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Sample records for profoundly impaired phenotypic

  1. Self-Concept of Severely to Profoundly Hearing-Impaired Children.

    Science.gov (United States)

    Warren, Charlotte; Hasenstab, Suzanne

    1986-01-01

    A study examined demographic, impairment-related, and parental variables that best predicted self-concept among 49 severely to profoundly hearing-impaired 5- to 11-year-olds. A strong relationship was observed between self-concept and parental indulgence, parental rejection, parental protection, parental discipline, and extent of language…

  2. Normality and Impairment following Profound Early Institutional Deprivation: A Longitudinal follow-up into Early Adolescence

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    Kreppner, Jana M.; Rutter, Michael; Beckett, Celia; Castle, Jenny; Colvert, Emma; Groothues, Christine; Hawkins, Amanda; O'Connor, Thomas G.; Stevens, Suzanne; Sonuga-Barke, Edmund J. S.

    2007-01-01

    Longitudinal analyses on normal versus impaired functioning across 7 domains were conducted in children who had experienced profound institutional deprivation up to the age of 42 months and were adopted from Romania into U.K. families. Comparisons were made with noninstitutionalized children adopted from Romania and with nondeprived within-U.K.…

  3. Visual impairments in people with severe and profound multiple disabilities: An inventory of visual functioning

    NARCIS (Netherlands)

    van den Broek, E.G.C.; Janssen, C.G.C.; van Ramshorst, T.; Deen, L.

    2006-01-01

    Background: The prevalence of visual impairments in people with severe and profound multiple disabilities (SPMD) is the subject of considerable debate and is difficult to assess. Methods: In a typical Dutch care organization, all clients with SPMD (n = 76) participated in the study and specific

  4. Static and Dynamic Balance in Congenital Severe to Profound Hearing-Impaired Children

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    Farideh HajiHeydari

    2011-09-01

    Full Text Available Background and Aim: Research conducted since the early 1900s has consistently identified differences between deaf and hearing children on performance of a wide variety of motor tasks, most notably balance. Our study was performed to test static and dynamic balance skills in congenital severe to profound hearing impaired children in comparison with normal age-matched children.Methods: This cross-sectional study was conducted on 30 severe to profound hearing impaired and 40 normal children with age 6 to 10 years old. Bruininks-Oseretsky test of motor proficiency 2, balance subset with 9 parts was used for evaluation of balance skills.Results: Hearing-impaired children showed 16.7 to 100% fail results in 7 parts of the balance subset. In normal children fail result was revealed just in 3 parts of the balance subset from 2.5 to 57.5%, and differences between two groups were significant (p<0.0001. There was a significant difference between two groups in two static balance skills of standing on one leg on a line and standing on one leg on a balance beam with eyes closed (p<0.0001.conclusion: It seems that development of static balance skills are longer than dynamic ones. Because severe to profound hearing-impaired children showed more weakness than normal children in both static and dynamic balance abilities, functional tests of balance proficiency can help to identify balance disorders in these children.

  5. Developmental dysgraphia with profound hearing impairment: intervention by auditory methods enabled by cochlear implant.

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    Fukushima, Kunihiro; Kawasaki, Akihiro; Nagayasu, Rie; Kunisue, Kazuya; Maeda, Yukihide; Kariya, Shin; Kataoka, Yuko; Nishizaki, Kazunori

    2008-06-01

    Learning disability combined with hearing impairment (LDHI) is a poor prognostic factor for the language development of hearing impaired children after educational intervention. A typical example of a child with LDHI and effective interventions provided by cochlear implants are presented in this report. A case of congenital cytomegaloviral infection that showed dysgraphia as well as profound deafness was reported and an underlying visual processing problem diagnosed in the present case caused the patient's dysgraphia. The dysgraphia could be circumvented by the use of auditory memory fairly established by a cochlear implant.

  6. Oral Communication Development in Severe to Profound Hearing Impaired Children After Receiving Aural Habilitation

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    Soleimani Farin

    2009-10-01

    Full Text Available Communication, cognition, language, and speech are interrelated and develop together. It should come as no surprise to us that the key to intervention with deaf children is to establish, as early as possible, a functional communication system for the child and the parents. Early intervention programs need to be multidisciplinary, technologically sound and most important, it should take cognizance of the specific context (community, country in which the child and family function. The main aim of this study was to obtain oral communication development regarding current status of the intervention (aural habilitation and speech therapyfor children with severe to profound hearing impairment in Iran. A prospective longitudinal study was undertaken on a consecutive group of children with severe to profound deafness. Nine severe to profound hearing-impaired children out of the primer 42 cases, who were detected below two years old, had been selected in the previous study to receive aural habilitation. The average of their speech intelligibility scores was near 70% at age 6, which was accounted as poor oral communication and only two of them were able to communicate by spoken language. An integrated intervention services continued again for one year and their oral communication skill was assessed by their speech intelligibility. The intelligibility test of children was recorded on audio-tape, when they read 10 questions such as where is your home. This can be answered only in one word. Each tape was presented to10 normal hearing listeners, and their task was to write down, the answers in Persian orthography. At the beginning (at age 6 the average speech intelligibility score of these children was 72% and only two of them had score of 90% and 100%. At age 7, all of the severe groups were over 90%, and only two profound ones achieved the score of 48% and 62%. All of severe groups develop oral communication, but profound ones had a semi-intelligible speech

  7. The Differential Effects of Attentional Focus in Children with Moderate and Profound Visual Impairments

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    Scott W. T. McNamara

    2017-10-01

    Full Text Available It has been consistently reported that an external focus of attention leads to better motor performance than an internal focus, but no research to date has explored this effect in a population with visual impairments (VI. External focus statements typically reference something in the environment (e.g., target that may be difficult to conceptualize for people with VI since they cannot generate a visual representation of the object of focus. Internal focus statements could be more closely identifiable with proprioception that is not impaired in this population. Recent studies have reported that sighted adults with temporarily obstructed vision are able to receive an external focus benefit when performing discrete tasks (i.e., golf putt and vertical jump, however, it is unclear if those with VI would experience the same benefit. The purpose of this investigation was to compare how an internal focus and external focus impact the balance of children with VI. Eighteen children with VI were grouped into a moderate (n = 11 and a profound VI group (n = 7. Participants completed a familiarization trial, an internal focus trial (i.e., focusing on feet and an external focus trial (i.e., focusing on markers in a counterbalanced order. The moderate VI group had a lower root mean square error while using an external focus (p = 0.04, while the profound VI group did not differ between conditions (p > 0.05. These results suggest that while performing a task reliant on sensory feedback, an external focus benefit may be dependent on the severity of VI. Further research is needed to examine whether external focus statements can be presented in a way that may be more intuitive to those with profound VI. These findings may help to influence how professionals in health-related fields (e.g., physical therapist and physical educators give instructions on motor performance to populations with VI.

  8. Noonan Syndrome: An Underestimated Cause of Severe to Profound Sensorineural Hearing Impairment. Which Clues to Suspect the Diagnosis?

    Science.gov (United States)

    Ziegler, Alban; Loundon, Natalie; Jonard, Laurence; Cavé, Hélène; Baujat, Geneviève; Gherbi, Souad; Couloigner, Vincent; Marlin, Sandrine

    2017-09-01

    To highlight Noonan syndrome as a clinically recognizable cause of severe to profound sensorineural hearing impairment. New clinical cases and review. Patients evaluated for etiological diagnosis by a medical geneticist in a reference center for hearing impairment. Five patients presenting with confirmed Noonan syndrome and profound sensorineural hearing impairment. Diagnostic and review of the literature. Five patients presented with profound sensorineural hearing impairment and molecularly confirmed Noonan syndrome. Sensorineural hearing impairment has been progressive for three patients. Cardiac echography identified pulmonary stenosis in two patients and was normal for the three other patients. Short stature was found in two patients. Mild intellectual disability was found in one patient. Inconspicuous clinical features as facial dysmorphism, cryptorchidism, or easy bruising were of peculiar interest to reach the diagnosis of Noonan syndrome. Profound sensorineural hearing impairment can be the main feature of Noonan syndrome. Associated features are highly variable; thus, detailed medical history and careful physical examination are mandatory to consider the diagnosis in case of a sensorineural hearing impairment.

  9. Non-nematode-derived double-stranded RNAs induce profound phenotypic changes in Meloidogyne incognita and Globodera pallida infective juveniles.

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    Dalzell, Johnathan J; McMaster, Steven; Johnston, Michael J; Kerr, Rachel; Fleming, Colin C; Maule, Aaron G

    2009-11-01

    Nine non-nematode-derived double-stranded RNAs (dsRNAs), designed for use as controls in RNA interference (RNAi) screens of neuropeptide targets, were found to induce aberrant phenotypes and an unexpected inhibitory effect on motility of root knot nematode Meloidogyne incognita J2s following 24h soaks in 0.1 mg/ml dsRNA; a simple soaking procedure which we have found to elicit profound knockdown of neuronal targets in Globodera pallida J2s. We have established that this inhibitory phenomenon is both time- and concentration-dependent, as shorter 4h soaks in 0.1 mg/ml dsRNA had no negative impact on M. incognita J2 stage worms, yet a 10-fold increase in concentration to 1 mg/ml for the same 4h time period had an even greater qualitative and quantitative impact on worm phenotype and motility. Further, a 10-fold increase of J2s soaked in 0.1 mg/ml dsRNA did not significantly alter the observed phenotypic aberration, which suggests that dsRNA uptake of the soaked J2s is not saturated under these conditions. This phenomenon was not initially observed in potato cyst nematode G. pallida J2s, which displayed no aberrant phenotype, or diminution of migratory activity in response to the same 0.1 mg/ml dsRNA 24h soaks. However, a 10-fold increase in dsRNA to 1mg/ml was found to elicit comparable irregularity of phenotype and inhibition of motility in G. pallida, to that initially observed in M. incognita following a 24h soak in 0.1 mg/ml dsRNA. Again, a 10-fold increase in the number of G. pallida J2s soaked in the same volume of 1 mg/ml dsRNA preparation did not significantly affect the observed phenotypic deviation. We do not observe any global impact on transcript abundance in either M. incognita or G. pallida J2s following 0.1 mg/ml dsRNA soaks, as revealed by reverse transcriptase-PCR and quantitative PCR data. This study aims to raise awareness of a phenomenon which we observe consistently and which we believe signifies a more expansive deficiency in our knowledge and

  10. Profound vision loss impairs psychological well-being in young and middle-aged individuals.

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    Garcia, Giancarlo A; Khoshnevis, Matin; Gale, Jesse; Frousiakis, Starleen E; Hwang, Tiffany J; Poincenot, Lissa; Karanjia, Rustum; Baron, David; Sadun, Alfredo A

    2017-01-01

    The aim of this study was to evaluate the effects of profound vision loss on psychological well-being in adolescents, young adults, and middle-aged adults with regard to mood, interpersonal interactions, and career-related goals. In addition, we assessed the significance of the resources that may be used to enhance psychological well-being in cases of profound vision loss, and in particular, examined the utility of low vision aids and the role of the ophthalmologist as a provider of emotional support. A questionnaire was issued to individuals aged 13-65 years with profound vision loss resulting from Leber's hereditary optic neuropathy (LHON). Depression prevalence was evaluated with questions regarding major depressive disorder symptomatology. Participants appraised the effects of vision loss on their interpersonal interactions and career goals by providing an impact rating (IR) on a 21-point psychometric scale from -10 to +10. Social well-being index was defined as the average of interpersonal IR and career IR. Subjects were additionally asked about the use of low vision aids and sources of emotional support. A total of 103 participants (mean age =26.4±11.2 years at LHON diagnosis; mean ± standard deviation) completed the questionnaire. Nearly half (49.5%) met the depression criteria after vision loss. Negative impacts on interpersonal interactions (median IR = -5) and career goals (median IR = -6) were observed; both ratings were worse ( P negative interpersonal IR and career IR. Sixty-eight percent of subjects used electronic vision aids; controlling for age, social well-being index was higher among these individuals than for those who did not use electronic aids ( P =0.03). Over half of the participants (52.4%) asserted that they derived emotional support from their ophthalmologist. Profound vision loss in adolescents, young adults, and middle-aged adults is associated with significant negative psychological and psychosocial effects, which are influenced by

  11. Rhyme and Syllable Recognition in Severe to Profound Hearing-Impaired Children

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    MohammadReza Keihani

    2003-09-01

    Full Text Available Objective: A research was conducted to assess the phonological awareness in hearing-impaired children in comparison to normal children. In this context, we discussed about the ability of these children in identification of rhyme and word segmentation to syllables. Method and Material: The sample of this study is composed of 320 children, 160 normal & 160 hearing-impaired with a hearing-loss. Of over 70 dB, studying in the 1st t 4th grade of the primary schools in Tehran. They are divided into two groups at each level (20 girls & 20 boys. Results: 1 Hearing-impaired children's scores on test related to rhyme and syllable is lower as compared with normal children. 2 Hearing-impaired children are more potent on test of word segmentation to syllables in comparison to that related to rhyme, while normal children are more successful on test of word segmentation to syllables as compared with that related to rhyme. Discussion: Hearing is an important factor in phonological awareness. Formal education at special schools doesn't compensate for the hearing impairment as to development of the phonological awareness.

  12. The impact of visual impairment on the ability to perform activities of daily living for persons with severe/profound intellectual disability.

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    Dijkhuizen, Annemarie; Hilgenkamp, Thessa I M; Krijnen, Wim P; van der Schans, Cees P; Waninge, Aly

    2016-01-01

    The ability to perform activities of daily living (ADL) as a component of participation is one of the factors that contribute to quality of life. The ability to perform ADL for persons experiencing severe/profound intellectual disability (ID) may be reduced due to their cognitive and physical capacities. However, until recently, the impact of the significantly prevalent visual impairments on the performance of activities of daily living has not yet been revealed within this group. The purpose of this prospective cross-sectional study was to investigate the impact of visual impairment on the performance of activities of daily living for persons with a severe/profound intellectual disability. The Barthel Index (BI) and Comfortable Walking Speed (CWS) were used to measure the ability of performing activities of daily living (ADL) in 240 persons with severe/profound ID and having Gross Motor Functioning Classification System (GMFCS) levels I, II or III; this included 120 persons with visual impairment. The impact of visual impairment on ADL was analyzed with linear regression. The results of the study demonstrated that visual impairment slightly affects the ability of performing activities of daily living (BI) for persons experiencing a severe/profound intellectual disability. GMFCS Levels II or III, profound ID level, and visual impairment each have the effect of lowering BI scores. GMFCS Levels II or III, and profound ID level each have the effect of increasing CWS scores, which indicates a lower walking speed. A main effect of visual impairment is present on CWS, but our results do show a substantive interaction effect between GMFCS level III and visual impairment on Comfortable Walking Speed in persons with a severe/profound intellectual disability. Visual impairment has a slight effect on ability to perform ADL in persons experiencing severe/profound ID. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Profound vision loss impairs psychological well-being in young and middle-aged individuals

    Directory of Open Access Journals (Sweden)

    Garcia GA

    2017-02-01

    Full Text Available Giancarlo A Garcia,1,2 Matin Khoshnevis,1,3 Jesse Gale,1,4 Starleen E Frousiakis,1,5 Tiffany J Hwang,1,6 Lissa Poincenot,1 Rustum Karanjia,1,7–9 David Baron,6 Alfredo A Sadun1,7 1Doheny Eye Institute, Los Angeles, CA, USA; 2University of California, Irvine School of Medicine, Irvine, CA, USA; 3Department of Ophthalmology, Temple University, Philadelphia, PA, USA; 4Wellington School of Medicine and Health Sciences, University of Otago, Wellington, NZ; 5Department of Ophthalmology, New York Medical College, Valhalla, NY, USA; 6Department of Psychiatry & The Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; 7Doheny Eye Centers, Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles California, CA, USA; 8Department of Ophthalmology, University of Ottawa, Ottawa, ON, Canada; 9Ottawa Hospital Health Research Institute, Ottawa, ON, Canada Purpose: The aim of this study was to evaluate the effects of profound vision loss on psychological well-being in adolescents, young adults, and middle-aged adults with regard to mood, interpersonal interactions, and career-related goals. In addition, we assessed the significance of the resources that may be used to enhance psychological well-being in cases of profound vision loss, and in particular, examined the utility of low vision aids and the role of the ophthalmologist as a provider of emotional support.Methods: A questionnaire was issued to individuals aged 13–65 years with profound vision loss resulting from Leber’s hereditary optic neuropathy (LHON. Depression prevalence was evaluated with questions regarding major depressive disorder symptomatology. Participants appraised the effects of vision loss on their interpersonal interactions and career goals by providing an impact rating (IR on a 21-point psychometric scale from −10 to +10. Social well-being index was defined as the average of interpersonal IR and career IR

  14. Implicit mentalizing persists beyond early childhood and is profoundly impaired in children with autism spectrum conditions

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    Tobias Schuwerk

    2016-10-01

    Full Text Available Implicit mentalizing, a fast, unconscious and rigid way of processing other's mental states has recently received much interest in typical social cognitive development in early childhood and in adults with autism spectrum conditions (ASC. This research suggests that already infants implicitly mentalize, and that adults with ASC have a sustained implicit mentalizing deficit. Yet, we have only sparse empirical evidence on implicit mentalizing beyond early childhood, and deviations thereof in children with ASC. Here, we administered an implicit mentalizing eye tracking task to assess the sensitivity to false beliefs to a group of 8-year-old children with and without ASC, matched for chronological age, verbal and nonverbal IQ. As previous research suggested that presenting outcomes of belief-based actions leads to fast learning from experience and false belief-congruent looking behavior in adults with ASC, we were also interested in whether already children with ASC learn from such information. Our results provide support for a persistent implicit mentalizing ability in neurotypical development beyond early childhood. Further, they confirmed an implicit mentalizing deficit in children with ASC, even when they are closely matched to controls for explicit mentalizing skills. In contrast to previous findings with adults, no experience-based modulation of anticipatory looking was observed. It seems that children with ASC have not yet developed compensatory general purpose learning mechanisms. The observed intact explicit, but impaired implicit mentalizing in ASC, and correlation patterns between mentalizing tasks and executive function tasks, are in line with theories on two dissociable mentalizing systems.

  15. Understanding minds: early cochlear implantation and the development of theory of mind in children with profound hearing impairment.

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    Sundqvist, Annette; Lyxell, Björn; Jönsson, Radoslava; Heimann, Mikael

    2014-03-01

    The present study investigates how auditory stimulation from cochlear implants (CI) is associated with the development of Theory of Mind (ToM) in severely and profoundly hearing impaired children with hearing parents. Previous research has shown that deaf children of hearing parents have a delayed ToM development. This is, however, not always the case with deaf children of deaf parents, who presumably are immersed in a more vivid signing environment. Sixteen children with CI (4.25 to 9.5 years of age) were tested on measures of cognitive and emotional ToM, language and cognition. Eight of the children received their first implant relatively early (before 27 months) and half of them late (after 27 months). The two groups did not differ in age, gender, language or cognition at entry of the study. ToM tests included the unexpected location task and a newly developed Swedish social-emotional ToM test. The tests aimed to test both cognitive and emotional ToM. A comparison group of typically developing hearing age matched children was also added (n=18). Compared to the comparison group, the early CI-group did not differ in emotional ToM. The late CI-group differed significantly from the comparison group on both the cognitive and emotional ToM tests. The results revealed that children with early cochlear implants solved ToM problems to a significantly higher degree than children with late implants, although the groups did not differ on language or cognitive measures at baseline. The outcome suggests that early cochlear implantation for deaf children in hearing families, in conjunction with early social and communicative stimulation in a language that is native to the parents, can provide a foundation for a more normalized ToM development. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Chronic obstructive pulmonary disease phenotypes and balance impairment

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    Voica AS

    2016-04-01

    Full Text Available Alina Sorina Voica,1 Cristian Oancea,1 Emanuela Tudorache,1 Alexandru F Crisan,2 Ovidiu Fira-Mladinescu,1 Voicu Tudorache,1 Bogdan Timar3 1Department of Pulmonology, Victor Babeş University of Medicine and Pharmacy, 2Pulmonary Rehabilitation Center, Hospital of Pneumoftiziology and Infectious Diseases “Dr Victor Babeş”, 3Department of Biostatistics and Medical Informatics, Victor Babeş University of Medicine and Pharmacy, Timişoara, Romania Background/objective: Chronic obstructive pulmonary disease (COPD is a respiratory disease that results in airflow limitation and respiratory distress, also having many nonrespiratory manifestations that affect both function and mobility. Preliminary evidence suggests that balance deficits constitute an important secondary impairment in individuals with COPD. Our objective was to investigate balance performance in two groups of COPD patients with different body compositions and to observe which of these groups are more likely to experience falls in the future.Methods: We included 27 stable COPD patients and 17 healthy individuals who performed a series of balance tests. The COPD patients were divided in two groups: emphysematous and bronchitic. Patients completed the activities balance confidence scale and the COPD assessment test questionnaire and afterward performed the Berg Balance Scale, timed up and go, single leg stance and 6-minute walking distance test. We analyzed the differences in the balance tests between the studied groups.Results: Bronchitic COPD was associated with a decreased value when compared to emphysematous COPD for the following variables: single leg stance (8.7 vs 15.6; P<0.001 and activities balance confidence (53.2 vs 74.2; P=0.001. Bronchitic COPD patients had a significantly higher value of timed up and go test compared to patients with emphysematous COPD (14.7 vs 12.8; P=0.001.Conclusion: Patients with COPD have a higher balance impairment than their healthy peers

  17. Comparison of Reading Comprehension Skill of Students with Severe to Profound Hearing Impairment from Second up to Fifth Grade of Exceptional Schools with Normal Hearing Students

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    Maryam Jalalipour

    2016-03-01

    Full Text Available Background: Reading is known as one of the most important learning tools. Research results consistently have shown that even a mild hearing impairment could affect the reading skills. Due to the reported differences in reading comprehension skills between hearing impaired students and their normal hearing peers, this research was conducted to compare the differences between the two groups. The other aim was to find any changes in the reading ability of hearing impaired group during elementary school. Methods: This study is a cross-sectional (descriptive–analytic one in which reading comprehension ability of 91 students with severe and profound hearing impairment (33 girls and 58 boys from 2nd up to 5th grade of exceptional schools were compared with 50 2nd grade normal hearing students in Ahvaz, Iran. The first section of Diagnostic Reading Test (Shirazi – Nilipour, 2004 was used in this study. Then the mean reading scores of hearing impaired students in each grade was compared with control group using SPSS 13 with Mann Whitney test. Results: There was a significant difference between average scores of hearing impaired students (boys and girls in 2nd to 5th grade with normal hearing students of 2nd grade (P<0.001. Reading comprehension scores of students with hearing impairment in higher grades had improved slightly, but it was still lower than that of the normal hearing students in the 2nd grade. Conclusion: It appears that reading comprehension skill of students with significant hearing impairment near the end of elementary school years becomes weaker than normal hearing students in the second grade. Therefore, it is essential to find and resolve the underlying reasons of this condition by all professionals who work in the field of education and rehabilitation of these students.

