeletal disorders in an altogether new light.

  5. Expanding the "Ports of Entry" for Speech-Language Pathologists: A Relational and Reflective Model for Clinical Practice

    Science.gov (United States)

    Geller, Elaine; Foley, Gilbert M.

    2009-01-01

    Purpose: To outline an expanded framework for clinical practice in speech-language pathology. This framework broadens the focus on discipline-specific knowledge and infuses mental health constructs within the study of communication sciences and disorders, with the objective of expanding the potential "ports or points of entry" (D. Stern, 1995) for…

  6. with Dilated Cardiomyopathy; Clinical and Prognostic Implications

    Directory of Open Access Journals (Sweden)

    Taylan Akgun

    2014-06-01

    Full Text Available The QRS represents the simultaneous activation of the right and left ventricles, although mostof the QRS waveform is derived from the larger left ventricular musculature. Although normalQRS duration is <100 millisecond (ms, its duration and shape are quite variable from patient topatient in idiopathic dilated cardiomyopathy (IDCM. Prolongation of QRS occurs in 14% to 47%of heart failure (HF patients. Left bundle branch block (LBBB is far more common than rightbundle branch block (RBBB. Dyssynchronous left ventricular activation due to LBBB and otherintraventricular conduction blocks provides the rationale for the use of cardiac resynchronizationtherapy with biventricular pacing in patients with IDCM. Fragmented QRS (fQRS is a markerof depolarization abnormality and present in significant number of the patients with IDCM andnarrow QRS complexes. It is associated with arrhythmic events and intraventricular dyssynchrony.The purpose of this manuscript is to present an overview on some clinical, echocardiographic andprognostic implications of various QRS morphologies in patients with IDCM.

  7. Clinical implications of de Barsy syndrome.

    Science.gov (United States)

    Warner, Lindsay L; Olsen, David A; Smith, Hugh M

    2017-11-17

    De Barsy syndrome is a rare, autosomal recessive syndrome characterized by cutis laxa, progeroid appearance, ophthalmic opacification, skeletal malformations, growth delays, and intellectual disability. The aim of this case series is to identify the anesthetic considerations in the clinical management of patients with de Barsy syndrome. A retrospective case review from 1968 to 2016 was performed at a single tertiary medical center to identify patients with de Barsy syndrome who underwent anesthesia for diagnostic and surgical procedures. We collected and analyzed the perioperative records and following data: age, sex, American Society of Anesthesiologists physical status, relevant comorbidities, surgical procedures, anesthesia management, and observed complications. Three patients underwent 64 unique anesthetics for a diverse collection of diagnostic and surgical procedures. An array of anesthetics and techniques were successfully used. Observations of the perioperative period found 7 episodes of intraoperative hyperthermia (>38.3°), a single difficult airway requiring fiberoptic bronchoscopic-guided intubation, and repeatedly difficult intravenous access. This expanded case series suggests that providers caring for patients with de Barsy syndrome should be aware of potential challenges with airway management, vascular access, and temperature monitoring. © 2017 John Wiley & Sons Ltd.

  8. Brain microbleeds: Epidemiology and clinical implications.

    Science.gov (United States)

    Boyano, I; Bravo, N; Miranda, J; Gil-Gregorio, P; Olazarán, J

    2016-06-22

    Brain microbleeds (BMB) are haemosiderin deposits contained within macrophages, which are displayed as hypointense images in some T2-weighted magnetic resonance imaging sequences. There are still many questions to be answered about the pathophysiology and clinical relevance of BMB. We conducted a literature review of the main epidemiological, clinical, and anatomical pathology studies of BMB performed in the general population, in patients at risk of or already suffering from a vascular disease, and in patients with cognitive impairment. We analysed the prevalence of BMB, risk factors, and potential pathophysiological mechanisms and clinical implications. The prevalence of BMB is highly variable (3%-27% in the general population, 6%-80% in patients with vascular risk factors or vascular disease, and 16%-45% in patients with cognitive impairment). BMB are associated with ageing, Alzheimer disease (AD), and in particular haemorrhagic or ischaemic cerebrovascular disease. The pathological substrate of BMB is either lipohyalinosis (subcortical BMB) or cerebral amyloid angiopathy (lobar BMB). BMB exacerbate cognitive impairment, possibly through cortical-subcortical and intracortical disconnection, and increase the risk of death, mostly due to vascular causes. BMB also increase the risk of cerebral haemorrhage, particularly in patients with multiple lobar BMB (probable erebral amyloid angiopathy). Therefore, anticoagulant treatment may be contraindicated in these patients. In patients with lower risk of bleeding, the new oral anticoagulants and the combination of clinical and magnetic resonance imaging follow-up could be helpful in the decision-making process. Copyright © 2016 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  9. In the Ethos of the Safety Net: An Expanded Role for Clinical Ethics Mediation.

    Science.gov (United States)

    McGreevy, Jolion

    2015-01-01

    Clinical ethics mediation is invaluable for resolving intractable disputes in the hospital. But it is also a critical day-to-day skill for clinicians, especially those who serve a disproportionate number of vulnerable patients. While mediation is typically reserved for intractable cases, there are two important opportunities to expand its use. First is preventative mediation, in which clinicians incorporate clinical ethics mediation into their daily routine in order to address value-laden conflicts before they reach the point at which outside consultation becomes necessary. Second is guided mediation, in which clinical teams resolve conflicts with patients or surrogates with guidance from an ethics consultant, who operates at some distance from the conflict and, rather than recommending a single action, counsels clinicians on the process they can use to resolve the conflict on their own. These approaches build the capacity of all clinicians to use clinical ethics mediation to improve the care of vulnerable patients. Copyright 2015 The Journal of Clinical Ethics. All rights reserved.

  10. Teachers' Experiences Collaborating in Expanded School Mental Health: Implications for Practice, Policy and Research

    Science.gov (United States)

    Mellin, Elizabeth A.; Ball, Annahita; Iachini, Aidyn; Togno, Nicole; Rodriguez, Ana Maria

    2017-01-01

    Teachers are critical partners in expanded school mental health (ESMH) collaborations that aim to bring educators, community mental health professionals and families together to leverage expertise and resources for addressing non-academic barriers to learning. Although teachers are in a unique position to observe the day-to-day mental health needs…

  11. Clinical implication of latent myofascial trigger point.

    Science.gov (United States)

    Celik, Derya; Mutlu, Ebru Kaya

    2013-08-01

    Myofascial trigger points (MTrPs) are hyperirritable points located within a taut band of skeletal muscle or fascia, which cause referred pain, local tenderness and autonomic changes when compressed. There are fundamental differences between the effects produced by the two basic types of MTrPs (active and latent). Active trigger points (ATrPs) usually produce referred pain and tenderness. In contrast, latent trigger points (LTrPs) are foci of hyperirritability in a taut band of muscle, which are clinically associated with a local twitch response, tenderness and/or referred pain upon manual examination. LTrPs may be found in many pain-free skeletal muscles and may be "activated" and converted to ATrPs by continuous detrimental stimuli. ATrPs can be inactivated by different treatment strategies; however, they never fully disappear but rather convert to the latent form. Therefore, the diagnosis and treatment of LTrPs is important. This review highlights the clinical implication of LTrPs.

  12. Polycystic ovary syndrome: clinical implication in perimenopause

    Directory of Open Access Journals (Sweden)

    Monika Lenart-Lipińska

    2014-12-01

    Full Text Available Polycystic ovary syndrome (PCOS, a hyperandrogenic disorder, is the commonest endocrinopathy in premenopausal women. This syndrome is associated with fertility problems, clinical manifestations of hyperandrogenism and metabolic disturbances, particularly insulin resistance and obesity. There is a great body of evidence that patients with PCOS present multiple cardiovascular risk factors and cluster components of metabolic syndrome from early ages. The presence of comorbidities such as abdominal obesity, insulin resistance, type 2 diabetes, hypertension places these females at an increased risk of future cardiovascular events. However, the extent to which PCOS components are present in perimenopausal women and the degree to which PCOS increases various risk factors in addition to the known risk of the perimenopausal period have not been fully determined. The perimenopausal period per se is associated with weight gain and an increased cardiovascular risk, which may be additionally aggravated by the presence of metabolic disturbances connected with PCOS. The phenotype of PCOS may improve with aging and it is still uncertain whether the presence of PCOS significantly increases the cardiovascular risk later in women’s life. Most recent data suggest that the prevalence of cardiovascular diseases and the related long-term consequences in females with PCOS seem to be lower than expected. This manuscript reviews long-term consequences of PCOS and considers their clinical implications in perimenopause.

  13. Clinical Skills Performed By Iranian Emergency Nurses: Perceived Competency Levels and Attitudes Toward Expanding Professional Roles.

    Science.gov (United States)

    Hassankhani, Hadi; Hasanzadeh, Firooz; Powers, Kelly A; Dadash Zadeh, Abbas; Rajaie, Rouzbeh

    2017-07-26

    Emergency nurses play an important role in the care of critically ill and injured patients, and their competency to perform clinical skills is vital to safe and effective patient care. The aim of this study was to evaluate the frequency of clinical skills performed and perceived competency levels among Iranian emergency nurses. In addition, attitudes toward expanding the professional roles of Iranian emergency nurses were also assessed. In this descriptive correlational study, 319 emergency nurses from 30 hospitals in northwest Iran participated. Data were collected using a self-report questionnaire. Descriptive statistics and Pearson's correlation coefficient were used to present the findings. Overall competency of the emergency nurses was 73.31 ± 14.2, indicating a good level of perceived competence. The clinical skills most frequently performed were in the domains of organizational and workload competencies (3.43 ± 0.76), diagnostic function (3.25 ± 0.82), and the helping role (3.17 ± 0.83). A higher level of perceived competence was found for skills within these domains. Less frequently, participants performed skills within the domains of effective management of rapidly changing situations (2.70 ± 0.94) and administering and monitoring therapeutic interventions (2.60 ± 0.97); a lower perceived level of competence was noted for these clinical skills. There was a significant correlation between frequency of performing clinical skills and perceived competency level (r = 0.651, P nurse managers and educators who may consider offering more frequent experiential and educational opportunities to emergency nurses. Expansion of nurses' roles could also result in increased experience in clinical skills and higher levels of competency. Research is needed to investigate nurses' clinical competence using direct and observed measures. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Can we clinically recognize a vascular depression? The role of personality in an expanded threshold model.

    Science.gov (United States)

    Turk, Bela R; Gschwandtner, Michael E; Mauerhofer, Michaela; Löffler-Stastka, Henriette

    2015-05-01

    The vascular depression (VD) hypothesis postulates that cerebrovascular disease may "predispose, precipitate, or perpetuate" a depressive syndrome in elderly patients. Clinical presentation of VD has been shown to differ to major depression in quantitative disability; however, as little research has been made toward qualitative phenomenological differences in the personality aspects of the symptom profile, clinical diagnosis remains a challenge.We attempted to identify differences in clinical presentation between depression patients (n = 50) with (n = 25) and without (n = 25) vascular disease using questionnaires to assess depression, affect regulation, object relations, aggressiveness, alexithymia, personality functioning, personality traits, and counter transference.We were able to show that patients with vascular dysfunction and depression exhibit significantly higher aggressive and auto-aggressive tendencies due to a lower tolerance threshold. These data indicate that VD is a separate clinical entity and secondly that the role of personality itself may be a component of the disease process. We propose an expanded threshold disease model incorporating personality functioning and mood changes. Such findings might also aid the development of a screening program, by serving as differential criteria, ameliorating the diagnostic procedure.

  15. Prostate cancer epigenetics and its clinical implications

    Directory of Open Access Journals (Sweden)

    Srinivasan Yegnasubramanian

    2016-01-01

    Full Text Available Normal cells have a level of epigenetic programming that is superimposed on the genetic code to establish and maintain their cell identity and phenotypes. This epigenetic programming can be thought as the architecture, a sort of cityscape, that is built upon the underlying genetic landscape. The epigenetic programming is encoded by a complex set of chemical marks on DNA, on histone proteins in nucleosomes, and by numerous context-specific DNA, RNA, protein interactions that all regulate the structure, organization, and function of the genome in a given cell. It is becoming increasingly evident that abnormalities in both the genetic landscape and epigenetic cityscape can cooperate to drive carcinogenesis and disease progression. Large-scale cancer genome sequencing studies have revealed that mutations in genes encoding the enzymatic machinery for shaping the epigenetic cityscape are among the most common mutations observed in human cancers, including prostate cancer. Interestingly, although the constellation of genetic mutations in a given cancer can be quite heterogeneous from person to person, there are numerous epigenetic alterations that appear to be highly recurrent, and nearly universal in a given cancer type, including in prostate cancer. The highly recurrent nature of these alterations can be exploited for development of biomarkers for cancer detection and risk stratification and as targets for therapeutic intervention. Here, we explore the basic principles of epigenetic processes in normal cells and prostate cancer cells and discuss the potential clinical implications with regards to prostate cancer biomarker development and therapy.

  16. Clinical implications of vitamin D deficiency

    Directory of Open Access Journals (Sweden)

    Beata Matyjaszek-Matuszek

    2015-06-01

    Full Text Available Vitamin D deficiency is a common medical problem worldwide and its prevalence rises along with latitude, obesity, sedentary lifestyle, limited sunlight exposure and aging. A great body of evidence has shown that patients with vitamin D deficiency have increased cardiovascular risks and total mortality. Conversely, the presence of comorbidities progressive with age such as abdominal obesity, insulin resistance, type 2 diabetes and hypertension places the patients at an increased risk of vitamin D deficiency. The multidirectional effect of vitamin D deficiency is present in different phases of the aging process. Based on the literature review, the risk factors for vitamin D insufficiency most often found in post-menopausal women include limited sun exposure and time spent outdoors, inadequate dietary vitamin D intake, winter season and increased age. Vitamin D supplementation in this group might offer prevention of falls and fractures and may be beneficial for cardiovascular health, what may be especially important in osteoporotic and elderly populations. Prevention and treatment processes involve education regarding sunlight exposure and pharmacological cholecalciferol supplementation according to the recommendations for Central Europe. This manuscript reviews the role of vitamin D and its deficiency and considers their clinical implications, with particular regard to peri- and postmenopausal women.

  17. Serotonin and migraine: biology and clinical implications.

    Science.gov (United States)

    Hamel, E

    2007-11-01

    Migraine is the most frequent neurological disorder in the adult population worldwide, affecting up to 12% of the general population and more frequent in women ( approximately 25%). It has a high impact on our society due to its disabling nature and, therein, reduced quality of life and increased absenteeism from work. Headache is the primary clinical manifestation and it has been associated with 'a hereditary or predisposed sensitivity of neurovascular reactions to certain stimuli or to cyclic changes in the central nervous system' (1). Amongst the many neurotransmitters in the brain, the serotonergic (serotonin, 5-HT) system from the brainstem raphe nucleus has been most convincingly implicated in migraine pathophysiology. The documented changes in 5-HT metabolism and in the processing of central 5-HT-mediated responses during and in between migraine attacks have led to the suggestion that migraine is a consequence of a central neurochemical imbalance that involves a low serotonergic disposition. Although the exact cascade of events that link abnormal serotonergic neurotransmission to the manifestation of head pain and the accompanying symptoms has yet to be fully understood, recent evidence suggests that a low 5-HT state facilitates activation of the trigeminovascular nociceptive pathway, as induced by cortical spreading depression. In this short review, we present and discuss the original and most recent findings that support a role for altered serotonergic neurotransmission in the manifestation of migraine headache.

  18. Prostate cancer epigenetics and its clinical implications.

    Science.gov (United States)

    Yegnasubramanian, Srinivasan

    2016-01-01

    Normal cells have a level of epigenetic programming that is superimposed on the genetic code to establish and maintain their cell identity and phenotypes. This epigenetic programming can be thought as the architecture, a sort of cityscape, that is built upon the underlying genetic landscape. The epigenetic programming is encoded by a complex set of chemical marks on DNA, on histone proteins in nucleosomes, and by numerous context-specific DNA, RNA, protein interactions that all regulate the structure, organization, and function of the genome in a given cell. It is becoming increasingly evident that abnormalities in both the genetic landscape and epigenetic cityscape can cooperate to drive carcinogenesis and disease progression. Large-scale cancer genome sequencing studies have revealed that mutations in genes encoding the enzymatic machinery for shaping the epigenetic cityscape are among the most common mutations observed in human cancers, including prostate cancer. Interestingly, although the constellation of genetic mutations in a given cancer can be quite heterogeneous from person to person, there are numerous epigenetic alterations that appear to be highly recurrent, and nearly universal in a given cancer type, including in prostate cancer. The highly recurrent nature of these alterations can be exploited for development of biomarkers for cancer detection and risk stratification and as targets for therapeutic intervention. Here, we explore the basic principles of epigenetic processes in normal cells and prostate cancer cells and discuss the potential clinical implications with regards to prostate cancer biomarker development and therapy.

  19. Expanding the clinical and mutational spectrum of Kaufman oculocerebrofacial syndrome with biallelic UBE3B mutations.

    Science.gov (United States)

    Basel-Vanagaite, Lina; Yilmaz, Rüstem; Tang, Sha; Reuter, Miriam S; Rahner, Nils; Grange, Dorothy K; Mortenson, Megan; Koty, Patrick; Feenstra, Heather; Farwell Gonzalez, Kelly D; Sticht, Heinrich; Boddaert, Nathalie; Désir, Julie; Anyane-Yeboa, Kwame; Zweier, Christiane; Reis, André; Kubisch, Christian; Jewett, Tamison; Zeng, Wenqi; Borck, Guntram

    2014-07-01

    Biallelic mutations of UBE3B have recently been shown to cause Kaufman oculocerebrofacial syndrome (also reported as blepharophimosis-ptosis-intellectual disability syndrome), an autosomal recessive condition characterized by hypotonia, developmental delay, intellectual disability, congenital anomalies, characteristic facial dysmorphic features, and low cholesterol levels. To date, six patients with either missense mutations affecting the UBE3B HECT domain or truncating mutations have been described. Here, we report on the identification of homozygous or compound heterozygous UBE3B mutations in six additional patients from five unrelated families using either targeted UBE3B sequencing in individuals with suggestive facial dysmorphic features, or exome sequencing. Our results expand the clinical and mutational spectrum of the UBE3B-related disorder in several ways. First, we have identified UBE3B mutations in individuals who previously received distinct clinical diagnoses: two sibs with Toriello-Carey syndrome as well as the patient reported to have a "new" syndrome by Buntinx and Majewski in 1990. Second, we describe the adult phenotype and clinical variability of the syndrome. Third, we report on the first instance of homozygous missense alterations outside the HECT domain of UBE3B, observed in a patient with mildly dysmorphic facial features. We conclude that UBE3B mutations cause a clinically recognizable and possibly underdiagnosed syndrome characterized by distinct craniofacial features, hypotonia, failure to thrive, eye abnormalities, other congenital malformations, low cholesterol levels, and severe intellectual disability. We review the UBE3B-associated phenotypes, including forms that can mimick Toriello-Carey syndrome, and suggest the single designation "Kaufman oculocerebrofacial syndrome".

  20. Neurobiology and clinical implications of lucid dreaming.

    Science.gov (United States)

    Mota-Rolim, Sérgio A; Araujo, John F

    2013-11-01

    Several lines of evidence converge to the idea that rapid eye movement sleep (REMS) is a good model to foster our understanding of psychosis. Both REMS and psychosis course with internally generated perceptions and lack of rational judgment, which is attributed to a hyperlimbic activity along with hypofrontality. Interestingly, some individuals can become aware of dreaming during REMS, a particular experience known as lucid dreaming (LD), whose neurobiological basis is still controversial. Since the frontal lobe plays a role in self-consciousness, working memory and attention, here we hypothesize that LD is associated with increased frontal activity during REMS. A possible way to test this hypothesis is to check whether transcranial magnetic or electric stimulation of the frontal region during REMS triggers LD. We further suggest that psychosis and LD are opposite phenomena: LD as a physiological awakening while dreaming due to frontal activity, and psychosis as a pathological intrusion of dream features during wake state due to hypofrontality. We further suggest that LD research may have three main clinical implications. First, LD could be important to the study of consciousness, including its pathologies and other altered states. Second, LD could be used as a therapy for recurrent nightmares, a common symptom of depression and post-traumatic stress disorder. Finally, LD may allow for motor imagery during dreaming with possible improvement of physical rehabilitation. In all, we believe that LD research may clarify multiple aspects of brain functioning in its physiological, altered and pathological states. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Synthetic Cannabinoids: Epidemiology, Pharmacodynamics, and Clinical Implications*

    Science.gov (United States)

    Castaneto, Marisol S.; Gorelick, David A.; Desrosiers, Nathalie A.; Hartman, Rebecca L.; Pirard, Sandrine; Huestis, Marilyn A.

    2014-01-01

    Background Synthetic cannabinoids (SC) are a heterogeneous group of compounds developed to probe the endogenous cannabinoid system or as potential therapeutics. Clandestine laboratories subsequently utilized published data to develop SC variations marketed as abuseable “designer drugs.” In the early 2000’s, SC became popular as “legal highs” under brand names such as “Spice” and “K2,” in part due to their ability to escape detection by standard cannabinoid screening tests. The majority of SC detected in herbal products have greater binding affinity to the cannabinoid CB1 receptor than does Δ9-tetrahydrocannabinol (THC), the primary psychoactive compound in the cannabis plant, and greater affinity at the CB1 than the CB2 receptor. In-vitro and animal in-vivo studies show SC pharmacological effects 2-100 times more potent than THC, including analgesic, anti-seizure, weight-loss, anti-inflammatory, and anti-cancer growth effects. SC produce physiological and psychoactive effects similar to THC, but with greater intensity, resulting in medical and psychiatric emergencies. Human adverse effects include nausea and vomiting, shortness of breath or depressed breathing, hypertension, tachycardia, chest pain, muscle twitches, acute renal failure, anxiety, agitation, psychosis, suicidal ideation, and cognitive impairment. Long-term or residual effects are unknown. Due to these public health consequences, many SC are classified as controlled substances. However, frequent structural modification by clandestine laboratories results in a stream of novel SC that may not be legally controlled or detectable by routine laboratory tests. Methods We present here a comprehensive review, based on a systematic electronic literature search, of SC epidemiology and pharmacology and their clinical implications. PMID:25220897

  2. Synthetic cannabinoids: epidemiology, pharmacodynamics, and clinical implications.

    Science.gov (United States)

    Castaneto, Marisol S; Gorelick, David A; Desrosiers, Nathalie A; Hartman, Rebecca L; Pirard, Sandrine; Huestis, Marilyn A

    2014-11-01

    Synthetic cannabinoids (SC) are a heterogeneous group of compounds developed to probe the endogenous cannabinoid system or as potential therapeutics. Clandestine laboratories subsequently utilized published data to develop SC variations marketed as abusable designer drugs. In the early 2000s, SC became popular as "legal highs" under brand names such as Spice and K2, in part due to their ability to escape detection by standard cannabinoid screening tests. The majority of SC detected in herbal products have greater binding affinity to the cannabinoid CB1 receptor than does Δ(9)-tetrahydrocannabinol (THC), the primary psychoactive compound in the cannabis plant, and greater affinity at the CB1 than the CB2 receptor. In vitro and animal in vivo studies show SC pharmacological effects 2-100 times more potent than THC, including analgesic, anti-seizure, weight-loss, anti-inflammatory, and anti-cancer growth effects. SC produce physiological and psychoactive effects similar to THC, but with greater intensity, resulting in medical and psychiatric emergencies. Human adverse effects include nausea and vomiting, shortness of breath or depressed breathing, hypertension, tachycardia, chest pain, muscle twitches, acute renal failure, anxiety, agitation, psychosis, suicidal ideation, and cognitive impairment. Long-term or residual effects are unknown. Due to these public health consequences, many SC are classified as controlled substances. However, frequent structural modification by clandestine laboratories results in a stream of novel SC that may not be legally controlled or detectable by routine laboratory tests. We present here a comprehensive review, based on a systematic electronic literature search, of SC epidemiology and pharmacology and their clinical implications. Published by Elsevier Ireland Ltd.

  3. Expanding the clinical and mutational spectrum of the Ehlers-Danlos syndrome, dermatosparaxis type.

    Science.gov (United States)

    Van Damme, Tim; Colige, Alain; Syx, Delfien; Giunta, Cecilia; Lindert, Uschi; Rohrbach, Marianne; Aryani, Omid; Alanay, Yasemin; Simsek-Kiper, Pelin Özlem; Kroes, Hester Y; Devriendt, Koen; Thiry, Marc; Symoens, Sofie; De Paepe, Anne; Malfait, Fransiska

    2016-09-01

    The Ehlers-Danlos syndrome (EDS), dermatosparaxis type, is a recessively inherited connective tissue disorder caused by deficient activity of ADAMTS-2, an enzyme that cleaves the aminoterminal propeptide domain of types I, II, and III procollagen. Only 10 EDS dermatosparaxis patients have been reported, all presenting a recognizable phenotype with characteristic facial gestalt, extreme skin fragility and laxity, excessive bruising, and sometimes major complications due to visceral and vascular fragility. We report on five new EDS dermatosparaxis patients and provide a comprehensive overview of the current knowledge of the natural history of this condition. We identified three novel homozygous loss-of-function mutations (c.2927_2928delCT, p.(Pro976Argfs*42); c.669_670dupG, p.(Pro224Argfs*24); and c.2751-2A>T) and one compound heterozygous mutation (c.2T>C, p.? and c.884_887delTGAA, p.(Met295Thrfs26*)) in ADAMTS2 in five patients from four unrelated families. Three of these displayed a phenotype that was strikingly milder than that of previously reported patients. This study expands the clinical and molecular spectrum of the dermatosparaxis type of EDS to include a milder phenotypic variant and stresses the importance of good clinical criteria. To address this, we propose an updated set of criteria that accurately captures the multisystemic nature of the dermatosparaxis type of EDS.Genet Med 18 9, 882-891.

  4. Boston keratoprosthesis – Clinical outcomes with wider geographic use and expanding indications – A systematic review

    Science.gov (United States)

    Al Arfaj, Khalid

    2015-01-01

    Over 2 decades of research, several design modifications, and improvements in post-operative management have made Boston keratoprosthesis (B-KPro) a viable option for patients with corneal blindness for whom traditional keratoplasty procedure has a very low probability of success. In this systematic review, we examined the indications, visual outcomes, complications and retention rate of the literature published in the past 10 years (2005–2014). While most of the studies report smaller datasets (typically <50 eyes), some of the recent multicenter studies have reported large datasets (up to 300 eyes). Most of the literature is published from the US; however, last few years have witnessed some papers reporting the successful use of B-Kpro from developing countries or arid climatic conditions (such as the Kingdom of Saudi Arabia). Due to differences in the causes of corneal blindness in different geographic regions, newer indications for B-Kpro are emerging (e.g. trachoma). Additionally, improving clinical outcomes and increasing surgeon confidence have also expanded indications to include cases of unilateral visual impairment and paediatric age. We observed that there is growing body of evidence of successful clinical use of B-KPro; however, financial challenges, lack of trained surgeons, shortage of donor corneas must be overcome to improve accessibility of B-KPro. PMID:26155082

  5. Boston keratoprosthesis - Clinical outcomes with wider geographic use and expanding indications - A systematic review.

    Science.gov (United States)

    Al Arfaj, Khalid

    2015-01-01

    Over 2 decades of research, several design modifications, and improvements in post-operative management have made Boston keratoprosthesis (B-KPro) a viable option for patients with corneal blindness for whom traditional keratoplasty procedure has a very low probability of success. In this systematic review, we examined the indications, visual outcomes, complications and retention rate of the literature published in the past 10 years (2005-2014). While most of the studies report smaller datasets (typically <50 eyes), some of the recent multicenter studies have reported large datasets (up to 300 eyes). Most of the literature is published from the US; however, last few years have witnessed some papers reporting the successful use of B-Kpro from developing countries or arid climatic conditions (such as the Kingdom of Saudi Arabia). Due to differences in the causes of corneal blindness in different geographic regions, newer indications for B-Kpro are emerging (e.g. trachoma). Additionally, improving clinical outcomes and increasing surgeon confidence have also expanded indications to include cases of unilateral visual impairment and paediatric age. We observed that there is growing body of evidence of successful clinical use of B-KPro; however, financial challenges, lack of trained surgeons, shortage of donor corneas must be overcome to improve accessibility of B-KPro.

  6. A Novel Method to Generate and Expand Clinical-Grade, Genetically Modified, Tumor-Infiltrating Lymphocytes

    Directory of Open Access Journals (Sweden)

    Marie-Andrée Forget

    2017-08-01

    Full Text Available Following the clinical success achieved with the first generation of adoptive cell therapy (ACT utilizing in vitro expanded tumor-infiltrating lymphocytes (TILs, the second and third generations of TIL ACT are evolving toward the use of genetically modified TIL. TIL therapy generally involves the transfer of a high number of TIL, ranging from 109 to 1011 cells. One of the technical difficulties in genetically modifying TIL, using a retroviral vector, is the ability to achieve large expansion of transduced TIL, while keeping the technique suitable to a Good Manufacturing Practices (GMP environment. Consequently, we developed and optimized a novel method for the efficient production of large numbers of GMP-grade, gene-modified TIL for the treatment of patients with ACT. The chemokine receptor CXCR2 was used as the gene of interest for methodology development. The optimized procedure is currently used in the production of gene-modified TIL for two clinical trials for the treatment of metastatic melanoma at MD Anderson Cancer Center.

  7. Expanding clinical laboratory tobacco product evaluation methods to loose-leaf tobacco vaporizers.

    Science.gov (United States)

    Lopez, Alexa A; Hiler, Marzena; Maloney, Sarah; Eissenberg, Thomas; Breland, Alison B

    2016-12-01

    Novel tobacco products entering the US market include electronic cigarettes (ECIGs) and products advertised to "heat, not burn" tobacco. There is a growing literature regarding the acute effects of ECIGs. Less is known about "heat, not burn" products. This study's purpose was to expand existing clinical laboratory methods to examine, in cigarette smokers, the acute effects of a "heat, not burn" "loose-leaf tobacco vaporizer" (LLTV). Plasma nicotine and breath carbon monoxide (CO) concentration and tobacco abstinence symptom severity were measured before and after two 10-puff (30-s interpuff interval) product use bouts separated by 60min. LLTV effects were compared to participants' own brand (OB) cigarettes and an ECIG (3.3V; 1.5ohm; 18mg/ml nicotine). Relative to OB, LLTV increased plasma nicotine concentration to a lesser degree, did not increase CO, and did not appear to reduce abstinence symptoms as effectively. Relative to ECIG, LLTV nicotine and CO delivery and abstinence symptom suppression did not differ. Participants reported that both the LLTV and ECIG were significantly less satisfying than OB. Results demonstrate that LLTVs are capable of delivering nicotine and suppressing tobacco abstinence symptoms partially; acute effects of these products can be evaluated using existing clinical laboratory methods. Results can inform tobacco product regulation and may be predictive of the extent that these products have the potential to benefit or harm overall public health. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Personal Narratives: Cultural Differences and Clinical Implications

    Science.gov (United States)

    Bliss, Lynn S.; McCabe, Allyssa

    2008-01-01

    A study was conducted to examine the misdiagnosis of cultural difference deficits and how mistaking deficits in narrative production for cultural differences can be avoided. Findings reveal the implications for intervention.

  9. Expanded clinical and experimental use of SOX11 - using a monoclonal antibody

    Directory of Open Access Journals (Sweden)

    Nordström Lena

    2012-06-01

    Full Text Available Abstract Background The transcription factor SOX11 is of diagnostic and prognostic importance in mantle cell lymphoma (MCL and epithelial ovarian cancer (EOC, respectively. Thus, there is an unmet clinical and experimental need for SOX11-targeting assays with low background, high specificity and robust performance in multiple applications, including immunohistochemistry (IHC-P and flow cytometry, which until now has been lacking. Methods We have developed SOX11-C1, a monoclonal mouse antibody targeting SOX11, and successfully evaluated its performance in western blots (WB, IHC-P, fluorescence microscopy and flow cytometry. Results We confirm the importance of SOX11 as a diagnostic antigen in MCL as 100% of tissue micro array (TMA cases show bright nuclear staining, using the SOX11-C1 antibody in IHC-P. We also show that previous reports of weak SOX11 immunostaining in a fraction of hairy cell leukemias (HCL are not confirmed using SOX11-C1, which is consistent with the lack of transcription. Thus, high sensitivity and improved specificity are demonstrated using the monoclonal SOX11-C1 antibody. Furthermore, we show for the first time that flow cytometry can be used to separate SOX11 positive and negative cell lines and primary tumors. Of note, SOX11-C1 shows no nonspecific binding to primary B or T cells in blood and thus, can be used for analysis of B and T cell lymphomas from complex clinical samples. Dilution experiments showed that low frequencies of malignant cells (~1% are detectable above background using SOX11 as a discriminant antigen in flow cytometry. Conclusions The novel monoclonal SOX11-specific antibody offers high sensitivity and improved specificity in IHC-P based detection of MCL and its expanded use in flow cytometry analysis of blood and tissue samples may allow a convenient approach to early diagnosis and follow-up of MCL patients.

  10. Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield.

    Science.gov (United States)

    Anazi, S; Maddirevula, S; Faqeih, E; Alsedairy, H; Alzahrani, F; Shamseldin, H E; Patel, N; Hashem, M; Ibrahim, N; Abdulwahab, F; Ewida, N; Alsaif, H S; Al Sharif, H; Alamoudi, W; Kentab, A; Bashiri, F A; Alnaser, M; AlWadei, A H; Alfadhel, M; Eyaid, W; Hashem, A; Al Asmari, A; Saleh, M M; AlSaman, A; Alhasan, K A; Alsughayir, M; Al Shammari, M; Mahmoud, A; Al-Hassnan, Z N; Al-Husain, M; Osama Khalil, R; Abd El Meguid, N; Masri, A; Ali, R; Ben-Omran, T; El Fishway, P; Hashish, A; Ercan Sencicek, A; State, M; Alazami, A M; Salih, M A; Altassan, N; Arold, S T; Abouelhoda, M; Wakil, S M; Monies, D; Shaheen, R; Alkuraya, F S

    2017-04-01

    Intellectual disability (ID) is a measurable phenotypic consequence of genetic and environmental factors. In this study, we prospectively assessed the diagnostic yield of genomic tools (molecular karyotyping, multi-gene panel and exome sequencing) in a cohort of 337 ID subjects as a first-tier test and compared it with a standard clinical evaluation performed in parallel. Standard clinical evaluation suggested a diagnosis in 16% of cases (54/337) but only 70% of these (38/54) were subsequently confirmed. On the other hand, the genomic approach revealed a likely diagnosis in 58% (n=196). These included copy number variants in 14% (n=54, 15% are novel), and point mutations revealed by multi-gene panel and exome sequencing in the remaining 43% (1% were found to have Fragile-X). The identified point mutations were mostly recessive (n=117, 81%), consistent with the high consanguinity of the study cohort, but also X-linked (n=8, 6%) and de novo dominant (n=19, 13%). When applied directly on all cases with negative molecular karyotyping, the diagnostic yield of exome sequencing was 60% (77/129). Exome sequencing also identified likely pathogenic variants in three novel candidate genes (DENND5A, NEMF and DNHD1) each of which harbored independent homozygous mutations in patients with overlapping phenotypes. In addition, exome sequencing revealed de novo and recessive variants in 32 genes (MAMDC2, TUBAL3, CPNE6, KLHL24, USP2, PIP5K1A, UBE4A, TP53TG5, ATOH1, C16ORF90, SLC39A14, TRERF1, RGL1, CDH11, SYDE2, HIRA, FEZF2, PROCA1, PIANP, PLK2, QRFPR, AP3B2, NUDT2, UFC1, BTN3A2, TADA1, ARFGEF3, FAM160B1, ZMYM5, SLC45A1, ARHGAP33 and CAPS2), which we highlight as potential candidates on the basis of several lines of evidence, and one of these genes (SLC39A14) was biallelically inactivated in a potentially treatable form of hypermanganesemia and neurodegeneration. Finally, likely causal variants in previously published candidate genes were identified (ASTN1, HELZ, THOC6, WDR45B, ADRA

  11. [Epigenetics in tumorigenesis: advances and clinical implications].

    Science.gov (United States)

    Wang, Xian huo; Zhao, Xiu juan; Qiu, Li hua; Wang, Hua qing; Wang, Xi

    2012-10-18

    Cancer is a leading cause of death worldwide and the total number of cases globally keeps increasing. For many years, cancer has been thought to be caused by a series of DNA sequence alterations and thus is thought to be a "genetic" disease. However, studies in the last decade, including the large-scale cancer genomics projects, have highlighted the rising importance of epigenetic regulation in cancer. Here, we review recent advances in understanding how chromatin-based epigenetic regulation participates in tumorigenesis and discuss the growing implications of these advances for developing novel strategies to prevent, diagnose, as well as treat cancer.

  12. Expanded transcanal transpromontorial approach to the internal auditory canal: Pilot clinical experience.

    Science.gov (United States)

    Presutti, Livio; Alicandri-Ciufelli, Matteo; Bonali, Marco; Rubini, Alessia; Pavesi, Giacomo; Feletti, Alberto; Masotto, Barbara; Anschuetz, Lukas; Marchioni, Daniele

    2017-11-01

    The aim of this study was to describe and evaluate the feasibility of an expanded transcanal transpromontorial approach, developed from the exclusive endoscopic transcanal transpromontorial approach. Retrospective case series. Retrospective chart review of 10 patients operated by an expanded transcanal transpromontorial approach in two tertiary referral centers (University Hospital of Modena, Italy and University Hospital of Verona, Italy). Data from charts and video documentation were collected and analyzed. Between April 2015 and January 2016, 10 patients underwent an expanded transcanal transpromontorial approach for vestibular schwannoma Koos stage I or II and were enrolled in the study. The size of the tumors ranged from 7 to 19 mm in maximum diameter. A gross total resection was achieved in all cases. One subject experienced postoperative cerebrospinal fluid otorhinorrhea and three subjects experienced temporary postoperative facial weakness, all of which completely resolved. The mean follow-up was 5 months. The expanded transcanal transpromontorial approach allowed bimanual dissection using a microscopic technique for the treatment of pathologies of the internal auditory canal and cerebellopontine angle. This novel approach resulted in minimal morbidity and comparable facial nerve preservation rates to the traditional approaches to the internal auditory canal. The expanded transpromontorial approach to the internal auditory canal holds promise for addressing pathology in this region of the temporal bone from the external auditory canal. 4. Laryngoscope, 127:2608-2614, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  13. The expanding role of the clinical haematologist in the new world of advanced therapy medicinal products.

    Science.gov (United States)

    Lowdell, Mark W; Thomas, Amy

    2017-01-01

    Advanced therapy medicinal products (ATMPs) represent the current pinnacle of 'patient-specific medicines' and will change the nature of medicine in the near future. They fall into three categories; somatic cell-therapy products, gene therapy products and cells or tissues for regenerative medicine, which are termed 'tissue engineered' products. The term also incorporates 'combination products' where a human cell or tissue is combined with a medical device. Plainly, many of these new medicines share similarities with conventional haematological stem cell transplant products and donor lymphocyte infusions as well as solid organ grafts and yet ATMPs are regulated as medicines and their development has remained predominantly in academic settings and within specialist centres. However, with the advent of commercialisation of dendritic cell vaccines, chimeric antigen receptor (CAR)-T cells and genetically modified autologous haematopoietic stem cells to cure single gene-defects in β-thalassaemia and haemophilia, the widespread availability of these therapies needs to be accommodated. Uniquely to ATMPs, the patient or an allogeneic donor is regularly part of the manufacturing process. All of the examples given above require procurement of blood, bone marrow or an apheresate from a patient as a starting material for manufacture. This can only occur in a clinical facility licensed for the procurement of human cells for therapeutic use and this is likely to fall to haematology departments, either as stem cell transplant programmes or as blood transfusion departments, to provide under a contract with the company that will manufacture and supply the final medicine. The resource implications associated with this can impact on all haematology departments, not just stem cell transplant units, and should not be under-estimated. © 2016 John Wiley & Sons Ltd.

  14. Exploring the scope of expanding advanced nursing practice in nurse-led clinics: a multiple-case study.

    Science.gov (United States)

    Shiu, Ann T Y; Lee, Diana T F; Chau, Janita P C

    2012-08-01

    This article is a report on a study to explore the development of expanding advanced nursing practice in nurse-led clinics in Hong Kong. Nurse-led clinics serviced by advanced practice nurses, a common international practice, have been adopted in Hong Kong since 1990s. Evaluations consistently show that this practice has good clinical outcomes and contributes to containing healthcare cost. However, similar to the international literature, it remains unclear as to what the elements of good advanced nursing practice are, and which directions Hong Kong should adopt for further development of such practice. A multiple-case study design was adopted with six nurse-led clinics representing three specialties as six case studies, and including two clinics each from continence, diabetes and wound care. Each case had four embedded units of analysis. They included non-participant observation of nursing activities (9 days), nurse interviews (N = 6), doctor interviews (N = 6) and client interviews (N = 12). The data were collected in 2009. Within- and cross-case analyses were conducted. The cross-case analysis demonstrated six elements of good advanced nursing practice in nurse-led clinics, and showed a great potential to expand the practice by reshaping four categories of current boundaries, including community-hospital, wellness-illness, public-private and professional-practice boundaries. From these findings, we suggest a model to advance the scope of advanced nursing practice in nurse-led clinics. The six elements may be applied as audit criteria for evaluation of advanced nursing practice in nurse-led clinics, and the proposed model provides directions for expanding such practice in Hong Kong and beyond. © 2011 Blackwell Publishing Ltd.

  15. Clinical Implications of the Brazelton Scale.

    Science.gov (United States)

    Soule, Bradley; And Others

    An exploration of the clinical usefulness of the Brazelton Neonatal Behavioral Scale was made. A specific pediatric problem was studied, i.e., a baby born to a heroin-addicted mother taking methadone. The control sample was a population of 41 babies who were part of a larger study. Both methadone and control infants were tested between 48 and 72…

  16. Clinical implications of advances in liver regeneration.

    Science.gov (United States)

    Kwon, Yong Jin; Lee, Kyeong Geun; Choi, Dongho

    2015-03-01

    Remarkable advances have been made recently in the area of liver regeneration. Even though liver regeneration after liver resection has been widely researched, new clinical applications have provided a better understanding of the process. Hepatic damage induces a process of regeneration that rarely occurs in normal undamaged liver. Many studies have concentrated on the mechanism of hepatocyte regeneration following liver damage. High mortality is usual in patients with terminal liver failure. Patients die when the regenerative process is unable to balance loss due to liver damage. During disease progression, cellular adaptations take place and the organ microenvironment changes. Portal vein embolization and the associating liver partition and portal vein ligation for staged hepatectomy are relatively recent techniques exploiting the remarkable progress in understanding liver regeneration. Living donor liver transplantation is one of the most significant clinical outcomes of research on liver regeneration. Another major clinical field involving liver regeneration is cell therapy using adult stem cells. The aim of this article is to provide an outline of the clinical approaches being undertaken to examine regeneration in liver diseases.

  17. [Diabetic cardiomyopathy. Pathophysiology and clinical implications].

    Science.gov (United States)

    Karnafel, W

    2000-01-01

    The accumulating body of data indicate that the occurrence of diabetic cardiomyopathy is an independent phenomenon from macroangiographic changes in coronary arteries and hypertension. Results from animal studies, human histological results and clinical observations provided support for this phenomenon. Although the clinical symptoms have been identified, however, the pathogenesis of diabetic cardiomyopathy is uncertain. The definition of diabetic cardiomyopathy describes both specific defects in the myocytes from diabetics and associated changes in the heart which have developed during the course of diabetes. The following defects in myocytes have been identified and are postulated to contribute to diabetic cardiomyopathy: The changes in carbohydrates metabolism, in fatty-acid metabolism, calcium and potassium transport, microvascular narrowing and micro aneurysms, hypertrophy, defects in collagen structure, myocardial fibrosis and perivascular fibrosis, abnormalities in conducting system, the decrease in the function of autonomic nerves. The clinical presentation of diabetic cardiomyopathy lead to the description of two phases of the disease. First, asymptomatic diabetic subjects with subclinical abnormalities of the left-ventricular diastolic function, measured by Doppler echocardiography. In the second phase--clinically evident diabetic cardiomyopathy is described by congestive cardiac failure without evident arteriosclerotic changes in coronary arteries and hypertension. Diabetic cardiomyopathy can be diagnosed early after the onset of diabetes mellitus and is independent phenomenon from late diabetic complications. The main cause of mortality in diabetic subjects is largely due to macroangiopathic changes in the coronary arteries (evaluated by coronarography), not the heart failure.

  18. Clinical and nutritional implications of radiation enteritis

    Energy Technology Data Exchange (ETDEWEB)

    Beer, W.H.; Fan, A.; Halsted, C.H.

    1985-01-01

    The clinical and nutritional significance of radiation enteritis was assessed in eight patients with chronic diarrhea which followed curative doses of radiotherapy for pelvic malignancies. Steatorrhea, found in seven malnourished patients, was ascribed to ileal disease or previous surgery, or to bacterial contamination of the small intestine. Lactose intolerance, assessed by breath hydrogen excretion after oral lactose and by jejunal lactase levels, was found in six patients. In a subgroup of five patients, the administration of two different defined formula liquid diets by nasoduodenal infusion decreased fecal fluid and energy losses by about one-half. Compared to Vivonex-HN, the infusion of Criticare-HN was associated with greater likelihood of intestinal gas production but a three-fold greater utilization of protein. Intestinal malabsorption and malnutrition in radiation enteritis has diverse etiologies. Whereas nutritional support by liquid diet limits fecal fluid and energy losses, these diets differ significantly in clinical tolerance and biologic value.

  19. Biological behaviour and clinical implications of micrometastases.

    LENUS (Irish Health Repository)

    Kell, M R

    2012-02-03

    BACKGROUND: The most important prognostic determinant in cancer is the identification of disseminated tumour burden (metastases). Micrometastases are microscopic (smaller than 2 mm) deposits of malignant cells that are segregated spatially from the primary tumour and depend on neovascular formation (angiogenesis) to propagate. METHODS: The electronic literature (1966 to present) on micrometastases and their implications in malignant melanoma and epithelial cancers was reviewed. RESULTS: Immunohistochemical techniques combined with serial sectioning offer the best accuracy for detection of nodal micrometastases. Molecular techniques should be reserved for blood samples or bone marrow aspirates. Detection of micrometastases in regional lymph nodes and\\/or bone marrow confers a poor prognosis in epithelial cancers. The concept of sentinel node biopsy combined with serial sectioning and dedicated screening for micrometastases may improve staging procedures. Strategies against angiogenesis may provide novel therapies to induce and maintain micrometastatic dormancy. CONCLUSION: The concept of micrometastases has resulted in a paradigm shift in the staging of epithelial tumours and our overall understanding of malignant processes.

  20. Cancer Genetics and Implications for Clinical Management.

    Science.gov (United States)

    Jamieson, Nigel B; Chang, David K; Biankin, Andrew V

    2015-10-01

    There is now compelling evidence that the molecular heterogeneity of cancer is associated with disparate phenotypes with variable outcomes and therapeutic responsiveness to therapy in histologically indistinguishable cancers. This diversity may explain why conventional clinical trial designs have mostly failed to show efficacy when patients are enrolled in an unselected fashion. Knowledge of the molecular phenotype has the potential to improve therapeutic selection and hence the early delivery of the optimal therapeutic regimen. Resolution of the challenges associated with a more stratified approach to health care will ensure more precise diagnostics and enhance therapeutic selection, which will improve overall outcomes. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Clinical implications of drug abuse epidemiology.

    Science.gov (United States)

    Schulden, Jeffrey D; Lopez, Marsha F; Compton, Wilson M

    2012-06-01

    Research on the epidemiology of illicit drug use disorders provides continued critical insights into the distribution and determinants of drug use and drug use disorders in the United States. This research serves as a foundation for understanding the etiology of these disorders, helping to disentangle the complex interrelationship of developmental, genetic, and environmental risk and protective factors. Building on an understanding of this research in substance abuse epidemiology, it is important for clinicians to understand the unique trends in drug use in the overall communities that they serve and the unique risk factors for given individuals. The generally high prevalence of substance use disorders, along with their high comorbidity with other psychiatric disorders and with the HIV epidemic, make prevention, evaluation, and referral for treatment for drug abuse an important part of routine clinical practice in a range of clinical settings, including primary care, psychiatric, and emergency department settings. Ongoing efforts to ensure insurance coverage parity for the treatment of mental health and substance use disorders offer the promise of continued improvements in the integration and availability of such services in the broader US health care system.

  2. Clinical Understanding of Spasticity: Implications for Practice

    Directory of Open Access Journals (Sweden)

    Rozina Bhimani

    2014-01-01

    Full Text Available Spasticity is a poorly understood phenomenon. The aim of this paper is to understand the effect of spasticity on daily life and identify bedside strategies that enhance patient’s function and improve comfort. Spasticity and clonus result from an upper motor neuron lesion that disinhibits the tendon stretch reflex; however, they are differentiated in the fact that spasticity results in a velocity dependent tightness of muscle whereas clonus results in uncontrollable jerks of the muscle. Clinical strategies that address function and comfort are paramount. This is a secondary content analysis using a qualitative research design. Adults experiencing spasticity associated with neuromuscular disorder were asked to participate during inpatient acute rehabilitation. They were asked to complete a semistructured interview to explain and describe the nature of their experienced spasticity on daily basis. Spasticity affects activities of daily living, function, and mobility. Undertreated spasticity can lead to pain, immobility, and risk of falls. There were missed opportunities to adequately care for patients with spasticity. Bedside care strategies identified by patients with spasticity are outlined. Uses of alternative therapies in conjunction with medications are needed to better manage spasticity. Patient reports on spasticity are important and should be part of clinical evaluation and practice.

  3. Viral asthma: implications for clinical practice

    Directory of Open Access Journals (Sweden)

    Roger Menendez

    2010-07-01

    Full Text Available Roger Menendez1, Michael D Goldman21Allergy and Asthma Center of El Paso, El Paso, TX, USA; 2Pulmonary Division, UCLA Gaffen School of Medicine, Los Angeles, CA, USAAbstract: The natural history of asthma appears to be driven primarily by the timing and duration of viral respiratory infections. From the very high rate of infections in childhood, to the more sporadic pattern seen in adults, the cycle of acute injury followed by an inefficient repair process helps explain the clinical patterns of asthma severity currently recognized by asthma guidelines. Why the asthmatic host responds to viral injury in a particular way is largely a mystery and the subject of intense investigation. The role of viruses in asthma extends not just to intermittent but to persistent disease, and to both the atopic as well as nonatopic phenotypes. Future therapeutic strategies should include primary prevention via the development of antiviral innate immunity-enhancing vaccines, as well as secondary prevention via the use of antiviral agents, or immunomodulators designed to boost the antiviral response or interrupt the proinflammatory cascade.Keywords: asthma, rhinoviruses, exacerbations, epidemiology, phenotypes, clinical trials

  4. Clinical Understanding of Spasticity: Implications for Practice

    Science.gov (United States)

    2014-01-01

    Spasticity is a poorly understood phenomenon. The aim of this paper is to understand the effect of spasticity on daily life and identify bedside strategies that enhance patient's function and improve comfort. Spasticity and clonus result from an upper motor neuron lesion that disinhibits the tendon stretch reflex; however, they are differentiated in the fact that spasticity results in a velocity dependent tightness of muscle whereas clonus results in uncontrollable jerks of the muscle. Clinical strategies that address function and comfort are paramount. This is a secondary content analysis using a qualitative research design. Adults experiencing spasticity associated with neuromuscular disorder were asked to participate during inpatient acute rehabilitation. They were asked to complete a semistructured interview to explain and describe the nature of their experienced spasticity on daily basis. Spasticity affects activities of daily living, function, and mobility. Undertreated spasticity can lead to pain, immobility, and risk of falls. There were missed opportunities to adequately care for patients with spasticity. Bedside care strategies identified by patients with spasticity are outlined. Uses of alternative therapies in conjunction with medications are needed to better manage spasticity. Patient reports on spasticity are important and should be part of clinical evaluation and practice. PMID:25276432

  5. Cybersecurity in the Clinical Setting: Nurses' Role in the Expanding "Internet of Things".

    Science.gov (United States)

    Billingsley, Luanne; McKee, Shawn A

    2016-08-01

    Nurses face growing complexity in their work. The expanding "Internet of Things" with "smart" technologies can reduce the burden. However, equipment and devices that connect to patients, the network, or to the Internet can be exploited by hackers. Nurses should be able to identify, understand, and protect against cybersecurity risks to safeguard patients. J Contin Educ Nurs. 2016;47(8):347-349. Copyright 2016, SLACK Incorporated.

  6. Episodic memories in anxiety disorders: Clinical implications

    Directory of Open Access Journals (Sweden)

    Armin eZlomuzica

    2014-04-01

    Full Text Available The aim of this review is to summarize research on the emerging role of episodic memories in the context of anxiety disorders (AD. The available literature on explicit-, autobiographical- and episodic memory function in AD including neuroimaging studies is critically discussed. We describe the methodological diversity of episodic memory research in AD and discuss the need for novel tests to measure episodic memory in a clinical setting. We argue that alterations in episodic memory functions might contribute to the etiology of AD. We further explain why future research on the interplay between episodic memory function and emotional disorders as well as its neuroanatomical foundations offers the promise to increase the effectiveness of modern psychological treatments. We conclude that one major task is to develop methods and training programs that might help patients suffering from AD to better understand, interpret and possibly actively use their episodic memories in a way that would support therapeutic interventions and counteract the occurrence of symptoms.

  7. Episodic Memories in Anxiety Disorders: Clinical Implications

    Science.gov (United States)

    Zlomuzica, Armin; Dere, Dorothea; Machulska, Alla; Adolph, Dirk; Dere, Ekrem; Margraf, Jürgen

    2014-01-01

    The aim of this review is to summarize research on the emerging role of episodic memories in the context of anxiety disorders (AD). The available literature on explicit, autobiographical, and episodic memory function in AD including neuroimaging studies is critically discussed. We describe the methodological diversity of episodic memory research in AD and discuss the need for novel tests to measure episodic memory in a clinical setting. We argue that alterations in episodic memory functions might contribute to the etiology of AD. We further explain why future research on the interplay between episodic memory function and emotional disorders as well as its neuroanatomical foundations offers the promise to increase the effectiveness of modern psychological treatments. We conclude that one major task is to develop methods and training programs that might help patients suffering from AD to better understand, interpret, and possibly actively use their episodic memories in a way that would support therapeutic interventions and counteract the occurrence of symptoms. PMID:24795583

  8. Characterization of ex vivo expanded tumor infiltrating lymphocytes from patients with malignant melanoma for clinical application

    DEFF Research Database (Denmark)

    Junker, Niels; Thor Straten, Per; Andersen, Mads Hald

    2011-01-01

    Clinical trials of adoptive transfer of autologous tumor infiltrating lymphocytes (TILs) to patients with advanced malignant melanoma have shown remarkable results with objective clinical responses in 50% of the treated patients. In order to initiate a clinical trial in melanoma, we have establis......Clinical trials of adoptive transfer of autologous tumor infiltrating lymphocytes (TILs) to patients with advanced malignant melanoma have shown remarkable results with objective clinical responses in 50% of the treated patients. In order to initiate a clinical trial in melanoma, we have...

  9. Mechanisms of fibrin polymerization and clinical implications.

    Science.gov (United States)

    Weisel, John W; Litvinov, Rustem I

    2013-03-07

    Research on all stages of fibrin polymerization, using a variety of approaches including naturally occurring and recombinant variants of fibrinogen, x-ray crystallography, electron and light microscopy, and other biophysical approaches, has revealed aspects of the molecular mechanisms involved. The ordered sequence of fibrinopeptide release is essential for the knob-hole interactions that initiate oligomer formation and the subsequent formation of 2-stranded protofibrils. Calcium ions bound both strongly and weakly to fibrin(ogen) have been localized, and some aspects of their roles are beginning to be discovered. Much less is known about the mechanisms of the lateral aggregation of protofibrils and the subsequent branching to yield a 3-dimensional network, although the αC region and B:b knob-hole binding seem to enhance lateral aggregation. Much information now exists about variations in clot structure and properties because of genetic and acquired molecular variants, environmental factors, effects of various intravascular and extravascular cells, hydrodynamic flow, and some functional consequences. The mechanical and chemical stability of clots and thrombi are affected by both the structure of the fibrin network and cross-linking by plasma transglutaminase. There are important clinical consequences to all of these new findings that are relevant for the pathogenesis of diseases, prophylaxis, diagnosis, and treatment.

  10. Conflicting dermatome maps: educational and clinical implications.

    Science.gov (United States)

    Downs, Mary Beth; Laporte, Cindy

    2011-06-01

    Sensory testing is a common noninvasive method of evaluating nerve function that relies on the knowledge of skin dermatomes and sensory fields of cutaneous nerves. Research to determine the extent of the dermatomes was conducted in Europe during the late nineteenth and early twentieth centuries. Experiments performed on cadavers, monkeys, and human patients prior to 1948 resulted in the creation of similar but somewhat different dermatome maps. A radically different map with long, swirling dermatomes was produced by Keegan and Garrett in 1948. This map was derived largely by examining compression of dorsal nerve roots by vertebral disc herniation. The maps appearing in textbooks are inconsistent. Some books show a version of the early maps, some show the Keegan and Garrett map, and others show maps that are not consistent with either. The purpose of this paper is to discuss the history of dermatome maps, including the experimental procedures by which each was obtained, and to relate the early maps to those found in textbooks commonly used in healthcare education programs. The paper discusses the significance of these maps as used for clinical diagnosis and the need for further research.

  11. Humanized animal exercise model for clinical implication.

    Science.gov (United States)

    Seo, Dae Yun; Lee, Sung Ryul; Kim, Nari; Ko, Kyung Soo; Rhee, Byoung Doo; Han, Jin

    2014-09-01

    Exercise and physical activity function as a patho-physiological process that can prevent, manage, and regulate numerous chronic conditions, including metabolic syndrome and age-related sarcopenia. Because of research ethics and technical difficulties in humans, exercise models using animals are requisite for the future development of exercise mimetics to treat such abnormalities. Moreover, the beneficial or adverse outcomes of a new regime or exercise intervention in the treatment of a specific condition should be tested prior to implementation in a clinical setting. In rodents, treadmill running (or swimming) and ladder climbing are widely used as aerobic and anaerobic exercise models, respectively. However, exercise models are not limited to these types. Indeed, there are no golden standard exercise modes or protocols for managing or improving health status since the types (aerobic vs. anaerobic), time (morning vs. evening), and duration (continuous vs. acute bouts) of exercise are the critical determinants for achieving expected beneficial effects. To provide insight into the understanding of exercise and exercise physiology, we have summarized current animal exercise models largely based on aerobic and anaerobic criteria. Additionally, specialized exercise models that have been developed for testing the effect of exercise on specific physiological conditions are presented. Finally, we provide suggestions and/or considerations for developing a new regime for an exercise model.

  12. Clinical implications and utility of field cancerization

    Directory of Open Access Journals (Sweden)

    Birch-Machin Mark A

    2007-03-01

    Full Text Available Abstract Cancer begins with multiple cumulative epigenetic and genetic alterations that sequencially transform a cell, or a group of cells in a particular organ. The early genetic events might lead to clonal expansion of pre-neoplastic daughter cells in a particular tumor field. Subsequent genomic changes in some of these cells drive them towards the malignant phenotype. These transformed cells are diagnosed histopathologically as cancers owing to changes in cell morphology. Conceivably, a population of daughter cells with early genetic changes (without histopathology remain in the organ, demonstrating the concept of field cancerization. With present technological advancement, including laser capture microdisection and high-throughput genomic technologies, carefully designed studies using appropriate control tissue will enable identification of important molecular signatures in these genetically transformed but histologically normal cells. Such tumor-specific biomarkers should have excellent clinical utility. This review examines the concept of field cancerization in several cancers and its possible utility in four areas of oncology; risk assessment, early cancer detection, monitoring of tumor progression and definition of tumor margins.

  13. Clinical implications and utility of field cancerization

    Science.gov (United States)

    Dakubo, Gabriel D; Jakupciak, John P; Birch-Machin, Mark A; Parr, Ryan L

    2007-01-01

    Cancer begins with multiple cumulative epigenetic and genetic alterations that sequencially transform a cell, or a group of cells in a particular organ. The early genetic events might lead to clonal expansion of pre-neoplastic daughter cells in a particular tumor field. Subsequent genomic changes in some of these cells drive them towards the malignant phenotype. These transformed cells are diagnosed histopathologically as cancers owing to changes in cell morphology. Conceivably, a population of daughter cells with early genetic changes (without histopathology) remain in the organ, demonstrating the concept of field cancerization. With present technological advancement, including laser capture microdisection and high-throughput genomic technologies, carefully designed studies using appropriate control tissue will enable identification of important molecular signatures in these genetically transformed but histologically normal cells. Such tumor-specific biomarkers should have excellent clinical utility. This review examines the concept of field cancerization in several cancers and its possible utility in four areas of oncology; risk assessment, early cancer detection, monitoring of tumor progression and definition of tumor margins. PMID:17362521

  14. Implications of caries diagnostic strategies for clinical management decisions

    DEFF Research Database (Denmark)

    Bælum, Vibeke; Hintze, Hanne; Wenzel, Ann

    2012-01-01

    OBJECTIVES: In clinical practice, a visual-tactile caries examination is frequently supplemented by bitewing radiography. This study evaluated strategies for combining visual-tactile and radiographic caries detection methods and determined their implications for clinical management decisions...... in a low-caries population. METHODS: Each of four examiners independently examined preselected contacting interproximal surfaces in 53 dental students aged 20-37 years using a visual-tactile examination and bitewing radiography. The visual-tactile examination distinguished between noncavitated...

  15. Peculiarities of insight: Clinical implications of self-representations

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Biosciences; Volume 41; Issue 1. Peculiarities of insight: Clinical implications of self-representations. Anjali Bhat. Clipboard Volume 41 Issue 1 March 2016 pp 3-8. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/jbsc/041/01/0003-0008. Keywords.

  16. Clinical implications of a phenomenological study: Being regarded ...

    African Journals Online (AJOL)

    Clinical implications of a phenomenological study: Being regarded as a threat while attempting to do one's best. Norma Cole. Abstract. Cultural messages promote putting forward one's best effort, and yet any level of success, or the effort itself, can lead to being regarded as a threat. People forming everyday social ...

  17. Clinical Implications of Dynamic Systems Theory for Phonological Development

    Science.gov (United States)

    Rvachew, Susan; Bernhardt, Barbara May

    2010-01-01

    Purpose: To examine treatment outcomes in relation to the complexity of treatment goals for children with speech sound disorders. Method: The clinical implications of dynamic systems theory in contrast with learnability theory are discussed, especially in the context of target selection decisions for children with speech sound disorders. Detailed…

  18. Natriuretic Peptides: Biochemistry, Physiology, Clinical Implication

    Directory of Open Access Journals (Sweden)

    I. A. Kozlova

    2009-01-01

    Full Text Available In the past years, the interest of theorists and clinicians has steadily increased in the myocardially secreted hormones – natriuretic peptides. At the Congress of the European Society of Anesthesiology (Munich, 2007, B-type natriuretic peptides were included into the list of the parameters of perioperative laboratory monitoring that is expedient in the practice of anesthetists and resuscitation specialists. The literature review shows the history of discovery and identification of different types of natriuretic peptides and considers the matters of their biochemistry. It also details information on the synthesis, secretion, and clearance of these peptides, as well as their receptor apparatus in various organs and tissues. The physiology of the regulatory system is described, as applied to the cardiovascular, excretory, central nervous systems, and the neuroendocrine one. Special attention is given to the current publications on the control of B-type natriuretic peptides as biomarkers of cardiac dysfunction. The diagnostic and prognostic values of peptides are analyzed in chronic circulatory insufficiency, coronary heart disease, and other car-diological and non-cardiological diseases. The prognostic value of elevated B-type natriuretic peptide levels in cardiac surgery is separately considered. It is concluded that the changes in the level of B-type natriuretic peptides in different clinical situations are the subject of numerous researches mainly made in foreign countries. The bulk of these researches are devoted to the study of peptides in cardiology and other areas of therapy. Studies on the use of peptides in reanimatology are relatively few and their results are rather discordant. The foregoing opens up wide prospects for studying the use of B-type natriuretic peptides in Russian intensive care and anesthesiology. Key words: natriuretic peptides, brain nautriuretic peptides, NT-proBNP.

  19. Intraluminal Palmaz stent implantation. First clinical case report on a balloon-expandable vessel prosthesis

    Energy Technology Data Exchange (ETDEWEB)

    Palmaz, J.C.; Richter, G.M.; Noeldge, G.; Kauffmann, G.W.; Wenz, W.

    1987-12-01

    A 74-year-old patient suffering from severe iliac artery stenosis and claudication was chosen to be the first candidate in the world to receive the Palmaz stent, a balloon-expandable intraluminal stent. This procedure was done in the Department of Radiology, University of Freiburg, FRG. The intervention and postprocedural course were uneventful. His walking distance improved from less than 100 m to unlimited walking capacity. The intra-arterial pressure gradient and ankle-arm pressure ratio also returned to normal.

  20. Supernatural impotence: historical review with anthropological and clinical implications.

    Science.gov (United States)

    Margolin, J; Witztum, E

    1989-12-01

    The historical and cultural background of the belief in supernatural impotence is presented, emphasizing its possible implications for clinical practice. A brief historical survey of the concept in Judaism and Christianity is followed by a short anthropological survey of supernatural impotence in different ethnic subcultures in Israel. A case demonstration exemplifies the connection between understanding the patient's cultural background and beliefs and the clinical competence of the therapist. The relationship between the clinical-therapeutic process in psychiatric practice and knowledge of the patient's cultural background and beliefs is stressed.

  1. Empirical Correlates and Expanded Interpretation of the MMPI-2-RF Restructured Clinical Scale 3 (Cynicism)

    Science.gov (United States)

    Ingram, Paul B.; Kelso, Kristy M.; McCord, David M.

    2011-01-01

    The recent release of the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) has received much attention from the clinical psychology community. Particular concerns have focused on Restructured Clinical Scale 3 (RC3; Cynicism). This article briefly reviews the major criticisms and responses regarding the restructuring of…

  2. Expanding the "ports of entry" for speech-language pathologists: a relational and reflective model for clinical practice.

    Science.gov (United States)

    Geller, Elaine; Foley, Gilbert M

    2009-02-01

    To outline an expanded framework for clinical practice in speech-language pathology. This framework broadens the focus on discipline-specific knowledge and infuses mental health constructs within the study of communication sciences and disorders, with the objective of expanding the potential "ports or points of entry" (D. Stern, 1995) for clinical intervention with young children who are language impaired. Specific mental health constructs are highlighted in this article. These include relationship-based learning, attachment theory, working dyadically (the client is the child and parent), reflective practice, transference-countertransference, and the use of self. Each construct is explored as to the way it has been applied in traditional and contemporary models of clinical practice. The underlying premise in this framework is that working from a relationally based and reflective perspective augments change and growth in both client and parent(s). The challenge is for speech-language pathologists to embed mental health constructs within their discipline-specific expertise. This leads to paying attention to both observable aspects of clients' behaviors as well as their internal affective states.

  3. CHD7 mutations and CHARGE syndrome : the clinical implications of an expanding phenotype

    NARCIS (Netherlands)

    Bergman, J. E. H.; Janssen, N.; Hoefsloot, L. H.; Jongmans, M. C. J.; Hofstra, R. M. W.; van Ravenswaaij-Arts, C. M. A.

    Background CHARGE syndrome is a highly variable, multiple congenital anomaly syndrome, of which the complete phenotypic spectrum was only revealed after identification of the causative gene in 2004. CHARGE is an acronym for ocular coloboma, congenital heart defects, choanal atresia, retardation of

  4. HBV DNA Integration: Molecular Mechanisms and Clinical Implications.

    Science.gov (United States)

    Tu, Thomas; Budzinska, Magdalena A; Shackel, Nicholas A; Urban, Stephan

    2017-04-10

    Chronic infection with the Hepatitis B Virus (HBV) is a major cause of liver-related morbidity and mortality. One peculiar observation in cells infected with HBV (or with closely‑related animal hepadnaviruses) is the presence of viral DNA integration in the host cell genome, despite this form being a replicative dead-end for the virus. The frequent finding of somatic integration of viral DNA suggests an evolutionary benefit for the virus; however, the mechanism of integration, its functions, and the clinical implications remain unknown. Here we review the current body of knowledge of HBV DNA integration, with particular focus on the molecular mechanisms and its clinical implications (including the possible consequences of replication-independent antigen expression and its possible role in hepatocellular carcinoma). HBV DNA integration is likely to influence HBV replication, persistence, and pathogenesis, and so deserves greater attention in future studies.

  5. HBV DNA Integration: Molecular Mechanisms and Clinical Implications

    Science.gov (United States)

    Tu, Thomas; Budzinska, Magdalena A.; Shackel, Nicholas A.; Urban, Stephan

    2017-01-01

    Chronic infection with the Hepatitis B Virus (HBV) is a major cause of liver-related morbidity and mortality. One peculiar observation in cells infected with HBV (or with closely‑related animal hepadnaviruses) is the presence of viral DNA integration in the host cell genome, despite this form being a replicative dead-end for the virus. The frequent finding of somatic integration of viral DNA suggests an evolutionary benefit for the virus; however, the mechanism of integration, its functions, and the clinical implications remain unknown. Here we review the current body of knowledge of HBV DNA integration, with particular focus on the molecular mechanisms and its clinical implications (including the possible consequences of replication-independent antigen expression and its possible role in hepatocellular carcinoma). HBV DNA integration is likely to influence HBV replication, persistence, and pathogenesis, and so deserves greater attention in future studies. PMID:28394272

  6. The Clinical Implications of Fatty Pancreas: A Concise Review.

    Science.gov (United States)

    Khoury, Tawfik; Asombang, Akwi W; Berzin, Tyler M; Cohen, Jonah; Pleskow, Douglas K; Mizrahi, Meir

    2017-10-01

    Fatty pancreas is a newly recognized condition which is poorly investigated until today as compared to nonalcoholic fatty liver disease. It is characterized by pancreatic fat accumulation and subsequent development of pancreatic and metabolic complications. Association of fatty pancreas have been described with type 2 diabetes mellitus, acute and chronic pancreatitis and even pancreatic carcinoma. In this review article, we provide an update on clinical implications, pathogenesis, diagnosis, treatment and outcomes.