  18. Environmentally profound

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Rushu [China Yangzte Three Gorges Project Development Corp., Yichang Hubei (China)

    1999-09-01

    The Three Gorges dam project on the Yangtze river will have a profound effect on the people, the environment and cultural heritage sites. The dam will be the world's biggest and will provide almost 85 BkWh of hydro power per annum. A noticeable benefit will be a greatly reduced incidence of flooding in the Jingjiang reaches of the river. Additional benefits will be improved local navigation, climate and enhanced water quality. The main unwelcome impacts were loss of farmland and resettlement of people but here the government have been particularly careful to provide the relocated people with a reasonable standard of new accommodation and farmland. The loss of natural vegetation will be small but there are endangered species of birds and animals living in the region. A number of negative environmental affects (dust noise, incidence of certain diseases) and how they are to be mitigated are mentioned. (UK)

  19. Blind rats are not profoundly impaired in the reference memory Morris water maze and cannot be clearly discriminated from rats with cognitive deficits in the cued platform task.

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    Lindner, M D; Plone, M A; Schallert, T; Emerich, D F

    1997-06-01

    The Morris water maze is commonly used to test cognitive function in rodent models of neurological disorders including age-related cognitive deficits. It is often assumed that the most profoundly impaired aged rats may be blind due to retinal degeneration, and it has been reported that animals with visual sensory deficits can be identified based on their performance in a cued platform task. The results of the present study demonstrate that blind rats can perform surprisingly well in the reference memory version of the Morris water maze, and that blind rats cannot be selectively excluded based on performance in the cued platform task since atropine-treated rats also perform poorly in the cued platform task. Future studies may be able to develop screening procedures that help to eliminate subjects with non-cognitive deficits, but the present results do not support the use of the cued platform or straight swim task as screening procedures. Experimenters must be careful to consider the role that visual sensory function and other non-cognitive factors may have in performance of the spatial learning Morris water maze, and also the role that severe cognitive deficits may have in performance of the cued platform task.

  20. The impact of visual impairment on the ability to perform activities of daily living for persons with severe/profound intellectual disability

    NARCIS (Netherlands)

    Dijkhuizen, Annemarie; Hilgenkamp, Thessa I.M.; Krijnen, Wim; van der Schans, Cees; Waninge, Aly

    2015-01-01

    Background The ability to perform activities of daily living (ADL) as a component of participation is one of the factors that contribute to the quality of life. The ability to perform ADL for persons experiencing severe/profound intellectual disability (ID) may be reduced due to their cognitive and

  1. The impact of visual impairment on the ability to perform activities of daily living for persons with severe/profound intellectual disability

    NARCIS (Netherlands)

    Dijkhuizen, Annemarie; Hilgenkamp, Thessa I. M.; Krijnen, Wim P.; Schans, van der Cees P.; Waninge, Aly

    Background: The ability to perform activities of daily living (ADL) as a component of participation is one of the factors that contribute to quality of life. The ability to perform ADL for persons experiencing severe/profound intellectual disability (ID) may be reduced due to their cognitive and

  2. What is profound?

    DEFF Research Database (Denmark)

    Sobisch, Jan-Ulrich

    2013-01-01

    Discussing the question, which elements on the path are to be considered profound. While a general view is that the most subtle practises are also the most profound, 'Jig-rten-mgon-po maintains that the most fundamental one's are to be considered the most profound....

  3. 'Non-vocalization': a phonological error process in the speech of severely and profoundly hearing impaired adults, from the point of view of the theory of phonology as human behaviour.

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    Halpern, Orly; Tobin, Yishai

    2008-01-01

    'Non-vocalization' (N-V) is a newly described phonological error process in hearing impaired speakers. In N-V the hearing impaired person actually articulates the phoneme but without producing a voice. The result is an error process looking as if it is produced but sounding as if it is omitted. N-V was discovered by video recording the speech of two groups, profoundly and severely hearing impaired adults in four elicitation tasks of varying difficulty, and analysing 2065 phonological error processes (substitutions, omissions, and N-V) according to 24 criteria resulting in 49,560 data points. Results, which are discussed in view of the theory 'Phonology as Human Behaviour' (PHB), indicate that: (a) The more communicative the error process was; the more effort was made for its production and the more frequent its distribution; (b) The easier the elicitation task was, the more frequent the use of communicative error processes; c) The more difficult the elicitation task was, the more frequent the use of the relatively less communicative and easier to produce error processes; and d) The process of N-V functioned like a communicative error process for the group of profoundly hearing impaired adults.

  4. Perinatal Western Diet Consumption Leads to Profound Plasticity and GABAergic Phenotype Changes within Hypothalamus and Reward Pathway from Birth to Sexual Maturity in Rat

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    Julie Paradis

    2017-08-01

    Full Text Available Perinatal maternal consumption of energy dense food increases the risk of obesity in children. This is associated with an overconsumption of palatable food that is consumed for its hedonic property. The underlying mechanism that links perinatal maternal diet and offspring preference for fat is still poorly understood. In this study, we aim at studying the influence of maternal high-fat/high-sugar diet feeding [western diet (WD] during gestation and lactation on the reward pathways controlling feeding in the rat offspring from birth to sexual maturity. We performed a longitudinal follow-up of WD and Control offspring at three critical time periods (childhood, adolescence, and adulthood and focus on investigating the influence of perinatal exposure to palatable diet on (i fat preference, (ii gene expression profile, and (iii neuroanatomical/architectural changes of the mesolimbic dopaminergic networks. We showed that WD feeding restricted to the perinatal period has a clear long-lasting influence on the organization of homeostatic and hedonic brain circuits but not on fat preference. We demonstrated a period specific evolution of the preference for fat that we correlated with specific brain molecular signatures. In offspring from WD fed dams, we observed during childhood the existence of fat preference associated with a higher expression of key gene involved in the dopamine (DA systems; at adolescence, a high-fat preference for both groups, progressively reduced during the 3 days test for the WD group and associated with a reduced expression of key gene involved in the DA systems for the WD group that could suggest a compensatory mechanism to protect them from further high-fat exposure; and finally at adulthood, a preference for fat that was identical to control rats but associated with profound modification in key genes involved in the γ-aminobutyric acid network, serotonin receptors, and polysialic acid–NCAM-dependent remodeling of the

  5. An Expanded Multi-Organ Disease Phenotype Associated with Mutations in YARS

    DEFF Research Database (Denmark)

    Tracewska-Siemiątkowska, Anna; Haer-Wigman, Lonneke; Bosch, Danielle G M

    2017-01-01

    Whole exome sequence analysis was performed in a Swedish mother-father-affected proband trio with a phenotype characterized by progressive retinal degeneration with congenital nystagmus, profound congenital hearing impairment, primary amenorrhea, agenesis of the corpus callosum, and liver disease...

  6. Assessing challenging behaviour in people with hearing impairments and profound intellectial disabilities : the development of an Individual behaviour observation and recording scale

    NARCIS (Netherlands)

    Buskermolen, M.; Hoekman, J.; Aldenkamp, A.P.

    2013-01-01

    Background and Objective: Studies on people with both Hearing Impairments (HI) and an Intellectual Disability (ID) are rare, although in clinical practice aggressive incidents such as destructive behaviour aimed at objects or other people and self-harming behaviour are mentioned as common problems.

  7. Phenotypic and molecular assessment of seven patients with 6p25 deletion syndrome: Relevance to ocular dysgenesis and hearing impairment

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    Ritch Robert

    2004-06-01

    Full Text Available Abstract Background Thirty-nine patients have been described with deletions involving chromosome 6p25. However, relatively few of these deletions have had molecular characterization. Common phenotypes of 6p25 deletion syndrome patients include hydrocephalus, hearing loss, and ocular, craniofacial, skeletal, cardiac, and renal malformations. Molecular characterization of deletions can identify genes that are responsible for these phenotypes. Methods We report the clinical phenotype of seven patients with terminal deletions of chromosome 6p25 and compare them to previously reported patients. Molecular characterization of the deletions was performed using polymorphic marker analysis to determine the extents of the deletions in these seven 6p25 deletion syndrome patients. Results Our results, and previous data, show that ocular dysgenesis and hearing impairment are the two most highly penetrant phenotypes of the 6p25 deletion syndrome. While deletion of the forkhead box C1 gene (FOXC1 probably underlies the ocular dysgenesis, no gene in this region is known to be involved in hearing impairment. Conclusions Ocular dysgenesis and hearing impairment are the two most common phenotypes of 6p25 deletion syndrome. We conclude that a locus for dominant hearing loss is present at 6p25 and that this locus is restricted to a region distal to D6S1617. Molecular characterization of more 6p25 deletion patients will aid in refinement of this locus and the identification of a gene involved in dominant hearing loss.

  8. Brief Report: Do the Nature of Communication Impairments in Autism Spectrum Disorders Relate to the Broader Autism Phenotype in Parents?

    Science.gov (United States)

    Taylor, Lauren J.; Maybery, Murray T.; Wray, John; Ravine, David; Hunt, Anna; Whitehouse, Andrew J. O.

    2013-01-01

    Extensive empirical evidence indicates that the lesser variant of Autism Spectrum Disorders (ASD) involves a communication impairment that is similar to, but milder than, the deficit in clinical ASD. This research explored the relationship between the broader autism phenotype (BAP) among parents, an index of genetic liability for ASD, and proband…

  9. Concerns of Indian Mothers with Children Having Severe-to-Profound Hearing Impairment at Diagnosis and after 1–3 Years of Therapy

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    Nachiketa Rout

    2012-01-01

    Full Text Available Counseling training in graduate programs continues to be underrepresented. If parental queries are not addressed adequately, they keep visiting one doctor after another. Objective. The aim of the study is to identify maternal needs of children with hearing impairment at two stages of habilitation, that is, just after diagnosis (group I and after receiving 1 to 3 years of language therapy (group II. Methods. Two groups of mothers were asked to speak their queries about aural habilitation of their children. Queries were recorded, summarized, and categorized as per their priorities. Results. Group I mothers wanted to know about how the child would learn to listen and speak (45%, causes of hearing loss (33.7%, understanding the ear and hearing (10.2%, understanding the audiogram (7%, and coping with emotional aspects of hearing loss (5%, while group II parents had priorities concerning speech development (24.5% followed by child independence and employment (17.3%, schooling (15.6%, problem behaviors (11%, amplification device (9.4%, duration of therapy (8%, future of the child (8%, and questions about how can my child get adjusted to the “normal” world (6%. Conclusions. Culture- and language-specific materials to explain these issues need to be developed.

  10. Galectin-3 impairment of MYCN-dependent apoptosis-sensitive phenotype is antagonized by nutlin-3 in neuroblastoma cells.

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    Veronica Veschi

    Full Text Available MYCN amplification occurs in about 20-25% of human neuroblastomas and characterizes the majority of the high-risk cases, which display less than 50% prolonged survival rate despite intense multimodal treatment. Somehow paradoxically, MYCN also sensitizes neuroblastoma cells to apoptosis, understanding the molecular mechanisms of which might be relevant for the therapy of MYCN amplified neuroblastoma. We recently reported that the apoptosis-sensitive phenotype induced by MYCN is linked to stabilization of p53 and its proapoptotic kinase HIPK2. In MYCN primed neuroblastoma cells, further activation of both HIPK2 and p53 by Nutlin-3 leads to massive apoptosis in vitro and to tumor shrinkage and impairment of metastasis in xenograft models. Here we report that Galectin-3 impairs MYCN-primed and HIPK2-p53-dependent apoptosis in neuroblastoma cells. Galectin-3 is broadly expressed in human neuroblastoma cell lines and tumors and is repressed by MYCN to induce the apoptosis-sensitive phenotype. Despite its reduced levels, Galectin-3 can still exert residual antiapoptotic effects in MYCN amplified neuroblastoma cells, possibly due to its specific subcellular localization. Importantly, Nutlin-3 represses Galectin-3 expression, and this is required for its potent cell killing effect on MYCN amplified cell lines. Our data further characterize the apoptosis-sensitive phenotype induced by MYCN, expand our understanding of the activity of MDM2-p53 antagonists and highlight Galectin-3 as a potential biomarker for the tailored p53 reactivation therapy in patients with high-risk neuroblastomas.

  11. Romk1 Knockout Mice Do Not Produce Bartter Phenotype but Exhibit Impaired K Excretion*

    Science.gov (United States)

    Dong, Ke; Yan, Qingshang; Lu, Ming; Wan, Laxiang; Hu, Haiyan; Guo, Junhua; Boulpaep, Emile; Wang, WenHui; Giebisch, Gerhard; Hebert, Steven C.; Wang, Tong

    2016-01-01

    Romk knock-out mice show a similar phenotype to Bartter syndrome of salt wasting and dehydration due to reduced Na-K-2Cl-cotransporter activity. At least three ROMK isoforms have been identified in the kidney; however, unique functions of any of the isoforms in nephron segments are still poorly understood. We have generated a mouse deficient only in Romk1 by selective deletion of the Romk1-specific first exon using an ES cell Cre-LoxP strategy and examined the renal phenotypes, ion transporter expression, ROMK channel activity, and localization under normal and high K intake. Unlike Romk−/− mice, there was no Bartter phenotype with reduced NKCC2 activity and increased NCC expression in Romk1−/− mice. The small conductance K channel (SK) activity showed no difference of channel properties or gating in the collecting tubule between Romk1+/+ and Romk1−/− mice. High K intake increased SK channel number per patch and increased the ROMK channel intensity in the apical membrane of the collecting tubule in Romk1+/+, but such regulation by high K intake was diminished with significant hyperkalemia in Romk1−/− mice. We conclude that 1) animal knockouts of ROMK1 do not produce Bartter phenotype. 2) There is no functional linking of ROMK1 and NKCC2 in the TAL. 3) ROMK1 is critical in response to high K intake-stimulated K+ secretion in the collecting tubule. PMID:26728465

  12. Romk1 Knockout Mice Do Not Produce Bartter Phenotype but Exhibit Impaired K Excretion.

    Science.gov (United States)

    Dong, Ke; Yan, Qingshang; Lu, Ming; Wan, Laxiang; Hu, Haiyan; Guo, Junhua; Boulpaep, Emile; Wang, WenHui; Giebisch, Gerhard; Hebert, Steven C; Wang, Tong

    2016-03-04

    Romk knock-out mice show a similar phenotype to Bartter syndrome of salt wasting and dehydration due to reduced Na-K-2Cl-cotransporter activity. At least three ROMK isoforms have been identified in the kidney; however, unique functions of any of the isoforms in nephron segments are still poorly understood. We have generated a mouse deficient only in Romk1 by selective deletion of the Romk1-specific first exon using an ES cell Cre-LoxP strategy and examined the renal phenotypes, ion transporter expression, ROMK channel activity, and localization under normal and high K intake. Unlike Romk(-/-) mice, there was no Bartter phenotype with reduced NKCC2 activity and increased NCC expression in Romk1(-/-) mice. The small conductance K channel (SK) activity showed no difference of channel properties or gating in the collecting tubule between Romk1(+/+) and Romk1(-/-) mice. High K intake increased SK channel number per patch and increased the ROMK channel intensity in the apical membrane of the collecting tubule in Romk1(+/+), but such regulation by high K intake was diminished with significant hyperkalemia in Romk1(-/-) mice. We conclude that 1) animal knockouts of ROMK1 do not produce Bartter phenotype. 2) There is no functional linking of ROMK1 and NKCC2 in the TAL. 3) ROMK1 is critical in response to high K intake-stimulated K(+) secretion in the collecting tubule. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Microbial-Host Co-metabolites Are Prodromal Markers Predicting Phenotypic Heterogeneity in Behavior, Obesity, and Impaired Glucose Tolerance

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    Marc-Emmanuel Dumas

    2017-07-01

    Full Text Available The influence of the gut microbiome on metabolic and behavioral traits is widely accepted, though the microbiome-derived metabolites involved remain unclear. We carried out untargeted urine 1H-NMR spectroscopy-based metabolic phenotyping in an isogenic C57BL/6J mouse population (n = 50 and show that microbial-host co-metabolites are prodromal (i.e., early markers predicting future divergence in metabolic (obesity and glucose homeostasis and behavioral (anxiety and activity outcomes with 94%–100% accuracy. Some of these metabolites also modulate disease phenotypes, best illustrated by trimethylamine-N-oxide (TMAO, a product of microbial-host co-metabolism predicting future obesity, impaired glucose tolerance (IGT, and behavior while reducing endoplasmic reticulum stress and lipogenesis in 3T3-L1 adipocytes. Chronic in vivo TMAO treatment limits IGT in HFD-fed mice and isolated pancreatic islets by increasing insulin secretion. We highlight the prodromal potential of microbial metabolites to predict disease outcomes and their potential in shaping mammalian phenotypic heterogeneity.

  14. Examining the Language Phenotype in Children with Typical Development, Specific Language Impairment, and Fragile X Syndrome

    Science.gov (United States)

    Haebig, Eileen; Sterling, Audra; Hoover, Jill

    2016-01-01

    Purpose: One aspect of morphosyntax, finiteness marking, was compared in children with fragile X syndrome (FXS), specific language impairment (SLI), and typical development matched on mean length of utterance (MLU). Method: Nineteen children with typical development (mean age = 3.3 years), 20 children with SLI (mean age = 4.9 years), and 17 boys…

  15. Clinical and Cognitive Phenotype of Mild Cognitive Impairment Evolving to Dementia with Lewy Bodies

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    Annachiara Cagnin

    2015-11-01

    Full Text Available Objective: The aim of this study was to determine which characteristics could better distinguish dementia with Lewy bodies (DLB from Alzheimer's disease (AD at the mild cognitive impairment (MCI stage, with particular emphasis on visual space and object perception abilities. Methods: Fifty-three patients with mild cognitive deficits that were eventually diagnosed with probable DLB (MCI-DLB: n = 25 and AD (MCI-AD: n = 28 at a 3-year follow-up were retrospectively studied. At the first visit, the patients underwent cognitive assessment including the Qualitative Scoring Mini Mental State Examination Pentagon Test and the Visual Object and Space Perception Battery. The Neuropsychiatric Inventory Questionnaire, Unified Parkinson's Disease Rating Scale (UPDRS and questionnaires for cognitive fluctuations and sleep disorders were also administered. Results: The best clinical predictor of DLB was the presence of soft extrapyramidal signs (mean UPDRS score: 4.04 ± 5.9 detected in 72% of patients, followed by REM sleep behavior disorder (60% and fluctuations (60%. Wrong performances in the pentagon's number of angles were obtained in 44% of DLB and 3.7% of AD patients and correlated with speed of visual attention. Executive functions, visual attention and visuospatial abilities were worse in DLB, while verbal episodic memory impairment was greater in AD. Deficits in the visual-perceptual domain were present in both MCI-DLB and AD. Conclusions: Poor performance in the pentagon's number of angles is specific of DLB and correlates with speed of visual attention. The dorsal visual stream seems specifically more impaired in MCI-DLB with respect to the ventral visual stream, the latter being involved in both DLB and AD. These cognitive features, associated with subtle extrapyramidal signs, should alert clinicians to a diagnostic hypothesis of DLB.

  16. Arid1b haploinsufficient mice reveal neuropsychiatric phenotypes and reversible causes of growth impairment.

    Science.gov (United States)

    Celen, Cemre; Chuang, Jen-Chieh; Luo, Xin; Nijem, Nadine; Walker, Angela K; Chen, Fei; Zhang, Shuyuan; Chung, Andrew S; Nguyen, Liem H; Nassour, Ibrahim; Budhipramono, Albert; Sun, Xuxu; Bok, Levinus A; McEntagart, Meriel; Gevers, Evelien F; Birnbaum, Shari G; Eisch, Amelia J; Powell, Craig M; Ge, Woo-Ping; Santen, Gijs We; Chahrour, Maria; Zhu, Hao

    2017-07-11

    Sequencing studies have implicated haploinsufficiency of ARID1B , a SWI/SNF chromatin-remodeling subunit, in short stature (Yu et al., 2015), autism spectrum disorder (O'Roak et al., 2012), intellectual disability (Deciphering Developmental Disorders Study, 2015), and corpus callosum agenesis (Halgren et al., 2012). In addition, ARID1B is the most common cause of Coffin-Siris syndrome, a developmental delay syndrome characterized by some of the above abnormalities (Santen et al., 2012; Tsurusaki et al., 2012; Wieczorek et al., 2013). We generated Arid1b heterozygous mice, which showed social behavior impairment, altered vocalization, anxiety-like behavior, neuroanatomical abnormalities, and growth impairment. In the brain, Arid1b haploinsufficiency resulted in changes in the expression of SWI/SNF-regulated genes implicated in neuropsychiatric disorders. A focus on reversible mechanisms identified Insulin-like growth factor (IGF1) deficiency with inadequate compensation by Growth hormone-releasing hormone (GHRH) and Growth hormone (GH), underappreciated findings in ARID1B patients. Therapeutically, GH supplementation was able to correct growth retardation and muscle weakness. This model functionally validates the involvement of ARID1B in human disorders, and allows mechanistic dissection of neurodevelopmental diseases linked to chromatin-remodeling.

  17. A PTPN11 allele encoding a catalytically impaired SHP2 protein in a patient with a Noonan syndrome phenotype.

    Science.gov (United States)

    Edwards, Jonathan J; Martinelli, Simone; Pannone, Luca; Lo, Ivan Fai-Man; Shi, Lisong; Edelmann, Lisa; Tartaglia, Marco; Luk, Ho-Ming; Gelb, Bruce D

    2014-09-01

    The RASopathies are a relatively common group of phenotypically similar and genetically related autosomal dominant genetic syndromes caused by missense mutations affecting genes participating in the RAS/mitogen-activated protein kinase (MAPK) pathway that include Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NSML, formerly LEOPARD syndrome). NS and NSML can be difficult to differentiate during infancy, but the presence of multiple lentigines, café au lait spots, and specific cardiac defects facilitate the diagnosis. Furthermore, individual PTPN11 missense mutations are highly specific to each syndrome and engender opposite biochemical alterations on the function of SHP-2, the protein product of that gene. Here, we report on a 5-year-old male with two de novo PTPN11 mutations in cis, c.1471C>T (p.Pro491Ser), and c.1492C>T (p.Arg498Trp), which are associated with NS and NSML, respectively. This boy's phenotype is intermediate between NS and NSML with facial dysmorphism, short stature, mild global developmental delay, pulmonic stenosis, and deafness but absence of café au lait spots or lentigines. The double-mutant SHP-2 was found to be catalytically impaired. This raises the question of whether clinical differences between NS and NSML can be ascribed solely to the relative SHP-2 catalytic activity. © 2014 Wiley Periodicals, Inc.

  18. Disruption of var2csa gene impairs placental malaria associated adhesion phenotype.

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    Nicola K Viebig

    Full Text Available Infection with Plasmodium falciparum during pregnancy is one of the major causes of malaria related morbidity and mortality in newborn and mothers. The complications of pregnancy-associated malaria result mainly from massive adhesion of Plasmodium falciparum-infected erythrocytes (IE to chondroitin sulfate A (CSA present in the placental intervillous blood spaces. Var2CSA, a member of the P. falciparum erythrocyte membrane protein 1 (PfEMP1 family is the predominant parasite ligand mediating CSA binding. However, experimental evidence suggests that other host receptors, such as hyaluronic acid (HA and the neonatal Fc receptor, may also support placental binding. Here we used parasites in which var2csa was genetically disrupted to evaluate the contribution of these receptors to placental sequestration and to identify additional adhesion receptors that may be involved in pregnancy-associated malaria. By comparison to the wild-type parasites, the FCR3delta var2csa mutants could not be selected for HA adhesion, indicating that var2csa is not only essential for IE cytoadhesion to the placental receptor CSA, but also to HA. However, further studies using different pure sources of HA revealed that the previously observed binding results from CSA contamination in the bovine vitreous humor HA preparation. To identify CSA-independent placental interactions, FCR3delta var2csa mutant parasites were selected for adhesion to the human placental trophoblastic BeWo cell line. BeWo selected parasites revealed a multi-phenotypic adhesion population expressing multiple var genes. However, these parasites did not cytoadhere specifically to the syncytiotrophoblast lining of placental cryosections and were not recognized by sera from malaria-exposed women in a parity dependent manner, indicating that the surface molecules present on the surface of the BeWo selected population are not specifically expressed during the course of pregnancy-associated malaria. Taken

  19. Sequence analysis and transcript identification within 1.5 MB of DNA deleted together with the NDP and MAO genes in atypical Norrie disease patients presenting with a profound phenotype.

    Science.gov (United States)

    Suárez-Merino, B; Bye, J; McDowall, J; Ross, M; Craig, I W

    2001-06-01

    Mutations at the Norrie disease gene locus, NDP, manifest in a broad range of defects. These range from a relatively mild, late-onset, exudative vitreoretinopathy to congenital blindness and sensorineural deafness combined, in some cases, with mental retardation. In addition, extensive deletions involving the NDP locus, located at Xp11.3, the adjacent monoamine oxidadase genes MAOA and MAOB, and additional material, result in a more severe pattern of symptoms. The phenotypes include all or some of the following; mental retardation, involuntary movements, hypertensive crises and hypogonadism. We extended an existing YAC contig to embrace the boundaries of three of the largest deletions and converted this into four PAC contigs. Computer analysis and experimental data have resulted in the identification of several putative loci, including a phosphatase inhibitor 2-like gene (dJ154.1) and a 250-bp sequence which resembles a homeobox domain (dA113.3), 1.2 Mb and 400 kb respectively from the MAO/NDP cluster. The pattern of expression of dJ154.1 suggests that it may represent an important factor contributing to the complex phenotypes of these deletion patients. Hum Mutat 17:523, 2001. Copyright 2001 Wiley-Liss, Inc.

  20. "Non-Vocalization": A Phonological Error Process in the Speech of Severely and Profoundly Hearing Impaired Adults, from the Point of View of the Theory of Phonology as Human Behaviour

    Science.gov (United States)

    Halpern, Orly; Tobin, Yishai

    2008-01-01

    "Non-vocalization" (N-V) is a newly described phonological error process in hearing impaired speakers. In N-V the hearing impaired person actually articulates the phoneme but without producing a voice. The result is an error process looking as if it is produced but sounding as if it is omitted. N-V was discovered by video recording the speech of…

  1. Impairment of fat oxidation under high- vs. low-glycemic index diet occurs before the development of an obese phenotype.

    Science.gov (United States)

    Isken, F; Klaus, S; Petzke, K J; Loddenkemper, C; Pfeiffer, A F H; Weickert, M O

    2010-02-01

    Exposure to high vs. low glycemic index (GI) diets increases fat mass and insulin resistance in obesity-prone C57BL/6J mice. However, the longer-term effects and potentially involved mechanisms are largely unknown. We exposed four groups of male C57BL/6J mice (n = 10 per group) to long-term (20 wk) or short-term (6 wk) isoenergetic and macronutrient matched diets only differing in starch type and as such GI. Body composition, liver fat, molecular factors of lipid metabolism, and markers of insulin sensitivity and metabolic flexibility were investigated in all four groups of mice. Mice fed the high GI diet showed a rapid-onset (from week 5) marked increase in body fat mass and liver fat, a gene expression profile in liver consistent with elevated lipogenesis, and, after long-term exposure, significantly reduced glucose clearance following a glucose load. The long-term high-GI diet also led to a delayed switch to both carbohydrate and fat oxidation in the postprandial state, indicating reduced metabolic flexibility. In contrast, no difference in carbohydrate oxidation was observed after short-term high- vs. low-GI exposure. However, fatty acid oxidation was significantly blunted as early as 3 wk after beginning of the high-GI intervention, at a time where most measured phenotypic markers including body fat mass were comparable between groups. Thus long-term high-GI feeding resulted in an obese, insulin-resistant, and metabolically inflexible phenotype in obesity-prone C57BL/6J mice. Early onset and significantly impaired fatty acid oxidation preceded these changes, thereby indicating a potentially causal involvement.

  2. Broad autism phenotype features of Chinese parents with autistic children and their associations with severity of social impairment in probands.

    Science.gov (United States)

    Shi, Li-Juan; Ou, Jian-Jun; Gong, Jing-Bo; Wang, Su-Hong; Zhou, Yuan-Yue; Zhu, Fu-Rong; Liu, Xu-Dong; Zhao, Jing-Ping; Luo, Xue-Rong

    2015-07-23

    Parents of children with autism have higher rates of broad autism phenotype (BAP) features than parents of typically developing children (TDC) in Western countries. This study was designed to examine the rate of BAP features in parents of children with autism and the relationship between parental BAP and the social impairment of their children in a Chinese sample. A total of 299 families with autistic children and 274 families with TDC participated in this study. Parents were assessed using the Broad Autism Phenotype Questionnaire (BAPQ), which includes self-report, informant-report, and best-estimate versions. Children were assessed using the Chinese version of the Social Responsiveness Scale (SRS). Parents of children with autism were significantly more likely to have BAP features than were parents of TDC; mothers and fathers in families with autistic children had various BAP features. The total scores of the informant and best-estimate BAPQ versions for fathers were significantly associated with their children's SRS total scores in the autism group, whereas the total scores of the three BAPQ versions for mothers were significantly associated with their children's SRS total scores in the TDC group. In the autism group, the total SRS scores of children with "BAP present" parents (informant and best-estimate) were higher than the total SRS scores of children with"BAP absent" parents. In the TDC group, the total SRS scores of children with "BAP present" parents were higher than the total SRS scores of children with"BAP absent" parents (best-estimate). Parents of autistic children were found to have higher rates of BAP than parents of TDC in a sample of Chinese parents. The BAP features of parents are associated with their children's social functioning in both autism families and TDC families, but the patterns of the associations are different.

  3. An expanded multi-organ disease phenotype associated with mutations in YARS

    NARCIS (Netherlands)

    Tracewska-Siemiątkowska, Anna; Haer-Wigman, Lonneke; Bosch, Danielle G.M.; Nickerson, Deborah; Bamshad, Michael J.; Möller, J. C.; Kjellström, U.; Andréasson, S.; Van De Vorst, Maartje; Rendtorff, Nanna Dahl; Möller, Claes; Kjellström, Ulrika; Andréasson, Sten; Cremers, Frans P. M.; Tranebjærg, Lisbeth

    2017-01-01

    Whole exome sequence analysis was performed in a Swedish mother–father-affected proband trio with a phenotype characterized by progressive retinal degeneration with congenital nystagmus, profound congenital hearing impairment, primary amenorrhea, agenesis of the corpus callosum, and liver disease. A

  4. T cells in chronic lymphocytic leukaemia display an exhausted phenotype and impaired functionality that can be restored by chemotherapy

    International Nuclear Information System (INIS)

    Gassner, F.

    2012-01-01

    In chronic lymphocytic leukaemia (CLL), beside a massive accumulation of neoplastic B cells, tumour-induced deficiencies in autologous T cells have been reported that impede efficient tumour control and might even support survival of the malignant clone. Here, we investigated our hypothesis that T cells in CLL, due to the persistent availability of tumour antigen, are exhausted, and that reduction of tumour load by chemotherapy might restore T cell functions. We could show that T cells in CLL patients and in a CLL mouse model display an exhausted phenotype, with high expression of the inhibitory surface receptor PD-1, that is clearly induced by the presence of tumour cells. Although the PD-1 ligand PD-L1 is not expressed on peripheral CLL cells, abundant expression could be shown in lymph node sections. Intriguingly, blocking the PD-1/PD-L1 pathway increased short term tumour lysis in a murine in vivo cytotoxicity assay. Furthermore, we present data that after cytoreduction by fludarabine, a standard chemotherapy agent for CLL, the surviving T cell pool consists mainly of fully functional memory T cells with high proliferative potential and increased secretion of pro-inflammatory Th1 cytokines. Taken together, we conclude that the impaired tumour surveillance observed in CLL might be rooted in the exhaustion of tumour-specific effector T cells. A combination of cytodepletion by chemotherapy and blockade of PD-1 might hence represent a novel therapeutic approach for CLL. (author) [de

  5. Impaired TCA cycle flux in mitochondria in skeletal muscle from type 2 diabetic subjects: marker or maker of the diabetic phenotype?

    Science.gov (United States)

    Gaster, Michael; Nehlin, Jan O; Minet, Ariane D

    2012-07-01

    The diabetic phenotype is complex, requiring elucidation of key initiating defects. Recent research has shown that diabetic myotubes express a primary reduced tricarboxylic acid (TCA) cycle flux. A reduced TCA cycle flux has also been shown both in insulin resistant offspring of T2D patients and exercising T2D patients in vivo. This review will discuss the latest advances in the understanding of the molecular mechanisms regulating the TCA cycle with focus on possible underlying mechanism which could explain the impaired TCA flux in insulin resistant human skeletal muscle in type 2 diabetes. A reduced TCA is both a marker and a maker of the diabetic phenotype.

  6. Molecular Etiology of Hearing Impairment in Inner Mongolia: mutations in SLC26A4 gene and relevant phenotype analysis

    Directory of Open Access Journals (Sweden)

    Wu Bailin

    2008-11-01

    Full Text Available Abstract Background The molecular etiology of hearing impairment in Chinese has not been thoroughly investigated. Study of GJB2 gene revealed that 30.4% of the patients with hearing loss in Inner Mongolia carried GJB2 mutations. The SLC26A4 gene mutations and relevant phenotype are analyzed in this study. Methods One hundred and thirty-five deaf patients were included. The coding exons of SLC26A4 gene were sequence analyzed in 111 patients, not including 22 patients carrying bi-allelic GJB2 mutations or one patient carrying a known GJB2 dominant mutation as well as one patient with mtDNA 1555A>G mutation. All patients with SLC26A4 mutations or variants were subjected to high resolution temporal bone CT scan and those with confirmed enlarged vestibular aqueduct and/or other inner ear malformation were then given further ultrasound scan of thyroid and thyroid hormone assays. Results Twenty-six patients (19.26%, 26/135 were found carrying SLC26A4 mutation. Among them, 17 patients with bi-allelic SLC26A4 mutations were all confirmed to have EVA or other inner ear malformation by CT scan. Nine patients were heterozygous for one SLC26A4 mutation, including 3 confirmed to be EVA or EVA and Mondini dysplasia by CT scan. The most common mutation, IVS7-2A>G, accounted for 58.14% (25/43 of all SLC26A4 mutant alleles. The shape and function of thyroid were confirmed to be normal by thyroid ultrasound scan and thyroid hormone assays in 19 of the 20 patients with EVA or other inner ear malformation except one who had cystoid change in the right side of thyroid. No Pendred syndrome was diagnosed. Conclusion In Inner Mongolia, China, mutations in SLC26A4 gene account for about 12.6% (17/135 of the patients with hearing loss. Together with GJB2 (23/135, SLC26A4 are the two most commonly mutated genes causing deafness in this region. Pendred syndrome is not detected in this deaf population. We established a new strategy that detects SLC26A4 mutations prior to the

  7. Molecular Etiology of Hearing Impairment in Inner Mongolia: mutations in SLC26A4 gene and relevant phenotype analysis

    Science.gov (United States)

    Dai, Pu; Yuan, Yongyi; Huang, Deliang; Zhu, Xiuhui; Yu, Fei; Kang, Dongyang; Yuan, Huijun; Wu, Bailin; Han, Dongyi; Wong, Lee-Jun C

    2008-01-01

    Background The molecular etiology of hearing impairment in Chinese has not been thoroughly investigated. Study of GJB2 gene revealed that 30.4% of the patients with hearing loss in Inner Mongolia carried GJB2 mutations. The SLC26A4 gene mutations and relevant phenotype are analyzed in this study. Methods One hundred and thirty-five deaf patients were included. The coding exons of SLC26A4 gene were sequence analyzed in 111 patients, not including 22 patients carrying bi-allelic GJB2 mutations or one patient carrying a known GJB2 dominant mutation as well as one patient with mtDNA 1555A>G mutation. All patients with SLC26A4 mutations or variants were subjected to high resolution temporal bone CT scan and those with confirmed enlarged vestibular aqueduct and/or other inner ear malformation were then given further ultrasound scan of thyroid and thyroid hormone assays. Results Twenty-six patients (19.26%, 26/135) were found carrying SLC26A4 mutation. Among them, 17 patients with bi-allelic SLC26A4 mutations were all confirmed to have EVA or other inner ear malformation by CT scan. Nine patients were heterozygous for one SLC26A4 mutation, including 3 confirmed to be EVA or EVA and Mondini dysplasia by CT scan. The most common mutation, IVS7-2A>G, accounted for 58.14% (25/43) of all SLC26A4 mutant alleles. The shape and function of thyroid were confirmed to be normal by thyroid ultrasound scan and thyroid hormone assays in 19 of the 20 patients with EVA or other inner ear malformation except one who had cystoid change in the right side of thyroid. No Pendred syndrome was diagnosed. Conclusion In Inner Mongolia, China, mutations in SLC26A4 gene account for about 12.6% (17/135) of the patients with hearing loss. Together with GJB2 (23/135), SLC26A4 are the two most commonly mutated genes causing deafness in this region. Pendred syndrome is not detected in this deaf population. We established a new strategy that detects SLC26A4 mutations prior to the temporal bone CT scan to

  8. Delineating the GRIN1 phenotypic spectrum

    DEFF Research Database (Denmark)

    Lemke, Johannes R; Geider, Kirsten; Helbig, Katherine L

    2016-01-01

    consequences of GRIN1 mutations were investigated in Xenopus laevis oocytes. RESULTS: We identified heterozygous de novo GRIN1 mutations in 14 individuals and reviewed the phenotypes of all 9 previously reported patients. These 23 individuals presented with a distinct phenotype of profound developmental delay......, severe intellectual disability with absent speech, muscular hypotonia, hyperkinetic movement disorder, oculogyric crises, cortical blindness, generalized cerebral atrophy, and epilepsy. Mutations cluster within transmembrane segments and result in loss of channel function of varying severity...... impairment as well as oculomotor and movement disorders being discriminating phenotypic features. Loss of NMDA receptor function appears to be the underlying disease mechanism. The identification of both heterozygous and homozygous mutations blurs the borders of dominant and recessive inheritance of GRIN1...

  9. Neuropsychological Impairments in Schizophrenia and Psychotic Bipolar Disorder: Findings from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) Study

    Science.gov (United States)

    Hill, S. Kristian; Reilly, James L.; Keefe, Richard S.E.; Gold, James M.; Bishop, Jeffrey R.; Gershon, Elliot S.; Tamminga, Carol A.; Pearlson, Godfrey D.; Keshavan, Matcheri S.; Sweeney, John A.

    2017-01-01

    Objective Familial neuropsychological deficits are well established in schizophrenia but remain less well characterized in other psychotic disorders. This study from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium 1) compares cognitive impairment in schizophrenia and bipolar disorder with psychosis, 2) tests a continuum model of cognitive dysfunction in psychotic disorders, 3) reports familiality of cognitive impairments across psychotic disorders, and 4) evaluates cognitive impairment among nonpsychotic relatives with and without cluster A personality traits. Method Participants included probands with schizophrenia (N=293), psychotic bipolar disorder (N=227), schizoaffective disorder (manic, N=110; depressed, N=55), their first-degree relatives (N=316, N=259, N=133, and N=64, respectively), and healthy comparison subjects (N=295). All participants completed the Brief Assessment of Cognition in Schizophrenia (BACS) neuropsychological battery. Results Cognitive impairments among psychotic probands, compared to healthy comparison subjects, were progressively greater from bipolar disorder (z=−0.77) to schizoaffective disorder (manic z=−1.08; depressed z=−1.25) to schizophrenia (z=−1.42). Profiles across subtests of the BACS were similar across disorders. Familiality of deficits was significant and comparable in schizophrenia and bipolar disorder. Of particular interest were similar levels of neuropsychological deficits in relatives with elevated cluster A personality traits across proband diagnoses. Nonpsychotic relatives of schizophrenia probands without these personality traits exhibited significant cognitive impairments, while relatives of bipolar probands did not. Conclusions Robust cognitive deficits are present and familial in schizophrenia and psychotic bipolar disorder. Severity of cognitive impairments across psychotic disorders was consistent with a continuum model, in which more prominent affective features and less

  10. Altered GPM6A/M6 dosage impairs cognition and causes phenotypes responsive to cholesterol in human and Drosophila.

    Science.gov (United States)

    Gregor, Anne; Kramer, Jamie M; van der Voet, Monique; Schanze, Ina; Uebe, Steffen; Donders, Rogier; Reis, André; Schenck, Annette; Zweier, Christiane

    2014-12-01

    Glycoprotein M6A (GPM6A) is a neuronal transmembrane protein of the PLP/DM20 (proteolipid protein) family that associates with cholesterol-rich lipid rafts and promotes filopodia formation. We identified a de novo duplication of the GPM6A gene in a patient with learning disability and behavioral anomalies. Expression analysis in blood lymphocytes showed increased GPM6A levels. An increase of patient-derived lymphoblastoid cells carrying membrane protrusions supports a functional effect of this duplication. To study the consequences of GPM6A dosage alterations in an intact nervous system, we employed Drosophila melanogaster as a model organism. We found that knockdown of Drosophila M6, the sole member of the PLP family in flies, in the wing, and whole organism causes malformation and lethality, respectively. These phenotypes as well as the protrusions of patient-derived lymphoblastoid cells with increased GPM6A levels can be alleviated by cholesterol supplementation. Notably, overexpression as well as loss of M6 in neurons specifically compromises long-term memory in the courtship conditioning paradigm. Our findings thus indicate a critical role of correct GPM6A/M6 levels for cognitive function and support a role of the GPM6A duplication for the patient's phenotype. Together with other recent findings, this study highlights compromised cholesterol homeostasis as a recurrent feature in cognitive phenotypes. © 2014 WILEY PERIODICALS, INC.

  11. Impaired glucose tolerance in first-episode drug-naïve patients with schizophrenia: relationships with clinical phenotypes and cognitive deficits.

    Science.gov (United States)

    Chen, D C; Du, X D; Yin, G Z; Yang, K B; Nie, Y; Wang, N; Li, Y L; Xiu, M H; He, S C; Yang, F D; Cho, R Y; Kosten, T R; Soares, J C; Zhao, J P; Zhang, X Y

    2016-11-01

    Schizophrenia patients have a higher prevalence of type 2 diabetes mellitus with impaired glucose tolerance (IGT) than normals. We examined the relationship between IGT and clinical phenotypes or cognitive deficits in first-episode, drug-naïve (FEDN) Han Chinese patients with schizophrenia. A total of 175 in-patients were compared with 31 healthy controls on anthropometric measures and fasting plasma levels of glucose, insulin and lipids. They were also compared using a 75 g oral glucose tolerance test and the homeostasis model assessment of insulin resistance (HOMA-IR). Neurocognitive functioning was assessed using the MATRICS Consensus Cognitive Battery (MCCB). Patient psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). Of the patients, 24.5% had IGT compared with none of the controls, and they also had significantly higher levels of fasting blood glucose and 2-h glucose after an oral glucose load, and were more insulin resistant. Compared with those patients with normal glucose tolerance, the IGT patients were older, had a later age of onset, higher waist or hip circumference and body mass index, higher levels of low-density lipoprotein and triglycerides and higher insulin resistance. Furthermore, IGT patients had higher PANSS total and negative symptom subscale scores, but no greater cognitive impairment except on the emotional intelligence index of the MCCB. IGT occurs with greater frequency in FEDN schizophrenia, and shows association with demographic and anthropometric parameters, as well as with clinical symptoms but minimally with cognitive impairment during the early course of the disorder.