  7. Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1

    Directory of Open Access Journals (Sweden)

    Ullmann Reinhard

    2011-08-01

    Full Text Available Abstract Background Heterozygous copy-number and missense variants in CNTNAP2 and NRXN1 have repeatedly been associated with a wide spectrum of neuropsychiatric disorders such as developmental language and autism spectrum disorders, epilepsy and schizophrenia. Recently, homozygous or compound heterozygous defects in either gene were reported as causative for severe intellectual disability. Methods 99 patients with severe intellectual disability and resemblance to Pitt-Hopkins syndrome and/or suspected recessive inheritance were screened for mutations in CNTNAP2 and NRXN1. Molecular karyotyping was performed in 45 patients. In 8 further patients with variable intellectual disability and heterozygous deletions in either CNTNAP2 or NRXN1, the remaining allele was sequenced. Results By molecular karyotyping and mutational screening of CNTNAP2 and NRXN1 in a group of severely intellectually disabled patients we identified a heterozygous deletion in NRXN1 in one patient and heterozygous splice-site, frameshift and stop mutations in CNTNAP2 in four patients, respectively. Neither in these patients nor in eight further patients with heterozygous deletions within NRXN1 or CNTNAP2 we could identify a defect on the second allele. One deletion in NRXN1 and one deletion in CNTNAP2 occurred de novo, in another family the deletion was also identified in the mother who had learning difficulties, and in all other tested families one parent was shown to be healthy carrier of the respective deletion or mutation. Conclusions We report on patients with heterozygous defects in CNTNAP2 or NRXN1 associated with severe intellectual disability, which has only been reported for recessive defects before. These results expand the spectrum of phenotypic severity in patients with heterozygous defects in either gene. The large variability between severely affected patients and mildly affected or asymptomatic carrier parents might suggest the presence of a second hit, not

  8. PSYCHOANALYTIC CLINIC IMPLICATED: CONNECTIONS WITH CULTURE, SOCIETY AND POLITICS

    Directory of Open Access Journals (Sweden)

    Miriam Debieux Rosa

    2017-09-01

    Full Text Available This article addresses the dilemmas of the advancement of psychoanalysis when taking into account certain problems, such as social exclusion, racism and others. These issues emerge when the psychoanalyst offers his or her listening in the pólis: in health care, assistance or education institutions, in communities. Such clinical-political psychoanalytic practices find the limits of its field and encourage the necessary dialogue with other fields of knowledge. On the other hand, they encourage the deepening of concepts and the creation of clinical devices compatible with the sociopolitical dimension of suffering. In the first part of the article, we discuss present the way that Freud articulates clinical practice, theory and social issues. Since then, however, the theoretical advance of psychoanalysis in its interface with culture has privileged artistic and religious facts, at the expense of the political, economic and social dimension. In the second part, we present our conception of clinical-political psychoanalytic or implicated psychoanalysis.

  9. Babesiosis in dogs and cats--expanding parasitological and clinical spectra.

    Science.gov (United States)

    Solano-Gallego, Laia; Baneth, Gad

    2011-09-08

    Canine babesiosis caused by different Babesia species is a protozoal tick-borne disease with worldwide distribution and global significance. Historically, Babesia infection in dogs was identified based on the morphologic appearance of the parasite in the erythrocyte. All large forms of Babesia were designated Babesia canis, whereas all small forms of Babesia were considered to be Babesia gibsoni. However, the development of molecular methods has demonstrated that other Babesia species such as Babesia conradae, Babesia microti like piroplasm, Theileria spp. and a yet unnamed large form Babesia spp. infect dogs and cause distinct diseases. Babesia rossi, B. canis and Babesia vogeli previously considered as subspecies are identical morphologically but differ in the severity of clinical manifestations which they induce, their tick vectors, genetic characteristics, and geographic distributions, and are therefore currently considered separate species. The geographic distribution of the causative agent and thus the occurrence of babesiosis are largely dependent on the habitat of relevant tick vector species, with the exception of B. gibsoni where evidence for dog to dog transmission indicates that infection can be transmitted among fighting dog breeds independently of the limitations of vector tick infestation. Knowledge of the prevalence and clinicopathological aspects of Babesia species infecting dogs around the world is of epidemiologic and medical interest. Babesiosis in domestic cats is less common and has mostly been reported from South Africa where infection is mainly due to Babesia felis, a small Babesia that causes anemia and icterus. In addition, Babesia cati was reported from India and sporadic cases of B. canis infection in domestic cats have been reported in Europe, B. canis presentii in Israel and B. vogeli in Thailand. Babesiosis caused by large Babesia spp. is commonly treated with imidocarb dipropionate with good clinical response while small Babesia spp

  10. Clinical evaluation of expanded mesh connective tissue graft in the treatment for multiple adjacent gingival recessions in the esthetic zone.

    Science.gov (United States)

    Shanmugam, M; Shivakumar, B; Meenapriya, B; Anitha, V; Ashwath, B

    2015-01-01

    Multiple approaches have been used to replace lost, damaged or diseased gingival tissues. The connective tissue graft (CTG) procedure is the golden standard method for root coverage. Although multiple sites often need grafting, the palatal mucosa supplies only a limited area of grafting material. To overcome this limitation, expanded mesh graft provides a method whereby a graft can be stretched to cover a large area. The aim of this study was to evaluate the effectiveness and the predictability of expanded mesh CTG (e-MCTG) in the treatment of adjacent multiple gingival recessions. Sixteen patients aged 20-50 years contributed to 55 sites, each site falling into at least three adjacent Miller's Class 1 or Class 2 gingival recession. The CTG obtained from the palatal mucosa was expanded to cover the recipient bed, which was 1.5 times larger than the graft. Clinical measurements were recorded at baseline and 3 months, 12 months postoperatively. A mean coverage of 1.96 mm ± 0.66 mm and 2.22 mm ± 0.68 mm was obtained at the end of 3(rd) and 12(th) month, respectively. Twelve months after surgery a statistically significant increase in CAL (2.2 mm ± 0.68 mm, P < 0.001) and increasing WKT (1.75 ± 0.78, P < 0.001) were obtained. In 80% of the treated sites, 100% root coverage was achieved (mean 93.5%). The results of this study demonstrated that multiple adjacent recessions were treated by using e-MCTG technique can be applied and highly predictable root coverage can be achieved.

  11. Clinical evaluation of expanded mesh connective tissue graft in the treatment for multiple adjacent gingival recessions in the esthetic zone

    Directory of Open Access Journals (Sweden)

    M Shanmugam

    2015-01-01

    Full Text Available Background: Multiple approaches have been used to replace lost, damaged or diseased gingival tissues. The connective tissue graft (CTG procedure is the golden standard method for root coverage. Although multiple sites often need grafting, the palatal mucosa supplies only a limited area of grafting material. To overcome this limitation, expanded mesh graft provides a method whereby a graft can be stretched to cover a large area. The aim of this study was to evaluate the effectiveness and the predictability of expanded mesh CTG (e-MCTG in the treatment of adjacent multiple gingival recessions. Materials and Methods: Sixteen patients aged 20-50 years contributed to 55 sites, each site falling into at least three adjacent Miller′s Class 1 or Class 2 gingival recession. The CTG obtained from the palatal mucosa was expanded to cover the recipient bed, which was 1.5 times larger than the graft. Clinical measurements were recorded at baseline and 3 months, 12 months postoperatively. Results: A mean coverage of 1.96 mm ± 0.66 mm and 2.22 mm ± 0.68 mm was obtained at the end of 3 rd and 12 th month, respectively. Twelve months after surgery a statistically significant increase in CAL (2.2 mm ± 0.68 mm, P < 0.001 and increasing WKT (1.75 ± 0.78, P < 0.001 were obtained. In 80% of the treated sites, 100% root coverage was achieved (mean 93.5%. Conclusions: The results of this study demonstrated that multiple adjacent recessions were treated by using e-MCTG technique can be applied and highly predictable root coverage can be achieved.

  12. Leveraging a Statewide Clinical Data Warehouse to Expand Boundaries of the Learning Health System.

    Science.gov (United States)

    Turley, Christine B; Obeid, Jihad; Larsen, Rick; Fryar, Katrina M; Lenert, Leslie; Bjorn, Arik; Lyons, Genevieve; Moskowitz, Jay; Sanderson, Iain

    2016-01-01

    Learning Health Systems (LHS) require accessible, usable health data and a culture of collaboration-a challenge for any single system, let alone disparate organizations, with macro- and micro-systems. Recently, the National Science Foundation described this important setting as a cyber-social ecosystem. In 2004, in an effort to create a platform for transforming health in South Carolina, Health Sciences South Carolina (HSSC) was established as a research collaboration of the largest health systems, academic medical centers and research intensive universities in South Carolina. With work beginning in 2010, HSSC unveiled an integrated Clinical Data Warehouse (CDW) in 2013 as a crucial anchor to a statewide LHS. This CDW integrates data from independent health systems in near-real time, and harmonizes the data for aggregation and use in research. With records from over 2.7 million unique patients spanning 9 years, this multi-institutional statewide clinical research repository allows integrated individualized patient-level data to be used for multiple population health and biomedical research purposes. In the first 21 months of operation, more than 2,800 de-identified queries occurred through i2b2, with 116 users. HSSC has developed and implemented solutions to complex issues emphasizing anti-competitiveness and participatory governance, and serves as a recognized model to organizations working to improve healthcare quality by extending the traditional borders of learning health systems.

  13. Expanding the clinical and neuroradiologic phenotype of primary microcephaly due to ASPM mutations.

    Science.gov (United States)

    Passemard, S; Titomanlio, L; Elmaleh, M; Afenjar, A; Alessandri, J-L; Andria, G; de Villemeur, T Billette; Boespflug-Tanguy, O; Burglen, L; Del Giudice, E; Guimiot, F; Hyon, C; Isidor, B; Mégarbané, A; Moog, U; Odent, S; Hernandez, K; Pouvreau, N; Scala, I; Schaer, M; Gressens, P; Gerard, B; Verloes, Alain

    2009-09-22

    To determine the spectrum of clinical, neuropsychological, and neuroradiologic features in patients with autosomal recessive primary microcephaly (MCPH) due to ASPM gene mutations. ASPM was sequenced in 52 unrelated MCPH probands. In patients with ASPM mutations, we evaluated the clinical phenotype, cognition, behavior, brain MRI, and family. We found homozygous or compound heterozygous ASPM loss-of-function mutations in 11 (22%) probands and 5 siblings. The probands harbored 18 different mutations, of which 16 were new. Microcephaly was severe after 1 year of age in all 16 patients, although in 4 patients the occipital-frontal circumference (OFC) at birth was decreased by only 2 SD. The OFC Z score consistently decreased after birth. Late-onset seizures occurred in 3 patients and significant pyramidal tract involvement in 1 patient. Intellectual quotients ranged from borderline-normal to severe mental retardation. Mild motor delay was noted in 7/16 patients. Language development was delayed in all patients older than 3 years. Brain MRI (n = 12) showed a simplified gyral pattern in 9 patients and several malformations including ventricle enlargement (n = 7), partial corpus callosum agenesis (n = 3), mild cerebellar hypoplasia (n = 1), focal cortical dysplasia (n = 1), and unilateral polymicrogyria (n = 1). Non-neurologic abnormalities consisted of short stature (n = 1), idiopathic premature puberty (n = 1), and renal dysplasia (n = 1). We provide a detailed description of features associated with ASPM mutations. Borderline microcephaly at birth, borderline-normal intellectual efficiency, and brain malformations can occur in ASPM-related primary hereditary microcephaly.

  14. Expanding the role of objectively structured clinical examinations in nephrology training.

    Science.gov (United States)

    Prince, Lisa K; Abbott, Kevin C; Green, Felicidad; Little, Dustin; Nee, Robert; Oliver, James D; Bohen, Erin M; Yuan, Christina M

    2014-06-01

    Objectively structured clinical examinations (OSCEs) are widely used in medical education, but we know of none described that are specifically for nephrology fellowship training. OSCEs use simulation to educate and evaluate. We describe a technically simple, multidisciplinary, low-cost OSCE developed by our program that contains both examination and training features and focuses on management and clinical knowledge of rare hemodialysis emergencies. The emergencies tested are venous air embolism, blood leak, dialysis membrane reaction, and hemolysis. Fifteen fellows have participated in the OSCE as examinees and/or preceptors since June 2010. All have passed the exercise. Thirteen responded to an anonymous survey in July 2013 that inquired about their confidence in managing each of the 4 tested emergencies pre- and post-OSCE. Fellows were significantly more confident in their ability to respond to the emergencies after the OSCE. Those who subsequently saw such an emergency reported that the OSCE experience was somewhat or very helpful in managing the event. The OSCE tested and trained fellows in the recognition and management of rare hemodialysis emergencies. OSCEs and simulation generally deserve greater use in nephrology subspecialty training; however, collaboration between training programs would be necessary to validate such exercises. Published by Elsevier Inc.

  15. Clinical implications of methicillin-resistant Staphylococcus aureus in pregnancy.

    Science.gov (United States)

    Beigi, Richard H

    2011-04-01

    Methicillin-resistant Staphylococcus aureus (MRSA) has become an increasingly aggressive and prevalent pathogen in medicine. This pattern has also been noted in obstetrics. This review will delineate the epidemiology and clinical implications of MRSA during pregnancy. Investigations have focused on prevalence of MRSA colonization in obstetrics and the associated morbidity. In addition, some attention has been focused on the neonatal implications of maternal colonization. Overall, the rates of maternal MRSA colonization noted in the United States have been low, in the range of 0.5-4%. The clinical impact of MRSA colonization among pregnant women has also been estimated to be modest. Roughly 357 invasive MRSA infections per 100,000 live births in the United States occur on an annual basis. It is however important to note that published estimates likely underestimate the full scope of MRSA in pregnancy given the lack of formal reporting, importance of related neonatal colonization and morbidity, the complicated treatment implications in pregnant women, the recognized high pathogenicity of MRSA infections, and propensity for recurrent infections among community-acquired MRSA strains. MRSA is an increasingly important pathogen in modern healthcare and in the obstetric population. Continued surveillance and research remains a top priority.

  16. A novel mutation expands the genetic and clinical spectrum of MYH7-related myopathies.

    Science.gov (United States)

    Clarke, Nigel F; Amburgey, Kimberly; Teener, James; Camelo-Piragua, Sandra; Kesari, Akanchha; Punetha, Jaya; Waddell, Leigh B; Davis, Mark; Laing, Nigel G; Monnier, Nicole; North, Kathryn N; Hoffman, Eric P; Dowling, James J

    2013-05-01

    MYH7 mutations are an established cause of Laing distal myopathy, myosin storage myopathy, and cardiomyopathy, as well as additional myopathy subtypes. We report a novel MYH7 mutation (p.Leu1597Arg) that arose de novo in two unrelated probands. Proband 1 has a myopathy characterized by distal weakness and prominent contractures and histopathology typical of multi-minicore disease. Proband 2 has an axial myopathy and histopathology consistent with congenital fiber type disproportion. These cases highlight the broad spectrum of clinical and histological patterns associated with MYH7 mutations, and provide further evidence that MYH7 is likely responsible for a greater proportion of congenital myopathies than currently appreciated. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. About signs and symptoms: can semiotics expand the view of clinical medicine?

    Science.gov (United States)

    Nessa, J

    1996-12-01

    Semiotics, the theory of sign and meaning, may help physicians complement the project of interpreting signs and symptoms into diagnoses. A sign stands for something. We communicate indirectly through signs, and make sense of our world by interpreting signs into meaning. Thus, through association and inference, we transform flowers into love, Othello into jealousy, and chest pain into heart attack. Medical semiotics is part of general semiotics, which means the study of life of signs within society. With special reference to a case story, elements from general semiotics, together with two theoreticians of equal importance, the Swiss linguist Ferdinand de Saussure and the American logician Charles Sanders Peirce, are presented. Two different modes of understanding clinical medicine are contrasted to illustrate the external link between what we believe or suggest, on the one hand, and the external reality on the other hand.

  18. Demonstrating Impact through Replicable Analysis: Implications of an Evaluation of Arkansas's Expanded Food and Nutrition Education Program

    Science.gov (United States)

    Phelps, Josh; Brite-Lane, Allison; Crook, Tina; Hakkak, Reza; Fuller, Serena

    2017-01-01

    The evaluation described in this article focused on the effectiveness of Arkansas's Extension-based Expanded Food and Nutrition Education Program (EFNEP) but demonstrates an analytic approach that may be useful across Extension programs. We analyzed data from 1,810 Arkansas EFNEP participants' entry and exit Behavior Checklists to assess…

  19. Expanding the clinical phenotype of patients with a ZDHHC9 mutation.

    Science.gov (United States)

    Masurel-Paulet, Alice; Kalscheuer, Vera M; Lebrun, Nicolas; Hu, Hao; Levy, Fabienne; Thauvin-Robinet, Christel; Darmency-Stamboul, Véronique; El Chehadeh, Salima; Thevenon, Julien; Chancenotte, Sophie; Ruffier-Bourdet, Marie; Bonnet, Marlène; Pinoit, Jean-Michel; Huet, Frédéric; Desportes, Vincent; Chelly, Jamel; Faivre, Laurence

    2014-03-01

    In 2007, 250 families with X-linked intellectual disability (XLID) were screened for mutations in genes on the X-chromosome, and in 4 of these families, mutations in the ZDHHC9 gene were identified. The ID was either isolated or associated with a marfanoid habitus. ZDHHC9 encodes a palmitoyl transferase that catalyzes the posttranslational modification of NRAS and HRAS. Since this first description, no additional patient with a ZDHHC9 mutation has been reported in the literature. Here, we describe a large family in which we identified a novel pathogenic ZDHHC9 nonsense mutation (p.Arg298*) by parallel sequencing of all X-chromosome exons. The mutation cosegregated with the clinical phenotype in this family. An 18-year-old patient and his 40-year-old maternal uncle were evaluated. Clinical examination showed normal growth parameters, lingual fasciculation, limited extension of the elbows and metacarpophalangeal joints, and acrocyanosis. There was neither facial dysmorphism nor marfanoid habitus. Brain MRI detected a dysplastic corpus callosum. Neuropsychological testing showed mild intellectual disability. They both displayed generalized anxiety disorder, and the younger patient also suffered from significant behavior impairment that required attention or treatment. Speech evaluation detected satisfactory spoken language since both were able to provide information and to understand conversations of everyday life. Occupational therapy examination showed impaired visual-spatial and visual-motor performance with poor drawing/graphic skills. These manifestations are not specific enough to guide ZDHHC9 screening in patients with ID, and emphasize the value of next generation sequencing for making a molecular diagnosis and genetic counseling in families with XLID. © 2013 Wiley Periodicals, Inc.

  20. Clinical implications of household food security: definitions, monitoring, and policy.

    Science.gov (United States)

    Cook, John T

    2002-01-01

    Poverty-related food insecurity is a reality that many clinicians in nutrition and health care encounter either directly or indirectly. It is associated with both overnutrition and undernutrition, but it is not congruent with malnutrition. Food insecurity affects human development and health throughout the lifecycle, but can be particularly harmful during critical or vulnerable stages early and late in life. Understanding the causes and consequences of food insecurity and knowing how to identify them can improve the quality and effectiveness of clinical care, and facilitate prevention and treatment of many kinds of health problems. Numerous public policies and programs exist to ameliorate and prevent poverty-related food insecurity. However, the resources to support them ebb and flow with the politics of annual state and federal budgetary cycles. Support and need for these social-safety-net programs also vary with business cycles. Unfortunately, need often expands as support shrinks along with employment and government revenues during recessions, and shrinks as support expands along with employment and government revenues during expansions.

  1. Expanding the basic science debate: the role of physics knowledge in interpreting clinical findings.

    Science.gov (United States)

    Goldszmidt, Mark; Minda, John Paul; Devantier, Sarah L; Skye, Aimee L; Woods, Nicole N

    2012-10-01

    Current research suggests a role for biomedical knowledge in learning and retaining concepts related to medical diagnosis. However, learning may be influenced by other, non-biomedical knowledge. We explored this idea using an experimental design and examined the effects of causal knowledge on the learning, retention, and interpretation of medical information. Participants studied a handout about several respiratory disorders and how to interpret respiratory exam findings. The control group received the information in standard "textbook" format and the experimental group was presented with the same information as well as a causal explanation about how sound travels through lungs in both the normal and disease states. Comprehension and memory of the information was evaluated with a multiple-choice exam. Several questions that were not related to the causal knowledge served as control items. Questions related to the interpretation of physical exam findings served as the critical test items. The experimental group outperformed the control group on the critical test items, and our study shows that a causal explanation can improve a student's memory for interpreting clinical details. We suggest an expansion of which basic sciences are considered fundamental to medical education.

  2. Clinical implications of panic symptoms in dental phobia.

    Science.gov (United States)

    Potter, Carrie M; Kinner, Dina G; Tellez, Marisol; Ismail, Amid I; Heimberg, Richard G

    2014-10-01

    The occurrence of panic symptoms in various anxiety disorders has been associated with more severely impaired and difficult-to-treat cases, but this has not been investigated in dental phobia. We examined the clinical implications of panic symptoms related to sub-clinical and clinically significant dental phobia. The sample consisted of 61 patients at a university dental clinic who endorsed symptoms of dental phobia, 25 of whom met criteria for a formal diagnosis of dental phobia. Participants with dental phobia endorsed more panic symptoms than did those with sub-clinical dental phobia. In the total sample, greater endorsement of panic symptoms was associated with higher dental anxiety, more avoidance of dental procedures, and poorer oral health-related quality of life. Among those with dental phobia, certain panic symptoms exhibited associations with specific anxiety-eliciting dental procedures. Panic symptoms may serve as indicators of clinically significant dental phobia and the need for augmented treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. A unique linkage of administrative and clinical registry databases to expand analytic possibilities in pediatric heart transplantation research.

    Science.gov (United States)

    Godown, Justin; Thurm, Cary; Dodd, Debra A; Soslow, Jonathan H; Feingold, Brian; Smith, Andrew H; Mettler, Bret A; Thompson, Bryn; Hall, Matt

    2017-12-01

    Large clinical, research, and administrative databases are increasingly utilized to facilitate pediatric heart transplant (HTx) research. Linking databases has proven to be a robust strategy across multiple disciplines to expand the possible analyses that can be performed while leveraging the strengths of each dataset. We describe a unique linkage of the Scientific Registry of Transplant Recipients (SRTR) database and the Pediatric Health Information System (PHIS) administrative database to provide a platform to assess resource utilization in pediatric HTx. All pediatric patients (1999-2016) who underwent HTx at a hospital enrolled in the PHIS database were identified. A linkage was performed between the SRTR and PHIS databases in a stepwise approach using indirect identifiers. To determine the feasibility of using these linked data to assess resource utilization, total and post-HTx hospital costs were assessed. A total of 3188 unique transplants were identified as being present in both databases and amenable to linkage. Linkage of SRTR and PHIS data was successful in 3057 (95.9%) patients, of whom 2896 (90.8%) had complete cost data. Median total and post-HTx hospital costs were $518,906 (IQR $324,199-$889,738), and $334,490 (IQR $235,506-$498,803) respectively with significant differences based on patient demographics and clinical characteristics at HTx. Linkage of the SRTR and PHIS databases is feasible and provides an invaluable tool to assess resource utilization. Our analysis provides contemporary cost data for pediatric HTx from the largest US sample reported to date. It also provides a platform for expanded analyses in the pediatric HTx population. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Challenges faced by professional nurses when implementing the Expanded Programme on Immunisation at rural clinics in Capricorn District, Limpopo

    Directory of Open Access Journals (Sweden)

    Tebogo M. Mothiba

    2016-03-01

    Full Text Available Background: Immunisation is the cornerstone of primary healthcare. Apart from the provision of safe water, immunisation remains the most cost-effective public health intervention currently available. Immunisation prevents infectious conditions that are debilitating, fatal and have the potential to cause huge public health burdens, both financially and socially, in South Africa.Aim: To determine the challenges faced by professional nurses when implementing the Expanded Programme on Immunisation (EPI at rural clinics in Capricorn District, Limpopo Province, South Africa.Setting: The study was conducted in selected primary healthcare clinics of Capricorn District, Limpopo Province.Methods: A qualitative explorative descriptive contextual research design was used to gather data related to the challenges faced by professional nurses when implementing EPI at rural clinics in Capricorn District.Results: The findings revealed that professional nurses had knowledge of the programme, but that they experienced several challenges during implementation of EPI that included staff shortages and problems related to maintenance of the vaccines’ potency.Conclusions: The Department of Health as well as the nursing administration should monitor policies and guidelines, and especially maintenance of a cold chain for vaccines, to ensure that they are practised throughout Limpopo Province. The problem of staff shortages also needs to be addressed so that the EPI can achieve its targeted objectives.Keywords: Professional nurse, knowledge, EPI-SA, immunisation

  5. Diet and Sleep Physiology: Public Health and Clinical Implications

    Directory of Open Access Journals (Sweden)

    Sarah Frank

    2017-08-01

    Full Text Available This mini-review examines the complex relationship between diet and sleep and explores the clinical and public health implications of the current evidence. Dietary quality and intake of specific nutrients can impact regulatory hormonal pathways to alter sleep quantity and quality. Sleep, in turn, affects the intake of total energy, as well as of specific foods and nutrients, through biological and behavioral mechanisms. Initial research in this field focused primarily on the effects of short sleep duration on nutritional quality. However, more recent studies have explored the dynamic relationship between long sleep duration and diet. Current evidence suggests that extremes of sleep duration alter sleep patterns, hormonal levels, and circadian rhythms, which contribute to weight-related outcomes and obesity, and other risk factors for the development of chronic disease such as type 2 diabetes and cardiovascular disease. These patterns may begin as early as childhood and have impacts throughout the life course. Given that non-communicable diseases are among the leading causes of death globally, deeper understanding of the interactions between sleep and nutrition has implications for both public health and clinical practice.

  6. Surgical treatment of osteoporotic degenerative spinal deformity with expandable pedicle screw fixation: 2-year follow-up clinical study.

    Science.gov (United States)

    Fu, J; Yao, Z M; Wang, Z; Cui, G; Ni, M; Li, X; Chen, J Y

    2017-12-14

    Osteoporotic bone offers poor purchase for the instrumentation in patients with degenerative spinal deformity (DSD), which could lead to several complications. Recently, augmentation methods to improve pedicle screw fixation have been proposed. This retrospective study was to investigate the clinical and radiographic outcomes of expandable pedicle screws (EPS) in patients with osteoporotic DSD. Expandable pedicle screws (EPS) provide excellent instrument fixation in patients with osteoporotic DSD, improving radiographic and clinical outcomes. A total of 27 (6 males and 21 females) DSD patients who underwent orthopedics operation with EPS were retrospectively studied. Full-length standing spinal radiographs were obtained in all patients pre- and postoperatively and again at the two-year follow-up. The functional evaluations before operation and at two-year follow-up were graded with Scoliosis Research Society outcomes instrument-22 (SRS-22) and Oswestry Disability Index (ODI) scoring system. All patients obtained good corrective outcomes on spinal deformity. The preoperative ODI score was 36.7% and reduced to 11.9% at two-year follow-up (p=0.0000). Before operation, the SRS-22 function, pain, appearance and mental scores were 2.7±0.4, 3±0.6, 2.7±0.5 and 2.9±0.6, respectively. The scores at two-year follow-up were significantly improved to 3.8±0.7, 4.2±0.6, 4.3±0.6 and 4.4±0.7, respectively (p=0.0000). The SRS-22 satisfaction score was 4.6±0.4 at two-year follow-up. No instances of screw breakage, loosening or pullout in any patient at follow-up. EPS provides excellent instrument fixation in patients with osteoporotic DSD, improving radiographic and clinical outcomes at two years' follow-up. Retrospective case series study. IV. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Expanded Dengue.

    Science.gov (United States)

    Kadam, D B; Salvi, Sonali; Chandanwale, Ajay

    2016-07-01

    The World Health Organization (WHO) has coined the term expanded dengue to describe cases which do not fall into either dengue shock syndrome or dengue hemorrhagic fever. This has incorporated several atypical findings of dengue. Dengue virus has not been enlisted as a common etiological agent in several conditions like encephalitis, Guillain Barre syndrome. Moreover it is a great mimic of co-existing epidemics like Malaria, Chikungunya and Zika virus disease, which are also mosquito-borne diseases. The atypical manifestations noted in dengue can be mutisystemic and multifacetal. In clinical practice, the occurrence of atypical presentation should prompt us to investigate for dengue. Knowledge of expanded dengue helps to clinch the diagnosis of dengue early, especially during ongoing epidemics, avoiding further battery of investigations. Dengue has proved to be the epidemic with the ability to recur and has a diverse array of presentation as seen in large series from India, Srilanka, Indonesia and Taiwan. WHO has given the case definition of dengue fever in their comprehensive guidelines. Accordingly, a probable case is defined as acute febrile illness with two or more of any findings viz. headache, retro-orbital pain, myalgia, arthralgia, rash, hemorrhagic manifestations, leucopenia and supportive serology. There have been cases of patients admitted with fever, altered mentation with or without neck stiffness and pyramidal tract signs. Some had seizures or status epilepticus as presentation. When they were tested for serology, dengue was positive. After ruling out other causes, dengue remained the only culprit. We have come across varied presentations of dengue fever in clinical practice and the present article throws light on atypical manifestations of dengue. © Journal of the Association of Physicians of India 2011.

  8. Clinical interpretation and implications of whole-genome sequencing.

    Science.gov (United States)

    Dewey, Frederick E; Grove, Megan E; Pan, Cuiping; Goldstein, Benjamin A; Bernstein, Jonathan A; Chaib, Hassan; Merker, Jason D; Goldfeder, Rachel L; Enns, Gregory M; David, Sean P; Pakdaman, Neda; Ormond, Kelly E; Caleshu, Colleen; Kingham, Kerry; Klein, Teri E; Whirl-Carrillo, Michelle; Sakamoto, Kenneth; Wheeler, Matthew T; Butte, Atul J; Ford, James M; Boxer, Linda; Ioannidis, John P A; Yeung, Alan C; Altman, Russ B; Assimes, Themistocles L; Snyder, Michael; Ashley, Euan A; Quertermous, Thomas

    2014-03-12

    Whole-genome sequencing (WGS) is increasingly applied in clinical medicine and is expected to uncover clinically significant findings regardless of sequencing indication. To examine coverage and concordance of clinically relevant genetic variation provided by WGS technologies; to quantitate inherited disease risk and pharmacogenomic findings in WGS data and resources required for their discovery and interpretation; and to evaluate clinical action prompted by WGS findings. An exploratory study of 12 adult participants recruited at Stanford University Medical Center who underwent WGS between November 2011 and March 2012. A multidisciplinary team reviewed all potentially reportable genetic findings. Five physicians proposed initial clinical follow-up based on the genetic findings. Genome coverage and sequencing platform concordance in different categories of genetic disease risk, person-hours spent curating candidate disease-risk variants, interpretation agreement between trained curators and disease genetics databases, burden of inherited disease risk and pharmacogenomic findings, and burden and interrater agreement of proposed clinical follow-up. Depending on sequencing platform, 10% to 19% of inherited disease genes were not covered to accepted standards for single nucleotide variant discovery. Genotype concordance was high for previously described single nucleotide genetic variants (99%-100%) but low for small insertion/deletion variants (53%-59%). Curation of 90 to 127 genetic variants in each participant required a median of 54 minutes (range, 5-223 minutes) per genetic variant, resulted in moderate classification agreement between professionals (Gross κ, 0.52; 95% CI, 0.40-0.64), and reclassified 69% of genetic variants cataloged as disease causing in mutation databases to variants of uncertain or lesser significance. Two to 6 personal disease-risk findings were discovered in each participant, including 1 frameshift deletion in the BRCA1 gene implicated in

  9. Typology of Internet gaming disorder and its clinical implications.

    Science.gov (United States)

    Lee, Seung-Yup; Lee, Hae Kook; Choo, Hyekyung

    2017-07-01

    Various perspectives exist regarding Internet gaming disorder. While the concept of behavioral addiction is gaining recognition, some view the phenomenon as merely excessive indulgence in online pastimes. Still, in recent years, complaints from patients or their family members about problems related to Internet use, particularly Internet gaming, have become more common. However, the clinical picture of Internet gaming disorder could be obscured by its heterogeneous manifestations with other intertwined factors, such as psychiatric comorbidities, neurodevelopmental factors, sociocultural factors, and game-related factors, which may influence the pathogenesis as well as the clinical course. To mitigate such problems, clinicians should be able to consider diverse aspects related to Internet gaming disorder. Classifying such a heterogeneous problem into subtypes that share a similar etiology or phenomenology may provide additional clues in the diagnostic process and allow us to designate available clinical resources for particularly vulnerable factors. In this review paper, we suggest a typology of 'impulsive/aggressive,' 'emotionally vulnerable,' 'socially conditioned,' and 'not otherwise specified' as subtypes of the heterogeneous phenomena of pathological Internet gaming. The implications of these subtypes for assessment and treatment planning will also be highlighted. © 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.

  10. Clinical implications of hepatitis B virus mutations: recent advances.

    Science.gov (United States)

    Lazarevic, Ivana

    2014-06-28

    Hepatitis B virus (HBV) infection is a major cause of acute and chronic hepatitis, and of its long-term complications. It is the most variable among DNA viruses, mostly because of its unique life cycle which includes the activity of error-prone enzyme, reverse transcriptase, and the very high virion production per day. In last two decades, numerous research studies have shown that the speed of disease progression, reliability of diagnostic methods and the success of antiviral therapy and immunization are all influenced by genetic variability of this virus. It was shown that mutations in specific regions of HBV genome could be responsible for unwanted clinical outcomes or evasion of detection by diagnostic tools, thus making the monitoring for these mutations a necessity in proper evaluation of patients. The success of the vaccination programs has now been challenged by the discovery of mutant viruses showing amino acid substitutions in hepatitis B surface antigen (HBsAg), which may lead to evasion of vaccine-induced immunity. However, the emergence of these mutations has not yet raised concern since it was shown that they develop slowly. Investigations of HBV genetic variability and clinical implications of specific mutations have resulted in significant advances over the past decade, particularly in regard to management of resistance to antiviral drugs. In the era of drugs with high genetic barrier for resistance, on-going monitoring for possible resistance is still essential since prolonged therapy is often necessary. Understanding the frequencies and clinical implications of viral mutations may contribute to improvement of diagnostic procedures, more proper planning of immunization programs and creating the most efficient therapeutic protocols.

  11. Nonfamilial Hypertrophic Cardiomyopathy: Prevalence, Natural History, and Clinical Implications.

    Science.gov (United States)

    Ingles, Jodie; Burns, Charlotte; Bagnall, Richard D; Lam, Lien; Yeates, Laura; Sarina, Tanya; Puranik, Rajesh; Briffa, Tom; Atherton, John J; Driscoll, Tim; Semsarian, Christopher

    2017-04-01

    Yield of causative variants in hypertrophic cardiomyopathy (HCM) is increased in some probands, suggesting different clinical subgroups of disease occur. We hypothesized that a negative family history and no sarcomere mutations represent a nonfamilial subgroup of HCM. We sought to determine the prevalence, natural history, and potential clinical implications of this nonfamilial subgroup of HCM. Four hundred and thirteen unrelated probands with HCM seen in a specialized HCM center between 2002 and 2015 and genetic testing performed were included in this retrospective cohort study. There were 251 (61%) probands with no reported family history of HCM, including 166 (40% of total) probands with no sarcomere mutation, that is, nonfamilial HCM. Quantified family pedigree data revealed no difference in mean number of first-degree relatives screened between nonfamilial and sarcomere-positive groups. Adjusted predictors of nonfamilial status were older age (odds ratio, 1.04; 95% confidence interval, 1.02-1.06; P =0.0001), male sex (odds ratio, 1.96; 95% confidence interval, 1.11-3.45; P =0.02), hypertension (odds ratio, 2.80; 95% confidence interval, 1.57-5.00; P =0.0005), and nonasymmetric septal morphology (odds ratio, 3.41; 95% confidence interval, 1.64-7.08; P =0.001). They had a less severe clinical course with greater event-free survival from major cardiac events ( P =0.04) compared with sarcomere-positive HCM probands. Genotype prediction scores showed good performance in identifying genotype-positive patients (area under the curve, 0.71-0.75) and, in combination with pedigree characteristics, were further improved. Approximately 40% of HCM probands have a nonfamilial subtype, with later onset and less severe clinical course. We propose a revised clinical pathway for management, highlighting the role of genetic testing, a detailed pedigree, and refined clinical surveillance recommendations for family members. © 2017 American Heart Association, Inc.

  12. Bridging the reductive and the synthetic: some reflections on the clinical implications of synchronicity.

    Science.gov (United States)

    Connolly, Angela

    2015-04-01

    When Jung introduced the concepts of synchronicity and the psychoid unconscious, he expanded analytical psychology into decidedly uncanny territory. Despite the early interest shown by Freud, anomalous phenomena such as telepathy have become a taboo subject in psychoanalysis. Today, however, there is an increasing interest in thought transference and synchronicity, thus opening the way for a fruitful exchange between different psychoanalytical schools on their clinical implications. I propose to examine some of the ambiguities of Jung's thinking, to clarify how we define synchronicity, the relationship between synchronicities and parapsychological events, and their clinical significance. At the present moment, we are still unsure if such events should be considered as normal and a way of facilitating individuation, or as an indication of psychopathology in the patient or in the analyst, just as we are uncertain about the particular characteristics of the intersubjective field that can lead to synchronicities. Making use of the typology of mind-matter correlations presented by Atmanspacher and Fach, and the distinction they draw between acategorial and non-categorial states of mind, I will use two clinical vignettes to illustrate the different states of mind in analyst and analysand that can lead to synchronicities. In particular I will focus on the relationship between analytical reverie and synchronicity. © 2015, The Society of Analytical Psychology.

  13. Clinical and biological implications of driver mutations in myelodysplastic syndromes.

    Science.gov (United States)

    Papaemmanuil, Elli; Gerstung, Moritz; Malcovati, Luca; Tauro, Sudhir; Gundem, Gunes; Van Loo, Peter; Yoon, Chris J; Ellis, Peter; Wedge, David C; Pellagatti, Andrea; Shlien, Adam; Groves, Michael John; Forbes, Simon A; Raine, Keiran; Hinton, Jon; Mudie, Laura J; McLaren, Stuart; Hardy, Claire; Latimer, Calli; Della Porta, Matteo G; O'Meara, Sarah; Ambaglio, Ilaria; Galli, Anna; Butler, Adam P; Walldin, Gunilla; Teague, Jon W; Quek, Lynn; Sternberg, Alex; Gambacorti-Passerini, Carlo; Cross, Nicholas C P; Green, Anthony R; Boultwood, Jacqueline; Vyas, Paresh; Hellstrom-Lindberg, Eva; Bowen, David; Cazzola, Mario; Stratton, Michael R; Campbell, Peter J

    2013-11-21

    Myelodysplastic syndromes (MDS) are a heterogeneous group of chronic hematological malignancies characterized by dysplasia, ineffective hematopoiesis and a variable risk of progression to acute myeloid leukemia. Sequencing of MDS genomes has identified mutations in genes implicated in RNA splicing, DNA modification, chromatin regulation, and cell signaling. We sequenced 111 genes across 738 patients with MDS or closely related neoplasms (including chronic myelomonocytic leukemia and MDS-myeloproliferative neoplasms) to explore the role of acquired mutations in MDS biology and clinical phenotype. Seventy-eight percent of patients had 1 or more oncogenic mutations. We identify complex patterns of pairwise association between genes, indicative of epistatic interactions involving components of the spliceosome machinery and epigenetic modifiers. Coupled with inferences on subclonal mutations, these data suggest a hypothesis of genetic "predestination," in which early driver mutations, typically affecting genes involved in RNA splicing, dictate future trajectories of disease evolution with distinct clinical phenotypes. Driver mutations had equivalent prognostic significance, whether clonal or subclonal, and leukemia-free survival deteriorated steadily as numbers of driver mutations increased. Thus, analysis of oncogenic mutations in large, well-characterized cohorts of patients illustrates the interconnections between the cancer genome and disease biology, with considerable potential for clinical application.

  14. Hemicrania Continua: Functional Imaging and Clinical Features With Diagnostic Implications.

    Science.gov (United States)

    Sahler, Kristen

    2013-04-10

    This review focuses on summarizing 2 pivotal articles in the clinical and pathophysiologic understanding of hemicrania continua (HC). The first article, a functional imaging project, identifies both the dorsal rostral pons (a region associated with the generation of migraines) and the posterior hypothalamus (a region associated with the generation of cluster and short-lasting unilateral neuralgiform headache with conjunctival injection and tearing [SUNCT]) as active during HC. The second article is a summary of the clinical features seen in a prospective cohort of HC patients that carry significant diagnostic implications. In particular, they identify a wider range of autonomic signs than what is currently included in the International Headache Society criteria (including an absence of autonomic signs in a small percentage of patients), a high frequency of migrainous features, and the presence of aggravation and/or restlessness during attacks. Wide variations in exacerbation length, frequency, pain description, and pain location (including side-switching pain) are also noted. Thus, a case is made for widening and modifying the clinical diagnostic criteria used to identify patients with HC. © 2013 American Headache Society.

  15. Left atrial mechanics: echocardiographic assessment and clinical implications.

    Science.gov (United States)

    Vieira, Maria J; Teixeira, Rogério; Gonçalves, Lino; Gersh, Bernard J

    2014-05-01

    The importance of the left atrium in cardiovascular performance has long been acknowledged. Quantitative assessment of left atrial (LA) function is laborious, requiring invasive pressure-volume loops and thus precluding its routine clinical use. In recent years, novel postprocessing imaging methodologies have emerged, providing a complementary approach for the assessment of the left atrium. Atrial strain and strain rate obtained using either Doppler tissue imaging or two-dimensional speckle-tracking echocardiography have proved to be feasible and reproducible techniques to evaluate LA mechanics. It is essential to fully understand the clinical applications, advantages, and limitations of LA strain and strain rate analysis. Furthermore, the technique's prognostic value and utility in therapeutic decisions also need further elucidation. The aim of this review is to provide a critical appraisal of LA mechanics. The authors describe the fundamental concepts and methodology of LA strain and strain rate analysis, the reference values reported with different imaging techniques, and the clinical implications. Copyright © 2014 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.

  16. Clinical Implications of Hedgehog Pathway Signaling in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Daniel L. Suzman

    2015-09-01

    Full Text Available Activity in the Hedgehog pathway, which regulates GLI-mediated transcription, is important in organogenesis and stem cell regulation in self-renewing organs, but is pathologically elevated in many human malignancies. Mutations leading to constitutive activation of the pathway have been implicated in medulloblastoma and basal cell carcinoma, and inhibition of the pathway has demonstrated clinical responses leading to the approval of the Smoothened inhibitor, vismodegib, for the treatment of advanced basal cell carcinoma. Aberrant Hedgehog pathway signaling has also been noted in prostate cancer with evidence suggesting that it may render prostate epithelial cells tumorigenic, drive the epithelial-to-mesenchymal transition, and contribute towards the development of castration-resistance through autocrine and paracrine signaling within the tumor microenvironment and cross-talk with the androgen pathway. In addition, there are emerging clinical data suggesting that inhibition of the Hedgehog pathway may be effective in the treatment of recurrent and metastatic prostate cancer. Here we will review these data and highlight areas of active clinical research as they relate to Hedgehog pathway inhibition in prostate cancer.

  17. Impulse control disorders in Parkinson's disease: clinical characteristics and implications

    Science.gov (United States)

    Leeman, Robert F; Potenza, Marc N

    2011-01-01

    SUMMARY Impulse control disorders (ICDs), specifically those related to excessive gambling, eating, sex and shopping, have been observed in a subset of people with Parkinson's disease (PD). Although some initial case reports claimed that dopamine replacement therapies, particularly dopamine agonists, cause ICDs, more recent, larger and better controlled studies indicate a more complicated picture. While dopamine replacement therapy use is related to ICDs, other vulnerabilities, some related to PD and/or its treatment directly and others seemingly unrelated to PD, have also been associated with ICDs in PD. This suggests a complex etiology with multiple contributing factors. As ICDs occur in a sizable minority of PD patients and can be associated with significant distress and impairment, further investigation is needed to identify factors that can predict who may be more likely to develop ICDs. Clinical implications are discussed and topics for future research are offered. PMID:21709778

  18. Some implications for the clinical use of music facilitated imagery.

    Science.gov (United States)

    Peach, S C

    1984-01-01

    In this study, Helen Bonny's Guided Imagery and Music technique provided the base experience for questionnaire responses from short-term psychiatric inpatients, students, and staff (total/n = 107). Independent measures of age range, sex, medication type, and recent relaxation practice were compared statistically with dependent responses of skin temperature, perceived ability to relax, production of images, and perceived helpfulness of the experience. Results demonstrated increases in skin temperature and relaxation perception and defined the average experience as manifesting three concurrent imagery modes. Among the man independent-dependent variable relationships, some significant differences in mean responses were present. These differences and their possible clinical implications are discussed; further research in the area, including replication, is recommended.

  19. Experience in production of (68)Ga-DOTA-NOC for clinical use under an Expanded Access IND.

    Science.gov (United States)

    Green, Mark A; Mathias, Carla J; Fletcher, James W

    2016-10-01

    [(68)Ga]Ga-DOTA-NOC was produced under an Expanded Access IND for 174 clinical PET/CT studies to evaluate patients with neuroendocrine tumors. Production employed either the TiO2-based Eckert & Ziegler (EZAG) (68)Ge/(68)Ga-generator (with fractionated elution), or the SiO2-based ITG (68)Ge/(68)Ga-generator. In both cases, [(68)Ga]Ga-DOTA-NOC was reliably produced, without pre-synthesis purification of the(68)Ga generator eluate, using readily-implemented manual synthesis procedures. [(68)Ga]Ga-DOTA-NOC radiochemical purity averaged 99.2±0.4%. Administered (68)Ga dose averaged 181±22 MBq, and administered peptide mass averaged 43.2±5.2µg (n=47) and 23.9±5.7µg (n=127), respectively, using the EZAG and ITG generators. At dose expiration, (68)Ge breakthrough in the final product averaged 2.7×10(-7)% and 5.4×10(-5%) using the EZAG and ITG generators, respectively. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Implications of caries diagnostic strategies for clinical management decisions.

    Science.gov (United States)

    Baelum, Vibeke; Hintze, Hanne; Wenzel, Ann; Danielsen, Bo; Nyvad, Bente

    2012-06-01

    In clinical practice, a visual-tactile caries examination is frequently supplemented by bitewing radiography. This study evaluated strategies for combining visual-tactile and radiographic caries detection methods and determined their implications for clinical management decisions in a low-caries population. Each of four examiners independently examined preselected contacting interproximal surfaces in 53 dental students aged 20-37 years using a visual-tactile examination and bitewing radiography. The visual-tactile examination distinguished between noncavitated and cavitated lesions while the radiographic examination determined lesion depth. Direct inspection of the surfaces following tooth separation for the presence of cavitated or noncavitated lesions was the validation method. The true-positive rate (i.e. the sensitivity) and the false-positive rate (i.e. 1-specificity) were calculated for each diagnostic strategy. Visual-tactile examination provided a true-positive rate of 34.2% and a false-positive rate of 1.5% for the detection of a cavity. The combination of a visual-tactile and a radiographic examination using the lesion in dentin threshold for assuming cavitation had a true-positive rate of 76.3% and a false-positive rate of 8.2%. When diagnostic observations were translated into clinical management decisions using the rule that a noncavitated lesion should be treated nonoperatively and a cavitated lesion operatively, our results showed that the visual-tactile method alone was the superior strategy, resulting in most correct clinical management decisions and most correct decisions regarding the choice of treatment. © 2011 John Wiley & Sons A/S.

  1. The genetic landscape of Alzheimer disease: clinical implications and perspectives.

    Science.gov (United States)

    Van Cauwenberghe, Caroline; Van Broeckhoven, Christine; Sleegers, Kristel

    2016-05-01

    The search for the genetic factors contributing to Alzheimer disease (AD) has evolved tremendously throughout the years. It started from the discovery of fully penetrant mutations in Amyloid precursor protein, Presenilin 1, and Presenilin 2 as a cause of autosomal dominant AD, the identification of the ɛ4 allele of Apolipoprotein E as a strong genetic risk factor for both early-onset and late-onset AD, and evolved to the more recent detection of at least 21 additional genetic risk loci for the genetically complex form of AD emerging from genome-wide association studies and massive parallel resequencing efforts. These advances in AD genetics are positioned in light of the current endeavor directing toward translational research and personalized treatment of AD. We discuss the current state of the art of AD genetics and address the implications and relevance of AD genetics in clinical diagnosis and risk prediction, distinguishing between monogenic and multifactorial AD. Furthermore, the potential and current limitations of molecular reclassification of AD to streamline clinical trials in drug development and biomarker studies are addressed.Genet Med 18 5, 421-430.

  2. Novel Findings into AIRE Genetics and Functioning: Clinical Implications.

    Science.gov (United States)

    De Martino, Lucia; Capalbo, Donatella; Improda, Nicola; Lorello, Paola; Ungaro, Carla; Di Mase, Raffaella; Cirillo, Emilia; Pignata, Claudio; Salerno, Mariacarolina

    2016-01-01

    Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), formerly known as autoimmune polyendocrine syndrome type 1, is a paradigm of a monogenic autoimmune disease caused by mutations of a gene, named autoimmune regulator (AIRE). AIRE acts as a transcription regulator that promotes immunological central tolerance by inducing the ectopic thymic expression of many tissue-specific antigens. Although the syndrome is a monogenic disease, it is characterized by a wide variability of the clinical expression with no significant correlation between genotype and phenotype. Indeed, many aspects regarding the exact role of AIRE and APECED pathogenesis still remain unraveled. In the last decades, several studies in APECED and in its mouse experimental counterpart have revealed new insights on how immune system learns self-tolerance. Moreover, novel interesting findings have extended our understanding of AIRE's function and regulation thus improving our knowledge on the pathogenesis of APECED. In this review, we will summarize recent novelties on molecular mechanisms underlying the development of APECED and their clinical implications.

  3. Kinase inhibitors and monoclonal antibodies in oncology: clinical implications.

    Science.gov (United States)

    Gharwan, Helen; Groninger, Hunter

    2016-04-01

    Molecularly targeted cancer therapies, such as small-molecule kinase inhibitors and monoclonal antibodies, constitute a rapidly growing and an important part of the oncology armamentarium. Unlike conventional (cytotoxic) chemotherapeutics, targeted therapies were designed to disrupt cancer cell pathogenesis at specific biological points essential for the development and progression of the tumour. These agents were developed to disrupt specific targets with the aim of minimizing treatment burden compared with conventional chemotherapy. Nevertheless the increasingly common use of targeted therapies has revealed some unanticipated, often clinically significant toxic effects, as well as compromising effective palliative and end-of-life management approaches. Although patients and clinicians welcome improvements in cancer prognosis, these changes can also impact patient quality-of-life. Therefore, as demand for oncology expertise increases, physicians need to apprise themselves of targeted therapies and their clinical implications, including drug-specific side effects, impact on quality of life, and cost issues, especially in relation to end-of-life care. This Review provides a useful summary and guide for professionals treating patients with malignant diseases.

  4. A Rare Chromosome 3 Imbalance and Its Clinical Implications

    Directory of Open Access Journals (Sweden)

    Karen Sims

    2012-01-01

    Full Text Available The duplication of chromosome 3q is a rare disorder with varying chromosomal breakpoints and consequently symptoms. Even rarer is the unbalanced outcome from a parental inv(3 resulting in duplicated 3q and a deletion of 3p. Molecular karyotyping should aid in precisely determining the length and breakpoints of the 3q+/3p− so as to better understand a child’s future development and needs. We report a case of an infant male with a 57.5 Mb duplication from 3q23-qter. This patient also has an accompanying 1.7 Mb deletion of 3p26.3. The duplicated segment in this patient encompasses the known critical region of 3q26.3-q27, which is implicated in the previously reported 3q dup syndrome; however, the accompanying 3p26.3 deletion is smaller than the previously reported cases. The clinical phenotype of this patient relates to previously reported cases of 3q+ that may suggest that the accompanying 1.7 Mb heterozygous deletion is not clinically relevant. Taken together, our data has refined the location and extent of the chromosome 3 imbalance, which will aid in better understanding the molecular underpinning of the 3q syndrome.

  5. Clinical implications of new mechanistic insights into atopic dermatitis.

    Science.gov (United States)

    Leung, Donald Y M

    2016-08-01

    The review will examine recent advances in our understanding of atopic dermatitis and how these mechanisms provide a framework for new approaches to the management of this common skin disease. The mechanisms by which epithelial skin barrier and immune responses contribute to the complex clinical phenotypes found in atopic dermatitis are being elucidated. Atopic dermatitis often precedes food allergy because reduced skin barrier function allows environmental food allergens to penetrate the skin leading to systemic allergen sensitization. There is increasing evidence that atopic dermatitis is a systemic disease. New treatments are focused on intervention in polarized immune responses leading to allergic diseases. This includes antagonism of IL-4 and IL-13 effects. Prevention strategies involve maintaining normal skin barrier function with emollients to prevent allergens and microbes from penetrating the skin. Recent work on the pathogenesis of atopic dermatitis has important implications for its clinical management, including the development of effective barrier creams and biologicals targeting specific polarized immune pathways resulting in skin inflammation.

  6. E-cadherin: Its dysregulation in carcinogenesis and clinical implications.

    Science.gov (United States)

    Wong, Sonia How Ming; Fang, Chee Mun; Chuah, Lay-Hong; Leong, Chee Onn; Ngai, Siew Ching

    2018-01-01

    E-cadherin is a transmembrane glycoprotein which connects epithelial cells together at adherens junctions. In normal cells, E-cadherin exerts its tumour suppressing role mainly by sequestering β-catenin from its binding to LEF (Lymphoid enhancer factor)/TCF (T cell factor) which serves the function of transcribing genes of the proliferative Wnt signaling pathway. Despite the ongoing debate on whether the loss of E-cadherin is the cause or effect of epithelial-mesenchymal transition (EMT), E-cadherin functional loss has frequently been associated with poor prognosis and survival in patients of various cancers. The dysregulation of E-cadherin expression that leads to carcinogenesis happens mostly at the epigenetic level but there are cases of genetic alterations as well. E-cadherin expression has been linked to the cellular functions of invasiveness reduction, growth inhibition, apoptosis, cell cycle arrest and differentiation. Studies on various cancers have shown that these different cellular functions are also interdependent. Recent studies have reported a rapid expansion of E-cadherin clinical relevance in various cancers. This review article summarises the multifaceted effect E-cadherin expression has on cellular functions in the context of carcinogenesis as well as its clinical implications in diagnosis, prognosis and therapeutics. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Statin-associated immune-mediated myopathy: biology and clinical implications.

    Science.gov (United States)

    Christopher-Stine, Lisa; Basharat, Pari

    2017-04-01

    In the last 6 years, our understanding of statin-associated myopathy expanded to include not only a toxic myopathy with limited and reversible side-effects but also an autoimmune variety in which statins likely induce an autoimmune myopathy that is both associated with a specific autoantibody and responsive to immunosuppression and immune modulation. This review widens the reader's understanding of statin myopathy to include an autoimmune process. Statin-associated immune-mediated myopathy provides an example of an environmental trigger (statins) directly implicated in an autoimmune disease associated with a genetic predisposition as well as potential risk factors including concomitant diseases and specific statins. Given a median exposure to statins of 38 months, providers should be aware that anti-3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) myopathy may occur even after several years of statin exposure. It is important for the reader to understand the clinical presentation of statin-associated immune-mediated myopathy and the difference in its clinical presentation to that of statins as direct myotoxins. Prompt recognition of such an entity allows the clinician to immediately stop the offending agent if it has not already been discontinued as well as to recognize that statin rechallenge is not a likely option, and that prompt treatment with immunosuppression and/or immunomodulation is usually of enormous benefit to the patient in restoring muscle strength and physical function. VIDEO ABSTRACT.

  8. Clinical Features, Molecular Heterogeneity, and Prognostic Implications in YARS2-Related Mitochondrial Myopathy

    NARCIS (Netherlands)

    Sommerville, Ewen W.; Ng, Yi Shiau; Alston, Charlotte L.; Dallabona, Cristina; Gilberti, Micol; He, Langping; Knowles, Charlotte; Chin, Sophie L.; Schaefer, Andrew M.; Falkous, Gavin; Murdoch, David; Longman, Cheryl; de Visser, Marianne; Bindoff, Laurence A.; Rawles, John M.; Dean, John C. S.; Petty, Richard K.; Farrugia, Maria E.; Haack, Tobias B.; Prokisch, Holger; McFarland, Robert; Turnbull, Douglass M.; Donnini, Claudia; Taylor, Robert W.; Gorman, Gráinne S.

    2017-01-01

    YARS2 mutations have been associated with a clinical triad of myopathy, lactic acidosis, and sideroblastic anemia in predominantly Middle Eastern populations. However, the identification of new patients expands the clinical and molecular spectrum of mitochondrial disorders. To review the clinical,

  9. Expanded vs. dense polytetrafluoroethylene membranes in vertical ridge augmentation around dental implants: a prospective randomized controlled clinical trial.

    Science.gov (United States)

    Ronda, Marco; Rebaudi, Alberto; Torelli, Lucio; Stacchi, Claudio

    2014-07-01

    This prospective randomized controlled trial was designed to test the performance of titanium-reinforced dense polytetrafluoroethylene (d-PTFE) membrane vs. titanium-reinforced expanded polytetrafluoroethylene (e-PTFE) membrane in achieving vertical bone regeneration, both associated with a composite grafting material. The study enrolled 23 patients requiring bone augmentation with guided bone regeneration (GBR) procedures for placing implants in atrophic posterior mandibles (available bone height membrane (control) or a d-PTFE membrane (test). Membrane removal was performed after 6 months, and changes in bone height were recorded. Seventy-eight implants were inserted in 26 mandibular sites contextually to vertical ridge augmentation procedures. The healing period was uneventful in all sites, and the vertical defects were satisfactorily filled with a newly formed hard tissue. Mean defect fill after 6 months was 5.49 mm (SD ± 1.58) at test sites and 4.91 mm (SD ± 1.78) at control sites. The normalized data (percentage changes against baseline) did not show any statistically significant difference between test and control groups (P = NS). Based on the data from this study, both d-PTFE and e-PTFE membranes showed identical clinical results in the treatment of vertical bone defects around implants, using the GBR technique. The membrane removal procedure was easier to perform in the d-PTFE group than in the e-PTFE group. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  10. Expanding the clinical and genetic spectrum of G6PD deficiency: The occurrence of BCGitis and novel missense mutation.

    Science.gov (United States)

    Khan, Taj Ali; Mazhar, Humaira; Nawaz, Mehboob; Kalsoom, Kalsoom; Ishfaq, Muhammad; Asif, Huma; Rahman, Hazir; Qasim, Muhammad; Naz, Farkhanda; Hussain, Mubashir; Khattak, Baharullah; Ullah, Waheed; Cabral-Marques, Otavio; Butt, Jawad; Iqbal, Asif

    2017-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway that ensures sufficient production of coenzyme nicotinamide adenine dinucleotide phosphate (NADPH) by catalyzing the reduction of NADP+ to NADPH. Noteworthy, the latter mediates the production of reactive oxygen species (ROS) by phagocytic cells such as neutrophils and monocytes. Therefore, patients with severe forms of G6PD deficiency may present impaired NADPH oxidase activity and become susceptible to recurrent infections. This fact, highlights the importance to characterize the immunopathologic mechanisms underlying the susceptibility to infections in patients with G6PD deficiency. Here we report the first two cases of G6PD deficiency with Bacille Calmette-Guérin (BCG) adverse effect, besides jaundice, hemolytic anemia and recurrent infections caused by Staphylococcus aureus. The qualitative G6PD screening was performed and followed by oxidative burst analysis using flow cytometry. Genetic and in silico analyses were carried out by Sanger sequencing and mutation pathogenicity predicted using bioinformatics tools, respectively. Activated neutrophils and monocytes from patients displayed impaired oxidative burst. The genetic analysis revealed the novel missense mutation c.1157T>A/p.L386Q in G6PD. In addition, in silico analysis indicated that this mutation is pathogenic, thereby hampering the oxidative burst of neutrophils and monocytes from patients. Our data expand the clinical and genetic spectrum of G6PD deficiency, and suggest that impaired oxidative burst in this severe primary immune deficiency is an underlying immunopathologic mechanism that predisposes to mycobacterial infections. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Clinical benefits and oncologic equivalence of self-expandable metallic stent insertion for right-sided malignant colonic obstruction.

    Science.gov (United States)

    Ji, Woong Bae; Kwak, Jung Myun; Kang, Dong Woo; Kwak, Han Deok; Um, Jun Won; Lee, Sun-Il; Min, Byung-Wook; Sung, Nak Song; Kim, Jin; Kim, Seon Hahn

    2017-01-01

    The efficacy of stenting for right-sided malignant colonic obstruction is unknown. This study aimed to evaluate the safety, feasibility, and clinical benefits of self-expandable metallic stent insertion for right-sided malignant colonic obstruction. Clinical data from patients who underwent right hemicolectomy for right colon cancer from January 2006 to July 2014 at three Korea University hospitals were retrospectively reviewed. A total of 39 patients who developed malignant obstruction in the right-sided colon were identified, and their data were analyzed. Stent insertion was attempted in 16 patients, and initial technical success was achieved in 14 patients (87.5 %). No stent-related immediate complications were reported. Complete relief from obstruction was achieved in all 14 patients. Twenty-five patients, including two patients who failed stenting, underwent emergency surgery. In the stent group, 93 % (13/14) of patients underwent elective laparoscopic surgery, and only one surgery was converted to an open procedure. All patients in the emergency group underwent emergency surgery within 24 h of admission. In the emergency group, only 12 % (3/25) of patients underwent laparoscopic surgery, with one surgery converted to an open procedure. All patients in both groups underwent either laparoscopy-assisted or open right/extended right hemicolectomy with primary anastomoses as the first operation. The operative times, retrieved lymph nodes, and pathologic stage did not differ between the two groups. Postoperative hospital stay (9.4 ± 3.4 days in the stent group vs. 12.4 ± 5.9 in the emergency group, p = 0.089) and time to resume oral food intake (3.2 ± 2.1 days in the stent group vs. 5.7 ± 3.4 in the emergency group, p = 0.019) were shorter in the stent group. And there were no significant differences in disease-free survival and overall survival between the two groups. Stent insertion appears to be safe and feasible in patients with right

  12. Variability of CSF Alzheimer's disease biomarkers: implications for clinical practice.

    Directory of Open Access Journals (Sweden)

    Stephanie J B Vos

    Full Text Available BACKGROUND: Cerebrospinal fluid (CSF biomarkers are increasingly being used for diagnosis of Alzheimer's disease (AD. OBJECTIVE: We investigated the influence of CSF intralaboratory and interlaboratory variability on diagnostic CSF-based AD classification of subjects and identified causes of this variation. METHODS: We measured CSF amyloid-β (Aβ 1-42, total tau (t-tau, and phosphorylated tau (p-tau by INNOTEST enzyme-linked-immunosorbent assays (ELISA in a memory clinic population (n = 126. Samples were measured twice in a single or two laboratories that served as reference labs for CSF analyses in the Netherlands. Predefined cut-offs were used to classify CSF biomarkers as normal or abnormal/AD pattern. RESULTS: CSF intralaboratory variability was higher for Aβ1-42 than for t-tau and p-tau. Reanalysis led to a change in biomarker classification (normal vs. abnormal of 26% of the subjects based on Aβ1-42, 10% based on t-tau, and 29% based on p-tau. The changes in absolute biomarker concentrations were paralleled by a similar change in levels of internal control samples between different assay lots. CSF interlaboratory variability was higher for p-tau than for Aβ1-42 and t-tau, and reanalysis led to a change in biomarker classification of 12% of the subjects based on Aβ1-42, 1% based on t-tau, and 22% based on p-tau. CONCLUSIONS: Intralaboratory and interlaboratory CSF variability frequently led to change in diagnostic CSF-based AD classification for Aβ1-42 and p-tau. Lot-to-lot variation was a major cause of intralaboratory variability. This will have implications for the use of these biomarkers in clinical practice.

  13. Variability of CSF Alzheimer's disease biomarkers: implications for clinical practice.

    Science.gov (United States)

    Vos, Stephanie J B; Visser, Pieter Jelle; Verhey, Frans; Aalten, Pauline; Knol, Dirk; Ramakers, Inez; Scheltens, Philip; Rikkert, Marcel G M Olde; Verbeek, Marcel M; Teunissen, Charlotte E

    2014-01-01

    Cerebrospinal fluid (CSF) biomarkers are increasingly being used for diagnosis of Alzheimer's disease (AD). We investigated the influence of CSF intralaboratory and interlaboratory variability on diagnostic CSF-based AD classification of subjects and identified causes of this variation. We measured CSF amyloid-β (Aβ) 1-42, total tau (t-tau), and phosphorylated tau (p-tau) by INNOTEST enzyme-linked-immunosorbent assays (ELISA) in a memory clinic population (n = 126). Samples were measured twice in a single or two laboratories that served as reference labs for CSF analyses in the Netherlands. Predefined cut-offs were used to classify CSF biomarkers as normal or abnormal/AD pattern. CSF intralaboratory variability was higher for Aβ1-42 than for t-tau and p-tau. Reanalysis led to a change in biomarker classification (normal vs. abnormal) of 26% of the subjects based on Aβ1-42, 10% based on t-tau, and 29% based on p-tau. The changes in absolute biomarker concentrations were paralleled by a similar change in levels of internal control samples between different assay lots. CSF interlaboratory variability was higher for p-tau than for Aβ1-42 and t-tau, and reanalysis led to a change in biomarker classification of 12% of the subjects based on Aβ1-42, 1% based on t-tau, and 22% based on p-tau. Intralaboratory and interlaboratory CSF variability frequently led to change in diagnostic CSF-based AD classification for Aβ1-42 and p-tau. Lot-to-lot variation was a major cause of intralaboratory variability. This will have implications for the use of these biomarkers in clinical practice.

  14. Estrogen-gut microbiome axis: Physiological and clinical implications.

    Science.gov (United States)

    Baker, James M; Al-Nakkash, Layla; Herbst-Kralovetz, Melissa M

    2017-09-01

    Low levels of gonadal circulating estrogen observed in post-menopausal women can adversely impact a diverse range of physiological factors, with clinical implications for brain cognition, gut health, the female reproductive tract and other aspects of women's health. One of the principal regulators of circulating estrogens is the gut microbiome. This review aims to shed light on the role of the gut microbiota in estrogen-modulated disease. The gut microbiota regulates estrogens through secretion of β-glucuronidase, an enzyme that deconjugates estrogens into their active forms. When this process is impaired through dysbiosis of gut microbiota, characterized by lower microbial diversity, the decrease in deconjugation results in a reduction of circulating estrogens. The alteration in circulating estrogens may contribute to the development of conditions discussed herein: obesity, metabolic syndrome, cancer, endometrial hyperplasia, endometriosis, polycystic ovary syndrome, fertility, cardiovascular disease (CVD) and cognitive function. The bi-directional relationship between the metabolic profile (including estrogen levels) and gut microbiota in estrogen-driven disease will also be discussed. Promising therapeutic interventions manipulating the gut microbiome and the metabolic profile of estrogen-driven disease, such as bariatric surgery and metformin, will be detailed. Modulation of the microbiome composition subsequently impacts the metabolic profile, and vice versa, and has been shown to alleviate many of the estrogen-modulated disease states. Last, we highlight promising research interventions in the field, such as dietary therapeutics, and discuss areas that provide exciting unexplored topics of study. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. DPP-4 inhibitors: pharmacological differences and their clinical implications.

    Science.gov (United States)

    Ceriello, Antonio; Sportiello, Liberata; Rafaniello, Concetta; Rossi, Francesco

    2014-09-01

    Recently, incretin-based therapy was introduced for the treatment of type 2 diabetes (T2D). In particular, dipeptidyl peptidase-4 inhibitors (DPP-4i) (sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin) play an increasing role in the management of T2D. An extensive literature search was performed to analyze the pharmacological characteristics of DPP-4i and their clinical implications. DPP-4i present significant pharmacokinetic differences. They also differ in chemical structure, in the interaction with distinct subsites of the enzyme and in different levels of selectivity and potency of enzyme inhibition. Moreover, disparities in the effects on glycated hemoglobin, glucagon-like peptide-1 and glucagon levels and on glucose variability have been observed. However, indirect comparisons indicate that all DPP-4i have a similar safety and efficacy profiles. DPP-4i are preferred in overweight/obese and elderly patients because of the advantages of minimal or no influence on weight gain and low risk of hypoglycemia. For the same reasons, DPP-4i can be safely combined with insulin. However, currently cardiovascular outcomes related to DPP-4i are widely debated and the available evidence is controversial. Today, long-term studies are still in progress and upcoming results will allow us to better define the strengths and limits of this therapeutic class.

  16. Genetic Heterogeneity in Colorectal Cancer and its Clinical Implications.

    Science.gov (United States)

    Barranha, Rui; Costa, José Luís; Carneiro, Fátima; Machado, José Carlos

    2015-01-01

    Despite the recent advances in the development of complementary diagnostic exams and modern targeted therapies, colorectal cancer remains a major cause of morbidity and mortality worldwide. In this context, a lot of research has been conducted in the last years to find new markers of poor prognosis. The existence of a complex tumour architecture formed by multiple subclones genetically heterogeneous has been increasingly considered in recent studies as an element of particular importance. This feature seems to influence factors as relevant as the representativeness of tumour biopsies for genetic diagnosis and the efficacy of targeted therapies.There is growing evidence suggesting a relation between genetic heterogeneity and the patientsâ prognosis. The widespread use of next-generation sequencing techniques will allow a better understanding of the true degree of genetic heterogeneity in colorectal tumours, its causes and impact on the course of the disease. In this review we intend to analyse the recent findings related to the genetic heterogeneity of colorectal cancer, as well as its major clinical implications.

  17. Clinical implications of dynamic systems theory for phonological development.

    Science.gov (United States)

    Rvachew, Susan; Bernhardt, Barbara May

    2010-02-01

    To examine treatment outcomes in relation to the complexity of treatment goals for children with speech sound disorders. The clinical implications of dynamic systems theory in contrast with learnability theory are discussed, especially in the context of target selection decisions for children with speech sound disorders. Detailed phonological analyses of pre-and posttreatment speech samples are provided for 6 children who received treatment in a previously published randomized controlled trial of contrasting approaches to target selection (Rvachew & Nowak, 2001). Three children received treatment for simple target phonemes that did not introduce any new feature contrasts into the children's phonological systems. Three children received treatment for complex targets that represented feature contrasts that were absent from the children's phonological systems. Children who received treatment for simple targets made more progress toward the acquisition of the target sounds and demonstrated emergence of complex untreated segments and feature contrasts. Children who received treatment for complex targets made little measurable gain in phonological development. Treatment outcomes will be enhanced if the clinician selects treatment targets at the segmental and prosodic levels of the phonological system in such a way as to stabilize the child's knowledge of subcomponents that form the foundation for the emergence of more complex phoneme contrasts.