  12. UVA-mediated down-regulation of MMP-2 and MT1-MMP coincides with impaired angiogenic phenotype of human dermal endothelial cells

    International Nuclear Information System (INIS)

    Cauchard, Jean-Hubert; Robinet, Arnaud; Poitevin, Stephane; Bobichon, Helene; Maziere, Jean-Claude; Bellon, Georges; Hornebeck, William

    2006-01-01

    UVA irradiation, dose-dependently (5-20 J/cm 2 ), was shown to impair the morphogenic differentiation of human microvascular endothelial cells (HMECs) on Matrigel. Parallely, UVA down-regulated the expression of MMP-2 and MT1-MMP, both at the protein and the mRNA levels. On the contrary, the production of MMP-1 and TIMP-1 by HMECs increased following UVA treatment. The inhibitory effect of UVA on MMP expression and pseudotubes formation was mediated by UVA-generated singlet oxygen ( 1 O 2 ). The contribution of MT1-MMP, but not TIMP-1, to the regulation of HMECs' angiogenic phenotype following UVA irradiation was suggested using elastin-derived peptides and TIMP-1 blocking antibody, respectively

  13. Observations on Working Psychoanalytically with a Profoundly Amnesic Patient

    Directory of Open Access Journals (Sweden)

    Paul A. Moore

    2017-08-01

    Full Text Available Individuals with profound amnesia are markedly impaired in explicitly recalling new episodic events, but appear to preserve the capacity to use information from other sources. Amongst these preserved capacities is the ability to form new memories of an emotional nature – a skill at the heart of developing and sustaining interpersonal relationships. The psychoanalytic study of individuals with profound amnesia might contribute to the understanding the importance of each memory system, including effects on key analytic processes such as transference and countertransference. However, psychoanalytic work in the presence of profound amnesia might also require important technical modifications. In the first report of its kind, we describe observations from a long term psychoanalytic process (72 sessions with an individual (JL who has profound amnesia after an anoxic episode. The nature of therapy was shaped by JL’s impairment in connecting elements that belong to distant (and even relatively close moments in the therapeutic process. However, we were also able to document areas of preservation, in what appears to be a functioning therapeutic alliance. As regards transference, the relationship between JL and his analyst can be viewed as the evolution of a narcissistic transference, and case material is provided that maps this into three phases: (i rejecting; (ii starting to take in; and (iii full use of the analytic space – where each phase exhibits differing degrees of permeability between JL and the analyst. This investigation appears to have important theoretical implications for psychoanalytic practice, and for psychotherapy in general – and not only with regard to brain injured populations. We especially note that it raises questions concerning the mechanism of therapeutic action in psychoanalysis and psychotherapy, and the apparent unimportance of episodic memory for many elements of therapeutic change.

  14. Mesenchymal phenotype predisposes lung cancer cells to impaired proliferation and redox stress in response to glutaminase inhibition.

    Directory of Open Access Journals (Sweden)

    Danielle B Ulanet

    Full Text Available Recent work has highlighted glutaminase (GLS as a key player in cancer cell metabolism, providing glutamine-derived carbon and nitrogen to pathways that support proliferation. There is significant interest in targeting GLS for cancer therapy, although the gene is not known to be mutated or amplified in tumors. As a result, identification of tractable markers that predict GLS dependence is needed for translation of GLS inhibitors to the clinic. Herein we validate a small molecule inhibitor of GLS and show that non-small cell lung cancer cells marked by low E-cadherin and high vimentin expression, hallmarks of a mesenchymal phenotype, are particularly sensitive to inhibition of the enzyme. Furthermore, lung cancer cells induced to undergo epithelial to mesenchymal transition (EMT acquire sensitivity to the GLS inhibitor. Metabolic studies suggest that the mesenchymal cells have a reduced capacity for oxidative phosphorylation and increased susceptibility to oxidative stress, rendering them unable to cope with the perturbations induced by GLS inhibition. These findings elucidate selective metabolic dependencies of mesenchymal lung cancer cells and suggest novel pathways as potential targets in this aggressive cancer type.

  15. Foveal Processing Under Concurrent Peripheral Load in Profoundly Deaf Adults

    Science.gov (United States)

    2016-01-01

    Development of the visual system typically proceeds in concert with the development of audition. One result is that the visual system of profoundly deaf individuals differs from that of those with typical auditory systems. While past research has suggested deaf people have enhanced attention in the visual periphery, it is still unclear whether or not this enhancement entails deficits in central vision. Profoundly deaf and typically hearing adults were administered a variant of the useful field of view task that independently assessed performance on concurrent central and peripheral tasks. Identification of a foveated target was impaired by a concurrent selective peripheral attention task, more so in profoundly deaf adults than in the typically hearing. Previous findings of enhanced performance on the peripheral task were not replicated. These data are discussed in terms of flexible allocation of spatial attention targeted towards perceived task demands, and support a modified “division of labor” hypothesis whereby attentional resources co-opted to process peripheral space result in reduced resources in the central visual field. PMID:26657078

  16. Cortical thickness in de novo patients with Parkinson disease and mild cognitive impairment with consideration of clinical phenotype and motor laterality.

    Science.gov (United States)

    Danti, S; Toschi, N; Diciotti, S; Tessa, C; Poletti, M; Del Dotto, P; Lucetti, C

    2015-12-01

    Parkinson's disease (PD) is a progressive neurodegenerative disorder with motor and non-motor symptoms, including cognitive deficits. Several magnetic resonance imaging approaches have been applied to investigate brain atrophy in PD. The aim of this study was to detect early structural cortical and subcortical changes in de novo PD whilst distinguishing cognitive status, clinical phenotype and motor laterality. Eighteen de novo PD with mild cognitive impairment (PD-MCI), 18 de novo PD without MCI (PD-NC) and 18 healthy control subjects were evaluated. In the PD-MCI group, nine were tremor dominant and nine were postural instability gait disorder (PIGD) phenotype; 11 had right-sided symptom dominance and seven had left-sided symptom dominance. FreeSurfer was used to measure cortical thickness/folding, subcortical structures and to study group differences as well as the association with clinical and neuropsychological data. Parkinson's disease with MCI showed regional thinning in the right frontal, right middle temporal areas and left insula compared to PD-NC. A reduction of the volume of the left and right thalamus and left hippocampus was found in PD-MCI compared to PD-NC. PD-MCI PIGD showed regional thinning in the right inferior parietal area compared to healthy controls. A decreased volume of the left thalamus was reported in PD-MCI with right-sided symptom dominance compared to PD-NC and PD-MCI with left-sided symptom dominance. When MCI was present, PD patients showed a fronto-temporo-parietal pattern of cortical thinning. This cortical pattern does not appear to be influenced by motor laterality, although one-sided symptom dominance may contribute to volumetric reduction of specific subcortical structures. © 2015 EAN.

  17. Circulating MiRNAs of 'Asian Indian Phenotype' Identified in Subjects with Impaired Glucose Tolerance and Patients with Type 2 Diabetes.

    Directory of Open Access Journals (Sweden)

    Paramasivam Prabu

    Full Text Available Several omics technologies are underway worldwide with an aim to unravel the pathophysiology of a complex phenotype such as type 2 diabetes mellitus (T2DM. While recent studies imply a clinically relevant and potential biomarker role of circulatory miRNAs in the etiology of T2DM, there is lack of data on this aspect in Indians--an ethnic population characterized to represent 'Asian Indian phenotype' known to be more prone to develop T2DM and cardiovascular disease than Europeans. We performed global serum miRNA profiling and the validation of candidate miRNAs by qRT-PCR in a cohort of subjects comprised of normal glucose tolerance (NGT, impaired glucose tolerance (IGT and patients with T2DM. Our study revealed 4 differentially expressed miRNAs (miR-128, miR-130b-3p, miR-374a-5p, miR-423-5p in subjects with IGT and T2DM patients compared to control subjects. They were positively or negatively correlated to cholesterol levels, HbA1C, HOMA-IR and fasting insulin. Interestingly, circulating level of miR-128 and miR-130b-3p were also altered in serum of diet-induced diabetic mice compared to control animals. Among the altered circulating miRNAs, miR-128 had never been described in previous studies/populations and appeared to be a 'New Lead' in Indians. It was positively correlated with cholesterol both in prediabetic subjects and in diet-induced diabetic mice, suggesting that its increased level might be associated with the development of dyslipedemia associated with T2DM. Our findings imply directionality towards biomarker potential of miRNAs in the prevention/diagnosis/treatment outcomes of diabetes.

  18. Circulating MiRNAs of 'Asian Indian Phenotype' Identified in Subjects with Impaired Glucose Tolerance and Patients with Type 2 Diabetes.

    Science.gov (United States)

    Prabu, Paramasivam; Rome, Sophie; Sathishkumar, Chandrakumar; Aravind, Sankaramoorthy; Mahalingam, Balakumar; Shanthirani, Coimbatore Subramanian; Gastebois, Caroline; Villard, Audrey; Mohan, Viswanathan; Balasubramanyam, Muthuswamy

    2015-01-01

    Several omics technologies are underway worldwide with an aim to unravel the pathophysiology of a complex phenotype such as type 2 diabetes mellitus (T2DM). While recent studies imply a clinically relevant and potential biomarker role of circulatory miRNAs in the etiology of T2DM, there is lack of data on this aspect in Indians--an ethnic population characterized to represent 'Asian Indian phenotype' known to be more prone to develop T2DM and cardiovascular disease than Europeans. We performed global serum miRNA profiling and the validation of candidate miRNAs by qRT-PCR in a cohort of subjects comprised of normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and patients with T2DM. Our study revealed 4 differentially expressed miRNAs (miR-128, miR-130b-3p, miR-374a-5p, miR-423-5p) in subjects with IGT and T2DM patients compared to control subjects. They were positively or negatively correlated to cholesterol levels, HbA1C, HOMA-IR and fasting insulin. Interestingly, circulating level of miR-128 and miR-130b-3p were also altered in serum of diet-induced diabetic mice compared to control animals. Among the altered circulating miRNAs, miR-128 had never been described in previous studies/populations and appeared to be a 'New Lead' in Indians. It was positively correlated with cholesterol both in prediabetic subjects and in diet-induced diabetic mice, suggesting that its increased level might be associated with the development of dyslipedemia associated with T2DM. Our findings imply directionality towards biomarker potential of miRNAs in the prevention/diagnosis/treatment outcomes of diabetes.

  19. Multifunctional liposomes delay phenotype progression and prevent memory impairment in a presymptomatic stage mouse model of Alzheimer disease.

    Science.gov (United States)

    Mancini, Simona; Balducci, Claudia; Micotti, Edoardo; Tolomeo, Daniele; Forloni, Gianluigi; Masserini, Massimo; Re, Francesca

    2017-07-28

    The failure of clinical trials largely focused on mild to moderate stages of Alzheimer disease has suggested to the scientific community that the effectiveness of Amyloid-β (Aβ)-centered treatments should be evaluated starting as early as possible, well before irreversible brain damage has occurred. Accordingly, also the preclinical development of new therapies should be carried out taking into account this suggestion. In the present investigation we evaluated the efficacy of a treatment with liposomes multifunctionalized for crossing the blood-brain barrier and targeting Aβ, carried out on young APP/PS1 Tg mice, taken as a model of pre-symptomatic disease stage. Liposomes were administered once a week to Tg mice for 7months, starting at the age of 5months and up to the age of 12 when they display AD-like cognitive and brain biochemical/anatomical features. The treatment prevented the onset of the long-term memory impairment and slowed down the deposition of brain Aβ; at anatomical level, prevented both ventricle enlargement and entorhinal cortex thickness reduction, otherwise occurring in untreated mice. Strikingly, these effects were maintained 3months after treatment discontinuation. An increase of Aβ levels in the liver was detected at the end of the treatment, then followed also by reduction of brain Amyloid Precursor Protein and increase of Aβ-degrading enzymes. These results suggest that the treatment promotes brain Aβ clearance by a peripheral 'sink' effect and ultimately affects Aβ turnover in the brain. Worth of note, the treatment was apparently not toxic for all the organs analyzed, in particular for brain, as suggested by the lower brain TNF-α and MDA levels, and by higher level of SOD activity in treated mice. Together, these findings promote a very early treatment with multi-functional liposomes as a well-tolerated nanomedicine-based approach, potentially suitable for a disease-modifying therapy of AD, able to delay or prevent relevant

  20. Achieving profound anesthesia using the intraosseous technique.

    Science.gov (United States)

    Coury, K A

    1997-10-01

    The intraosseous technique has been described as a useful adjunct to primary anesthetic administration. It has several advantages (Table 3) over other supplemental techniques in that it is relatively simple to implement into routine practice, it affords fast, predictable results, and it is relatively painless. The technique has been shown to be very successful in achieving profound pulpal anesthesia when administered as a supplement to the inferior alveolar nerve block and is effective in achieving profound anesthesia in irreversibly inflamed teeth, especially mandibular molars.

  1. Dim light at night interferes with the development of the short-day phenotype and impairs cell-mediated immunity in Siberian hamsters (Phodopus sungorus).

    Science.gov (United States)

    Aubrecht, Taryn G; Weil, Zachary M; Nelson, Randy J

    2014-10-01

    Winter is a challenging time to survive and breed outside of the tropics. Animals use day length (photoperiod) to regulate seasonally appropriate adaptations in anticipation of challenging winter conditions. The net result of these photoperiod-mediated adjustments is enhanced immune function and increased survival. Thus, the ability to discriminate day length information is critical for survival and reproduction in small animals. However, during the past century, urban and suburban development has rapidly expanded and filled the night sky with light from various sources, obscuring crucial light-dark signals, which alters physiological interpretation of day lengths. Furthermore, reduced space, increased proximity to people, and the presence of light at night may act as stressors for small animals. Whereas acute stressors typically enhance immune responses, chronic exposure to stressors often impairs immune responses. Therefore, we hypothesized that the combination of dim light at night and chronic stress interferes with enhanced cell-mediated immunity observed during short days. Siberian hamsters (Phodopus sungorus) were assigned to short or long days with dark nights (0 lux) or dim (5 lux) light at night for 10 weeks. Following 2 weeks of chronic restraint (6 hr/day), a model of chronic stress, delayed type hypersensitivity (DTH) responses were assessed. Both dim light at night and restraint reduced the DTH response. Dim light at night during long nights produced an intermediate short day phenotype. These results suggest the constant presence of light at night could negatively affect survival of photoperiodic rodents by disrupting the timing of breeding and immune responses. © 2014 Wiley Periodicals, Inc.

  2. Signal processing for the profoundly deaf.

    Science.gov (United States)

    Boothyroyd, A

    1990-01-01

    Profound deafness, defined here as a hearing loss in excess of 90 dB, is characterized by high thresholds, reduced hearing range in the intensity and frequency domains, and poor resolution in the frequency and time domains. The high thresholds call for hearing aids with unusually high gains or remote microphones that can be placed close to the signal source. The former option creates acoustic feedback problems for which digital signal processing may yet offer solutions. The latter option calls for carrier wave technology that is already available. The reduced frequency and intensity ranges would appear to call for frequency and/or amplitude compression. It might also be argued, however, that any attempts to compress the acoustic signal into the limited hearing range of the profoundly deaf will be counterproductive because of poor frequency and time resolution, especially when the signal is present in noise. In experiments with a 2-channel compression system, only 1 of 9 subjects showed an improvement of perception with the introduction of fast-release (20 ms) compression. The other 8 experienced no benefit or a slight deterioration of performance. These results support the concept of providing the profoundly deaf with simpler, rather than more complex, patterns, perhaps through the use of feature extraction hearing aids. Data from users of cochlear implants already employing feature extraction techniques also support this concept.

  3. Otolithic organ function in patients with profound sensorineural hearing loss

    Directory of Open Access Journals (Sweden)

    Yujuan Zhou

    2016-06-01

    Full Text Available Profound sensorineural hearing loss (PSHL is not uncommonly encountered in otology. In clinics, there is a high incidence of otolithic damage in patients with PSHL, but relevant reports are few. Sharing a continuous membranous structure and similar receptor cell ultrastructures, the cochlea and vestibule may be susceptible to the same harmful factors. Disorders of the inner ear may result in a variety of manifestations, including vertigo, spatial disorientation, blurred vision, impaired articulation, and hearing impairment. Considering the diversity of clinical symptoms associated with PSHL with otolithic dysfunction, it may be frequently misdiagnosed, and objective means of testing the function of otolithic organs should be recommended for hearing-impaired patients. Vestibular-evoked myogenic potentials (VEMPs via air-conducted sound are of great importance for the diagnosis of otolithic function. Hearing devices such as cochlear implants are commonly accepted treatments for PSHL, and early identification and treatment of vestibular disorders may increase the success rate of cochlear implantation. Therefore, it is necessary to increase awareness of otolithic functional states in patients with PSHL.

  4. A Vibrotactile Interface to Motivate Movement for Children with Severe to Profound Disabilities

    DEFF Research Database (Denmark)

    Manresa-Yee, Cristina; Morrison, Ann; Larsen, Jeppe Veirum

    2014-01-01

    V-Sense is a vibrotactile interface that encourages children with severe or profound cognitive, sensory and physical impairments to move. The interface makes use of touch, in particular vibrations, as a supportive function to motivate users' actions. Specifically, we propose a vibrotactile...

  5. Bipolar Affective Disorder in a Patient of Profound Deafness.

    Science.gov (United States)

    Zubair, Usama Bin; Mumtaz, Humza; Mansoor, Sawera

    2018-03-01

    Profound deafness is a lifelong impairment, leading to the physical disability as well as poor psychological adjustment. We herein present a mental health disorder rarely seen among the patients of profound deafness. A 16-year deaf and dumb girl, previously treated for depression, presented with unusual laughter, irritability, flight of ideas, decreased sleep, ideas of self importance, and decreased social functioning and educational performance. These problems were understood by the parents via sign language, who interpreted them to the interviewer. Her Young Mania Rating Scale (YMRS) score was 19 and Brief Psychiatric Rating Scale (BPRS) score was 52. She was diagnosed as a case of bipolar affective disorder (BPAD). Marked improvement in the symptoms and social and educational performance was noted after two weeks of the treatment with sodium valproate, resperidone and clonazepam. Treatment options were explained to the patient with risks and benefits, and she was involved in the decision-making. This case report highlights the importance of accurately diagnosing and managing a rare mental health disorder among the physically handicapped people, especially those who cannot communicate effectively and explain their unusual subjective experiences.

  6. External ear anomalies and hearing impairment in Noonan Syndrome.

    Science.gov (United States)

    van Trier, Dorothée C; van Nierop, Josephine; Draaisma, Jos M Th; van der Burgt, Ineke; Kunst, Henricus; Croonen, Ellen A; Admiraal, Ronald J C

    2015-06-01

    This is the first cohort in which hearing impairment and external ear anomalies in Noonan Syndrome are described extensively. Retrospective analysis of the otorhinolaryngological and clinical genetic data from 97 Noonan Syndrome (NS) patients. Forty-four NS patients were seen by an otorhinolaryngologist for the analysis of hearing impairment. In our cohort 80 of the 97 patients were genetically tested. In 71 of these mutations were found: in 48 patients a mutation in PTPN11, in 10 patients in SOS1, in 5 patients in SHOC2, in 5 patients in RAF1, in 1 patient in MAP2K2, in 1 patient in KRAS and in 1 patient in A2ML1. External ear anomalies were reported in 75 NS patients (77%). In 69 patients the ears were low-set, 28 patients had posteriorly rotated ears, 14 patients showed protruding ears and 18 had thickened helices. Hearing impairment was detected in 34 NS patients. Nine patients had sensorineural hearing impairment, two a permanent conductive hearing impairment, two other patients had mixed hearing impairment and 20 patients had conductive hearing impairment in the past, caused by otitis media with effusion. Their temporary conductive hearing impairment resolved between the ages of 2 and 18 years. Sensorineural hearing impairment varied between mild high-frequency hearing impairment and profound (uni- and bilateral) hearing impairment and was progressive in three patients. Four NS patients received cochlear implants for their severe sensorineural hearing impairment. The cohort is small for genotype-phenotype correlations, but sensorineural hearing impairment, especially the bilateral severe hearing impairment, was only seen in patients with a PTPN11 mutation. NS is characterized by dysmorphic external ear anomalies and both sensorineural and conductive hearing impairment. Audiological examinations are recommended in all patients with Noonan Syndrome. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Profound bradycardia associated with NIV removal.

    Science.gov (United States)

    Echevarria, C; Bourke, S C; Gibson, G J

    2012-01-01

    A patient with lower-limb onset ALS presented with a one-month history of vasovagal episodes and a one-week history of cough productive of green sputum and lethargy. She was drowsy and in acute on chronic type-two respiratory failure. She responded to non-invasive ventilation, however she suffered recurrent episodes of profound bradycardia on removal of the mask, which gradually resolved over ten days. We have reviewed the literature and offer a potential explanation for these events.

  8. Asystole Following Profound Vagal Stimulation During Hepatectomy

    Directory of Open Access Journals (Sweden)

    Preeta John

    2008-01-01

    Full Text Available Asystole in a non laparoscopic upper abdominal surgery following intense vagal stimulation is a rare event. This case report highlights the need for awareness of such a complication when a thoracic epidural anaesthetic has been given in addition to a general anaesthetic for an upper abdominal procedure. A combined thoracic epidural and general anaesthetic was given. The anterior abdominal wall was retracted forty minutes after administration of the epidural bolus. This maneuver resulted in a profound vagal response with bradycardia and asystole. The patient was resuscitated successfully with a cardiac massage, atropine and adrenaline and the surgery was resumed. Surgery lasted eleven hours and was uneventful.

  9. Vitamin B12-impaired metabolism produces apoptosis and Parkinson phenotype in rats expressing the transcobalamin-oleosin chimera in substantia nigra.

    Directory of Open Access Journals (Sweden)

    Carlos Enrique Orozco-Barrios

    was responsible for apoptosis in N1E-115 cells and rat substantia nigra and for Parkinson-like phenotype. This suggests evaluating whether vitamin B12 deficit could aggravate the PD in patients under Levodopa therapy by impairing S-adenosylmethionine synthesis in substantia nigra.

  10. Persistent Thalamic Sound Processing Despite Profound Cochlear Denervation

    Directory of Open Access Journals (Sweden)

    Anna R. Chambers

    2016-08-01

    Full Text Available Neurons at higher stages of sensory processing can partially compensate for a sudden drop in input from the periphery through a homeostatic plasticity process that increases the gain on weak afferent inputs. Even after a profound unilateral auditory neuropathy where > 95% of synapses between auditory nerve fibers and inner hair cells have been eliminated with ouabain, central gain can restore the cortical processing and perceptual detection of basic sounds delivered to the denervated ear. In this model of profound auditory neuropathy, cortical processing and perception recover despite the absence of an auditory brainstem response (ABR or brainstem acoustic reflexes, and only a partial recovery of sound processing at the level of the inferior colliculus (IC, an auditory midbrain nucleus. In this study, we induced a profound cochlear neuropathy with ouabain and asked whether central gain enabled a compensatory plasticity in the auditory thalamus comparable to the full recovery of function previously observed in the auditory cortex (ACtx, the partial recovery observed in the IC, or something different entirely. Unilateral ouabain treatment in adult mice effectively eliminated the ABR, yet robust sound-evoked activity persisted in a minority of units recorded from the contralateral medial geniculate body (MGB of awake mice. Sound-driven MGB units could decode moderate and high-intensity sounds with accuracies comparable to sham-treated control mice, but low-intensity classification was near chance. Pure tone receptive fields and synchronization to broadband pulse trains also persisted, albeit with significantly reduced quality and precision, respectively. MGB decoding of temporally modulated pulse trains and speech tokens were both greatly impaired in ouabain-treated mice. Taken together, the absence of an ABR belied a persistent auditory processing at the level of the MGB that was likely enabled through increased central gain. Compensatory

  11. An Expanded Multi-Organ Disease Phenotype Associated with Mutations in YARS

    DEFF Research Database (Denmark)

    Tracewska-Siemiątkowska, Anna; Haer-Wigman, Lonneke; Bosch, Danielle G M

    2017-01-01

    Whole exome sequence analysis was performed in a Swedish mother-father-affected proband trio with a phenotype characterized by progressive retinal degeneration with congenital nystagmus, profound congenital hearing impairment, primary amenorrhea, agenesis of the corpus callosum, and liver disease....... A homozygous variant c.806T > C, p.(F269S) in the tyrosyl-tRNA synthetase gene (YARS) was the only identified candidate variant consistent with autosomal recessive inheritance. Mutations in YARS have previously been associated with both autosomal dominant Charcot-Marie-Tooth syndrome and a recently reported...

  12. Demographic Characteristics and Impairments of Louisiana Students with Usher's Syndrome.

    Science.gov (United States)

    Brown, S. C.

    1987-01-01

    Of 51 Louisiana students with Usher's Syndrome (a genetic condition characterized by hearing loss and progressive blindness), 71 percent manifested visual impairment and hearing loss, 9 percent had neither, 10 percent had visual impairments but a less-than-profound hearing loss, and 10 percent had profound hearing loss and no visual impairment.…

  13. Staffs' documentation of participation for adults with profound intellectual disability or profound intellectual and multiple disabilities.

    Science.gov (United States)

    Talman, Lena; Gustafsson, Christine; Stier, Jonas; Wilder, Jenny

    2017-06-21

    This study investigated what areas of International Classification of Functioning, Disability and Health were documented in implementation plans for adults with profound intellectual disability or profound intellectual and multiple disabilities with focus on participation. A document analysis of 17 implementation plans was performed and International Classification of Functioning, Disability and Health was used as an analytic tool. One hundred and sixty-three different codes were identified, especially in the components Activities and participation and Environmental factors. Participation was most frequently coded in the chapters Community, social and civic life and Self-care. Overall, the results showed that focus in the implementation plans concerned Self-care and Community, social and civic life. The other life areas in Activities and participation were seldom, or not at all, documented. A deeper focus on participation in the implementation plans and all life areas in the component Activities and participation is needed. It is important that the documentation clearly shows what the adult wants, wishes, and likes in everyday life. It is also important to ensure that the job description for staff contains both life areas and individual preferences so that staff have the possibility to work to fulfill social and individual participation for the target group. Implications for rehabilitation There is a need for functioning working models to increase participation significantly for adults with profound intellectual disability or profound intellectual and multiple disabilities. For these adults, participation is achieved through the assistance of others and support and services carried out must be documented in an implementation plan. The International Classification of Functioning, Disability and Health can be used to support staff and ensure that information about the most important factors in an individual's functioning in their environment is not omitted in

  14. FTLD-TDP with motor neuron disease, visuospatial impairment and a progressive supranuclear palsy-like syndrome: broadening the clinical phenotype of TDP-43 proteinopathies. A report of three cases

    Directory of Open Access Journals (Sweden)

    Holmerová Iva

    2011-05-01

    Full Text Available Abstract Background Frontotemporal lobar degeneration with ubiquitin and TDP-43 positive neuronal inclusions represents a novel entity (FTLD-TDP that may be associated with motor neuron disease (FTLD-MND; involvement of extrapyramidal and other systems has also been reported. Case presentation We present three cases with similar clinical symptoms, including Parkinsonism, supranuclear gaze palsy, visuospatial impairment and a behavioral variant of frontotemporal dementia, associated with either clinically possible or definite MND. Neuropathological examination revealed hallmarks of FTLD-TDP with major involvement of subcortical and, in particular, mesencephalic structures. These cases differed in onset and progression of clinical manifestations as well as distribution of histopathological changes in the brain and spinal cord. Two cases were sporadic, whereas the third case had a pathological variation in the progranulin gene 102 delC. Conclusions Association of a "progressive supranuclear palsy-like" syndrome with marked visuospatial impairment, motor neuron disease and early behavioral disturbances may represent a clinically distinct phenotype of FTLD-TDP. Our observations further support the concept that TDP-43 proteinopathies represent a spectrum of disorders, where preferential localization of pathogenetic inclusions and neuronal cell loss defines clinical phenotypes ranging from frontotemporal dementia with or without motor neuron disease, to corticobasal syndrome and to a progressive supranuclear palsy-like syndrome.

  15. CD4:8 ratio >5 is associated with a dominant naive T-cell phenotype and impaired physical functioning in CMV-seropositive very elderly people: results from the BELFRAIL study.

    Science.gov (United States)

    Adriaensen, Wim; Derhovanessian, Evelyna; Vaes, Bert; Van Pottelbergh, Gijs; Degryse, Jean-Marie; Pawelec, Graham; Hamprecht, Klaus; Theeten, Heidi; Matheï, Catharina

    2015-02-01

    A subset of older people is at increased risk of hospitalization and dependency. Emerging evidence suggests that immunosenescence reflected by an inverted CD4:8 ratio and cytomegalovirus (CMV) seropositivity plays an important role in the pathophysiology of functional decline. Nevertheless, the relation between CD4:8 ratio and functional outcome has rarely been investigated. Here, CD4:8 ratio and T-cell phenotypes of 235 community-dwelling persons aged ≥81.5 years in the BELFRAIL study and 25 younger persons (mean age 28.5 years) were analyzed using polychromatic flow cytometry. In the elderly persons, 7.2% had an inverted CD4:8 ratio, which was associated with CMV seropositivity, less naive, and more late-differentiated CD4+ and CD8+ T cells. However, 32.8% had a CD4:8 ratio >5, a phenotype associated with a higher proportion of naive T cells and absent in young donors. In CMV seropositives, this subgroup had lower proportions of late-differentiated CD4+ and CD8+ T cells and weaker anti-CMV immunoglobulin G reactivity. This novel naive T-cell-dominated phenotype was counterintuitively associated with a higher proportion of those with impaired physical functioning in the very elderly people infected with CMV. This underscores the notion that in very elderly people, not merely CMV infection but also the state of its accompanying immune dysregulation is of crucial importance with regard to physical impairment. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Antisocial and seizure susceptibility phenotypes in an animal model of epilepsy are normalized by impairment of brain corticotropin-releasing factor.

    Science.gov (United States)

    Turner, Laura H; Lim, Chen E; Heinrichs, Stephen C

    2007-02-01

    Social interaction phenotyping is an unexplored niche in animal modeling of epilepsy despite the sensitivity of affiliative behaviors to emotionality and stress, which are known seizure triggers. Thus, the present studies examined the social phenotype of seizure-susceptible El and nonsusceptible ddY strains both in untreated animals and following preexposure to a handling stressor. The second aim of the present studies was to evaluate the dependence of sociability in El mice on the proconvulsive, stress neuropeptide corticotropin-releasing factor (CRF) using CRF-SAP, a conjugate of CRF and the toxin saporin, which selectively reduced CRF peptide levels in the basolateral amygdala of El mice. El mice exhibited lower social investigation times than ddY counterparts, whereas central administration of CRF-SAP normalized social investigation times relative to ddY controls. Moreover, handling-induced seizures in El mice were reduced by 50% following treatment with CRF-SAP relative to saporin alone-injected El controls. The results of this study suggest that tonically activated CRF systems in the El mouse brain suppress affiliative behavior and facilitate evoked seizures.

  17. The Effect of Frequency Transposition on Speech Perception in Adolescents and Young Adults with Profound Hearing Loss

    Science.gov (United States)

    Gou, J.; Smith, J.; Valero, J.; Rubio, I.

    2011-01-01

    This paper reports on a clinical trial evaluating outcomes of a frequency-lowering technique for adolescents and young adults with severe to profound hearing impairment. Outcomes were defined by changes in aided thresholds, speech perception, and acceptance. The participants comprised seven young people aged between 13 and 25 years. They were…

  18. Prebiotic milk oligosaccharides prevent development of obese phenotype, impairment of gut permeability, and microbial dysbiosis in high fat-fed mice.

    Science.gov (United States)

    Hamilton, M Kristina; Ronveaux, Charlotte C; Rust, Bret M; Newman, John W; Hawley, Melissa; Barile, Daniela; Mills, David A; Raybould, Helen E

    2017-05-01

    Microbial dysbiosis and increased intestinal permeability are targets for prevention or reversal of weight gain in high-fat (HF) diet-induced obesity (DIO). Prebiotic milk oligosaccharides (MO) have been shown to benefit the host intestine but have not been used in DIO. We hypothesized that supplementation with bovine MO would prevent the deleterious effect of HF diet on the gut microbiota and intestinal permeability and attenuate development of the obese phenotype. C57BL/6 mice were fed a control diet, HF (40% fat/kcal), or HF + prebiotic [6%/kg bovine milk oligosaccharides (BMO) or inulin] for 1, 3, or 6 wk. Gut microbiota and intestinal permeability were assessed in the ileum, cecum, and colon. Addition of BMO to the HF diet significantly attenuated weight gain, decreased adiposity, and decreased caloric intake; inulin supplementation also lowered weight gain and adiposity, but this did not reach significance. BMO and inulin completely abolished the HF diet-induced increase in paracellular and transcellular permeability in the small and large intestine. Both BMO and inulin increased abundance of beneficial microbes Bifidobacterium and Lactobacillus in the ileum. However, inulin supplementation altered phylogenetic diversity and decreased species richness. We conclude that addition of BMO to the HF diet completely prevented increases in intestinal permeability and microbial dysbiosis and was partially effective to prevent weight gain in DIO. NEW & NOTEWORTHY This study provides the first report of the effects of prebiotic bovine milk oligosaccharides on the host phenotype of high-fat diet-induced obesity in mice. Copyright © 2017 the American Physiological Society.

  19. Proximal processes of children with profound multiple disabilities

    OpenAIRE

    Wilder, Jenny

    2008-01-01

    In this thesis four empirical studies dealt with children with profound multiple disabilities and their parents with regard to: (a) how parents perceived interaction with their children (b) how observed child/parent interaction was linked to behavior style of the children as perceived by the parents (c) how parents of children with profound multiple disabilities perceived child/parent interaction and behavior style of their children in comparison to parents to children without disabilities ma...

  20. Experience with cochlear implants in Greenlanders with profound hearing loss living in Greenland

    DEFF Research Database (Denmark)

    Homøe, Preben; Andersen, Ture; Grøntved, Aksel

    2013-01-01

    OBJECTIVE: Cochlear implant (CI) treatment was introduced to the world in the 1980s and has become a routine treatment for congenital or acquired severe-to-profound hearing loss. CI treatment requires access to a highly skilled team of ear, nose and throat specialists, audiologists and speech...... years are in need of a CI every second year in Greenland often due to sequelae from meningitis, which may cause postinfectious deafness. Screening of new-borns for hearing has been started in Greenland establishing the basis for early diagnosis of congenital hearing impairment and subsequent...

  1. Human dignity and the profoundly disabled: a theological perspective.

    Science.gov (United States)

    Matthews, Pia

    2011-01-01

    One challenge to the concept of human dignity is that it is a rootless notion invoked simply to mask inequalities that inevitably exist between human beings. This privileging of humans is speciesist and its weak point is the profoundly disabled human being. This article argues that far from being a weak point, the profoundly disabled person is a source of strength and witness to the intrinsic dignity that all human beings have by virtue of being human. The disabled represent the reality of human existence that is both strong and fragile. Although human dignity can be understood philosophically its depth is rooted in Christian theological insights. The profoundly disabled occupy a privileged position and share in a theology of mission since they testify to the interdependence of every human being and human dependence on God to a myopic world that only values strength, autonomy and independence.

  2. The management of children with Down syndrome and profound hearing loss.

    Science.gov (United States)

    Phelan, E; Pal, R; Henderson, L; Green, K M J; Bruce, I A

    2016-01-01

    Although, the association between Down syndrome (DS) and conductive hearing loss is well recognized, the fact that a small proportion of these children may have a severe to profound sensorineural hearing loss that could benefit from cochlear implantation (CI) is less well understood. The management of significant co-morbidities in children with DS can delay initial diagnosis of hearing impairment and assessment of suitability for CI can likewise be challenging, due to difficulties conditioning to behavioural hearing tests. We performed a retrospective case note review of three children with DS referred to the Manchester Cochlear Implant Programme. Three illustrative cases are described including CI in a 4 years old. Using conventional outcome measurement instruments, the outcome could be considered to be suboptimal with a Categories of Auditory Performance score of 4 at 6 months post-op and at last follow up. In part, this is likely to reflect the delay in implantation, but the role of cognitive impairment must be considered. The cases described emphasize the importance of comprehensive radiological and audiological assessment in children with DS being considered for CI. The influence of cognitive impairment upon outcome of CI must be taken into account, but should not be considered a contra-indication to implantation in children with DS. Benefit that might be considered limited when quantified using existing general outcome measurement instruments, may have a significant impact upon psychosocial development and quality of life in children with significant cognitive impairment, or other additional needs.

  3. Music Training for Severely and Profoundly Retarded Individuals.

    Science.gov (United States)

    Kesler, Buford; Richmond, Bert O.

    Investigated were the effects of sex, ability and training method on the musical instrument playing ability of 16 institutionalized severely and profoundly retarded persons ages 7 to 20 years. Ss were randomly assigned to one of four treatment groups, and the time required to reach criterion playing a familiar tune was recorded. Data indicated…

  4. Acceleration of Object Permanence with Severely and Profoundly Retarded Children.

    Science.gov (United States)

    Kahn, James V.

    Examined was the effectiveness of training four severely and profoundly retarded children (3-6 years old) to improve their level of functioning on a measure of object permanence and to demonstrate generalization to other areas of sensorimotor intelligence. Ss were given a pretest and posttest on the I. Uzgiris and J. Hunt instrument which consists…

  5. Factors which Motivate Job Acceptance and Profoundly Mentally Retarded Children.

    Science.gov (United States)

    Marozas, Donald S.; May, Deborah C.

    1980-01-01

    The study involving 360 Pennsylvania teachers was designed to identify factors which motivate job acceptance among teachers of severely and profoundly mentally retarded children. The responses of 235 teachers indicated that challenge and practicum experiences were the two most prevalent motivational factors underlying job acceptance. (Author)

  6. Pre-Language Activities for the Profoundly Mentally Retarded.

    Science.gov (United States)

    Poole, Marilyn R.; And Others

    Provided are sample lesson plans for a program to develop pre-language skills in profoundly retarded children and adults. Characteristic of the suggested activities is the stimulation of all sensory channels through structured infant-like play activities in five general areas: oral stimulation, sensory arousal, motor stimulation, vocal play, and…

  7. A Grounded Theory of Effective Reading by Profoundly Deaf Adults

    Science.gov (United States)

    Silvestri, Julia; Wang, Ye

    2018-01-01

    The purpose of the study was to uncover and describe psycholinguistic and sociocognitive factors facilitating effective reading by signing adults who are profoundly deaf and do not use hearing technology. The sample comprised four groups, each consisting of 15 adults, for a total of 60 participants. The four groups were "deaf…

  8. Deming's System of Profound Knowledge: An Overview for International Educators.

    Science.gov (United States)

    Evans, Thomas J.

    W. Edwards Deming called for the transformation to a new style of organizational management based on greater cooperation between managers and employees. This transformation could be achieved by introducing "profound knowledge" into the system. This paper is a presentation outline that was used to introduce the basics of Deming's theory…

  9. Do colors exist? and other profound physics questions

    CERN Document Server

    Cottrell, Seth Stannard

    2018-01-01

    Why do polished stones look wet? How does the Twin Paradox work? Why are orbits ellipses? How can we be sure that pi never repeats? How does a quantum computer break encryption? Discover the answers to these, and other profound physics questions! This fascinating book presents a collection of articles based on conversations and correspondences between the author and complete strangers about physics and math. The author, a researcher in mathematical physics, responds to dozens of questions posed by inquiring minds from all over the world, ranging from the everyday to the profound. Rather than unnecessarily complex explanations mired in mysterious terminology and symbols, the reader is presented with the reasoning, experiments, and mathematics in a casual, conversational, and often comical style. Neither over-simplified nor over-technical, the lucid and entertaining writing will guide the reader from the each innocent question to a better understanding of the weird and beautiful universe around us. Advance prai...

  10. Maturation of the mitochondrial redox response to profound asphyxia in fetal sheep.

    Directory of Open Access Journals (Sweden)

    Paul P Drury

    Full Text Available Fetal susceptibility to hypoxic brain injury increases over the last third of gestation. This study examined the hypothesis that this is associated with impaired mitochondrial adaptation, as measured by more rapid oxidation of cytochrome oxidase (CytOx during profound asphyxia.Chronically instrumented fetal sheep at 0.6, 0.7, and 0.85 gestation were subjected to either 30 min (0.6 gestational age (ga, n = 6, 25 min (0.7 ga, n = 27 or 15 min (0.85 ga, n = 17 of complete umbilical cord occlusion. Fetal EEG, cerebral impedance (to measure brain swelling and near-infrared spectroscopy-derived intra-cerebral oxygenation (ΔHb = HbO(2 - Hb, total hemoglobin (THb and CytOx redox state were monitored continuously. Occlusion was associated with profound, rapid fall in ΔHb in all groups to a plateau from 6 min, greatest at 0.85 ga compared to 0.6 and 0.7 ga (p<0.05. THb initially increased at all ages, with the greatest rise at 0.85 ga (p<0.05, followed by a progressive fall from 7 min in all groups. CytOx initially increased in all groups with the greatest rise at 0.85 ga (p<0.05, followed by a further, delayed increase in preterm fetuses, but a striking fall in the 0.85 group after 6 min of occlusion. Cerebral impedance (a measure of cytotoxic edema increased earlier and more rapidly with greater gestation. In conclusion, the more rapid rise in CytOx and cortical impedance during profound asphyxia with greater maturation is consistent with increasing dependence on oxidative metabolism leading to earlier onset of neural energy failure before the onset of systemic hypotension.

  11. Differentiating characteristics of deafblindness and autism in people with congenital deafblindness and profound intellectual disability.

    Science.gov (United States)

    Hoevenaars-van den Boom, M A A; Antonissen, A C F M; Knoors, H; Vervloed, M P J

    2009-06-01

    In persons with deafblindness, it is hard to distinguish autism spectrum disorders from several deafblind specific behaviours caused by the dual sensory impairments, especially when these persons are also intellectually disabled. As a result, there is an over-diagnosis of autism in persons who are deafblind leading to unsuitable interventions. Autism as specified by the DSM-IV was studied in 10 persons with congenital deafblindness with profound intellectual disabilities. Behaviours of people with deafblindness and autism (n = 5) and of people with deafblindness without autism (n = 5) were observed in a semi-standardised assessment. All people with deafblindness showed impairments in social interaction, communication and language. In contrast to persons without autism, people with deafblindness and autism showed significantly more impairments in reciprocity of social interaction, quality of initiatives to contact and the use of adequate communicative signals and functions. No differences between the groups were found for quantity and persistence of stereotyped behaviour, quality of play and exploration and adequate problem-solving strategies. This study indicates that there are some possibilities to differentiate autism from behaviours specific for deafblindness. It also confirms the large overlap in overt behaviours between people with deafblindness and persons with autism.

  12. Attentional Processes in Young Children with Congenital Visual Impairment

    Science.gov (United States)

    Tadic, Valerie; Pring, Linda; Dale, Naomi

    2009-01-01

    The study investigated attentional processes of 32 preschool children with congenital visual impairment (VI). Children with profound visual impairment (PVI) and severe visual impairment (SVI) were compared to a group of typically developing sighted children in their ability to respond to adult directed attention in terms of establishing,…

  13. A novel KCNQ4 one-base deletion in a large pedigree with hearing loss: implication for the genotype-phenotype correlation.