  18. Clinical implications of microRNAs in human glioblastoma

    Directory of Open Access Journals (Sweden)

    Masahiro eMizoguchi

    2013-02-01

    Full Text Available Glioblastoma (GBM is one of the most common and dismal brain tumors in adults. Further elucidation of the molecular pathogenesis of GBM is mandatory to improve the overall survival of patients. A novel small non-coding RNA molecule, microRNA (miRNA, appears to represent one of the most attractive target molecules contributing to the pathogenesis of various types of tumors. Recent global analyses have revealed that several miRNAs are clinically implicated in GBM, with some reports indicating the association of miRNA dysregulation with acquired temozolomide (TMZ resistance. More recent studies have revealed that miRNAs could play a role in cancer stem cell (CSC properties, contributing to treatment resistance. In addition, greater impact might be expected from miRNA-targeted therapies based on tumor-derived exosomes that contain numerous functional miRNAs, which could be transferred between tumor cells and surrounding structures. Tumor-derived miRNAs are now considered to be a novel molecular mechanism promoting the progression of GBM. Establishment of miRNA-targeted therapies based on miRNA dysregulation of CSCs could provide effective therapeutic strategies for TMZ-resistant GBM. Recent progress has revealed that miRNAs are not only putative biological markers for diagnosis, but also one of the most promising targets for GBM treatment. Herein, we summarize the translational aspects of miRNAs in the diagnosis and treatment of GBM.

  19. Etiopathology of chronic tubular, glomerular and renovascular nephropathies: Clinical implications

    Directory of Open Access Journals (Sweden)

    Ortiz Alberto

    2011-01-01

    Full Text Available Abstract Chronic kidney disease (CKD comprises a group of pathologies in which the renal excretory function is chronically compromised. Most, but not all, forms of CKD are progressive and irreversible, pathological syndromes that start silently (i.e. no functional alterations are evident, continue through renal dysfunction and ends up in renal failure. At this point, kidney transplant or dialysis (renal replacement therapy, RRT becomes necessary to prevent death derived from the inability of the kidneys to cleanse the blood and achieve hydroelectrolytic balance. Worldwide, nearly 1.5 million people need RRT, and the incidence of CKD has increased significantly over the last decades. Diabetes and hypertension are among the leading causes of end stage renal disease, although autoimmunity, renal atherosclerosis, certain infections, drugs and toxins, obstruction of the urinary tract, genetic alterations, and other insults may initiate the disease by damaging the glomerular, tubular, vascular or interstitial compartments of the kidneys. In all cases, CKD eventually compromises all these structures and gives rise to a similar phenotype regardless of etiology. This review describes with an integrative approach the pathophysiological process of tubulointerstitial, glomerular and renovascular diseases, and makes emphasis on the key cellular and molecular events involved. It further analyses the key mechanisms leading to a merging phenotype and pathophysiological scenario as etiologically distinct diseases progress. Finally clinical implications and future experimental and therapeutic perspectives are discussed.

  20. The image schema and innate archetypes: theoretical and clinical implications.

    Science.gov (United States)

    Merchant, John

    2016-02-01

    Based in contemporary neuroscience, Jean Knox's 2004 JAP paper 'From archetypes to reflective function' honed her position on image schemas, thereby introducing a model for archetypes which sees them as 'reliably repeated early developmental achievements' and not as genetically inherited, innate psychic structures. The image schema model is used to illustrate how the analyst worked with a patient who began life as an unwanted pregnancy, was adopted at birth and as an adult experienced profound synchronicities, paranormal/telepathic phenomena and visions. The classical approach to such phenomena would see the intense affectivity arising out of a ruptured symbiotic mother-infant relationship constellating certain archetypes which set up the patient's visions. This view is contrasted with Knox's model which sees the archetype an sich as a developmentally produced image schema underpinning the emergence of later imagery. The patient's visions can then be understood to arise from his psychoid body memory related to his traumatic conception and birth. The contemporary neuroscience which supports this view is outlined and a subsequent image schema explanation is presented. Clinically, the case material suggests that a pre-birth perspective needs to be explored in all analytic work. Other implications of Knox's image schema model are summarized. © 2016, The Society of Analytical Psychology.

  1. Etiopathology of chronic tubular, glomerular and renovascular nephropathies: Clinical implications

    Science.gov (United States)

    2011-01-01

    Chronic kidney disease (CKD) comprises a group of pathologies in which the renal excretory function is chronically compromised. Most, but not all, forms of CKD are progressive and irreversible, pathological syndromes that start silently (i.e. no functional alterations are evident), continue through renal dysfunction and ends up in renal failure. At this point, kidney transplant or dialysis (renal replacement therapy, RRT) becomes necessary to prevent death derived from the inability of the kidneys to cleanse the blood and achieve hydroelectrolytic balance. Worldwide, nearly 1.5 million people need RRT, and the incidence of CKD has increased significantly over the last decades. Diabetes and hypertension are among the leading causes of end stage renal disease, although autoimmunity, renal atherosclerosis, certain infections, drugs and toxins, obstruction of the urinary tract, genetic alterations, and other insults may initiate the disease by damaging the glomerular, tubular, vascular or interstitial compartments of the kidneys. In all cases, CKD eventually compromises all these structures and gives rise to a similar phenotype regardless of etiology. This review describes with an integrative approach the pathophysiological process of tubulointerstitial, glomerular and renovascular diseases, and makes emphasis on the key cellular and molecular events involved. It further analyses the key mechanisms leading to a merging phenotype and pathophysiological scenario as etiologically distinct diseases progress. Finally clinical implications and future experimental and therapeutic perspectives are discussed. PMID:21251296

  2. Three-dimensional imaging provides valuable clinical data to aid in unilateral tissue expander-implant breast reconstruction.

    Science.gov (United States)

    Tepper, Oren M; Karp, Nolan S; Small, Kevin; Unger, Jacob; Rudolph, Lauren; Pritchard, Ashley; Choi, Mihye

    2008-01-01

    The current approach to breast reconstruction remains largely subjective and is based on physical examination and visual-estimates of breast size. Thus, the overall success of breast reconstruction is limited by the inability of plastic surgeons to objectively assess breast volume and shape, which may result in suboptimal outcomes. A potential solution to this obstacle may be three-dimensional (3D) imaging, which can provide unique clinical data that was previously unattainable to plastic surgeons. The following study represents a prospective analysis of patient volunteers undergoing unilateral tissue expander (TE)-implant reconstruction by one of the two senior authors (MC, NSK). All patients underwent unilateral mastectomy with immediate or delayed insertion of a TE, followed by an exchange for a permanent silicone or saline implant. 3D scans were obtained during routine pre- and postoperative office visits. The 3D breast-volume calculations served as a guide for surgical management. Twelve patients have completed 3D-assisted unilateral breast reconstruction to date. These patients represent a wide range of body habitus and breast size/shape; 3D volume range from 136 to 518 cm(3). The mean baseline breast asymmetry in this group was 12.0 +/- 10.8%. Contralateral symmetry procedures were performed in eleven patients, consisting of the following: mastopexy (n = 6), augmentation (n = 1), mastopexy/augmentation (n = 2), and reduction mammoplasty (n = 2). Reconstruction was completed in a total number of 2 (n = 10) or 3 (n = 2) operations. Overall breast symmetry improved at the completion of reconstruction in the majority of patients, with an average postoperative symmetry of 95.1 +/- 4.4% (relative to 88% preoperatively). 3D imaging serves a valuable adjunct to TE-implant breast reconstruction. This technology provides volumetric data that can help guide breast reconstruction, such as in choosing the initial TE size, total volume of expansion, and final implant size

  3. Production of erythrocytes from directly isolated or Delta1 Notch ligand expanded CD34+ hematopoietic progenitor cells: process characterization, monitoring and implications for manufacture.

    Science.gov (United States)

    Glen, Katie E; Workman, Victoria L; Ahmed, Forhad; Ratcliffe, Elizabeth; Stacey, Adrian J; Thomas, Robert J

    2013-09-01

    Economic ex vivo manufacture of erythrocytes at 10(12) cell doses requires an efficiently controlled bio-process capable of extensive proliferation and high terminal density. High-resolution characterization of the process would identify production strategies for increased efficiency, monitoring and control. CD34(+) cord blood cells or equivalent cells that had been pre-expanded for 7 days with Delta1 Notch ligand were placed in erythroid expansion and differentiation conditions in a micro-scale ambr suspension bioreactor. Multiple culture parameters were varied, and phenotype markers and metabolites measured to identify conserved trends and robust monitoring markers. The cells exhibited a bi-modal erythroid differentiation pattern with an erythroid marker peak after 2 weeks and 3 weeks of culture; differentiation was comparatively weighted toward the second peak in Delta1 pre-expanded cells. Both differentiation events were strengthened by omission of stem cell factor and dexamethasone. The cumulative cell proliferation and death, or directly measured CD45 expression, enabled monitoring of proliferative rate of the cells. The metabolic activities of the cultures (glucose, glutamine and ammonia consumption or production) were highly variable but exhibited systematic change synchronized with the change in differentiation state. Erythroid differentiation chronology is partly determined by the heterogeneous CD34(+) progenitor compartment with implications for input control; Delta1 ligand-mediated progenitor culture can alter differentiation profile with control benefits for engineering production strategy. Differentiation correlated changes in cytokine response, markers and metabolic state will enable scientifically designed monitoring and timing of manufacturing process steps. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  4. Evaluation of the Expanded Disability Status Scale and the Multiple Sclerosis Functional Composite as clinical endpoints in multiple sclerosis clinical trials: quantitative meta-analyses.

    Science.gov (United States)

    Bin Sawad, Aseel; Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa; Turkistani, Fatema

    2016-12-01

    This study compared the sensitivity of the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC) as clinical endpoints in multiple sclerosis (MS) clinical trials. Medline (1946 through 12 September 2014) and Embase (1974 through 12 September 2014) databases searches were conducted using keywords and Medical Subject Heading (MeSH) terms related to MS, EDSS, and MSFC. Only studies that used the EDSS and MSFC as endpoints were assessed. All statistical analyses were conducted using comprehensive meta-analysis (CMA). The percentages of the overall changes in EDSS and MSFC were compared. The relative risks were calculated in randomized clinical trials (RCTs). A total of 123 studies were identified. There were nine studies (6 case series and 3 RCTs) included in the analysis. In the case series, the EDSS change rate in MS patients was 33.5% (95% CI: 12.9-63.2%) and the MSFC change rate was 30.3% (95% CI: 9.2-65.2%). In RCTs, patients who take the drug would be 22.9 times as likely as patients who did not take the drug to experience a change in the EDSS scale (RR = 22.9, 95% CI = 0.996-1.517, p = 0.055). Patients who take the drug would be 48.9 times as likely as patients who did not take the drug to experience a change in the MSFC scale (RR = 48.9, 95% CI = CI = 0.916-2.419, p = 0.108). This study focused only on MS patient improvement (positive changes) on the EDSS and MSFC. More studies are needed to include patient deterioration (negative changes) on EDSS and MSFC. There is controversy about the sensitivity of the EDSS and MSFC in detecting the progression of MS disease. The EDSS and MSFC are effective tools to assess the clinical severity and progression of MS disease. MSFC is more sensitive than EDSS in detecting the progression of MS disease.

  5. Vaccinations Administered During Off-Clinic Hours at a National Community Pharmacy: Implications for Increasing Patient Access and Convenience

    Science.gov (United States)

    Goad, Jeffery A.; Taitel, Michael S.; Fensterheim, Leonard E.; Cannon, Adam E.

    2013-01-01

    PURPOSE Approximately 50,000 adults die annually from vaccine-preventable diseases in the United States. Most traditional vaccine providers (eg, physician offices) administer vaccinations during standard clinic hours, but community pharmacies offer expanded hours that allow patients to be vaccinated at convenient times. We analyzed the types of vaccines administered and patient populations vaccinated during off-clinic hours in a national community pharmacy, and their implications for vaccination access and convenience. METHODS We retrospectively reviewed data for all vaccinations given at the Walgreens pharmacy chain between August 2011 and July 2012. The time of vaccination was categorized as occurring during traditional hours (9:00 am–6:00 pm weekdays) or off-clinic hours, consisting of weekday evenings, weekends, and federal holidays. We compared demographic characteristics and types of vaccine. We used a logistic regression model to identify predictors of being vaccinated during off-clinic hours. RESULTS During the study period, pharmacists administered 6,250,402 vaccinations, of which 30.5% were provided during off-clinic hours: 17.4% were provided on weekends, 10.2% on evenings, and 2.9% on holidays. Patients had significantly higher odds of off-clinic vaccination if they were younger than 65 years of age, were male, resided in an urban area, and did not have any chronic conditions. CONCLUSIONS A large proportion of adults being vaccinated receive their vaccines during evening, weekend, and holiday hours at the pharmacy, when traditional vaccine providers are likely unavailable. Younger, working-aged, healthy adults, in particular, a variety of immunizations during off-clinic hours. With the low rates of adult and adolescent vaccination in the United States, community pharmacies are creating new opportunities for vaccination that expand access and convenience. PMID:24019274

  6. Clinical implications of microsatellite instability in T1 colorectal cancer.

    Science.gov (United States)

    Kang, Jeonghyun; Lee, Hak Woo; Kim, Im-kyung; Kim, Nam Kyu; Sohn, Seung-Kook; Lee, Kang Young

    2015-01-01

    The estimation of regional lymph node metastasis (LNM) risk in T1 colorectal cancer is based on histologic examination and imaging of the primary tumor. High-frequency microsatellite instability (MSI-H) is likely to decrease the possibility of metastasis to either regional lymph nodes or distant organs in colorectal cancers. This study evaluated the clinical implications of MSI in T1 colorectal cancer with emphasis on the usefulness of MSI as a predictive factor for regional LNM. A total of 133 patients who underwent radical resection for T1 colorectal cancer were included. Genomic DNA was extracted from normal and tumor tissues and amplified by polymerase chain reaction (PCR). Five microsatellite markers, BAT-25, BAT-26, D2S123, D5S346, and D17S250, were used. MSI and clinicopathological parameters were evaluated as potential predictors of LNM using univariate and multivariate analyses. Among 133 T1 colorectal cancer patients, MSI-H, low-frequency microsatellite instability (MSI-L), and microsatellite stable (MSS) colorectal cancers accounted for 7.5%, 6%, and 86.5%, respectively. MSI-H tumors showed a female predominance, a proximal location and more retrieved lymph nodes. Twenty-two patients (16.5%) had regional LNM. Lymphovascular invasion and depth of invasion were significantly associated with LNM. There was no LNM in 10 MSI-H patients; however, MSI status was not significantly correlated with LNM. Disease-free survival did not differ between patients with MSI-H and those with MSI-L/MSS. MSI status could serve as a negative predictive factor in estimating LNM in T1 colorectal cancer, given that LNM was not detected in MSI-H patients. However, validation of our result in a different cohort is necessary.

  7. Clinical Outcome after the Use of a New Craniocaudal Expandable Implant for Vertebral Compression Fracture Treatment: One Year Results from a Prospective Multicentric Study

    OpenAIRE

    Noriega, David; Kr?ger, Antonio; Ardura, Francisco; Hansen-Algenstaedt, Nils; Hassel, Frank; Barreau, Xavier; Beyerlein, J?rg

    2015-01-01

    The purpose of this prospective multicentric observational study was to confirm the safety and clinical performance of a craniocaudal expandable implant used in combination with high viscosity PMMA bone cement for the treatment of vertebral compression fractures. Thirty-nine VCFs in 32 patients were treated using the SpineJack minimally invasive surgery protocol. Outcome was determined by using the Visual Analogue Scale for measuring pain, the Oswestry Disability Index for scoring functional ...

  8. Expanding Empathy in Our Clinical Work: A Response to Wickramasekera II's (2015) "Mysteries of Hypnosis and the Self Are Revealed by the Psychology and Neuroscience of Empathy.".

    Science.gov (United States)

    Kaklauskas, Francis J; Clements, Carla June

    2016-01-01

    Empathy is a central tenet of psychotherapeutic process. This article builds upon Wickramasekera II's (2015) "Mysteries of Hypnosis and the Self are Revealed by the Psychology and Neuroscience of Empathy," with particular focus on "empathetic involvement theory." A brief transtheoretical and research review of empathy is provided. A couple's therapy case illustration is provided to elucidate how one can expand "empathetic involvement theory" into clinical practice. Emphasis is placed upon the dimensions of sensation and body/mind connectedness.

  9. Expanding subjectivities

    DEFF Research Database (Denmark)

    Lundgaard Andersen, Linda; Soldz, Stephen

    2012-01-01

    A major theme in recent psychoanalytic thinking concerns the use of therapist subjectivity, especially “countertransference,” in understanding patients. This thinking converges with and expands developments in qualitative research regarding the use of researcher subjectivity as a tool to understa...

  10. Expander Codes

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 10; Issue 1. Expander Codes - The Sipser–Spielman Construction. Priti Shankar. General Article Volume 10 ... Author Affiliations. Priti Shankar1. Department of Computer Science and Automation, Indian Institute of Science Bangalore 560 012, India.

  11. DMPD: Innate immunity and toll-like receptors: clinical implications of basic scienceresearch. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15069387 Innate immunity and toll-like receptors: clinical implications of basic science...te immunity and toll-like receptors: clinical implications of basic scienceresearch. PubmedID 15069387 Title... Innate immunity and toll-like receptors: clinical implications of basic sciencer

  12. Gastrointestinal Motility Disorders and Their Clinical Implications in Cirrhosis

    Directory of Open Access Journals (Sweden)

    Eleni Theocharidou

    2017-01-01

    Full Text Available Gastrointestinal motility is impaired in a substantial proportion of patients with cirrhosis. Cirrhosis-related autonomic neuropathy, increased nitric oxide production, and gut hormonal changes have been implicated. Oesophageal dysmotility has been associated with increased frequency of abnormal gastro-oesophageal reflux. Impaired gastric emptying and accommodation may result in early satiety and may have an impact on the nutritional status of these patients. Small intestinal dysmotility might be implicated in small intestinal bacterial overgrowth and increased bacterial translocation. The latter has been implicated in the pathophysiology of hepatic encephalopathy and spontaneous bacterial peritonitis. Enhanced colonic motility is usually associated with the use of lactulose. Pharmacological interventions aiming to alter gastrointestinal motility in cirrhosis could potentially have a beneficial effect reducing the risk of hepatic decompensation and improving prognosis.

  13. Partition expanders

    Czech Academy of Sciences Publication Activity Database

    Gavinsky, Dmitry; Pudlák, Pavel

    2017-01-01

    Roč. 60, č. 3 (2017), s. 378-395 ISSN 1432-4350 R&D Projects: GA ČR GBP202/12/G061 Institutional support: RVO:67985840 Keywords : expanders * pseudorandomness * communication complexity Subject RIV: BA - General Mathematics Impact factor: 0.645, year: 2016 http://link.springer.com/article/10.1007%2Fs00224-016-9738-5

  14. A gene expression signature for RSV: clinical implications and limitations.

    Directory of Open Access Journals (Sweden)

    Peter J M Openshaw

    2013-11-01

    Full Text Available Peter Openshaw discusses the challenges in advancing respiratory syncytial virus (RSV treatments and the implications of a study by Mejias and colleagues using a newly identified gene signature for diagnosis and prediction of RSV severity. Please see later in the article for the Editors' Summary.

  15. Sexual Objectification of Women: Clinical Implications and Training Considerations

    Science.gov (United States)

    Szymanski, Dawn M.; Carr, Erika R.; Moffitt, Lauren B.

    2011-01-01

    This article focuses on the implications of theory and empirical research on the sexual objectification of women. Drawing largely from the American Psychological Association's 2007 "Guidelines for Psychological Practice With Girls and Women," the 2007 "Report of the American Psychological Association's Task Force on the Sexualization of Girls,"…

  16. Women's involvement in clinical trials: historical perspective and future implications.

    Science.gov (United States)

    Liu, Katherine A; Mager, Natalie A Dipietro

    2016-01-01

    The importance of considering the differences between the male and female sex in clinical decision-making is crucial. However, it has been acknowledged in recent decades that clinical trials have not always adequately enrolled women or analyzed sex-specific differences in the data. As these deficiencies have hindered the progress of understanding women's response to medications, agencies in the United States have worked towards the inclusion of women in clinical trials and appropriate analysis of sex-specific data from clinical trials. This review outlines the history and progress of women's inclusion in clinical trials for prescription drugs and presents considerations for researchers, clinicians, and academicians on this issue.

  17. Do newly marketed generic medicines expand markets using descriptive time series analysis and mixed logit models? Korea as an exemplar and its implications.

    Science.gov (United States)

    Kwon, Hye-Young; Godman, Brian

    2016-04-14

    clinics and hospitals appreciably using newly marketed generics. However lower doses of statins were prescribed. Policy makers do recognize that generic availability can save costs so should be encouraged. However, this is a concern when generic availability appreciably expands the market, potentially increasing the financial burden. This needs to be addressed. Additionally in Korea, the quality of prescribing should be monitored, especially focusing on clinics and secondary hospitals.

  18. Successful technical and clinical outcome using a second generation balloon expandable coronary stent for transplant renal artery stenosis: Our experience

    Science.gov (United States)

    Salsamendi, Jason; Pereira, Keith; Baker, Reginald; Bhatia, Shivank S; Narayanan, Govindarajan

    2015-01-01

    Transplant renal artery stenosis (TRAS) is a vascular complication frequently seen because of increase in the number of renal transplantations. Early diagnosis and management is essential to optimize a proper graft function. Currently, the endovascular treatment of TRAS using angioplasty and/or stenting is considered the treatment of choice with the advantage that it does not preclude subsequent surgical correction. Treatment of TRAS with the use of stents, particularly in tortuous transplant renal anatomy presents a unique challenge to an interventional radiologist. In this study, we present three cases from our practice highlighting the use of a balloon-expandable Multi-Link RX Ultra coronary stent system (Abbott Laboratories, Abbott Park, Illinois, USA) for treating high grade focal stenosis along very tortuous renal arterial segments. Cobalt–Chromium alloy stent scaffold provides excellent radial force, whereas the flexible stent design conforms to the vessel course allowing for optimal stent alignment. PMID:26629289

  19. Successful technical and clinical outcome using a second generation balloon expandable coronary stent for transplant renal artery stenosis: Our experience.

    Science.gov (United States)

    Salsamendi, Jason; Pereira, Keith; Baker, Reginald; Bhatia, Shivank S; Narayanan, Govindarajan

    2015-10-01

    Transplant renal artery stenosis (TRAS) is a vascular complication frequently seen because of increase in the number of renal transplantations. Early diagnosis and management is essential to optimize a proper graft function. Currently, the endovascular treatment of TRAS using angioplasty and/or stenting is considered the treatment of choice with the advantage that it does not preclude subsequent surgical correction. Treatment of TRAS with the use of stents, particularly in tortuous transplant renal anatomy presents a unique challenge to an interventional radiologist. In this study, we present three cases from our practice highlighting the use of a balloon-expandable Multi-Link RX Ultra coronary stent system (Abbott Laboratories, Abbott Park, Illinois, USA) for treating high grade focal stenosis along very tortuous renal arterial segments. Cobalt-Chromium alloy stent scaffold provides excellent radial force, whereas the flexible stent design conforms to the vessel course allowing for optimal stent alignment.

  20. Clinical Implications of Intestinal Stem Cell Markers in Colorectal Cancer

    DEFF Research Database (Denmark)

    Espersen, Maiken Lise Marcker; Olsen, Jesper; Linnemann, Dorte

    2015-01-01

    Colorectal cancer (CRC) still has one of the highest incidence and mortality rate among cancers. Therefore, improved differential diagnostics and personalized treatment are still needed. Several intestinal stem cell markers have been found to be associated with CRC and might have a prognostic...... and predictive significance in CRC patients. This review provides an overview of the intestinal stem cell markers leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), B cell–specific Moloney murine leukemia virus insertion site 1 (BMI1), Musashi1 (MSI1), and sex-determining region y-box 9 (SOX9......) and their implications in human CRC. The exact roles of the intestinal stem cell markers in CRC development and progression remain unclear; however, high expression of these stem cell markers have a potential prognostic significance and might be implicated in chemotherapy resistance...

  1. Pharmacogenomics of human uridine diphospho-glucuronosyltransferases and clinical implications.

    Science.gov (United States)

    Guillemette, C; Lévesque, É; Rouleau, M

    2014-09-01

    Glucuronidation by uridine diphospho-glucuronosyltransferase enzymes (UGTs) is a major phase II biotransformation pathway and, complementary to phase I metabolism and membrane transport, one of the most important cellular defense mechanisms responsible for the inactivation of therapeutic drugs, other xenobiotics, and endogenous molecules. Interindividual variability in UGT pathways is significant and may have profound pharmacological and toxicological implications. Several genetic and genomic processes underlie this variability and are discussed in relation to drug metabolism and diseases such as cancer.

  2. Genetic Characteristics of Glioblastoma: Clinical Implications of Heterogeneity

    Directory of Open Access Journals (Sweden)

    Qian Li

    2015-01-01

    Full Text Available Glioblastoma multiforme (GBM is a heterogeneous group of tumors, each with its own distinct molecular and genetic signatures. This heterogeneity is a major clinical hurdle for classifying tumors and for devising effective personalized therapies targeting the disease pathways. Herein, the primary genetic and epigenetic alterations in GBM that have been used as therapeutic targets in clinical settings nowadays, with or without clinical benefits for patients, as well as the future directions for developing novel strategies were discussed.

  3. Expanding versus non expanding universe

    CERN Document Server

    Alfonso-Faus, Antonio

    2012-01-01

    In cosmology the number of scientists using the framework of an expanding universe is very high. This model, the big-bang, is now overwhelmingly present in almost all aspects of society. It is the main stream cosmology of today. A small number of scientists are researching on the possibility of a non-expanding universe. The existence of these two groups, one very large and the other very small, is a good proof of the use of the scientific method: it does not drive to an absolute certainty. All models have to be permanently validated, falsified. Ockham's razor, a powerful philosophical tool, will probably change the amount of scientists working in each of these groups. We present here a model where a big-bang is unnecessary. It ends, in a finite time, in a second INFLATION, or a disaggregation to infinity. We also discuss the possibilities of a non-expanding universe model. Only a few references will be cited, mainly concerned with our own work in the past, thus purposely avoiding citing the many thousands of ...

  4. Two-year Clinical Outcomes Post Implantation of Epic(TM) Self-Expanding Nitinol Stents for the Aortoiliac Occlusive Disease in Patients with Peripheral Arterial Disease.

    Science.gov (United States)

    Tsujimura, Takuya; Iida, Osamu; Fujita, Masashi; Masuda, Masaharu; Okamoto, Shin; Ishihara, Takayuki; Nanto, Kiyonori; Kanda, Takashi; Okuno, Shota; Matsuda, Yasuhiro; Fujihara, Masahiko; Yokoi, Yoshiaki; Mano, Toshiaki

    2017-10-05

    We investigated 2-year clinical outcomes after implantaton of Epic(TM) self-expanding nitinol stents for patients with peripheral artery disease (PAD) due to the aortoiliac occlusive disease (AIOD). This study was a multicenter and retrospective study. From February 2013 through October 2014, 292 lesions (chronic total occlusion, 21%; TASC Ⅱ C/D, 35%) in 217 consecutive patients (74±8 years; male, 81%; diabetes mellitus, 47%; dialysis, 21%; critical limb ischemia, 29%) who had undergone endovascular therapy (EVT) with Epic(TM) self-expanding nitinol stents for PAD with AIOD were analyzed. The primary endpoints were 2-year primary patency and target lesion revascularization (TLR)-free rate. The primary patency and freedom from TLR were determined by Kaplan-Meier analysis. Additionally, predictors for loss of patency were estimated by Cox proportional hazard model. The mean follow-up duration was 19.1±8.5 months. Primary patency was 87.3% at 2 years. Freedom from TLR rate was 94.1% at 2 years. Multivariate analysis revealed that the presence of diabetes mellitus was associated with a loss of patency. The Epic(TM) self-expanding nitinol stent was demonstrated to be safe and effectivene for AIOD when tested for two years in patients with PAD.

  5. Molecular characterisation of sinonasal carcinomas and their clinical implications.

    Science.gov (United States)

    López, Fernando; Llorente, José Luis; Costales, María; García-Inclán, Cristina; Pérez-Escuredo, Jhudit; Alvarez-Marcos, César; Hermsen, Mario; Suárez, Carlos

    2013-01-01

    Sinonasal carcinomas are rare tumours with an unfavourable prognosis whose management is difficult and complex, leading to high morbidity and mortality despite improvements in the field of surgery and radiotherapy. An elevated number of these tumours can be attributed to occupational exposure. In comparison with other head and neck malignancies, studies of molecular changes in these tumours are infrequent. This review was focused on findings about the epidemiology and molecular and phenotypic characterisation of sinonasal carcinomas, which can potentially be useful for diagnosis and treatment. The increasing knowledge about the molecular biology that underlies their carcinogenesis may help to identify precursor lesions, prognostic markers and markers that predict chemoradiotherapy response and, finally, to identify potential molecular targets that will expand treatment options. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  6. Clinical implications of mutation analysis in primary hyperoxaluria type 1

    NARCIS (Netherlands)

    van Woerden, Christiaan S.; Groothoff, Jaap W.; Wijburg, Frits A.; Annink, Carla; Wanders, Ronald J. A.; Waterham, Hans R.

    2004-01-01

    BACKGROUND: Primary hyperoxaluria type 1 (PH1) is an inborn error of glyoxylate metabolism with an extensive clinical and genetic heterogeneity. Although over 50 disease-causing mutations have been identified, the relationship between genotype and clinical outcome remains unclear. The aim of this

  7. Clinical practice models in nursing education: implication for students' mobility.

    Science.gov (United States)

    Dobrowolska, B; McGonagle, I; Jackson, C; Kane, R; Cabrera, E; Cooney-Miner, D; Di Cara, V; Pajnkihar, M; Prlić, N; Sigurdardottir, A K; Kekuš, D; Wells, J; Palese, A

    2015-03-01

    In accordance with the process of nursing globalization, issues related to the increasing national and international mobility of student and qualified nurses are currently being debated. Identifying international differences and comparing similarities for mutual understanding, development and better harmonization of clinical training of undergraduate nursing students is recommended. The aim of the study was to describe and compare the nature of the nursing clinical practice education models adopted in different countries. A qualitative approach involving an expert panel of nurses was adopted. The Nominal Group Technique was employed to develop the initial research instrument for data collection. Eleven members of the UDINE-C network, representing institutions engaged in the process of professional nursing education and research (universities, high schools and clinical institutes), participated. Three data collection rounds were implemented. An analysis of the findings was performed, assuring rigour. Differences and homogeneity are reported and discussed regarding: (a) the clinical learning requirements across countries; (b) the prerequisites and clinical learning process patterns; and (c) the progress and final evaluation of the competencies achieved. A wider discussion is needed regarding nursing student exchange and internalization of clinical education in placements across European and non-European countries. A clear strategy for nursing education accreditation and harmonization of patterns of organization of clinical training at placements, as well as strategies of student assessment during this training, are recommended. There is also a need to develop international ethical guidelines for undergraduate nursing students gaining international experience. © 2015 International Council of Nurses.

  8. Clinical Phenotypes of Fontan Failure: Implications for Management.

    Science.gov (United States)

    Book, Wendy M; Gerardin, Jennifer; Saraf, Anita; Marie Valente, Anne; Rodriguez, Fred

    2016-07-01

    Fontan failure has been variably and inconsistently described in the literature, leading to challenges in comparing studies and evaluating treatments. Development of a conceptual framework to describe clinical phenotypes will aid in consistent terminology in the literature. In the heart failure literature, several key concepts have been described-"heart failure" is a clinical syndrome of various etiologies, with phenotype-specific response to therapies. As the congenital heart disease community struggles to grapple with "Fontan failure," these concepts come to light. Fontan failure in the context of four clinical phenotypes, including evaluation, potential management strategies, and future directions is discussed. © 2016 Wiley Periodicals, Inc.

  9. Clinical implications of genomics for cancer risk genetics.

    Science.gov (United States)

    Thomas, David M; James, Paul A; Ballinger, Mandy L

    2015-06-01

    The study of human genetics has provided substantial insight into cancer biology. With an increase in sequencing capacity and a reduction in sequencing costs, genomics will probably transform clinical cancer genetics. A heritable basis for many cancers is accepted, but so far less than half the genetic drivers have been identified. Genomics will increasingly be applied to populations irrespective of family history, which will change the framework of phenotype-directed genetic testing. Panel testing and whole genome sequencing will identify novel, polygenic, and de-novo determinants of cancer risk, often with lower penetrance, which will challenge present binary clinical classification systems and management algorithms. In the future, genotype-stratified public screening and prevention programmes could form part of tailored population risk management. The integration of research with clinical practice will result in so-called discovery cohorts that will help identify clinically significant genetic variation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Complete morphometric analysis of jugular foramen and its clinical implications

    Directory of Open Access Journals (Sweden)

    Sushant Swaroop Das

    2016-01-01

    Conclusion: This study gives knowledge about the various parameters, anatomical variations of jugular foramen in both sexes of an adult Indian population, and its clinical impact on the surgeries of this region.

  11. Myasthenia gravis and pregnancy: clinical implications and neonatal outcome

    Directory of Open Access Journals (Sweden)

    Estanol Bruno

    2004-11-01

    Full Text Available Abstract Background The myasthenia gravis is twice as common in women as in men and frequently affects young women in the second and third decades of life, overlapping with the childbearing years. Generally, during pregnancy in one third of patients the disease exacerbates, whereas in two thirds it remains clinically unchanged. Complete remission can occur in some patients. Methods To describe the clinical course, delivery and neonatal outcome of 18 pregnant women with the diagnosis of myasthenia gravis. Retrospective chart review of pregnant patients with myasthenia gravis, followed at the National Institute of Perinatology in Mexico City over an 8-year period. Data was abstracted from the medical records on the clinical course during pregnancy, delivery and neonatal outcome. Results From January 1, 1996 to December 31, 2003 18 patients with myasthenia gravis were identified and included in the study. The mean ± SD maternal age was 27.4 ± 4.0 years. During pregnancy 2 women (11% had an improvement in the clinical symptoms of myasthenia gravis, 7 women (39% had clinical worsening of the condition of 9 other patients (50% remained clinically unchanged. Nine patients delivered vaginally, 8 delivered by cesarean section and 1 pregnancy ended in fetal loss. Seventeen infants were born at mean ± SD gestational age of 37.5 ± 3.0 weeks and a mean birth weight of 2710 ± 73 g. Only one infant presented with transient neonatal myasthenia gravis. No congenital anomalies were identified in any of the newborns. Conclusions The clinical course of myasthenia gravis during pregnancy is variable, with a significant proportion of patients experiencing worsening of the clinical symptoms. However, neonatal transient myasthenia was uncommon in our patient population.

  12. The pathophysiology of the trigeminal autonomic cephalalgias, with clinical implications

    DEFF Research Database (Denmark)

    Barloese, Mads C J

    2018-01-01

    The hallmark of primary headaches belonging to the group known as the trigeminal autonomic cephalalgias is unilateral headache accompanied by cranial autonomic symptoms. Being relatively rare and poorly understood, they represent a clinical challenge, leading to underdiagnosis and undertreatment....... presentation for cluster headache, paroxysmal hemicrania, short-lasting unilateral neuralgiform headache with conjunctival injection and tearing, and hemicrania continua is covered, along with our current understanding of the common pathophysiology and clinical manifestations....

  13. Metabolic fuel and clinical implications for female reproduction.

    Science.gov (United States)

    Mircea, Carmen N; Lujan, Marla E; Pierson, Roger A

    2007-11-01

    Reproduction is a physiologically costly process that consumes significant amounts of energy. The physiological mechanisms controlling energy balance are closely linked to fertility. This close relationship ensures that pregnancy and lactation occur only in favourable conditions with respect to energy. The primary metabolic cue that modulates reproduction is the availability of oxidizable fuel. An organism's metabolic status is transmitted to the brain through metabolic fuel detectors. There are many of these detectors at both the peripheral (e.g., leptin, insulin, ghrelin) and central (e.g., neuropeptide Y, melanocortin, orexins) levels. When oxidizable fuel is scarce, the detectors function to inhibit the release of gonadotropin-releasing hormone and luteinizing hormone, thereby altering steroidogenesis, reproductive cyclicity, and sexual behaviour. Infertility can also result when resources are abundant but food intake fails to compensate for increased energy demands. Examples of these conditions in women include anorexia nervosa and exercise-induced amenorrhea. Infertility associated with obesity appears to be less related to an effect of oxidizable fuel on the hypothalamic-pituitary-ovarian axis. Impaired insulin sensitivity may play a role in the etiology of these conditions, but their specific etiology remains unresolved. Research into the metabolic regulation of reproductive function has implications for elucidating mechanisms of impaired pubertal development, nutritional amenorrhea, and obesity-related infertility. A better understanding of these etiologies has far-reaching implications for the prevention and management of reproductive dysfunction and its associated comorbidities.

  14. The placebo mystique: Implications for clinical trial methodology.

    Science.gov (United States)

    Clifford, Vanessa

    2011-06-01

    The World Medical Association Declaration of Helsinki states that the use of a placebo in a clinical trial can only be justified ethically when no proven active treatment is available as a comparison. Despite this, placebos remain a popular choice as controls in clinical trials. Recent literature reviews have suggested that reliance on placebos may, in part, be because of methodological misconceptions about the need for placebos to control for the 'placebo effect'. This study aimed to assess doctors' understanding of the requirements for placebo use in clinical trials. Two hundred doctors working in tertiary hospitals in Melbourne, Australia were surveyed in regards to their understanding of the role of the placebo and placebo effects in clinical trials. There was a 72% response rate. Doctors were specifically asked if a placebo was required in a randomised clinical trial, in preference to another form of control, to control for the 'placebo effect'. The majority of respondents (62%) incorrectly believed that placebos are essential to control for the 'placebo effect' in a randomised clinical trial. Misconceptions about the methodological requirement for placebos in randomised controlled trials may influence researcher decisions to use placebo controls in unethical situations. © 2011 The Author. Journal of Paediatrics and Child Health © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

  15. Cartilage Regeneration in Human with Adipose Tissue-Derived Stem Cells: Current Status in Clinical Implications

    Directory of Open Access Journals (Sweden)

    Jaewoo Pak

    2016-01-01

    Full Text Available Osteoarthritis (OA is one of the most common debilitating disorders among the elderly population. At present, there is no definite cure for the underlying causes of OA. However, adipose tissue-derived stem cells (ADSCs in the form of stromal vascular fraction (SVF may offer an alternative at this time. ADSCs are one type of mesenchymal stem cells that have been utilized and have demonstrated an ability to regenerate cartilage. ADSCs have been shown to regenerate cartilage in a variety of animal models also. Non-culture-expanded ADSCs, in the form of SVF along with platelet rich plasma (PRP, have recently been used in humans to treat OA and other cartilage abnormalities. These ADSCs have demonstrated effectiveness without any serious side effects. However, due to regulatory issues, only ADSCs in the form of SVF are currently allowed for clinical uses in humans. Culture-expanded ADSCs, although more convenient, require clinical trials for a regulatory approval prior to uses in clinical settings. Here we present a systematic review of currently available clinical studies involving ADSCs in the form of SVF and in the culture-expanded form, with or without PRP, highlighting the clinical effectiveness and safety in treating OA.

  16. Biology of obesity and weight regain: Implications for clinical practice.

    Science.gov (United States)

    Rogge, Mary Madeline; Gautam, Bibha

    2017-10-01

    Weight loss is recommended as first-line therapy for many chronic illnesses, including obesity. Most patients who do successfully lose weight are unable to maintain their reduced weight. Recent research findings are reviewed and synthesized to explain the biology of obesity, adaptation to weight loss, and weight regain. Weight regain is a common consequence of successful weight loss. Current obesity management strategies fail to take into consideration the underlying genetic and environmental causes of obesity. Available treatment modalities create a negative energy balance that stimulates integrated, persistent neurologic, endocrine, muscle, and adipose tissue adaptation to restore body weight and fat mass, independent of lifestyle changes. Understanding the pathophysiology of obesity and weight loss alters nurse practitioners' responsibilities in caring for patients with obesity. They are responsible for expanding assessment and intervention strategies and offering people with obesity realistic expectations for weight loss and regain. They are obligated to explain weight regain when it occurs to minimize patient frustration. Nurse practitioners have the opportunity to adopt new approaches to patient advocacy, especially in the areas of public policy to improve diagnostic tools and adjunctive therapy for people with obesity. ©2017 American Association of Nurse Practitioners.

  17. Expanding the Aperture of Psychological Assessment: Introduction to the Special Section on Innovative Clinical Assessment Technologies and Methods

    Science.gov (United States)

    Trull, Timothy J.

    2007-01-01

    Contemporary psychological assessment is dominated by tried-and-true methods like clinical interviewing, self-report questionnaires, intellectual assessment, and behavioral observation. These approaches have served as the mainstays of psychological assessment for decades. To be sure, these methods have survived over the years because clinicians…

  18. Expanding Local Cancer Clinical Trial Options: Analysis of the Economic Impact of the Midwest Cancer Alliance in Kansas.

    Science.gov (United States)

    Gafford, J Atlee; Gurley-Calvez, Tami; Krebill, Hope; Lai, Sue Min; Christiadi; Doolittle, Gary C

    2017-09-01

    Patients benefit from receiving cancer treatment closer to home when possible and at high-volume regional centers when specialized care is required. The purpose of this analysis was to estimate the economic impact of retaining more patients in-state for cancer clinical trials and care, which might offset some of the costs of establishing broader cancer trial and treatment networks. Kansas Cancer Registry data were used to estimate the number of patients retained in-state for cancer care following the expansion of local cancer clinical trial options through the Midwest Cancer Alliance based at the University of Kansas Medical Center. The 2014 economic impact of this enhanced local clinical trial network was estimated in four parts: Medical spending was estimated on the basis of National Cancer Institute cost-of-care estimates. Household travel cost savings were estimated as the difference between in-state and out-of-state travel costs. Trial-related grant income was calculated from administrative records. Indirect and induced economic benefits to the state were estimated using an economic impact model. The authors estimated that the enhanced local cancer clinical trial network resulted in approximately $6.9 million in additional economic activity in the state in 2014, or $362,000 per patient retained in-state. This estimate includes $3.6 million in direct spending and $3.3 million in indirect economic activity. The enhanced trial network also resulted in 45 additional jobs. Retaining patients in-state for cancer care and clinical trial participation allows patients to remain closer to home for care and enhances the state economy.

  19. Amyotrophic Lateral Sclerosis and Metabolomics: Clinical Implication and Therapeutic Approach

    Directory of Open Access Journals (Sweden)

    Alok Kumar

    2013-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is one of the most common motor neurodegenerative disorders, primarily affecting upper and lower motor neurons in the brain, brainstem, and spinal cord, resulting in paralysis due to muscle weakness and atrophy. The majority of patients die within 3–5 years of symptom onset as a consequence of respiratory failure. Due to relatively fast progression of the disease, early diagnosis is essential. Metabolomics offer a unique opportunity to understand the spatiotemporal metabolic crosstalks through the assessment of body fluids and tissue. So far, one of the most challenging issues related to ALS is to understand the variation of metabolites in body fluids and CNS with the progression of disease. In this paper we will review the changes in metabolic profile in response to disease progression condition and also see the therapeutic implication of various drugs in ALS patients.

  20. Potential Clinical Implications of the Urotensin II Receptor Antagonists

    Directory of Open Access Journals (Sweden)

    Emilie Kane

    2011-07-01

    Full Text Available Urotensin-II (UII, which binds to its receptor UT, plays an important role in the heart, kidneys, pancreas, adrenal gland and CNS. In the vasculature, it acts as a potent endothelium-independent vasoconstrictor and endothelium-dependent vasodilator. In disease states, this constriction-dilation equilibrium is disrupted. There is an upregulation of the UII system in heart disease, metabolic syndrome and kidney failure. The increase in UII release and UT expression suggest that UII system may be implicated in the pathology and pathogenesis of these diseases by causing an increase in ACAT-1 activity leading to SMC proliferation and foam cell infiltration, insulin resistance (DMII, as well as inflammation, high blood pressure and plaque formation. Recently, UT antagonists such as SB-611812, palosuran, and most recently a piperazino-isoindolinone based antagonist have been developed in the hope of better understanding the UII system and treating its associated diseases.

  1. Amyotrophic Lateral Sclerosis and Metabolomics: Clinical Implication and Therapeutic Approach

    Science.gov (United States)

    Kumar, Alok; Ghosh, Devlina; Singh, R. L.

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is one of the most common motor neurodegenerative disorders, primarily affecting upper and lower motor neurons in the brain, brainstem, and spinal cord, resulting in paralysis due to muscle weakness and atrophy. The majority of patients die within 3–5 years of symptom onset as a consequence of respiratory failure. Due to relatively fast progression of the disease, early diagnosis is essential. Metabolomics offer a unique opportunity to understand the spatiotemporal metabolic crosstalks through the assessment of body fluids and tissue. So far, one of the most challenging issues related to ALS is to understand the variation of metabolites in body fluids and CNS with the progression of disease. In this paper we will review the changes in metabolic profile in response to disease progression condition and also see the therapeutic implication of various drugs in ALS patients. PMID:26317018

  2. Fibrosis in nonalcoholic Fatty liver disease: mechanisms and clinical implications.

    Science.gov (United States)

    Angulo, Paul; Machado, Mariana Verdelho; Diehl, Anna Mae

    2015-05-01

    Nonalcoholic fatty liver disease (NAFLD) is tightly associated with obesity and the metabolic syndrome in the United States and other Western countries. It is also the liver disease most rapidly increasing in prevalence in the United States, and has become a major indication for liver transplantation worldwide. Compelling evidence shows that the degree of liver fibrosis dictates liver prognosis in NAFLD. This review focuses on fibrosis based on clinical and basic perspectives. The authors summarize the physiopathology of fibrosis development and progression in NAFLD, highlighting its molecular mechanisms, clinical consequences of fibrosis, the diagnostic approach and management strategies. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  3. Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients

    DEFF Research Database (Denmark)

    Sausen, Mark; Phallen, Jillian; Adleff, Vilmos

    2015-01-01

    Pancreatic adenocarcinoma has the worst mortality of any solid cancer. In this study, to evaluate the clinical implications of genomic alterations in this tumour type, we perform whole-exome analyses of 24 tumours, targeted genomic analyses of 77 tumours, and use non-invasive approaches to examine...... imaging. These observations provide genetic predictors of outcome in pancreatic cancer and have implications for new avenues of therapeutic intervention....

  4. Clinical implications of early loss of a lower deciduous canine.

    Science.gov (United States)

    Martins-Júnior, Paulo Antônio; Marques, Leandro Silva

    2012-01-01

    In crowded dental arches, the permanent lateral incisors often erupt and resorb the mesial portion of the root of deciduous canines, causing their premature loss. Therefore, knowledge on clinical aspects related to etiologic factors is necessary to pediatric orthodontists and clinical dentists for diagnosis and treatment with regard to incisor crowding and adjustment. The aim of the present study was to describe a clinical case characterized by the unilateral loss of a lower deciduous canine, offering clinical considerations on this issue and discussing the various procedures implemented to prevent potential problems. A patient, 8 years of age, had the lower right deciduous canine prematurely lost, resulting in a deviation from the midline to the same side of the loss caused by the migration of the permanent incisors. The antimeric canine was removed and a fixed apparatus was attached to the lower arch associated to a spring to correct the midline. Next, a lip bumper device was employed to promote the vestibular conduction of the lower incisors to accommodate the permanent canines in the arch. Although early loss of deciduous canines occurs frequently, treatment possibilities are controversial and further studies on the subject are necessary Orthodontic evaluation should be always considered to minimize the need to extract permanent teeth and/or future orthodontic treatment.

  5. Clinical implications of ST segment time-course recovery patterns ...

    African Journals Online (AJOL)

    Arun Kumar Agnihotri

    Angiographic findings were used as the gold standard with which to compare the results of the exercise stress test and the sensitivity and specificity determined. The parameters analysed were: the clinical features (chest pain, breathlessness) and demographics of the sample population, the onset of ST depression, the.

  6. Recent NIMH Clinical Trials and Implications for Practice

    Science.gov (United States)

    Vitiello, Benedetto; Kratochvil, Christopher J.

    2008-01-01

    Optimal treatment of adolescent depression requires the use of antidepressants such as fluoxetine, and the addition of cognitive-behavioral therapy (CBT) offers better potential. Second-step pharmacological treatment of the disorder offers a success rate of around 50%. Clinical trial for the use of sertraline and CBT in treating…

  7. Smith-Magenis Syndrome: Genetic Basis and Clinical Implications

    Science.gov (United States)

    Finucane, Brenda; Haas-Givler, Barbara

    2009-01-01

    Smith-Magenis syndrome (SMS) is a neurobehavioral disorder associated with deletions and mutations of the "RAI1" gene on chromosome 17p11.2. Clinical features of the syndrome include intellectual disability, sleep disturbance, craniofacial differences, and a distinctive profile of stereotypic and self-injurious behaviors. Although the functional…

  8. A clinical and pharmacokinetic study of the combination of etravirine plus raltegravir in HIV patients with expanded intolerance or resistance

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    Sara Bañón

    2014-11-01

    Full Text Available Introduction: The combination of etravirine (ETR plus raltegravir (RAL could be an option for HIV patients with resistance, intolerance or important interactions with other drugs. However, there are few data on the efficacy, safety and pharmacokinetics of this dual therapy, taking into account the effect of HCV co-infection or the possible induction of ETR in the drug metabolism of RAL. Material and Methods: Cohort study of HIV patients initiating ETR plus RAL as dual therapy. Plasma trough levels of RAL were measured by LC/MS after at least one month on therapy. Results: A total of 25 patients have been included in this combination since 2009. Mean age was 46 years, 72% were male, and 20 patients (80% had HCV co-infection (seven patients with fibrosis 3–4. Median nadir CD4+ count was 109 (60–209, and 21 patients had an HIV RNA level below 50 copies/mL. Median time on previous therapy was 473 months (IQR, 395–570, and reasons for this dual therapy was toxicity/intolerance in 19, and interactions in nine (two chemotherapy, three DAAs, two methadone, two other. After a median follow up of 722 days (473–1088: 53.3 patients-year, there were no cases of blips or virological failure. Six patients (24% discontinued therapy after more than 1.5 year on therapy, in four cases due to lost follow up and in two due to simplification after finishing the reason for interaction. There were no cases of liver toxicity, and only two patients increased slightly transaminases values (grade 1 and 2. Total cholesterol and triglycerides levels decrease significantly after initiation (TC, from 182 to 165 at one year; p=0.01; TG from 185 to 143 mg/dL; p=0.01. CT/HDL ratio decreases from 4.35 to 4.28 after six months. Geometric mean plasma trough level of RAL was 166 ng/mL (IQR, 40–249 and only one patient (6% was below the in vitro IC50 of the wild type. Conclusions: The combination of ETR plus RAL as dual therapy is effective and safe in patients with expanded

  9. TRIPLE ACTION PALATE EXPANDER

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    Svetlana Yordanova

    2011-09-01

    Full Text Available Malocclusion correction essentially involves expansion of the maxilla, protrusion of anterior teeth and opening the bite. Expansion is often the stage preceding the treatment with fixed appliances. The elevation of the occlusion using accomplished with different devices (bite planes -fixed or removable, composite material on the occlusall surface of molars carries the risk of breaking or debonding them.The present article proposes an expanding appliance with triple action as a therapeutic means of choice in an orthodontic treatment with fixed appliances. The expander can simultaneously be used to protrude upper teeth, to expand the upper jaw and disarticulate the occlusion. It can be easily fabricated in clinical conditions, causes no discomfort and does not hamper oral hygiene because it can be removed and cleaned.

  10. Autoinflammatory diseases in adults. Clinical characteristics and prognostic implications.

    Science.gov (United States)

    González García, A; Patier de la Peña, J L; Ortego Centeno, N

    2017-03-01

    Autoinflammatory diseases are clinical conditions with inflammatory manifestations that present in a periodic or persistent manner and are caused by acquired or hereditary disorders of the innate immune response. In general, these diseases are more common in childhood, but cases have been reported in adults and are therefore important for all specialists. There are few references on these diseases in adults due to their low prevalence and underdiagnosis. The aim of this study is to review the scientific literature on these disorders to systematise their clinical, prognostic and treatment response characteristics in adults. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  11. Curvature affects Doppler investigation of vessels: implications for clinical practice.

    Science.gov (United States)

    Balbis, S; Roatta, S; Guiot, C

    2005-01-01

    In clinical practice, blood velocity estimations from Doppler examination of curved vascular segments are normally different from those of nearby straight segments. The observed "accelerations," sometimes considered as a sort of stochastic disturbances, can actually be related to very specific physical effects due to vessel curvature (i.e., the development of nonaxial velocity [NAV] components) and the spreading of the axial velocity direction in the Doppler sample volume with respect to the insonation axis. The relevant phenomena and their dependence on the radius of curvature of the vessels and on the insonation angle are investigated with a beam-vessel geometry as close as possible to clinical setting, with the simplifying assumptions of steady flow, mild vessel curvature, uniform ultrasonic beam and complete vessel insonation. The insonation angles that minimize the errors are provided on the basis of the study results.

  12. Clinical Implications of the Transversus Abdominis Plane Block in Adults

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    Mark J. Young

    2012-01-01

    Full Text Available The transversus abdominis plane (TAP block is a relatively new regional anesthesia technique that provides analgesia to the parietal peritoneum as well as the skin and muscles of the anterior abdominal wall. It has a high margin of safety and is technically simple to perform, especially under ultrasound guidance. A growing body of evidence supports the use of TAP blocks for a variety of abdominal procedures, yet, widespread adoption of this therapeutic adjunct has been slow. In part, this may be related to the limited sources for anesthesiologists to develop an appreciation for its sound anatomical basis and the versatility of its clinical application. As such, we provide a brief historical perspective on the TAP block, describe relevant anatomy, review current techniques, discuss pharmacologic considerations, and summarize the existing literature regarding its clinical utility with an emphasis on recently published studies that have not been included in other systematic reviews or meta-analyses.

  13. Functional aspects of His bundle physiology and pathophysiology: Clinical implications.

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    Scherlag, Benjamin J; Lazzara, Ralph

    In this review we present evidence from many experimental studies which challenge the concept of predestination of His bundle fibers. Using both intra- and extracellular His bundle pacing in the context of atrio-ventricular block and the development of bundle branch blocks these experimental studies provide the underlying mechanisms for the recent clinical findings showing the benefits of permanent His bundle pacing. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Self-sufficiency in intern supply: the impact of expanded medical schools, medical places and rural clinical schools in Queensland.

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    Eley, Diann S; Zhang, Jianzhen; Wilkinson, David

    2009-08-01

    The doctor shortage in Australia generally, and the rural shortage in particular, has led to an increase in medical schools, medical places and rural training. If effective, these strategies will first impact on the intern workforce. We studied the source of interns in Queensland. Analysis of number, source and location of interns by Rural, Remote and Metropolitan Area (RRMA) classification (an index of remoteness) from university and health department records (2003-2008). Odds ratios compared the likelihood of intern supply from Queensland universities and rural clinical schools. Most interns in Queensland graduated from Queensland universities in 2007 (287 [72%]) and 2008 (344 [84%]). Proportions increased across all three RRMA groups from: 82% to 93% in RRMA1; 56% to 68% in RRMA2 and 67% to 79% in RRMA3. The University of Queensland (UQ) provides most interns in all RRMA locations including RRMA3, and this increased from 2007 (n = 33 [35%]) to 2008 (n = 57 [58%]). Interns from interstate decreased from 61 (15%) in 2007 to 40 (10%) in 2008. Interns from overseas fell from 53 (13%) in 2007 to 27 (7%) in 2008. Rural clinical schools compared with traditional urban-based schools were more likely to supply interns to RRMA3 than RRMA1 hospitals in 2007 (OR, 8.8; 95% CI, 4.6-16.7; P self-sufficiency in intern supply and will achieve this in the next few years. Rural clinical schools are playing an important role in producing interns for RRMA3 hospitals. Due to its large cohort, UQ remains the major provider across all RRMA groups.

  15. On the Science of Consciousness: Epistemological Reflections and Clinical Implications.

    Science.gov (United States)

    Facco, Enrico; Lucangeli, Daniela; Tressoldi, Patrizio

    Consciousness has been one of the most important and tantalizing issues ever since the origin of philosophy and medicine. The concept of consciousness and the so-called "hard problem" (i.e., the mind-brain relationship) are highly complex topics that have yet to be elucidated, involving the realms of both science and philosophy with profound epistemological implications. In the lively debate on the foundations of the science of consciousness there are several potential biases of an essentially philosophical nature, such as those related to the paradigm and axioms adopted, and the ostensible logical contradiction between monism and dualism. Their origin dates back largely to Descartes' thinking and the birth of the new sciences as a compromise with the Inquisition, but they have been handed down through the Enlightenment and Positivism. A proper investigation of consciousness and the world of subjectivity demands a careful reflection on the paradigm of scientific medicine to identify possible flaws and overcome the limits of the mechanistic-reductionist approach. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. [Colonic diverticulosis and its complications: pathogenesis, classification and clinical implications].

    Science.gov (United States)

    von Rahden, B H A; Germer, C-T

    2013-12-01

    Current understanding of the pathogenesis of colonic diverticulosis and its complications has certain implications for current therapy concepts, which are summarised here. Colonic diverticula in the Western world are pseudodiverticula predominating in the sigmoid colon. Pathogenesis is multifactorial and includes low-fibre diet, dysmotility, increased intraluminal pressure and morphological changes. Uncomplicated diverticulitis results from microperforations, contradicting the hypothesis of the "abscessed diverticulum". Administration of antibiotics for treatment is controversial. Complicated sigmoid diverticulitis is characterised by an intensive inflammatory infiltrate with macrophages. Immunosuppression and especially steroid intake are identified as risk factors. Nowadays, elective or emergency resection is generally recommended as therapy of first choice. However, contrary concepts with merely conservative treatment or drainage--even for perforated diverticulitis--are emerging. The pathogenesis of chronically recurrent diverticulitis is poorly understood and concepts are changing. Resection after the second episode is replaced by a risk-adapted strategy. Diverticular bleeding occurs due to rupture of a vas rectum at the fundus of the diverticulum. Conservative and endoscopic management is the first line and surgical resection plays a role as salvage-strategy in case of recurrent and life-threatening bleeding. Localising the bleeding, i.e., with angiography, is crucial prior to surgery. The pathophysiology of colonic diverticulosis is complex and incompletely understood and linked with several controversial issues, regarding treatment strategies. Georg Thieme Verlag KG Stuttgart · New York.

  17. Chemistry, Metabolism, and Toxicology of Cannabis: Clinical Implications

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    M.M. Srinivas Bharath

    2012-12-01

    Full Text Available Cannabis is one of the most widely abused substances throughout the world. The primary psychoactive constituent of cannabis, delta 9-tetrahydrocannabinol (Δ9_THC, produces a myriad of pharmacological effects in animals and humans. Although it is used as a recreational drug, it can potentially lead to dependence and behavioral disturbances and its heavy use may increase the risk for psychotic disorders.Many studies that endeavor to understand the mechanism of action of cannabis concentrate on pharmacokinetics and pharmacodynamics of cannabinoids in humans. However, there is limited research on the chronic adverse effects and retention of cannabinoids in human subjects.Cannabis can be detected in body fluids following exposure through active/passive inhalation and exposure through breastfeeding. Cannabis detection is directly dependent on accurate analytical procedures for detection of metabolites and verification of recent use.In this review, an attempt has been made to summarize the properties of cannabis and its derivatives, and to discuss the implications of its use with emphasis on bioavailability, limit of detection, carry over period and passive inhalation, important factors for detection and diagnosis.

  18. Clinical characteristics and diagnosis of atypical odontalgia: implications for dentists.

    Science.gov (United States)

    Ram, Saravanan; Teruel, Antonia; Kumar, Satish K S; Clark, Glenn

    2009-02-01

    Atypical odontalgia (AO) is a poorly understood and commonly misdiagnosed condition for which patients often undergo multiple unsuccessful dental or surgical procedures. The authors conducted a study to determine the prevalence and describe the characteristics of patients with AO seen at the University of Southern California Orofacial Pain and Oral Medicine Center (USC OFP-OM Center), Los Angeles. The authors conducted a retrospective record review from a database of more than 3,000 patient records from June 2003 to August 2007 to identify patients diagnosed with AO. The authors identified 64 patients (44 women and 20 men) between the ages of 26 and 93 years as having a diagnosis of AO. Of those 64 patients, 71 percent initially consulted a dentist regarding their pain, and 79 percent had undergone dental treatment that failed to resolve the pain. The pain of 64 percent of the patients had no known cause. Dentists, who often are the first health care providers to see patients with AO, must be aware of this condition and must follow the appropriate steps to determine its diagnosis. Dentists and physicians should understand the implications and importance of early diagnosis of patients with AO and of referral to pain specialists for treatment.

  19. Tumor interstitial fluid formation, characterization and clinical implications

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    Marek eWagner

    2015-05-01

    Full Text Available The interstitium, situated between the blood and lymph vessels and the cells, consists of a solid or matrix phase and a fluid phase, together constituting the tissue microenvironment. In the present review we focus on the interstitial fluid phase of solid tumors (TIF, i.e. the fluid bathing the tumor and stroma cells, also including immune cells. This is a component of the internal milieu of a solid tumor that has attracted regained attention. Access to this compartment may provide important insight into how tumors develop and how they respond to therapy. TIF is formed by transcapillary filtration, and since fluid is not readily available we discuss available techniques for TIF isolation, results from subsequent characterization and implications of recent findings with respect to transcapillary fluid balance and uptake of macromolecular therapeutic agents. It has recently been shown that local gradients exist in signaling substances from neoplastic tissue to plasma that may provide new insight into the biology of tumors. The emergence of sensitive proteomic technologies has made the interstitial fluid compartment in general, but that of tumors in particular, a highly valuable source for tissue specific proteins that may serve as biomarker candidates. Potential biomarkers will appear locally at high concentrations in the tissue of interest and will eventually appear in the plasma where they are diluted. Access to fluid that reliably reflects the local microenvironment enables us to identify substances that can be used in early detection and monitoring of disease.

  20. Pancreatic Cancer Genomes: Implications for Clinical Management and Therapeutic Development.

    Science.gov (United States)

    Dreyer, Stephan B; Chang, David K; Bailey, Peter; Biankin, Andrew V

    2017-04-01

    Pancreatic cancer has become the third leading cause of cancer-related death, with little improvement in outcomes despite decades of research. Surgery remains the only chance of cure, yet only 20% of patients will be alive at 5 years after pancreatic resection. Few chemotherapeutics provide any improvement in outcome, and even then, for approved therapies, the survival benefits are marginal. Genomic sequencing studies of pancreatic cancer have revealed a small set of consistent mutations found in most pancreatic cancers and beyond that, a low prevalence for targetable mutations. This may explain the failure of conventional clinical trial designs to show any meaningful survival benefit, except in small and undefined patient subgroups. With the development of next-generation sequencing technology, genomic sequencing and analysis can be performed in a clinically meaningful turnaround time. This can identify therapeutic targets in individual patients and personalize treatment selection. Incorporating preclinical discovery and molecularly guided therapy into clinical trial design has the potential to significantly improve outcomes in this lethal malignancy. In this review, we discuss the findings of recent large-scale genomic sequencing projects in pancreatic cancer and the potential relevance of these data to therapeutic development. Clin Cancer Res; 23(7); 1638-46. ©2017 AACRSee all articles in this CCR Focus section, "Pancreatic Cancer: Challenge and Inspiration." ©2017 American Association for Cancer Research.

  1. The genetics of Hodgkin lymphoma: an overview and clinical implications.

    Science.gov (United States)

    Borchmann, Sven; Engert, Andreas

    2017-09-01

    The goal of this review is to give an overview of the genetics of classical Hodgkin lymphoma. Copy number changes, somatic mutations, genome-wide association studies, changes in gene expression, familial classical Hodgkin lymphoma and epigenetic changes will be reviewed. In doing so, special focus is placed on the way recent discoveries have influenced clinical research, diagnostics, treatment and remission monitoring. Furthermore, emphasis is put on how these advances can help to advance the treatment of elderly patients who have a markedly worse prognosis than younger patients. Frequent amplifications of the 9p24.1 locus in classical Hodgkin lymphoma could be the basis for the success of immune checkpoint inhibitors targeting PD-1 or PD-L1 in this disease. The same amplification also affects the JAK/STAT pathway, which has also been targeted in recent clinical trials. Hodgkin lymphoma-specific copy number alterations and mutations have recently been found to be detectable in cell-free DNA. This could provide the basis for advances in the detection of residual disease during treatment and while monitoring patients in remission. The advent of new technologies such as massive parallel sequencing has improved our understanding of the genetics of classical Hodgkin lymphoma. Some of these discoveries are now being translated into clinical research in the form of new diagnostics and treatments.

  2. Primary empty sella and GH deficiency: prevalence and clinical implications

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    Maurizio Poggi

    2012-01-01

    Full Text Available Primary empty sella (PES is a particular anatomical condition characterized by the herniation of liquor within the sella turcica. The pathogenesis of this alteration, frequently observed in general population, is not yet completely understood. Recently reports demonstrated, in these patients, that hormonal pituitary dysfunctions, specially growth hormone (GH/insulin-like growth factor (IGF-I axis ones, could be relevant. The aim of this paper is to evaluate GH/IGF-I axis in a group of adult patients affected by PES and to verify its clinical relevance. We studied a population of 28 patients with a diagnosis of PES. In each patient we performed a basal study of thyroid, adrenal and gonadal - pituitary axis and a dynamic evaluation of GH/IGF-I after GH-releasing hormone (GHRH plus arginine stimulation test. To evaluate the clinical significance of GH/IGF-I axis dysfunction we performed a metabolic and bone status evaluation in every patients. We found the presence of GH deficit in 11 patients (39.2 %. The group that displayed a GH/IGF-I axis dysfunction showed an impairment in metabolic profile and bone densitometry. This study confirms the necessity to screen the pituitary function in patients affected by PES and above all GH/IGF-I axis. Moreover the presence of GH deficiency could be clinically significant.

  3. Expanding the National Drug Abuse Treatment Clinical Trials Network to address the management of substance use disorders in general medical settings

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    Tai B

    2014-07-01

    Full Text Available Betty Tai, Steven Sparenborg, Udi E Ghitza, David Liu Center for the Clinical Trials Network, National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland, USA Abstract: The Patient Protection and Affordable Care Act (2010 and the Mental Health Parity and Addiction Equity Act (2008 expand substance use disorder (SUD care services in the USA into general medical settings. Care offered in these settings will engage substance-using patients in an integrated and patient-centered environment that addresses physical and mental health comorbidities and follows a chronic care model. This expansion of SUD services presents a great need for evidence-based practices useful in general medical settings, and reveals several research gaps to be addressed. The National Drug Abuse Treatment Clinical Trials Network of the National Institute on Drug Abuse can serve an important role in this endeavor. High-priority research gaps are highlighted in this commentary. A discussion follows on how the National Drug Abuse Treatment Clinical Trials Network can transform to address changing patterns in SUD care to efficiently generate evidence to guide SUD treatment practice within the context of recent US health care legislation. Keywords: Patient Protection and Affordable Care Act, National Drug Abuse Treatment Clinical Trials Network, substance use disorders, practice-based research network, electronic health records

  4. Alcohol Use Disorders: Implications for the Clinical Toxicologist

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    Michael McDonough

    2015-03-01

    Full Text Available Alcohol use disorders (AUDs are a health problem of high prevalence in most communities and such problems account for 5% of the total burden of disease worldwide. Clinical toxicologists are commonly required to treat patients having AUDs and associated drug/alcohol-related harm. There have been recent changes to some of the diagnostic criteria (notably in DSM V relevant to AUDs, with older terms “alcohol abuse” and “alcohol dependence” no longer being classified. AUDs may sometimes not be clearly recognizable and use of evidence-based screening interventions can help identify such conditions and lead to effective brief interventions (e.g. SBIRT programs in emergency departments. AUDs are viewed as chronic disorders of alcohol consumption occurring across a spectrum of severity. While most AUDs are mild to moderate in severity and usually self-limiting conditions, more severe presentations are more commonly encountered by physicians in emergency settings. Hence, clinical toxicologists are more likely to see patients within the more severe form of disorder, at end of the spectrum of AUDs. Among this group of patients, multi-morbidity and particularly high mortality risk exists, and thus they usually require management collaboration with specialist services. Patients with AUDs are most likely to be recognized by a clinical toxicologist in the following scenarios: following acute heavy alcohol ingestion and subsequently developing acute alcohol intoxication (ethanol toxidrome, following accidental or intentional drug overdosage where alcohol has also been consumed, following acute alcohol consumption that has been associated with behavioral risk-taking and/or self-harming (e.g. poisoning, envenomation, etc., when alcohol withdrawal reactions are severe requiring hospitalization and possibly following an adverse drug reaction.

  5. Clinical implications of sleep disordered breathing in acute myocardial infarction.

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    Doron Aronson

    Full Text Available Sleep disordered breathing (SDB, characterized by nightly intermittent hypoxia, is associated with multiple pathophysiologic alterations that may adversely affect patients with acute myocardial infarction (AMI. This prospective study investigated whether the metabolic perturbations associated with SDB are present when these patients develop AMI and if they affect clinical outcomes.We prospectively enrolled 180 AMI patients. SDB was defined as oxygen desaturation index (ODI >5 events/hour based on a Watch Pat-100 sleep study. Blood samples were obtained for high-sensitivity C-reactive protein (hs-CRP and markers of oxidative stress (lipid peroxides [PD] and serum paraoxonase-1 [PON-1] (arylesterase activity. Echocardiography was performed to evaluate cardiac dimensions and pulmonary artery systolic pressure.SDB was present in 116 (64% patients. Hs-CRP levels, PD and PON-1 were similar in patients with and without SDB. Echocardiography revealed higher left atrial dimension (4.1 ± 0.5 vs 3.8 ± 0.5 cm; P = 0.003 and a significant positive correlation between ODI and pulmonary artery systolic pressure (r = 0.41, P<0.0001. After a median follow up of 68 months, no significant differences were observed between the study groups with regard to clinical outcomes, including death, heart failure, myocardial infarction and unstable angina.There is a high prevalence of previously undiagnosed SDB among patients with AMI. SDB in the setting of AMI is associated with higher pulmonary artery systolic pressure. SDB was not associated with adverse clinical outcomes.