    Science.gov (United States)

    Kamada, Fumiaki; Kure, Shigeo; Kudo, Takayuki; Suzuki, Yoichi; Oshima, Takeshi; Ichinohe, Akiko; Kojima, Kanako; Niihori, Tetsuya; Kanno, Junko; Narumi, Yoko; Narisawa, Ayumi; Kato, Kumi; Aoki, Yoko; Ikeda, Katsuhisa; Kobayashi, Toshimitsu; Matsubara, Yoichi

    2006-01-01

    Autosomal-dominant, nonsyndromic hearing impairment is clinically and genetically heterogeneous. We encountered a large Japanese pedigree in which nonsyndromic hearing loss was inherited in an autosomal-dominant fashion. A genome-wide linkage study indicated linkage to the DFNA2 locus on chromosome 1p34. Mutational analysis of KCNQ4 encoding a potassium channel revealed a novel one-base deletion in exon 1, c.211delC, which generated a profoundly truncated protein without transmembrane domains (p.Q71fsX138). Previously, six missense mutations and one 13-base deletion, c.211_223del, had been reported in KCNQ4. Patients with the KCNQ4 missense mutations had younger-onset and more profound hearing loss than patients with the 211_223del mutation. In our current study, 12 individuals with the c.211delC mutation manifested late-onset and pure high-frequency hearing loss. Our results support the genotype-phenotype correlation that the KCNQ4 deletions are associated with later-onset and milder hearing impairment than the missense mutations. The phenotypic difference may be caused by the difference in pathogenic mechanisms: haploinsufficiency in deletions and dominant-negative effect in missense mutations.

  14. Phenotype Development in Adolescents With Tourette Syndrome

    DEFF Research Database (Denmark)

    Groth, Camilla; Debes, Nanette Mol; Skov, Liselotte

    2017-01-01

    Tourette syndrome (TS) is a neurodevelopmental disorder characterized by frequent comorbidities and a wide spectrum of phenotype presentations. This study aimed to describe the development of phenotypes in TS and tic-related impairment in a large longitudinal study of 226 children and adolescents...... followed up after 6 years. The participants were clinically examined to assess tic severity and impairment, obsessive compulsive disorder (OCD), and attention-deficit/hyperactivity disorder (ADHD). The development in phenotypes changed toward less comorbidity with 40% TS-only (no OCD or ADHD) (TS without...... OCD or ADHD) at baseline and 55% at follow-up.Tic-related impairment was expected to improve with an age-related tic decline, but surprisingly the impairment score did not reflect the tic decline. Sex, vocal and motor tics, and OCD and ADHD severity were highly significantly correlated...

  15. SOX10 mutation causes Waardenburg syndrome associated with distinctive phenotypic features in an Iranian family: A clue for phenotype-directed genetic analysis.

    Science.gov (United States)

    Jalilian, Nazanin; Tabatabaiefar, Mohammad Amin; Alimadadi, Hossein; Noori-Daloii, Mohammad Reza

    2017-05-01

    Waardenburg syndrome (WS) is a neurocristopathy characterized by hearing impairment and pigmentary disturbances in hair, eyes, and skin. WS is clinically heterogeneous and can be subdivided into four major types (WS1-WS4) where WS4 or Shah-Waardenburg is diagnosed when WS2 is accompanied by Hirschsprung disease (HD). Mutations of SOX10, EDN3/EDNRB have been identified in association with WS4. This study was aimed to determine the pathogenic variant in an Iranian pedigree affected with WS4. A two-generation pedigree with three affected members and considerable phenotypic heterogeneity was recruited. The proband was a 15-year-old boy, with severe to profound sensorineural hearing impairment, heterochromia iridis, hypoplastic blue eyes and Hirschprung disease. The other two also presented characteristics of WS2 and complained of chronic constipation with normal anorectal reflex. Sequencing of all exons and exon-intron boundaries of SOX10, EDN3/EDNRB revealed a heterozygous variant c.422T > C in exon 3 of SOX10 confirmed by a series of evidence to be pathogenic. It resulted in p.L141P at the protein level. Leucin 141 is located in Nuclear Export signal, HMG box of the protein. This study is the first report of a WS4 family in the Iranian population. The mutation is associated with distinctive phenotypic profile (association of anosmia and chronic constipation with SOX10 mutations) and could further improve diagnosis and counseling of WS in the Iranian population and can contribute to phenotype-directed genetic analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Profound hyper natremia due to central diabetes insipidus

    International Nuclear Information System (INIS)

    Vaqar, A.; Javaid, K.H.; Parveen, R.; Sadaf, R.

    2012-01-01

    Diabetes insipidus is a rare endocrine disorder in paediatric patients. Polyuria is a cardinal manifestation that is extremely difficult to recognize in diapered infants. Careful urine quantification is the key to diagnosis in appropriate clinical setting. We report a case of a 4 months old infant presenting with an acute life threatening event following an episode of vomiting and decreased oral intake. She had profound hyper natremia which persisted after stabilization. Polyuria unrecognized by the mother was revealed by 24-hour urine output measurement. A diagnosis of diabetes insipidus was made after appropriate laboratory investigations including serum and urine osmolality. The central nature of the disease was confirmed by neuroimaging which showed holoprosencephaly. (author)

  17. Outcomes of laryngohyoid suspension techniques in an ovine model of profound oropharyngeal dysphagia.

    Science.gov (United States)

    Johnson, Christopher M; Venkatesan, Naren N; Siddiqui, M Tausif; Cates, Daniel J; Kuhn, Maggie A; Postma, Gregory M; Belafsky, Peter C

    2017-12-01

    To evaluate the efficacy of various techniques of laryngohyoid suspension in the elimination of aspiration utilizing a cadaveric ovine model of profound oropharyngeal dysphagia. Animal study. The head and neck of a Dorper cross ewe was placed in the lateral fluoroscopic view. Five conditions were tested: baseline, thyroid cartilage to hyoid approximation (THA), thyroid cartilage to hyoid to mandible (laryngohyoid) suspension (LHS), LHS with cricopharyngeus muscle myotomy (LHS-CPM), and cricopharyngeus muscle myotomy (CPM) alone. Five 20-mL trials of barium sulfate were delivered into the oropharynx under fluoroscopy for each condition. Outcome measures included the penetration aspiration scale (PAS) and the National Institutes of Health (NIH) Swallow Safety Scale (NIH-SSS). Median baseline PAS and NIH-SSS scores were 8 and 6, respectively, indicating severe impairment. THA scores were not improved from baseline. LHS alone reduced the PAS to 1 (P = .025) and NIH-SSS to 2 (P = .025) from baseline. LHS-CPM reduced the PAS to 1 (P = .025) and NIH-SSS to 0 (P = .025) from baseline. CPM alone did not improve scores. LHS-CPM displayed improved NIH-SSS over LHS alone (P = .003). This cadaveric model represents end-stage profound oropharyngeal dysphagia such as what could result from severe neurological insult. CPM alone failed to improve fluoroscopic outcomes in this model. Thyrohyoid approximation also failed to improve outcomes. LHS significantly improved both PAS and NIH-SSS. The addition of CPM to LHS resulted in improvement over suspension alone. NA. Laryngoscope, 127:E422-E427, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  18. Cancer prevention knowledge of people with profound hearing loss.

    Science.gov (United States)

    Zazove, Philip; Meador, Helen E; Reed, Barbara D; Sen, Ananda; Gorenflo, Daniel W

    2009-03-01

    Deaf persons, a documented minority population, have low reading levels and difficulty communicating with physicians. The effect of these on their knowledge of cancer prevention recommendations is unknown. A cross-sectional study of 222 d/Deaf persons in Michigan, age 18 and older, chose one of four ways (voice, video of a certified American Sign Language interpreter, captions, or printed English) to complete a self-administered computer video questionnaire about demographics, hearing loss, language history, health-care utilization, and health-care information sources, as well as family and social variables. Twelve questions tested their knowledge of cancer prevention recommendations. The outcome measures were the percentage of correct answers to the questions and the association of multiple variables with these responses. Participants averaged 22.9% correct answers with no gender difference. Univariate analysis revealed that smoking history, types of medical problems, last physician visit, and women having previous cancer preventive tests did not affect scores. Improved scores occurred with computer use (p = 0.05), higher education (p internet (p = 0.02), and believing that smoking is bad (p bad (p = 0.05) were associated with improved scores. Persons with profound hearing loss have poor knowledge of recommended cancer prevention interventions. English use in multiple settings was strongly associated with increased knowledge.

  19. Histones induce rapid and profound thrombocytopenia in mice

    Science.gov (United States)

    Bhandari, Ashish A.

    2011-01-01

    Histones are released from dying cells and contribute to antimicrobial defense during infection. However, extracellular histones are a double-edged sword because they also damage host tissue and may cause death. We studied the interactions of histones with platelets. Histones bound to platelets, induced calcium influx, and recruited plasma adhesion proteins such as fibrinogen to induce platelet aggregation. Hereby fibrinogen cross-linked histone-bearing platelets and triggered microaggregation. Fibrinogen interactions with αIIbβ3 integrins were not required for this process but were necessary for the formation of large platelet aggregates. Infused histones associated with platelets in vivo and caused a profound thrombocytopenia within minutes after administration. Mice lacking platelets or αIIbβ3 integrins were protected from histone-induced death but not from histone-induced tissue damage. Heparin, at high concentrations, prevented histone interactions with platelets and protected mice from histone-induced thrombocytopenia, tissue damage, and death. Heparin and histones are evolutionary maintained. Histones may combine microbicidal with prothrombotic properties to fight invading microbes and maintain hemostasis after injury. Heparin may provide an innate counter mechanism to neutralize histones and diminish collateral tissue damage. PMID:21700775

  20. Cochlear implantation in autistic children with profound sensorineural hearing loss.

    Science.gov (United States)

    Lachowska, Magdalena; Pastuszka, Agnieszka; Łukaszewicz-Moszyńska, Zuzanna; Mikołajewska, Lidia; Niemczyk, Kazimierz

    2016-11-19

    Cochlear implants have become the method of choice for the treatment of severe-to-profound hearing loss in both children and adults. Its benefits are well documented in the pediatric and adult population. Also deaf children with additional needs, including autism, have been covered by this treatment. The aim of this study was to assess the benefits from cochlear implantation in deafened children with autism as the only additional disability. This study analyzes data of six children. The follow-up time was at least 43 months. The following data were analyzed: medical history, reaction to music and sound, Ling's six sounds test, onomatopoeic word test, reaction to spoken child's name, response to requests, questionnaire given to parents, sound processor fitting sessions and data. After cochlear implantation each child presented other communication skills. In some children, the symptoms of speech understanding were observed. No increased hyperactivity associated with daily use cochlear implant was observed. The study showed that in autistic children the perception is very important for a child's sense of security and makes contact with parents easier. Our study showed that oral communication is not likely to be a realistic goal in children with cochlear implants and autism. The implantation results showed benefits that varied among those children. The traditional methods of evaluating the results of cochlear implantation in children with autism are usually insufficient to fully assess the functional benefits. These benefits should be assessed in a more comprehensive manner taking into account the limitations of communication resulting from the essence of autism. It is important that we share knowledge about these complex children with cochlear implants. Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  1. RhoE deficiency produces postnatal lethality, profound motor deficits and neurodevelopmental delay in mice.

    Directory of Open Access Journals (Sweden)

    Enric Mocholí

    Full Text Available Rnd proteins are a subfamily of Rho GTPases involved in the control of actin cytoskeleton dynamics and other cell functions such as motility, proliferation and survival. Unlike other members of the Rho family, Rnd proteins lack GTPase activity and therefore remain constitutively active. We have recently described that RhoE/Rnd3 is expressed in the Central Nervous System and that it has a role in promoting neurite formation. Despite their possible relevance during development, the role of Rnd proteins in vivo is not known. To get insight into the in vivo function of RhoE we have generated mice lacking RhoE expression by an exon trapping cassette. RhoE null mice (RhoE gt/gt are smaller at birth, display growth retardation and early postnatal death since only half of RhoE gt/gt mice survive beyond postnatal day (PD 15 and 100% are dead by PD 29. RhoE gt/gt mice show an abnormal body position with profound motor impairment and impaired performance in most neurobehavioral tests. Null mutant mice are hypoactive, show an immature locomotor pattern and display a significant delay in the appearance of the hindlimb mature responses. Moreover, they perform worse than the control littermates in the wire suspension, vertical climbing and clinging, righting reflex and negative geotaxis tests. Also, RhoE ablation results in a delay of neuromuscular maturation and in a reduction in the number of spinal motor neurons. Finally, RhoE gt/gt mice lack the common peroneal nerve and, consequently, show a complete atrophy of the target muscles. This is the first model to study the in vivo functions of a member of the Rnd subfamily of proteins, revealing the important role of Rnd3/RhoE in the normal development and suggesting the possible involvement of this protein in neurological disorders.

  2. Heterogeneity in Phenotype of Usher-Congenital Hyperinsulinism Syndrome

    DEFF Research Database (Denmark)

    Al Mutair, Angham N; Brusgaard, Klaus; Bin-Abbas, Bassam

    2013-01-01

    OBJECTIVETo evaluate the phenotype of 15 children with congenital hyperinsulinism (CHI) and profound hearing loss, known as homozygous 11p15-p14 deletion syndrome (MIM #606528).METHODSProspective clinical follow-up and genetic analysis by direct sequencing, Multiplex Ligation-dependent Probe Ampl.......CONCLUSIONSThe phenotype of homozygous 11p15-p14 deletion syndrome, or Usher-CHI syndrome, includes any severity of neonatal-onset CHI and severe, sensorineural hearing loss. Retinitis pigmentosa and nonautoimmune diabetes may occur in adolescence.......OBJECTIVETo evaluate the phenotype of 15 children with congenital hyperinsulinism (CHI) and profound hearing loss, known as homozygous 11p15-p14 deletion syndrome (MIM #606528).METHODSProspective clinical follow-up and genetic analysis by direct sequencing, Multiplex Ligation-dependent Probe...

  3. The Nature of Stable Insomnia Phenotypes

    Science.gov (United States)

    Pillai, Vivek; Roth, Thomas; Drake, Christopher L.

    2015-01-01

    Study Objectives: We examined the 1-y stability of four insomnia symptom profiles: sleep onset insomnia; sleep maintenance insomnia; combined onset and maintenance insomnia; and neither criterion (i.e., insomnia cases that do not meet quantitative thresholds for onset or maintenance problems). Insomnia cases that exhibited the same symptom profile over a 1-y period were considered to be phenotypes, and were compared in terms of clinical and demographic characteristics. Design: Longitudinal. Setting: Urban, community-based. Participants: Nine hundred fifty-four adults with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition based current insomnia (46.6 ± 12.6 y; 69.4% female). Interventions: None. Measurements and results: At baseline, participants were divided into four symptom profile groups based on quantitative criteria. Follow-up assessment 1 y later revealed that approximately 60% of participants retained the same symptom profile, and were hence judged to be phenotypes. Stability varied significantly by phenotype, such that sleep onset insomnia (SOI) was the least stable (42%), whereas combined insomnia (CI) was the most stable (69%). Baseline symptom groups (cross-sectionally defined) differed significantly across various clinical indices, including daytime impairment, depression, and anxiety. Importantly, however, a comparison of stable phenotypes (longitudinally defined) did not reveal any differences in impairment or comorbid psychopathology. Another interesting finding was that whereas all other insomnia phenotypes showed evidence of an elevated wake drive both at night and during the day, the “neither criterion” phenotype did not; this latter phenotype exhibited significantly higher daytime sleepiness despite subthreshold onset and maintenance difficulties. Conclusions: By adopting a stringent, stability-based definition, this study offers timely and important data on the longitudinal trajectory of specific insomnia phenotypes. With

  4. Cornelia de Lange Syndrome: Evolution of the Phenotype

    Science.gov (United States)

    Passarge, Eberhard; And Others

    1971-01-01

    The medical case history of a 2-year-old girl who developed, during the second year of life, the classical phenotype (typical appearance) indicative of the deLange syndrome, with both mental and physical impairment. (KW)

  5. Nanotechnological Inventions and Nanomaterials Produce A Profound Effect

    Directory of Open Access Journals (Sweden)

    VLASOV Vladimir Alexeevich

    2015-02-01

    Full Text Available The inventions in the area of nanotechnologies and nanomaterials produce a profound effect in construction, housing and communal services and adjacent economic fields as they allow us: to increase mechanical strength, coefficient of elasticity, alkali resistance and temperature of products vitrification; to obtain nanostructured coatings with the property of shape memory on the steel; to raise the dynamics of coal burning and its full burnout in the boilers of thermoelectric power station; to produce metal nanopowders with increased stored energy 10–15% etc. For example, the invention «Epoxy composition for high strength, alkali resistant structures» refers to epoxy composition used as a binder for production of high strength, thermal- and alkali-resistant glass-fiber material which can be applied in the manufacture process of construction reinforcement to strengthen concrete structures. The invention «The method to produce nanostructured reaction foil» can be used to join different materials including metal alloys, ceramics, amorphous materials and elements of microelectronic devices that are sensible to the heating. This process provides decreased labour-output ratio and energy consumption as well as the condition to manufacture foil with specified stored energy and high mechanical properties. The invention «The method of intensification of burning lowreactionary coal in the boilers of thermoelectric power station» refers to the thermal energy and can be implemented at the thermal plants. The increased dynamics of inflaming and burning leads to full burnout of powdered-coal low-reactionary fuel and decreased mechanical underfiring. The specialists may be also interested in the following inventions: fine dispersed organic suspension of carbon metal-containing nanostructures and the method to produce it; the dispersion of carbon nanotubes; the composition for reinforcement of building structures; the reinforced plate element made of

  6. Impaired spatial learning strategies and novel object recognition in mice haploinsufficient for the dual specificity tyrosine-regulated kinase-1A (Dyrk1A.

    Directory of Open Access Journals (Sweden)

    Glòria Arqué

    Full Text Available BACKGROUND: Pathogenic aneuploidies involve the concept of dosage-sensitive genes leading to over- and underexpression phenotypes. Monosomy 21 in human leads to mental retardation and skeletal, immune and respiratory function disturbances. Most of the human condition corresponds to partial monosomies suggesting that critical haploinsufficient genes may be responsible for the phenotypes. The DYRK1A gene is localized on the human chromosome 21q22.2 region, and has been proposed to participate in monosomy 21 phenotypes. It encodes a dual-specificity kinase involved in neuronal development and in adult brain physiology, but its possible role as critical haploinsufficient gene in cognitive function has not been explored. METHODOLOGY/PRINCIPAL FINDINGS: We used mice heterozygous for a Dyrk1A targeted mutation (Dyrk1A+/- to investigate the implication of this gene in the cognitive phenotypes of monosomy 21. Performance of Dyrk1A+/- mice was assayed 1/ in a navigational task using the standard hippocampally related version of the Morris water maze, 2/ in a swimming test designed to reveal potential kinesthetic and stress-related behavioral differences between control and heterozygous mice under two levels of aversiveness (25 degrees C and 17 degrees C and 3/ in a long-term novel object recognition task, sensitive to hippocampal damage. Dyrk1A+/- mice showed impairment in the development of spatial learning strategies in a hippocampally-dependent memory task, they were impaired in their novel object recognition ability and were more sensitive to aversive conditions in the swimming test than euploid control animals. CONCLUSIONS/SIGNIFICANCE: The present results are clear examples where removal of a single gene has a profound effect on phenotype and indicate that haploinsufficiency of DYRK1A might contribute to an impairment of cognitive functions and stress coping behavior in human monosomy 21.

  7. Evidence for a Broad Autism Phenotype

    NARCIS (Netherlands)

    K. de Groot (Kristel); J.W. van Strien (Jan)

    2017-01-01

    textabstractThe broad autism phenotype implies the existence of a continuum ranging from individuals displaying almost no autistic traits to severely impaired diagnosed individuals. Recent studies have linked this variation in autistic traits to several domains of functioning. However, studies

  8. phenotype correlation of methylene tetrahydrofolate reductase ...

    African Journals Online (AJOL)

    Rabah M. Shawky

    2014-06-21

    Jun 21, 2014 ... children with autism and to correlate them with different phenotypes. Subjects and ... of impairments in communication, reciprocal social interac- tions, and ... isolation was obtained from peripheral blood samples using the spin ... IQ, while ten of them (50%) had mild mental retardation and six patients (30%) ...

  9. The nature of stable insomnia phenotypes.

    Science.gov (United States)

    Pillai, Vivek; Roth, Thomas; Drake, Christopher L

    2015-01-01

    We examined the 1-y stability of four insomnia symptom profiles: sleep onset insomnia; sleep maintenance insomnia; combined onset and maintenance insomnia; and neither criterion (i.e., insomnia cases that do not meet quantitative thresholds for onset or maintenance problems). Insomnia cases that exhibited the same symptom profile over a 1-y period were considered to be phenotypes, and were compared in terms of clinical and demographic characteristics. Longitudinal. Urban, community-based. Nine hundred fifty-four adults with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition based current insomnia (46.6 ± 12.6 y; 69.4% female). None. At baseline, participants were divided into four symptom profile groups based on quantitative criteria. Follow-up assessment 1 y later revealed that approximately 60% of participants retained the same symptom profile, and were hence judged to be phenotypes. Stability varied significantly by phenotype, such that sleep onset insomnia (SOI) was the least stable (42%), whereas combined insomnia (CI) was the most stable (69%). Baseline symptom groups (cross-sectionally defined) differed significantly across various clinical indices, including daytime impairment, depression, and anxiety. Importantly, however, a comparison of stable phenotypes (longitudinally defined) did not reveal any differences in impairment or comorbid psychopathology. Another interesting finding was that whereas all other insomnia phenotypes showed evidence of an elevated wake drive both at night and during the day, the 'neither criterion' phenotype did not; this latter phenotype exhibited significantly higher daytime sleepiness despite subthreshold onset and maintenance difficulties. By adopting a stringent, stability-based definition, this study offers timely and important data on the longitudinal trajectory of specific insomnia phenotypes. With the exception of daytime sleepiness, few clinical differences are apparent across stable phenotypes.

  10. Transitioning hearing aid users with severe and profound loss to a new gain/frequency response: benefit, perception, and acceptance.