  6. Expandable gastroretentive dosage forms.

    Science.gov (United States)

    Klausner, Eytan A; Lavy, Eran; Friedman, Michael; Hoffman, Amnon

    2003-06-24

    Expandable gastroretentive dosage forms (GRDFs) have been designed for the past 3 decades. They were originally created for possible veterinary use, but later the design was modified for enhanced drug therapy in humans. These GRDFs are easily swallowed and reach a significantly larger size in the stomach due to swelling or unfolding processes that prolong their gastric retention time (GRT). After drug release, their dimensions are minimized with subsequent evacuation from the stomach. Gastroretentivity is enhanced by the combination of substantial dimensions with high rigidity of the dosage form to withstand the peristalsis and mechanical contractility of the stomach. Positive results were obtained in preclinical and clinical studies evaluating GRT of expandable GRDFs. Narrow absorption window drugs compounded in such systems have improved in vivo absorption properties. These findings are an important step towards the implementation of expandable GRDFs in the clinical setting. The current review deals with expandable GRDFs reported in articles and patents, and describes the physiological basis of their design. Using the dog as a preclinical screening model prior to human studies, relevant imaging techniques and pharmacokinetic-pharmacodynamic aspects of such delivery systems are also discussed.

  7. Vestibular implants studied in animal models: clinical and scientific implications.

    Science.gov (United States)

    Lewis, Richard F

    2016-12-01

    Damage to the peripheral vestibular system can result in debilitating postural, perceptual, and visual symptoms. A potential new treatment for this clinical problem is to replace some aspects of peripheral vestibular function with an implant that senses head motion and provides this information to the brain by stimulating branches of the vestibular nerve. In this review I consider animal studies performed at our institution over the past 15 years, which have helped elucidate how the brain processes information provided by a vestibular (semicircular canal) implant and how this information could be used to improve the problems experienced by patients with peripheral vestibular damage. Copyright © 2016 the American Physiological Society.

  8. Surgical Burn Wound Infections and Their Clinical Implications

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    Posluszny, Joseph A.; Conrad, Peggie; Halerz, Marcia; Shankar, Ravi; Gamelli, Richard L.

    2011-01-01

    Typically, burn wound infections are classified by the organisms present in the wound within the first several days following injury or later, by routine surveillance cultures. With universal acceptance of early excision and grafting, classification of burn wound colonization in unexcised burn wounds is less relevant shifting clinical significance to open burn-related surgical wound infections (SWI). To better characterize SWIs and their clinical relevance, we identified the pathogens responsible for SWIs, their impact on rates of regrafting, and the relationship between SWI and nosocomial infection (NI) pathogens. Epidemiologic and clinical data for 71 adult patients with ≥20% TBSA burn were collected. Following excision and grafting, if a grafted site had clinical characteristics of infection, a wound culture swab was obtained and organism identified. Surveillance cultures were not obtained. SWI pathogen, anatomic location, post-burn day of occurrence and need for regrafting were compiled. A positive culture obtained from an isolated anatomic location at any time point after excision and grafting of that location was considered a distinct infection. Pathogens responsible for NIs (urinary tract infections, pneumonia, bloodstream and catheter-related bloodstream infections, pseudomembranous colitis and donor site infections) and their post-burn day were identified. The profiles of SWI pathogens and NI pathogens were then compared. Of the 71 patients included, 2 withdrew, 6 had no excision or grafting performed and 1 had incomplete data. Of the 62 remaining, 24 (39%) developed a SWI. In these 24 patients, 70 distinct infections were identified of which 46% required regrafting. Candida species (24%), Pseudomonas aeruginosa (22%), Serratia marcescens (11%) and Staphylococcus aureus (11%) comprised the majority of pathogens. The development of a SWI with the need for regrafting increased overall length of stay, area of autograft, number of operative events and was

  9. Expanding the Clinical and Genetic Spectrum of KRT1, KRT2 and KRT10 Mutations in Keratinopathic Ichthyosis.

    Science.gov (United States)

    Hotz, Alrun; Oji, Vinzenz; Bourrat, Emmanuelle; Jonca, Nathalie; Mazereeuw-Hautier, Juliette; Betz, Regina C; Blume-Peytavi, Ulrike; Stieler, Karola; Morice-Picard, Fanny; Schönbuchner, Ines; Markus, Susanne; Schlipf, Nina; Fischer, Judith

    2016-05-01

    Twenty-six families with keratinopathic ichthyoses (epidermolytic ichthyosis, superficial epidermolytic ichthyosis or congenital reticular ichthyosiform erythroderma) were studied. Epidermolytic ichthyosis is caused by mutations in the genes KRT1 or KRT10, mutations in the gene KRT2 lead to superficial epidermolytic ichthyosis, and congenital reticular ichthyosiform erythroderma is caused by frameshift mutations in the genes KRT10 or KRT1, which lead to the phenomenon of revertant mosaicism. In this study mutations were found in KRT1, KRT2 and KRT10, including 8 mutations that are novel pathogenic variants. We report here the first case of a patient with congenital reticular ichthyosiform erythroderma carrying a mutation in KRT10 that does not lead to an arginine-rich reading frame. Novel clinical features found in patients with congenital reticular ichthyosiform erythroderma are described, such as mental retardation, spasticity, facial dysmorphisms, symblepharon and malposition of the 4th toe.

  10. Expanding the clinical phenotype of the 3q29 microdeletion syndrome and characterization of the reciprocal microduplication

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    Friedrich Christopher A

    2008-04-01

    Full Text Available Abstract Background Interstitial deletions of 3q29 have been recently described as a microdeletion syndrome mediated by nonallelic homologous recombination between low-copy repeats resulting in an ~1.6 Mb common-sized deletion. Given the molecular mechanism causing the deletion, the reciprocal duplication is anticipated to occur with equal frequency, although only one family with this duplication has been reported. Results In this study we describe 14 individuals with microdeletions of 3q29, including one family with a mildly affected mother and two affected children, identified among 14,698 individuals with idiopathic mental retardation who were analyzed by array CGH. Eleven individuals had typical 1.6-Mb deletions. Three individuals had deletions that flank, span, or partially overlap the commonly deleted region. Although the clinical presentations of individuals with typical-sized deletions varied, several features were present in multiple individuals, including mental retardation and microcephaly. We also identified 19 individuals with duplications of 3q29, five of which appear to be the reciprocal duplication product of the 3q29 microdeletion and 14 of which flank, span, or partially overlap the common deletion region. The clinical features of individuals with microduplications of 3q29 also varied with few common features. De novo and inherited abnormalities were found in both the microdeletion and microduplication cohorts illustrating the need for parental samples to fully characterize these abnormalities. Conclusion Our report demonstrates that array CGH is especially suited to identify chromosome abnormalities with unclear or variable presentations.

  11. Polymorphic metabolism of opioid narcotic drugs: possible clinical implications.

    Science.gov (United States)

    Mikus, G; Somogyi, A A; Bochner, F; Chen, Z R

    1991-01-01

    The oxidative metabolism of many drugs is under genetic control. The enzyme responsible for this reaction for this group of drugs is cytochrome P-450IID6. Humans can be classified either as extensive metabolisers or, if lacking this enzyme, poor metabolisers. The incidence of poor metabolisers in caucasian subjects is 7-10%. The hepatic O-demethylation of codeine to morphine, quantitatively a minor metabolic process, represents this type of genetic polymorphism and has been studied in human pharmacokinetic studies, human urinary recovery studies, and in human and rat liver microsome experiments. Based on the current understanding that the analgesic effect of codeine is mediated primarily through morphine, one might anticipate that poor metabolisers would not obtain pain relief from codeine. The clinical significance of this polymorphism to the antidiarrhoeal and antitussive properties of codeine is not known. Others opioids (dihydrocodeine, hydrocodone, oxycodone, and thebaine) are structurally similar to codeine and their metabolism (O-demethylation at the 3 position) might also be under genetic control. Pharmacogenetics may play an important role in explaining the wide variability of the clinical response to many opioid drugs.

  12. Ethnic and genetic causes of neutropenia: clinical and therapeutic implications.

    Science.gov (United States)

    D'Angelo, Guido

    2009-01-01

    The white blood cell count represents clinical data linked with different pathologic conditions, as well as with lifestyle. Another very important condition that affects the number of leukocytes is race and ethnic group-the geographic zone of origin. Genetic studies have identified the gene that controls the expression of the Duffy antigen receptor for chemokine (DARC), which is associated with the ethnic group to which individuals belong. The single-nucleotide polymorphism strongly associated with race is DARC rs2814778. Currently, it is the only condition that can explain the difference in white blood cell count between different ethnic groups. In a society increasingly characterized by multiracial issues, the leukopenia and/or neutropenia in ethnic groups must be known and accurately assessed clinically. Improved knowledge of this association may help in optimizing therapeutic approaches, mainly for African patients with severe diseases, cancer in particular. Recently, preclinical data have also suggested a link between the Duffy antigen and coagulation. This review also discusses the main causes of genetic neutropenia.

  13. Clinical implication for endometriosis associated with ovarian cancer

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    Pao-Ling Torng

    2017-11-01

    Full Text Available We reviewed current literature regarding the association of endometriosis and epithelial ovarian cancer based on epidemiology studies, molecular researches and clinical observations. Our methods include a review of literature research of MEDLINE, PubMed, Cochrane Library of Systematic Reviews and reference search in selected papers. The life time risk of epithelial ovarian cancer in women with endometriosis is low, yet there might be a cluster of individuals who have higher risk of developing epithelial ovarian cancer from endometriosis. Endometriosis associated ovarian cancer (EAOC is predominant in particular histological subtypes of epithelial ovarian carcinoma and are related to some specific molecular aberrations. Clinical observations showed age as an important variable to the development of EAOC. Rapid growth of tumor and solid components in sonography are key features to detect malignant transformation of endometriosis. Evidence is not clear about prophylactic oophorectomy in preventing EAOC in patients with endometriosis. This review provided rationale data for identifying, monitoring, counseling and management of women with endometriosis who are potentially high risk for malignant transformation. Keywords: Endometriosis, Epithelial ovarian cancer, Malignant transformation

  14. Clinical and economic implications of urinary tract infections.

    Science.gov (United States)

    Steiger, Samantha N; Comito, Rachel R; Nicolau, David P

    2017-08-01

    Urinary tract infections represent one of the most frequent reasons for hospitalization. As a result of their prevalence from community-based origins as well as those which develop in hospital setting, this constellation of infections represents a tremendous burden to the global healthcare system. Areas covered: Over the last several decades the management of these infections has become more complicated due to the underlying comorbid conditions of the patients as well as escalating antimicrobial resistance to many of the most frequently used oral and parenteral agents. One such example is the emergence of extend spectrum β-lactamase-producing (ESBL) bacteria that render many of the most frequently utilized oral and parenteral penicillin and cephalosporin based regimens of little clinical utility. As such new treatment strategies are required to effectively manage the growing population of patients with multi-drug resistant bacteria. Expert commentary: Herein, we review some of the current literature which reveals the challenges associated with the contemporary management of UTIs, while presenting strategies such as the implementation of clinical pathways that have the potential to enhance the quality and efficiency of care while reducing the overall cost of care.

  15. Potential clinical implications of recent matrix metalloproteinase inhibitor design strategies.

    Science.gov (United States)

    Amar, Sabrina; Fields, Gregg B

    2015-01-01

    Analysis of matrix metalloproteinases (MMPs) expression profiles in various pathologies correlated with their presence in promoting disease progression. Drugs were designed to inhibit MMPs in an extreme manner by chelating the active site zinc ion. This approach did not distinguish between the 24 members of the MMP family and had devastating consequences during clinical trials. Subsequent knockout mouse studies showed that some MMPs are beneficial in regulating tumor growth, metastasis and indirectly stimulating the immune system. The broad-spectrum inhibitor approach was rethought and modified in order to increase specificity by taking into account the non-conserved secondary binding sites or differences in structures within MMPs and also generating antibodies. These showed interesting results in vitro and in vivo. The recent technological advances that allow us to better understand the function and structure of MMPs are aiding in the development of selective inhibitors.

  16. Clinical Implications of Glucose Variability: Chronic Complications of Diabetes

    Directory of Open Access Journals (Sweden)

    Hye Seung Jung

    2015-06-01

    Full Text Available Glucose variability has been identified as a potential risk factor for diabetic complications; oxidative stress is widely regarded as the mechanism by which glycemic variability induces diabetic complications. However, there remains no generally accepted gold standard for assessing glucose variability. Representative indices for measuring intraday variability include calculation of the standard deviation along with the mean amplitude of glycemic excursions (MAGE. MAGE is used to measure major intraday excursions and is easily measured using continuous glucose monitoring systems. Despite a lack of randomized controlled trials, recent clinical data suggest that long-term glycemic variability, as determined by variability in hemoglobin A1c, may contribute to the development of microvascular complications. Intraday glycemic variability is also suggested to accelerate coronary artery disease in high-risk patients.

  17. Breast Cancer Biology: Clinical Implications for Breast Radiation Therapy.

    Science.gov (United States)

    Horton, Janet K; Jagsi, Reshma; Woodward, Wendy A; Ho, Alice

    2018-01-01

    Historically, prognosis and treatment decision making for breast cancer patients have been dictated by the anatomic extent of tumor spread. However, in recent years, "breast cancer" has proven to be a collection of unique phenotypes with distinct prognoses, patterns of failure, and treatment responses. Recent advances in biologically based assays and targeted therapies designed to exploit these unique phenotypes have profoundly altered systemic therapy practice patterns and treatment outcomes. Data associating locoregional outcomes with tumor biology are emerging. However, the likelihood of obtaining level I evidence for fundamental radiation therapy questions within each of the specific subtypes in the immediate future is low. As such, this review aims to summarize the existing data and provide practical context for the incorporation of breast tumor biology into clinical practice. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. [Cardio-renal axis: pathophysiological evidences and clinical implications].

    Science.gov (United States)

    Di Lullo, Luca; Ronco, Claudio

    2017-03-01

    According to the recent definition proposed by the Consensus conference on Acute Dialysis Quality Initiative Group, the term cardio-renal syndrome CRS has been used to define different clinical conditions in which heart and kidney dysfunction overlap. Type 1 CRS acute cardio - renal syndrome is characterized by acute worsening of cardiac function leading to AKI in the setting of active cardiac disease such as ADHF, while type - 2 CRS occurs in a setting of chronic heart disease. Type 3 CRS is closely link to acute kidney injury, while type 4 represent cardiovascular involvement in chronic kidney disese patients. Type 5 CRS represent cardiac and renal involvement in several diseases such as sepsis, hepato - renal syndrome and immune - mediated diseases. Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.

  19. Clinical implications of The Red Book: Liber Novus.

    Science.gov (United States)

    Bright, George

    2012-09-01

    In this presentation I consider whether the importance of Spirit in Liber Novus may render the task of its clinical application peculiarly problematic. Freud's experimentation on himself is briefly compared with Jung's self-experimentation of which Liber Novus is the record. Taking up the theme of the vas from Gaillard's paper, I refer to Jung's two major contributions to the elaboration of the Freudian frame: the necessity for the analyst to have been analysed, and the positive value of countertransference. In an epilogue, I briefly discuss a dream related to the preparation of this report for publication, emphasizing the theme of the disturbing effects of Spirit as a key theme both in Liber Novus itself and in any attempt to assimilate it on the part of the contemporary analyst. © 2012, The Society of Analytical Psychology.

  20. Pathogenesis and clinical implications of optic disk hemorrhage in glaucoma.

    Science.gov (United States)

    Suh, Min Hee; Park, Ki Ho

    2014-01-01

    The association between optic disk hemorrhage and glaucoma has been studied for many years. Recently, randomized clinical trials have confirmed that disk hemorrhage is a risk factor for development and progression of glaucoma. Disk hemorrhage is more commonly detected in open-angle glaucoma with normal tension than in open-angle glaucoma with high tension. Development of disk hemorrhage possibly is associated with the biomechanical properties of the lamina cribrosa and surrounding tissues, including the intraocular pressure (IOP)-cerebrospinal pressure gradient, arterial pressure, and venous pressure. Disk hemorrhage may be a marker of rapid glaucoma progression, in that localized subclinical structural change predisposes to disk hemorrhage, after which subsequent disease progression is accelerated, and recurrent optic disk hemorrhages are related to rapid structural progression of glaucomatous damage. IOP-lowering therapy can be helpful in halting post-hemorrhage glaucoma progression. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Prescription opioid abuse, pain and addiction: clinical issues and implications.

    Science.gov (United States)

    Ling, Walter; Mooney, Larissa; Hillhouse, Maureen

    2011-05-01

    Prescription opioid misuse in the USA has increased over threefold since 1990 to epidemic proportions, with substantial increases in prescription opioid use also reported in other countries, such as Australia and New Zealand. The broad availability of prescription pain medications, coupled with public misconceptions about their safety and addictive potential, have contributed to the recent surge in non-medical use of prescription opioids and corresponding increases in treatment admissions for problems related to opioid misuse. Given competing pressures faced by physicians to both diagnose and treat pain syndromes and identify individuals at risk for addictive disorders, the use of opioids in the treatment of pain poses a significant clinical challenge. This paper reviews the interaction between pain and opioid addiction with a focus on clinical management issues, including risk factors for opioid dependence in patients with chronic pain and the use of assessment tools to identify and monitor at-risk individuals. Treatment options for opioid dependence and pain are reviewed, including the use of the partial µ agonist buprenorphine in the management of concurrent pain and opioid addiction. Physicians should strive to find a reasonable balance between minimising potential adverse effects of opioid medications without diminishing legitimate access to opioids for analgesia. The article discusses the need to identify methods for minimising risks and negative consequences associated with opioid analgesics and poses research directions, including the development of abuse-deterrent opioid formulations, genetic risk factors for opioid dependence and opioid-induced hyperalgesia as a potential target for medication therapy. © 2011 Australasian Professional Society on Alcohol and other Drugs.

  2. ALS and MMN mimics in patients with BSCL2 mutations: the expanding clinical spectrum of SPG17 hereditary spastic paraplegia.

    Science.gov (United States)

    Musacchio, Thomas; Zaum, Ann-Kathrin; Üçeyler, Nurcan; Sommer, Claudia; Pfeifroth, Nora; Reiners, Karlheinz; Kunstmann, Erdmute; Volkmann, Jens; Rost, Simone; Klebe, Stephan

    2017-01-01

    Silver syndrome/SPG17 is a motor manifestation of mutations in the BSCL2 gene and usually presents as a complicated form of hereditary spastic paraplegia (HSP). We present clinical data, follow-up, and genetic results of seven patients with Silver syndrome/SPG17 including a family with a variable intrafamilial phenotype ranging from subclinical signs to a severe and rapidly progressing amyotrophic lateral sclerosis (ALS)-like phenotype. For molecular diagnosis of the family, we used the TruSight Exome sequencing panel consisting of 2761 genes. We filtered for variants common to affected family members and for exclusive variants in the ALS-like index patient to find possible modifier mutations. We found that de novo mutations and/or incomplete penetrance in BSCL2 has been taken into account for Silver syndrome/SPG17 and confirm the large phenotypical heterogeneity of BSCL2 mutations. Our findings broaden the reported spectrum of the disease to an ALS-like and multifocal motor neuropathy phenotype and underline the need for further research for genetic modifiers due to the striking interindividual and intrafamilial variability.

  3. Fragile X-Associated Tremor Ataxia Syndrome: The Expanding Clinical Picture, Pathophysiology, Epidemiology, and Update on Treatment

    Directory of Open Access Journals (Sweden)

    Deborah A. Hall

    2012-05-01

    Full Text Available Fragile X-associated tremor/ataxia syndrome (FXTAS is a progressive degenerative movement disorder characterized by kinetic tremor, cerebellar gait ataxia, parkinsonism, and cognitive decline. This disorder occurs in both males and females, frequently in families with children who have fragile X syndrome. The clinical features of this disorder, both classic and newly described, are summarized in this paper. In screening studies, fragile X mental retardation 1 (FMR1 gene premutation (55–200 CGG expansions are most frequently seen in men with ataxia who have tested negative for spinocerebellar ataxias. Since the original description, the classic FXTAS phenotype has now been reported in females and in carriers of smaller (45–54 CGG and larger (>200 CGG expansions in FMR1. Premutation carriers may present with a Parkinson disease phenotype or hypotension, rather than with tremor and/or ataxia. Parkinsonism and gait ataxia may also be seen in individuals with gray zone (41–54 CGG expansions. Studies regarding medication to treat the symptoms in FXTAS are few in number and suggest that medications targeted to specific symptoms, such as kinetic tremor or gait ataxia, may be most beneficial. Great progress has been made in regards to FXTAS research, likely given the readily available gene test and the screening of multiple family members, including parents and grandparents, of fragile X syndrome children. Expansion of genotypes and phenotypes in the disorder may suggest that a broader disease definition might be necessary in the future.

  4. How motorcycle helmets affect trauma mortality: Clinical and policy implications.

    Science.gov (United States)

    Lee, Jwo-Leun; Chen, Tzu-Chun; Huang, Hung-Chang; Chen, Ray-Jade

    2017-08-18

    Motorcycles are the most popular vehicles in Taiwan, where more than 14.8 million motorcycles (1 motorcycle per 1.6 people) are in service. Despite the mandatory helmet law passed in 1997, less than 80% of motorcyclists in Taiwan wear helmets. The objective of this study was to analyze the effect of using motorcycle helmets on fatality rates. A clinical data set including 2,868 trauma patients was analyzed; the cross-sectional registration database was administered by a university medical center in Central Taiwan. A path analysis framework and multiple logistic regressions were used to estimate the marginal effect of helmet use on mortality. Using a helmet did not directly reduce the mortality rate but rather indirectly reduced the mortality rate through intervening variables such as the severity of head injuries, number of craniotomies, and complications during therapeutic processes. Wearing a helmet can reduce the fatality rate by 1.3%, the rate of severe head injury by 34.5%, the craniotomy rate by 7.8%, and the rate of complications during therapeutic processes by 1.5%. These rates comprise 33.3% of the mortality rate for people who do not wear helmets, 67.3% of the severe head injury rate, 60.0% of the craniotomy rate, and 12.2% of the rate of complications during therapeutic processes. Wearing a helmet and trauma system designation are crucial factors that reduce the fatality rate.

  5. Pancreatic cancer: Translational research aspects and clinical implications

    Science.gov (United States)

    Ansari, Daniel; Chen, Bi-Cheng; Dong, Lei; Zhou, Meng-Tao; Andersson, Roland

    2012-01-01

    Despite improvements in surgical techniques and adjuvant chemotherapy, the overall mortality rates in pancreatic cancer have generally remained relatively unchanged and the 5-year survival rate is actually below 2%. This paper will address the importance of achieving an early diagnosis and identifying markers for prognosis and response to therapy such as genes, proteins, microRNAs or epigenetic modifications. However, there are still major hurdles when translating investigational biomarkers into routine clinical practice. Furthermore, novel ways of secondary screening in high-risk individuals, such as artificial neural networks and modern imaging, will be discussed. Drug resistance is ubiquitous in pancreatic cancer. Several mechanisms of drug resistance have already been revealed, including human equilibrative nucleoside transporter-1 status, multidrug resistance proteins, aberrant signaling pathways, microRNAs, stromal influence, epithelial-mesenchymal transition-type cells and recently the presence of cancer stem cells/cancer-initiating cells. These factors must be considered when developing more customized types of intervention (“personalized medicine”). In the future, multifunctional nanoparticles that combine a specific targeting agent, an imaging probe, a cell-penetrating agent, a biocompatible polymer and an anti-cancer drug may become valuable for the management of patients with pancreatic cancer. PMID:22509073

  6. Dairy products on metabolic health: current research and clinical implications.

    Science.gov (United States)

    Da Silva, Marine S; Rudkowska, Iwona

    2014-03-01

    Dairy products have been thought to have a beneficial role in the metabolic syndrome (MetS). MetS constitutes a cluster of risk factors for an increased mortality, including obesity, impaired glucose homeostasis, hypertension and atherogenic dyslipidemia. Individuals with MetS are also often in a chronic, low-grade inflammatory state. The objective of this review is to examine recent meta-analyses and clinical studies on the association between dairy products consumption and these MetS risk factors. Findings from studies demonstrate that weight loss related to dairy product intake is due to the combination of an energy-restricted diet with consumption of dairy products. Further, a limited number of studies have shown beneficial effects of dairy consumption on plasma lipids, blood pressure, glucose homeostasis or inflammatory and oxidative stress profiles. Overall, this review article suggests that adults should consume at least 2-3 servings of dairy products per day within a well-balanced diet and a healthy lifestyle for metabolic health. Yet, higher dairy product consumption may have additional beneficial effects, but more well-designed intervention studies are needed to ascertain these effects. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. Clinical implications and pathological associations of circulating mitochondrial DNA.

    Science.gov (United States)

    Tuboly, Eszter; Mcllroy, Daniel; Briggs, Gabrielle; Lott, Natalie; Balogh, Zsolt J

    2017-01-01

    Mitochondria are membrane-enclosed organelles, the energy-producing centers in almost all eukaryotic cells. The evolutionary emergence of mitochondria is a result of the endocytosis of a-proteobacteria. There are several characteristic features which refer to its prokaryotic ancestors including its independent sets of double-stranded mitochondrial DNA, which is uniquely circular in form and contains a significant amount of unmethylated DNA as CpG islands. Resent research has proven that free mitochondrial DNA found in blood was associated with innate immunomodulation in a broad-range of clinical conditions. Upon release, mitochondrial DNA acts as a danger-associated molecular pattern in the circulation, it is recognized by pattern recognition receptors and it facilitates inflammatory responses. Besides its high receptor activation potential, mitochondrial DNA is likely to perform direct crosstalk with activated leukocytes and to be contributed to other anti-microbial activities. Here we highlight the pathological conditions where cell free mtDNA is involved, describe the potential sources and mechanisms of extracellular mtDNA release and explore evidence for its mechanism of action after being excreted and potential therapeutic strategies.

  8. Psychiatric caregiver stress: clinical implications of compassion fatigue.

    Science.gov (United States)

    Franza, Francesco; Del Buono, Gianfranco; Pellegrino, Ferdinando

    2015-09-01

    The capacity to work productively is a key component of health and emotional well-being. People who work in health care can be exposed to the fatigue of care. Compassion fatigue has been described as an occupational hazard specific to clinical work related severe emotional distress. In our study, we have evaluated compassion fatigue in a mental health group (47 psychiatric staff) and its relationship with inpatients (237 inpatients) affected by some psychiatric disorders. At baseline, the more significant data indicate a high percentage of Job Burnout and Compassion Fatigue in psychiatric nurses (respectively, 39.28%, 28.57%). Significant Compassion Fatigue percentage is present also in psychologist group (36.36%). Finally, in psychiatrists, the exposure to patients increased vicarious trauma (28.57%), but not job burnout. After a year of participation in Balint Groups, the psychiatric staff presented an overall reduction in total mean score in any administered scale (CBI: pBurnout: pfatigue causes concern among mental health professionals, and Balint Groups may represent a therapeutic strategy to help health professionals to face difficulties in challenging work environments.

  9. A European Spectrum of Pharmacogenomic Biomarkers: Implications for Clinical Pharmacogenomics.

    Directory of Open Access Journals (Sweden)

    Clint Mizzi

    Full Text Available Pharmacogenomics aims to correlate inter-individual differences of drug efficacy and/or toxicity with the underlying genetic composition, particularly in genes encoding for protein factors and enzymes involved in drug metabolism and transport. In several European populations, particularly in countries with lower income, information related to the prevalence of pharmacogenomic biomarkers is incomplete or lacking. Here, we have implemented the microattribution approach to assess the pharmacogenomic biomarkers allelic spectrum in 18 European populations, mostly from developing European countries, by analyzing 1,931 pharmacogenomics biomarkers in 231 genes. Our data show significant inter-population pharmacogenomic biomarker allele frequency differences, particularly in 7 clinically actionable pharmacogenomic biomarkers in 7 European populations, affecting drug efficacy and/or toxicity of 51 medication treatment modalities. These data also reflect on the differences observed in the prevalence of high-risk genotypes in these populations, as far as common markers in the CYP2C9, CYP2C19, CYP3A5, VKORC1, SLCO1B1 and TPMT pharmacogenes are concerned. Also, our data demonstrate notable differences in predicted genotype-based warfarin dosing among these populations. Our findings can be exploited not only to develop guidelines for medical prioritization, but most importantly to facilitate integration of pharmacogenomics and to support pre-emptive pharmacogenomic testing. This may subsequently contribute towards significant cost-savings in the overall healthcare expenditure in the participating countries, where pharmacogenomics implementation proves to be cost-effective.

  10. Pharmacogenetics of ATP-binding cassette transporters and clinical implications.

    Science.gov (United States)

    Cascorbi, Ingolf; Haenisch, Sierk

    2010-01-01

    Drug resistance is a severe limitation of chemotherapy of various malignancies. In particular efflux transporters of the ATP-binding cassette family such as ABCB1 (P-glycoprotein), the ABCC (multidrug resistance-associated protein) family, and ABCG2 (breast cancer resistance protein) have been identified as major determinants of chemoresistance in tumor cells. Bioavailability depends not only on the activity of drug metabolizing enzymes but also to a major extent on the activity of drug transport across biomembranes. They are expressed in the apical membranes of many barrier tissues such as the intestine, liver, blood-brain barrier, kidney, placenta, testis, and in lymphocytes, thus contributing to plasma, liquor, but also intracellular drug disposition. Since expression and function exhibit a broad variability, it was hypothesized that hereditary variances in the genes of membrane transporters could explain at least in part interindividual differences of pharmacokinetics of a variety of anticancer drugs and many others contributing to the clinical outcome of certain leukemias and further malignancies.

  11. Sickle cell trait diagnosis: clinical and social implications.

    Science.gov (United States)

    Naik, Rakhi P; Haywood, Carlton

    2015-01-01

    The sickle hemoglobin (HbS) point mutation has independently undergone evolutionary selection at least five times in the world because of its overwhelming malarial protective effects in the heterozygous state. In 1949, homozygous Hb S or sickle cell disease (SCD) became the first inherited condition identified at the molecular level; however, since then, both SCD and heterozygous Hb S, sickle cell trait (SCT), have endured a long and complicated history. Hasty adoption of early mass screening programs for SCD, recent implementation of targeted screening mandates for SCT in athletics, and concerns about stigmatization have evoked considerable controversy regarding research and policy decisions for SCT. Although SCT is a largely protective condition in the context of malaria, clinical sequelae, such as exercise-related injury, renal complications, and venous thromboembolism can occur in affected carriers. The historical background of SCD and SCT has provided lessons about how research should be conducted in the modern era to minimize stigmatization, optimize study conclusions, and inform genetic counseling and policy decisions for SCT. © 2015 by The American Society of Hematology. All rights reserved.

  12. Genetics of tuberous sclerosis complex: implications for clinical practice

    Directory of Open Access Journals (Sweden)

    Caban C

    2016-12-01

    Full Text Available Carolina Caban,1,2 Nubaira Khan,1,2 Daphne M Hasbani,3 Peter B Crino1,2 1Department of Neurology, 2Shriners Hospitals Pediatric Research Center, Temple University School of Medicine, 3Department of Neurology, St. Christopher’s Hospital for Children, Drexel University College of Medicine, Philadelphia, PA, USA Abstract: Tuberous sclerosis complex (TSC is a multisystem disorder that results from heterozygous mutations in either TSC1 or TSC2. The primary organ systems that are affected include the brain, skin, lung, kidney, and heart, all with variable frequency, penetrance, and severity. Neurological features include epilepsy, autism, and intellectual disability. There are more than 1,500 known pathogenic variants for TSC1 and TSC2, including deletion, nonsense, and missense mutations, and all pathogenic mutations are inactivating, leading to loss of function effects on the encoded proteins TSC1 and TSC2. These proteins form a complex to constitutively inhibit mechanistic target of rapamycin (mTOR signaling cascade, and as a consequence, mTOR signaling is constitutively active within all TSC-associated lesions. The mTOR inhibitors rapamycin (sirolimus and everolimus have been shown to reduce the size of renal and brain lesions and improve pulmonary function in TSC, and these compounds may also decrease seizure frequency. The clinical application of mTOR inhibitors in TSC has provided one of the first examples of precision medicine in a neurodevelopmental disorder. Keywords: TSC, epilepsy, genetics, mTOR, rapamycin

  13. Combination of inhaled corticosteroids and beta(2)-agonists in asthma - Clinical and economic implications

    NARCIS (Netherlands)

    RuttenvanMolken, MPMH; Kerstjens, HAM

    1996-01-01

    The current asthma management guidelines recommend that all but patients with the mildest disease should be treated with a combination of inhaled corticosteroids and beta(2)-agonists, the latter preferably on an as-needed basis, This article reviews the clinical implications of these

  14. Resource utilization implications of treatment were able to be assessed from appropriately reported clinical trial data

    NARCIS (Netherlands)

    Poole-Wilson, Philip A.; Kirwan, Bridget-Anne; Voko, Zoltan; de Brouwer, Sophie; Dunselman, Peter H. J. M.; van Dalen, Frederik J.; Lubsen, Jacobus

    Background and Objective: Published clinical trial data rarely allow assessment of the health care resource utilization implications of treatment. We give an example of how these can be assessed given appropriate tabulation of data. Methods: Data from a trial comparing long-acting nifedipine

  15. The voice of the child in parental divorce: implications for clinical ...

    African Journals Online (AJOL)

    The voice of the child in parental divorce: implications for clinical practice and mental health practitioners. ... The seven themes were: (i) What is a divorcement; (ii) Stories of loss; (iii) Stories of gain; (iv) Stories of change; (v) Stories of stability; (vi) Healing stories; and (vii) Complicating stories. Conclusion: On the basis of the ...

  16. Persistent primitive hypoglossal artery associated with Chiari II malformation: Diagnosis and clinical implications

    Directory of Open Access Journals (Sweden)

    Gupta Mudit

    2010-01-01

    Full Text Available We present a case of persistent primitive hypoglossal artery (PPHA associated with Chiari II malformation and discuss the clinical implications. There has been one reported case of PPHA associated with Chiari 1 malformation, but none in association with Chiari II. Our patient also had a widened hypoglossal canal, with cerebrospinal fluid (CSF sac herniation through it.

  17. Herpes Simplex Virus Infection in a University Health Population: Clinical Manifestations, Epidemiology, and Implications

    Science.gov (United States)

    Horowitz, Robert; Aierstuck, Sara; Williams, Elizabeth A.; Melby, Bernette

    2010-01-01

    Objective: The authors described clinical presentations of oral and genital herpes simplex virus (HSV) infections in a university health population and implications of these findings. Participants and Methods: Using a standardized data collection tool, 215 records of patients with symptomatic culture-positive HSV infections were reviewed. Results:…

  18. Cervical spine alignment, sagittal deformity, and clinical implications: a review.

    Science.gov (United States)

    Scheer, Justin K; Tang, Jessica A; Smith, Justin S; Acosta, Frank L; Protopsaltis, Themistocles S; Blondel, Benjamin; Bess, Shay; Shaffrey, Christopher I; Deviren, Vedat; Lafage, Virginie; Schwab, Frank; Ames, Christopher P

    2013-08-01

    This paper is a narrative review of normal cervical alignment, methods for quantifying alignment, and how alignment is associated with cervical deformity, myelopathy, and adjacent-segment disease (ASD), with discussions of health-related quality of life (HRQOL). Popular methods currently used to quantify cervical alignment are discussed including cervical lordosis, sagittal vertical axis, and horizontal gaze with the chin-brow to vertical angle. Cervical deformity is examined in detail as deformities localized to the cervical spine affect, and are affected by, other parameters of the spine in preserving global sagittal alignment. An evolving trend is defining cervical sagittal alignment. Evidence from a few recent studies suggests correlations between radiographic parameters in the cervical spine and HRQOL. Analysis of the cervical regional alignment with respect to overall spinal pelvic alignment is critical. The article details mechanisms by which cervical kyphotic deformity potentially leads to ASD and discusses previous studies that suggest how postoperative sagittal malalignment may promote ASD. Further clinical studies are needed to explore the relationship of cervical malalignment and the development of ASD. Sagittal alignment of the cervical spine may play a substantial role in the development of cervical myelopathy as cervical deformity can lead to spinal cord compression and cord tension. Surgical correction of cervical myelopathy should always take into consideration cervical sagittal alignment, as decompression alone may not decrease cord tension induced by kyphosis. Awareness of the development of postlaminectomy kyphosis is critical as it relates to cervical myelopathy. The future direction of cervical deformity correction should include a comprehensive approach in assessing global cervicalpelvic relationships. Just as understanding pelvic incidence as it relates to lumbar lordosis was crucial in building our knowledge of thoracolumbar deformities, T

  19. Emotional sequelae of abortion: implications for clinical practice.

    Science.gov (United States)

    Lemkau, J P

    1988-12-01

    Without ambivalence, psychotherapy would be unnecessary; however there is a great deal of ambivalence about abortion so it is a therapy issue. In our society abortion decision are made in an ambivalent environment. Even when a woman makes a free decision to have a legal abortion, an emotional sequelae can ensue. This article reviews literature and relates professional experience about the psychological problems and treatment of women before and after having an abortion. A feeling of relief is the typical reaction to an abortion for the woman. The issues involved in the decision process are the woman's own health and happiness as well as that of her future family. The issues include medical and interpersonal ones and often present a moral crisis. Issues such as education, occupation, and relationships must be considered. Three major types of reactions seem to follow an abortion. The 1st is a positive feeling of happiness and relief. The 2nd and 3rd are negative, one being socially based guilt and the other being individually based guilt. Identifying abortion related issues in psychotherapy is not always easy, since they are no usually directly presented to the therapist. They often manifest themselves as symptoms of other problems. Research suggests that unmarried young women without children have a harder time resolving all the issues involved in making an abortion decision. One effective method of discovering emotional problems is to determine the reasons for delaying an abortion. If a woman is having problems making the decision is must be for an important reason. Just as important is the aftermath of the abortion. Attempts should be made to discover as much information about the procedure itself, the recovery time and any repercussions of the procedure. Neither research nor clinical experience has shown that abortion related psychotherapy is different than other forms of treatment. Griefwork, educational approaches, reviews of the decision making process and

  20. Clinical implications of medulloblastoma subgroups: incidence of CSF diversion surgery.

    Science.gov (United States)

    Schneider, Christian; Ramaswamy, Vijay; Kulkarni, Abhaya V; Rutka, James T; Remke, Marc; Tabori, Uri; Hawkins, Cynthia; Bouffet, Eric; Taylor, Michael D

    2015-03-01

    While medulloblastoma was initially thought to comprise a single homogeneous entity, it is now accepted that it in fact comprises 4 discrete subgroups, each with its own distinct demographics, clinical presentation, transcriptomics, genetics, and outcome. Hydrocephalus is a common complication of medulloblastoma and not infrequently requires CSF diversion. The authors report the incidence of CSF diversion surgery in each of the subgroups of medulloblastoma (Wnt, Shh, Group 3, and Group 4). The medical and imaging records for patients who underwent surgery for medulloblastoma at The Hospital for Sick Children were retrospectively reviewed. The primary outcome was the requirement for CSF diversion surgery either before or within 60 days of tumor resection. The modified Canadian Preoperative Prediction Rule for Hydrocephalus (mCPPRH) was compared among subgroups. Of 143 medulloblastoma patients, treated from 1991 to 2013, sufficient data were available for 130 patients (15 with Wnt, 30 with Shh, 30 with Group 3, and 55 with Group 4 medulloblastomas). Of these, 28 patients (22%) ultimately underwent CSF diversion surgery: 0% with Wnt, 29% with Shh, 29% with Group 3, and 43% with Group 4 tumors. Patients in the Wnt subgroup had a lower incidence of CSF diversion than all other patients combined (p = 0.04). Wnt patients had a lower mCPPRH score (lower risk of CSF diversion, p = 0.045), were older, had smaller ventricles at diagnosis, and had no leptomeningeal metastases. The overall rate of CSF diversion surgery for Shh, Group 3, and Group 4 medulloblastomas is around 30%, but no patients in the present series with a Wnt medulloblastoma required shunting. The low incidence of hydrocephalus in patients with Wnt medulloblastoma likely reflects both host factors (age) and disease factors (lack of metastases). The absence of hydrocephalus in patients with Wnt medulloblastomas likely contributes to their excellent rate of survival and may also contribute to a higher quality

  1. Proprioceptive neuromuscular facilitation stretching : mechanisms and clinical implications.

    Science.gov (United States)

    Sharman, Melanie J; Cresswell, Andrew G; Riek, Stephan

    2006-01-01

    Proprioceptive neuromuscular facilitation (PNF) stretching techniques are commonly used in the athletic and clinical environments to enhance both active and passive range of motion (ROM) with a view to optimising motor performance and rehabilitation. PNF stretching is positioned in the literature as the most effective stretching technique when the aim is to increase ROM, particularly in respect to short-term changes in ROM. With due consideration of the heterogeneity across the applied PNF stretching research, a summary of the findings suggests that an 'active' PNF stretching technique achieves the greatest gains in ROM, e.g. utilising a shortening contraction of the opposing muscle to place the target muscle on stretch, followed by a static contraction of the target muscle. The inclusion of a shortening contraction of the opposing muscle appears to have the greatest impact on enhancing ROM. When including a static contraction of the target muscle, this needs to be held for approximately 3 seconds at no more than 20% of a maximum voluntary contraction. The greatest changes in ROM generally occur after the first repetition and in order to achieve more lasting changes in ROM, PNF stretching needs to be performed once or twice per week. The superior changes in ROM that PNF stretching often produces compared with other stretching techniques has traditionally been attributed to autogenic and/or reciprocal inhibition, although the literature does not support this hypothesis. Instead, and in the absence of a biomechanical explanation, the contemporary view proposes that PNF stretching influences the point at which stretch is perceived or tolerated. The mechanism(s) underpinning the change in stretch perception or tolerance are not known, although pain modulation has been suggested.

  2. Private inherited microdeletion/microduplications: implications in clinical practice.

    Science.gov (United States)

    Mencarelli, Maria Antonietta; Katzaki, Eleni; Papa, Filomena Tiziana; Sampieri, Katia; Caselli, Rossella; Uliana, Vera; Pollazzon, Marzia; Canitano, Roberto; Mostardini, Rosa; Grosso, Salvatore; Longo, Ilaria; Ariani, Francesca; Meloni, Ilaria; Hayek, Josef; Balestri, Paolo; Mari, Francesca; Renieri, Alessandra

    2008-01-01

    The introduction of array-CGH analysis is allowing the identification of novel genomic disorders. However, this new high-resolution technique is also opening novel diagnostic challenges when inherited private CNVs of unclear clinical significance are found. Oligo array-CGH analysis of 84 patients with mild to severe mental retardation associated with multiple congenital anomalies revealed 10 private CNVs inherited from a healthy parent. Three were deletions (7q31, 14q21.1, Xq25) and seven duplications (12p11.22, 12q21.31, 13q31.1, 17q12, Xp22.31, Xq28) ranging between 0.1 and 3.8Mb. Six rearrangements were not polymorphic. Four overlapped polymorphic regions to the extent of 10-61%. In one case the size was different between the proband and the healthy relative. Three small rearrangements were gene deserts. The remaining seven had a mean gene content of five (ranging from 1 to 18). None of the rearranged genes is known to be imprinted. Three disease-genes were found in three different cases: KAL1 in dupXp22.31, STS in another dupXp22.31 and TCF2 in dup17q12. The patient carrying the last duplication presents sex reversal, Peters' anomaly and renal cysts and the duplication is located 4Mb away from the HSD17B1 gene, coding a key enzyme of testosterone biosynthesis. Considering the overlap with polymorphic regions, size-identity within the family, gene content, kind of rearrangement and size of rearrangement we suggest that at least in five cases the relationship to the phenotype has not to be excluded. We recommend to maintain caution when asserting that chromosomal abnormalities inherited from a healthy parent are benign. A more complex mechanism may in fact be involved, such as a concurrent variation in the other allele or in another chromosome that influences the phenotype.

  3. [Local estrogen therapy--clinical implications--2012 update].

    Science.gov (United States)

    Kokot-Kierepa, Marta; Bartuzi, Aleksandra; Kulik-Rechberger, Beata; Rechberger, Tomasz

    2012-10-01

    sustained-release intra-vaginal estradiol ring and a low-dose estradiol and estriol tablets are useful therapeutic options in the treatment of this condition. Moreover; a low dose treatment with a minimised systemic absorption rate may be considered in women with a history of breast cancer and associated severe vulvovaginal atrophy. It should be mentioned that vaginal lubricants once applied on a regular basis may also be effective in alleviating the symptoms of vaginal atrophy and should be offered to women wishing to avoid the use of local vaginal estrogen preparations and in cases where local estrogen therapy is contraindicated. Vaginal dehydroepiandrosterone (DHEA), vaginal testosterone, and tissue selective estrogen complexes are new, emerging therapies; however more clinical studies are necessary to confirm their efficacy and safety in the treatment of postmenopausal vulvovaginal atrophy.

  4. Clinical leadership in contemporary clinical practice: implications for nursing in Australia.

    Science.gov (United States)

    Davidson, P M; Elliott, D; Daly, J

    2006-04-01

    Leadership in the clinical practice environment is important to ensure both optimal patient outcomes and successive generations of motivated and enthusiastic clinicians. The present paper seeks to define and describe clinical leadership and identify the facilitators and barriers to clinical leadership. We also describe strategies to develop clinical leaders in Australia. Key drivers to the development of nursing leaders are strategies that recognize and value clinical expertise. These include models of care that highlight the importance of the nursing role; evidence-based practice and measurement of clinical outcomes; strategies to empower clinicians and mechanisms to ensure participation in clinical decision-making. Significant barriers to clinical leadership are organizational structures that preclude nurses from clinical decision making; the national shortage of nurses; fiscal constraints; absence of well evaluated models of care and trends towards less skilled clinicians. Systematic, strategic initiatives are required to nurture and develop clinical leaders. These strategies need to be collegial collaborations between the academic and health care sectors in order to provide a united voice for advancing the nursing profession.

  5. Implications of expanding indications for drug treatment to prevent fracture in older men in United States: cross sectional and longitudinal analysis of prospective cohort study.

    Science.gov (United States)

    Ensrud, Kristine E; Taylor, Brent C; Peters, Katherine W; Gourlay, Margaret L; Donaldson, Meghan G; Leslie, William D; Blackwell, Terri L; Fink, Howard A; Orwoll, Eric S; Schousboe, John

    2014-07-03

    To quantify incremental effects of applying different criteria to identify men who are candidates for drug treatment to prevent fracture and to examine the extent to which fracture probabilities vary across distinct categories of men defined by these criteria. Cross sectional and longitudinal analysis of a prospective cohort study. Multicenter Osteoporotic Fractures in Men (MrOS) study in the United States. 5880 untreated community dwelling men aged 65 years or over classified into four distinct groups: osteoporosis by World Health Organization criteria alone; osteoporosis by National Osteoporosis Foundation (NOF) but not WHO criteria; no osteoporosis but at high fracture risk (at or above NOF derived FRAX intervention thresholds recommended for US); and no osteoporosis and at low fracture risk (below NOF derived FRAX intervention thresholds recommended for US). Proportion of men identified for drug treatment; predicted 10 year probabilities of hip and major osteoporotic fracture calculated using FRAX algorithm with femoral neck bone mineral density; observed 10 year probabilities for confirmed incident hip and major osteoporotic (hip, clinical vertebral, wrist, or humerus) fracture events calculated using cumulative incidence estimation, accounting for competing risk of mortality. 130 (2.2%) men were identified as having osteoporosis by using the WHO definition, and an additional 422 were identified by applying the NOF definition (total osteoporosis prevalence 9.4%). Application of NOF derived FRAX intervention thresholds led to 936 (15.9%) additional men without osteoporosis being identified as at high fracture risk, raising the total prevalence of men potentially eligible for drug treatment to 25.3%. Observed 10 year hip fracture probabilities were 20.6% for men with osteoporosis by WHO criteria alone, 6.8% for men with osteoporosis by NOF (but not WHO) criteria, 6.4% for men without osteoporosis but classified as at high fracture risk, and 1.5% for men without

  6. Clinical Outcome after the Use of a New Craniocaudal Expandable Implant for Vertebral Compression Fracture Treatment: One Year Results from a Prospective Multicentric Study

    Directory of Open Access Journals (Sweden)

    David Noriega

    2015-01-01

    Full Text Available The purpose of this prospective multicentric observational study was to confirm the safety and clinical performance of a craniocaudal expandable implant used in combination with high viscosity PMMA bone cement for the treatment of vertebral compression fractures. Thirty-nine VCFs in 32 patients were treated using the SpineJack minimally invasive surgery protocol. Outcome was determined by using the Visual Analogue Scale for measuring pain, the Oswestry Disability Index for scoring functional capacity, and the self-reporting European Quality of Life scores for the quality of life. Safety was evaluated by reporting all adverse events. The occurrence of cement leakages was assessed by either radiographs or CT scan or both. Statistically significant improvements were found regarding pain, function, and quality of life. The global pain score reduction at 1 year was 80.9% compared to the preoperative situation and the result of the Oswestry Disability Index showed a decrease from 65.0% at baseline to 10.5% at 12 months postoperatively. The cement leakage rate was 30.8%. No device- or surgery-related complications were found. This observational study demonstrates promising and persistent results consisting of immediate and sustained pain relief and durable clinical improvement after the procedure and throughout the 1-year follow-up period.

  7. Clinical outcome after the use of a new craniocaudal expandable implant for vertebral compression fracture treatment: one year results from a prospective multicentric study.

    Science.gov (United States)

    Noriega, David; Krüger, Antonio; Ardura, Francisco; Hansen-Algenstaedt, Nils; Hassel, Frank; Barreau, Xavier; Beyerlein, Jörg

    2015-01-01

    The purpose of this prospective multicentric observational study was to confirm the safety and clinical performance of a craniocaudal expandable implant used in combination with high viscosity PMMA bone cement for the treatment of vertebral compression fractures. Thirty-nine VCFs in 32 patients were treated using the SpineJack minimally invasive surgery protocol. Outcome was determined by using the Visual Analogue Scale for measuring pain, the Oswestry Disability Index for scoring functional capacity, and the self-reporting European Quality of Life scores for the quality of life. Safety was evaluated by reporting all adverse events. The occurrence of cement leakages was assessed by either radiographs or CT scan or both. Statistically significant improvements were found regarding pain, function, and quality of life. The global pain score reduction at 1 year was 80.9% compared to the preoperative situation and the result of the Oswestry Disability Index showed a decrease from 65.0% at baseline to 10.5% at 12 months postoperatively. The cement leakage rate was 30.8%. No device- or surgery-related complications were found. This observational study demonstrates promising and persistent results consisting of immediate and sustained pain relief and durable clinical improvement after the procedure and throughout the 1-year follow-up period.

  8. A review of pharmacological interactions between HIV or hepatitis C virus medications and opioid agonist therapy: implications and management for clinical practice.

    Science.gov (United States)

    Bruce, R Douglas; Moody, David E; Altice, Frederick L; Gourevitch, Marc N; Friedland, Gerald H

    2013-05-01

    Global access to opioid agonist therapy and HIV/hepatitis C virus (HCV) treatment is expanding but when used concurrently, problematic pharmacokinetic and pharmacodynamic interactions may occur. Articles published from 1966 to 2012 in Medline were reviewed using the following keywords: HIV, AIDS, HIV therapy, HCV, HCV therapy, antiretroviral therapy, highly active antiretroviral therapy, drug interactions, methadone and buprenorphine. In addition, a review of abstracts from national and international meetings and conference proceedings was conducted; selected reports were reviewed as well. The metabolism of both opioid and antiretroviral therapies, description of their known interactions and clinical implications and management of these interactions were reviewed. Important pharmacokinetic and pharmacodynamic drug interactions affecting either methadone or HIV medications have been demonstrated within each class of antiretroviral agents. Drug interactions between methadone, buprenorphine and HIV medications are known and may have important clinical consequences. Clinicians must be alert to these interactions and have a basic knowledge regarding their management.

  9. Financial and clinical governance implications of clinical coding accuracy in neurosurgery: a multidisciplinary audit.

    Science.gov (United States)

    Haliasos, N; Rezajooi, K; O'neill, K S; Van Dellen, J; Hudovsky, Anita; Nouraei, Sar

    2010-04-01

    Clinical coding is the translation of documented clinical activities during an admission to a codified language. Healthcare Resource Groupings (HRGs) are derived from coding data and are used to calculate payment to hospitals in England, Wales and Scotland and to conduct national audit and benchmarking exercises. Coding is an error-prone process and an understanding of its accuracy within neurosurgery is critical for financial, organizational and clinical governance purposes. We undertook a multidisciplinary audit of neurosurgical clinical coding accuracy. Neurosurgeons trained in coding assessed the accuracy of 386 patient episodes. Where clinicians felt a coding error was present, the case was discussed with an experienced clinical coder. Concordance between the initial coder-only clinical coding and the final clinician-coder multidisciplinary coding was assessed. At least one coding error occurred in 71/386 patients (18.4%). There were 36 diagnosis and 93 procedure errors and in 40 cases, the initial HRG changed (10.4%). Financially, this translated to pound111 revenue-loss per patient episode and projected to pound171,452 of annual loss to the department. 85% of all coding errors were due to accumulation of coding changes that occurred only once in the whole data set. Neurosurgical clinical coding is error-prone. This is financially disadvantageous and with the coding data being the source of comparisons within and between departments, coding inaccuracies paint a distorted picture of departmental activity and subspecialism in audit and benchmarking. Clinical engagement improves accuracy and is encouraged within a clinical governance framework.

  10. Outcome models in clinical studies: implications for designing and evaluating trials in clinical nutrition.

    Science.gov (United States)

    Koller, Michael; Schütz, Tatjana; Valentini, Luzia; Kopp, Ina; Pichard, Claude; Lochs, Herbert

    2013-08-01

    The selection of appropriate outcome variables in clinical nutrition is particularly challenging, since nutrition is an adjunct therapy in most cases. Therefore, its effect may be confounded with the primary therapy, and classic biomedical outcomes may not reflect the effect of the nutritional intervention. This paper scrutinizes different alternatives to the biomedical perspective. Five different outcome models are proposed and analyzed for their suitability in clinical nutrition studies: biomedical, patient-centered/-reported, health economic, decision-making, and integration of classical and patient-reported endpoints. Most published studies in the field of clinical nutrition make use of biomedical endpoints, but the growing importance of patient-centered/-reported and health economic outcomes is recognized. We recommend avoiding to focus solely on biomedical endpoints in clinical nutrition studies. The availability and value of a broader set of outcome-models should be acknowledged. Patient-centered/-reported, health economic or combined endpoints are particularly useful to assess the effect of nutritional therapies, especially when applied in conjunction with a primary therapy. The proposed outcome models can also contribute to refine clinical nutrition guidelines in assessing the clinical relevance of the study results. Copyright © 2012. Published by Elsevier Ltd.

  11. Sources of variation in primary care clinical workflow: implications for the design of cognitive support.

    Science.gov (United States)

    Militello, Laura G; Arbuckle, Nicole B; Saleem, Jason J; Patterson, Emily; Flanagan, Mindy; Haggstrom, David; Doebbeling, Bradley N

    2014-03-01

    This article identifies sources of variation in clinical workflow and implications for the design and implementation of electronic clinical decision support. Sources of variation in workflow were identified via rapid ethnographic observation, focus groups, and interviews across a total of eight medical centers in both the Veterans Health Administration and academic medical centers nationally regarded as leaders in developing and using clinical decision support. Data were reviewed for types of variability within the social and technical subsystems and the external environment as described in the sociotechnical systems theory. Two researchers independently identified examples of variation and their sources, and then met with each other to discuss them until consensus was reached. Sources of variation were categorized as environmental (clinic staffing and clinic pace), social (perception of health information technology and real-time use with patients), or technical (computer access and information access). Examples of sources of variation within each of the categories are described and discussed in terms of impact on clinical workflow. As technologies are implemented, barriers to use become visible over time as users struggle to adapt workflow and work practices to accommodate new technologies. Each source of variability identified has implications for the effective design and implementation of useful health information technology. Accommodating moderate variability in workflow is anticipated to avoid brittle and inflexible workflow designs, while also avoiding unnecessary complexity for implementers and users.

  12. Microbial Biofilms and Breast Tissue Expanders

    Directory of Open Access Journals (Sweden)

    Melissa J. Karau

    2013-01-01

    Full Text Available We previously developed and validated a vortexing-sonication technique for detection of biofilm bacteria on the surface of explanted prosthetic joints. Herein, we evaluated this technique for diagnosis of infected breast tissue expanders and used it to assess colonization of breast tissue expanders. From April 2008 to December 2011, we studied 328 breast tissue expanders at Mayo Clinic, Rochester, MN, USA. Of seven clinically infected breast tissue expanders, six (85.7% had positive cultures, one of which grew Propionibacterium species. Fifty-two of 321 breast tissue expanders (16.2%, 95% CI, 12.3–20.7% without clinical evidence of infection also had positive cultures, 45 growing Propionibacterium species and ten coagulase-negative staphylococci. While vortexing-sonication can detect clinically infected breast tissue expanders, 16 percent of breast tissue expanders appear to be asymptomatically colonized with normal skin flora, most commonly, Propionibacterium species.

  13. Biological and Clinical Implications of Comorbidities in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Jose A. Santiago

    2017-12-01

    Full Text Available A wide spectrum of comorbidities has been associated with Parkinson’s disease (PD, a progressive neurodegenerative disease that affects more than seven million people worldwide. Emerging evidence indicates that chronic diseases including diabetes, depression, anemia and cancer may be implicated in the pathogenesis and progression of PD. Recent epidemiological studies suggest that some of these comorbidities may increase the risk of PD and precede the onset of motor symptoms. Further, drugs to treat diabetes and cancer have elicited neuroprotective effects in PD models. Nonetheless, the mechanisms underlying the occurrence of these comorbidities remain elusive. Herein, we discuss the biological and clinical implications of comorbidities in the pathogenesis, progression, and clinical management, with an emphasis on personalized medicine applications for PD.

  14. Expanding Pharmacist Services in Québec: A Health Reform Analysis of Bill 41 and its Implications for Equity in Financing Care

    Directory of Open Access Journals (Sweden)

    Renée Carter

    2014-12-01

    Full Text Available On 8 December 2011, Québec’s Minister of Health and Social Services amended the province’s Pharmacy Act by introducing Bill 41 to expand pharmacists’ role in patient care. Québec is the only Canadian province with a legal mandate for prescription drug insurance coverage for all residents, with public coverage offered only to those who do not have access to private health insurance through their employer. Bill 41 aims to increase access to health care and reduce physician wait times by extending the scope of pharmacist services to mirror that of physicians (e.g., modify the form of the medication and its dosage. The reform is currently pending due to disputes between the Ministry of Health and Social Services and the Quebec Association of Pharmacy Owners over remuneration for pharmacists. Should Bill 41 come into force, it is unclear whether the expansion of pharmacists’ roles, which in principle would duplicate physician services, should be considered part of the public basket of medically necessary care. Current negotiations suggest that only those with public coverage will also be covered for expanded services thereby placing equity of finance for those with private insurance in question.

  15. Structure and diagnosis of adult attention-deficit/hyperactivity disorder: analysis of expanded symptom criteria from the Adult ADHD Clinical Diagnostic Scale.

    Science.gov (United States)

    Kessler, Ronald C; Green, Jennifer Greif; Adler, Lenard A; Barkley, Russell A; Chatterji, Somnath; Faraone, Stephen V; Finkelman, Matthew; Greenhill, Laurence L; Gruber, Michael J; Jewell, Mark; Russo, Leo J; Sampson, Nancy A; Van Brunt, David L

    2010-11-01

    Controversy exists about the appropriate criteria for a diagnosis of adult attention-deficit/hyperactivity disorder (ADHD). To examine the structure and symptoms most predictive of DSM-IV adult ADHD. The data are from clinical interviews in enriched subsamples of the National Comorbidity Survey Replication (n = 131) and a survey of a large managed health care plan (n = 214). The physician-administered Adult ADHD Clinical Diagnostic Scale (ACDS) was used to assess childhood ADHD and expanded symptoms of current adult ADHD. Analyses examined the stability of symptoms from childhood to adulthood, the structure of adult ADHD, and the adult symptoms most predictive of current clinical diagnoses. The ACDS was administered telephonically by clinical research interviewers with extensive experience in the diagnosis and treatment of adult ADHD. An enriched sample of community respondents. Diagnoses of DSM-IV /ACDS adult ADHD. Almost half of the respondents (45.7%) who had childhood ADHD continued to meet the full DSM-IV criteria for current adult ADHD, with 94.9% of these patients having current attention-deficit disorder and 34.6% having current hyperactivity disorder. Adult persistence was much greater for inattention than for hyperactivity/impulsivity. Additional respondents met the full criteria for current adult ADHD despite not having met the full childhood criteria. A 3-factor structure of adult symptoms included executive functioning (EF), inattention/hyperactivity, and impulsivity. Stepwise logistic regression found EF problems to be the most consistent and discriminating predictors of adult DSM-IV /ACDS ADHD. These findings document the greater persistence of inattentive than of hyperactive/impulsive childhood symptoms of ADHD in adulthood but also show that inattention is not specific to ADHD because it is strongly associated with other adult mental disorders. In comparison, EF problems are more specific and consistently important predictors of DSM-IV adult ADHD

  16. From clinical practice guidelines, to clinical guidance in practice - implications for design of computerized guidance

    DEFF Research Database (Denmark)

    Lyng, Karen Marie

    2010-01-01

    . The transformation from protocols was executed according to a standard operating procedure. Each activity type had a standardized template ensuring uniformity across second order guiding artifacts within a clinic. The guiding artifacts were multi-functional and a wide variety of standardized graphical attributes...

  17. Early and long-term clinical and radiological follow-up results of expanded-polytetrafluoroethylene-covered stent-grafts for transjugular intrahepatic portosystemic shunt procedures

    Energy Technology Data Exchange (ETDEWEB)

    Maleux, Geert; Heye, Sam; Thijs, Maria; Wilms, Guy [University Hospitals Gasthuisberg, Department of Radiology, Leuven (Belgium); Nevens, Frederik; Verslype, Chris [University Hospitals Gasthuisberg, Department of Hepatology, Leuven (Belgium); Wilmer, Alexander [University Hospitals Gasthuisberg, Department of Medical Intensive Care Unit, Leuven (Belgium)

    2004-10-01

    The purpose of this study was to assess the therapeutic efficacy and immediate and long-term safety of expanded-tetrafluoroethylene covered stent-grafts for transjugular intrahepatic portosystemic shunts in patients with portal hypertension-related complications. A cohort of 56 patients suffering from severe portal hypertension-related complications underwent implantation of an expanded-polytetrafluoroethylene-covered stent-graft. All patients suffered from severe liver cirrhosis graded Child-Pugh A (n=8; 16%), B (n=13; 21%) or C (n=35; 63%). In 44 patients, the stent-graft was placed during the initial TIPS procedure (de novo TIPS); in the other 12 patients, the stent-graft was placed to repermeabilize the previously placed bare stent (TIPS revision). Follow-up was performed with clinical assessment, duplex ultrasound and, if abnormal or inconclusive, with invasive venography and pressure measurements. Per- en immediate post-procedural complications occurred in four patients (4/56, 7%). None of them was lethal. During follow-up, stent occlusion appeared in one patient and stenosis in two; no recurrence of bleeding was noted in all patients treated for variceal bleeding (n=28), and 24 of the 28 patients (86%) suffering from refractory ascites and/or hepatic hydrothorax were free of regular paracenteses and/or drainage of pleural effusion after shunt creation. The 30-day and global mortality for the total study population (n=56) was, respectively, 7% (n=4) and 28.5% (n=16). In the patient subgroup with variceal bleeding (n=28), 30-day mortality was 3.5% (n=1) and global mortality 14.2% (n=4). In the ascites and/or hydrothorax subgroup (n=28), 8.1% (n=3) mortality at 30 days was found and global mortality was 32.4% (n=12). In 10 patients of the 56 studied patients (18%), isolated hepatic encephalopathy occurred, which was lethal in 4 (Child C) patients (7%). Three of these four patients died within the 1st month after TIPS placement. A very high primary patency rate

  18. UNMASKING MASKED HYPERTENSION: PREVALENCE, CLINICAL IMPLICATIONS, DIAGNOSIS, CORRELATES, AND FUTURE DIRECTIONS

    Science.gov (United States)

    Peacock, James; Diaz, Keith M.; Viera, Anthony J.; Schwartz, Joseph E.; Shimbo, Daichi

    2014-01-01

    ‘Masked hypertension’ is defined as having non-elevated clinic blood pressure (BP) with elevated out-of-clinic average BP, typically determined by ambulatory BP monitoring. Approximately 15–30% of adults with non-elevated clinic BP have masked hypertension. Masked hypertension is associated with increased risks of cardiovascular morbidity and mortality compared to sustained normotension (non-elevated clinic and ambulatory BP), which is similar to or approaching the risk associated with sustained hypertension (elevated clinic and ambulatory BP). The confluence of increased cardiovascular risk and a failure to be diagnosed by the conventional approach of clinic BP measurement makes masked hypertension a significant public health concern. However, many important questions remain. First, the definition of masked hypertension varies across studies. Further, the best approach in the clinical setting to exclude masked hypertension also remains unknown. It is unclear whether home BP monitoring is an adequate substitute for ambulatory BP monitoring in identifying masked hypertension. Few studies have examined the mechanistic pathways that may explain masked hypertension. Finally, scarce data are available on the best approach to treating individuals with masked hypertension. Herein, we review the current literature on masked hypertension including definition, prevalence, clinical implications, special patient populations, correlates, issues related to diagnosis, treatment, and areas for future research. PMID:24573133

  19. Information-seeking behavior of nursing students and clinical nurses: implications for health sciences librarians.

    Science.gov (United States)

    Dee, Cheryl; Stanley, Ellen E

    2005-04-01

    This research was conducted to provide new insights on clinical nurses' and nursing students' current use of health resources and libraries and deterrents to their retrieval of electronic clinical information, exploring implications from these findings for health sciences librarians. Questionnaires, interviews, and observations were used to collect data from twenty-five nursing students and twenty-five clinical nurses. Nursing students and clinical nurses were most likely to rely on colleagues and books for medical information, while other resources they frequently cited included personal digital assistants, electronic journals and books, and drug representatives. Significantly more nursing students than clinical nurses used online databases, including CINAHL and PubMed, to locate health information, and nursing students were more likely than clinical nurses to report performing a database search at least one to five times a week. Nursing students made more use of all available resources and were better trained than clinical nurses, but both groups lacked database-searching skills. Participants were eager for more patient care information, more database training, and better computer skills; therefore, health sciences librarians have the opportunity to meet the nurses' information needs and improve nurses' clinical information-seeking behavior.

  20. Transportation conditions for prompt use of ex vivo expanded and freshly harvested clinical-grade bone marrow mesenchymal stromal/stem cells for bone regeneration.

    Science.gov (United States)

    Veronesi, Elena; Murgia, Alba; Caselli, Anna; Grisendi, Giulia; Piccinno, Maria Serena; Rasini, Valeria; Giordano, Rosaria; Montemurro, Tiziana; Bourin, Philippe; Sensebé, Luc; Rojewski, Markus T; Schrezenmeier, Hubert; Layrolle, Pierre; Ginebra, Maria Pau; Panaitescu, Carmen Bunu; Gómez-Barrena, Enrique; Catani, Fabio; Paolucci, Paolo; Burns, Jorge S; Dominici, Massimo

    2014-03-01

    Successful preliminary studies have encouraged a more translational phase for stem cell research. Nevertheless, advances in the culture of human bone marrow-derived mesenchymal stromal/stem cells (hBM-MSC) and osteoconductive qualities of combined biomaterials can be undermined if necessary cell transportation procedures prove unviable. We aimed at evaluating the effect of transportation conditions on cell function, including the ability to form bone in vivo, using procedures suited to clinical application. hBM-MSC expanded in current Good Manufacturing Practice (cGMP) facilities (cGMP-hBM-MSC) to numbers suitable for therapy were transported overnight within syringes and subsequently tested for viability. Scaled-down experiments mimicking shipment for 18 h at 4°C tested the influence of three different clinical-grade transportation buffers (0.9% saline alone or with 4% human serum albumin [HSA] from two independent sources) compared with cell maintenance medium. Cell viability after shipment was >80% in all cases, enabling evaluation of (1) adhesion to plastic flasks and hydroxyapatite tricalcium phosphate osteoconductive biomaterial (HA/β-TCP 3D scaffold); (2) proliferation rate; (3) ex vivo osteogenic differentiation in contexts of 2D monolayers on plastic and 3D HA/β-TCP scaffolds; and (4) in vivo ectopic bone formation after subcutaneous implantation of cells with HA/β-TCP scaffold into NOD/SCID mice. Von Kossa staining was used to assess ex vivo osteogenic differentiation in 3D cultures, providing a quantifiable test of 3D biomineralization ex vivo as a rapid, cost-effective potency assay. Near-equivalent capacities for cell survival, proliferation, and osteogenic differentiation were found for all transportation buffers. Moreover, cGMP-hBM-MSC transported from a production facility under clinical-grade conditions of 4% HSA in 0.9% saline to a destination 18 h away showed prompt adhesion to HA/β-TCP 3D scaffold and subsequent in vivo bone formation

  1. An analysis of clinical consultation activities in clinical chemistry: implications for transformation and resident training in chemical pathology.

    Science.gov (United States)

    Schmidt, Robert L; Garcia, Christopher A; Panlener, Jeanne; Ashwood, Edward R; Jackson, Brian R; Hussong, Jerry W

    2014-05-01

    Clinical consultation is a key role of pathologists. Many have advocated that pathologists expand their consulting activities to improve laboratory utilization. Although many have suggested that residency programs need to provide experience in clinical consultation, little has been written on the nature of consultation or on the methods of training. To characterize the content of consultations and to describe training in consultation in chemical pathology within the residency program at the University of Utah, Salt Lake City. Retrospective review of the consultation database for the period between July 2011 and July 2012. Residents performed an average of 159 consultations a month covering 276 topics during the course of a year. Each topic involved 1 or more specific tests. Eighty percent of the topics received fewer than 12 calls. The most common topics involved virus testing (eg, hepatitis B virus, hepatitis C virus, human immunodeficiency virus). Consultations most often involved test interpretation (53%), selection (38%), and performance characteristics (21%). Twenty-seven percent of consultations involved 2 or more consultation categories (eg, interpretation and performance). Consultation calls in chemical pathology are widely distributed across topics. Consultations most often involve test interpretation and selection. Methods to assess the effectiveness of consultations and resident teaching should be devised.

  2. Pharmacokinetic drug-drug interaction and their implication in clinical management

    Directory of Open Access Journals (Sweden)

    Palleria Caterina

    2013-01-01

    Full Text Available Drug-drug interactions (DDIs are one of the commonest causes of medication error in developed countries, particularly in the elderly due to poly-therapy, with a prevalence of 20-40%. In particular, poly-therapy increases the complexity of therapeutic management and thereby the risk of clinically important DDIs, which can both induce the development of adverse drug reactions or reduce the clinical efficacy. DDIs can be classify into two main groups: pharmacokinetic and pharmacodynamic. In this review, using Medline, PubMed, Embase, Cochrane library and Reference lists we searched articles published until June 30 2012, and we described the mechanism of pharmacokinetic DDIs focusing the interest on their clinical implications.