    Science.gov (United States)

    Convery, Elizabeth; Keidser, Gitte

    2011-03-01

    Adults with severe and profound hearing loss tend to be long-term, full-time users of amplification who are highly reliant on their hearing aids. As a result of these characteristics, they are often reluctant to update their hearing aids when new features or signal-processing algorithms become available. Due to the electroacoustic constraints of older devices, many severely and profoundly hearing-impaired adults continue to wear hearing aids that provide more low- and mid-frequency gain and less high-frequency gain than would be prescribed by the National Acoustic Laboratories' revised formula with profound correction factor (NAL-RP). To investigate the effect of a gradual change in gain/frequency response on experienced hearing-aid wearers with moderately severe to profound hearing loss. Double-blind, randomized controlled trial. Twenty-three experienced adult hearing-aid users with severe and profound hearing loss participated in the study. Participants were selected for inclusion in the study if the gain/frequency response of their own hearing aids differed significantly from their NAL-RP prescription. Participants were assigned either to a control or to an experimental group balanced for aided ear three-frequency pure-tone average (PTA) and age. Participants were fitted with Siemens Artis 2 SP behind-the-ear (BTE) hearing aids that were matched to the gain/frequency response of their own hearing aids for a 65 dB SPL input level. The experimental group progressed incrementally to their NAL-RP targets over the course of 15 wk, while the control group maintained their initial settings throughout the study. Aided speech discrimination testing, loudness scaling, and structured questionnaires were completed at 3, 6, 9, 12, and 15 wk postfitting. A paired comparison between the old and new gain/frequency responses was completed at 1 and 15 wk postfitting. Statistical analysis was conducted to examine differences between the experimental and control groups and changes

  11. A Replication to Increase Happiness Indices among Some People with Profound Multiple Disabilities.

    Science.gov (United States)

    Ivancic, Martin T.; And Others

    1997-01-01

    The happiness indices in a Fun Time activity were systematically increased for three of four people with profound multiple disabilities by providing their preferred stimuli. The fourth showed decreased unhappiness. However, three people with profound disabilities and minimal movement failed to show any indices of happiness or unhappiness.…

  12. Teaching Individuals with Profound Multiple Disabilities to Access Preferred Stimuli with Multiple Microswitches

    Science.gov (United States)

    Tam, Gee May; Phillips, Katrina J.; Mudford, Oliver C.

    2011-01-01

    We replicated and extended previous research on microswitch facilitated choice making by individuals with profound multiple disabilities. Following an assessment of stimulus preferences, we taught 6 adults with profound multiple disabilities to emit 2 different responses to activate highly preferred stimuli. All participants learnt to activate…

  13. Visual Impairment

    Science.gov (United States)

    ... site Sitio para adolescentes Body Mind Sexual Health Food & Fitness Diseases & Conditions Infections Drugs & Alcohol School & Jobs Sports Expert Answers (Q&A) Staying Safe Videos for Educators Search English Español Visual Impairment KidsHealth / For Teens / Visual Impairment What's in ...

  14. Classic Bartter syndrome complicated with profound growth hormone deficiency: a case report.

    Science.gov (United States)

    Adachi, Masanori; Tajima, Toshihiro; Muroya, Koji; Asakura, Yumi

    2013-12-30

    Classic Bartter syndrome is a salt-wasting tubulopathy caused by mutations in the CLCNKB (chloride channel Kb) gene. Although growth hormone deficiency has been suggested as a cause for persistent growth failure in patients with classic Bartter syndrome, in our opinion the diagnoses of growth hormone deficiency has been unconvincing in some reports. Moreover, Gitelman syndrome seems to have been confused with Bartter syndrome in some cases in the literature. In the present work, we describe a new case with CLCNKB gene mutations and review the reported cases of classic Bartter syndrome associated with growth hormone deficiency. Our patient was a Japanese boy diagnosed as having classic Bartter syndrome at eight months of age. The diagnosis of Bartter syndrome was confirmed by CLCNKB gene analysis, which revealed compound heterozygous mutations with deletion of exons 1 to 3 (derived from his mother) and ΔL130 (derived from his father). His medical therapy consisted of potassium (K), sodium chloride, spironolactone, and anti-inflammatory agents; this regime was started at eight months of age. Our patient was very short (131.1cm, -4.9 standard deviation) at 14.3 years and showed profoundly impaired growth hormone responses to pharmacological stimulants: 0.15μg/L to insulin-induced hypoglycemia and 0.39μg/L to arginine. His growth response to growth hormone therapy was excellent. The present case strengthens the association between classic Bartter syndrome and growth hormone deficiency. We propose that growth hormone status should be considered while treating children with classic Bartter syndrome.

  15. A Recurrent De Novo Variant in NACC1 Causes a Syndrome Characterized by Infantile Epilepsy, Cataracts, and Profound Developmental Delay.

    Science.gov (United States)

    Schoch, Kelly; Meng, Linyan; Szelinger, Szabolcs; Bearden, David R; Stray-Pedersen, Asbjorg; Busk, Oyvind L; Stong, Nicholas; Liston, Eriskay; Cohn, Ronald D; Scaglia, Fernando; Rosenfeld, Jill A; Tarpinian, Jennifer; Skraban, Cara M; Deardorff, Matthew A; Friedman, Jeremy N; Akdemir, Zeynep Coban; Walley, Nicole; Mikati, Mohamad A; Kranz, Peter G; Jasien, Joan; McConkie-Rosell, Allyn; McDonald, Marie; Wechsler, Stephanie Burns; Freemark, Michael; Kansagra, Sujay; Freedman, Sharon; Bali, Deeksha; Millan, Francisca; Bale, Sherri; Nelson, Stanley F; Lee, Hane; Dorrani, Naghmeh; Goldstein, David B; Xiao, Rui; Yang, Yaping; Posey, Jennifer E; Martinez-Agosto, Julian A; Lupski, James R; Wangler, Michael F; Shashi, Vandana

    2017-02-02

    Whole-exome sequencing (WES) has increasingly enabled new pathogenic gene variant identification for undiagnosed neurodevelopmental disorders and provided insights into both gene function and disease biology. Here, we describe seven children with a neurodevelopmental disorder characterized by microcephaly, profound developmental delays and/or intellectual disability, cataracts, severe epilepsy including infantile spasms, irritability, failure to thrive, and stereotypic hand movements. Brain imaging in these individuals reveals delay in myelination and cerebral atrophy. We observe an identical recurrent de novo heterozygous c.892C>T (p.Arg298Trp) variant in the nucleus accumbens associated 1 (NACC1) gene in seven affected individuals. One of the seven individuals is mosaic for this variant. NACC1 encodes a transcriptional repressor implicated in gene expression and has not previously been associated with germline disorders. The probability of finding the same missense NACC1 variant by chance in 7 out of 17,228 individuals who underwent WES for diagnoses of neurodevelopmental phenotypes is extremely small and achieves genome-wide significance (p = 1.25 × 10 -14 ). Selective constraint against missense variants in NACC1 makes this excess of an identical missense variant in all seven individuals more remarkable. Our findings are consistent with a germline recurrent mutational hotspot associated with an allele-specific neurodevelopmental phenotype in NACC1. Copyright © 2017 American Society of Human Genetics. All rights reserved.

  16. Maternal supplementation with conjugated linoleic acid in the setting of diet-induced obesity normalises the inflammatory phenotype in mothers and reverses metabolic dysfunction and impaired insulin sensitivity in offspring.

    Science.gov (United States)

    Segovia, Stephanie A; Vickers, Mark H; Zhang, Xiaoyuan D; Gray, Clint; Reynolds, Clare M

    2015-12-01

    Maternal consumption of a high-fat diet significantly impacts the fetal environment and predisposes offspring to obesity and metabolic dysfunction during adulthood. We examined the effects of a high-fat diet during pregnancy and lactation on metabolic and inflammatory profiles and whether maternal supplementation with the anti-inflammatory lipid conjugated linoleic acid (CLA) could have beneficial effects on mothers and offspring. Sprague-Dawley rats were fed a control (CD; 10% kcal from fat), CLA (CLA; 10% kcal from fat, 1% total fat as CLA), high-fat (HF; 45% kcal from fat) or high fat with CLA (HFCLA; 45% kcal from fat, 1% total fat as CLA) diet ad libitum 10days prior to and throughout gestation and lactation. Dams and offspring were culled at either late gestation (fetal day 20, F20) or early postweaning (postnatal day 24, P24). CLA, HF and HFCLA dams were heavier than CD throughout gestation. Plasma concentrations of proinflammatory cytokines interleukin-1β and tumour necrosis factor-α were elevated in HF dams, with restoration in HFCLA dams. Male and female fetuses from HF dams were smaller at F20 but displayed catch-up growth and impaired insulin sensitivity at P24, which was reversed in HFCLA offspring. HFCLA dams at P24 were protected from impaired insulin sensitivity as compared to HF dams. Maternal CLA supplementation normalised inflammation associated with consumption of a high-fat diet and reversed associated programming of metabolic dysfunction in offspring. This demonstrates that there are critical windows of developmental plasticity in which the effects of an adverse early-life environment can be reversed by maternal dietary interventions. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Misperceiving Bullshit as Profound Is Associated with Favorable Views of Cruz, Rubio, Trump and Conservatism.

    Directory of Open Access Journals (Sweden)

    Stefan Pfattheicher

    Full Text Available The present research investigates the associations between holding favorable views of potential Democratic or Republican candidates for the US presidency 2016 and seeing profoundness in bullshit statements. In this contribution, bullshit is used as a technical term which is defined as communicative expression that lacks content, logic, or truth from the perspective of natural science. We used the Bullshit Receptivity scale (BSR to measure seeing profoundness in bullshit statements. The BSR scale contains statements that have a correct syntactic structure and seem to be sound and meaningful on first reading but are actually vacuous. Participants (N = 196; obtained via Amazon Mechanical Turk rated the profoundness of bullshit statements (using the BSR and provided favorability ratings of three Democratic (Hillary Clinton, Martin O'Malley, and Bernie Sanders and three Republican candidates for US president (Ted Cruz, Marco Rubio, and Donald Trump. Participants also completed a measure of political liberalism/conservatism. Results revealed that favorable views of all three Republican candidates were positively related to judging bullshit statements as profound. The smallest correlation was found for Donald Trump. Although we observe a positive association between bullshit and support for the three Democrat candidates, this relationship is both substantively small and statistically insignificant. The general measure of political liberalism/conservatism was also related to judging bullshit statements as profound in that individuals who were more politically conservative had a higher tendency to see profoundness in bullshit statements. Of note, these results were not due to a general tendency among conservatives to see profoundness in everything: Favorable views of Republican candidates and conservatism were not significantly related to profoundness ratings of mundane statements. In contrast, this was the case for Hillary Clinton and Martin O

  18. Misperceiving Bullshit as Profound Is Associated with Favorable Views of Cruz, Rubio, Trump and Conservatism.

    Science.gov (United States)

    Pfattheicher, Stefan; Schindler, Simon

    2016-01-01

    The present research investigates the associations between holding favorable views of potential Democratic or Republican candidates for the US presidency 2016 and seeing profoundness in bullshit statements. In this contribution, bullshit is used as a technical term which is defined as communicative expression that lacks content, logic, or truth from the perspective of natural science. We used the Bullshit Receptivity scale (BSR) to measure seeing profoundness in bullshit statements. The BSR scale contains statements that have a correct syntactic structure and seem to be sound and meaningful on first reading but are actually vacuous. Participants (N = 196; obtained via Amazon Mechanical Turk) rated the profoundness of bullshit statements (using the BSR) and provided favorability ratings of three Democratic (Hillary Clinton, Martin O'Malley, and Bernie Sanders) and three Republican candidates for US president (Ted Cruz, Marco Rubio, and Donald Trump). Participants also completed a measure of political liberalism/conservatism. Results revealed that favorable views of all three Republican candidates were positively related to judging bullshit statements as profound. The smallest correlation was found for Donald Trump. Although we observe a positive association between bullshit and support for the three Democrat candidates, this relationship is both substantively small and statistically insignificant. The general measure of political liberalism/conservatism was also related to judging bullshit statements as profound in that individuals who were more politically conservative had a higher tendency to see profoundness in bullshit statements. Of note, these results were not due to a general tendency among conservatives to see profoundness in everything: Favorable views of Republican candidates and conservatism were not significantly related to profoundness ratings of mundane statements. In contrast, this was the case for Hillary Clinton and Martin O'Malley. Overall, small

  19. Impaired Driving

    Science.gov (United States)

    ... Get the Facts What Works: Strategies to Increase Car Seat and Booster Seat ... narcotics. 3 That’s one percent of the 111 million self-reported episodes of alcohol-impaired driving among U.S. ...

  20. Pro-social 50-kHz ultrasonic communication in rats: Post-weaning but not post-adolescent social isolation leads to social impairmentsphenotypic rescue by re-socialization

    Directory of Open Access Journals (Sweden)

    Dominik eSeffer

    2015-05-01

    Full Text Available Rats are highly social animals and social play during adolescence has an important role for social development, hence post-weaning social isolation is widely used to study the adverse effects of juvenile social deprivation and to induce behavioral phenotypes relevant to neuropsychiatric disorders, like schizophrenia. Communication is an important component of the rat’s social behavior repertoire, with ultrasonic vocalizations (USV serving as situation-dependent affective signals. High-frequency 50-kHz USV occur in appetitive situations and induce approach behavior, supporting the notion that they serve as social contact calls; however, post-weaning isolation effects on the behavioral changes displayed by the receiver in response to USV have yet to be studied. We therefore investigated the impact of post-weaning isolation on socio-affective information processing as assessed by means of our established 50-kHz USV radial maze playback paradigm. We showed that post-weaning social isolation specifically affected the behavioral response to playback of pro-social 50-kHz but not alarm 22-kHz USV. While group-housed rats showed the expected preference, i.e. approach, towards 50-kHz USV, the response was even stronger in short-term isolated rats (i.e. 1 day, possibly due to a higher level of social motivation. In contrast, no approach was observed in long-term isolated rats (i.e. 4 weeks. Importantly, deficits in approach were reversed by peer-mediated re-socialization and could not be observed after post-adolescent social isolation, indicating a critical period for social development during adolescence. Together, these results highlight the importance of social experience for affiliative behavior, suggesting a critical involvement of play behavior on socio-affective information processing in rats.

  1. Reversal of profound rocuronium neuromuscular blockade by sugammadex in anesthetized rhesus monkeys.

    NARCIS (Netherlands)

    Boer, H.D. de; Egmond, J. van; Pol, F. van de; Bom, A.; Booij, L.H.D.J.

    2006-01-01

    BACKGROUND: Reversal of neuromuscular blockade can be accomplished by chemical encapsulation of rocuronium by sugammadex, a synthetic gamma-cyclodextrin derivative. The current study determined the feasibility of reversal of rocuronium-induced profound neuromuscular blockade with sugammadex in the

  2. Asthma phenotypes in childhood.

    Science.gov (United States)

    Reddy, Monica B; Covar, Ronina A

    2016-04-01

    This review describes the literature over the past 18 months that evaluated childhood asthma phenotypes, highlighting the key aspects of these studies, and comparing these studies to previous ones in this area. Recent studies on asthma phenotypes have identified new phenotypes on the basis of statistical analyses (using cluster analysis and latent class analysis methodology) and have evaluated the outcomes and associated risk factors of previously established early childhood asthma phenotypes that are based on asthma onset and patterns of wheezing illness. There have also been investigations focusing on immunologic, physiologic, and genetic correlates of various phenotypes, as well as identification of subphenotypes of severe childhood asthma. Childhood asthma remains a heterogeneous condition, and investigations into these various presentations, risk factors, and outcomes are important since they can offer therapeutic and prognostic relevance. Further investigation into the immunopathology and genetic basis underlying childhood phenotypes is important so therapy can be tailored accordingly.

  3. The combination of vestibular impairment and congenital sensorineural hearing loss predisposes patients to ocular anomalies, including Usher syndrome.

    Science.gov (United States)

    Kletke, S; Batmanabane, V; Dai, T; Vincent, A; Li, S; Gordon, K A; Papsin, B C; Cushing, S L; Héon, E

    2017-07-01

    The co-occurrence of hearing impairment and visual dysfunction is devastating. Most deaf-blind etiologies are genetically determined, the commonest being Usher syndrome (USH). While studies of the congenitally deaf population reveal a variable degree of visual problems, there are no effective ophthalmic screening guidelines. We hypothesized that children with congenital sensorineural hearing loss (SNHL) and vestibular impairment were at an increased risk of having USH. A retrospective chart review of 33 cochlear implants recipients for severe to profound SNHL and measured vestibular dysfunction was performed to determine the ocular phenotype. All the cases had undergone ocular examination and electroretinogram (ERG). Patients with an abnormal ERG underwent genetic testing for USH. We found an underlying ocular abnormality in 81.81% (27/33) of cases; of which 75% had refractive errors, and 50% of those patients showed visual improvement with refractive correction. A total of 14 cases (42.42%; 14/33) had generalized rod-cone dysfunction on ERG suggestive of Usher syndrome type 1, confirmed by mutational analysis. This work shows that adding vestibular impairment as a criterion for requesting an eye exam and adding the ERG to detect USH increases the chances of detecting ocular anomalies, when compared with previous literature focusing only on congenital SNHL. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Physical Impairment

    Science.gov (United States)

    Trewin, Shari

    Many health conditions can lead to physical impairments that impact computer and Web access. Musculoskeletal conditions such as arthritis and cumulative trauma disorders can make movement stiff and painful. Movement disorders such as tremor, Parkinsonism and dystonia affect the ability to control movement, or to prevent unwanted movements. Often, the same underlying health condition also has sensory or cognitive effects. People with dexterity impairments may use a standard keyboard and mouse, or any of a wide range of alternative input mechanisms. Examples are given of the diverse ways that specific dexterity impairments and input mechanisms affect the fundamental actions of Web browsing. As the Web becomes increasingly sophisticated, and physically demanding, new access features at the Web browser and page level will be necessary.

  5. Postural control in children with typical development and children with profound hearing loss

    Directory of Open Access Journals (Sweden)

    Monteiro de Sousa AM

    2012-05-01

    Full Text Available Aneliza Maria Monteiro de Sousa,1 Jônatas de França Barros,2 Brígido Martins de Sousa Neto31Faculty of Health Sciences, University of Brasilia, Brasilia, Federal District, Brazil; 2Department of Physical Education at the Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil; 3University Center UNIEURO, Brasilia, Federal District, BrazilPurpose: To describe the behavior of the postural control in children with profound sensorineural hearing loss and compare the results of experimental tests with hearing children aged 7 to 10 years.Patients and methods: This is a cross-sectional study where 100 children were divided into experimental and control groups. We used a force platform, AccuSway Plus, where the tests were conducted under the experimental conditions: open base, eyes open (OBEO; open base, eyes closed (OBEC; closed base, eyes open (CBEO; closed base, eyes closed (CBEC. The body sway velocity (V of the center of pressure, the displacement in the anteroposterior direction (COPap and mediolateral (COPml of the center of pressure were the parameters to evaluate the postural control. For statistical analysis we used the nonparametric Mann–Whitney U test, with a significance level of 5%.Results: In comparisons of variables between the groups, the experimental group outperformed by at least 75% of the control group values. In terms of global trends, the experimental group shows higher values of body oscillations in all experimental conditions and variables evaluated. Children with hearing loss had poorer balance performance compared to the group of hearing. The inferential analysis revealed a statistically significant difference in the balance between deaf and hearing children in the OBEC experimental condition in relation to the COPml parameter (P = 0.04. There were no statistically significant differences in comparisons between the sexes when the groups were analyzed separately. The prevalence of unknown etiology

  6. Experience with cochlear implants in Greenlanders with profound hearing loss living in Greenland

    Directory of Open Access Journals (Sweden)

    Preben Homøe

    2013-08-01

    Full Text Available Objective. Cochlear implant (CI treatment was introduced to the world in the 1980s and has become a routine treatment for congenital or acquired severe-to-profound hearing loss. CI treatment requires access to a highly skilled team of ear, nose and throat specialists, audiologists and speech-language pathologists for evaluation, surgery and rehabilitation. In particular, children treated with CI are in need of long-term post-operative auditory training and other follow-up support. Design. The study is retrospective with updated information on present performance. Results. Since 2001, a total of 11 Greenlandic patients living in Greenland have been treated with CI, 7 children and 4 adults. Of these children, 4 use oral communication only and are full-time CI-users, 2 with full-time use of CI are still in progress with use of oral communication, and 1 has not acquired oral language yet, but has started auditory and speech training. Six children attend mainstream public school while one child is in kindergarten. Of the adults, only 1 has achieved good speech perception with full-time use of CI while 3 do not use the CI. Discussion. From an epidemiological point of view, approximately 1–3 children below 6 years are in need of a CI every second year in Greenland often due to sequelae from meningitis, which may cause postinfectious deafness. Screening of new-borns for hearing has been started in Greenland establishing the basis for early diagnosis of congenital hearing impairment and subsequent intervention. The logistics and lack of availability of speech therapists in Greenland hampers possibilities for optimal language and speech therapy of CI patients in Greenland. This study aims at describing the results of CI treatment in Greenlanders and the outcome of the CI operations along with the auditory and speech/language outcomes. Finally, we present a suggestion for the future CI treatment and recommendations for an increased effort in the

  7. 1Protein Energy Malnutrition Impairs Homeostatic Proliferation of Memory CD8 T cells

    Science.gov (United States)

    Iyer, Smita S.; Chatraw, Janel Hart; Tan, Wendy G.; Wherry, E. John; Becker, Todd C.; Ahmed, Rafi; Kapasi, Zoher F.