  3. Clinical implications of non-invasive measurement of central aortic blood pressure.

    Science.gov (United States)

    Stepień, Mariusz; Banach, Maciej; Jankowski, Piotr; Rysz, Jacek

    2010-11-01

    Central arterial systolic blood pressure is a very important factor in the pathophysiology of cardiovascular diseases. Central arterial pressure is a better predictor of cardiovascular risk than peripheral brachial blood pressure. Measurement of central blood pressure is useful for a diagnosis of spurious systolic hypertension in young people. Antihypertensive drugs have a different impact on central blood pressure, for example angiotensin converting enzyme inhibitors, antagonists of angiotensin II receptors, calcium channel blockers more effectively lower central blood pressure than betablockers, despite all of those drugs (including beta-blockers) having a similar impact on peripheral pressure. This mechanism may be responsible for the beneficial effect of some antihypertensive drugs on cardiovascular end points observed in clinical trials, despite a low peripheral hypotensive effect. However, further clinical trials are required to provide more evidence for the prognostic and therapeutic implications of the measurement of central blood pressure before adopting its routine application in clinical practice.

  4. Terror management theory applied clinically: implications for existential-integrative psychotherapy.

    Science.gov (United States)

    Lewis, Adam M

    2014-01-01

    Existential psychotherapy and Terror Management Theory (TMT) offer explanations for the potential psychological effects of death awareness, although their respective literatures bases differ in clarity, research, and implications for treating psychopathology. Existential therapy is often opaque to many therapists, in part due to the lack of consensus on what constitutes its practice, limited published practical examples, and few empirical studies examining its efficacy. By contrast, TMT has an extensive empirical literature base, both within social psychology and spanning multiple disciplines, although previously unexplored within clinical and counseling psychology. This article explores the implications of a proposed TMT integrated existential therapy (TIE), bridging the gap between disciplines in order to meet the needs of the aging population and current challenges facing existential therapists.

  5. Clinical implications of omics and systems medicine: focus on predictive and individualized treatment.

    Science.gov (United States)

    Benson, M

    2016-03-01

    Many patients with common diseases do not respond to treatment. This is a key challenge to modern health care, which causes both suffering and enormous costs. One important reason for the lack of treatment response is that common diseases are associated with altered interactions between thousands of genes, in combinations that differ between subgroups of patients who do or do not respond to a given treatment. Such subgroups, or even distinct disease entities, have been described recently in asthma, diabetes, autoimmune diseases and cancer. High-throughput techniques (omics) allow identification and characterization of such subgroups or entities. This may have important clinical implications, such as identification of diagnostic markers for individualized medicine, as well as new therapeutic targets for patients who do not respond to existing drugs. For example, whole-genome sequencing may be applied to more accurately guide treatment of neurodevelopmental diseases, or to identify drugs specifically targeting mutated genes in cancer. A study published in 2015 showed that 28% of hepatocellular carcinomas contained mutated genes that potentially could be targeted by drugs already approved by the US Food and Drug Administration. A translational study, which is described in detail, showed how combined omics, computational, functional and clinical studies could identify and validate a novel diagnostic and therapeutic candidate gene in allergy. Another important clinical implication is the identification of potential diagnostic markers and therapeutic targets for predictive and preventative medicine. By combining computational and experimental methods, early disease regulators may be identified and potentially used to predict and treat disease before it becomes symptomatic. Systems medicine is an emerging discipline, which may contribute to such developments through combining omics with computational, functional and clinical studies. The aims of this review are to provide

  6. Clinical Implications of Direct Immunofluorescence Findings in Patients With Ocular Mucous Membrane Pemphigoid.

    Science.gov (United States)

    Labowsky, Mary T; Stinnett, Sandra S; Liss, Jason; Daluvoy, Melissa; Hall, Russell P; Shieh, Christine

    2017-11-01

    To examine the clinical implications of positive or negative direct immunofluorescence biopsies (DIF) in patients with clinically typical ocular mucous membrane pemphigoid (MMP). Retrospective cohort study. The study population was patients with clinically typical ocular MMP disease with documented DIF results who were followed for at least 1 year at the Duke University multidisciplinary ocular MMP clinic. Data were collected by chart review and included patient demographics, clinical examination findings, and history of autoimmune disease and/or malignancy, as well as topical, systemic, and surgical treatments received. Main outcome measures included MMP Disease Area Index, Foster stages, proportion legally blind, duration of follow-up, and use of systemic immunosuppression and ocular procedures in treatment. In multivariable analysis restricted to 55 patients, patients with negative and positive biopsies were similar in the outcome measures; however, positive-biopsy patients were more likely to be treated with systemic immunosuppression and were followed for longer at our clinic. Patients with isolated ocular disease were also more likely to have negative biopsies compared to those who also had extraocular disease. Patients who had conjunctival biopsies were more likely to have a negative direct immunofluorescence result than patients with biopsies from other sites. We encourage clinicians and patients to consider treatment with systemic immunosuppression even in the absence of diagnosis confirmation by DIF. Furthermore, this study supports current standard of care to pursue a nonocular biopsy of normal-appearing, perilesional skin or oral mucosa when possible. Published by Elsevier Inc.

  7. Clinical errors and therapist discomfort with client disclosure of troublesome pornography use: Implications for clinical practice and error reduction.

    Science.gov (United States)

    Walters, Nathan T; Spengler, Paul M

    2016-09-01

    Mental health professionals are increasingly aware of the need for competence in the treatment of clients with pornography-related concerns. However, while researchers have recently sought to explore efficacious treatments for pornography-related concerns, few explorations of potential clinical judgment issues have occurred. Due to the sensitive, and at times uncomfortable, nature of client disclosures of sexual concerns within therapy, therapists are required to manage their own discomfort while retaining fidelity to treatment. The present paper explores clinician examples of judgment errors that may result from feelings of discomfort, and specifically from client use of pornography. Issues of potential bias, bias management techniques, and therapeutic implications are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  8. Spondylolysis and spondylolisthesis: prevalence of different forms of instability and clinical implications.

    Science.gov (United States)

    Niggemann, Pascal; Kuchta, Johannes; Beyer, Hans-Konrad; Grosskurth, D; Schulze, Thorsten; Delank, Karl-Stefan

    2011-10-15

    Imaging study with an evaluation of incidences and clinical correlation. To evaluate the incidence of 3 different types of instabilities in patients with spondylolysis or isthmic spondylolisthesis. Clinical findings are correlated with imaging findings, and the imaging findings are analyzed with regard to their clinical implications. Spondylolysis and isthmic spondylolisthesis are common disorders. An unstable slip is the most well-known form of instability, but other forms also exist. However, the incidence of these instabilities and their clinical implications are yet unclear. A total of 140 patients with 141 levels of spondylolysis identified by MRI (magnetic resonance imaging) were included in this study. Using positional MRI, the instability of the slip, an increased angular movement, and movement in the spondylolytic cleft were assessed. On the basis of clinical findings, the patients were classified as presenting with either radicular or nonradicular symptoms. The incidence of the instabilities was recorded and correlated with the incidence of radicular symptoms. Fifteen patients had an unstable slip (anterior instability); 35, an increased angular movement (angular instability); and 34 patients, a movement in the spondylolytic cleft (posterior instability). All forms of instability could be found together. No instability at all was found in 76 patients. Radicular symptoms were found significantly more often in patients with one or more of the described instabilities compared with patients without instability. All 3 described forms of instability are common in spondylolysis or isthmic spondylolisthesis and associated with radicular pain. This finding stresses the value of positional MRI in the evaluation of patients with spondylolysis and isthmic spondylolisthesis, especially if radicular symptoms are present.

  9. Clinical neurorehabilitation - implications of the Reorganization of Elementary Functions (REF) model

    DEFF Research Database (Denmark)

    Rytter, Hana Malá; Mogensen, Jesper

    as ‘function’. After brain injury, the EFs of the affected structure are irreversibly lost. However, during neurorehabilitation, the remaining EFs are reorganized into novel ASs. Creation and utilization of these novel ASs constitutes the basis for functional recovery. The degree to which recovery appears...... possible is a reflection of how successful the new ASs network is in achieving the surface phenomenon under consideration. This model has several implications relative to clinical neurorehabilitation. One of these concerns the degree to which results of rehabilitation training can be expected to generalize...

  10. [Sarcolemma tissue of prepubertal concealed penis: pathological characterization and clinical implication].

    Science.gov (United States)

    Chen, Hai-Tao; Yang, Xing-Hai

    2013-03-01

    To evaluate the histopathological characteristics and clinical implication of sarcolemma tissue in prepubertal concealed penis. After measurement of the penile length, 10 prepubertal children with congenital concealed penis underwent modified Devine's operation (treatment group), and another 10 normal prepubertal children received circumcision (control group). The anatomic features of the penile sarcolemma tissue was observed intraoperatively, and its fibrosis was evaluated by Masson trichrome staining. The penile length of the treatment group was significantly shorter than that of the control group preoperatively ([1.49 +/- 0.17 ] cm vs [4.26 +/- 0.23 ] cm, P penis, and the key to its management is drastic removal of all the fibrous sarcolemma tissue.

  11. The genetics of autism: key issues, recent findings, and clinical implications.

    Science.gov (United States)

    El-Fishawy, Paul; State, Matthew W

    2010-03-01

    Autism spectrum disorders (ASDs) are highly heritable. Gene discovery promises to help illuminate the pathophysiology of these syndromes, yielding opportunities for the development of novel treatments and understanding of their natural history. Although the underlying genetic architecture of ASDs is not yet known, the literature demonstrates that it is not a monogenic disorder with mendelian inheritance, rather a group of complex genetic syndromes with risk deriving from genetic variations in multiple genes. This article reviews the origins of the common versus rare variant debate, highlights recent findings in the field, and addresses the clinical implications of common and rare variant discoveries. Copyright 2010 Elsevier Inc. All rights reserved.

  12. The obesity paradox in the elderly: potential mechanisms and clinical implications.

    Science.gov (United States)

    Oreopoulos, Antigone; Kalantar-Zadeh, Kamyar; Sharma, Arya M; Fonarow, Gregg C

    2009-11-01

    The prevalence of overweight and obesity in the elderly has become a growing concern. Recent evidence indicates that in the elderly, obesity is paradoxically associated with a lower, not higher, mortality risk. Although obesity in the general adult population is associated with higher mortality, this relationship is unclear for persons of advanced age and has lead to great controversy regarding the relationship between obesity and mortality in the elderly, the definition of obesity in the elderly, and the need for its treatment in this population. This article examines the evidence on these controversial issues, explores potential explanations for these findings, discusses the clinical implications, and provides recommendations for further research in this area.

  13. Clinical and research implications of the evaluation of women's group therapy for anorgasmia: a review.

    Science.gov (United States)

    Kuriansky, J B; Sharpe, L

    1981-01-01

    This paper reviews some important clinical and research implications of studies which have evaluated the effectiveness of short-term behavioral group therapy for anorgasmia. Though formal research data on curative factors is very sparse, the experience of sharing within a group, and the focus on arousal seem consistent with treatment outcome; however, the emphasis on assertiveness and the woman-only approach may have countertherapeutic as well as therapeutic effects. A potentially important intervening variable is the woman's level of ego development. The use of certain assessment scales and criteria for success of treatment are critiqued, and recommendations made for further study.

  14. Imaging of Mucosal Inflammation: Current Technological Developments, Clinical Implications, and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Maximilian J. Waldner

    2017-10-01

    Full Text Available In recent years, various technological developments markedly improved imaging of mucosal inflammation in patients with inflammatory bowel diseases. Although technological developments such as high-definition-, chromo-, and autofluorescence-endoscopy led to a more precise and detailed assessment of mucosal inflammation during wide-field endoscopy, probe-based and stationary confocal laser microscopy enabled in vivo real-time microscopic imaging of mucosal surfaces within the gastrointestinal tract. Through the use of fluorochromes with specificity against a defined molecular target combined with endoscopic techniques that allow ultrastructural resolution, molecular imaging enables in vivo visualization of single molecules or receptors during endoscopy. Molecular imaging has therefore greatly expanded the clinical utility and applications of modern innovative endoscopy, which include the diagnosis, surveillance, and treatment of disease as well as the prediction of the therapeutic response of individual patients. Furthermore, non-invasive imaging techniques such as computed tomography, magnetic resonance imaging, scintigraphy, and ultrasound provide helpful information as supplement to invasive endoscopic procedures. In this review, we provide an overview on the current status of advanced imaging technologies for the clinical non-invasive and endoscopic evaluation of mucosal inflammation. Furthermore, the value of novel methods such as multiphoton microscopy, optoacoustics, and optical coherence tomography and their possible future implementation into clinical diagnosis and evaluation of mucosal inflammation will be discussed.

  15. Awareness in Alzheimer's disease and associated dementias: theoretical framework and clinical implications.

    Science.gov (United States)

    Clare, Linda; Marková, Ivana S; Roth, Ilona; Morris, Robin G

    2011-11-01

    Awareness can be defined as a reasonable or realistic perception or appraisal of a given aspect of one's situation, functioning or performance, or of the resulting implications, expressed explicitly or implicitly. Disturbances of awareness have significant implications for people with dementia and their caregivers. The construction of awareness has been extensively studied in dementia, but a lack of conceptual and methodological clarity in this area means that few clear findings have emerged. This article presents a framework for conceptualizing awareness in people with Alzheimer's disease and associated dementias that can guide research and influence practice. This article begins by considering the general concept of awareness and the ways in which neurological damage can place constraints on awareness. Within an integrative biopsychosocial model that acknowledges the influence of neurocognitive, psychological, and social variables on awareness, challenges for empirical research on awareness in dementia are addressed, and a 'levels of awareness' framework is presented within which awareness operates at four levels of increasing complexity, providing a means of differentiating among awareness phenomena. Approaches to mapping awareness phenomena are discussed, and directions for future research and clinical practice are outlined. The levels of awareness framework should act as a stimulus to further research in this area, resulting in a more coherent understanding of the nature of awareness deficits, the implications of these for people with dementia and their caregivers, and the possibilities for targeted and effective interventions.

  16. Reproductive tourism in Argentina: clinic accreditation and its implications for consumers, health professionals and policy makers.

    Science.gov (United States)

    Smith, Elise; Behrmann, Jason; Martin, Carolina; Williams-Jones, Bryn

    2010-08-01

    A subcategory of medical tourism, reproductive tourism has been the subject of much public and policy debate in recent years. Specific concerns include: the exploitation of individuals and communities, access to needed health care services, fair allocation of limited resources, and the quality and safety of services provided by private clinics. To date, the focus of attention has been on the thriving medical and reproductive tourism sectors in Asia and Eastern Europe; there has been much less consideration given to more recent 'players' in Latin America, notably fertility clinics in Chile, Brazil, Mexico and Argentina. In this paper, we examine the context-specific ethical and policy implications of private Argentinean fertility clinics that market reproductive services via the internet. Whether or not one agrees that reproductive services should be made available as consumer goods, the fact is that they are provided as such by private clinics around the world. We argue that basic national regulatory mechanisms are required in countries such as Argentina that are marketing fertility services to local and international publics. Specifically, regular oversight of all fertility clinics is essential to ensure that consumer information is accurate and that marketed services are safe and effective. It is in the best interests of consumers, health professionals and policy makers that the reproductive tourism industry adopts safe and responsible medical practices.

  17. PET/CT WITH 68Ga-PSMA IN PROSTATE CANCER: RADIOPHARMACEUTICAL BACKGROUND AND CLINICAL IMPLICATIONS.

    Science.gov (United States)

    Giovacchini, Giampiero; Giovannini, Elisabetta; Riondato, Mattia; Ciarmiello, Andrea

    2017-11-01

    In the last twenty years, positron emission tomography / computed tomography (PET/CT) with radiolabeled choline, represented the most powerful imaging modality for prostate cancer (PCa). However, the low positive detection rate of the technique for PSA PET/CT predicts PCa-specific survival, have not yet been investigated. Numerous clinical studies have been published, some of them with histopathological verification so that despite the recent introduction in the clinical field reliable estimation of sensitivity and specificity of 68Ga-PSMA PET/CT have been obtained through meta-analyses. Most clinical studies with PET/CT with 68Ga-PSMA are retrospective, single-institutional studies and in many cases include heterogeneous patient cohorts. Thus, multidisciplinary, well-throughout prospective trials are needed to better define the clinical implications of 68Ga-PSMA PET/CT in PCa patients. The increasing availability of positron emission tomography / magnetic resonance (PET/MR) hybrid devices promotes the use of this radiopharmaceutical especially at initial staging when identification of tumor localization and of extra-prostatic disease represent clinically relevant questions. PSMA cold ligands can also be labeled with beta emitters with good chemical stability so that 68Ga-PSMA PET/CT can be used to guide radiometabolic therapy of advanced metastatic PCa patients through 177Lu-labeled PSMA ligands. `. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Zone-dependent changes in human vertebral trabecular bone: clinical implications

    DEFF Research Database (Denmark)

    Thomsen, Jesper Skovhus; Ebbesen, Ebbe Nils; Mosekilde, Lis

    2002-01-01

    We have previously shown that there are pronounced age-related changes in human vertebral cancellous bone density and microarchitecture. However, the magnitude of these changes seemed to be dependent on zone location in the vertebral body-the central third vs. the areas adjacent to the endplates...... this was significant only for trabecular separation. The described differences might have significant clinical implications concerning quantitative computed tomography (QCT) scanning, X-ray analyses, and assessment of fracture liability in the human spine, but the underlying pathogenesis is still not known. This study...... shows that the human vertebral body can be described as two distinct zones with very specific age-related changes in density and microstructure. This zone-specificity is important for the correct interpretation of clinical data....

  19. Central Hyperexcitability in Chronic Musculoskeletal Pain: A Conceptual Breakthrough with Multiple Clinical Implications

    Directory of Open Access Journals (Sweden)

    Jan Lidbeck

    2002-01-01

    Full Text Available Recent investigations of dysfunctional pain processing in the central nervous system have contributed much knowledge about the development of chronic musculoskeletal pain. Many common chronic musculoskeletal pain syndromes - including regional myofascial pain syndromes, whiplash pain syndromes, refractory work-related neck-shoulder pain, certain types of chronic low back pain, fibromyalgia and others - may essentially be explained by abnormalities in central pain modulation. The growing awareness of dysfunctional central pain modulation may be a conceptual breakthrough leading to a better understanding of common chronic pain disorders. A new paradigm will have multiple clinical implications, including re-evaluation of clinical practice routines and rehabilitation methods, and will focus on controversial issues of medicolegal concern. The concept of dysfunctional central pain processing will also necessitate a mechanism-based classification of pain for the selection of individual treatment and rehabilitation programs for subgroups of patients with chronic musculoskeletal pain due to different pathophysiological mechanisms.

  20. The biology, function and clinical implications of exosomes in lung cancer.

    Science.gov (United States)

    Zhou, Li; Lv, Tangfeng; Zhang, Qun; Zhu, Qingqing; Zhan, Ping; Zhu, Suhua; Zhang, Jianya; Song, Yong

    2017-10-28

    Exosomes are 30-100 nm small membrane vesicles of endocytic origin that are secreted by all types of cells, and can also be found in various body fluids. Increasing evidence implicates that exosomes confer stability and can deliver their cargos such as proteins and nucleic acids to specific cell types, which subsequently serve as important messengers and carriers in lung carcinogenesis. Here, we describe the biogenesis and components of exosomes mainly in lung cancer, we summarize their function in lung carcinogenesis (epithelial mesenchymal transition, oncogenic cell transformation, angiogenesis, metastasis and immune response in tumor microenvironment), and importantly we focus on the clinical potential of exosomes as biomarkers and therapeutics in lung cancer. In addition, we also discuss current challenges that might impede the clinical use of exosomes. Further studies on the functional roles of exosomes in lung cancer requires thorough research. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Key issues in the management of patients with systemic lupus erythematosus: latest developments and clinical implications

    Science.gov (United States)

    Jordan, Natasha; D’Cruz, David

    2015-01-01

    Systemic lupus erythematous (SLE) is a chronic multisystem disease with significant associated morbidity and mortality. A deeper understanding of the pathogenesis of SLE has led to the development of biologic agents, primarily targeting B cells and others inhibiting costimulatory molecules, type I interferons and cytokines such as interleukin-6. Several of these agents have been studied in clinical trials; some have shown promise while others have yielded disappointing results. Economic and regulatory issues continue to hamper the availability of such therapies for SLE patients. With increasing recognition that recurrent flares of disease activity lead to long-term damage accrual, one of the most important recent developments in patient management has been the concept of treat-to-target in SLE while minimizing patient exposure to excessive corticosteroid and other immunosuppressive therapy. This article reviews these key issues in SLE management, outlining recent developments and clinical implications for patients. PMID:26622325

  2. Isolated persistent left superior vena cava: A case report and its clinical implications

    Directory of Open Access Journals (Sweden)

    Samarjit Bisoyi

    2017-01-01

    Full Text Available The venous anomaly of a persistent left superior vena cava (PLSVC affects 0.3%-0.5% of the general population. PLSVC with absent right superior vena cava, also termed as "isolated PLSVC," is an extremely rare venous anomaly. Almost half of the patients with isolated PLSVC have cardiac anomalies in the form of atrial septal defect, endocardial cushion defects, or tetralogy of Fallot. Isolated PLSVC is usually innocuous. Its discovery, however, has important clinical implications. It can pose clinical difficulties with central venous access, cardiothoracic surgeries, and pacemaker implantation. When it drains to the left atrium, it may create a right to left shunt. In this case report, we present the incidental finding of isolated PLSVC in a patient who underwent aortic valve replacement. Awareness about this condition and its variations is important to avoid complications.

  3. Adult Dental Health Survey 2009: implications of findings for clinical practice and oral health policy.

    Science.gov (United States)

    Watt, R G; Steele, J G; Treasure, E T; White, D A; Pitts, N B; Murray, J J

    2013-01-01

    This is the final paper in a series reporting on the results of the 2009 Adult Dental Health Survey. Since 1968 national adult surveys have been repeated every decade with broadly similar methods providing a unique overview of trends in oral health over a 40-year period. This paper aims to explore the implications for dentists and oral health policy of the key results from the Adult Dental Health Survey 2009. Although repeat, cross-sectional, epidemiological surveys provide very valuable data on trends in disease patterns, they do not provide answers to test causal relationships and therefore cannot identify the causes for the significant improvements in oral health over the last 40 years. Evidence would indicate, however, that broad societal shifts in population norms and behaviours, combined with changes in clinical diagnostic criteria, treatment planning and clinical procedures are the main reasons for the changes that have taken place. Key implications of the survey results include the need to monitor, support and maintain the good state of oral health of the increasing proportion of younger adults with relatively simple treatment needs. A smaller number of young and middle aged adults but a significant proportion of older adults will have far more complex treatment needs requiring advanced restorative and periodontal care. Future oral health policy will need to address oral health inequalities, encourage skill mix and promote and facilitate the dental profession to deliver appropriate and high quality care relevant to the needs of their local population.

  4. The Adolescent "Expanded Medical Home": School-Based Health Centers Partner with a Primary Care Clinic to Improve Population Health and Mitigate Social Determinants of Health.

    Science.gov (United States)

    Riley, Margaret; Laurie, Anna R; Plegue, Melissa A; Richarson, Caroline R

    2016-01-01

    Access to high-quality health care is a crucial social determinant of health. We describe the implementation of an "expanded medical home" partnering a primary care practice (the Ypsilanti Health Center [YHC]) with local school-based health centers (the Regional Alliance for Healthy Schools [RAHS]), and to assess whether this model improves access to and quality of care for shared patients. Using the Consolidated Framework for Implementation Research, we define the steps in, barriers to, and facilitating factors in implementing the expanded medical home model. Visits and quality measures were assessed for patients seen by YHC only versus YHC/RAHS at baseline and during the intervention. At baseline, patients seen at YHC/RAHS had higher compliance with most quality metrics compared with those seen at YHC only. The proportion of shared patients significantly increased because of the intervention (P < .001). Overall, patients seen in the expanded medical home had a higher likelihood of receiving quality metric services than patients in YHC only (odds ratio, 1.8; 95% confidence interval, 1.57-2.05) across all measures. Thoughtful and intentional implementation of an expanded medical home partnership between primary care physicians and school-based health centers increases the number of shared high-risk adolescent patients. Shared patients have improved compliance with quality measures, which may lead to long-term improved health equity. © Copyright 2016 by the American Board of Family Medicine.

  5. Dentoskeletal outcomes of a rapid maxillary expander with differential opening in patients with bilateral cleft lip and palate: A prospective clinical trial.

    Science.gov (United States)

    Garib, Daniela; Lauris, Rita De Cássia Moura Carvalho; Calil, Louise Resti; Alves, Arthur César De Medeiros; Janson, Guilherme; De Almeida, Araci Malagodi; Cevidanes, Lúcia Helena Soares; Lauris, José Roberto Pereira

    2016-10-01

    The purpose of this 2-arm parallel study was to evaluate the dentoskeletal effects of rapid maxillary expansion with differential opening (EDO) compared with the hyrax expander in patients with complete bilateral cleft lip and palate. A sample of patients with complete bilateral cleft lip and palate was prospectively and consecutively recruited. Eligibility criteria included participants in the mixed dentition with lip and palate repair performed during early childhood and maxillary arch constriction with a need for maxillary expansion before the alveolar bone graft procedure. The participants were consecutively divided into 2 study groups. The experimental and control groups comprised patients treated with rapid maxillary expansion using EDO and the hyrax expander, respectively. Cone-beam computed tomography examinations and digital dental models of the maxillary dental arches were obtained before expansion and 6 months postexpansion. Standardized cone-beam computed tomography coronal sections were used for measuring maxillary transverse dimensions and posterior tooth inclinations. Digital dental models were used for assessing maxillary dental arch widths, arch perimeters, arch lengths, palatal depths, and posterior tooth inclinations. Blinding was used only during outcome assessment. The chi-square test was used to compare the sex ratios between groups (P variables before expansion. No significant differences were found between the EDO and the hyrax expander groups regarding skeletal changes. The EDO promoted significantly greater increases of intercanine width (difference, 3.63 mm) and smaller increases in canine buccal tipping than the conventional hyrax expander. No serious harm was observed other than transitory variable pressure sensations on the maxillary alveolar process in both groups. The EDO produced skeletal changes similar to the conventional hyrax expander. The differential expander is an adequate alternative to conventional rapid maxillary

  6. Intra-tumor heterogeneity in head and neck cancer and its clinical implications

    Directory of Open Access Journals (Sweden)

    Edmund A. Mroz

    2016-06-01

    Full Text Available The presence of heritable differences among cancer cells within a tumor, called intra-tumor genetic heterogeneity, has long been suspected of playing a role in poor responses to therapy. Research over the past decade has documented the existence of such heterogeneity within tumors of individual patients and documented its potential clinical significance. The research methods for identifying this heterogeneity were not, however, readily adaptable to widespread clinical application. After a brief review of this background, we describe the development of a measure of intra-tumor genetic heterogeneity, based on whole-exome sequencing of individual tumor samples, that could be applied to biopsy specimens in a clinical setting. This measure has now been used in head and neck squamous cell carcinoma (HNSCC to document, for the first time, a relation of high intra-tumor genetic heterogeneity to shorter overall survival in a large, multi-institutional study. The implications of heterogeneity for research and clinical care thus now need to be addressed. Keywords: Head and neck squamous cell carcinoma, Intra-tumor genetic heterogeneity, Next-generation sequencing, Targeted therapy

  7. Clinical Implications of Associations between Headache and Gastrointestinal Disorders: A Study Using the Hallym Smart Clinical Data Warehouse

    Directory of Open Access Journals (Sweden)

    Sang-Hwa Lee

    2017-10-01

    gastritis was significantly higher in patients with TTH compared with controls (p < 0.001. However, no differences were observed in the prevalence of HP infection between the groups.ConclusionThe observed association in this study may suggest that primary headache sufferers who experience migraines or TTH are more prone to GI disorders, which may have various clinical implications. Further research concerning the etiology of the association between headaches and GI disorders is warranted.

  8. Clinical Implications of Associations between Headache and Gastrointestinal Disorders: A Study Using the Hallym Smart Clinical Data Warehouse.

    Science.gov (United States)

    Lee, Sang-Hwa; Lee, Jae-June; Kwon, Youngsuk; Kim, Jong-Ho; Sohn, Jong-Hee

    2017-01-01

    higher in patients with TTH compared with controls ( p  < 0.001). However, no differences were observed in the prevalence of HP infection between the groups. The observed association in this study may suggest that primary headache sufferers who experience migraines or TTH are more prone to GI disorders, which may have various clinical implications. Further research concerning the etiology of the association between headaches and GI disorders is warranted.

  9. Helical distribution of hypertrophy in patients with hypertrophic cardiomyopathy: prevalence and clinical implications.

    Science.gov (United States)

    Viliani, Dafne; Pozo, Eduardo; Aguirre, Norma; Cecconi, Alberto; Olivera, María J; Caballero, Paloma; Jiménez-Borreguero, Luis J; Alfonso, Fernando

    2017-11-01

    Recently a novel pattern of helical distribution of hypertrophy has been described in patients with hypertrophic cardiomyopathy (HCM). Our aim was to determine its prevalence and potential implications in an unselected cohort. One-hundred- and eight consecutive patients diagnosed with HCM by cardiac magnetic resonance (CMR) were included (median clinical follow up of 1718 days). All clinical and complementary test information was prospectively collected. The presence of a helical pattern was assessed by a simple measurement of the maximal left ventricle (LV) wall thickness (LVWT) for each of the 17 classical LV segments and it was classified in one of three types according to its extension. A helical distribution was detected in 58% of patients, and was associated to a higher incidence of left ventricular outflow tract obstruction (LVOT; 35% vs. 10%; p = 0.005) and systolic anterior motion of the mitral valve (SAM; 30% vs. 13%, p = 0.053). No significant difference in the maximal LVWT was observed. However, the presence of a helical pattern showed a significant association with non sustained ventricular tachycardia (NSVT; 22% vs. 7%; p = 0.029) and was associated to a higher risk of sudden cardiac death (SCD) calculated with the European society of cardiology (ESC) calculator (p = 0.006). Notably, patients with a more extense spiral had a higher incidence of heart failure (75% vs. 34%, p = 0.012) and all-cause death (21 vs. 3%, p = 0.049). A helical pattern is frequent in HCM and can be readily assessed on CMR standard cine sequences. In conclusion, a helical pattern carries negative clinical implications and is associated to a higher estimated risk of SCD.

  10. A Sound Therapy-Based Intervention to Expand the Auditory Dynamic Range for Loudness among Persons with Sensorineural Hearing Losses: A Randomized Placebo-Controlled Clinical Trial

    Science.gov (United States)

    Formby, Craig; Hawley, Monica L.; Sherlock, LaGuinn P.; Gold, Susan; Payne, JoAnne; Brooks, Rebecca; Parton, Jason M.; Juneau, Roger; Desporte, Edward J.; Siegle, Gregory R.

    2015-01-01

    The primary aim of this research was to evaluate the validity, efficacy, and generalization of principles underlying a sound therapy–based treatment for promoting expansion of the auditory dynamic range (DR) for loudness. The basic sound therapy principles, originally devised for treatment of hyperacusis among patients with tinnitus, were evaluated in this study in a target sample of unsuccessfully fit and/or problematic prospective hearing aid users with diminished DRs (owing to their elevated audiometric thresholds and reduced sound tolerance). Secondary aims included: (1) delineation of the treatment contributions from the counseling and sound therapy components to the full-treatment protocol and, in turn, the isolated treatment effects from each of these individual components to intervention success; and (2) characterization of the respective dynamics for full, partial, and control treatments. Thirty-six participants with bilateral sensorineural hearing losses and reduced DRs, which affected their actual or perceived ability to use hearing aids, were enrolled in and completed a placebo-controlled (for sound therapy) randomized clinical trial. The 2 × 2 factorial trial design was implemented with or without various assignments of counseling and sound therapy. Specifically, participants were assigned randomly to one of four treatment groups (nine participants per group), including: (1) group 1—full treatment achieved with scripted counseling plus sound therapy implemented with binaural sound generators; (2) group 2—partial treatment achieved with counseling and placebo sound generators (PSGs); (3) group 3—partial treatment achieved with binaural sound generators alone; and (4) group 4—a neutral control treatment implemented with the PSGs alone. Repeated measurements of categorical loudness judgments served as the primary outcome measure. The full-treatment categorical-loudness judgments for group 1, measured at treatment termination, were

  11. A Sound Therapy-Based Intervention to Expand the Auditory Dynamic Range for Loudness among Persons with Sensorineural Hearing Losses: A Randomized Placebo-Controlled Clinical Trial.

    Science.gov (United States)

    Formby, Craig; Hawley, Monica L; Sherlock, LaGuinn P; Gold, Susan; Payne, JoAnne; Brooks, Rebecca; Parton, Jason M; Juneau, Roger; Desporte, Edward J; Siegle, Gregory R

    2015-05-01

    The primary aim of this research was to evaluate the validity, efficacy, and generalization of principles underlying a sound therapy-based treatment for promoting expansion of the auditory dynamic range (DR) for loudness. The basic sound therapy principles, originally devised for treatment of hyperacusis among patients with tinnitus, were evaluated in this study in a target sample of unsuccessfully fit and/or problematic prospective hearing aid users with diminished DRs (owing to their elevated audiometric thresholds and reduced sound tolerance). Secondary aims included: (1) delineation of the treatment contributions from the counseling and sound therapy components to the full-treatment protocol and, in turn, the isolated treatment effects from each of these individual components to intervention success; and (2) characterization of the respective dynamics for full, partial, and control treatments. Thirty-six participants with bilateral sensorineural hearing losses and reduced DRs, which affected their actual or perceived ability to use hearing aids, were enrolled in and completed a placebo-controlled (for sound therapy) randomized clinical trial. The 2 × 2 factorial trial design was implemented with or without various assignments of counseling and sound therapy. Specifically, participants were assigned randomly to one of four treatment groups (nine participants per group), including: (1) group 1-full treatment achieved with scripted counseling plus sound therapy implemented with binaural sound generators; (2) group 2-partial treatment achieved with counseling and placebo sound generators (PSGs); (3) group 3-partial treatment achieved with binaural sound generators alone; and (4) group 4-a neutral control treatment implemented with the PSGs alone. Repeated measurements of categorical loudness judgments served as the primary outcome measure. The full-treatment categorical-loudness judgments for group 1, measured at treatment termination, were significantly

  12. Measuring attachment and parental bonding in psychosis and its clinical implications.

    Science.gov (United States)

    Mathews, S; Onwumere, J; Bissoli, S; Ruggeri, M; Kuipers, E; Valmaggia, L

    2016-04-01

    Attachment theory proposes that psychological functioning and affect regulations are influenced by the attachment we form with others. Early relationships with parents or caregivers lay the foundations for attachment styles. These styles are proposed to influence how we relate to others during our life can be modified by the relationships and events we experience in our lifespan. A secure attachment style is associated with a capacity to manage distress, comfort with autonomy and the ability to form relationships with others, whereas insecure attachment can lead to dysfunctional relationships, emotional and behaviour avoidance. Attachment theory provides a useful framework to inform our understanding of relationship difficulties in people with psychosis. This paper aims to complement recent systematic reviews by providing an overview of attachment theory, its application to psychosis, including an understanding of measurement issues and the clinical implications offered. A narrative review was completed of the measures of attachment and parental bonding in psychosis. Its clinical implications are also discussed. The paper also explores the link between insecure attachment styles and illness course, social functioning and symptomatology. The following questions are addressed: What are the key attachment measures that have been used within the attachment and psychosis literature? What are the results of studies that have measured attachment or parental bonding in psychosis and what clinical implications can we derive from it? What are some of the key questions for future research from these findings in relation to the onset of psychosis research field? The most commonly used measures of attachment in psychosis research are reviewed. Self-report questionnaires and semi-structured interviews have mainly been used to examine attachment styles in adult samples and in recent years comprise a measure specifically developed for a psychosis group. The review suggests that

  13. Practitioner Review: Multilingualism and neurodevelopmental disorders - an overview of recent research and discussion of clinical implications.

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    Uljarević, Mirko; Katsos, Napoleon; Hudry, Kristelle; Gibson, Jenny L

    2016-11-01

    Language and communication skills are essential aspects of child development, which are often disrupted in children with neurodevelopmental disorders. Cutting edge research in psycholinguistics suggests that multilingualism has potential to influence social, linguistic and cognitive development. Thus, multilingualism has implications for clinical assessment, diagnostic formulation, intervention and support offered to families. We present a systematic review and synthesis of the effects of multilingualism for children with neurodevelopmental disorders and discuss clinical implications. We conducted systematic searches for studies on multilingualism in neurodevelopmental disorders. Keywords for neurodevelopmental disorders were based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition categories as follows; Intellectual Disabilities, Communication Disorders, Autism Spectrum Disorder (ASD), Attention-Deficit/Hyperactivity Disorder, Specific Learning Disorder, Motor Disorders, Other Neurodevelopmental Disorders. We included only studies based on empirical research and published in peer-reviewed journals. Fifty studies met inclusion criteria. Thirty-eight studies explored multilingualism in Communication Disorders, 10 in ASD and two in Intellectual Disability. No studies on multilingualism in Specific Learning Disorder or Motor Disorders were identified. Studies which found a disadvantage for multilingual children with neurodevelopmental disorders were rare, and there appears little reason to assume that multilingualism has negative effects on various aspects of functioning across a range of conditions. In fact, when considering only those studies which have compared a multilingual group with developmental disorders to a monolingual group with similar disorders, the findings consistently show no adverse effects on language development or other aspects of functioning. In the case of ASD, a positive effect on communication and social functioning has

  14. Clinical Features, Molecular Heterogeneity, and Prognostic Implications in YARS2-Related Mitochondrial Myopathy.

    Science.gov (United States)

    Sommerville, Ewen W; Ng, Yi Shiau; Alston, Charlotte L; Dallabona, Cristina; Gilberti, Micol; He, Langping; Knowles, Charlotte; Chin, Sophie L; Schaefer, Andrew M; Falkous, Gavin; Murdoch, David; Longman, Cheryl; de Visser, Marianne; Bindoff, Laurence A; Rawles, John M; Dean, John C S; Petty, Richard K; Farrugia, Maria E; Haack, Tobias B; Prokisch, Holger; McFarland, Robert; Turnbull, Douglass M; Donnini, Claudia; Taylor, Robert W; Gorman, Gráinne S

    2017-06-01

    YARS2 mutations have been associated with a clinical triad of myopathy, lactic acidosis, and sideroblastic anemia in predominantly Middle Eastern populations. However, the identification of new patients expands the clinical and molecular spectrum of mitochondrial disorders. To review the clinical, molecular, and genetic features of YARS2-related mitochondrial disease and to demonstrate a new Scottish founder variant. An observational case series study was conducted at a national diagnostic center for mitochondrial disease in Newcastle upon Tyne, England, and review of cases published in the literature. Six adults in a well-defined mitochondrial disease cohort and 11 additional cases described in the literature were identified with YARS2 variants between January 1, 2000, and January 31, 2015. The spectrum of clinical features and disease progression in unreported and reported patients with pathogenic YARS2 variants. Seventeen patients (median [interquartile range] age at onset, 1.5 [9.8] years) with YARS2-related mitochondrial myopathy were identified. Fifteen individuals (88%) exhibited an elevated blood lactate level accompanied by generalized myopathy; only 12 patients (71%) manifested with sideroblastic anemia. Hypertrophic cardiomyopathy (9 [53%]) and respiratory insufficiency (8 [47%]) were also prominent clinical features. Central nervous system involvement was rare. Muscle studies showed global cytochrome-c oxidase deficiency in all patients tested and severe, combined respiratory chain complex activity deficiencies. Microsatellite genotyping demonstrated a common founder effect shared between 3 Scottish patients with a p.Leu392Ser variant. Immunoblotting from fibroblasts and myoblasts of an affected Scottish patient showed normal YARS2 protein levels and mild respiratory chain complex defects. Yeast modeling of novel missense YARS2 variants closely correlated with the severity of clinical phenotypes. The p.Leu392Ser variant is likely a newly identified

  15. Clinical and public health implications of acute and early HIV detection and treatment: a scoping review

    Science.gov (United States)

    Rutstein, Sarah E.; Ananworanich, Jintanat; Fidler, Sarah; Johnson, Cheryl; Sanders, Eduard J.; Sued, Omar; Saez-Cirion, Asier; Pilcher, Christopher D.; Fraser, Christophe; Cohen, Myron S.; Vitoria, Marco; Doherty, Meg; Tucker, Joseph D.

    2017-01-01

    Abstract Introduction: The unchanged global HIV incidence may be related to ignoring acute HIV infection (AHI). This scoping review examines diagnostic, clinical, and public health implications of identifying and treating persons with AHI. Methods: We searched PubMed, in addition to hand-review of key journals identifying research pertaining to AHI detection and treatment. We focused on the relative contribution of AHI to transmission and the diagnostic, clinical, and public health implications. We prioritized research from low- and middle-income countries (LMICs) published in the last fifteen years. Results and Discussion: Extensive AHI research and limited routine AHI detection and treatment have begun in LMIC. Diagnostic challenges include ease-of-use, suitability for application and distribution in LMIC, and throughput for high-volume testing. Risk score algorithms have been used in LMIC to screen for AHI among individuals with behavioural and clinical characteristics more often associated with AHI. However, algorithms have not been implemented outside research settings. From a clinical perspective, there are substantial immunological and virological benefits to identifying and treating persons with AHI – evading the irreversible damage to host immune systems and seeding of viral reservoirs that occurs during untreated acute infection. The therapeutic benefits require rapid initiation of antiretrovirals, a logistical challenge in the absence of point-of-care testing. From a public health perspective, AHI diagnosis and treatment is critical to: decrease transmission via viral load reduction and behavioural interventions; improve pre-exposure prophylaxis outcomes by avoiding treatment initiation for HIV-seronegative persons with AHI; and, enhance partner services via notification for persons recently exposed or likely transmitting. Conclusions: There are undeniable clinical and public health benefits to AHI detection and treatment, but also substantial

  16. The asthma–COPD overlap syndrome: how is it defined and what are its clinical implications?

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    van den Berge M

    2016-02-01

    Full Text Available Maarten van den Berge,1,2 René Aalbers,31Department of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, 2GRIAC Research Institute, University Medical Center Groningen, University of Groningen, 3Department of Pulmonary Diseases, Martini Hospital, Groningen, the Netherlands Abstract: It is increasingly recognized that both asthma and chronic obstructive pulmonary disease (COPD are heterogeneous diseases with a large inter-individual variability with respect to their clinical expression, disease progression, and responsiveness to the available treatments. The introduction of asthma–COPD overlap syndrome (ACOS may lead to a better clinical characterization and improved treatment of patients with obstructive airways disease. However, it is still in its early phase and several improvements will have to be made. First, a clear definition of ACOS and preferably also its sub-phenotypes, eg, asthma–ACOS and COPD–ACOS, is urgently needed. That would also allow researchers to design clinical studies in well-defined patients. The latter is important since the interpretation of clinical studies performed so far is hampered by the use of many different definitions of ACOS. Second, future studies are needed to investigate the role of state-of-the-art techniques such as computed tomography, genetics, and genomics in the phenotyping of patients with obstructive airways disease, ie, asthma, COPD, and ACOS. Third, longitudinal studies are now needed to better define the clinical implications of ACOS with respect to the long-term outcome and treatment of ACOS and its sub-phenotypes compared to only asthma or COPD. Keywords: ACOS, asthma, COPD, inflammation, remodeling, overlap phenotype

  17. Opiate Analgesics as Negative Modulators of Adult Hippocampal Neurogenesis: Potential Implications in Clinical Practice

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    Valeria Bortolotto

    2017-05-01

    Full Text Available During the past decade, studies of the mechanisms and functional implications of adult hippocampal neurogenesis (ahNG have significantly progressed. At present, it is proposed that adult born neurons may contribute to a variety of hippocampal-related functions, including specific cognitive aspects and mood regulation. Several groups focussed on the factors that regulate proliferation and fate determination of adult neural stem/progenitor cells (NSC/NPC, including clinically relevant drugs. Opiates were the first drugs shown to negatively impact neurogenesis in the adult mammalian hippocampus. Since that initial report, a vast array of information has been collected on the effect of opiate drugs, by either modulating proliferation of stem/progenitor cells or interfering with differentiation, maturation and survival of adult born neurons. The goal of this review is to critically revise the present state of knowledge on the effect of opiate drugs on the different developmental stages of ahNG, as well as the possible underlying mechanisms. We will also highlight the potential impact of deregulated hippocampal neurogenesis on patients undergoing chronic opiate treatment. Finally, we will discuss the differences in the negative impact on ahNG among clinically relevant opiate drugs, an aspect that may be potentially taken into account to avoid long-term deregulation of neural plasticity and its associated functions in the clinical practice.

  18. Frequency and clinical implications of the isolation of rare nontuberculous mycobacteria.

    Science.gov (United States)

    Kim, Junghyun; Seong, Moon-Woo; Kim, Eui-Chong; Han, Sung Koo; Yim, Jae-Joon

    2015-01-09

    To date, more than 125 species of nontuberculous mycobacteria (NTM) have been identified. In this study, we investigated the frequency and clinical implication of the rarely isolated NTM from respiratory specimens. Patients with NTM isolated from their respiratory specimens between July 1, 2010 and June 31, 2012 were screened for inclusion. Rare NTM were defined as those NTM not falling within the group of eight NTM species commonly identified at our institution: Mycobacterium avium, M. intracellulare, M. abscessus, M. massiliense, M. fortuitum, M. kansasii, M. gordonae, and M. peregrinum. Clinical, radiographic and microbiological data from patients with rare NTM were reviewed and analyzed. During the study period, 73 rare NTM were isolated from the respiratory specimens of 68 patients. Among these, M. conceptionense was the most common (nine patients, 12.3%). The median age of the 68 patients with rare NTM was 68 years, while 39 of the patients were male. Rare NTM were isolated only once in majority of patient (64 patients, 94.1%). Among the four patients from whom rare NTM were isolated two or more times, only two showed radiographic aggravation caused by rare NTM during the follow-up period. Most of the rarely identified NTM species were isolated from respiratory specimens only once per patient, without concomitant clinical aggravation. Clinicians could therefore observe such patients closely without invasive work-ups or treatment, provided the patients do not have decreased host immunity towards mycobacteria.

  19. Transporter-Mediated Disposition of Opioids: Implications for Clinical Drug Interactions.

    Science.gov (United States)

    Gharavi, Robert; Hedrich, William; Wang, Hongbing; Hassan, Hazem E

    2015-08-01

    Opioid-related deaths, abuse, and drug interactions are growing epidemic problems that have medical, social, and economic implications. Drug transporters play a major role in the disposition of many drugs, including opioids; hence they can modulate their pharmacokinetics, pharmacodynamics and their associated drug-drug interactions (DDIs). Our understanding of the interaction of transporters with many therapeutic agents is improving; however, investigating such interactions with opioids is progressing relatively slowly despite the alarming number of opioids-mediated DDIs that may be related to transporters. This review presents a comprehensive report of the current literature relating to opioids and their drug transporter interactions. Additionally, it highlights the emergence of transporters that are yet to be fully identified but may play prominent roles in the disposition of opioids, the growing interest in transporter genomics for opioids, and the potential implications of opioid-drug transporter interactions for cancer treatments. A better understanding of drug transporters interactions with opioids will provide greater insight into potential clinical DDIs and could help improve opioids safety and efficacy.

  20. What Expands in an Expanding Universe?

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    JOSÉ A. DE FREITAS PACHECO

    2015-12-01

    Full Text Available ABSTRACT In the present investigation, the possible effects of the expansion of the Universe on systems bonded either by gravitational or electromagnetic forces, are reconsidered. It will be shown that the acceleration (positive or negative of the expanding background, is the determinant factor affecting planetary orbits and atomic sizes. In the presently accepted cosmology (ΛCDM all bonded systems are expanding at a decreasing rate that tends to be zero as the universe enters in a de Sitter phase. It is worth mentioning that the estimated expansion rates are rather small and they can be neglected for all practical purposes.

  1. What Expands in an Expanding Universe?

    Science.gov (United States)

    Pacheco, José A De Freitas

    2015-01-01

    In the present investigation, the possible effects of the expansion of the Universe on systems bonded either by gravitational or electromagnetic forces, are reconsidered. It will be shown that the acceleration (positive or negative) of the expanding background, is the determinant factor affecting planetary orbits and atomic sizes. In the presently accepted cosmology (ΛCDM) all bonded systems are expanding at a decreasing rate that tends to be zero as the universe enters in a de Sitter phase. It is worth mentioning that the estimated expansion rates are rather small and they can be neglected for all practical purposes.

  2. Gestational Diabetes Mellitus: a review of the diagnosis, clinical implications and management

    Directory of Open Access Journals (Sweden)

    Vincent Wing-Ming Wong

    2013-04-01

    Full Text Available Gestational diabetes mellitus (GDM is a condition that affects the wellbeing of mother and fetus. Women with GDM are at risk of type 2 diabetes mellitus in the future, while fetal exposure to hyperglycaemia in-utero may affect their glycometabolic profile later in life. Appropriate screening and management of this problem is important in ensuring good pregnancy outcomes. In this review, the clinical implications, the various ways to screen and diagnose GDM, and management strategies during pregnancy will be discussed. For years, insulin is the mainstay of treatment if medical nutrition therapy fails to maintain adequate glycaemic control, but use of other oral pharmacotherapy may gain greater acceptance in the future. Following delivery, ongoing follow-up of these women is worthwhile as early intervention through lifestyle or pharmacotherapy may prevent the development of diabetes.

  3. Low Hepcidin in Diabetes Mellitus: Examining the Molecular Links and Their Clinical Implications.

    Science.gov (United States)

    Vela, Driton; Sopi, Ramadan B; Mladenov, Mitko

    2017-06-26

    The relationship between iron and glucose metabolism has been evidenced strongly, but the molecular mediation of this connection is just being revealed. The discovery of hepcidin as the prime controller of iron metabolism has paved the way for understanding the main actors behind this mediation. Recent data suggest that insulin therapy and probably other diabetes drugs can influence hepcidin production, thus influencing the iron load in cells. Correcting iron load through hepcidin expression could be a novel and important mechanism of action of antidiabetes drugs. This effect would further establish the protective role of antidiabetes therapy and might even affect prevention strategies in diabetes. In this review, we summarize the recent data about iron-glucose links through hepcidin expression, the molecular mediation of this interplay and the clinical implications of these findings. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

  4. The roles of time of day and sleep quality in modulating glucose regulation: clinical implications.

    Science.gov (United States)

    Scheen, A J; Van Cauter, E

    1998-01-01

    Consistent variations in glucose regulation across the 24-hour cycle are present in normal subjects. These diurnal variations are altered in various states of impaired glucose tolerance (aging, obesity, diabetes). Changes in insulin secretion, clearance and/or action across the day have been demonstrated. Studies in subjects receiving continuous intravenous glucose infusion have shown that major alterations of glucose tolerance occur during sleep and that sleep quality markedly influences glucose utilization. Diurnal variations in glucose tolerance result from the alternation of wake and sleep states as well as from intrinsic effects of circadian rhythmicity. The important roles of physiological variations in levels of counterregulatory hormones which are markedly dependent on sleep (i.e. growth hormone) or circadian rhythmicity (i.e. cortisol) have only begun to be appreciated. The modulatory effects of sleep and circadian rhythmicity on glucose regulation may have important clinical implications for the diagnosis and treatment of abnormalities of carbohydrate metabolism.

  5. Quantifying discipline practices using absolute versus relative frequencies: clinical and research implications for child welfare.

    Science.gov (United States)

    Lindhiem, Oliver; Shaffer, Anne; Kolko, David J

    2014-01-01

    In the parent intervention outcome literatures, discipline practices are generally quantified as absolute frequencies or, less commonly, as relative frequencies. These differences in methodology warrant direct comparison as they have critical implications for study results and conclusions among treatments targeted at reducing parental aggression and harsh discipline. In this study, we directly compared the absolute frequency method and the relative frequency method for quantifying physically aggressive, psychologically aggressive, and nonaggressive discipline practices. Longitudinal data over a 3-year period came from an existing data set of a clinical trial examining the effectiveness of a psychosocial treatment in reducing parental physical and psychological aggression and improving child behavior (N = 139). Discipline practices (aggressive and nonaggressive) were assessed using the Conflict Tactics Scale. The two methods yielded different patterns of results, particularly for nonaggressive discipline strategies. We suggest that each method makes its own unique contribution to a more complete understanding of the association between parental aggression and intervention effects.

  6. The mandible and its foramen: anatomy, anthropology, embryology and resulting clinical implications.

    Science.gov (United States)

    Lipski, M; Tomaszewska, I M; Lipska, W; Lis, G J; Tomaszewski, K A

    2013-11-01

    The aim of this paper is to summarise the knowledge about the anatomy, embryology and anthropology of the mandible and the mandibular foramen and also to highlight the most important clinical implications of the current studies regarding anaesthesia performed in the region of the mandible. An electronic journal search was undertaken to identify all the relevant studies published in English. The search included MEDLINE and EMBASE databases and years from 1950 to 2012. The subject search used a combination of controlled vocabulary and free text based on the search strategy for MEDLINE using key words: 'mandible', 'mandibular', 'foramen', 'anatomy', 'embryology', 'anthropology', and 'mental'. The reference lists of all the relevant studies and existing reviews were screened for additional relevant publications. Basing on relevant manuscripts, this short review about the anatomy, embryology and anthropology of the mandible and the mandibular foramen was written.

  7. The effects of violent media on adolescent inkblot responses: implications for clinical and forensic assessments.

    Science.gov (United States)

    Hess, T H; Hess, K D; Hess, A K

    1999-04-01

    Two experiments were conducted to assess the degree to which violent media stimulate violent fantasy as depicted on inkblot responses. In Experiment I, 41 gifted high school students were exposed to a bucolic or violent film clip and then were asked to produce inkblot responses. In Experiment II, a second sample of 43 additional students were exposed to a verbal description of the bucolic or violent scene to assess whether the "hot" or "cooler" media (McLuhan, 1964) had different effects on the inkblot responses. In both experiments, the media exposure led to increased levels of violent responses, and in both cases males produced more violent responses. There was no sex by media interaction effect. Implications for clinical and forensic assessments are presented.

  8. Roles of Ubiquitination and SUMOylation on Prostate Cancer: Mechanisms and Clinical Implications

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    Zhenbang Chen

    2015-02-01

    Full Text Available The initiation and progression of human prostate cancer are highly associated with aberrant dysregulations of tumor suppressors and proto-oncogenes. Despite that deletions and mutations of tumor suppressors and aberrant elevations of oncogenes at the genetic level are reported to cause cancers, emerging evidence has revealed that cancer progression is largely regulated by posttranslational modifications (PTMs and epigenetic alterations. PTMs play critical roles in gene regulation, cellular functions, tissue development, diseases, malignant progression and drug resistance. Recent discoveries demonstrate that ubiquitination and SUMOylation are complicated but highly-regulated PTMs, and make essential contributions to diseases and cancers by regulation of key factors and signaling pathways. Ubiquitination and SUMOylation pathways can be differentially modulated under various stimuli or stresses in order to produce the sustained oncogenic potentials. In this review, we discuss some new insights about molecular mechanisms on ubiquitination and SUMOylation, their associations with diseases, oncogenic impact on prostate cancer (PCa and clinical implications for PCa treatment.

  9. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines.

    Science.gov (United States)

    Grundy, Scott M; Cleeman, James I; Merz, C Noel Bairey; Brewer, H Bryan; Clark, Luther T; Hunninghake, Donald B; Pasternak, Richard C; Smith, Sidney C; Stone, Neil J

    2004-08-04

    The Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program issued an evidence-based set of guidelines on cholesterol management in 2001. Since the publication of ATP III, 5 major clinical trials of statin therapy with clinical end points have been published. These trials addressed issues that were not examined in previous clinical trials of cholesterol-lowering therapy. The present document reviews the results of these recent trials and assesses their implications for cholesterol management. Therapeutic lifestyle changes (TLC) remain an essential modality in clinical management. The trials confirm the benefit of cholesterol-lowering therapy in high-risk patients and support the ATP III treatment goal of low-density lipoprotein cholesterol (LDL-C) III treatment algorithm are the following. In high-risk persons, the recommended LDL-C goal is <100 mg/dL, but when risk is very high, an LDL-C goal of <70 mg/dL is a therapeutic option, ie, a reasonable clinical strategy, on the basis of available clinical trial evidence. This therapeutic option extends also to patients at very high risk who have a baseline LDL-C < 100 mg/dL. Moreover, when a high-risk patient has high triglycerides or low high-density lipoprotein cholesterol (HDL-C), consideration can be given to combining a fibrate or nicotinic acid with an LDL-lowering drug. For moderately high-risk persons (2+ risk factors and 10-year risk 10% to 20%), the recommended LDL-C goal is <130 mg/dL, but an LDL-C goal <100 mg/dL is a therapeutic option on the basis of recent trial evidence. The latter option extends also to moderately high-risk persons with a baseline LDL-C of 100 to 129 mg/dL. When LDL-lowering drug therapy is employed in high-risk or moderately high-risk persons, it is advised that intensity of therapy be sufficient to achieve at least a 30% to 40% reduction in LDL-C levels. Moreover, any person at high risk or moderately high risk who has lifestyle-related risk factors (eg

  10. Ocular gene transfer in the spotlight: implications of newspaper content for clinical communications.

    Science.gov (United States)

    Benjaminy, Shelly; Bubela, Tania

    2014-07-16

    Ocular gene transfer clinical trials are raising hopes for blindness treatments and attracting media attention. News media provide an accessible health information source for patients and the public, but are often criticized for overemphasizing benefits and underplaying risks of novel biomedical interventions. Overly optimistic portrayals of unproven interventions may influence public and patient expectations; the latter may cause patients to downplay risks and over-emphasize benefits, with implications for informed consent for clinical trials. We analyze the news media communications landscape about ocular gene transfer and make recommendations for improving communications between clinicians and potential trial participants in light of media coverage. We analyzed leading newspaper articles about ocular gene transfer (1990-2012) from United States (n = 55), Canada (n = 26), and United Kingdom (n = 77) from Factiva and Canadian Newsstand databases using pre-defined coding categories. We evaluated the content of newspaper articles about ocular gene transfer for hereditary retinopathies, exploring representations of framing techniques, research design, risks/benefits, and translational timelines. The dominant frame in 61% of stories was a celebration of progress, followed by human-interest in 30% of stories. Missing from the positive frames were explanations of research design; articles conflated clinical research with treatment. Conflicts-of-interest and funding sources were similarly omitted. Attention was directed to the benefits of gene transfer, while risks were only reported in 43% of articles. A range of visual outcomes was described from slowing vision loss to cure, but the latter was the most frequently represented even though it is clinically infeasible. Despite the prominence of visual benefit portrayals, 87% of the articles failed to provide timelines for the commencement of clinical trials or for clinical implementation. Our analysis confirms

  11. The clinical implications of molecular monitoring and analyses of inherited retinal diseases.

    Science.gov (United States)

    Chacón-Camacho, Oscar F; García-Montaño, Leopoldo A; Zenteno, Juan C

    2017-11-01

    Retinal dystrophies (RDs) are the most common cause of inherited blindness and one of the most genetically heterogeneous human diseases. RDs arise from mutations in genes involved in development and function of photoreceptors or other retinal cells. Identification of the genetic defect causing RD allows accurate diagnosis, prognosis, and counseling in affected patients. Molecular diagnosis is a tremendous challenge in RDs due to their locus and phenotypic heterogeneity. As conventional DNA sequencing approaches are impractical in such situation, Next Generation Sequencing (NGS)-based protocols are needed to identify RD-causing mutations. This is being accomplished by sequencing RD gene panels or by whole exome or whole genome sequencing approaches. Areas covered: This review discusses the current strategies for molecular diagnosis in RDs including their advantages and limitations, as well as their utility in diagnosis of non-syndromic versus syndromic RDs. Results of ongoing gene therapy protocols in RDs are also presented. Expert commentary: Molecular diagnosis in RD improves the medical management of patients. Importantly, demand for molecular screening for RDs is greatly expanding not only as a result of increasing development and availability of NGS technologies, but also of the growing number of gene-based clinical trials offering a potential treatment to patients.

  12. The biology of cancer stem cells and its clinical implication in hepatocellular carcinoma.

    Science.gov (United States)

    Yoon, Seung Kew

    2012-01-01

    Hepatocellular carcinoma (HCC) is a highly malignant tumor with limited treatment options in its advanced state. The molecular mechanisms underlying HCC remain unclear because of the complexity of its multi-step development process. Cancer stem cells (CSCs) are defined as a small population of cells within a tumor that possess the capability for self-renewal and the generation of heterogeneous lineages of cancer cells. To date, there have been two theories concerning the mechanism of carcinogenesis, i.e., the stochastic (clonal evolution) model and the hierarchical (cancer stem cell-driven) model. The concept of the CSC has been established over the past decade, and the roles of CSCs in the carcinogenic processes of various cancers, including HCC, have been emphasized. Previous experimental and clinical evidence indicated the existence of liver CSCs; however, the potential mechanistic links between liver CSCs and the development of HCC in humans are not fully understood. Although definitive cell surface markers for liver CSCs have not yet been found, several putative markers have been identified, which allow the prospective isolation of CSCs from HCC. The identification and characterization of CSCs in HCC is essential for a better understanding of tumor initiation or progression in relation to signaling pathways. These markers could be used along with clinical parameters for the prediction of chemoresistance, radioresistance, metastasis and survival and may represent potential targets for the development of new molecular therapies against HCC. This review describes the current evidence for the existence and function of liver CSCs and discuss the clinical implications of CSCs in patients demonstrating resistance to conventional anti-cancer therapies, as well as clinical outcomes. Such data may provide a future perspective for targeted therapy in HCC.

  13. Visible aging signs as risk markers for ischemic heart disease: Epidemiology, pathogenesis and clinical implications.

    Science.gov (United States)

    Christoffersen, Mette; Tybjærg-Hansen, Anne

    2016-01-01

    Association of common aging signs (i.e., male pattern baldness, hair graying, and facial wrinkles) as well as other age-related appearance factors (i.e., arcus corneae, xanthelasmata, and earlobe crease) with increased risk of ischemic heart disease was initially described in anecdotal reports from clinicians observing trends in the physical appearance of patients with ischemic heart disease. Following these early observations numerous epidemiological studies have reported these associations. Since the prevalences of both visible aging signs and ischemic heart disease have a strong correlation with increasing age, it has been extensively debated whether the observed associations could be entirely explained by a common association with age. Furthermore, the etiologies of the visible aging signs are rarely fully understood, and pathophysiological explanations for these associations remain controversial, and are mostly speculative. As a consequence of inconsistent findings and lack of mechanistic explanations for the observed associations with ischemic heart disease, consensus on the clinical importance of these visible aging signs has been lacking. The aim of this review is for each of the visible aging signs to (i) review the etiology, (ii) to discuss the current epidemiological evidence for an association with risk of ischemic heart disease, and (iii) to present possible pathophysiological explanations for these associations. Finally this review discusses the potential clinical implications of these findings. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Current computational modelling trends in craniomandibular biomechanics and their clinical implications.

    Science.gov (United States)

    Hannam, A G

    2011-03-01

    Computational models of interactions in the craniomandibular apparatus are used with increasing frequency to study biomechanics in normal and abnormal masticatory systems. Methods and assumptions in these models can be difficult to assess by those unfamiliar with current practices in this field; health professionals are often faced with evaluating the appropriateness, validity and significance of models which are perhaps more familiar to the engineering community. This selective review offers a foundation for assessing the strength and implications of a craniomandibular modelling study. It explores different models used in general science and engineering and focuses on current best practices in biomechanics. The problem of validation is considered at some length, because this is not always fully realisable in living subjects. Rigid-body, finite element and combined approaches are discussed, with examples of their application to basic and clinically relevant problems. Some advanced software platforms currently available for modelling craniomandibular systems are mentioned. Recent studies of the face, masticatory muscles, tongue, craniomandibular skeleton, temporomandibular joint, dentition and dental implants are reviewed, and the significance of non-linear and non-isotropic material properties is emphasised. The unique challenges in clinical application are discussed, and the review concludes by posing some questions which one might reasonably expect to find answered in plausible modelling studies of the masticatory apparatus. © 2010 Blackwell Publishing Ltd.

  15. Clinical implications of the recent homeopathic medicine and its application to oriental medicine

    Directory of Open Access Journals (Sweden)

    Ok-Byung,Choi

    2007-02-01

    Full Text Available Objectives : The purpose of this study is to analyze the practical implications of homeopathic medicines, their status, their preparation systems and registration rules, recognized by the European Union and other countries. Contents : This paper covers the background of homeopathic medical principle, homeopathy throughout the world, the medicine status and clinical research, increases of the drug potency, the practical regulation of treatment, preparation techniques of homeopathic drugs and registration rules and the clinical practice. Homeopathy has been currently practised in over eighty countries throughout the world, especially in Europe. It had attracted considerable attentions in South and North America (notably in USA, Brazil, and Argentina, India and Pakistan. Although it is not dominantly popular in North America, constant growth has been nevertheless noted. Over the last thirty years, homeopathy has also developed or appeared in South Africa, Tunisia, Morocco, Venezuela, Israel, and Australia, etc. Result & suggestion : As over 300 million patients have put their trust in homeopathy, the study of the integration of homeopathy to oriental medicine, its development and feasibility in Korea are urgently needed. The products, substances, compositions of Homeopathic drugs are very similar to those of oriental medicine theory. Therefore their preparations and applications should prescribed and practised exclusively by oriental doctors. Applying the homeopathic theory and its preparation techniques to oriental medicine, the herbal acupuncture preparation should be modernized and various oriental products are to be developed. To this end, government and herbal acupuncture society need to interact each other for the development of oriental medicine.

  16. The role of memory in posttraumatic stress disorder: implications for clinical practice

    Directory of Open Access Journals (Sweden)

    Marcelo Montagner Rigoli

    Full Text Available Abstract Introduction: Posttraumatic stress disorder (PTSD is a highly prevalent disorder with important social consequences. Several models have been developed with the aim of understanding the mechanisms underlying its symptoms. Intrusions are idiosyncratic symptoms that commonly take the form of involuntary recollection of images or flashbacks about the traumatic event. Objective: To review how memory is conceptualized in each of these models and the implications for clinical practice. Methods: A narrative review of the literature was conducted through analysis of the perspectives of memory in theoretical models of PTSD. Results: Two main perspectives were identified: 1 models in which specific mechanisms of memory for processing traumatic events are proposed, especially those based on clinical studies, and 2 models in which common mnemonic mechanisms are utilized to explain the phenomenon, primarily based on basic experimental research studies investigating memory. The different theories based on these approaches have led to distinct psychotherapy interventions. Conclusion: In order to clarify these discrepancies, future research should aim for the methodological rigor of experimental studies, while maintaining the ecological applicability of findings. Cognitive experimental psychopathology is therefore an area on which research funding should be focused. Such studies could elucidate the role of mnemonic aspects in PTSD and how they impact psychological treatments.

  17. Delay of gratification in old age: assessment, age-related effects, and clinical implications.

    Science.gov (United States)

    Drobetz, Reinhard; Maercker, Andreas; Forstmeier, Simon

    2012-02-01

    Delay of gratification (DoG), the ability to reject immediately available smaller rewards in favor of later larger rewards, has been a topic of continuous research interest for almost 60 years. Although numerous studies have explored this construct and its effects on wellbeing, social behavior, cognitive abilities, and academic success in children, DoG studies in adulthood and old age are scarce. Instead, delay discounting (DD), that is, the degree to which individuals devalue delayed rewards, has been used in samples of adults and older individuals, and is of particular interest in clinical studies. Findings from DD research suggest that the preference for delayed rewards increases from childhood to early adulthood, and then decreases from middle age to old age. The main aim of this review is to elucidate the importance of DoG in adulthood and old age. First, the review explores the theoretical status of DoG by specifying the relationships and distinctions between DoG and related constructs. Second, it provides an overview of DoG measurements, from traditional to novel. Third, the effects of DoG on development and wellbeing are explored. Fourth, age-related differences in DoG are summarized. Lastly, the review closes with conclusions, clinical implications, and the outlook for possible further research directions.

  18. Emerging roles of innate lymphoid cells in inflammatory diseases: Clinical implications.

    Science.gov (United States)

    Kortekaas Krohn, I; Shikhagaie, M M; Golebski, K; Bernink, J H; Breynaert, C; Creyns, B; Diamant, Z; Fokkens, W J; Gevaert, P; Hellings, P; Hendriks, R W; Klimek, L; Mjösberg, J; Morita, H; Ogg, G S; O'Mahony, L; Schwarze, J; Seys, S F; Shamji, M H; Bal, S M

    2017-10-25

    Innate lymphoid cells (ILC) represent a group of lymphocytes that lack specific antigen receptors and are relatively rare as compared to adaptive lymphocytes. ILCs play important roles in allergic and nonallergic inflammatory diseases due to their location at barrier surfaces within the airways, gut, and skin, and they respond to cytokines produced by activated cells in their local environment. Innate lymphoid cells contribute to the immune response by the release of cytokines and other mediators, forming a link between innate and adaptive immunity. In recent years, these cells have been extensively characterized and their role in animal models of disease has been investigated. Data to translate the relevance of ILCs in human pathology, and the potential role of ILCs in diagnosis, as biomarkers and/or as future treatment targets are also emerging. This review, produced by a task force of the Immunology Section of the European Academy of Allergy and Clinical Immunology (EAACI), encompassing clinicians and researchers, highlights the role of ILCs in human allergic and nonallergic diseases in the airways, gastrointestinal tract, and skin, with a focus on new insights into clinical implications, therapeutic options, and future research opportunities. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  19. The role of memory in posttraumatic stress disorder: implications for clinical practice.

    Science.gov (United States)

    Rigoli, Marcelo Montagner; Silva, Gustavo Ramos; Oliveira, Fernando Rainho de; Pergher, Giovanni Kuckartz; Kristensen, Christian Haag

    2016-06-27

    Posttraumatic stress disorder (PTSD) is a highly prevalent disorder with important social consequences. Several models have been developed with the aim of understanding the mechanisms underlying its symptoms. Intrusions are idiosyncratic symptoms that commonly take the form of involuntary recollection of images or flashbacks about the traumatic event. To review how memory is conceptualized in each of these models and the implications for clinical practice. A narrative review of the literature was conducted through analysis of the perspectives of memory in theoretical models of PTSD. Two main perspectives were identified: 1) models in which specific mechanisms of memory for processing traumatic events are proposed, especially those based on clinical studies, and 2) models in which common mnemonic mechanisms are utilized to explain the phenomenon, primarily based on basic experimental research studies investigating memory. The different theories based on these approaches have led to distinct psychotherapy interventions. In order to clarify these discrepancies, future research should aim for the methodological rigor of experimental studies, while maintaining the ecological applicability of findings. Cognitive experimental psychopathology is therefore an area on which research funding should be focused. Such studies could elucidate the role of mnemonic aspects in PTSD and how they impact psychological treatments.

  20. Molecular biology of anal squamous cell carcinoma: implications for future research and clinical intervention.

    Science.gov (United States)

    Bernardi, Maria-Pia; Ngan, Samuel Y; Michael, Michael; Lynch, A Craig; Heriot, Alexander G; Ramsay, Robert G; Phillips, Wayne A

    2015-12-01

    Anal squamous cell carcinoma is a human papillomavirus-related disease, in which no substantial advances in treatment have been made in over 40 years, especially for those patients who develop disease relapse and for whom no surgical options exist. HPV can evade the immune system and its role in disease progression can be exploited in novel immunotherapy platforms. Although several studies have investigated the expression and inactivation (through loss of heterozygosity) of tumour suppressor genes in the pathways to cancer, no clinically valuable biomarkers have emerged. Regulators of apoptosis, including survivin, and agents targeting the PI3K/AKT pathway, offer opportunities for targeted therapy, although robust data are scarce. Additionally, antibody therapy targeting EGFR may prove effective, although its safety profile in combination with standard chemoradiotherapy has proven to be suboptimal. Finally, progress in the treatment of anal cancer has remained stagnant due to a lack of preclinical models, including cell lines and mouse models. In this Review, we discuss the molecular biology of anal squamous cell carcinoma, clinical trials in progress, and implications for novel therapeutic targets. Future work should focus on preclinical models to provide a resource for investigation of new molecular pathways and for testing novel targets. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. A rare variant of the ulnar artery with important clinical implications: a case report

    Directory of Open Access Journals (Sweden)

    Casal Diogo

    2012-11-01

    Full Text Available Abstract Background Variations in the major arteries of the upper limb are estimated to be present in up to one fifth of people, and may have significant clinical implications. Case presentation During routine cadaveric dissection of a 69-year-old fresh female cadaver, a superficial brachioulnar artery with an aberrant path was found bilaterally. The superficial brachioulnar artery originated at midarm level from the brachial artery, pierced the brachial fascia immediately proximal to the elbow, crossed superficial to the muscles that originated from the medial epicondyle, and ran over the pronator teres muscle in a doubling of the antebrachial fascia. It then dipped into the forearm fascia, in the gap between the flexor carpi radialis and the palmaris longus. Subsequently, it ran deep to the palmaris longus muscle belly, and superficially to the flexor digitorum superficialis muscle, reaching the gap between the latter and the flexor carpi ulnaris muscle, where it assumed is usual position lateral to the ulnar nerve. Conclusion As far as the authors could determine, this variant of the superficial brachioulnar artery has only been described twice before in the literature. The existence of such a variant is of particular clinical significance, as these arteries are more susceptible to trauma, and can be easily confused with superficial veins during medical and surgical procedures, potentially leading to iatrogenic distal limb ischemia.

  2. A standardized approach to the Fugl-Meyer assessment and its implications for clinical trials.

    Science.gov (United States)

    See, Jill; Dodakian, Lucy; Chou, Cathy; Chan, Vicky; McKenzie, Alison; Reinkensmeyer, David J; Cramer, Steven C

    2013-10-01

    Standardizing scoring reduces variability and increases accuracy. A detailed scoring and training method for the Fugl-Meyer motor assessment (FMA) is described and assessed, and implications for clinical trials considered. A standardized FMA scoring approach and training materials were assembled, including a manual, scoring sheets, and instructional video plus patient videos. Performance of this approach was evaluated for the upper extremity portion. Inter- and intrarater reliability in 31 patients were excellent (intraclass correlation coefficient = 0.98-0.99), validity was excellent (r = 0.74-0.93, P versus 0.9 ± 4.9 points posttraining. The current approach was implemented without incident into training for a phase II trial. Among 66 patients treated with robotic therapy, change in FMA was smaller (P ≤ .01) at the high and low ends of baseline FMA scores. Training with the current method improved accuracy, and reduced variance, of FMA scoring; the 20% FMA variance reduction with training would decrease sample size requirements from 137 to 88 in a theoretical trial aiming to detect a 7-point FMA difference. Minimal detectable change was much smaller than FMA minimal clinically important difference. The variation in FMA gains in relation to baseline FMA suggests that future trials consider a sliding outcome approach when FMA is an outcome measure. The current training approach may be useful for assessing motor outcomes in restorative stroke trials.

  3. Nociception affects motor output: a review on sensory-motor interaction with focus on clinical implications.

    Science.gov (United States)

    Nijs, Jo; Daenen, Liesbeth; Cras, Patrick; Struyf, Filip; Roussel, Nathalie; Oostendorp, Rob A B

    2012-02-01

    Research has provided us with an increased understanding of nociception-motor interaction. Nociception-motor interaction is most often processed without conscious thoughts. Hence, in many cases neither patients nor clinicians are aware of the interaction. It is aimed at reviewing the scientific literature on nociception-motor interaction, with emphasis on clinical implications. Narrative review. Chronic nociceptive stimuli result in cortical relay of the motor output in humans, and a reduced activity of the painful muscle. Nociception-induced motor inhibition might prevent effective motor retraining. In addition, the sympathetic nervous system responds to chronic nociception with enhanced sympathetic activation. Not only motor and sympathetic output pathways are affected by nociceptive input, afferent pathways (proprioception, somatosensory processing) are influenced by tonic muscle nociception as well. The clinical consequence of the shift in thinking is to stop trying to restore normal motor control in case of chronic nociception. Activation of central nociceptive inhibitory mechanisms, by decreasing nociceptive input, might address nociception-motor interactions.

  4. Clinical implications of local field potentials for understanding and treating movement disorders.

    Science.gov (United States)

    Thompson, John A; Lanctin, David; Ince, Nuri Firat; Abosch, Aviva

    2014-01-01

    Deep brain stimulation (DBS) for the treatment of movement disorders has provided researchers with an opportunity to record electrical oscillatory activity from electrodes implanted in deep brain structures. Extracellular activity recorded from a population of neurons, termed local field potentials (LFPs), has shed light on the pathophysiology of movement disorders and holds the potential to lead to refinement in existing treatments. This paper reviews the clinical significance of LFPs recorded from macroelectrodes implanted in basal ganglia and thalamic targets for the treatment of Parkinson's disease, essential tremor and dystonia. Neural population dynamics and subthreshold events, which are undetectable by single-unit recordings, can be examined with frequency band analysis of LFPs (frequency range: 1-250 Hz). Of clinical relevance, reliable correlations between motor symptoms and components of the LFP power spectrum suggest that LFPs may serve as a biomarker for movement disorders. In particular, Parkinson's rigidity has been shown to correlate with the power of beta oscillations (13-30 Hz), and essential tremor coheres with oscillations of 8-27 Hz. Furthermore, evidence indicates that the optimal contacts for DBS programming can be predicted from the anatomic location of beta and gamma bands (48-200 Hz). LFP analysis has implications for improved electrode targeting and the development of a real-time, individualized, 'closed-loop' stimulation system. 2014 S. Karger AG, Basel.

  5. Effects of cervical sympathetic nerve stimulation on the cerebral microcirculation: possible clinical implications.

    Science.gov (United States)

    Passatore, M; Deriu, F; Roatta, S; Grassi, C; Micieli, G

    1996-01-01

    The action of bilateral cervical sympathetic nerve (CSN) stimulation on mean cerebral blood flow (CBF) and on its rhythmical fluctuations was studied in normotensive rabbits by using laser-Doppler flowmetry (LDF). A reduction in mean CBF, mediated by alpha-adrenoceptors, was the predominant effect; it was more often present and larger in size in the vascular beds supplied by the carotid than in those supplied by the vertebro-basilar system. This suggests that the sympathetic action facilitates a redistribution of blood flow to the brain stem. The effect induced by CSN stimulation on CBF spontaneous oscillations was a consistent decrease in amplitude and an increase in frequency, irrespective of the changes produced on the mean level of CBF. The possible implications of the sympathetic action on the state of the blood-brain barrier (BBB) are discussed. Experimental and clinical data dealing with the influence of sympathetic activation on the cerebrovascular system have been compared. As a result the possibility of analysing the spontaneous oscillations of CBF for clinical purposes is suggested.

  6. HIV-1 Genetic Variability in Cuba and Implications for Transmission and Clinical Progression.

    Science.gov (United States)

    Blanco, Madeline; Machado, Liuber Y; Díaz, Héctor; Ruiz, Nancy; Romay, Dania; Silva, Eladio

    2015-10-01

    INTRODUCTION Serological and molecular HIV-1 studies in Cuba have shown very low prevalence of seropositivity, but an increasing genetic diversity attributable to introduction of many HIV-1 variants from different areas, exchange of such variants among HIV-positive people with several coinciding routes of infection and other epidemiologic risk factors in the seropositive population. The high HIV-1 genetic variability observed in Cuba has possible implications for transmission and clinical progression. OBJECTIVE Study genetic variability for the HIV-1 env, gag and pol structural genes in Cuba; determine the prevalence of B and non-B subtypes according to epidemiologic and behavioral variables and determine whether a relationship exists between genetic variability and transmissibility, and between genetic variability and clinical disease progression in people living with HIV/AIDS. METHODS Using two molecular assays (heteroduplex mobility assay and nucleic acid sequencing), structural genes were characterized in 590 people with HIV-1 (480 men and 110 women), accounting for 3.4% of seropositive individuals in Cuba as of December 31, 2013. Nonrandom sampling, proportional to HIV prevalence by province, was conducted. Relationships between molecular results and viral factors, host characteristics, and patients' clinical, epidemiologic and behavioral variables were studied for molecular epidemiology, transmission, and progression analyses. RESULTS Molecular analysis of the three HIV-1 structural genes classified 297 samples as subtype B (50.3%), 269 as non-B subtypes (45.6%) and 24 were not typeable. Subtype B prevailed overall and in men, mainly in those who have sex with men. Non-B subtypes were prevalent in women and heterosexual men, showing multiple circulating variants and recombinant forms. Sexual transmission was the predominant form of infection for all. B and non-B subtypes were encountered throughout Cuba. No association was found between subtypes and

  7. Clinical Ethology and canine aggression in Montevideo: implications of race and gender

    Directory of Open Access Journals (Sweden)

    Belino, Maria

    2011-07-01

    Full Text Available Statistics about clinical data is lacking in Uruguay. Herein, we present an account of canine behavioral problems recorded from different sources: a clinical reports on canine behaviour, from 30 veterinary clinics in Montevideo city from 2005 to 2007 (n = 179; b records of dog attacks to people (n = 992 reported at the Servicio de Atención al Mordido (Ministerio de Salud Pública, same period; and c conflicts from records of Comisión Nacional Honoraria de Zoonosis (n = 44,000. Based on these data we discus common behavioral problems, types of aggression involved, the frequency of male / female, if they were neutered or not and the age at the onset of the first episodes of aggression. For each record we obtained an aggressive risk factor associated to breed. The results are consistent with international reports, where the aggression was the most common behavioral problem (58.9%, and dominance aggression has the highest proportion (56%. The RDPCC records revealed that the proportion of animals involved in aggression is similar in both genders. However, SAM-MSP records showed that males (71% were a significantly greater proportion than females (29%. Our data from RDPCC showed that 100% of males involved in aggression towards people were whole, while 38.5% females were castrated. The first signs of canine aggression towards people were observed in first year of life in 56.5% of cases. On the other hand, while the RDPCC record suggests that Cocker breed tended to show more attacks of aggression toward people, the SAM-MSP record pointed to the German Shepher as the more aggressive breed. The Rottweiler and Uruguayan Cimarron, occupied the first and third place respectively in the aggressive risk factor rank associated to breed, both in RDPCC and SAM-MSP set of records. This is the first descriptive work on dog behavior problems and aggression in Montevideo, where also is shows the implication of the Cimarron uruguayo race in aggression.

  8. Interchangeability among reference insulin analogues and their biosimilars: regulatory framework, study design and clinical implications.

    Science.gov (United States)

    Dowlat, H A; Kuhlmann, M K; Khatami, H; Ampudia-Blasco, F J

    2016-08-01

    Biosimilars are regulated differently from small-molecule generic, chemically derived medicines. The complexity of biological products means that small changes in manufacturing or formulation may result in changes in efficacy and safety of the final product. In the face of this complexity, the regulatory landscape for biosimilars continues to evolve, and global harmonization regarding requirements is currently lacking. It is essential that clinicians and patients are reassured that biosimilars are equally safe and effective as their reference product, and this is particularly important when interchangeability, defined as 'changing one medicine for another one which is expected to achieve the same clinical effect in a given clinical setting in any one patient', is considered. Although the automatic substitution (i.e. substitution without input from the prescribing healthcare provider) of biosimilars for reference products is currently not permitted by the majority of countries, this may change in the future. In order to demonstrate interchangeability between reference products and a biosimilar, more stringent and specific studies of the safety and efficacy of biosimilars are likely to be needed; however, guidance on the design of and the need for any such studies is currently limited. The present article provides an overview of the current regulatory framework around the demonstration of interchangeability with biosimilars, with a specific focus on biosimilar insulin analogues, and details experiences with other biosimilar products. In addition, designs for studies to evaluate interchangeability with a biosimilar insulin analogue product are proposed and a discussion about the implications of interchangeability in clinical practice is included. © 2016 John Wiley & Sons Ltd.

  9. Role of obesity and lipotoxicity in the development of nonalcoholic steatohepatitis: pathophysiology and clinical implications.

    Science.gov (United States)

    Cusi, Kenneth

    2012-04-01

    As obesity reaches epidemic proportions, nonalcoholic fatty liver disease (NAFLD) is becoming a frequent cause of patient referral to gastroenterologists. There is a close link between dysfunctional adipose tissue in NAFLD and common conditions such as metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. This review focuses on the pathophysiology of interactions between adipose tissue and target organs in obesity and the resulting clinical implications for the management of nonalcoholic steatohepatitis. The release of fatty acids from dysfunctional and insulin-resistant adipocytes results in lipotoxicity, caused by the accumulation of triglyceride-derived toxic metabolites in ectopic tissues (liver, muscle, pancreatic beta cells) and subsequent activation of inflammatory pathways, cellular dysfunction, and lipoapoptosis. The cross talk between dysfunctional adipocytes and the liver involves multiple cell populations, including macrophages and other immune cells, that in concert promote the development of lipotoxic liver disease, a term that more accurately describes the pathophysiology of nonalcoholic steatohepatitis. At the clinical level, adipose tissue insulin resistance contributes to type 2 diabetes mellitus and cardiovascular disease. Treatments that rescue the liver from lipotoxicity by restoring adipose tissue insulin sensitivity (eg, significant weight loss, exercise, thiazolidinediones) or preventing activation of inflammatory pathways and oxidative stress (ie, vitamin E, thiazolidinediones) hold promise in the treatment of NAFLD, although their long-term safety and efficacy remain to be established. Better understanding of pathways that link dysregulated adipose tissue, metabolic dysfunction, and liver lipotoxicity will result in improvements in the clinical management of these challenging patients. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

  10. Over-expressions of AMPK subunits in ovarian carcinomas with significant clinical implications

    Directory of Open Access Journals (Sweden)

    Li Cuilan

    2012-08-01

    clinical implications in ovarian cancer development.

  11. Layouts of Expander Graphs

    OpenAIRE

    Dujmović, Vida; Sidiropoulos, Anastasios; Wood, David R.

    2015-01-01

    Bourgain and Yehudayoff recently constructed $O(1)$-monotone bipartite expanders. By combining this result with a generalisation of the unraveling method of Kannan, we construct 3-monotone bipartite expanders, which is best possible. We then show that the same graphs admit 3-page book embeddings, 2-queue layouts, 4-track layouts, and have simple thickness 2. All these results are best possible.

  12. Peripheral muscle abnormalities in cystic fibrosis: Etiology, clinical implications and response to therapeutic interventions.

    Science.gov (United States)

    Gruet, Mathieu; Troosters, Thierry; Verges, Samuel

    2017-09-01

    Peripheral muscle dysfunction is an important systemic consequence of cystic fibrosis (CF) with major clinical implications, such as exercise intolerance and reduced quality of life. Evidence is now accumulating that lack of physical activity is unlikely to be the sole explanation for peripheral muscle dysfunction of patients with CF. Particularly, the demonstration of CFTR expression in both murine and human skeletal muscle suggests the potential implication of intrinsic CF-related factors. By combining data from both human and animal models, this review describes CF peripheral muscle abnormalities and critically reviews the advances in understanding the impact of the underlying mechanisms. We also describe how peripheral muscles respond to intervention in this population. Methodological concerns and directions for future research are also considered. Peripheral muscle atrophy and weakness is prevalent in patients with CF and associated with reduced aerobic and anaerobic performances. Further investigations are however needed to confirm alterations in peripheral muscle endurance and fatigability. Physical inactivity is probably the major contributor of peripheral muscle abnormalities in patients with CF with mild-to-moderate phenotypes. However, the relative influence of additional factors (e.g. inflammation, metabolic abnormalities) probably increases with disease severity making specific and individualized interventions necessary in severe patients. Exercise training is the most effective intervention to address peripheral muscle dysfunction but other strategies, such as neuromuscular electrical stimulation and nutritional or hormonal supplementation may be of interest in some patients. Investigations are needed to determine whether pharmacological interventions such as CFTR modulators are effective to address this condition. To better elucidate the etiology of peripheral muscle dysfunction in CF, future studies should combine measurements at the cellular level

  13. Heterogeneous Contributing Factors in MPM Disease Development and Progression: Biological Advances and Clinical Implications

    Science.gov (United States)

    Tolani, Bhairavi; Acevedo, Luis A.; Hoang, Ngoc T.; He, Biao

    2018-01-01

    Malignant pleural mesothelioma (MPM) tumors are remarkably aggressive and most patients only survive for 5–12 months; irrespective of stage; after primary symptoms appear. Compounding matters is that MPM remains unresponsive to conventional standards of care; including radiation and chemotherapy. Currently; instead of relying on molecular signatures and histological typing; MPM treatment options are guided by clinical stage and patient characteristics because the mechanism of carcinogenesis has not been fully elucidated; although about 80% of cases can be linked to asbestos exposure. Several molecular pathways have been implicated in the MPM tumor microenvironment; such as angiogenesis; apoptosis; cell-cycle regulation and several growth factor-related pathways predicted to be amenable to therapeutic intervention. Furthermore, the availability of genomic data has improved our understanding of the pathobiology of MPM. The MPM genomic landscape is dominated by inactivating mutations in several tumor suppressor genes; such as CDKN2A; BAP1 and NF2. Given the complex heterogeneity of the tumor microenvironment in MPM; a better understanding of the interplay between stromal; endothelial and immune cells at the molecular level is required; to chaperone the development of improved personalized therapeutics. Many recent advances at the molecular level have been reported and several exciting new treatment options are under investigation. Here; we review the challenges and the most up-to-date biological advances in MPM pertaining to the molecular pathways implicated; progress at the genomic level; immunological progression of this fatal disease; and its link with developmental cell pathways; with an emphasis on prognostic and therapeutic treatment strategies. PMID:29342862

  14. Age-related aspects and clinical implications of diagnosis and treatment of personality disorders in older adults

    NARCIS (Netherlands)

    van Alphen, S.P.J.; Bolwerk, N.; Videler, A.C.; Tummers, J.H.A.; van Royen, R.J.J.; Barendse, H.P.J.; Verheul, R.; Rosowsky, E.

    2014-01-01

    To investigate age-related diagnostic and therapeutic aspects of personality disorders in later life (≥ 60 years) and implications in clinical practice, such as the introduction of a specific mental health care program, diagnostic assessment procedure, and treatment criteria for personality

  15. Phase 1 clinical trial using mbIL21 ex vivo-expanded donor-derived NK cells after haploidentical transplantation.

    Science.gov (United States)

    Ciurea, Stefan O; Schafer, Jolie R; Bassett, Roland; Denman, Cecele J; Cao, Kai; Willis, Dana; Rondon, Gabriela; Chen, Julianne; Soebbing, Doris; Kaur, Indreshpal; Gulbis, Alison; Ahmed, Sairah; Rezvani, Katayoun; Shpall, Elizabeth J; Lee, Dean A; Champlin, Richard E

    2017-10-19

    Relapse has emerged as the most important cause of treatment failure after allogeneic hematopoietic stem cell transplantation (HSCT). To test the hypothesis that natural killer (NK) cells can decrease the risk of leukemia relapse, we initiated a phase 1 dose-escalation study of membrane-bound interleukin 21 (mbIL21) expanded donor NK cells infused before and after haploidentical HSCT for high-risk myeloid malignancies. The goals were to determine the safety, feasibility, and maximum tolerated dose. Patients received a melphalan-based reduced-intensity conditioning regimen and posttransplant cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis. NK cells were infused on days -2, +7, and +28 posttransplant. All NK expansions achieved the required cell number, and 11 of 13 patients enrolled received all 3 planned NK-cell doses (1 × 105/kg to 1 × 108/kg per dose). No infusional reactions or dose-limiting toxicities occurred. All patients engrafted with donor cells. Seven patients (54%) developed grade 1-2 acute GVHD (aGVHD), none developed grade 3-4 aGVHD or chronic GVHD, and a low incidence of viral complications was observed. One patient died of nonrelapse mortality; 1 patient relapsed. All others were alive and in remission at last follow-up (median, 14.7 months). NK-cell reconstitution was quantitatively, phenotypically, and functionally superior compared with a similar group of patients not receiving NK cells. In conclusion, this trial demonstrated production feasibility and safety of infusing high doses of ex vivo-expanded NK cells after haploidentical HSCT without adverse effects, increased GVHD, or higher mortality, and was associated with significantly improved NK-cell number and function, lower viral infections, and low relapse rate posttransplant. © 2017 by The American Society of Hematology.

  16. Research on the Premotor Symptoms of Parkinson’s Disease: Clinical and Etiological Implications

    Science.gov (United States)

    Burton, Edward A.; Ross, G. Webster; Huang, Xuemei; Savica, Rodolfo; Abbott, Robert D.; Ascherio, Alberto; Caviness, John N.; Gao, Xiang; Gray, Kimberly A.; Hong, Jau-Shyong; Kamel, Freya; Jennings, Danna; Kirshner, Annette; Lawler, Cindy; Liu, Rui; Miller, Gary W.; Nussbaum, Robert; Peddada, Shyamal D.; Rick, Amy Comstock; Ritz, Beate; Siderowf, Andrew D.; Tanner, Caroline M.; Tröster, Alexander I.; Zhang, Jing

    2013-01-01

    Background: The etiology and natural history of Parkinson’s disease (PD) are not well understood. Some non-motor symptoms such as hyposmia, rapid eye movement sleep behavior disorder, and constipation may develop during the prodromal stage of PD and precede PD diagnosis by years. Objectives: We examined the promise and pitfalls of research on premotor symptoms of PD and developed priorities and strategies to understand their clinical and etiological implications. Methods: This review was based on a workshop, Parkinson’s Disease Premotor Symptom Symposium, held 7–8 June 2012 at the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina. Discussion: Research on premotor symptoms of PD may offer an excellent opportunity to characterize high-risk populations and to better understand PD etiology. Such research may lead to evaluation of novel etiological hypotheses such as the possibility that environmental toxicants or viruses may initiate PD pathogenesis in the gastrointestinal tract or olfactory bulb. At present, our understanding of premotor symptoms of PD is in its infancy and faces many obstacles. These symptoms are often not specific to PD and have low positive predictive value for early PD diagnosis. Further, the pathological bases and biological mechanisms of these premotor symptoms and their relevance to PD pathogenesis are poorly understood. Conclusion: This is an emerging research area with important data gaps to be filled. Future research is needed to understand the prevalence of multiple premotor symptoms and their etiological relevance to PD. Animal experiments and mechanistic studies will further understanding of the biology of these premotor symptoms and test novel etiological hypothesis. Citation: Chen H, Burton EA, Ross GW, Huang X, Savica R, Abbott RD, Ascherio A, Caviness JN, Gao X, Gray KA, Hong JS, Kamel F, Jennings D, Kirshner A, Lawler C, Liu R, Miller GW, Nussbaum R, Peddada SD, Comstock Rick A, Ritz

  17. Clinical-Genetic Associations in the Prospective Huntington at Risk Observational Study (PHAROS): Implications for Clinical Trials.

    Science.gov (United States)

    Biglan, Kevin Michael; Shoulson, Ira; Kieburtz, Karl; Oakes, David; Kayson, Elise; Shinaman, M Aileen; Zhao, Hongwei; Romer, Megan; Young, Anne; Hersch, Steven; Penney, Jack; Marder, Karen; Paulsen, Jane; Quaid, Kimberly; Siemers, Eric; Tanner, Caroline; Mallonee, William; Suter, Greg; Dubinsky, Richard; Gray, Carolyn; Nance, Martha; Bundlie, Scott; Radtke, Dawn; Kostyk, Sandra; Baic, Corrine; Caress, James; Walker, Francis; Hunt, Victoria; O'Neill, Christine; Chouinard, Sylvain; Factor, Stewart; Greenamyre, Timothy; Wood-Siverio, Cathy; Corey-Bloom, Jody; Song, David; Peavy, Guerry; Moskowitz, Carol; Wesson, Melissa; Samii, Ali; Bird, Thomas; Lipe, Hillary; Blindauer, Karen; Marshall, Frederick; Zimmerman, Carol; Goldstein, Jody; Rosas, Diana; Novak, Peter; Caviness, John; Adler, Charles; Duffy, Amy; Wheelock, Vicki; Tempkin, Teresa; Richman, David; Seeberger, Lauren; Albin, Roger; Chou, Kelvin L; Racette, Brad; Perlmutter, Joel S; Perlman, Susan; Bordelon, Yvette; Martin, Wayne; Wieler, Marguerite; Leavitt, Blair; Raymond, Lynn; Decolongon, Joji; Clarke, Lorne; Jankovic, Joseph; Hunter, Christine; Hauser, Robert A; Sanchez-Ramos, Juan; Furtado, Sarah; Suchowersky, Oksana; Klimek, Mary Lou; Guttman, Mark; Sethna, Rustom; Feigin, Andrew; Cox, Marie; Shannon, Barbara; Percy, Alan; Dure, Leon; Harrison, Madaline; Johnson, William; Higgins, Donald; Molho, Eric; Nickerson, Constance; Evans, Sharon; Hobson, Douglas; Singer, Carlos; Galvez-Jimenez, Nestor; Shannon, Kathleen; Comella, Cynthia; Ross, Christopher; Saint-Hilaire, Marie H; Testa, Claudia; Rosenblatt, Adam; Hogarth, Penelope; Weiner, William; Como, Peter; Kumar, Rajeev; Cotto, Candace; Stout, Julie; Brocht, Alicia; Watts, Arthur; Eberly, Shirley; Weaver, Christine; Foroud, Tatiana; Gusella, James; MacDonald, Marcy; Myers, Richard; Fahn, Stanley; Shults, Clifford

    2016-01-01

    Identifying measures that are associated with the cytosine-adenine-guanine (CAG) expansion in individuals before diagnosis of Huntington disease (HD) has implications for designing clinical trials. To identify the earliest features associated with the motor diagnosis of HD in the Prospective Huntington at Risk Observational Study (PHAROS). A prospective, multicenter, longitudinal cohort study was conducted at 43 US and Canadian Huntington Study Group research sites from July 9, 1999, through December 17, 2009. Participants included 983 unaffected adults at risk for HD who had chosen to remain unaware of their mutation status. Baseline comparability between CAG expansion (≥37 repeats) and nonexpansion (Huntington disease mutation status in individuals with CAG expansion vs without CAG expansion. Unified Huntington's Disease Rating Scale motor (score range, 0-124; higher scores indicate greater impairment), cognitive (symbol digits modality is the total number of correct responses in 90 seconds; lower scores indicate greater impairment), behavioral (score range, 0-176; higher scores indicate greater behavioral symptoms), and functional (Total Functional Capacity score range, 0-13; lower scores indicate reduced functional ability) domains were assessed at baseline and every 9 months up to a maximum of 10 years. Among the 983 research participants at risk for HD in the longitudinal cohort, 345 (35.1%) carried the CAG expansion and 638 (64.9%) did not. The mean (SD) duration of follow-up was 5.8 (3.0) years. At baseline, participants with expansions had more impaired motor (3.0 [4.2] vs 1.9 [2.8]; P < .001), cognitive (P < .05 for all measures except Verbal Fluency, P = .52), and behavioral domain scores (9.4 [11.4] vs 6.5 [8.5]; P < .001) but not significantly different measures of functional capacity (12.9 [0.3] vs 13.0 [0.2]; P = .23). With findings reported as mean slope (95% CI), in the longitudinal analyses, participants with CAG expansions

  18. The expanding clinical phenotype of the tRNA{sup Leu(UUR)} A{r_arrow}G mutation at np 3243 of mitochondrial DNA: Diabetic embryopathy associated with mitochondrial cytopathy

    Energy Technology Data Exchange (ETDEWEB)

    Feigenbaum, A.; Chitayat, D.; Robinson, B.; MacGregor, D.; Myint, T. [Univ. of Toronto, Ontario (Canada)] [and others

    1996-04-24

    We describe a family which demonstrates and expands the extreme clinical variability now known to be associated with the A{r_arrow}G transition at nucleotide position 3243 of the mitochondrial DNA. The propositus presented at birth with clinical manifestations consistent with diabetic embryopathy including anal atresia, caudal dysgenesis, and multicystic dysplastic kidneys. His co-twin was normal at birth, but at 3 months of life, presented with intractable seizures later associated with developmental delay. The twins` mother developed diabetes mellitus type I at the age of 20 years and gastrointestinal problems at 22 years. Since age 19 years, the maternal aunt has had recurrent strokes, seizures, mental deterioration and deafness, later diagnosed as MELAS syndrome due to the tRNA{sup Leu(UUR)} A{r_arrow}G mutation. A maternal uncle had diabetes mellitus type I, deafness, and normal intellect, and died at 35 years after recurrent strokes. This pedigree expands the known clinical phenotype associated with tRNA{sup Leu(UUR)} A{r_arrow}G mutation and raises the possibility that, in some cases, diabetic embryopathy may be due to a mitochondrial cytopathy that affects both the mother`s pancreas (and results in diabetes mellitus and the metabolic dysfunction associated with it) and the embryonic/fetal and placental tissues which make the embryo more vulnerable to this insult. 33 refs., 1 tab.

  19. Clinical implications of blood eosinophil count in patients with non-asthma–COPD overlap syndrome COPD

    Directory of Open Access Journals (Sweden)

    Song JH

    2017-08-01

    Full Text Available Jin Hwa Song,1 Chang-Hoon Lee,1 Jin Woo Kim,2 Won-Yeon Lee,3 Ji Ye Jung,4 Joo Hun Park,5 Ki Suck Jung,6 Kwang Ha Yoo,7 Yong Bum Park,8 Deog Keom Kim9 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, 2Division of Pulmonology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, 3Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Gangwon-do, 4Division of Pulmonology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, 5Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon, 6Division of Pulmonary Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University Medical School, Anyang, Gyeonggi-do, 7Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, 8Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Kangdong Sacred Heart Hospital, 9Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Republic of Korea Background: Recent studies that assessed the relevance of the blood eosinophil count as a biomarker in patients with COPD may have overestimated it because they included patients with asthma–COPD overlap syndrome (ACOS. We investigated the clinical implications of the blood eosinophil count in patients with non-ACOS COPD.Patients and methods: From a Korean COPD Subtype Study (KOCOSS cohort, we selected patients with non-ACOS COPD after excluding ACOS patients according to Spanish criteria. Clinical characteristics and the incidence of moderate-to-severe exacerbation were compared

  20. Transplantation of autologous ex vivo expanded human conjunctival epithelial cells for treatment of pterygia: A prospective open-label single arm multicentric clinical trial

    Directory of Open Access Journals (Sweden)

    Viraf Sam Vasania

    2014-01-01

    Conclusion: We have, for the 1 st time, standardized a protocol for preparing autologous hCjEC grafts that can be safely transported to multiple centers across the country for transplantation. The clinical outcome was satisfactory for treating pterygia.

  1. Radiation-induced bystander effect: The important part of ionizing radiation response. Potential clinical implications

    Directory of Open Access Journals (Sweden)

    Maria Wideł

    2009-08-01

    Full Text Available It has long been a central radiobiological dogma that the damaging effects of ionizing radiation, such as cell death, cytogenetic changes, apoptosis, mutagenesis, and carcinogenesis, are the results of the direct ionization of cell structures, particularly DNA, or indirect damage via water radiolysis products. However, several years ago attention turned to a third mechanism of radiation, termed the “bystander effect” or “radiation-induced bystander effect” (RIBE. This is induced by agents and signals emitted by directly irradiated cells and manifests as a lowering of survival, cytogenetic damage, apoptosis enhancement, and biochemical changes in neighboring non-irradiated cells. The bystander effect is mainly observed in in vitro experiments using very low doses of alpha particles (range; mGy, cGy, but also after conventional irradiation (X-rays, gamma rays at low as well as conventional doses. The mechanisms responsible for the bystander effect are complex and still poorly understood. It is believed that molecular signals released from irradiated cells induce different signaling ways in non-irradiated neighboring cells, leading to the observed events. The molecular signals may be transmitted through gap junction intercellular communication and through a medium transfer mechanism. The nature of these transmitted factors are diverse, and still not defi nitely established. It seems that RIBE may have important clinical implications for health risk associated with radiation exposure. Potentially, this effectmay have important implications in the creation of whole-body or localized side effects in tissues beyond the irradiation fi eld and also in low-dose radiological and radioisotope diagnostics. Factors emitted by irradiated cells may result in the risk of genetic instability, mutations, and second primary cancer induction. They might also have their own part in inducing and extending post-radiation side effects in normal tissue. The

  2. Adrenal Disorders and the Paediatric Brain: Pathophysiological Considerations and Clinical Implications

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    Vincenzo Salpietro

    2014-01-01

    Full Text Available Various neurological and psychiatric manifestations have been recorded in children with adrenal disorders. Based on literature review and on personal case-studies and case-series we focused on the pathophysiological and clinical implications of glucocorticoid-related, mineralcorticoid-related, and catecholamine-related paediatric nervous system involvement. Childhood Cushing syndrome can be associated with long-lasting cognitive deficits and abnormal behaviour, even after resolution of the hypercortisolism. Exposure to excessive replacement of exogenous glucocorticoids in the paediatric age group (e.g., during treatments for adrenal insufficiency has been reported with neurological and magnetic resonance imaging (MRI abnormalities (e.g., delayed myelination and brain atrophy due to potential corticosteroid-related myelin damage in the developing brain and the possible impairment of limbic system ontogenesis. Idiopathic intracranial hypertension (IIH, a disorder of unclear pathophysiology characterised by increased cerebrospinal fluid (CSF pressure, has been described in children with hypercortisolism, adrenal insufficiency, and hyperaldosteronism, reflecting the potential underlying involvement of the adrenal-brain axis in the regulation of CSF pressure homeostasis. Arterial hypertension caused by paediatric adenomas or tumours of the adrenal cortex or medulla has been associated with various hypertension-related neurological manifestations. The development and maturation of the central nervous system (CNS through childhood is tightly regulated by intrinsic, paracrine, endocrine, and external modulators, and perturbations in any of these factors, including those related to adrenal hormone imbalance, could result in consequences that affect the structure and function of the paediatric brain. Animal experiments and clinical studies demonstrated that the developing (i.e., paediatric CNS seems to be particularly vulnerable to alterations induced by

  3. [Molecular Aspects of Thyroid Tumors with Emphasis on MicroRNA and Their Clinical Implications].

    Science.gov (United States)

    Ludvíková, M; Kholová, I; Kalfeřt, D

    Central to neoplastic transformation and tumor progression is alteration of the signaling pathways that control cell proliferation and apoptosis. The key mechanisms for this neoplastic process are genetic changes (mutations of cancer-related genes) and recently identified epigenetic changes that involve DNA methylation, chromatin remodeling (which has a profound effect on the control of gene expression), and noncoding, regulatory RNA (notably, microRNA - miRNA). MiRNAs control expression of their target gene post-transcriptionally. These molecular factors have potential as diagnostic, prognostic, and predictive molecular markers. Epithelial tumors of the thyroid gland are a histogenetically, morphologically, and pathobiologically heterogeneous group of neoplasms and require new, molecular approaches in clinical practice. This review aims to present contemporary scientific knowledge of this molecular (genetic and epigenetic) field of sporadic thyroid tumors of follicular cell origin and their potential clinical implications. The fundamental mutations (BRAFV600E, RET/PTC, RAS, and PAX8-PPARG) in selected tumor types are described comprehensively. Special attention is paid to miRNAs, including their biogenesis, function, and expression profiles in the most common thyroid tumors - follicular adenoma, follicular carcinoma, and papillary carcinoma. Thyroid cancer medicine has recently entered a new, molecular era. Comprehensive knowledge of all molecular aspects may improve diagnostics and management of thyroid neoplasms through the introduction of novel, progressive treatment strategies for this cancer. Further research on signaling pathway-related targets, standardization of methods, and evaluation of results are required.Key words: thyroid tumors - cancerogenesis - genetics - epigenetics - microRNA The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript

  4. HER2 in situ hybridization in breast cancer: clinical implications of polysomy 17 and genetic heterogeneity.

    Science.gov (United States)

    Hanna, Wedad M; Rüschoff, Josef; Bilous, Michael; Coudry, Renata A; Dowsett, Mitch; Osamura, Robert Y; Penault-Llorca, Frédérique; van de Vijver, Marc; Viale, Giuseppe

    2014-01-01

    Trastuzumab-containing therapy is a standard of care for patients with HER2+ breast cancer. HER2 status is routinely assigned using in situ hybridization to assess HER2 gene amplification, but interpretation of in situ hybridization results may be challenging in tumors with chromosome 17 polysomy or intratumoral genetic heterogeneity. Apparent chromosome 17 polysomy, defined by increased chromosome enumeration probe 17 (CEP17) signal number, is a common genetic aberration in breast cancer and represents an alternative mechanism for increasing HER2 copy number. Some studies have linked elevated CEP17 count ('polysomy') with adverse clinicopathologic features and HER2 overexpression, although there are numerous discrepancies in the literature. There is evidence that elevated CEP17 ('polysomy') count might account for trastuzumab response in tumors with normal HER2:CEP17 ratios. Nonetheless, recent studies establish that apparent 'polysomy' (CEP17 increase) is usually related to focal pericentromeric gains rather than true polysomy. Assigning HER2 status may also be complex where multiple cell subclones with distinct HER2 amplification characteristics coexist within the same tumor. Such genetic heterogeneity affects up to 40% of breast cancers when assessed according to a College of American Pathologists guideline, although other definitions have been proposed. Recent data have associated heterogeneity with unfavorable clinicopathologic variables and poor prognosis. Genetically heterogeneous tumors harboring HER2-amplified subclones have the potential to benefit from trastuzumab, but this has yet to be evaluated in clinical studies. In this review, we discuss the implications of apparent polysomy 17 and genetic heterogeneity for assigning HER2 status in clinical practice. Among our recommendations, we support the use of mean HER2 copy number rather than HER2:CEP17 ratio to define HER2 positivity in cases where coamplification of the centromere might mask HER2

  5. Clinical implications of a possible role of vitamin D in multiple sclerosis.

    Science.gov (United States)

    Pierrot-Deseilligny, Charles

    2009-09-01

    Hypovitaminosis D is currently one of the most studied environmental risk factors for multiple sclerosis (MS) and is potentially the most promising in terms of new clinical implications. These practical consequences, which could be applied to MS patients without further delay, constitute the main purpose of this review. Vitamin D is involved in a number of important general actions, which were not even suspected until quite recently. In particular, this vitamin could play an immunomodulatory role in the central nervous system. Many and varied arguments support a significant role for vitamin D in MS. In animal studies, vitamin D prevents and improves experimental autoimmune encephalomyelitis. Epidemiologically, latitude, past exposure to sun and the serum level of vitamin D influence the risk of MS, with, furthermore, significant links existing between these different factors. Clinically, most MS patients have low serum levels of vitamin D and are in a state of insufficiency or even deficiency compared to the international norm, which has been established on a metabolic basis. Large therapeutic trials using vitamin D are still lacking but the first results of phase I/II studies are promising. In the meantime, while awaiting the results of future therapeutic trials, it can no longer be ignored that many MS patients have a lack of vitamin D, which could be detected by a serum titration and corrected using an appropriate vitamin D supplementation in order to restore their serum level to within the normal range. From a purely medical point of view, vitamin D supplementation appears in this light to be unavoidable in order to improve the general state of these patients. Furthermore, it cannot currently be ruled out that this supplementation could also be neurologically beneficial.

  6. Integrative analysis of epigenetic modulation in melanoma cell response to decitabine: clinical implications.

    Directory of Open Access Journals (Sweden)

    Ruth Halaban

    Full Text Available Decitabine, an epigenetic modifier that reactivates genes otherwise suppressed by DNA promoter methylation, is effective for some, but not all cancer patients, especially those with solid tumors. It is commonly recognized that to overcome resistance and improve outcome, treatment should be guided by tumor biology, which includes genotype, epigenotype, and gene expression profile. We therefore took an integrative approach to better understand melanoma cell response to clinically relevant dose of decitabine and identify complementary targets for combined therapy. We employed eight different melanoma cell strains, determined their growth, apoptotic and DNA damage responses to increasing doses of decitabine, and chose a low, clinically relevant drug dose to perform whole-genome differential gene expression, bioinformatic analysis, and protein validation studies. The data ruled out the DNA damage response, demonstrated the involvement of p21(Cip1 in a p53-independent manner, identified the TGFbeta pathway genes CLU and TGFBI as markers of sensitivity to decitabine and revealed an effect on histone modification as part of decitabine-induced gene expression. Mutation analysis and knockdown by siRNA implicated activated beta-catenin/MITF, but not BRAF, NRAS or PTEN mutations as a source for resistance. The importance of protein stability predicted from the results was validated by the synergistic effect of Bortezomib, a proteasome inhibitor, in enhancing the growth arrest of decitabine in otherwise resistant melanoma cells. Our integrative analysis show that improved therapy can be achieved by comprehensive analysis of cancer cells, identified biomarkers for patient's selection and monitoring response, as well as targets for improved combination therapy.

  7. Impact of new-onset persistent left bundle branch block on late clinical outcomes in patients undergoing transcatheter aortic valve implantation with a balloon-expandable valve.

    Science.gov (United States)

    Urena, Marina; Webb, John G; Cheema, Asim; Serra, Vicenç; Toggweiler, Stefan; Barbanti, Marco; Cheung, Anson; Ye, Jian; Dumont, Eric; DeLarochellière, Robert; Doyle, Daniel; Al Lawati, Hatim A; Peterson, Marc; Chisholm, Robert; Igual, Albert; Ribeiro, Henrique Barbosa; Nombela-Franco, Luis; Philippon, François; Garcia Del Blanco, Bruno; Rodés-Cabau, Josep

    2014-02-01

    The aim of this study was to determine the impact of new-onset persistent left bundle branch block (NOP-LBBB) on late outcomes after transcatheter aortic valve implantation (TAVI). The impact of NOP-LBBB after TAVI remains controversial. A total of 668 consecutive patients who underwent TAVI with a balloon-expandable valve without pre-existing LBBB or permanent pacemaker implantation (PPI) were included. Electrocardiograms were obtained at baseline, immediately after the procedure, and daily until hospital discharge. Patients were followed at 1, 6, and 12 months and yearly thereafter. New-onset LBBB occurred in 128 patients (19.2%) immediately after TAVI and persisted at hospital discharge in 79 patients (11.8%). At a median follow-up of 13 months (range 3 to 27 months), there were no differences in mortality rate between the NOP-LBBB and no NOP-LBBB groups (27.8% vs. 28.4%; adjusted-hazard ratio: 0.87 [95% confidence interval (CI): 0.55 to 1.37]; p = 0.54). There were no differences between groups regarding cardiovascular mortality (p = 0.82), sudden death (p = 0.87), rehospitalizations for all causes (p = 0.11), or heart failure (p = 0.55). NOP-LBBB was the only factor associated with an increased rate of PPI during the follow-up period (13.9% vs. 3.0%; hazard ratio: 4.29 [95% CI: 2.03 to 9.07], p < 0.001. NOP-LBBB was also associated with a lack of left ventricular ejection fraction improvement and poorer New York Heart Association functional class at follow-up (p < 0.02 for both). NOP-LBBB occurred in ∼1 of 10 patients who had undergone TAVI with a balloon-expandable valve. NOP-LBBB was associated with a higher rate of PPI, a lack of improvement in left ventricular ejection fraction, and a poorer functional status, but did not increase the risk of global or cardiovascular mortality or rehospitalizations at 1-year follow-up. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  8. Activation of sigma-1 receptor chaperone in the treatment of neuropsychiatric diseases and its clinical implication

    Directory of Open Access Journals (Sweden)

    Kenji Hashimoto

    2015-01-01

    Full Text Available Endoplasmic reticulum (ER protein sigma-1 receptor represents unique chaperone activity in the central nervous system, and it exerts a potent influence on a number of neurotransmitter systems. Several lines of evidence suggest that activation of sigma-1 receptor plays a role in the pathophysiology of neuropsychiatric diseases, as well as in the mechanisms of some therapeutic drugs and neurosteroids. Preclinical studies showed that some selective serotonin reuptake inhibitors (SSRIs; fluvoxamine, fluoxetine, excitalopram, donepezil, and ifenprodil act as sigma-1 receptor agonists. Furthermore, sigma-1 receptor agonists could improve the N-methyl-D-aspartate (NMDA antagonist phencyclidine (PCP-induced cognitive deficits in mice. A study using positron emission tomography have demonstrated that an oral administration of fluvoxamine or donepezil could bind to sigma-1 receptor in the healthy human brain, suggesting that sigma-1 receptor might be involved in the therapeutic mechanisms of these drugs. Moreover, case reports suggest that sigma-1 receptor agonists, including fluvoxamine, and ifenprodil, may be effective in the treatment of cognitive impairment in schizophrenia, delirium in elderly people, and flashbacks in post-traumatic stress disorder. In this review article, the author would like to discuss the clinical implication of sigma-1 receptor agonists, including endogenous neurosteroids, in the neuropsychiatric diseases.

  9. The genetic basis of familial adenomatous polyposis and its implications for clinical practice and risk management

    Directory of Open Access Journals (Sweden)

    Leoz ML

    2015-04-01

    Full Text Available Maria Liz Leoz, Sabela Carballal, Leticia Moreira, Teresa Ocaña, Francesc Balaguer Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS, Barcelona, Catalonia, Spain Abstract: Familial adenomatous polyposis (FAP is an inherited disorder that represents the most common gastrointestinal polyposis syndrome. Germline mutations in the APC gene were initially identified as responsible for FAP, and later, several studies have also implicated the MUTYH gene as responsible for this disease, usually referred to as MUTYH-associated polyposis (MAP. FAP and MAP are characterized by the early onset of multiple adenomatous colorectal polyps, a high lifetime risk of colorectal cancer (CRC, and in some patients the development of extracolonic manifestations. The goal of colorectal management in these patients is to prevent CRC mortality through endoscopic and surgical approaches. Individuals with FAP and their relatives should receive appropriate genetic counseling and join surveillance programs when indicated. This review is focused on the description of the main clinical and genetic aspects of FAP associated with germline APC mutations and MAP. Keywords: colorectal cancer, familial adenomatous polyposis, MAP, APC, MUTYH

  10. Endothelial nitric oxide synthase: From biochemistry and gene structure to clinical implications of NOS3 polymorphisms.

    Science.gov (United States)

    Oliveira-Paula, Gustavo H; Lacchini, Riccardo; Tanus-Santos, Jose E

    2016-01-10

    Nitric oxide (NO) is an important vasodilator with a well-established role in cardiovascular homeostasis. While mediator is synthesized from L-arginine by neuronal, endothelial, and inducible nitric oxide synthases (NOS1,NOS3 and NOS2 respectively), NOS3 is the most important isoform for NO formation in the cardiovascular system. NOS3 is a dimeric enzyme whose expression and activity are regulated at transcriptional, posttranscriptional,and posttranslational levels. The NOS3 gene, which encodes NOS3, exhibits a number of polymorphic sites including single nucleotide polymorphisms (SNPs), variable number of tandem repeats (VNTRs), microsatellites, and insertions/deletions. Some NOS3 polymorphisms show functional effects on NOS3 expression or activity, thereby affecting NO formation. Interestingly, many studies have evaluated the effects of functional NOS3 polymorphisms on disease susceptibility and drug responses. Moreover, some studies have investigated how NOS3 haplotypes may impact endogenous NO formation and disease susceptibility. In this article,we carried out a comprehensive review to provide a basic understanding of biochemical mechanisms involved in NOS3 regulation and how genetic variations in NOS3 may translate into relevant clinical and pharmacogenetic implications.

  11. A case report of embryo donation: ethical and clinical implications for psychologists.

    Science.gov (United States)

    Rizk, Marianne; Pawlak, Stacey

    2016-10-01

    Third-party reproduction is a growing field, and an increasing body of literature considers the ethics of embryo donation. Due to the psychosocial complexities that generally accompany the donation and/or use of donor embryos, psychologists can play a pivotal role in these specialised fertility cases. While laws in the USA are in place to regulate the medical procedures involved in embryo donation, only unenforceable guidelines exist for psychologists specialising in fertility cases. The presentation of this case study aims to: (1) clarify the ethical concerns that fertility psychologists should consider in similar situations by assessing whether American Society of Reproductive Medicine (ASRM) and the American Psychological Association (APA) guidelines compete or complement one another within this case of embryo donation and (2) consider the interests, obligations and rights of all parties involved. Several principles, standards and guidelines that must be considered are described. Overall, the APA Ethics Code and the ASRM Guidelines appear to complement one another for most aspects of this case. Fertility psychologists should consider the clinical implications of the interests, rights and duties of all involved parties, including themselves. 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/

  12. Beat-to-beat variability of cardiac action potential duration: underlying mechanism and clinical implications.

    Science.gov (United States)

    Nánási, Péter P; Magyar, János; Varró, András; Ördög, Balázs

    2017-10-01

    Beat-to-beat variability of cardiac action potential duration (short-term variability, SV) is a common feature of various cardiac preparations, including the human heart. Although it is believed to be one of the best arrhythmia predictors, the underlying mechanisms are not fully understood at present. The magnitude of SV is basically determined by the intensity of cell-to-cell coupling in multicellular preparations and by the duration of the action potential (APD). To compensate for the APD-dependent nature of SV, the concept of relative SV (RSV) has been introduced by normalizing the changes of SV to the concomitant changes in APD. RSV is reduced by I Ca , I Kr , and I Ks while increased by I Na , suggesting that ion currents involved in the negative feedback regulation of APD tend to keep RSV at a low level. RSV is also influenced by intracellular calcium concentration and tissue redox potential. The clinical implications of APD variability is discussed in detail.

  13. Effects of radiation on T regulatory cells in normal states and cancer: mechanisms and clinical implications.

    Science.gov (United States)

    Liu, Shu; Sun, Xiangdong; Luo, Jinhua; Zhu, Hongcheng; Yang, Xi; Guo, Qing; Song, Yaqi; Sun, Xinchen

    2015-01-01

    Radiation remains an important component of cancer treatment. In addition to inducing tumor cell death through direct cytotoxic effects, radiation can also promote the regression of tumor via augment of immune response. Regulatory T cells (Tregs) are a unique subpopulation of CD4 positive cells, which are characterized by expression of the forkhead box P3 (Foxp3) transcription factor and high levels of CD25. Mounting evidence has shown that Tregs are implicated in the development and progression of various types of cancer, which makes Tregs an important target in cancer therapeutics. Generally, lymphocytes are regarded as radiosensitive. However, Tregs have been demonstrated to be relatively resistant to radiotherapy, which is partly mediated by downregulation of pro-apoptotic proteins and upregulation of anti-apoptotic proteins. Moreover, radiotherapy can increase the production of Tregs and the recruitment of Tregs to local tumor microenvironment. Tregs can attenuate radiation-induced tumor death, which cause the resistance of tumor to radiotherapy. Recent experimental studies and clinical trails have demonstrated that the combination of radiation with medications that target Tregs is promising in the treatment of several types of neoplasms. In this review, we discussed the effect of radiation on Tregs in physiological states and cancer. Further, we presented an overview of therapies that target Tregs to enhance the efficacy of radiation in cancer therapeutics.

  14. Quantifying Discipline Practices Using Absolute vs. Relative Frequencies: Clinical and Research Implications for Child Welfare

    Science.gov (United States)

    Lindhiem, Oliver; Shaffer, Anne; Kolko, David J.

    2014-01-01

    In the parent intervention outcome literatures, discipline practices are generally quantified as absolute frequencies or, less commonly, as relative frequencies. These differences in methodology warrant direct comparison as they have critical implications for study results and conclusions among treatments targeted at reducing parental aggression and harsh discipline. In this study, we directly compared the absolute frequency method and the relative frequency method for quantifying physically aggressive, psychologically aggressive, and nonaggressive discipline practices. Longitudinal data over a 3-year period came from an existing data set of a clinical trial examining the effectiveness of a psychosocial treatment in reducing parental physical and psychological aggression and improving child behavior (N = 139; Kolko et al., 2009). Discipline practices (both aggressive and nonaggressive) were assessed using the Conflict Tactics Scale (CTS; Straus et al., 1998). The two methods yielded different patterns of results, particularly for nonaggressive discipline strategies. We suggest that each method makes its own unique contribution to a more complete understanding of the association between parental aggression and intervention effects. PMID:24106146

  15. Cue-induced craving in pathological buying: empirical evidence and clinical implications.

    Science.gov (United States)

    Trotzke, Patrick; Starcke, Katrin; Pedersen, Anya; Brand, Matthias

    2014-01-01

    Pathological buying is associated with marked distress and impaired functioning in important life domains. It is currently under debate whether pathological buying can be considered a behavioral addiction. In analogy to results reported in addicted individuals, craving reactions elicited by addiction-related cues might be an underlying mechanism for the etiology and pathogenesis of pathological buying. In the present study, 30 pathological buyers and 30 matched control participants were examined with a cue-reactivity paradigm consisting of shopping and control cues. Skin conductance responses, as well as subjective ratings for arousal, valence, and urge to buy, were assessed. Subjective craving reactions were measured before and after the cue-reactivity paradigm. On a physiological level, skin conductance responses toward shopping cues were higher in pathological buyers (mean [M; standard deviation {SD}] = 0.26 [0.13]) compared with control participants (M [SD] = 0.19 [0.09]; t(58) = 2.29, p = .025, d = 0.60). On a behavioral level, the individuals with pathological buying rated the shopping cues as more arousing and more positive, and reported a greater urge to buy compared with control participants and with control cues. An increase in subjective craving after completing the cue-reactivity paradigm was observed only in the pathological buyers (Mpre [SD] = 1.95 [1.47], Mpost [SD] = 2.87 [1.79]; t(29) = 5.07, p buying. The results demonstrate similarities between pathological buying and substance or behavioral addictions and provide implications for clinical treatment.

  16. Clinical implications of antimitochondrial antibodies in type 1 autoimmune hepatitis: a longitudinal study.

    Science.gov (United States)

    Mishima, Shiho; Omagari, Katsuhisa; Ohba, Kazuo; Kadokawa, Yoshiko; Masuda, Jun-ichi; Mishima, Ryosuke; Kinoshita, Hideki; Hayashida, Kenji; Isomoto, Hajime; Shikuwa, Saburo; Mizuta, Yohei; Kohno, Shigeru

    2008-01-01

    Autoimmune hepatitis (AIH) is a chronic liver disease characterized by the presence of antinuclear antibodies. However, antimitochondrial antibodies (AMA) and bile duct changes, which are the characteristics of primary biliary cirrhosis (PBC), can be detected in AIH patients. Twenty patients with definite AIH were prospectively followed-up, and the serial changes in AMA profiles were determined. We also examined the correlations between these antibodies and histopathological findings in the liver. Of the 20 patients, 7 (35%) had bile duct injury, and 2 of these 7 patients also showed chronic nonsuppurative destructive cholangitis or ductopenia of interlobular bile ducts histopathologically. Serologically, 7 patients (35%) were positive for AMA at least once by immunoblotting during the follow-up periods. There were no significant differences in biochemical hepatobiliary indices, the presence of bile duct lesions, or the changes in biochemical profiles between AMA-positive and AMA-negative AIH patients during the follow-up periods. We confirmed that AMA and certain histopathological findings that are characteristics of PBC can be seen in some AIH patients. However, there was no significant correlation between AMA positivity and the histopathological findings in the liver, or biochemical hepatobiliary indices. Thus, the clinical implications of AMA in AIH patients remain unclear.

  17. A Neurophysiological and Neuropsychological Consideration of Mindful Movement: Clinical and Research Implications.

    Science.gov (United States)

    Russell, Tamara Anne; Arcuri, Silvia Maria

    2015-01-01

    In this article, we present ideas related to three key aspects of mindfulness training: the regulation of attention via noradrenaline, the importance of working memory and its various components (particularly the central executive and episodic buffer), and the relationship of both of these to mind-wandering. These same aspects of mindfulness training are also involved in the preparation and execution of movement and implicated in the pathophysiology of psychosis. We argue that by moving in a mindful way, there may be an additive effect of training as the two elements of the practice (mindfulness and movement) independently, and perhaps synergistically, engage common underlying systems (the default mode network). We discuss how working with mindful movement may be one route to mindfulness training for individuals who would struggle to sit still to complete the more commonly taught mindfulness practices. Drawing on our clinical experience working with individuals with severe and enduring mental health conditions, we show the real world application of these ideas and how they can be used to help those who are suffering and for whom current treatments are still far from adequate.

  18. White and brown adipose stem cells: from signaling to clinical implications.

    Science.gov (United States)

    Algire, Carolyn; Medrikova, Dasa; Herzig, Stephan

    2013-05-01

    Epidemiological studies estimate that by the year 2030, 2.16 billion people worldwide will be overweight and 1.12 billion will be obese [1]. Besides its now established function as an endocrine organ, adipose tissue plays a fundamental role as an energy storage compartment. As such, adipose tissue is capable of extensive expansion or retraction depending on the energy balance or disease state of the host, a plasticity that is unparalleled in other organs and - under conditions of excessive energy intake - significantly contributes to the afore mentioned obesity pandemic. Expansion of adipose tissue is driven by both hypertrophy and hyperplasia of adipocytes, which can renew frequently to compensate for cell death. This underlines the importance of adipocyte progenitor cells within the distinct adipose tissue depots to control both energy storage and endocrine functions of adipose tissue. Here we summarize recent findings on the identity and plasticity of adipose stem cells, the involved signaling cascades, and potential clinical implications of these cells for the treatment of metabolic dysfunction in obesity. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Mechanical ventilation in Duchenne patients with chronic respiratory insufficiency: clinical implications of 20 years published experience.

    Science.gov (United States)

    Toussaint, M; Chatwin, M; Soudon, P

    2007-01-01

    Chronic respiratory insufficiency is inevitable in the course of disease progression in patients with Duchenne muscular dystrophy (DMD). Without mechanical ventilation (MV), morbidity and mortality are highly likely towards the end of the second decade of life. The present review reports evidence and clinical implications regarding DMD patients treated with MV. There is no doubt that nocturnal hypercapnia precedes daytime hypercapnia. Historical comparisons have provided evidence that non-invasive intermittent positive pressure ventilation (NIPPV) at night is effective and improves quality of life and survival by 5-10 years. By contrast, the optimal criteria and timing for initiation of NIPPV are inconsistent. A recent randomized study however demonstrated the benefits of commencing NIPPV as soon as nocturnal hypoventilation is detected (Ward S, et al., Randomised controlled trial of non-invasive ventilation (NIV) for nocturnal hypoventilation in neuromuscular and chest wall disease patients with daytime normocapnia. Thorax 2005; 60: 1019-24). The respective role of the three hypotheses of the indirect action of nocturnal NIPPV on daytime blood gases may be complimentary; the main improvement may be due to improved ventilatory response to CO2. The ultimate time to offer full time ventilation with the most advantageous interface is lacking in evidence. Full time NIV is possible with a combination of a nasal mask during the night and a mouthpiece during the day, however tracheostomy may be provided when mechanical techniques of cough-assistance are useless to treat chronic cough insufficiency.

  20. The Implications of Endoscopic Ulcer in Early Gastric Cancer: Can We Predict Clinical Behaviors from Endoscopy?

    Science.gov (United States)

    Lee, Yoo Jin; Kim, Jie-Hyun; Park, Jae Jun; Youn, Young Hoon; Park, Hyojin; Kim, Jong Won; Choi, Seung Ho; Noh, Sung Hoon

    2016-01-01

    The presence of ulcer in early gastric cancer (EGC) is important for the feasibility of endoscopic resection, only a few studies have examined the clinicopathological implications of endoscopic ulcer in EGC. To determine the role of endoscopic ulcer as a predictor of clinical behaviors in EGC. Data of 3,270 patients with EGC who underwent surgery between January 2005 and December 2012 were reviewed. Clinicopathological characteristics were analyzed in relation to the presence and stage of ulcer in EGC. Based on endoscopic findings, the stage of ulcer was categorized as active, healing, or scar. Logistic regression analysis was performed to analyze factors associated with lymph node metastasis (LNM). 2,343 (71.7%) patients had endoscopic findings of ulceration in EGC. Submucosal (SM) invasion, LNM, lymphovascular invasion (LVI), perineural invasion, and undifferentiated-type histology were significantly higher in ulcerative than non-ulcerative EGC. Comparison across different stages of ulcer revealed that SM invasion, LNM, and LVI were significantly associated with the active stage, and that these features exhibited significant stage-based differences, being most common at the active stage, and least common at the scar stage. The presence of endoscopic ulcer and active status of the ulcer were identified as independent risk factors for LNM. Ulcerative EGC detected by endoscopy exhibited more aggressive behaviors than non-ulcerative EGC. Additionally, the endoscopic stage of ulcer may predict the clinicopathological behaviors of EGC. Therefore, the appearance of ulcers should be carefully evaluated to determine an adequate treatment strategy for EGC.

  1. Prevalence and clinical implications of renal artery stenosis in pediatric moyamoya disease.

    Science.gov (United States)

    Baek, Jin Wook; Jo, Kyung-Il; Park, Jeong Jin; Jeon, Pyoung; Kim, Keon Ha

    2016-01-01

    Until recently, extracranial involvement of moyamoya disease (MMD) had not been fully elucidated. The purpose of this study was to determine the prevalence and clinical implications of renal artery stenosis in pediatric MMD patients. This retrospective study included 101 pediatric (renal angiography. Baseline characteristics, including hypertension (HT) and angiographic findings, were retrospectively evaluated. The median age was 8 (range 2-16) years. Six patients (5.9%) had HT. Renal artery stenosis was identified in 8 patients (7.9%). Five of 8 renal artery stenosis patients had HT. Statistical analysis showed that advanced stages of MMD and HT were associated with renal artery stenosis (p Renal artery stenosis was not uncommon in pediatric MMD. Renal artery evaluation could help determine the cause of HT in advanced pediatric MMD cases. Further prospective and large-scale studies may be helpful in elucidating the extracranial manifestation of MMD. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  2. The clinical implications of variants of vena cava inferior and aorta on retroperitoneal surgery

    Directory of Open Access Journals (Sweden)

    S. V. Mukhtarulina

    2014-12-01

    Full Text Available Objective: to study variants of retroperitoneal vascular structure and its clinical implications on retroperitoneal surgery in patients with cervical cancer IA–IIB stage.Materials and methods. 101 patients who underwent paraaortic and bilateral pelvic lymphadenectomy were included in this study. 10 patients of the first group with anomalies of inferior vena cava, renal arteries and veins, common iliac vein and ovarian vessels were compared with 91 patients of the second group without anomalies.Results. Variants of major retroperitoneal vascular structure were present in 10 (9.9 % patients. Supernumerary renal arteries and veins observed in 5 (4.9 % patients; retroaortic left renal vein type I and II – in 3 (3.0 % patients. Double vena cava inferior detected in 1 (1.0 % patient. Patients with variants of retroperitoneal vascular structures hadn’t vessel injury. There was no difference in intraoperative hemorrhage, transfusion red blood cell, rate of intraoperative hemoglobin and removed paraaortic lymph nodes between the groups. Risk factors for intraoperative bleeding in patients with cervical cancer, depending on the presence or absence of anomalies of retroperitoneal vessels had no significant difference.Conclusion. Despite the fact that the variants of retroperitoneal vascular structures are rare (9.9 %, the success of retroperitoneal surgery is associated with the knowledge of vascular variations which decrease serious, life-threatening complications.

  3. The clinical implications of variants of vena cava inferior and aorta on retroperitoneal surgery

    Directory of Open Access Journals (Sweden)

    S. V. Mukhtarulina

    2014-01-01

    Full Text Available Objective: to study variants of retroperitoneal vascular structure and its clinical implications on retroperitoneal surgery in patients with cervical cancer IA–IIB stage.Materials and methods. 101 patients who underwent paraaortic and bilateral pelvic lymphadenectomy were included in this study. 10 patients of the first group with anomalies of inferior vena cava, renal arteries and veins, common iliac vein and ovarian vessels were compared with 91 patients of the second group without anomalies.Results. Variants of major retroperitoneal vascular structure were present in 10 (9.9 % patients. Supernumerary renal arteries and veins observed in 5 (4.9 % patients; retroaortic left renal vein type I and II – in 3 (3.0 % patients. Double vena cava inferior detected in 1 (1.0 % patient. Patients with variants of retroperitoneal vascular structures hadn’t vessel injury. There was no difference in intraoperative hemorrhage, transfusion red blood cell, rate of intraoperative hemoglobin and removed paraaortic lymph nodes between the groups. Risk factors for intraoperative bleeding in patients with cervical cancer, depending on the presence or absence of anomalies of retroperitoneal vessels had no significant difference.Conclusion. Despite the fact that the variants of retroperitoneal vascular structures are rare (9.9 %, the success of retroperitoneal surgery is associated with the knowledge of vascular variations which decrease serious, life-threatening complications.

  4. A randomized controlled clinical multicenter trial comparing the clinical and histological performance of a new, modified polylactide-co-glycolide acid membrane to an expanded polytetrafluorethylene membrane in guided bone regeneration procedures.

    Science.gov (United States)

    Schneider, David; Weber, Franz E; Grunder, Ueli; Andreoni, Claude; Burkhardt, Rino; Jung, Ronald E

    2014-02-01

    To compare the clinical and histological outcomes of a resorbable modified polylactide/polyglycolide acid (PLGA) test membrane and a titanium-reinforced expanded polytetrafluorethylene (ePTFE) control membrane used for guided bone regeneration (GBR) around dental implants. A total of 40 patients with peri-implant dehiscence-type defects were randomly allocated to a GBR procedure using either a modified PLGA test or an ePTFE control membrane. Soft tissue condition, implant integration, adverse events and quality of life were recorded during the 6-month healing period. At re-entry peri-implant bone defect dimensions were measured and compared with values recorded at implant/GBR surgery. A biopsy was retrieved for qualitative and quantitative histological analyses. A comparison between the groups was conducted using non-parametric statistical tests. Soft tissue complications were observed in five test patients and two control patients. Except for soft tissue complications and incomplete regeneration, no procedure- or device-related adverse events were observed. The vertical bone defect component was, in mean, reduced by-5.1 mm (95% CI -6.8, -3.3) in the test group and -6.9 mm (95% CI -8.2, -5.5 mm) in the control group. The mean residual vertical defect height measured 1.2 ± 2.4 mm in the test group and 0.3 ± 1.1 mm in the control group meaning a mean defect resolution of 81% in the test group and 96% in the control group (P = 0.161). The horizontal bone thickness at implant shoulder level decreased from a mean of 3.2 mm to 1.4 mm (-56%, mean -1.7 mm, 95% CI -2.3, -1.1) in the test group and from 3.3 mm to 2.5 mm (-24%, mean -0.8 mm, 95% CI -1.3, -0.3) in the control group (P = 0.022). Qualitative and quantitative histological analyses did not show significant differences in the tissue composition between groups. Peri-implant GBR was successfully performed using either of the membranes. The control membrane was able to better maintain the horizontal thickness of

  5. Expanding the clinical spectrum of B4GALT7 deficiency: homozygous p.R270C mutation with founder effect causes Larsen of Reunion Island syndrome

    Science.gov (United States)

    Cartault, François; Munier, Patrick; Jacquemont, Marie-Line; Vellayoudom, Jeannine; Doray, Bérénice; Payet, Christine; Randrianaivo, Hanitra; Laville, Jean-Marc; Munnich, Arnold; Cormier-Daire, Valérie

    2015-01-01

    First described as a variant of Larsen syndrome in Reunion Island (LRS) in the southern Indian Ocean, ‘Larsen of Reunion Island syndrome' is characterized by dwarfism, hyperlaxity, multiple dislocations and distinctive facial features. It overlaps with Desbuquois dysplasia, Larsen syndrome and spondyloepiphyseal dysplasia with dislocations ascribed to CANT1, FLNB and CHST3 mutations, respectively. We collected the samples of 22 LRS cases. After exclusion of CANT1, FLNB and CHST3 genes, an exome sequencing was performed in two affected second cousins and one unaffected sister. We identified a homozygous missense mutation in B4GALT7, NM_007255.2: c.808C>T p.(Arg270Cys) named p.R270C, in the two affected cases, not present in the unaffected sister. The same homozygous mutation was subsequently identified in the remaining 20 LRS cases. Our findings demonstrate that B4GALT7 is the causative gene for LRS. The identification of a unique homozygous mutation argues in favor of a founder effect. B4GALT7 encodes a galactosyltransferase, required for the initiation of glycoaminoglycan side chain synthesis of proteoglycans. This study expands the phenotypic spectrum of B4GALT7 mutations, initially described as responsible for the progeroid variant of Ehlers–Danlos syndrome. It further supports a common physiopathological basis involving proteoglycan synthesis in skeletal disorders with dislocations. PMID:24755949

  6. Urea Cycle Defects: Early-Onset Disease Associated with A208T Mutation in OTC Gene—Expanding the Clinical Phenotype

    Directory of Open Access Journals (Sweden)

    Ana Isabel Sánchez

    2017-01-01

    Full Text Available Ornithine transcarbamylase deficiency (OMIM: 311250 is the most common disorder of urea cycle disorders, accounting for nearly 50% of all cases. We report a case of a two-month- old male patient, who attends our medical genetics consultation because of low citrulline levels and elevated glutamine to citrulline ratio detected by expanded newborn screening with tandem mass spectrometry. He is an asymptomatic male with a normal physical examination and appropriate neurodevelopmental milestones. The patient has a family history of one older brother who died at 18 months old from severe and sudden hyperammonemia and a maternal aunt who suddenly died at two years old. He had high plasma ammonium concentration and a confirmed OTC mutation (p.A208T. Usually, this mutation causes OTC deficiency of late onset in adult males. However, this report raises awareness about mutations previously described as a late-onset causing disease, which can cause severe hyperammonemia and high risk of dying at an early age.

  7. Expanding Thurston maps

    CERN Document Server

    Bonk, Mario

    2017-01-01

    This monograph is devoted to the study of the dynamics of expanding Thurston maps under iteration. A Thurston map is a branched covering map on a two-dimensional topological sphere such that each critical point of the map has a finite orbit under iteration. It is called expanding if, roughly speaking, preimages of a fine open cover of the underlying sphere under iterates of the map become finer and finer as the order of the iterate increases. Every expanding Thurston map gives rise to a fractal space, called its visual sphere. Many dynamical properties of the map are encoded in the geometry of this visual sphere. For example, an expanding Thurston map is topologically conjugate to a rational map if and only if its visual sphere is quasisymmetrically equivalent to the Riemann sphere. This relation between dynamics and fractal geometry is the main focus for the investigations in this work.

  8. Medical physics in radiotherapy: The importance of preserving clinical responsibilities and expanding the profession's role in research, education, and quality control

    Science.gov (United States)

    Malicki, Julian

    2015-01-01

    Medical physicists have long had an integral role in radiotherapy. In recent decades, medical physicists have slowly but surely stepped back from direct clinical responsibilities in planning radiotherapy treatments while medical dosimetrists have assumed more responsibility. In this article, I argue against this gradual withdrawal from routine therapy planning. It is essential that physicists be involved, at least to some extent, in treatment planning and clinical dosimetry for each and every patient; otherwise, physicists can no longer be considered clinical specialists. More importantly, this withdrawal could negatively impact treatment quality and patient safety. Medical physicists must have a sound understanding of human anatomy and physiology in order to be competent partners to radiation oncologists. In addition, they must possess a thorough knowledge of the physics of radiation as it interacts with body tissues, and also understand the limitations of the algorithms used in radiotherapy. Medical physicists should also take the lead in evaluating emerging challenges in quality and safety of radiotherapy. In this sense, the input of physicists in clinical audits and risk assessment is crucial. The way forward is to proactively take the necessary steps to maintain and advance our important role in clinical medicine. PMID:25949219

  9. Medical physics in radiotherapy: The importance of preserving clinical responsibilities and expanding the profession's role in research, education, and quality control.

    Science.gov (United States)

    Malicki, Julian

    2015-01-01

    Medical physicists have long had an integral role in radiotherapy. In recent decades, medical physicists have slowly but surely stepped back from direct clinical responsibilities in planning radiotherapy treatments while medical dosimetrists have assumed more responsibility. In this article, I argue against this gradual withdrawal from routine therapy planning. It is essential that physicists be involved, at least to some extent, in treatment planning and clinical dosimetry for each and every patient; otherwise, physicists can no longer be considered clinical specialists. More importantly, this withdrawal could negatively impact treatment quality and patient safety. Medical physicists must have a sound understanding of human anatomy and physiology in order to be competent partners to radiation oncologists. In addition, they must possess a thorough knowledge of the physics of radiation as it interacts with body tissues, and also understand the limitations of the algorithms used in radiotherapy. Medical physicists should also take the lead in evaluating emerging challenges in quality and safety of radiotherapy. In this sense, the input of physicists in clinical audits and risk assessment is crucial. The way forward is to proactively take the necessary steps to maintain and advance our important role in clinical medicine.

  10. Demographic variables, clinical aspects, and medicolegal implications in a population of patients with adjustment disorder

    Directory of Open Access Journals (Sweden)

    Anastasia A

    2016-04-01

    suggest that AD may have a distinct profile in demographic and clinical terms. Increased scientific attention is hoped, particularly focused on addressing a better definition of diagnostic criteria, whose correctness and accuracy are critical, especially in situations with medicolegal implications. Keywords: adjustment disorder, diagnostic criteria, stressor, mobbing, medicolegal

  11. Biology and clinical implications of CD133{sup +} liver cancer stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Stephanie, E-mail: stefma@hku.hk [Department of Clinical Oncology, State Key Laboratory for Liver Research, LKS Faculty of Medicine, The University of Hong Kong (Hong Kong)

    2013-01-15

    in CD133{sup +} liver CSC research with regard to identification, regulation and clinical implications will be discussed.

  12. A comparison of skin expansion and contraction between one expander and two expanders: a preliminary study.

    Science.gov (United States)

    Zhang, Gan-lin; Zhang, Jin-ming; Ji, Chen-yang; Meng, Hong; Huang, Jian-hua; Luo, He-yuan; Zhang, Hua-sheng; Liu, Xiao-tao; Hong, Xiao-fang

    2013-12-01

    This study aimed to compare the difference between the skin expansion and contraction rates for an expanded flap with one versus two expanders. The study cohort comprised 24 cases of two overlapping expanders and 15 cases of a single implanted expander involving 22 patients. The method of "wet-cloth sampling" was applied to measure the expanded flap area and the initial unexpanded area and to calculate the skin expansion rate. Two points 5 cm apart in the center of the expanded flap were selected before the second surgical stage. After removal of the expander, the distance between the two fixed points was measured and recorded. The contraction rate of the expanded flap then was calculated. During the same period of expansion in the two groups (p = 0.06, >0.01), the skin expansion rate was 3.5 ± 0.9 % in the group with two overlapping expanders and 2.6 ± 0.6 % in the control group. The difference between the two groups was statistically significant (p = 0.002, 0.05). We fitted a linear regression model that was Y = 0.533 − 0.003X, where Y was the contraction rate of the expanded flap and X was the period of expansion. The contraction rate of the expanded flap was negatively correlated with the period of expansion. Compared with the traditional method of implanting a single expander, the new method of overlapping two expanders in a single cavity increased the skin expansion rate. The instantly expanded flap contraction rate did not differ significantly between the two groups, so the amount of expanded skin area absolutely increased. The clinical application of the new method is worth promoting. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

  13. Clinical-Grade-Expanded Regulatory T Cells Prevent Graft-versus-Host Disease While Allowing a Powerful T Cell-Dependent Graft-versus-Leukemia Effect in Murine Models.

    Science.gov (United States)

    Del Papa, Beatrice; Ruggeri, Loredana; Urbani, Elena; Baldoni, Stefano; Cecchini, Debora; Zei, Tiziana; Iacucci Ostini, Roberta; Crescenzi, Barbara; Carotti, Alessandra; Pierini, Antonio; Sportoletti, Paolo; Di Bartolomeo, Paolo; Falzetti, Franca; Mecucci, Cristina; Velardi, Andrea; Martelli, Massimo F; Di Ianni, Mauro

    2017-11-01

    We developed a good manufacturing practices-compatible expansion protocol to improve number and purity of regulatory T cells (Tregs) available for clinical trials. Six clinical-grade separation procedures were performed, followed by expansion with high-dose interleukin (IL)-2, anti-CD3/anti-CD28 TCR stimulation, and rapamycin for 19 days achieving a median of 8.5-fold (range, 6.25 to 13.7) expansion. FOXP3 expression was stably maintained over the culture period, while the percentage of CD127 was significantly reduced. The in vitro suppression assay showed a strong Mixed Lymphocytes Reaction inhibition. In vitro amplification did not induce any karyotypic modification. To evaluate the graft-versus-host disease (GVHD)/graft-versus-leukemia (GVL) bifunctional axis, expanded Tregs and conventional T cells (Tcons) were tested in NOD/SCID/IL2Rgnull mice injected with primary acute myeloid leukemia (AML) cells, AML cell line, acute lymphoid leukemia Philadelphia cell line, or Burkitt-like lymphoma cell line. All mice that received leukemia cells together with expanded Tregs and Tcons were rescued from leukemia and survived without GVHD, showing that Treg expansion procedure did not compromise GVHD control and the strong Tcon-mediated GVL activity. This report might represent the basis for treating high-risk leukemia and/or relapsed/refractory leukemia patients with high-dose Treg/Tcons. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  14. What do clinicians want from us? An evaluation of Brighton and Sussex University Hospitals NHS Trust clinical librarian service and its implications for developing future working patterns.

    Science.gov (United States)

    Brookman, Amanda; Lovell, Alan; Henwood, Flis; Lehmann, Judy

    2006-12-01

    The Clinical Librarian (CL) Service at Brighton was established in 2003 with the aim of providing high-quality evidence to designated teams and fostering an evidence-based culture. To evaluate the CL service at Brighton and discuss the implication of the findings. A combination of internally collected data (n = 167), and an external evaluation of the service by questionnaires (n = 86) of users and non-users and interviews (n = 9) of users. Internal data suggest that the service is valued by its users and that patient care and continuing professional development are the most common uses for searches (confirmed by the external study); that searches generally result in some change in knowledge; and that this knowledge is disseminated. The external study found that visibility of the CL was crucial to the effectiveness of the role and that clinicians used the service mostly to get access to a wider range of resources and/or to save time. Users wanted the CL to include evaluative annotation with the results, and for the CL role to become more embedded in the team. Interview results expanded on the issues of integration of the CL and the need for annotation of results. To be most effective, CLs would be dedicated to one team, but financial constraints make this unlikely. Alternative working patterns are suggested as a possible compromise.

  15. Prostatic Artery Embolization (PAE) for Symptomatic Benign Prostatic Hyperplasia (BPH): Part 1, Pathological Background and Clinical Implications

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Fei, E-mail: feisun@ccmijesususon.com; Crisóstomo, Verónica, E-mail: crisosto@ccmijesususon.com; Báez-Díaz, Claudia, E-mail: cbaez@ccmijesususon.com; Sánchez, Francisco M., E-mail: msanchez@ccmijesususon.com [Jesús Usón Minimally Invasive Surgery Centre (Spain)

    2016-01-15

    Pathological features of benign prostatic hyperplasia (BPH) dictate various responses to prostatic artery embolization (PAE). Typically, BPH originates in the transition zone and periurethral region, where should be considered the primary target area in PAE procedures. Given that histological heterogeneity of components in hyperplasia nodules, epithelial or stromal, identifying the more responsive nodules to PAE will have clinical implications. Since some lower urinary tract symptoms (LUTS) in patients with BPH are usually related to bladder outlet obstruction-induced changes in bladder function rather than to outflow obstruction directly, proper selection of candidate patients prior to PAE is of great clinical importance. BPH is a typical chronic progressive condition, suggesting PAE could aim not only to relieve LUTS but also to delay or prevent the clinical progression. Awareness of the pathological background of BPH is essential for interventional radiologists to improve clinical outcomes and develop new treatment strategies in clinical practice of PAE.

  16. Critical Review of Data Evaluation in Teaching Clinics of Traditional Chinese Medicine Outside China: Implications for Education.

    Science.gov (United States)

    Jiang, Jian; Peng, Wenbo; Gu, Tieguang; King, Catherine; Yin, J Kevin

    2016-01-01

    The increasing acceptance of traditional Chinese medicine (TCM) worldwide has highlighted the importance of ensuring the provision of high-quality TCM clinical education. This clinical training should be partly guided by a robust assessment of patient data outcomes in TCM teaching clinics. We undertook a comprehensive literature review to examine the data evaluation in TCM teaching clinics outside China and its implications for TCM education. Literature was retrieved via MEDLINE (from 1946 to January 2015), EMBASE (from 1980 to February 2015), and Google Scholar for studies conducted outside China. The search was restricted to English articles reporting empirical findings related to the assessments of patient data in TCM teaching clinics, with implications for TCM education in countries other than China. Only seven articles from six studies met the inclusion criteria. The characteristics and main symptoms of patients who received any TCM treatment in the context of teaching clinics among all included studies were similar. Symptom relief as well as a high level of patient satisfaction with TCM treatment were found in TCM teaching clinics. Conventional healthcare providers and other complementary practitioners were not the main source of referral to TCM practitioners but rather patients׳ friends/relatives. Patients received acupuncture treatment more frequently than treatments utilizing Chinese herbal medicine in teaching clinics. A standardized and consistent framework for patient records within TCM teaching clinics is currently lacking. There was no robust study which "translated" TCM clinic data evaluation findings into implications for TCM education and clinical training. Recognizing that TCM evolves over time and its practice varies in different settings, there is an urgent need to conduct large-scale, rigorous evaluations of TCM clinic data to address the findings of our review, with the purpose of better informing TCM education and clinical training in

  17. Research on the premotor symptoms of Parkinson's disease: clinical and etiological implications.

    Science.gov (United States)

    Chen, Honglei; Burton, Edward A; Ross, G Webster; Huang, Xuemei; Savica, Rodolfo; Abbott, Robert D; Ascherio, Alberto; Caviness, John N; Gao, Xiang; Gray, Kimberly A; Hong, Jau-Shyong; Kamel, Freya; Jennings, Danna; Kirshner, Annette; Lawler, Cindy; Liu, Rui; Miller, Gary W; Nussbaum, Robert; Peddada, Shyamal D; Rick, Amy Comstock; Ritz, Beate; Siderowf, Andrew D; Tanner, Caroline M; Tröster, Alexander I; Zhang, Jing

    2013-01-01

    The etiology and natural history of Parkinson's disease (PD) are not well understood. Some non-motor symptoms such as hyposmia, rapid eye movement sleep behavior disorder, and constipation may develop during the prodromal stage of PD and precede PD diagnosis by years. We examined the promise and pitfalls of research on premotor symptoms of PD and developed priorities and strategies to understand their clinical and etiological implications. This review was based on a workshop, Parkinson's Disease Premotor Symptom Symposium, held 7-8 June 2012 at the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina. Research on premotor symptoms of PD may offer an excellent opportunity to characterize high-risk populations and to better understand PD etiology. Such research may lead to evaluation of novel etiological hypotheses such as the possibility that environmental toxicants or viruses may initiate PD pathogenesis in the gastrointestinal tract or olfactory bulb. At present, our understanding of premotor symptoms of PD is in its infancy and faces many obstacles. These symptoms are often not specific to PD and have low positive predictive value for early PD diagnosis. Further, the pathological bases and biological mechanisms of these premotor symptoms and their relevance to PD pathogenesis are poorly understood. This is an emerging research area with important data gaps to be filled. Future research is needed to understand the prevalence of multiple premotor symptoms and their etiological relevance to PD. Animal experiments and mechanistic studies will further understanding of the biology of these premotor symptoms and test novel etiological hypothesis.

  18. Clinical implications of Pseudomonas aeruginosa location in the lungs of patients with cystic fibrosis.

    Science.gov (United States)

    Moore, J E; Mastoridis, P

    2017-06-01

    Pseudomonas aeruginosa is the leading cause of lung infection in patients with cystic fibrosis (CF) and is associated with significant morbidity and mortality. Antibiotics are regarded as the foundational pharmacological treatment for the suppressive management of chronic P. aeruginosa infections and to eradicate the first infection by P. aeruginosa. Inhalation remains a preferred route for drug administration, providing direct access to the site of infection while minimizing systemic side effects. Effective suppressive management of P. aeruginosa infections, however, requires an understanding of the location of the bacteria in the lungs and consideration of the factors that could limit access of the inhaled antibiotic to the infected area. This review provides a systematic assessment of the scientific literature to gain insight into the location of P. aeruginosa in the lungs of patients with CF and its clinical implications. The characteristics of antibiotic inhalation systems are also discussed in this context. We reviewed evidence-based literature from both human and animal studies in which P. aeruginosa lung location was reported. Relevant publications were identified through a screening strategy and summarized by reported P. aeruginosa location. Most areas of the conductive and respiratory zones of the lungs are susceptible to P. aeruginosa colonization. Deposition of an inhaled antibiotic is dependent on the device and formulation characteristics, as well as the ability of the patient to generate sufficient inhaled volume. As patients with CF often experience a decline in lung function, the challenge is to ensure that the inhaled antibiotic can be delivered throughout the bronchial tree. An effective drug delivery system that can target P. aeruginosa in both the respiratory and conductive zones is required. The chosen inhalation device should also offer a drug formulation that can be quickly and effectively delivered to specific lung locations, with

  19. Accessory neurovascular foramina on the lingual surface of mandible: Incidence, topography, and clinical implications

    Directory of Open Access Journals (Sweden)

    B V Murlimanju

    2012-01-01

    Full Text Available Context: It was suggested that the accessory neurovascular foramina of the mandible might be of significance in relation to the effectiveness of local anesthesia following the routine inferior alveolar nerve block. Aims: To investigate the incidence of neurovascular foramina over the lingual surface of the mandible in South Indian population. Settings and Design: The study was conducted at the department of anatomy. Materials and Methods: The study included 67 human adult dry mandibles, the exact ages and sexes of which were not known. The location and number of neurovascular foramina were topographically analyzed. Statistical Analysis Used: Descriptive statistics. Results: The foramina were observed in 64 mandibles (95.5% and were often multiple in most of the cases. They were located between the two medial incisors in 8 mandibles (1.9%, between the medial and lateral incisor in 34 mandibles (50.7%; 25-bilateral; 7-right; 2-left, between the lateral incisor and canine in 7 mandibles (10.4%; 2-bilateral; 3-right; 2-left, between the canine and first premolar in 6 cases (8.9%; 3 on each side. Foramina were also present around the genial tubercle in 56 mandibles (83.6%. Among them, 52 mandibles showed a single foramen just above the genial tubercle, 34 mandibles had foramina below the tubercles, 13 mandibles had foramina on the right side of genial tubercle and 17 were having on the left side. Conclusion: Since the anatomical details of these foramina are important to various fields of dentistry and oncology, the present investigation was undertaken. The clinical significance and implications are emphasized.

  20. Small aortic root in aortic valve stenosis: clinical characteristics and prognostic implications.

    Science.gov (United States)

    Bahlmann, Edda; Cramariuc, Dana; Minners, Jan; Lønnebakken, Mai Tone; Ray, Simon; Gohlke-Baerwolf, Christa; Nienaber, Christoph A; Jander, Nikolaus; Seifert, Reinhard; Chambers, John B; Kuck, Karl Heinz; Gerdts, Eva

    2017-04-01

    In aortic valve stenosis (AS), having a small aortic root may influence both the assessment of AS severity and the treatment strategy. The aim was to test the prognostic implications of having a small aortic root in AS within a large prospective study. We used data from 4.3-year follow-up of 1560 patients with asymptomatic, initially mostly moderate AS enrolled in the Simvastatin and Ezetimibe in Aortic Stenosis study. A small aortic root was defined as inner aortic sinotubular junction diameter indexed for body height <1.4 cm/m in women and <1.5 cm/m in men. A small aortic root was found in 270 patients (17.3%) at baseline. Having a small aortic root was associated with larger aortic root wall thickness, higher pressure recovery, lower systemic arterial compliance, left ventricular mass index, and female sex in a multivariable logistic regression analysis (all P < 0.05). In the Cox regression analysis, having a small aortic root at baseline was associated with higher hazard rates of ischaemic cardiovascular events (n = 268; HR 1.55, 95% CI 1.16-2.06), non-haemorrhagic stroke (n = 55; HR 1.88, 95% CI 1.04-3.41), and cardiovascular death (n = 81; HR 2.08, 95% CI 1.28-3.39) (all P < 0.05) after adjusting for confounders, including randomized study treatment, sex, hypertension, AS severity, and aortic valve replacement. In AS patients without known cardiovascular disease or diabetes, having a small aortic root was associated with increased ischaemic cardiovascular events and mortality. The results suggest a relation between the presence of a small aortic root and that of subclinical atherosclerosis. ClinicalTrials.gov identifier: NCT00092677.

  1. Normative Tandem Gait in Collegiate Student-Athletes: Implications for Clinical Concussion Assessment.

    Science.gov (United States)

    Oldham, Jessie R; DiFabio, Melissa S; Kaminski, Thomas W; DeWolf, Ryan M; Buckley, Thomas A

    Impaired balance is common after concussion. The third edition of the Sport Concussion Assessment Tool (SCAT-3) recommends the Balance Error Scoring System (BESS) and/or tandem gait for postconcussion balance assessment. The limitations of the BESS are well documented; however, tandem gait has received little attention throughout concussion literature. The purpose of this study was to provide normative data for tandem gait in collegiate student-athletes based on sport type, concussion history, and gender. Tandem gait will be influenced by concussion history, sport, and gender. Cohort study. Level 3. Four hundred collegiate student-athletes from both collision/contact (n = 200) and limited contact/noncontact (n = 200) sports performed 4 tandem gait trials, consistent with SCAT-3 guidelines. The dependent variables included the best of the 4 trials (BEST), the mean of the 4 trials (MEAN), and the mean of each of the trials individually (ORDER). Separate multivariate analyses of variance were performed for each of the independent variables to determine effect on BEST and MEAN trial times. Significant main effects were followed up with a 1-way analysis of variance (ANOVA). A separate 1-way ANOVA was used to assess ORDER differences. The mean BEST was 10.37 ± 1.76 seconds, and the MEAN was 11.32 ± 0.70 seconds. There were no significant differences in BEST or MEAN tandem gait times, respectively, between those with and without concussion history ( P = 0.41 and P = 0.69, respectively), sport type ( P = 0.57 and P = 0.42, respectively), or gender ( P = 0.73 and P = 0.49, respectively). There were significant differences ( P history, collision sport participation, and gender do not appear to influence performance, but ORDER could have significant clinical implications. Clinicians may use these data to distinguish important determinants of tandem gait performance and improve awareness when returning an individual to play after a concussion.

  2. Clinical Implications of TiGRT Algorithm for External Audit in Radiation Oncology

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    Daryoush Shahbazi-Gahrouei

    2017-01-01

    Full Text Available Background: Performing audits play an important role in quality assurance program in radiation oncology. Among different algorithms, TiGRT is one of the common application software for dose calculation. This study aimed to clinical implications of TiGRT algorithm to measure dose and compared to calculated dose delivered to the patients for a variety of cases, with and without the presence of inhomogeneities and beam modifiers. Materials and Methods: Nonhomogeneous phantom as quality dose verification phantom, Farmer ionization chambers, and PC-electrometer (Sun Nuclear, USA as a reference class electrometer was employed throughout the audit in linear accelerators 6 and 18 MV energies (Siemens ONCOR Impression Plus, Germany. Seven test cases were performed using semi CIRS phantom. Results: In homogeneous regions and simple plans for both energies, there was a good agreement between measured and treatment planning system calculated dose. Their relative error was found to be between 0.8% and 3% which is acceptable for audit, but in nonhomogeneous organs, such as lung, a few errors were observed. In complex treatment plans, when wedge or shield in the way of energy is used, the error was in the accepted criteria. In complex beam plans, the difference between measured and calculated dose was found to be 2%–3%. All differences were obtained between 0.4% and 1%. Conclusions: A good consistency was observed for the same type of energy in the homogeneous and nonhomogeneous phantom for the three-dimensional conformal field with a wedge, shield, asymmetric using the TiGRT treatment planning software in studied center. The results revealed that the national status of TPS calculations and dose delivery for 3D conformal radiotherapy was globally within acceptable standards with no major causes for concern.

  3. The Implications of Endoscopic Ulcer in Early Gastric Cancer: Can We Predict Clinical Behaviors from Endoscopy?

    Directory of Open Access Journals (Sweden)

    Yoo Jin Lee

    Full Text Available The presence of ulcer in early gastric cancer (EGC is important for the feasibility of endoscopic resection, only a few studies have examined the clinicopathological implications of endoscopic ulcer in EGC.To determine the role of endoscopic ulcer as a predictor of clinical behaviors in EGC.Data of 3,270 patients with EGC who underwent surgery between January 2005 and December 2012 were reviewed. Clinicopathological characteristics were analyzed in relation to the presence and stage of ulcer in EGC. Based on endoscopic findings, the stage of ulcer was categorized as active, healing, or scar. Logistic regression analysis was performed to analyze factors associated with lymph node metastasis (LNM.2,343 (71.7% patients had endoscopic findings of ulceration in EGC. Submucosal (SM invasion, LNM, lymphovascular invasion (LVI, perineural invasion, and undifferentiated-type histology were significantly higher in ulcerative than non-ulcerative EGC. Comparison across different stages of ulcer revealed that SM invasion, LNM, and LVI were significantly associated with the active stage, and that these features exhibited significant stage-based differences, being most common at the active stage, and least common at the scar stage. The presence of endoscopic ulcer and active status of the ulcer were identified as independent risk factors for LNM.Ulcerative EGC detected by endoscopy exhibited more aggressive behaviors than non-ulcerative EGC. Additionally, the endoscopic stage of ulcer may predict the clinicopathological behaviors of EGC. Therefore, the appearance of ulcers should be carefully evaluated to determine an adequate treatment strategy for EGC.

  4. Clinical implications of the coexpression of SRC1 and NANOG in HER-2-overexpressing breast cancers

    Directory of Open Access Journals (Sweden)

    Jin CY

    2016-09-01

    Full Text Available Chengyan Jin,1 Xingyi Zhang,1 Mei Sun,2 Yifan Zhang,1 Guangxin Zhang,1 Bin Wang1 1Department of Thoracic Surgery, 2Department of Pathology, The Second Affiliated Hospital of Jilin University, Changchun, People’s Republic of China Objective: Given the lack of clarity on the expression status of SRC1 protein in breast cancer, we attempted to ascertain the clinical implications of the expression of this protein in breast cancer.Methods: Samples from 312 breast cancer patients who were followed up for 5 years were analyzed in this study. The associations of SRC1 expression and clinicopathological factors with the prognosis of breast cancer were determined.Results: The 312 breast cancer patients underwent radical resection, and 155 (49.68% of them demonstrated high expression of SRC1 protein. No significant differences were found for tumor size, estrogen receptor expression, or progesterone receptor expression (P=0.191, 0.888, or 0.163, respectively. It is noteworthy that SRC1 expression was found to be related to HER-2 and Ki-67 expression (P=0.044 and P=0.001, respectively. According to logistic regression analysis, SRC1 expression was also significantly correlated with Ki-67 and HER-2 expression (P=0.032 and P=0.001, respectively. Survival analysis showed that patients with a high expression of SRC1 and NANOG and those with SRC1 and NANOG coexpression had significantly poorer postoperative disease-specific survival than those with no expression in the HER-2-positive group (P=0.032, 0.01, and P=0.01, respectively.Conclusion: High SRC1 protein expression was related to the prognosis of HER-2-overexpressing breast cancers. Keywords: breast cancer, prognosis, molecular classification, SRC1, NANOG

  5. Clinical Implications of Human Population Differences in Genome-wide Rates of Functional Genotypes

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    Ali eTorkamani

    2012-11-01

    Full Text Available There have been a number of recent successes in the use of whole genome sequencing and sophisticated bioinformatics techniques to identify pathogenic DNA sequence variants responsible for individual idiopathic congenital conditions. However, the success of this identification process is heavily influenced by the ancestry or genetic background of a patient with an idiopathic condition. This is so because potential pathogenic variants in a patient’s genome must be contrasted with variants in a reference set of genomes made up of other individuals’ genomes of the same ancestry as the patient. We explored the effect of ignoring the ancestries of both an individual patient and the individuals used to construct reference genomes. We pursued this exploration in two major steps. We first considered variation in the per-genome number and rates likely functional derived (i.e., non-ancestral, based on the chimp genome single nucleotide variants and small indels in 52 individual whole human genomes sampled from 10 different global populations. We took advantage of a suite of computational and bioinformatics techniques to predict the functional effect of over 24 million genomic variants, both coding and non-coding, across these genomes. We found that the typical human genome harbors ~5.5-6.1 million total derived variants, of which ~12,000 are likely to have a functional effect (~5000 coding and ~7000 non-coding. We also found that the rates of functional genotypes per the total number of genotypes in individual whole genomes differ dramatically between human populations. We then created tables showing how the use of comparator or reference genome panels comprised of genomes from individuals that do not have the same ancestral background as a patient can negatively impact pathogenic variant identification. Our results have important implications for clinical sequencing initiatives.

  6. A20 Haploinsufficiency Aggravates Transplant Arteriosclerosis in Mouse Vascular Allografts: Implications for Clinical Transplantation.

    Science.gov (United States)

    Moll, Herwig P; Lee, Andy; Peterson, Clayton R; Revuelta Cervantes, Jesus; Wojcik, Brandon M; Parulkar, Anshul; Mele, Alessandra; LoGerfo, Philip J; Siracuse, Jeffrey J; Csizmadia, Eva; da Silva, Cleide G; Ferran, Christiane

    2016-11-01

    Inflammation is central to the pathogenesis of transplant arteriosclerosis (TA). We questioned whether physiologic levels of anti-inflammatory A20 influence TA severity. We performed major histocompatibility complex mismatched aorta to carotid artery interposition grafts, using wild type (WT) or A20 heterozygote (HET) C57BL/6 (H-2) donors and BALB/c (H-2) recipients, and conversely BALB/c donors and WT/HET recipients. We analyzed aortic allografts by histology, immunohistochemistry, immunofluorescence, and gene profiling (quantitative real-time reverse-transcriptase polymerase chain reaction). We validated select in vivo A20 targets in human and mouse smooth muscle cell (SMC) cultures. We noted significantly greater intimal hyperplasia in HET versus WT allografts, indicating aggravated TA. Inadequate upregulation of A20 in HET allografts after transplantation was associated with excessive NF-кB activation, gauged by higher levels of IkBα, p65, VCAM-1, ICAM-1, CXCL10, CCL2, TNF, and IL-6 (mostly localized to SMC). Correspondingly, cytokine-induced upregulation of TNF and IL-6 in human and mouse SMC cultures inversely correlated with A20 expression. Aggravated TA in HET versus WT allografts correlated with increased intimal SMC proliferation, and a higher number of infiltrating IFNγ and Granzyme B CD4 T cells and natural killer cells, and lower number of FoxP3 regulatory T cells. A20 haploinsufficiency in allograft recipients did not influence TA. A20 haploinsufficiency in vascular allografts aggravates lesions of TA by exacerbating inflammation, SMC proliferation, and infiltration of pathogenic T cells. A20 single nucleotide polymorphisms associating with lower A20 expression or function in donors of vascularized allografts may inform risk and severity of TA, highlighting the clinical implications of our findings.

  7. Novel genes associated with amyotrophic lateral sclerosis: diagnostic and clinical implications.

    Science.gov (United States)

    Chia, Ruth; Chiò, Adriano; Traynor, Bryan J

    2018-01-01

    The disease course of amyotrophic lateral sclerosis (ALS) is rapid and, because its pathophysiology is unclear, few effective treatments are available. Genetic research aims to understand the underlying mechanisms of ALS and identify potential therapeutic targets. The first gene associated with ALS was SOD1, identified in 1993 and, by early 2014, more than 20 genes had been identified as causative of, or highly associated with, ALS. These genetic discoveries have identified key disease pathways that are therapeutically testable and could potentially lead to the development of better treatments for people with ALS. Since 2014, seven additional genes have been associated with ALS (MATR3, CHCHD10, TBK1, TUBA4A, NEK1, C21orf2, and CCNF), all of which were identified by genome-wide association studies, whole genome studies, or exome sequencing technologies. Each of the seven novel genes code for proteins associated with one or more molecular pathways known to be involved in ALS. These pathways include dysfunction in global protein homoeostasis resulting from abnormal protein aggregation or a defect in the protein clearance pathway, mitochondrial dysfunction, altered RNA metabolism, impaired cytoskeletal integrity, altered axonal transport dynamics, and DNA damage accumulation due to defective DNA repair. Because these novel genes share common disease pathways with other genes implicated in ALS, therapeutics targeting these pathways could be useful for a broad group of patients stratified by genotype. However, the effects of these novel genes have not yet been investigated in animal models, which will be a key step to translating these findings into clinical practice. WHERE NEXT?: The identification of these seven novel genes has been important in unravelling the molecular mechanisms underlying ALS. However, our understanding of what causes ALS is not complete, and further genetic research will provide additional detail about its causes. Increased genetic knowledge will

  8. [Food addiction: Definition, measurement and limits of the concept, associated factors, therapeutic and clinical implications].

    Science.gov (United States)

    Cathelain, Sarah; Brunault, Paul; Ballon, Nicolas; Réveillère, Christian; Courtois, Robert

    2016-12-01

    Addictions, which are characterized by the inability to control a behavior despite existence of physical or psychological consequences, have biological, psychological and social determinants. Although the possibility of developing an addiction to some psychoactive substances (e.g. alcohol, tobacco, cannabis) and to gambling (i.e., gambling disorder) is now well demonstrated, the possibility to develop a non-drug addiction (i.e., behavioral addiction) to certain behaviors which provide pleasure (e.g. eating, having sex, buying things) is still in debate. The concept of food addiction, which refers to people who exhibit substance dependence criteria in relation to some high-fat and high-sugar foods, was recently proposed by applying substance dependence DSM criteria to eating behavior. To assess food addiction, the Yale Food Addiction Scale is now the only self-administered questionnaire (diagnosis and estimate of the number of symptoms of food addiction). Prevalence for food addiction is higher in overweight and obese patients, and in patients with certain psychopathological characteristics (i.e., depression, Attention Deficit Hyperactivity Disorder, high impulsivity), in patients who are single and in patients with neurobiological alterations in the reward system. However, it is still unclear whether food addiction is necessary associated with subsequent increase in body weight and/or obesity. An increasing number of studies demonstrated that drug addiction and food addiction shares some similar clinical, neurobiological and psychopathological and sociocultural risk factors. To test the pertinence to include food addiction as an addiction, it would be interesting to conduct future studies in patients who may experience harms related to their food addiction, including not only patients with obesity, but also patients with metabolic syndrome, type 2 diabetes, hypertension, dyslipidemia, atherosclerosis, stroke, or coronary heart disease. Food addiction is a clinical

  9. HIV/AIDS and lipodystrophy: Implications for clinical management in resource-limited settings

    Directory of Open Access Journals (Sweden)

    Julia L Finkelstein

    2015-01-01

    common in resource-limited settings, and has considerable implications for risk of metabolic diseases, quality of life and adherence. Comprehensive evidence-based interventions are urgently needed to reduce the burden of HIV and lipodystrophy, and inform clinical management in resource-limited settings.

  10. HIV/AIDS and lipodystrophy: implications for clinical management in resource-limited settings.

    Science.gov (United States)

    Finkelstein, Julia L; Gala, Pooja; Rochford, Rosemary; Glesby, Marshall J; Mehta, Saurabh

    2015-01-01

    Lipodystrophy is a term used to describe a metabolic complication of fat loss, fat gain, or a combination of fat loss and gain, which is associated with some antiretroviral (ARV) therapies given to HIV-infected individuals. There is limited research on lipodystrophy in low- and middle-income countries, despite accounting for more than 95% of the burden of HIV/AIDS. The objective of this review was to evaluate the prevalence, pathogenesis and prognosis of HIV-related lipoatrophy, lipohypertrophy and mixed syndrome, to inform clinical management in resource-limited settings. We conducted a structured literature search using MEDLINE electronic databases. Relevant MeSH terms were used to identify published human studies on HIV and lipoatrophy, lipohypertrophy, or mixed syndrome in low-, low-middle- and upper-middle-income countries through 31 March 2014. The search resulted in 5296 articles; after 1599 studies were excluded (958 reviews, 641 non-human), 3697 studies were extracted for further review. After excluding studies conducted in high-income settings (n=2808), and studies that did not meet inclusion criteria (n = 799), 90 studies were included in this review. Of the 90 studies included in this review, only six were from low-income countries and eight were from lower middle-income economies. These studies focused on lipodystrophy prevalence, risk factors and side effects of antiretroviral therapy (ART). In most studies, lipodystrophy developed after the first six months of therapy, particularly with the use of stavudine. Lipodystrophy is associated with increased risk of cardiometabolic complications. This is disconcerting and anticipated to increase, given the rapid scale-up of ART worldwide, the increasing number and lifespan of HIV-infected patients on long-term therapy, and the emergence of obesity and non-communicable diseases in settings with extensive HIV burden. Lipodystrophy is common in resource-limited settings, and has considerable implications for

  11. Olive Oil-related Anti-inflammatory Effects on Atherosclerosis: Potential Clinical Implications.

    Science.gov (United States)

    Wongwarawipat, Tanakal; Papageorgiou, Nikolaos; Bertsias, Dimitrios; Siasos, Gerasimos; Tousoulis, Dimitris

    2017-11-15

    Atherosclerosis is characterized by a chronic low-grade inflammatory process which can result in atherothrombosis and a number of cardiovascular diseases (CVD). It is believed to be caused by multiple processes that involve inflammation and immunity. Mediterranean Diet (MedD) has been discovered to possess anti-inflammatory properties and associated with a reduction in the CVD risk and mortality. Its main component, extra-virgin olive oil (EVOO), is believed to be largely responsible for these effects and therefore, has been investigated in various studies. The present review article aims to summarize the available literature on the anti-inflammatory and cardio-protective effects of EVOO. A search based on the key concepts "olive oil", "atherosclerosis", "inflammation" and "cardiovascular disease" was performed to retrieve relevant studies and articles on the association between the consumption of EVOO and the levels of inflammatory biomarkers as well as CVD incidence and mortality from online databases; Pubmed, Embase and Cochrane Library. Consumption of EVOO is associated with a reduction in inflammatory biomarkers and molecules implicated in atherosclerosis as well as CVD incidence and mortality as well as other complications such as heart failure and atrial fibrillation. Moreover, these anti-inflammatory and cardioprotective effects of EVOO are mostly attributable to its high content of polyphenol molecules. Currently available evidence supports the anti-inflammatory and cardio-protective roles of EVOO. However, there is limited amount of available randomized controlled trials especially lacking those investigating the use of EVOO as secondary prevention, heterogeneity of study design, limited generalization to wide population groups, and inability to determine the minimum intake of EVOO required to clinically achieve the anti-inflammatory and cardioprotective effects. Therefore, more high-quality randomized controlled trials still need to be carried out to

  12. Integrating substance abuse care with community diabetes care: implications for research and clinical practice

    Directory of Open Access Journals (Sweden)

    Ghitza UE

    2013-01-01

    Full Text Available Udi E Ghitza,1 Li-Tzy Wu,2 Betty Tai11Center for the Clinical Trials Network, National Institute on Drug Abuse, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD, 2Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USAAbstract: Cigarette smoking and alcohol use are prevalent among individuals with diabetes in the US, but little is known about screening and treatment for substance use disorders in the diabetic population. This commentary discusses the scope and clinical implications of the public health problem of coexisting substance use and diabetes, including suggestions for future research. Diabetes is the seventh leading cause of death in the US, and is associated with many severe health complications like cardiovascular disease, stroke, kidney damage, and limb amputations. There are an estimated 24 million adults in the US with type 2 diabetes. Approximately 20% of adults aged 18 years or older with diabetes report current cigarette smoking. The prevalence of current alcohol use in the diabetic population is estimated to be around 50%–60% in epidemiological surveys and treatment-seeking populations. Cigarette smoking is associated with an increased risk of type 2 diabetes in a dose-dependent manner and is an independent modifiable risk factor for development of type 2 diabetes. Diabetic patients with an alcohol or other drug use disorder show a higher rate of adverse health outcomes. For example, these patients experience more frequent and severe health complications as well as an increased risk of hospitalization, and require longer hospital stays. They are also less likely to seek routine care for diabetes or adhere to diabetes treatment than those without an alcohol or other drug use disorder. The Affordable Care Act of 2010 and the Mental Health Parity Act and Addiction Equity Act of 2008 provide opportunities for facilitating integration of

  13. Do expanded seven-day NHS services improve clinical outcomes? Analysis of comparative institutional performance from the "NHS Services, Seven Days a Week" project 2013-2016.

    Science.gov (United States)

    Gan, Hoong-Wei; Wong, Danny Jon Nian; Dean, Benjamin John Floyd; Hall, Alistair Scott

    2017-08-10

    The cause of adverse weekend clinical outcomes remains unknown. In 2013, the "NHS Services, Seven Days a Week" project was initiated to improve access to services across the seven-day week. Three years on, we sought to analyse the impact of such changes across the English NHS. Aggregated trust-level data on crude mortality rates, Summary Hospital-Level Mortality Indicator (SHMI), mean length of stay (LOS), A&E admission and four-hour breach rates were obtained from national Hospital Episode Statistics and A&E datasets across the English NHS, excluding mental and community health trusts. Trust annual reports were analysed to determine the presence of any seven-day service reorganisation in 2013-2014. Funnel plots were generated to compare institutional performance and a difference in differences analysis was performed to determine the impact of seven-day changes on clinical outcomes between 2013 and 2014, 2014-2015 and 2015-2016. Data was summarised as mean (SD). Of 159 NHS trusts, 79 (49.7%) instituted seven-day changes in 2013-2014. Crude mortality rates, A&E admission rates and mean LOS remained relatively stable between 2013 and 2016, whilst A&E four-hour breach rates nearly doubled from 5.3 to 9.7%. From 2013 to 2014 to 2014-2015 and 2015-2016, there were no significant differences in the change in crude mortality (2014-2015 p = 0.8, 2015-2016 p = 0.9), SHMI (2014-2015 p = 0.5, 2015-2016 p = 0.5), mean LOS (2014-2015 p = 0.5, 2015-2016 p = 0.4), A&E admission (2014-2015 p = 0.6, 2015-2016 p = 1.0) or four-hour breach rates (2014-2015 p = 0.06, 2015-2016 p = 0.6) between trusts that had implemented seven-day changes compared to those which had not. Adverse weekend clinical outcomes may not be ameliorated by large scale reorganisations aimed at improving access to health services across the week. Such changes may negatively impact care quality without additional financial investment, as demonstrated by worsening of some outcomes. Detailed

  14. Silicon microfabricated beam expander

    Energy Technology Data Exchange (ETDEWEB)

    Othman, A., E-mail: aliman@ppinang.uitm.edu.my; Ibrahim, M. N.; Hamzah, I. H.; Sulaiman, A. A. [Faculty of Electrical Engineering, Universiti Teknologi MARA Malaysia, 40450, Shah Alam, Selangor (Malaysia); Ain, M. F. [School of Electrical and Electronic Engineering, Engineering Campus, Universiti Sains Malaysia, Seri Ampangan, 14300,Nibong Tebal, Pulau Pinang (Malaysia)

    2015-03-30

    The feasibility design and development methods of silicon microfabricated beam expander are described. Silicon bulk micromachining fabrication technology is used in producing features of the structure. A high-precision complex 3-D shape of the expander can be formed by exploiting the predictable anisotropic wet etching characteristics of single-crystal silicon in aqueous Potassium-Hydroxide (KOH) solution. The beam-expander consist of two elements, a micromachined silicon reflector chamber and micro-Fresnel zone plate. The micro-Fresnel element is patterned using lithographic methods. The reflector chamber element has a depth of 40 µm, a diameter of 15 mm and gold-coated surfaces. The impact on the depth, diameter of the chamber and absorption for improved performance are discussed.

  15. Radiological Results and Clinical Patient Outcome After Implantation of a Hydraulic Expandable Vertebral Body Replacement following Traumatic Vertebral Fractures in the Thoracic and Lumbar Spine: A 3-Year Follow-Up.

    Science.gov (United States)

    Kreinest, Michael; Schmahl, Dorothee; Grützner, Paul A; Matschke, Stefan

    2017-04-15

    A prospective monocentric study. The aim of the current study was the analysis of patient outcome and radiological results 3 years after implantation of a hydraulic expandable vertebral body replacement (VBR) system. Around 70% to 90% of all traumatic spinal fractures are located in the thoracic and lumbar spine. Dorso-ventral stabilization is a frequently used procedure in traumatic vertebral body fracture treatment. VBR systems can be used to bridge bony defects. In the current study, a new VBR expanded by water pressure with adjustable endplates is used. All patients who suffered a singular traumatic fracture to a thoracic or lumbar vertebral body (Th 5-L 5) in the period from November 2009 to December 2010 and (i) underwent dorsal instrumentation and (ii) afterwards received the implantation of a hydraulic VBR were included in this study. The clinical outcome (visual analogue scale [VAS] spine score, questionnaire) and radiological findings (sagittal angle, implant subsidence, and implant position) 3 years after implantation were analyzed. The follow-up was successful for n = 47 patients (follow-up rate: 89%). Most of the patients (n = 40) were "generally/very satisfied" with their outcome. The mean rating of the VAS spine score was 65.2 ± 23.1 (range: 20.5-100.0). The analysis of the radiological data showed an average subsidence of the implants of 1.1 ± 1.2 mm (range 0.0-5.0 mm). After the initial operation, the local sagittal angle remained stable in the follow-up 3 years later both for the thoracic spine and lumbar spine. Furthermore, no change in the implant's position was observed. The implantation of a hydraulically expandable VBR allows a permanent stable fixation after traumatic fractures of the thoracic and lumbar spine. 2.

  16. Gonorrhea Treatment Failures With Oral and Injectable Expanded Spectrum Cephalosporin Monotherapy vs Dual Therapy at 4 Canadian Sexually Transmitted Infection Clinics, 2010-2013.

    Science.gov (United States)

    Singh, Ameeta E; Gratrix, Jennifer; Martin, Irene; Friedman, Dara S; Hoang, Linda; Lester, Richard; Metz, Gila; Ogilvie, Gina; Read, Ron; Wong, Tom

    2015-06-01

    Antimicrobial resistance has developed to all antibiotics used to treat gonorrhea (GC), and trends in GC antimicrobial resistance have prompted changes in treatment guidelines. We examined treatment failures in sexually transmitted infection clinics. Four Canadian sexually transmitted infection clinics reviewed treatment regimens, minimum inhibitory concentrations for cephalosporins and azithromycin, anatomical infection sites, and treatment outcomes for GC infections between January 2010 and September 2013, in individuals who returned for test of cure within 30 days of treatment. Treatment failure was defined as the absence of reported sexual contact during the posttreatment period and (i) positive for Neisseria gonorrhoeae on culture of specimens taken at least 72 hours after treatment or (ii) positive nucleic acid amplification test specimens taken at least 2 to 3 weeks after treatment, and matching sequence type pretreatment and posttreatment. χ Test and Fisher exact test were used to assess association of categorical variables. Of 389 specimens reviewed, GC treatment failures occurred in 13 specimens treated with cefixime 400-mg single dose (17.8% treatment failure rate regardless of anatomical site) and in 1 oropharyngeal specimen treated with cefixime 800-mg single dose. No treatment failures occurred using either ceftriaxone monotherapy or cefixime/ceftriaxone combined with azithromycin or doxycycline. In contrast to oral cefixime monotherapy, no treatment failures were identified with injectable ceftriaxone monotherapy or combination GC treatment. Our data support the use of combination treatment of GC with an extended spectrum cephalosporin (including oral cefixime) with azithromycin or doxycycline as well as ceftriaxone monotherapy.

  17. The clinical implications of cognitive impairment and allostatic load in bipolar disorder

    National Research Council Canada - National Science Library

    Vieta, E; Popovic, D; Rosa, A R; Solé, B; Grande, I; Frey, B N; Martinez-Aran, A; Sanchez-Moreno, J; Balanzá-Martínez, V; Tabarés-Seisdedos, R; Kapczinski, F

    2013-01-01

    ...) and its practical implications. PubMed searches were conducted on English-language articles published from 1970 to June 2011 using the search terms allostatic load, oxidative stress, staging, and bipolar disorder cross-referenced...

  18. Comparative pharmacokinetics and pharmacodynamics of platelet adenosine diphosphate receptor antagonists and their clinical implications.

    Science.gov (United States)

    Floyd, Christopher N; Passacquale, Gabriella; Ferro, Albert

    2012-07-01

    only a single CYP-mediated step to produce its active metabolite and ticagrelor is not a pro-drug. Enhanced IPA by both prasugrel and ticagrelor is achieved at the expense of increased major bleeding, although this is partially mitigated in the case of ticagrelor due to its reversible IPA. However, the reversible binding of ticagrelor to the P2Y(12) receptor requires a twice-daily dosing regimen. Due to limited data from clinical studies, the use of prasugrel is currently restricted to individuals undergoing percutaneous coronary intervention who are ≤75 years old and have a body weight ≥60 kg. The clinical data for ticagrelor are more comprehensive and this drug therefore has a place in the management of patients with acute coronary syndrome at moderate-to-high risk of ischaemic events, irrespective of treatment strategy. Here we review in detail the pharmacokinetics and pharmacodynamics of clopidogrel, prasugrel and ticagrelor, and explore the implications of the differences in these parameters for their clinical use.

  19. Clinical Implications of Basic Science Discoveries: Immune Homeostasis and the Microbiome-Dietary and Therapeutic Modulation and Implications for Transplantation.

    Science.gov (United States)

    Fishman, J A; Thomson, A W

    2015-07-01

    Links between the human microbiome and the innate and adaptive immune systems and their impact on autoimmune and inflammatory diseases are only beginning to be recognized. Characterization of the complex human microbial community is facilitated by culture-independent nucleic acid sequencing tools and bioinformatics systems. Specific organisms and microbial antigens are linked with initiation of innate immune responses that, depending on the context, may be associated with tolerogenic or effector immune responses. Further complexity is introduced by preclinical data that demonstrate the impacts of dietary manipulation on the prevention of genetically determined, systemic autoimmune disorders and on gastrointestinal microbiota. Investigation of interactions of complex microbial populations with the human immune system may provide new targets for clinical management in allotransplantation. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  20. Mechanisms and Clinical Implications of the Placebo Effect: Is There a Potential for the Elderly? A Mini-Review

    Science.gov (United States)

    Bingel, Ulrike; Colloca, Luana; Vase, Lene

    2011-01-01

    In recent years, the placebo effect has been a topic of considerable interest both in the scientific and the clinical community. In this time, the placebo effect has evolved from being considered a nuisance in clinical and pharmacological research to becoming a neurobiological phenomenon worthy of scientific investigation in its own right. Recent research shows that placebo effects are genuine psychobiological events attributable to the overall therapeutic context, and that these effects can be robust in both laboratory and clinical settings. These psychosocially induced biochemical changes in a patient's brain and body may in turn affect the course of a disease and the response to a therapy. Here we summarize and discuss the current insights into placebo mechanisms and discuss the potentially widespread implications for research and clinical practice. Even though a systematic knowledge of placebo effects across the lifespan is lacking, we aim at highlighting specific aspects related to the care of elderly patients and those suffering from neurodegenerative diseases. PMID:20975261

  1. The expanded clinical profile and the efficacy of colchicine therapy in Egyptian children suffering from familial mediterranean fever: a descriptive study

    Directory of Open Access Journals (Sweden)

    Talaat Hala Salah El-Din

    2012-12-01

    Full Text Available Abstract Background Familial Mediterranean fever (FMF is an autosomal recessive disease characterized by self-limiting recurrent attacks of fever and serosal inflammation, leading to abdominal, thoracic or articular pain. Objective To detect variable clinical presentations and genotypic distribution of different groups of FMF patients and the efficacy of colchicine therapy in treatment of these groups of FMF after one year. Methods A cross-sectional study was conducted on 70 patients already diagnosed with FMF and following-up at the Rheumatology Clinic, Children's Hospital - Cairo University. Diagnosis of FMF was determined according to Tel Hashomer criteria for FMF. All patients were subjected to a questionnaire including detailed history with emphasis on clinical manifestations and colchicine dose to control attacks. Mutational analysis was performed for all study subjects covering 12 mutations in the MEFV gene: E148Q, P369S, F479L, M680I (G/C, M680I (G/A, I692del, M694V, M694I, K695R, V726A, A744S and R761H. Response to colchicine treatment was evaluated as complete, incomplete and unresponsive. Results Out of the 70 patients- 40 males and 30 females- fever was the most common presenting feature, followed by abdominal pain, and arthritis; documented in 95.7%, 94.3%, and 77.1% of cases respectively. Mutational analysis detected gene mutation on both alleles in 20 patients (homozygotes, on only 1 allele in 40 patients (heterozygotes, and on none of the alleles (uncharacterized cases. Mild to moderate disease severity score (according to Tel Hashomer key to severity score was detected in a significant proportion of heterozygotes and the uncharacterized group than the homozygotes. All patients received colchicine therapy; 22.9% of them showed complete response, 74.3% showed incomplete response and 2.9% showed no response to therapy. The colchicine dose needed to control attacks was significantly lower in heterozygotes than the homozygotes(P=0

  2. Attitudes of psychology students to depression and its treatment: Implications for clinical practice.

    Science.gov (United States)

    Economou, M; Peppou, L E; Geroulanou, K; Kontoangelos, K; Prokopi, A; Pantazi, A; Zervakaki, A; Stefanis, C N

    2017-01-01

    . The core misconception espoused pertains to the view that major depression is not a medical illness; a finding which can also be interpreted in light of the lingering controversy on the medicalization of normal sadness and human predicament. The clinical implications of these findings are substantial. Mental health professionals-educators should reflect on their own beliefs and attitudes towards depression, as they may convey stigmatizing messages to their students and thus perpetuate the stigmatization of the illness. Concomitantly, psychology students' attitudes to depression and its treatment might render them incapable of understanding their patients, responding to their needs and providing them with appropriate help, while they may hinder their effective collaboration with psychiatrists.

  3. Revisions to the 2009 American Society of Clinical Oncology/Oncology Nursing Society chemotherapy administration safety standards: expanding the scope to include inpatient settings.

    Science.gov (United States)

    Jacobson, Joseph O; Polovich, Martha; Gilmore, Terry R; Schulmeister, Lisa; Esper, Peg; Lefebvre, Kristine B; Neuss, Michael N

    2012-01-01

    In November 2009, the American Society of Clinical Oncology (ASCO) and the Oncology Nursing Society (ONS) jointly published a set of 31 voluntary chemotherapy safety standards for adult patients with cancer, as the end result of a highly structured, multistakeholder process. The standards were explicitly created to address patient safety in the administration of parenteral and oral chemotherapeutic agents in outpatient oncology settings. In January 2011, a workgroup consisting of ASCO and ONS members was convened to review feedback received since publication of the standards, to address interim changes in practice, and to modify the standards as needed. The most significant change to the standards is to extend their scope to the inpatient setting. This change reflects the conviction that the same standards for chemotherapy administration safety should apply in all settings. The proposed set of standards has been approved by the Board of Directors for both ASCO and ONS and has been posted for public comment. Comments were used as the basis for final editing of the revised standards. The workgroup recognizes that the safety of oral chemotherapy usage, nononcology medication reconciliation, and home chemotherapy administration are not adequately addressed in the original or revised standards. A separate process, cosponsored by ASCO and ONS, will address the development of safety standards for these areas.

  4. Urate levels predict survival in amyotrophic lateral sclerosis: Analysis of the expanded Pooled Resource Open-Access ALS clinical trials database.

    Science.gov (United States)

    Paganoni, Sabrina; Nicholson, Katharine; Chan, James; Shui, Amy; Schoenfeld, David; Sherman, Alexander; Berry, James; Cudkowicz, Merit; Atassi, Nazem

    2017-08-31

    Urate has been identified as a predictor of amyotrophic lateral sclerosis (ALS) survival in some but not all studies. Here we leverage the recent expansion of the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database to study the association between urate levels and ALS survival. Pooled data of 1,736 ALS participants from the PRO-ACT database were analyzed. Cox proportional hazards regression models were used to evaluate associations between urate levels at trial entry and survival. After adjustment for potential confounders (i.e., creatinine and body mass index), there was an 11% reduction in risk of reaching a survival endpoint during the study with each 1-mg/dL increase in uric acid levels (adjusted hazard ratio 0.89, 95% confidence interval 0.82-0.97, P ALS and confirms the utility of the PRO-ACT database as a powerful resource for ALS epidemiological research. Muscle Nerve 2017. © 2017 Wiley Periodicals, Inc.

  5. Changes in drug transport and metabolism and their clinical implications in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Dietrich, Christoph G; Rau, Monika; Jahn, Daniel; Geier, Andreas

    2017-06-01

    The incidence of non-alcoholic fatty liver disease (NAFLD) is rising, especially in Western countries. Drug treatment in patients with NAFLD is common since it is linked to other conditions like diabetes, obesity, and cardiovascular disease. Consequently, changes in drug metabolism may have serious clinical implications. Areas covered: A literature search for studies in animal models or patients with obesity, fatty liver, non-alcoholic steatohepatitis (NASH) or NASH cirrhosis published before November 2016 was performed. After discussing epidemiology and animal models for NAFLD, we summarized both basic as well as clinical studies investigating changes in drug transport and metabolism in NAFLD. Important drug groups were assessed separately with emphasis on clinical implications for drug treatment in patients with NAFLD. Expert opinion: Given the frequency of NAFLD even today, a high degree of drug treatment in NAFLD patients appears safe and well-tolerated despite considerable changes in hepatic uptake, distribution, metabolism and transport of drugs in these patients. NASH causes changes in biliary excretion, systemic concentrations, and renal handling of drugs leading to alterations in drug efficacy or toxicity under specific circumstances. Future clinical drug studies should focus on this special patient population in order to avoid serious adverse events in NAFLD patients.

  6. Clinical reasoning in the real world is mediated by bounded rationality: implications for diagnostic clinical practice guidelines.

    Science.gov (United States)

    Bonilauri Ferreira, Ana Paula Ribeiro; Ferreira, Rodrigo Fernando; Rajgor, Dimple; Shah, Jatin; Menezes, Andrea; Pietrobon, Ricardo

    2010-04-20

    Little is known about the reasoning mechanisms used by physicians in decision-making and how this compares to diagnostic clinical practice guidelines. We explored the clinical reasoning process in a real life environment. This is a qualitative study evaluating transcriptions of sixteen physicians' reasoning during appointments with patients, clinical discussions between specialists, and personal interviews with physicians affiliated to a hospital in Brazil. FOUR MAIN THEMES WERE IDENTIFIED: simple and robust heuristics, extensive use of social environment rationality, attempts to prove diagnostic and therapeutic hypothesis while refuting potential contradictions using positive test strategy, and reaching the saturation point. Physicians constantly attempted to prove their initial hypothesis while trying to refute any contradictions. While social environment rationality was the main factor in the determination of all steps of the clinical reasoning process, factors such as referral letters and number of contradictions associated with the initial hypothesis had influence on physicians' confidence and determination of the threshold to reach a final decision. Physicians rely on simple heuristics associated with environmental factors. This model allows for robustness, simplicity, and cognitive energy saving. Since this model does not fit into current diagnostic clinical practice guidelines, we make some propositions to help its integration.

  7. Clinical reasoning in the real world is mediated by bounded rationality: implications for diagnostic clinical practice guidelines.

    Directory of Open Access Journals (Sweden)

    Ana Paula Ribeiro Bonilauri Ferreira

    Full Text Available BACKGROUND: Little is known about the reasoning mechanisms used by physicians in decision-making and how this compares to diagnostic clinical practice guidelines. We explored the clinical reasoning process in a real life environment. METHOD: This is a qualitative study evaluating transcriptions of sixteen physicians' reasoning during appointments with patients, clinical discussions between specialists, and personal interviews with physicians affiliated to a hospital in Brazil. RESULTS: FOUR MAIN THEMES WERE IDENTIFIED: simple and robust heuristics, extensive use of social environment rationality, attempts to prove diagnostic and therapeutic hypothesis while refuting potential contradictions using positive test strategy, and reaching the saturation point. Physicians constantly attempted to prove their initial hypothesis while trying to refute any contradictions. While social environment rationality was the main factor in the determination of all steps of the clinical reasoning process, factors such as referral letters and number of contradictions associated with the initial hypothesis had influence on physicians' confidence and determination of the threshold to reach a final decision. DISCUSSION: Physicians rely on simple heuristics associated with environmental factors. This model allows for robustness, simplicity, and cognitive energy saving. Since this model does not fit into current diagnostic clinical practice guidelines, we make some propositions to help its integration.

  8. Expandable LED array interconnect

    Science.gov (United States)

    Yuan, Thomas Cheng-Hsin; Keller, Bernd

    2011-03-01

    A light emitting device that can function as an array element in an expandable array of such devices. The light emitting device comprises a substrate that has a top surface and a plurality of edges. Input and output terminals are mounted to the top surface of the substrate. Both terminals comprise a plurality of contact pads disposed proximate to the edges of the substrate, allowing for easy access to both terminals from multiple edges of the substrate. A lighting element is mounted to the top surface of the substrate. The lighting element is connected between the input and output terminals. The contact pads provide multiple access points to the terminals which allow for greater flexibility in design when the devices are used as array elements in an expandable array.

  9. Grazing incidence beam expander

    Energy Technology Data Exchange (ETDEWEB)

    Akkapeddi, P.R.; Glenn, P.; Fuschetto, A.; Appert, Q.; Viswanathan, V.K.

    1985-01-01

    A Grazing Incidence Beam Expander (GIBE) telescope is being designed and fabricated to be used as an equivalent end mirror in a long laser resonator cavity. The design requirements for this GIBE flow down from a generic Free Electron Laser (FEL) resonator. The nature of the FEL gain volume (a thin, pencil-like, on-axis region) dictates that the output beam be very small. Such a thin beam with the high power levels characteristic of FELs would have to travel perhaps hundreds of meters or more before expanding enough to allow reflection from cooled mirrors. A GIBE, on the other hand, would allow placing these optics closer to the gain region and thus reduces the cavity lengths substantially. Results are presented relating to optical and mechanical design, alignment sensitivity analysis, radius of curvature analysis, laser cavity stability analysis of a linear stable concentric laser cavity with a GIBE. Fabrication details of the GIBE are also given.

  10. Expanding the HAWC Observatory

    Energy Technology Data Exchange (ETDEWEB)

    Mori, Johanna [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-08-17

    The High Altitude Water Cherenkov Gamma-Ray Observatory is expanding its current array of 300 water tanks to include 350 outrigger tanks to increase sensitivity to gamma rays above 10 TeV. This involves creating and testing hardware with which to build the new tanks, including photomultiplier tubes, high voltage supply units, and flash analog to digital converters. My responsibilities this summer included preparing, testing and calibrating that equipment.

  11. Fluctuations in the emotional intelligence of therapy students during clinical placements: Implication for educators, supervisors, and students.

    Science.gov (United States)

    Gribble, Nigel; Ladyshewsky, Richard K; Parsons, Richard

    2017-01-01

    This study investigated the changes in emotional intelligence (EI) of occupational therapy, physiotherapy, and speech pathology students (therapy students). Clinical placements have multiple benefits including the development of interprofessional skills, enhancing practice skills and interpersonal skills. Higher EI competencies have been shown to have a positive impact on patient outcomes, teamwork skills, dealing with stress, and patient satisfaction. Data for this study were collected at two time points: before third-year therapy students commenced extended clinical placements (T1 with 261 students) and approximately 7 months later after students had completed one or more clinical placements (T2 with 109 students). EI was measured using the Emotional Quotient Inventory 2.0 (EQ-i2.0). Only one EI score, assertiveness, demonstrated a significant decline. No EI score showed a significant increase. A third or more of the students showed increases of five points or more in self-actualisation, emotional expression, independence, reality testing and optimism. However, of concern were the five EI scores where therapy students' EI scores decreased by more than five points: assertiveness (where 38% of students declined), problem solving (37%), impulse control (35%), self-actualisation (35%), and stress tolerance (33%). With EI scores declining for some students during clinical placements, there are implications for clinical supervisors and interprofessional facilitators as clinical performance may decline concurrently. There is a range of potential reasons that clinical placements could negatively influence the EI competencies of a therapy student, including poor clinical supervision, conflict between a student, and supervisor and failing a clinical placement. The research suggests that interprofessional facilitators and university educators might consider students undertaking EI tests before clinical placements.

  12. Family Violence and Migrant Women: Implications for Practice. Migrant Clinicians Network Clinical Supplement.

    Science.gov (United States)

    Rodriguez, Rachel; And Others

    1993-01-01

    This newsletter supplement is devoted to the theme of domestic violence affecting migrant women. It contains four articles describing programs providing violence prevention education to migrant women and children. "Family Violence and Migrant Women: Implications for Practice" (Rachel Rodriguez) discusses the social isolation of migrant women;…

  13. Clinical Implications of Power Toothbrushing on Fluoride Delivery: Effects on Biofilm Plaque Metabolism and Physiology

    OpenAIRE

    Aspiras, M.; Stoodley, P.; Nistico, L.; M. Longwell; Jager, M. de

    2010-01-01

    Dental biofilms are implicated in the formation of caries and periodontal disease. A major constituent of the supragingival biofilm is Streptococcus mutans, which produces lactic acid from sucrose fermentation, enhancing enamel demineralization and eventual caries development. Caries prevention through F inhibits enamel demineralization and promotes remineralization. Fluoride also exerts effects on metabolic activities in the supragingival biofilm such as aerobic respiration, acid fermentatio...

  14. Apoptosis and Vocal Fold Disease: Clinically Relevant Implications of Epithelial Cell Death

    Science.gov (United States)

    Novaleski, Carolyn K.; Carter, Bruce D.; Sivasankar, M. Preeti; Ridner, Sheila H.; Dietrich, Mary S.; Rousseau, Bernard

    2017-01-01

    Purpose: Vocal fold diseases affecting the epithelium have a detrimental impact on vocal function. This review article provides an overview of apoptosis, the most commonly studied type of programmed cell death. Because apoptosis can damage epithelial cells, this article examines the implications of apoptosis on diseases affecting the vocal fold…

  15. Acute changes in clinical breast measurements following bra removal: Implications for surgical practice

    Directory of Open Access Journals (Sweden)

    Joanna Scurr

    2015-03-01

    Conclusions: Internipple distance and breast projection can be measured first following bra removal, followed by sternal notch to nipple distance, any measures associated with the vertical nipple position should be made more than 6 min after bra removal. These guidelines have implications for breast surgery, particularly for unilateral reconstruction based on the residual breast position.

  16. Replacing the mercury manometer with an oscillometric device in a hypertension clinic: implications for clinical decision making.

    Science.gov (United States)

    Stergiou, G S; Lourida, P; Tzamouranis, D

    2011-11-01

    Oscillometric devices are being widely used for ambulatory, home and office blood pressure (BP) measurement, and several of them have been validated using established protocols. This cross-sectional study assessed the impact on antihypertensive treatment decisions of replacing the mercury sphygmomanometer by a validated oscillometric device. Consecutive subjects attending a hypertension clinic had triplicate simultaneous same-arm BP measurements using a mercury sphygmomanometer and a validated professional oscillometric device. For each device, uncontrolled hypertension was defined as average BP ≥140/90 mm Hg (systolic/diastolic). A total of 5108 simultaneous BP measurements were obtained from 763 subjects in 1717 clinic visits. In 24% of all visits, the mercury and the oscillometric BP measurements led to different conclusion regarding the diagnosis of uncontrolled hypertension. In 4.9% of the visits, the diagnostic disagreement was considered as 'clinically important' (BP exceeding the diagnostic threshold by >5 mm Hg). These data suggest that the replacement of the mercury sphygmomanometer by a validated professional oscillometric device will result into different treatment decisions in about 5% of the cases. Therefore, and because of the known problems when using mercury devices and the auscultatory technique in clinical practise, the oscillometric devices are regarded as reliable alternatives to the mercury sphygmomanometer for office use.

  17. Editorial: Acknowledging complexity and heterogeneity in causality--implications of recent insights into neuropsychology of childhood disorders for clinical practice.

    Science.gov (United States)

    Coghill, David

    2014-07-01

    From a clinical perspective research that tries to unravel the causal processes that underpin mental health problems can often seem esoteric and far removed from day to day clinical decision making. Indeed even though there are now a plethora of evidence based clinical guidelines that aim to support the translational process it still takes many years for new scientific understanding of a condition to permeate routine clinical practice, via this route. At the same time, however, a clinician's personal and informal interpretation of what is causing their patients' problems can have very important clinical implications and impact directly on; their formulation of a patient's presentation, the way in which they transmit this to the patient and their family and any treatment decisions that are made. Clinicians who are able to stay up to date with the latest evidence and scientific debate about what is and is not known about the underlying causes of mental health problems should be at an advantage in this regard. But for the busy clinician, 'just' staying up to date with the huge amount of new directly related to this topic is in itself a big ask in itself - critically appraising this evidence, in a balanced way, another thing altogether. To facilitate this process it is necessary for researchers to make every effort to include a balanced, clear and relevant discussion of the translational implications of their findings. In particular they must try to avoid overselling a message that may attract a lot of initial attention but that may, in time, prove to be a false dawn or an over simplification. © 2014 The Authors. Journal of Child Psychology and Psychiatry. © 2014 Association for Child and Adolescent Mental Health.

  18. Role of inflammation and infection in the pathogenesis of human acute liver failure: Clinical implications for monitoring and therapy.

    Science.gov (United States)

    Donnelly, Mhairi C; Hayes, Peter C; Simpson, Kenneth J

    2016-07-14

    Acute liver failure is a rare and devastating clinical condition. At present, emergency liver transplantation is the only life-saving therapy in advanced cases, yet the feasibility of transplantation is affected by the presence of systemic inflammation, infection and resultant multi-organ failure. The importance of immune dysregulation and acquisition of infection in the pathogenesis of acute liver failure and its associated complications is now recognised. In this review we discuss current thinking regarding the role of infection and inflammation in the pathogenesis of and outcome in human acute liver failure, the implications for the management of such patients and suggest directions for future research.

  19. Clinical implications of basic science discoveries: janus resurrected--two faces of B cell and plasma cell biology.

    Science.gov (United States)

    Woodle, E S; Rothstein, D M

    2015-01-01

    B cells play a complex role in the immune response. In addition to giving rise to plasma cells (PCs) and promoting T cell responses via antigen presentation, they perform immunoregulatory functions. This knowledge has created concerns regarding nonspecific B cell depletional therapy because of the potential to paradoxically augment immune responses. Recent studies now indicate that PCs have immune functions beyond immunoglobulin synthesis. Evidence for a new role for PCs as potent regulatory cells (via IL-10 and IL-35 production) is discussed including the implications for PC-targeted therapies currently being developed for clinical transplantation. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

  20. Trichorhinophalangeal syndrome II, expanding the clinical spectrum

    African Journals Online (AJOL)

    Rabah M. Shawky

    2014-06-17

    Jun 17, 2014 ... families and to assure orthopedic follow up and management of growth, hearing and speech problems. Although the syn- drome is considered rare, dermatologist must be aware of the patients complaining of a premature onset of androgenic pattern alopecia [22]. Also some additional features not reported ...

  1. Clinical application of cardiac computed tomography: implications for chest pain assessment

    OpenAIRE

    Nasis, Arthur

    2017-01-01

    Chest pain is a common and potentially life-threatening symptom that represents a global health and economic challenge. The prompt and accurate evaluation of chest pain has considerable implications for patient morbidity and mortality as well as on health care economics, however accurate identification of the aetiology of a patient’s chest pain is associated with many diagnostic challenges and potential pitfalls. Most current diagnostic strategies for chest pain focus on the detection of acut...

  2. The expanding universe

    CERN Document Server

    Lew, Kristi

    2011-01-01

    People have always been fascinated with the stars above and the universe that contains them. Over the years, astronomers have developed numerous theories to explain how the universe began, how it works, and what its ultimate fate will be. But all of the scientists' questions are far from answered. The Expanding Universe goes beyond the creation of the universe to explain how scientists think the universe works, grows, and changes, including what great thinkers Isaac Newton and Albert Einstein had to say about its fate. Readers will also learn about how researchers are slowly shedding light on

  3. Expanding Your Horizon 2015

    CERN Multimedia

    Kaltenhauser, Kristin

    2015-01-01

    Expanding your horizons is a bi-annual “Science Day” for girls aged 11 to 14, held at the University of Geneva on 14 November. The girls had the opportunity to take part in hands-on workshops held by local professional women in the field of science, mathematics, engineering and technology. For the fourth time, CERN was part of this event, offering three workshops as well as a booth at the Discovery Fair, including Higgnite, an interactive visualization of the Higgs Field.

  4. Systematic review of emergency medicine clinical practice guidelines: Implications for research and policy.

    Science.gov (United States)

    Venkatesh, Arjun K; Savage, Dan; Sandefur, Benjamin; Bernard, Kenneth R; Rothenberg, Craig; Schuur, Jeremiah D

    2017-01-01

    Over 25 years, emergency medicine in the United States has amassed a large evidence base that has been systematically assessed and interpreted through ACEP Clinical Policies. While not previously studied in emergency medicine, prior work has shown that nearly half of all recommendations in medical specialty practice guidelines may be based on limited or inconclusive evidence. We sought to describe the proportion of clinical practice guideline recommendations in Emergency Medicine that are based upon expert opinion and low level evidence. Systematic review of clinical practice guidelines (Clinical Policies) published by the American College of Emergency Physicians from January 1990 to January 2016. Standardized data were abstracted from each Clinical Policy including the number and level of recommendations as well as the reported class of evidence. Primary outcomes were the proportion of Level C equivalent recommendations and Class III equivalent evidence. The primary analysis was limited to current Clinical Policies, while secondary analysis included all Clinical Policies. A total of 54 Clinical Policies including 421 recommendations and 2801 cited references, with an average of 7.8 recommendations and 52 references per guideline were included. Of 19 current Clinical Policies, 13 of 141 (9.2%) recommendations were Level A, 57 (40.4%) Level B, and 71 (50.4%) Level C. Of 845 references in current Clinical Policies, 67 (7.9%) were Class I, 272 (32.3%) Class II, and 506 (59.9%) Class III equivalent. Among all Clinical Policies, 200 (47.5%) recommendations were Level C equivalent, and 1371 (48.9%) of references were Class III equivalent. Emergency medicine clinical practice guidelines are largely based on lower classes of evidence and a majority of recommendations are expert opinion based. Emergency medicine appears to suffer from an evidence gap that should be prioritized in the national research agenda and considered by policymakers prior to developing future quality

  5. Updates on breast cancer genetics: Clinical implications of detecting syndromes of inherited increased susceptibility to breast cancer.

    Science.gov (United States)

    Cobain, Erin F; Milliron, Kara J; Merajver, Sofia D

    2016-10-01

    Since the initial discovery that pathogenic germline alterations in BRCA 1/2 increase susceptibility to breast and ovarian cancer, many additional genes have now been discovered that also increase breast cancer risk. Given that several more genes have now been implicated in hereditary breast cancer syndromes, there is increased clinical use of multigene panel testing to evaluate patients with a suspected genetic predisposition to breast cancer. While this is most certainly a cost-effective approach, broader testing strategies have resulted in a higher likelihood of identifying moderate-penetrance genes, for which management guidelines regarding breast cancer risk reduction have not been firmly established. In addition, the testing of more genes has led to increased detection of variants of uncertain significance. We review the current knowledge regarding both high- and moderate-risk hereditary breast cancer syndromes, as well as additional genes implicated in hereditary breast cancer for which there is limited data. Furthermore, strategies for cancer risk reduction in mutation carriers as well as therapeutic implications for those patients who harbor pathogenic germline alterations are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Microenvironmental influence on pre-clinical activity of polo-like kinase inhibition in multiple myeloma: implications for clinical translation.

    Directory of Open Access Journals (Sweden)

    Douglas W McMillin

    Full Text Available Polo-like kinases (PLKs play an important role in cell cycle progression, checkpoint control and mitosis. The high mitotic index and chromosomal instability of advanced cancers suggest that PLK inhibitors may be an attractive therapeutic option for presently incurable advanced neoplasias with systemic involvement, such as multiple myeloma (MM. We studied the PLK 1, 2, 3 inhibitor BI 2536 and observed potent (IC50<40 nM and rapid (commitment to cell death <24 hrs in vitro activity against MM cells in isolation, as well as in vivo activity against a traditional subcutaneous xenograft mouse model. Tumor cells in MM patients, however, don't exist in isolation, but reside in and interact with the bone microenvironment. Therefore conventional in vitro and in vivo preclinical assays don't take into account how interactions between MM cells and the bone microenvironment can potentially confer drug resistance. To probe this question, we performed tumor cell compartment-specific bioluminescence imaging assays to compare the preclinical anti-MM activity of BI 2536 in vitro in the presence vs. absence of stromal cells or osteoclasts. We observed that the presence of these bone marrow non-malignant cells led to decreased anti-MM activity of BI 2536. We further validated these results in an orthotopic in vivo mouse model of diffuse MM bone lesions where tumor cells interact with non-malignant cells of the bone microenvironment. We again observed that BI 2536 had decreased activity in this in vivo model of tumor-bone microenvironment interactions highlighting that, despite BI 2536's promising activity in conventional assays, its lack of activity in microenvironmental models raises concerns for its clinical development for MM. More broadly, preclinical drug testing in the absence of relevant tumor microenvironment interactions may overestimate potential clinical activity, thus explaining at least in part the gap between preclinical vs. clinical efficacy in MM

  7. Psychometric Assessment of the Chinese Version of the Abbreviated Expanded Prostate Cancer Index Composite (EPIC-26) and the Clinical Practice Version (EPIC-CP) in Chinese Men With Prostate Cancer.

    Science.gov (United States)

    Lam, Wendy W T; Tse, Michael A; Ng, Chris N L; Chung, Edward K M; Fielding, Richard

    2017-06-01

    The Expanded Prostate Cancer Index Composite (EPIC) instrument was designed to assess a range of health-related quality-of-life issues specifically relevant to patients with prostate cancer. This study examined the validity and reliability of Chinese versions of the 26-item EPIC and of the 16-item EPIC for Clinical Practice (EPIC-CP) in Chinese patients with prostate cancer. A Chinese version of the 26-item EPIC and the 16-item EPIC-CP were self-completed by 252 Chinese patients with prostate cancer who were recruited from three community-based cancer service centers. Confirmatory factors analysis assessed the factor structures of the EPIC and the EPIC-CP. Internal consistency and construct and clinical validities of the factor structures were assessed. Confirmatory factor analysis revealed that the original factor structure of both EPIC-26 and EPIC-CP showed good fit to this sample. A correlated model was superior to a hierarchical model in both EPIC-26 and EPIC-CP supporting the utility of the domain scores over the total scores. Cronbach α ranged from 0.55 to 0.91 for EPIC-26 and 0.44 to 0.67 for EPIC-CP. Construct validity was supported by correlations between EPIC-26/EPIC-CP and psychological distress measures. Clinical validity was supported by differentiation between patients with and without prostatectomy. These Chinese versions of the five-factor EPIC-26 and the EPIC-CP are valid and practical measures for assessing a range of health-related quality-of-life issues related to the diagnosis and treatment of prostate cancer, highlighting their utility in assessing health-related quality of life for patients diagnosed with prostate cancer. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  8. Prevalence and clinical implications of cyclin D1 expression in diffuse large B-cell lymphoma (DLBCL) treated with immunochemotherapy

    DEFF Research Database (Denmark)

    Ok, Chi Young; Xu-Monette, Zijun Y; Tzankov, Alexandar

    2014-01-01

    patients who were diagnosed with DLBCL as part of the International DLBCL rituximab with cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (R-CHOP) Consortium Program and performed clinical, immunohistochemical, and genetic analyses with a focus on cyclin D1. All patients who were cyclin D......BACKGROUND: Cyclin D1 expression has been reported in a subset of patients with diffuse large B-cell leukemia (DLBCL), but studies have been few and generally small, and they have demonstrated no obvious clinical implications attributable to cyclin D1 expression. METHODS: The authors reviewed 1435......1-positive according to immunohistochemistry were also assessed for rearrangements of the cyclin D1 gene (CCND1) using fluorescence in situ hybridization. Gene expression profiling was performed to compare patients who had DLBCL with and without cyclin D1 expression. RESULTS: In total, 30 patients...

  9. Proprioception: where are we now? A commentary on clinical assessment, changes across the life course, functional implications and future interventions.

    Science.gov (United States)

    Suetterlin, Karen Joan; Sayer, Avan Aihie

    2014-05-01

    Proprioception, the sense of where one is in space, is essential for effective interaction with the environment. A lack of or reduction in proprioceptive acuity has been directly correlated with falls and with reduced functional independence in older people. Proprioceptive losses have also been shown to negatively correlate with functional recovery post stroke and play a significant role in other conditions such as Parkinson's disease. However, despite its central importance to many geriatric syndromes, the clinical assessment of proprioception has remained remarkably static. We look at approaches to the clinical assessment of proprioception, changes in proprioception across the life course, functional implications of proprioception in health and disease and the potential for targeted interventions in the future such as joint taping, and proprioception-specific rehabilitation and footwear.

  10. Identification of subtypes in subjects with mild-to-moderate airflow limitation and its clinical and socioeconomic implications

    Science.gov (United States)

    Lee, Jin Hwa; Rhee, Chin Kook; Kim, Kyungjoo; Kim, Jee-Ae; Kim, Sang Hyun; Yoo, Kwang Ha; Kim, Woo Jin; Park, Yong Bum; Park, Hye Yun; Jung, Ki-Suck

    2017-01-01

    Purpose The purpose of this study was to identify subtypes in patients with mild-to-moderate airflow limitation and to appreciate their clinical and socioeconomic implications. Methods Subjects who were aged ≥20 years and had forced expiratory volume in 1 second (FEV1) ≥60% predicted and FEV1/forced vital capacity ratio of total medical expense to household income, the mean ratio was highest in the COPD group. Conclusion Clinical and epidemiological heterogeneities of subjects with mild-to-moderate airflow limitation and a different level of health care utilization by each subtype are shown. Identification of a subtype with high health care demand could be a priority for effective utilization of limited resources. PMID:28442900

  11. Controversies in the physiological basis of the 'anaerobic threshold' and their implications for clinical cardiopulmonary exercise testing.

    Science.gov (United States)

    Hopker, J G; Jobson, S A; Pandit, J J

    2011-02-01

    This article reviews the notion of the 'anaerobic threshold' in the context of cardiopulmonary exercise testing. Primarily, this is a review of the proposed mechanisms underlying the ventilatory and lactate response to incremental exercise, which is important to the clinical interpretation of an exercise test. Since such tests are often conducted for risk stratification before major surgery, a failure to locate or justify the existence of an anaerobic threshold will have some implications for clinical practice. We also consider alternative endpoints within the exercise response that might be better used to indicate a patient's capacity to cope with the metabolic demands encountered both during and following major surgery. © 2011 The Authors. Anaesthesia © 2011 The Association of Anaesthetists of Great Britain and Ireland.

  12. Re-conceptualizing risk in genetic counseling: implications for clinical practice.

    Science.gov (United States)

    Austin, Jehannine C

    2010-06-01

    Risk communication is an important component of genetic counseling. However, many authors have noted that after genetic counseling, subjective risk frequently does not match the objective risk provided by the counselor. This inevitably leads to the conclusion that the risk communication process was not "effective". There has been much discussion about how this problem can be better addressed, such that our clients recall numeric risks more accurately after genetic counseling. This article draws on the risk and probability literature from other fields (including psychology, economics, philosophy and climate change) to deconstruct the concepts of "risk" and risk perception to attempt to expand upon and develop thought and discussion about and investigation of the risk communication process in genetic counseling.

  13. Influence networks among substance abuse treatment clinics: implications for the dissemination of innovations.

    Science.gov (United States)

    Johnson, Kimberly; Quanbeck, Andrew; Maus, Adam; Gustafson, David H; Dearing, James W

    2015-09-01

    Understanding influence networks among substance abuse treatment clinics may speed the diffusion of innovations. The purpose of this study was to describe influence networks in Massachusetts, Michigan, New York, Oregon, and Washington and test two expectations, using social network analysis: (1) Social network measures can identify influential clinics; and (2) Within a network, some weakly connected clinics access out-of-network sources of innovative evidence-based practices and can spread these innovations through the network. A survey of 201 clinics in a parent study on quality improvement provided the data. Network measures and sociograms were obtained from adjacency matrixes created by UCINet. We used regression analysis to determine whether network status relates to clinics' adopting innovations. Findings suggest that influential clinics can be identified and that loosely linked clinics were likely to join the study sooner than more influential clinics but were not more likely to have improved outcomes than other organizations. Findings identify the structure of influence networks for SUD treatment organizations and have mixed results on how those structures impacted diffusion of the intervention under study. Further study is necessary to test whether use of knowledge of the network structure will have an effect on the pace and breadth of dissemination of innovations.

  14. Psychotic experiences in a mental health clinic sample : implications for suicidality, multimorbidity and functioning

    NARCIS (Netherlands)

    Kelleher, I.; Devlin, N.; Wigman, J. T. W.; Kehoe, A.; Murtagh, A.; Fitzpatrick, C.; Cannon, M.

    Background Recent community-based research has suggested that psychotic experiences act as markers of severity of psychopathology. There has, however, been a lack of clinic-based research. We wished to investigate, in a clinical sample of adolescents referred to a state-funded mental health service,

  15. Stability of the elbow joint: relevant anatomy and clinical implications of in vitro biomechanical studies

    NARCIS (Netherlands)

    de Haan, J.; Schep, N. W. L.; Eygendaal, D.; Kleinrensink, G.-J.; Tuinebreijer, W. E.; den Hartog, D.

    2011-01-01

    The aim of this literature review is to describe the clinical anatomy of the elbow joint based on information from in vitro biomechanical studies. The clinical consequences of this literature review are described and recommendations are given for the treatment of elbow joint dislocation.The PubMed

  16. Identifying metabolic syndrome in a clinical cohort: Implications for prevention of chronic disease

    Directory of Open Access Journals (Sweden)

    Allison Martin

    2016-12-01

    The utility of the harmonised equation in the clinical setting was confirmed in this overweight clinical cohort. Those classified as having MetS were more likely to be older, overweight/obese individuals and they had a substantially higher risk of developing CVD and insulin resistance than those without MetS.

  17. Women’s involvement in clinical trials: historical perspective and future implications

    Directory of Open Access Journals (Sweden)

    Liu KA

    2016-03-01

    Full Text Available The importance of considering the differences between the male and female sex in clinical decision-making is crucial. However, it has been acknowledged in recent decades that clinical trials have not always adequately enrolled women or analyzed sex-specific differences in the data. As these deficiencies have hindered the progress of understanding women’s response to medications, agencies in the United States have worked towards the inclusion of women in clinical trials and appropriate analysis of sex-specific data from clinical trials. This review outlines the history and progress of women’s inclusion in clinical trials for prescription drugs and presents considerations for researchers, clinicians, and academicians on this issue.

  18. Resource implications of preparing individual participant data from a clinical trial to share with external researchers.

    Science.gov (United States)

    Tudur Smith, Catrin; Nevitt, Sarah; Appelbe, Duncan; Appleton, Richard; Dixon, Pete; Harrison, Janet; Marson, Anthony; Williamson, Paula; Tremain, Elizabeth

    2017-07-17

    Demands are increasingly being made for clinical trialists to actively share individual participant data (IPD) collected from clinical trials using responsible methods that protect the confidentiality and privacy of clinical trial participants. Clinical trialists, particularly those receiving public funding, are often concerned about the additional time and money that data-sharing activities will require, but few published empirical data are available to help inform these decisions. We sought to evaluate the activity and resources required to prepare anonymised IPD from a clinical trial in anticipation of a future data-sharing request. Data from two UK publicly funded clinical trials were used for this exercise: 2437 participants with epilepsy recruited from 90 hospital outpatient clinics in the SANAD trial and 146 children with neuro-developmental problems recruited from 18 hospitals in the MENDS trial. We calculated the time and resources required to prepare each anonymised dataset and assemble a data pack ready for sharing. The older SANAD trial (published 2007) required 50 hours of staff time with a total estimated associated cost of £3185 whilst the more recently completed MENDS trial (published 2012) required 39.5 hours of staff time with total estimated associated cost of £2540. Clinical trial researchers, funders and sponsors should consider appropriate resourcing and allow reasonable time for preparing IPD ready for subsequent sharing. This process would be most efficient if prospectively built into the standard operational design and conduct of a clinical trial. Further empirical examples exploring the resource requirements in other settings is recommended. SANAD: International Standard Randomised Controlled Trials Registry: ISRCTN38354748 . Registered on 25 April 2003. EU Clinical Trials Register Eudract 2006-004025-28 . Registered on 16 May 2007. International Standard Randomised Controlled Trials Registry: ISRCTN05534585 /MREC 07/MRE08

  19. Professional approaches in clinical judgements among senior and junior doctors: implications for medical education

    Directory of Open Access Journals (Sweden)

    Pilhammar Ewa

    2009-05-01

    Full Text Available Abstract Background Clinical experience has traditionally been highly valued in medical education and clinical healthcare. On account of its multi-faceted nature, clinical experience is mostly difficult to articulate, and is mainly expressed in clinical situations as professional approaches. Due to retirement, hospitals in Scandinavia will soon face a substantial decrease in the number of senior specialist doctors, and it has been discussed whether healthcare will suffer an immense loss of experienced-based knowledge when this senior group leaves the organization. Both senior specialists and junior colleagues are often involved in clinical education, but the way in which these two groups vary in professional approaches and contributions to clinical education has not been so well described. Cognitive psychology has contributed to the understanding of how experience may influence professional approaches, but such studies have not included the effect of differences in position and responsibilities that junior and senior doctors hold in clinical healthcare. In the light of the discussion above, it is essential to describe the professional approaches of senior doctors in relation to those of their junior colleagues. This study therefore aims to describe and compare the professional approaches of junior and senior doctors when making clinical judgements. Methods Critical incident technique was used in interviews with nine senior doctors and nine junior doctors in internal medicine. The interviews were subjected to qualitative content analysis. Result Senior and junior doctors expressed a variety of professional approaches in clinical judgement as follows: use of theoretical knowledge, use of prior experience of cases and courses of events, use of ethical and moral values, meeting and communicating with the patient, focusing on available information, relying on their own ability, getting support and guidance from others and being directed by the

  20. The relationship between senior management team culture and clinical governance: Empirical investigation and managerial implications.

    Science.gov (United States)

    Prenestini, Anna; Calciolari, Stefano; Lega, Federico; Grilli, Roberto

    2015-01-01

    Health care organizations are pressured to improve the cost-effectiveness of service delivery. Clinical governance is an important trigger to improve care quality and safety and rank high in the reform agenda of health systems. The senior management team culture plays a major role in establishing clinical governance practices, because it strongly influences the values, attitudes, and behaviors of the members of an organization. The aim of this study was to investigate the relationship between senior management team culture and clinical governance in the public health care organizations of three Italian regions. The assessment of senior management culture was conducted using the Competing Values Framework and a corresponding instrument adapted for the Italian context. Clinical governance was assessed using an ad hoc instrument focused on the senior management team's perception and attitude toward clinical governance. The survey achieved a 54% response rate. The results of four different models demonstrate that organizations characterized by different dominant cultures are associated with significant differences in attitudes toward clinical governance. In particular, on average, dominant cultures with a prevailing external focus are associated with a more positive attitude toward clinical governance. The selection and appointments of top managers should consider the style of leadership that is most apt to facilitate the growth of rational and developmental cultures. Furthermore, the training of top managers and leading doctors should reinforce leadership aptitude and approaches that are consistent with the desired organizational cultures.

  1. Increasing workload and changing referral patterns in paediatric cardiology outreach clinics: implications for consultant staffing

    Science.gov (United States)

    Wagstaff, M; Rigby, M; Redington, A

    1998-01-01

    Objective—To assess the workload of, and referral patterns to, paediatric cardiology outreach clinics to provide data for future planning.
Design—Descriptive study of outpatient attendance during 1991 and 1996.
Setting—Five district general hospitals with unchanged local demographics and referral patterns during the study period.
Methods—Postal, telephone, and on site survey of clinic records and case notes.
Results—The number of outpatients increased by 61%, with a consequent increase in the number of clinics held and patients seen in each clinic. The number of patients aged between 10 and 15 years doubled.
Conclusion—These data confirm the impression that demands for paediatric cardiology services are increasing. The increased need for attendance at outreach clinics has inevitable consequences for the clinical, teaching, and research activities of specialists in tertiary centres. An increase in the number of paediatric cardiologists, or development of local expertise (general paediatricians with an interest in cardiology), will be required. Furthermore, the increasingly large cohort of older teenagers and young adults with congenital heart disease underscores the need for the development of specialist facilities.

 Keywords: paediatric clinics;  workload;  congenital heart disease PMID:9602652

  2. Implications of the BIA-102474-101 study for review of first-into-human clinical trials.

    Science.gov (United States)

    Eddleston, Michael; Cohen, Adam F; Webb, David J

    2016-04-01

    Over the past 10 years, thousands of first-into-human (FIH) clinical trials have been performed in Europe, with few severe adverse events (SAEs). Each has received detailed prior safety review at both the local clinical research facility and at national drug regulatory authority level. The recent fatal SAE in the BIA-102474-101 clinical trial shows the limitations of this process. Although criticized for not sequentially dosing subjects both within and between cohorts - as recommended by the European Medicines Agency for high-risk compounds after the TeGenero clinical trial disaster in 2006 - BIA-102474-101 was not considered to be high risk. Indeed, compounds with similar mechanisms of action had previously been taken through phase I and II trials without incident, and higher doses had been safely given for longer durations to nonhuman primates. If the available data are comprehensive and accurate, and further investigation does not reveal unreported warning signs, this study has serious implications for ongoing and future review of FIH clinical trials. All preclinical study documents and clinical data collected during the BIA-102474-101 trial should be made available urgently so that lessons can be learnt. In the meantime, reviewers and clinical researchers should always ask for information on drug and target interactions and full reports of preclinical toxicity studies, and plan sequential dosing with longer delays between patients and cohorts, particularly if late SAEs might be anticipated. The use of individual patient pharmacokinetic and dynamic data should guide sequential dosing. A process for systematic risk assessment, like that currently used in the Netherlands, should be applied routinely to all trials with novel compounds. © 2016 The British Pharmacological Society.

  3. What Do People Believe About Memory? Implications for the Science and Pseudoscience of Clinical Practice

    Science.gov (United States)

    Lynn, Steven Jay; Evans, James; Laurence, Jean-Roch; Lilienfeld, Scott O

    2015-01-01

    We examine the evidence concerning what people believe about memory. We focus on beliefs regarding the permanence of memory and whether memory can be repressed and accurately recovered. We consider beliefs about memory among the undergraduate and general population, mental health professionals, judges, jurors, and law enforcement officers to provide a broad canvass that extends to the forensic arena, as well as to psychiatry, psychology, and allied disciplines. We discuss the implications of these beliefs for the education of the general public and mental health professionals regarding the science and pseudoscience of memory and the use of suggestive procedures in psychotherapy. PMID:26720822

  4. What Do People Believe About Memory? Implications for the Science and Pseudoscience of Clinical Practice.

    Science.gov (United States)

    Lynn, Steven Jay; Evans, James; Laurence, Jean-Roch; Lilienfeld, Scott O

    2015-12-01

    We examine the evidence concerning what people believe about memory. We focus on beliefs regarding the permanence of memory and whether memory can be repressed and accurately recovered. We consider beliefs about memory among the undergraduate and general population, mental health professionals, judges, jurors, and law enforcement officers to provide a broad canvass that extends to the forensic arena, as well as to psychiatry, psychology, and allied disciplines. We discuss the implications of these beliefs for the education of the general public and mental health professionals regarding the science and pseudoscience of memory and the use of suggestive procedures in psychotherapy.

  5. Hormetic Response to Low-Dose Radiation: Focus on the Immune System and Its Clinical Implications

    Directory of Open Access Journals (Sweden)

    Jiuwei Cui

    2017-01-01

    Full Text Available The interrelationship between ionizing radiation and the immune system is complex, multifactorial, and dependent on radiation dose/quality and immune cell type. High-dose radiation usually results in immune suppression. On the contrary, low-dose radiation (LDR modulates a variety of immune responses that have exhibited the properties of immune hormesis. Although the underlying molecular mechanism is not fully understood yet, LDR has been used clinically for the treatment of autoimmune diseases and malignant tumors. These advancements in preclinical and clinical studies suggest that LDR-mediated immune modulation is a well-orchestrated phenomenon with clinical potential. We summarize recent developments in the understanding of LDR-mediated immune modulation, with an emphasis on its potential clinical applications.

  6. Expanding hollow metal rings

    Science.gov (United States)

    Peacock, Harold B [Evans, GA; Imrich, Kenneth J [Grovetown, GA

    2009-03-17

    A sealing device that may expand more planar dimensions due to internal thermal expansion of a filler material. The sealing material is of a composition such that when desired environment temperatures and internal actuating pressures are reached, the sealing materials undergoes a permanent deformation. For metallic compounds, this permanent deformation occurs when the material enters the plastic deformation phase. Polymers, and other materials, may be using a sealing mechanism depending on the temperatures and corrosivity of the use. Internal pressures are generated by either rapid thermal expansion or material phase change and may include either liquid or solid to gas phase change, or in the gaseous state with significant pressure generation in accordance with the gas laws. Sealing material thickness and material composition may be used to selectively control geometric expansion of the seal such that expansion is limited to a specific facing and or geometric plane.

  7. Nothing New (Ethically Under the Sun: Policy & Clinical Implications of Nanomedicine

    Directory of Open Access Journals (Sweden)

    MacDonald, Chris

    2012-06-01

    Full Text Available Nanotechnology research is beginning to see widespread coverage in the media and popular science literatures, but discussions of hopes and fears about nanotechnology have already become polarised into utopian and dystopian visions. More moderate discussions focus on the near-term applications of nanotechnologies, and on potential benefits and harms. However, in exploring the social and ethical implications of nanotechnology (or nanomedicine, the focus of this paper, important lessons should be learned from experiences in other fields. In particular, studies of the ethical, legal, and social issues (ELSI of genetics research have successfully mapped out many of the issues (and social and political responses that arise when new technologies are deployed. It is our contention that, for the most part, the ethical and social issues arising in nanomedicine are not altogether new, and thus do not require novel ethical principles or frameworks, nor a massive investment in ‘NELSI’ research. Instead, what is needed is support for the development of a culture of ethics amongst scientists and clinicians, basic scientific and medical knowledge for bioethicists, and a social competency for citizens to participate actively in debates about the implications of new technologies in general.

  8. Clinical Implications of Daytime Sleepiness for the Academic Performance of Middle School Age Adolescents with ADHD

    Science.gov (United States)

    Langberg, Joshua M.; Dvorsky, Melissa R.; Marshall, Stephen; Evans, Steven W.

    2013-01-01

    This study investigated the relative impact of total time slept per night and daytime sleepiness on the academic functioning of 100 middle school age youth (Mage = 11.9) with Attention-Deficit/Hyperactivity Disorder (ADHD). The primary goal of the study was to determine if total time slept per night and/or daytime sleepiness, as measured by youth self-report on the Pediatric Daytime Sleepiness Scale (PDSS), predicted academic functioning above and beyond symptoms of ADHD and relevant covariates, such as intelligence, achievement scores, and parent education level. Self-reported daytime sleepiness but not self-reported total time slept per night was significantly associated with all academic outcomes. When examined in a hierarchical regression model, self-reported daytime sleepiness significantly predicted parent-rated homework problems and academic impairment and teacher-rated academic competence above and beyond symptoms of ADHD and relevant covariates but did not predict GPA or teacher-rated academic impairment. The implications of these findings for better understanding the association between ADHD and sleep and the functional implications of this relationship are discussed. PMID:23509927

  9. Public health care system, a quasi-experimental study: Acceptance and attitude to implicate clinical services

    Directory of Open Access Journals (Sweden)

    Gillani Syed Wasif

    2017-03-01

    Full Text Available A six-month longitudinal intervention arm study with a pre-post cross-sectional questionnaire-based survey was performed. A 3-phase objective structured clinical examination (OSCE design was utilized for evaluation of acceptance and attitude of pharmacy students towards clinical pharmacy services. The pre-OSCE survey showed increased disagreement with the role of clinical pharmacists, compared to a significant positive shift in attitude towards their services in the healthcare team after 6 months of the trial. Responses improved for awareness (the current healthcare system could be improved by involving pharmacists, p < 0.02 and positive attitude categories (doctors and nurses would be happy to welcome the services of competent clinical pharmacists as part of their team, p < 0.01 in addition to competency (pharmacists have sufficient clinical training to advise doctors and nurses, p < 0.01. The predictive model suggested a strong positive effect on patient interaction, medical information tasks, clinical decisions on drug-related problems (DRPs, and communication with healthcare professionals (R2 = 0.41, F = 1.51, p < 0.001.

  10. Clinical implications of in silico mathematical modeling for glioblastoma: a critical review.

    Science.gov (United States)

    Protopapa, Maria; Zygogianni, Anna; Stamatakos, Georgios S; Antypas, Christos; Armpilia, Christina; Uzunoglu, Nikolaos K; Kouloulias, Vassilis

    2018-01-01

    Glioblastoma remains a clinical challenge in spite of years of extensive research. Novel approaches are needed in order to integrate the existing knowledge. This is the potential role of mathematical oncology. This paper reviews mathematical models on glioblastoma from the clinical doctor's point of view, with focus on 3D modeling approaches of radiation response of in vivo glioblastomas based on contemporary imaging techniques. As these models aim to provide a clinically useful tool in the era of personalized medicine, the integration of the latest advances in molecular and imaging science and in clinical practice by the in silico models is crucial for their clinical relevance. Our aim is to indicate areas of GBM research that have not yet been addressed by in silico models and to point out evidence that has come up from in silico experiments, which may be worth considering in the clinic. This review examines how close these models have come in predicting the outcome of treatment protocols and in shaping the future of radiotherapy treatments.

  11. Carbohydrate plasma expanders for passive tumor targeting

    DEFF Research Database (Denmark)

    Hoffmann, Stefan; Caysa, Henrike; Kuntsche, Judith

    2013-01-01

    The objective of this study was to investigate the suitability of carbohydrate plasma volume expanders as a novel polymer platform for tumor targeting. Many synthetic polymers have already been synthesized for targeted tumor therapy, but potential advantages of these carbohydrates include...... inexpensive synthesis, constant availability, a good safety profile, biodegradability and the long clinical use as plasma expanders. Three polymers have been tested for cytotoxicity and cytokine activation in cell cultures and conjugated with a near-infrared fluorescent dye: hydroxyethyl starches (HES 200 k...

  12. Contemporary clinical trials in ventricular tachycardia and fibrillation: implications of ESVEM, CASCADE, and CASH for clinical management.

    Science.gov (United States)

    Anderson, J L

    1995-10-01

    Recent clinical trials in patients with ventricular tachycardia (VT) or fibrillation (VF) have occurred in the setting of the disappointing results of postinfarction secondary prevention studies using Class I antiarrhythmics (e.g., CAST). ESVEM addressed in a randomized trial whether electrophysiologic study (EPS) or Holter monitoring (HM) is a more accurate predictor of long-term antiarrhythmic drug efficacy in VT/VF patients (N=486) and what the relative efficacy of various antiarrhythmic agents is for VT/VF. Surprisingly, arrhythmia recurrence rates were not significantly different by the method of determining an efficacy prediction. However, arrhythmia recurrence and mortality were lower (by about 50% at 1 year) in patients treated with sotalol (a mixed Class II/III agent) than with other drugs (Class I). CASCADE evaluated empiric amiodarone versus guided (EPS or HM) standard (Class I) therapy in survivors of out-of-hospital cardiac arrest due to VF. The primary endpoint of cardiac death, resuscitated VF, or syncopal shock (in ICD patients) was reduced by amiodarone compared with conventional therapy (9% vs 23% at 1 year). An interim report of the ongoing CASH study suggested in 230 survivors of cardiac arrest that propafenone (Class IC) provided less effective prophylaxis (approximately 20% 1-year mortality) compared with randomly assigned therapies with amiodarone, metoprolol, or an ICD (approximately 14% mortality rates) and was excluded from further study. These studies have led to a paradigm shift in the approach to antiarrhythmic therapy of VT/VF: drugs with antisympathetic plus Class III (refractoriness prolonging) action (i.e., sotalol, amiodarone) are superior to traditional drugs with Class I( conduction slowing) effects, even when guided by EPS or HM.

  13. Clinical implications of chronic heart failure phenotypes defined by cluster analysis.

    Science.gov (United States)

    Ahmad, Tariq; Pencina, Michael J; Schulte, Phillip J; O'Brien, Emily; Whellan, David J; Piña, Ileana L; Kitzman, Dalane W; Lee, Kerry L; O'Connor, Christopher M; Felker, G Michael

    2014-10-28

    Classification of chronic heart failure (HF) is on the basis of criteria that may not adequately capture disease heterogeneity. Improved phenotyping may help inform research and therapeutic strategies. This study used cluster analysis to explore clinical phenotypes in chronic HF patients. A cluster analysis was performed on 45 baseline clinical variables from 1,619 participants in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) study, which evaluated exercise training versus usual care in chronic systolic HF. An association between identified clusters and clinical outcomes was assessed using Cox proportional hazards modeling. Differential associations between clinical outcomes and exercise testing were examined using interaction testing. Four clusters were identified (ranging from 248 to 773 patients in each), in which patients varied considerably among measures of age, sex, race, symptoms, comorbidities, HF etiology, socioeconomic status, quality of life, cardiopulmonary exercise testing parameters, and biomarker levels. Differential associations were observed for hospitalization and mortality risks between and within clusters. Compared with cluster 1, risk of all-cause mortality and/or all-cause hospitalization ranged from 0.65 (95% confidence interval [95% CI]: 0.54 to 0.78) for cluster 4 to 1.02 (95% CI: 0.87 to 1.19) for cluster 3. However, for all-cause mortality, cluster 3 had a disproportionately lower risk of 0.61 (95% CI: 0.44 to 0.86). Evidence suggested differential effects of exercise treatment on changes in peak oxygen consumption and clinical outcomes between clusters (p for interaction Cluster analysis of clinical variables identified 4 distinct phenotypes of chronic HF. Our findings underscore the high degree of disease heterogeneity that exists within chronic HF patients and the need for improved phenotyping of the syndrome. (Exercise Training Program to Improve Clinical Outcomes in Individuals With

  14. Convergence of nanotechnology with radiation therapy—insights and implications for clinical translation

    Science.gov (United States)

    Chatterjee, Dev Kumar; Wolfe, Tatiana; Lee, Jihyoun; Brown, Aaron P; Singh, Pankaj Kumar; Bhattarai, Shanta Raj; Diagaradjane, Parmeswaran; Krishnan, Sunil

    2014-01-01

    Improvements in accuracy and efficacy in treating tumors with radiation therapy (RT) over the years have been fueled by parallel technological and conceptual advances in imaging and image-guidance techniques, radiation treatment machines, computational methods, and the understanding of the biology of tumor response to RT. Recent advances in our understanding of the hallmarks of cancer and the emergence of strategies to combat these traits of cancer have resulted in an expanding repertoire of targeted therapeutics, many of which can be exploited for enhancing the efficacy of RT. Complementing this advent of new treatment options is the evolution of our knowledge of the interaction between nanoscale materials and human tissues (nanomedicine). As with the changes in RT paradigms when the field has encountered newer and maturing disciplines, the incorporation of nanotechnology innovations into radiation oncology has the potential to refine or redefine its principles and revolutionize its practice. This review provides a summary of the principles, applications, challenges and outlook for the use of metallic nanoparticles in RT. PMID:25279336

  15. Extracorporeal Ultrasound-Guided High Intensity Focused Ultrasound: Implications from the Present Clinical Trials

    Directory of Open Access Journals (Sweden)

    Tinghe Yu

    2014-01-01

    Full Text Available Extracorporeal ultrasound-guided high intensity focused ultrasound (HIFU has been clinically used for 15 years, and over 36000 cases have been reported. However, there yet lacked a consensus in the clinical values, suggesting the necessity of checking clinical findings. Clinical trials were searched and data reevaluated. HIFU was hardly performed alone; almost all present anticancer means have been applied during an HIFU treatment, and a specific regimen varied between trials; there were heterogeneity and disagreement between trials. The complexity made it difficult to distinguish the effect of HIFU. Based upon evaluable data, the efficacy of HIFU was similar to that of radio frequency, chemoembolization, chemotherapy, radiotherapy, or hormone therapy; a combined therapy did not improve the efficacy. The survival rate of HIFU plus radiotherapy was lower than that of radical surgery in liver cancers. Adverse events had no downtrend in the past years. HIFU was not a standardized procedure where the intensity and insonation mode were modified constantly throughout a treatment, limiting an evaluation from the perspective of ultrasonics. These implied that HIFU should be applied as an alternative at most occasions. The present clinical trials had defects making against the understating of HIFU.

  16. Advances in quantifying apolipoproteins using LC-MS/MS technology: implications for the clinic.

    Science.gov (United States)

    van den Broek, Irene; Sobhani, Kimia; Van Eyk, Jennifer E

    2017-10-01

    Apolipoproteins play a key role in pre-, pro-, and anti-atherosclerotic processes and have become important circulating biomarkers for the prediction of cardiovascular disease (CVD) risk. Whereas currently clinical immunoassays are not available for most apolipoproteins and lack the capacity for multiplexing, liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) allows simultaneous, highly-specific, and precise quantification of multiple apolipoproteins. Areas covered: We discuss LC-MS/MS methods for quantification of apolipoproteins reported in the literature and highlight key requirements for clinical use. Besides the advances in sample preparation and LC-MS/MS technologies, this overview also discusses advances in proteoform analysis and applications of dried blood/plasma collection. Expert commentary: Standardized quantification using LC-MS/MS technology has been demonstrated for apolipoprotein A-I and B. However, for implementation in clinical CVD risk assessment, LC-MS/MS must bring significant added clinical value in comparison to fast, standardized, and straightforward clinical (immuno)assays. Ongoing advances in accuracy and multiplexing capacity of LC-MS/MS, nonetheless, bear potential to enable standardized and interpretable personalized profiling of a patient's CVD risk by simultaneous quantification of multiple apolipoproteins and -variants. We, moreover, anticipate further personalization of CVD risk assessment by the potential of LC-MS/MS to enable simultaneous genotyping and remote monitoring using dried blood/plasma collection devices.

  17. Contrast extravasation into an acute spontaneous intracerebral hematoma: multidetector CT angiographic findings and clinical implications

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seong Eun; Yu, Hyeon; Baik, Hye Won; Lee, Hwa Yeon; Kwak, Byung Kook; Lee, Jong Beum; Kim, Yang Soo; Lee, Yong Chul [Chung-Ang University Hospital, Seoul (Korea, Republic of)

    2007-05-15

    The purpose of this study was to evaluate multidetector row CT (MDCT) angiographic findings and their clinical significance for contrast extravasation into a spontaneous intracerebral hematoma (ICH). MDCT angiographic studies and clinical records of 115 patients with spontaneous ICH were retrospectively reviewed. Cases were divided into two groups according to the presence or absence of contrast extravasation. The cases in the two groups were compared to determine the differences in radiological and clinical findings. The contrast extravasation group was divided into two subgroups according to radiological findings as follows: single or multiple dot-like contrast extravasation (Type A) and beaded-tubular (with or without dot-like extravasation) contrast extravasation (Type B). Contrast extravasation was seen in 38 patients (33%). It was associated with a larger hematoma volume, more frequent intraventricular hemorrhage (IVH) and subarachnoid hemorrhage (SAH), a shorter time interval from onset to the time of the CT scan, lower Glasgow coma scale (GCS), and a higher mortality rate. Type A and B contrast extravasation were observed in 16 (42%) and 22 (58%) patients, respectively. The rate of IVH and the clinical outcome of patients with Type B showed a significant correlation. Two types of contrast extravasation into an ICH show a significant difference in the rate of IVH and in clinical outcome. Detecting the presence of contrast extravasation and classifying them according to the morphologic patterns are important in predicting a prognosis.

  18. Seroprevalence and Seroconversion of Dengue and Implications for Clinical Diagnosis in Amazonian Children

    Directory of Open Access Journals (Sweden)

    Antonio Camargo Martins

    2014-01-01

    Full Text Available This study aimed to evaluate the prevalence of serum IgG dengue in children in an Amazonian population, to assess the seroconversion rate in 12 months, and to estimate how many seropositive children had a prior clinical diagnosis of dengue. We conducted a population-based study between 2010 and 2011, with children aged 6 months to 12 years that were living in the urban area of a small town in the Brazilian Amazon. The prevalence of IgG antibodies against dengue antigens was determined by indirect ELISA technique, and seronegative children were reexamined after 12 months to determine seroconversion rates. Results showed seroprevalence of IgG antibodies against dengue type of 2.9%, with no significant association between age, race, and sex. In seropositive children, only 8.4% had received a clinical diagnosis of dengue, and the ratio of clinically diagnosed cases and subclinical cases was 1 : 11. The seroconversion rate between 2010 and 2011 was 1.4% (CI 3.8% to 35.1%. The seroprevalence of dengue in this pediatric population was low, and the vast majority of cases were not clinically detected, suggesting a difficulty in making the clinical diagnosis in children and a high frequency of asymptomatic infections.

  19. Clinical implications of spirituality to mental health: review of evidence and practical guidelines

    Directory of Open Access Journals (Sweden)

    Alexander Moreira-Almeida

    2014-04-01

    Full Text Available Objective: Despite empirical evidence of a relationship between religiosity/spirituality (R/S and mental health and recommendations by professional associations that these research findings be integrated into clinical practice, application of this knowledge in the clinic remains a challenge. This paper reviews the current state of the evidence and provides evidence-based guidelines for spiritual assessment and for integration of R/S into mental health treatment. Methods: PubMed searches of relevant terms yielded 1,109 papers. We selected empirical studies and reviews that addressed assessment of R/S in clinical practice. Results: The most widely acknowledged and agreed-upon application of R/S to clinical practice is the need to take a spiritual history (SH, which may improve patient compliance, satisfaction with care, and health outcomes. We found 25 instruments for SH collection, several of which were validated and of good clinical utility. Conclusions: This paper provides practical guidelines for spiritual assessment and integration thereof into mental health treatment, as well as suggestions for future research on the topic.

  20. Bone conduction errors at high frequencies: implications for clinical and medico-legal practice.

    Science.gov (United States)

    Lightfoot, G R; Hughes, J B

    1993-04-01

    The magnitude and origin of audiometric air-bone gaps in the range 3 kHz to 8 kHz was investigated in 20 normal subjects. The average gap ranged from a minimum of about 3 dB at 3 kHz to a maximum of about 19 dB at 6 kHz. Approximately 5 dB of the gap at high frequencies is caused by excess air-radiated sound from the bone vibrator. A larger error appears to result from discrepancies between the air and bone conduction standards to which audiometers are calibrated. These errors may influence diagnosis and we recommend that bone conduction tests at frequencies greater than 4 kHz are avoided. These findings have implications for medico-legal work where small air-bone gaps have diagnostic significance.

  1. Arboviruses emerging in Brazil: challenges for clinic and implications for public health

    Directory of Open Access Journals (Sweden)

    Maria Rita Donalisio

    Full Text Available ABSTRACT Arboviruses have been emerging in different parts of the world due to genetic changes in the virus, alteration of the host and vector population dynamics, or because of anthropogenic environmental factors. These viruses’ capacity for adaptation is notable, as well as the likelihood of their emergence and establishment in new geographic areas. In Brazilian epidemiologic scenario, the most common arboviruses are DENV, CHIKV, and ZIKV, although others may spread in the country. Little is yet known of the impact of viral co-circulation, which would theoretically result in more intense viremia or other immunological alterations that could trigger autoimmune diseases, such as Guillain-Barré syndrome. The impact on morbidity and mortality intensifies as extensive epidemics lead to a high number of affected individuals, severe cases, and implications for health services, mainly due to the absence of treatment, vaccines, and effective prevention and control measures.

  2. Birth cohort testing for hepatitis C virus: implications for clinical social workers in health care settings.

    Science.gov (United States)

    Sims, Omar T; Whalen, Christopher C; Nackerud, Larry G; Bride, Brian E

    2013-01-01

    The Centers for Disease Control and Prevention recommends one-time hepatitis C virus (HCV) testing for baby boomers born between 1945-1965 in the United States. This public health initiative is known as birth cohort (baby boomer) testing for HCV. The intent of birth cohort testing is to identify and mobilize undiagnosed HCV-infected persons into care and treatment. Subsequently, clinical social workers in health care settings can anticipate a substantial increase in the number of HCV-infected persons presenting for care and treatment. The purpose of this article is to inform clinical social workers in health care settings of HCV, the standard of care and treatment for HCV, and clinical dilemmas associated with HCV patient care. Epidemiology and natural history of HCV, the standard of care and treatment for HCV, and etiology and management of neuropsychiatric adverse effects associated with patient care are discussed.

  3. Clinical implications of infection with a novel metastrongyloid species in the red panda (Ailurus fulgens).

    Science.gov (United States)

    Willesen, Jakob L; Meyland-Smith, Frederik; Wiinberg, Bo; Monrad, Jesper; Bertelsen, Mads F

    2012-06-01

    In a recent survey, 30% of the European red panda (Ailurus fulgens) population was found to be infected with a newly discovered metastrongyloid nematode. In a following prospective study, four naturally infected captive-bred red pandas infected with this parasite were examined and compared with two uninfected control animals. On clinical examination, no abnormalities were detected with respect to vital parameters and cardiovascular system in all six examined animals. Similarly, few and nonspecific changes were recorded on serum biochemistry. No changes on pulmonary pattern were noted on thoracic radiographs. Vertebral heart scores were between 7.2 to 8.6, and no difference was noted between infected and control animals. Two animals had slightly prolonged clotting time and reaction time on thromboelastography but not likely to be of clinical relevance. In conclusion, infection with the newly identified metastrongyloid nematode in the red pandas seems to have little or no clinical importance.

  4. Targeted next-generation sequencing reveals novel USH2A mutations associated with diverse disease phenotypes: implications for clinical and molecular diagnosis.

    Directory of Open Access Journals (Sweden)

    Xue Chen

    Full Text Available USH2A mutations have been implicated in the disease etiology of several inherited diseases, including Usher syndrome type 2 (USH2, nonsyndromic retinitis pigmentosa (RP, and nonsyndromic deafness. The complex genetic and phenotypic spectrums relevant to USH2A defects make it difficult to manage patients with such mutations. In the present study, we aim to determine the genetic etiology and to characterize the correlated clinical phenotypes for three Chinese pedigrees with nonsyndromic RP, one with RP sine pigmento (RPSP, and one with USH2. Family histories and clinical details for all included patients were reviewed. Ophthalmic examinations included best corrected visual acuities, visual field measurements, funduscopy, and electroretinography. Targeted next-generation sequencing (NGS was applied using two sequence capture arrays to reveal the disease causative mutations for each family. Genotype-phenotype correlations were also annotated. Seven USH2A mutations, including four missense substitutions (p.P2762A, p.G3320C, p.R3719H, and p.G4763R, two splice site variants (c.8223+1G>A and c.8559-2T>C, and a nonsense mutation (p.Y3745*, were identified as disease causative in the five investigated families, of which three reported to have consanguineous marriage. Among all seven mutations, six were novel, and one was recurrent. Two homozygous missense mutations (p.P2762A and p.G3320C were found in one individual family suggesting a potential double hit effect. Significant phenotypic divergences were revealed among the five families. Three families of the five families were affected with early, moderated, or late onset RP, one with RPSP, and the other one with USH2. Our study expands the genotypic and phenotypic variability relevant to USH2A mutations, which would help with a clear insight into the complex genetic and phenotypic spectrums relevant to USH2A defects, and is complementary for a better management of patients with such mutations. We have

  5. BRCA1 and BRCA2: Lack of Certainty and Its Clinical Implications

    Directory of Open Access Journals (Sweden)

    Samuel J Haryono

    2017-02-01

    • Functional analysis: should an in vitro assay demonstrate a loss of protein function, it is probable. The ultimate solution is not yet available. However, there is clinical significance for families with VUSs, only if that can confidently be classified as the presence or absence of the associated disease. That condition may be achieved by increasing the availability of genetic testing so that there can be a larger, open-access repertoire of VUSs.  Keywords: BRCA1, BRCA2, VUS, interpretation, clinical management

  6. Clinical picture and treatment implication in a child with Capgras syndrome: a case report.

    Science.gov (United States)

    Mazzone, Luigi; Armando, Marco; De Crescenzo, Franco; Demaria, Francesco; Valeri, Giovanni; Vicari, Stefano

    2012-11-27

    Capgras syndrome is a delusional misidentification syndrome characterized by the patient's belief that his or her relatives have been replaced by impostors. Here we describe the clinical picture and the therapeutic approach to an 11-year-old Caucasian girl with Capgras syndrome. A complete psychopathological assessment was conducted during the acute phase, at one month, two months and six months since diagnosis. Subsequent follow-up evaluations in this patient allowed us to detect improvements in the psychotic symptoms following treatment with risperidone and selective serotonin reuptake inhibitors, suggesting that this combined therapy may significantly improve the clinical outcome in patients who have Capgras syndrome.

  7. Emotional Intelligence in Internal Medicine Residents: Educational Implications for Clinical Performance and Burnout

    Science.gov (United States)

    Satterfield, Jason; Swenson, Sara; Rabow, Michael

    2009-01-01

    We measured emotional intelligence (EQ; the ability to perceive, understand, and manage emotions in the self and others) in a sample of 28 internal medicine residents at the beginning and end of an academic year. EQ scores increased significantly over the course of the year. Higher EQ scores at the end of the year were significantly related to higher ratings for overall clinical performance and medical interviewing. Higher EQ scores also correlated with lower levels of burnout. Results suggest that clinically significant changes in EQ can occur over the course of medical training. Further study should determine if and how educational interventions can affect EQ, EQ-related performance, and burnout. PMID:20407619

  8. An Expanded CAG Repeat in Huntingtin Causes +1 Frameshifting*

    OpenAIRE

    Saffert, Paul; Adamla, Frauke; Schieweck, Rico; Atkins, John F.; Ignatova, Zoya

    2016-01-01

    Maintenance of triplet decoding is crucial for the expression of functional protein because deviations either into the −1 or +1 reading frames are often non-functional. We report here that expression of huntingtin (Htt) exon 1 with expanded CAG repeats, implicated in Huntington pathology, undergoes a sporadic +1 frameshift to generate from the CAG repeat a trans-frame AGC repeat-encoded product. This +1 recoding is exclusively detected in pathological Htt variants, i.e. those with expanded re...

  9. Treatment outcomes in a rural HIV clinic in South Africa: Implications ...

    African Journals Online (AJOL)

    Objective: To assess the treatment outcomes of an HIV clinic in rural Limpopo province, South Africa. Methods: A retrospective cohort study involving medical records review of HIV-positive patients initiated on antiretroviral treatment (ART) was conducted from December 2007 to November 2008 at Letaba Hospital. Data on ...

  10. Teaching as a Clinical Practice Profession: Implications for Teacher Preparation and State Policy. Issue Brief

    Science.gov (United States)

    Alter, Jamie; Coggshall, Jane G.

    2009-01-01

    This Issue Brief, written through a collaboration between two federally funded technical assistance and research dissemination centers, the New York Comprehensive Center (NYCC) and the National Comprehensive Center for Teacher Quality (TQ Center), describes what "teaching as a clinical practice profession" means to those in the field of teacher…

  11. Cross-Cultural Value Orientations: Clinical Implications from an Analysis of the Theory and Research.

    Science.gov (United States)

    Scott, David Laurel

    The purpose of this paper is to consider what relevant clinical applications can be generated from a thorough review and critique of the theoretical and empirical literature pertaining to cross-cultural value orientations. The Kluckhohn and Strodtbeck (1961) theory of value orientations and their Value Schedule was presented. The 3 elements of…

  12. Molar Functional Relations and Clinical Behavior Analysis: Implications for Assessment and Treatment

    Science.gov (United States)

    Waltz, Thomas J.; Follette, William C.

    2009-01-01

    The experimental analysis of behavior has identified several molar functional relations that are highly relevant to clinical behavior analysis. These include matching, discounting, momentum, and variability. Matching provides a broader analysis of how multiple sources of reinforcement influence how individuals choose to allocate their time and…

  13. A Marginal Structural Model Analysis for Loneliness: Implications for Intervention Trials and Clinical Practice

    Science.gov (United States)

    VanderWeele, Tyler J.; Hawkley, Louise C.; Thisted, Ronald A.; Cacioppo, John T.

    2011-01-01

    Objective: Clinical scientists, policymakers, and individuals must make decisions concerning effective interventions that address health-related issues. We use longitudinal data on loneliness and depressive symptoms and a new class of causal models to illustrate how empirical evidence can be used to inform intervention trial design and clinical…

  14. Clinical Polymorphism of Stargardt Disease in a Large Consanguineous Tunisian Family; Implications for Nosology

    Directory of Open Access Journals (Sweden)

    Leila El Matri

    2013-01-01

    Full Text Available Purpose: To describe the polymorphic expression of Stargardt disease in a large Tunisian family with clinical intra- and interfamilial variation of the condition. Methods: Twelve subjects from two related families with autosomal recessive Stargardt disease were enrolled. A detailed clinical examination including visual acuity and visual field measurement, fundus photography, fluorescein angiography, electroretinography (ERG and color vision testing was performed for all subjects. Results: The youngest child from family A manifested typical Stargardt disease while her two brothers presented with Stargardt disease-fundus flavimaculatus (STGD-FFM and her two sisters demonstrated a peculiar phenotype overlapping Stargardt disease and cone-rod dystrophy; their phenotypic manifestation corresponded well with ERG groups I, II and III, respectively. This uncommon occurrence of an age-related decline in ERG amplitude and worsening of fundus changes is suggestive of a grading pattern in Stargardt disease. Their two cousins in family B, displayed the STGD-FFM phenotype. Despite clinically similar STGD-FFM patterns in both families, age of onset and progression of the phenotype in family B differed from family A. Conclusion: This is the first report on phenotypic variation of Stargardt disease in a large Tunisian family. Regarding phenotype and severity of visual symptoms, family A demonstrated Stargardt disease at various stages of progression. In addition, STGDFFM appeared to be an independent clinical entity in family B. These findings imply that further parameters are required to classify Stargardt′s disease.

  15. The challenges surrounding preclinical testing in transcatheter device development and the implications on the clinic.

    Science.gov (United States)

    Holzer, Ralf; Goble, Jake; Hijazi, Ziyad

    2017-02-01

    Transcatheter devices have contributed significantly to the advances achieved in treating many cardiovascular conditions over the last few decades. Sophisticated and detailed preclinical testing is not only a regulatory requirement to support an investigational device exemption (IDE) application, but more crucially its success and accuracy is needed to safeguard patients during the subsequent clinical testing stages. Areas covered: This article covers the regulatory background as well as specific considerations related to pre-clinical testing of transcatheter devices. Expert commentary: The lifecycle of a device is complex, but the period of commercialization may be short with little time for manufacturers to recuperate the costs associated with device development and (pre) clinical testing. Regulatory bodies such as the FDA require comprehensive data on pre-clinical testing prior to considering approval of an investigational device exemption to start trials in humans, which should include some data on safety and efficacy of a device. Preclinical testing needs to evaluate a variety of factors, such biocompatibility, material performance, durability, toxicology, particulation, protection against user error and device malfunction, potential hazards, and many more.

  16. The Development of English as a Second Language with and without Specific Language Impairment: Clinical Implications

    Science.gov (United States)

    Paradis, Johanne

    2016-01-01

    Purpose: The purpose of this research forum article is to provide an overview of typical and atypical development of English as a second language (L2) and to present strategies for clinical assessment with English language learners (ELLs). Method: A review of studies examining the lexical, morphological, narrative, and verbal memory abilities of…

  17. Congenital analbuminaemia: biochemical and clinical implications. A case report and literature review

    NARCIS (Netherlands)

    Koot, Bart G. P.; Houwen, Roderick; Pot, Dirk-Jan; Nauta, Jeroen

    2004-01-01

    Congenital analbuminaemia was diagnosed in a small-for-gestational-age neonate presenting with placental and body oedema, an unusual presentation of this rare autosomal recessive disorder. A review of 39 reported cases in the literature shows that the clinical symptoms are always remarkably mild and

  18. Pulmonary Arteriovenous Malformations After the Superior Cavopulmonary Shunt: Mechanisms and Clinical Implications

    OpenAIRE

    Kavarana, Minoo N.; Jones, Jeffrey A.; Stroud, Robert E.; Bradley, Scott M.; Ikonomidis, John S.; Mukherjee, Rupak

    2014-01-01

    Children with functional single ventricle heart disease are commonly palliated down a staged clinical pathway toward a Fontan completion procedure (total cavopulmonary connection). The Fontan physiology is fraught with long term complications associated with lower body systemic venous hypertension, eventually resulting in significant morbidity and mortality. The bidirectional Glenn shunt or superior cavopulmonary connection (SCPC) is commonly the transitional stage in single ventricle surgica...

  19. Accessory atlantoaxial ligament avulsion fracture of the axis: Are there any clinical implications?

    Directory of Open Access Journals (Sweden)

    Hamid Reza Niknejad

    2016-01-01

    Full Text Available Injuries to the craniocervical support structures are frequently observed in neurotrauma cases. Stability of this region is of vital importance. Literature has mainly focused on three major ligaments of the craniocervical junction: The tectorial membrane, the transverse ligament, and the alar ligaments. However, the accessory atlantoaxial ligament (ALL also seems to be involved in craniocervical stability as shown in cadaveric specimens. Still, the biomechanical importance of this structure needs to be determined, especially in trauma settings. Here, we describe a case of isolated traumatic injury to this structure and discuss the clinical outcome. A 64 year old polytrauma patient with a remarkable avulsion fracture at the site of the insertion of the ALL was admitted to our center. We evaluated the patient both clinical and radiological at admission, after 3 months and after 1 year. We clinically assessed the upper cervical rotational stability using the cervical flexion rotation test. We observed no rotational instability or any other clinical repercussions at the long term after an isolated ALL injury. This case shows that isolated traumatic damage to the ALL is possible. Unilateral damage to the ALL probably does not cause rotational instability of the craniocervical junction. In case a similar avulsion fracture is observed, we recommend performing a magnetic resonance imaging of the craniovertebral region to assess for any ligamentous lesions.

  20. Increasing Complexity of Clinical Research in Gastroenterology: Implications for Training Clinician-Scientists

    Science.gov (United States)

    Scott, Frank I.; McConnell, Ryan A.; Lewis, Matthew E.; Lewis, James D.

    2014-01-01

    Background Significant advances have been made in clinical and epidemiologic research methods over the past 30 years. We sought to demonstrate the impact of these advances on published research in gastroenterology from 1980 to 2010. Methods Three journals (Gastroenterology, Gut, and American Journal of Gastroenterology) were selected for evaluation given their continuous publication during the study period. Twenty original clinical articles were randomly selected from each journal from 1980, 1990, 2000, and 2010. Each article was assessed for topic studied, whether the outcome was clinical or physiologic, study design, sample size, number of authors and centers collaborating, and reporting of statistical methods such as sample size calculations, p-values, confidence intervals, and advanced techniques such as bioinformatics or multivariate modeling. Research support with external funding was also recorded. Results A total of 240 articles were included in the study. From 1980 to 2010, there was a significant increase in analytic studies (pgastroenterology and hepatology over the last three decades. This increase highlights the need for advanced training of clinical investigators to conduct future research. PMID:22475957

  1. The influence of family history on prostate cancer risk : implications for clinical management

    NARCIS (Netherlands)

    Madersbacher, Stephan; Alcaraz, Antonio; Emberton, Mark; Hammerer, Peter; Ponholzer, Anton; Schroeder, Fritz H.; Tubaro, Andrea

    A family history of prostate cancer has long been identified as an important risk factor for developing the disease. This risk factor can be easily assessed in clinical practice and current guidelines recommend to initiate prostate cancer early detection 5 years earlier (i.e. around the age of 40

  2. Technology assessment, transfer, and management: the implications to the professional development of clinical engineering.

    Science.gov (United States)

    Goodman, G R

    1991-01-01

    Technology, as applied in healthcare, is an encompassing term for products, equipment, procedures and services allied in some way with healthcare. This paper discusses technology as the word applies to healthcare. Areas of activity under the umbrella of technology--technology transfer, technology assessment and technology management--will be defined and discussed from the standpoint of their interaction with clinical engineering. The clinical engineering profession has approached participation in each of these activities in a nonsystematic manner, resulting in limited impact and a limited role. To go beyond its present role, the profession must study the processes of technology assessment, transfer, and management to understand their components, critical paths, strengths and weaknesses. This research should be undertaken by a joint group of clinical engineers representing practitioners and academia. Existing key players or professions should be identified, the role clinical engineers wish to pursue as a professional group and the skills required to assure competency should be declared, and appropriate resources for acquiring knowledge and experience identified.

  3. Review of Visual Speech Perception by Hearing and Hearing-Impaired People: Clinical Implications

    Science.gov (United States)

    Woodhouse, Lynn; Hickson, Louise; Dodd, Barbara

    2009-01-01

    Background: Speech perception is often considered specific to the auditory modality, despite convincing evidence that speech processing is bimodal. The theoretical and clinical roles of speech-reading for speech perception, however, have received little attention in speech-language therapy. Aims: The role of speech-read information for speech…

  4. The dimensions of the tarsal sinus and canal in different foot positions and its clinical implications

    NARCIS (Netherlands)

    Kleipool, R. P.; Blankevoort, L.; Ruijter, J. M.; Kerkhoffs, G. M. M. J.; Oostra, R. J.

    2017-01-01

    This study presents a reference for the dimensions of the tarsal sinus and canal in healthy adults in different foot positions to facilitate understanding of the kinematics of the subtalar joint, the effect of an implant, and other clinical issues. In a 3D CT stress test on 20 subjects, the right

  5. Calcium sensing receptor as a novel mediator of adipose tissue dysfunction: mechanisms and potential clinical implications

    Directory of Open Access Journals (Sweden)

    Roberto Bravo

    2016-09-01

    Full Text Available Obesity is currently a serious worldwide public health problem, reaching pandemic levels. For decades, dietary and behavioral approaches have failed to prevent this disease from expanding, and health authorities are challenged by the elevated prevalence of co-morbid conditions. Understanding how obesity-associated diseases develop from a basic science approach is recognized as an urgent task to face this growing problem. White adipose tissue is an active endocrine organ, with a crucial influence on whole-body homeostasis. White adipose tissue dysfunction plays a key role linking obesity with its associated diseases such as type 2 diabetes mellitus, cardiovascular disease and some cancers. Among the regulators of white adipose tissue physiology, the calcium-sensing receptor has arisen as a potential mediator of white adipose tissue dysfunction. Expression of the receptor has been described in human preadipocytes, adipocytes, and the human adipose cell lines LS14 and SW872. The evidence suggests that calcium-sensing receptor activation in the visceral (i.e. unhealthy white adipose tissue is associated with an increased proliferation of adipose progenitor cells and elevated adipocyte differentiation. In addition, exposure of adipose cells to calcium-sensing receptor activators in vitro elevates proinflammatory cytokine expression and secretion. An increased proinflammatory environment in white adipose tissue plays a key role in the development of white adipose tissue dysfunction that leads to peripheral organ fat deposition and insulin resistance, among other consequences. We propose that calcium-sensing receptor may be one relevant therapeutic target in the struggle to confront the health consequences of the current worldwide obesity pandemic.

  6. Epigenetics and Vascular Diseases: Influence of Non-coding RNAs and Their Clinical Implications.

    Science.gov (United States)

    Elia, Leonardo; Quintavalle, Manuela

    2017-01-01

    Epigenetics refers to heritable mechanisms able to modulate gene expression that do not involve alteration of the genomic DNA sequence. Classically, mechanisms such as DNA methylation and histone modifications were part of this classification. Today, this field of study has been expanded and includes also the large class of non-coding RNAs (ncRNAs). Indeed, with the extraordinary possibilities introduced by the next-generation sequencing approaches, our knowledge of the mammalian transcriptome has greatly improved. Today, we have identifying thousands of ncRNAs, and unsurprisingly, a direct association between ncRNA dysregulation and development of cardiovascular pathologies has been identified. This class of gene modulators is further divided into short-ncRNAs and long-non-coding RNAs (lncRNAs). Among the short-ncRNA sub-group, the best-characterized players are represented by highly conserved RNAs named microRNAs (miRNAs). miRNAs principally inhibit gene expression, and their involvement in cardiovascular diseases has been largely studied. On the other hand, due to the different roles played by lncRNAs, their involvement in cardiovascular pathology development is still limited, and further studies are needed. For instance, in order to define their roles in the cellular processes associated with the development of diseases, we need to better characterize the details of their mechanisms of action; only then might we be able to develop innovative therapeutic strategies. In this review, we would like to give an overview of the current knowledge on the function of ncRNAs and their involvement in the development of vascular diseases.

  7. Implications of Variability in Clinical Bedside Swallowing Assessment Practices by Speech Language Pathologists.

    Science.gov (United States)

    McAllister, Sue; Kruger, Samantha; Doeltgen, Sebastian; Tyler-Boltrek, Emma

    2016-10-01

    Speech language pathology (SLP) clinical bedside swallowing assessments (CBSA) are a cornerstone of quality care for patients in acute hospitals who have dysphagia. The CBSA informs clinical diagnosis and decisions regarding further instrumental assessment, and is used to develop a management plan and monitor progress. However, self-report and retrospective research shows that SLPs are highly variable in their use of assessment components considered by experts to be important for quality CBSA, casting doubt on the validity and reliability of CBSA. This prospective study describes the components included by SLPs when designing a standardised evidence based dysphagia assessment protocol for acute care patients and observed patterns of component use. The findings confirm that SLPs use the CBSA for multiple purposes beyond diagnosis of aspiration risk and dysphagia presence/severity. They are highly variable in their use of certain components, but also demonstrate consistent use of a core set. It is apparent that SLPs prioritise the application of clinical reasoning to tailor their CBSA to the patient over following a highly structured item-based protocol. The variability in component use likely reflects a complex clinical reasoning process that draws on a wide variety of information combined with expert knowledge as is also observed in many other medical specialties. Rather than promoting the standardisation of CBSA protocols that constrain SLP practice to strict item-based assessment protocols, consideration should be given to promoting the value and facilitating the clinical reasoning process that supports the utility of the CBSA for diagnosis, patient centred management and treatment planning.

  8. Clinical Implications of Serum Albumin Levels in Acute Heart Failure: Insights From DOSE-AHF and ROSE-AHF.

    Science.gov (United States)

    Grodin, Justin L; Lala, Anuradha; Stevens, Susanna R; DeVore, Adam D; Cooper, Lauren B; AbouEzzeddine, Omar F; Mentz, Robert J; Groarke, John D; Joyce, Emer; Rosenthal, Julie L; Vader, Justin M; Tang, W H Wilson

    2016-11-01

    Hypoalbuminemia is common in patients with chronic heart failure and, as a marker of disease severity, is associated with an adverse prognosis. Whether hypoalbuminemia contributes to (or is associated with) worse outcomes in acute heart failure (AHF) is unclear. We sought to determine the implications of low serum albumin in patients receiving decongestive therapies for AHF. Baseline serum albumin levels were measured in 456 AHF subjects randomized in the DOSE-AHF and ROSE-AHF trials. We assessed the relationship between admission albumin levels (both as a continuous variable and stratified by median albumin [≥3.5 g/dL]) and worsening renal function (WRF), worsening heart failure (WHF), and clinical decongestion by 72 hours; 7-day cardiorenal biomarkers; and post-discharge outcomes. The mean baseline albumin level was 3.5 ± 0.5 g/dL. Albumin was not associated with WRF, WHF, or clinical decongestion by 72 hours. Furthermore, there was no association between continuous albumin levels and symptom change according to visual analog scale or weight change by 72 hours. Albumin was not associated with 60-day mortality, rehospitalization, or unscheduled emergency room visits. Baseline serum albumin levels were not associated with short-term clinical outcomes for AHF patients undergoing decongestive therapies. These data suggest that serum albumin may not be a helpful tool to guide decongestion strategies. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Update on the everolimus-eluting coronary stent system: results and implications from the SPIRIT clinical trial program

    Directory of Open Access Journals (Sweden)

    R Michael Kirchner

    2009-12-01

    Full Text Available R Michael Kirchner, J Dawn AbbottDepartment of Cardiology, Rhode Island Hospital, Brown Medical School, Providence, RI, USAAbstract: Drug-eluting stents (DES have had a major impact in interventional cardiology. Compared to bare metal stents, they significantly reduce restenosis and the need for target vessel revascularization. Four DES are available in the US, the first-generation sirolimuseluting (Cypher® and paclitaxel-eluting (Taxus® stents and later approved second-generation everolimus-eluting (Xience V® and zotarolimus-eluting (Endeavor® stents. The Xience V stent was approved on the basis of clinical efficacy and safety data from 3 studies in the SPIRIT clinical trial program. Within this trial series, the Xience V was superior to its bare metal stent counterpart, the Vision® stent, and noninferior to the paclitaxel-eluting stent for target vessel failure at 9 months. This review provides a comprehensive assessment of the data derived from both the pre- and post-approval randomized controlled trials and registry studies of Xience V that comprise the SPIRIT clinical trial program including recently published mid-term outcomes. The implications of the results in terms of interventional practice will be discussed.Keywords: cobalt-chromium, drug-eluting stent, everolimus, percutaneous coronary intervention, Xience V

  10. Expander chunked codes

    Science.gov (United States)

    Tang, Bin; Yang, Shenghao; Ye, Baoliu; Yin, Yitong; Lu, Sanglu

    2015-12-01

    Chunked codes are efficient random linear network coding (RLNC) schemes with low computational cost, where the input packets are encoded into small chunks (i.e., subsets of the coded packets). During the network transmission, RLNC is performed within each chunk. In this paper, we first introduce a simple transfer matrix model to characterize the transmission of chunks and derive some basic properties of the model to facilitate the performance analysis. We then focus on the design of overlapped chunked codes, a class of chunked codes whose chunks are non-disjoint subsets of input packets, which are of special interest since they can be encoded with negligible computational cost and in a causal fashion. We propose expander chunked (EC) codes, the first class of overlapped chunked codes that have an analyzable performance, where the construction of the chunks makes use of regular graphs. Numerical and simulation results show that in some practical settings, EC codes can achieve rates within 91 to 97 % of the optimum and outperform the state-of-the-art overlapped chunked codes significantly.

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