    2011-01-01

    Nutrition is a critical but poorly understood determinant of immunity. There is abundant epidemiological evidence linking protein malnutrition to impaired vaccine efficacy and increased susceptibility to infections; yet, the role of dietary protein in immune memory homeostasis remains poorly understood. Here we show that protein energy malnutrition (PEM) induced in mice by low-protein (LP) feeding has a detrimental impact on CD8 memory. Relative to adequate-protein (AP) fed controls, LP feeding in lymphocytic choriomeningitis virus (LCMV) immune mice resulted in a 2-fold decrease in LCMV-specific CD8 memory T cells. Adoptive transfer of memory cells, labeled with a division tracking dye, from AP mice into naive LP or AP mice demonstrated that PEM caused profound defects in homeostatic proliferation. Remarkably, this defect occurred despite the lymphopenic environment in LP hosts. While antigen-specific memory cells in LP and AP hosts were phenotypically similar, memory cells in LP hosts were markedly less-responsive to poly(I:C)-induced acute proliferative signals. Furthermore, upon recall, memory cells in LP hosts displayed reduced proliferation and protection from challenge with LCMV-clone 13 resulting in impaired viral clearance in the liver. The findings show a metabolic requirement of dietary protein in sustaining functional CD8 memory and suggest that interventions to optimize dietary protein intake may improve vaccine efficacy in malnourished individuals. PMID:22116826

  8. Protein energy malnutrition impairs homeostatic proliferation of memory CD8 T cells.

    Science.gov (United States)

    Iyer, Smita S; Chatraw, Janel Hart; Tan, Wendy G; Wherry, E John; Becker, Todd C; Ahmed, Rafi; Kapasi, Zoher F

    2012-01-01

    Nutrition is a critical but poorly understood determinant of immunity. There is abundant epidemiological evidence linking protein malnutrition to impaired vaccine efficacy and increased susceptibility to infections; yet, the role of dietary protein in immune memory homeostasis remains poorly understood. In this study, we show that protein-energy malnutrition induced in mice by low-protein (LP) feeding has a detrimental impact on CD8 memory. Relative to adequate protein (AP)-fed controls, LP feeding in lymphocytic choriomeningitis virus (LCMV)-immune mice resulted in a 2-fold decrease in LCMV-specific CD8 memory T cells. Adoptive transfer of memory cells, labeled with a division tracking dye, from AP mice into naive LP or AP mice demonstrated that protein-energy malnutrition caused profound defects in homeostatic proliferation. Remarkably, this defect occurred despite the lymphopenic environment in LP hosts. Whereas Ag-specific memory cells in LP and AP hosts were phenotypically similar, memory cells in LP hosts were markedly less responsive to polyinosinic-polycytidylic acid-induced acute proliferative signals. Furthermore, upon recall, memory cells in LP hosts displayed reduced proliferation and protection from challenge with LCMV-clone 13, resulting in impaired viral clearance in the liver. The findings show a metabolic requirement of dietary protein in sustaining functional CD8 memory and suggest that interventions to optimize dietary protein intake may improve vaccine efficacy in malnourished individuals.

  9. Novel mutation in Sjogren-Larsson syndrome is associated with divergent neurologic phenotypes.

    Science.gov (United States)

    Davis, Kathleen; Holden, Kenton R; S'Aulis, Dana; Amador, Claudia; Matheus, M Gisele; Rizzo, William B

    2013-10-01

    Sjögren-Larsson syndrome is an inherited disorder of lipid metabolism caused by mutations in the ALDH3A2 gene that codes for fatty aldehyde dehydrogenase, which results in accumulation of fatty aldehydes and alcohols and is characterized by ichthyosis, intellectual disability, and spastic diplegia/quadriplegia. The authors describe 2 unrelated Honduran patients who carried the same novel homozygous nonsense mutation (c.1309A>T, p.K437X) and ALDH3A2 DNA haplotype, but widely differed in disease severity. One patient exhibited spastic quadriplegia with unusual neuroregression, whereas the other patient had the usual static form of spastic diplegia with neurodevelopmental disabilities. Biochemical analyses showed a similar profound deficiency of fatty aldehyde dehydrogenase activity and impaired fatty alcohol metabolism in both patients' cultured fibroblasts. These results indicate that variation in the neurologic phenotype of Sjögren-Larsson syndrome is not strictly determined by the ALDH3A2 mutation or the biochemical defect as expressed in cultured fibroblasts, but by unidentified epigenetic/environmental factors, gene modifiers, or other mechanisms.

  10. Clinical phenotypes of asthma

    NARCIS (Netherlands)

    Bel, Elisabeth H.

    2004-01-01

    PURPOSE OF REVIEW: Asthma is a phenotypically heterogeneous disorder and, over the years, many different clinical subtypes of asthma have been described. A precise definition of asthma phenotypes is now becoming more and more important, not only for a better understanding of pathophysiologic

  11. [Inadequacy of the paradigms of special education to subjects with severe and profound grade intellectual disability - the need for pragmatic realism in psychiatry and special pedagogy].

    Science.gov (United States)

    Sipowicz, Kasper; Żuraw, Hanna; Witusik, Andrzej; Mokros, Łukasz; Najbert, Edyta; Pietras, Tadeusz

    2018-05-25

    People with severe and profound grade disabilities are the subject of interest in psychiatry, clinical psychology and special pedagogy. Unfortunately, the paradigmatic approach to special education based on postmodern philosophy is in contrast to the biomedical approach that is based on the positivist and Cartesian models. The paper is an attempt to systematize the similarities and differences between the humanistic approach and the modern biomedical model, which, despite the apparent differences, do not differ so much from each other. Work with a person disabled intellectually in the severe or profound degree is governed by the principles of methodical realism, taking into account to an equal extent the principal deficits, the concomitant diseases, limitations and the social context. The deeper the impairment and disability is, the smaller is the role of the humanistic paradigm in work with the client in the medical management and educational process. Changing the paradigms of special pedagogy has drawn attention to the social context of disability, separating, however, special pedagogy from modern medicine and psychology, cognitive-oriented and psychometry-based. The postmodern paradigm has become an ideology, which makes it difficult to work with deeply disabled people. Only the multidirectional approach including a variety of paradigms makes it possible to provide integrational aid to people with severe and profound grade intellectual disabilities. Working with such a disabled person should take into account equally the biomedical and humanistic aspects. © 2018 MEDPRESS.

  12. DMPD: Gram-negative endotoxin: an extraordinary lipid with profound effects oneukaryotic signal transduction. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 1916089 Gram-negative endotoxin: an extraordinary lipid with profound effects oneuk...ep;5(12):2652-60. (.png) (.svg) (.html) (.csml) Show Gram-negative endotoxin: an extraordinary lipid with profound effects...tive endotoxin: an extraordinary lipid with profound effects oneukaryotic signal transduction. Authors Raetz

  13. ProFound: Source Extraction and Application to Modern Survey Data

    Science.gov (United States)

    Robotham, A. S. G.; Davies, L. J. M.; Driver, S. P.; Koushan, S.; Taranu, D. S.; Casura, S.; Liske, J.

    2018-05-01

    We introduce PROFOUND, a source finding and image analysis package. PROFOUND provides methods to detect sources in noisy images, generate segmentation maps identifying the pixels belonging to each source, and measure statistics like flux, size, and ellipticity. These inputs are key requirements of PROFIT, our recently released galaxy profiling package, where the design aim is that these two software packages will be used in unison to semi-automatically profile large samples of galaxies. The key novel feature introduced in PROFOUND is that all photometry is executed on dilated segmentation maps that fully contain the identifiable flux, rather than using more traditional circular or ellipse-based photometry. Also, to be less sensitive to pathological segmentation issues, the de-blending is made across saddle points in flux. We apply PROFOUND in a number of simulated and real-world cases, and demonstrate that it behaves reasonably given its stated design goals. In particular, it offers good initial parameter estimation for PROFIT, and also segmentation maps that follow the sometimes complex geometry of resolved sources, whilst capturing nearly all of the flux. A number of bulge-disc decomposition projects are already making use of the PROFOUND and PROFIT pipeline, and adoption is being encouraged by publicly releasing the software for the open source R data analysis platform under an LGPL-3 license on GitHub (github.com/asgr/ProFound).

  14. A Prognostic Model for Development of Profound Shock among Children Presenting with Dengue Shock Syndrome.

    Directory of Open Access Journals (Sweden)

    Phung Khanh Lam

    Full Text Available To identify risk factors and develop a prediction model for the development of profound and recurrent shock amongst children presenting with dengue shock syndrome (DSS.We analyzed data from a prospective cohort of children with DSS recruited at the Paediatric Intensive Care Unit of the Hospital for Tropical Disease in Ho Chi Minh City, Vietnam. The primary endpoint was "profound DSS", defined as ≥2 recurrent shock episodes (for subjects presenting in compensated shock, or ≥1 recurrent shock episodes (for subjects presenting initially with decompensated/hypotensive shock, and/or requirement for inotropic support. Recurrent shock was evaluated as a secondary endpoint. Risk factors were pre-defined clinical and laboratory variables collected at the time of presentation with shock. Prognostic model development was based on logistic regression and compared to several alternative approaches.The analysis population included 1207 children of whom 222 (18% progressed to "profound DSS" and 433 (36% had recurrent shock. Independent risk factors for both endpoints included younger age, earlier presentation, higher pulse rate, higher temperature, higher haematocrit and, for females, worse hemodynamic status at presentation. The final prognostic model for "profound DSS" showed acceptable discrimination (AUC=0.69 for internal validation and calibration and is presented as a simple score-chart.Several risk factors for development of profound or recurrent shock among children presenting with DSS were identified. The score-chart derived from the prognostic models should improve triage and management of children presenting with DSS in dengue-endemic areas.

  15. Attuning: A Communication Process between People with Severe and Profound Intellectual Disability and Their Interaction Partners.

    Science.gov (United States)

    Griffiths, Colin; Smith, Martine

    2016-03-01

    People with severe and profound intellectual disability typically demonstrate a limited ability to communicate effectively. Most of their communications are non-verbal, often idiosyncratic and ambiguous. This article aims to identify the process that regulates communications of this group of people with others and to describe the methodological approach that was used to achieve this. In this qualitative study, two dyads consisting of a person with severe or profound intellectual and multiple disability and a teacher or carer were filmed as they engaged in school-based activities. Two 1-hour videotapes were transcribed and analysed using grounded theory. Attuning was identified within the theory proposed here as a central process that calibrates and regulates communication. Attuning is conceptualized as a bidirectional, dyadic communication process. Understanding this process may support more effective communication between people with severe or profound intellectual and multiple disability and their interaction partners. © 2015 John Wiley & Sons Ltd.

  16. Prevalence of Auditory Neuropathy in a Population of Children with Severe to Profound Hearing Loss

    Directory of Open Access Journals (Sweden)

    Nader Saki

    2013-04-01

    Full Text Available Background: The purpose of this investigation is to determine auditory neuropathy in the students with severe to profound hearing losses in Ahwaz.Materials and Methods: In this cross-sectional study, 212 children of 7-11 year old with severe to profound hearing loss performed ordinary audiometric evaluations as well as ABR and OAE. The patients with normal DPOAE who had no record of acoustic reflex having normal ABR, were considered as the patients with auditory neuropathy. Results: The neuropathic complication found in 14 children was appeared in 8 ones as one-sided (57.14% and in 6 ones (42.86% as two-sided. 68% of the patients as diagnosed had a very low Speech Discrimination Score (SDS.Conclusion: we must be very vigilant in auditory neuropathy diagnosis for the purpose to be successful in appropriate treatment of severe to profound hearing losses.

  17. Targeting phenotypically tolerant Mycobacterium tuberculosis

    Science.gov (United States)

    Gold, Ben; Nathan, Carl

    2016-01-01

    While the immune system is credited with averting tuberculosis in billions of individuals exposed to Mycobacterium tuberculosis, the immune system is also culpable for tempering the ability of antibiotics to deliver swift and durable cure of disease. In individuals afflicted with tuberculosis, host immunity produces diverse microenvironmental niches that support suboptimal growth, or complete growth arrest, of M. tuberculosis. The physiological state of nonreplication in bacteria is associated with phenotypic drug tolerance. Many of these host microenvironments, when modeled in vitro by carbon starvation, complete nutrient starvation, stationary phase, acidic pH, reactive nitrogen intermediates, hypoxia, biofilms, and withholding streptomycin from the streptomycin-addicted strain SS18b, render M. tuberculosis profoundly tolerant to many of the antibiotics that are given to tuberculosis patients in a clinical setting. Targeting nonreplicating persisters is anticipated to reduce the duration of antibiotic treatment and rate of post-treatment relapse. Some promising drugs to treat tuberculosis, such as rifampicin and bedaquiline, only kill nonreplicating M. tuberculosis in vitro at concentrations far greater than their minimal inhibitory concentrations against replicating bacilli. There is an urgent demand to identify which of the currently used antibiotics, and which of the molecules in academic and corporate screening collections, have potent bactericidal action on nonreplicating M. tuberculosis. With this goal, we review methods of high throughput screening to target nonreplicating M. tuberculosis and methods to progress candidate molecules. A classification based on structures and putative targets of molecules that have been reported to kill nonreplicating M. tuberculosis revealed a rich diversity in pharmacophores. However, few of these compounds were tested under conditions that would exclude the impact of adsorbed compound acting during the recovery phase of

  18. Family influences on the cognitive development of profoundly deaf children: exploring the effects of socioeconomic status and siblings.

    Science.gov (United States)

    Macaulay, Catrin E; Ford, Ruth M

    2013-10-01

    We evaluated the cognitive development of 48 profoundly deaf children from hearing families (born 1994-2002, mean age M = 8.0 years at time of test, none of whom had received early auditory-verbal therapy) as a function of family socioeconomic status and number of siblings. Overall, the deaf children matched a younger group of 47 hearing controls (M = 4.6 years) on verbal ability, theory of mind, and cognitive inhibition. Partial correlations (controlling for age) revealed positive relations in the hearing group between maternal education and inhibition, between number of younger siblings and references to emotions, and between number of close-in-age siblings and references to desires and false beliefs. In the deaf group, there were positive relations between household income and memory span, between maternal education and references to false beliefs, and between number of younger siblings and nonverbal ability. In contrast, deaf children with a greater number of older siblings aged ≤12 years showed inferior memory span, inhibition, belief understanding, picture-sequencing accuracy, and mental-state language, suggesting that they failed to compete successfully with older siblings for their parents' attention and material resources. We consider the implications of the findings for understanding birth-order effects on deaf and language-impaired children.

  19. Classroom Procedures for the Measurement of Behavior State among Students with Profound Disabilities.

    Science.gov (United States)

    Guy, Barbara; And Others

    1993-01-01

    This study examined whether teacher-implemented classroom measurement procedures of short duration are as reliable as methods used in research studies to determine behavior state (e.g., awake active, awake inactive, asleep, drowsed) of six students with profound mental disabilities. Results indicated that more frequent but briefer measurements…

  20. The Role of Sound in Residential Facilities for People With Profound Intellectual and Multiple Disabilities

    NARCIS (Netherlands)

    van den Bosch, Kirsten A.; Andringa, Tjeerd C.; Baskent, Deniz; Vlaskamp, Carla

    2016-01-01

    Attention to the auditory environment of people with profound intellectual and multiple disabilities (PIMD) is limited, both in research and practice. As there is a dynamic interplay between the quality of the auditory environment and well-being, a study was undertaken to test the validity of the

  1. The Influence of Phonological Mechanisms in Written Spelling of Profoundly Deaf Children

    Science.gov (United States)

    Colombo, Lucia; Arfe, Barbara; Bronte, Tiziana

    2012-01-01

    In the present study, the effect of phonological and working memory mechanisms involved in spelling Italian single words was explored in two groups of children matched for grade level: a group of normally hearing children and a group of pre-verbally deaf children, with severe-to-profound hearing loss. Three-syllable and four-syllable familiar…

  2. A Data Based Multidimensional Oral Hygiene Curriculum for the Severely and Profoundly Handicapped.

    Science.gov (United States)

    Feldman, David; Elliott, Thomas A.

    A multidimensional oral hygiene curriculum appropriate for the moderately to profoundly retarded and composed of tooth brushing, flossing, and gum stimulation/massage is proposed. Task analyses are included for manual tooth brushing, utilizing an oral irrigation appliance, manual flossing, and use of an adaptive aid for flossing. Also provided are…

  3. Operationalizing quality of life for people with profound multiple disabilities : a Delphi study

    NARCIS (Netherlands)

    Petry, K.; Maes, B.; Vlaskamp, C.

    Background: In a recent study, we constructed an item pool that contains items on the quality of life (QOL) and related aspects of support of people with profound multiple disabilities (PMD). In the present study, a panel of experts assessed the content and the structure of this item pool in order

  4. The Curriculum for Children with Severe and Profound Learning Difficulties at Stephen Hawking School

    Science.gov (United States)

    Rayner, Matthew

    2011-01-01

    The increasing number of children with profound and multiple learning difficulties means that many schools for children with severe learning difficulties are having to review the curriculum that they offer. In addition, these schools are continuing to question whether a subject-based approach, in line with the National Curriculum, is the most…

  5. Reversal of rocuronium-induced profound neuromuscular block by sugammadex in Duchenne muscular dystrophy.

    NARCIS (Netherlands)

    Boer, H.D. de; Egmond, J. van; Booij, L.H.D.J.; Driessen, J.J.

    2009-01-01

    A case is reported in which a child with Duchenne muscular dystrophy received a dose of sugammadex to reverse a rocuronium-induced profound neuromuscular block. Sugammadex is the first selective relaxant binding agent and reverses rocuronium- and vecuronium-induced neuromuscular block. A fast and

  6. Connections that Count: Brain-Computer Interface Enables the Profoundly Paralyzed to Communicate

    Science.gov (United States)

    ... Home Current Issue Past Issues Connections that Count: Brain-Computer Interface Enables the Profoundly Paralyzed to Communicate Past Issues / ... of this page please turn Javascript on. A brain-computer interface (BCI) system This brain-computer interface (BCI) system ...

  7. A Preliminary Investigation of the Suitability of Aquatics for People with Severe and Profound Intellectual Disabilities

    Science.gov (United States)

    Aherne, Cian; Coughlan, Barry

    2017-01-01

    Background: Aquatics is an under-researched but possibly appropriate form of activity for people with severe to profound intellectual disabilities (SPIDs). Aim: The current pilot study investigates the suitability of an aquatics programme for service users with SPIDs. Method: Four service users with SPID completed an 8-12-session aquatics…

  8. Determining alertness in individuals with profound intellectual and multiple disabilities : the reliability of an observation list

    NARCIS (Netherlands)

    Munde, V.S.; Vlaskamp, C.; Ruijssenaars, A.J.J.M.; Nakken, H.

    In the support of individuals with profound intellectual and multiple disabilities (PIMD), assessing the level of alertness is a recurring issue for parents and other direct support persons. Although observations show clear advantages above and beyond other assessment methods, there are problems

  9. Social Peer Interactions in Persons with Profound Intellectual and Multiple Disabilities: A Literature Review

    Science.gov (United States)

    Nijs, Sara; Maes, Bea

    2014-01-01

    Social interactions may positively influence developmental and quality of life outcomes. Research in persons with profound intellectual and multiple disabilities (PIMD) mostly investigated interactions with caregivers. This literature review focuses on peer interactions of persons with PIMD. A computerized literature search of three databases was…

  10. The pros and cons of inclusive education for children with Profound Intellectual and Multiple Disabilities

    NARCIS (Netherlands)

    Everaarts, Sanne; de Boer, Anke; van der Putten, Annette; Minnaert, Alexander

    2016-01-01

    Aim: Although children with disabilities have the right to be included into the school system, children with Profound Intellectual and Multiple Disabilities (PIMD) are often not included. The aim of this study is to gather knowledge about inclusive education for children with PIMD by identifying

  11. Bereavement and Loss: Developing a Memory Box to Support a Young Woman with Profound Learning Disabilities

    Science.gov (United States)

    Young, Hannah; Garrard, Brenda

    2016-01-01

    Supporting bereaved people with profound learning disabilities still remains an under-researched area. Moreover, the barriers of communication and disenfranchised grief mean that they often do not receive the support they require, leading to emotional and behavioural difficulties. This article describes research using a case study design, which…

  12. Is more profound knowledge in the field of radiation nece--ssary for doctors

    International Nuclear Information System (INIS)

    Klener, V.

    1981-01-01

    Reasons are listed why doctors should have more profound knowledge in the field of radiation. Despite imperceptibility by human senses of ionizing radiation, the parameters characterizing irradiation can accurately be measured. The units of the said parameters are listed and characterized and the relationships are explained of the radiation dose and non-stochastic and stochastic radiation effects. (Ha)

  13. HEART RATE AND PHYSICAL ACTIVITY PATTERNS IN PERSONS WITH PROFOUND INTELLECTUAL AND MULTIPLE DISABILITIES

    NARCIS (Netherlands)

    Waninge, Aly; van der Putten, Annette A. J.; Stewart, Roy E.; Steenbergen, Bert; van Wijck, Ruud; van der Schans, Cees P.

    2013-01-01

    Because physical fitness and health are related to physical activity, it is important to gain an insight into the physical activity levels of persons with profound intellectual and multiple disabilities (PIMD). The purpose of this study was to examine heart rate patterns to measure the activity

  14. Attentional Processes in Interactions between People with Profound Intellectual and Multiple Disabilities and Direct Support Staff

    Science.gov (United States)

    Ine, Hostyn; Heleen, Neerinckx; Bea, Maes

    2011-01-01

    Few studies have examined joint attention in interactions with persons with profound intellectual and multiple disabilities (PIMD), despite its important role in high-quality interaction. The purpose of this study is to describe the attention-directing behaviours of persons with PIMD and their direct support staff and the attention episodes…

  15. Interaction between Persons with Profound Intellectual and Multiple Disabilities and Their Partners: A Literature Review

    Science.gov (United States)

    Hostyn, Ine; Maes, Bea

    2009-01-01

    Background: High quality interactions are of crucial importance for quality of life of persons with profound intellectual and multiple disabilities (PIMD). This literature review describes and synthesises studies addressing the interaction between persons with PIMD and their partners. Method: A computerised literature search using defined…

  16. Attuning: A Communication Process between People with Severe and Profound Intellectual Disability and Their Interaction Partners

    Science.gov (United States)

    Griffiths, Colin; Smith, Martine

    2016-01-01

    Background: People with severe and profound intellectual disability typically demonstrate a limited ability to communicate effectively. Most of their communications are non-verbal, often idiosyncratic and ambiguous. This article aims to identify the process that regulates communications of this group of people with others and to describe the…

  17. Structural modification of resveratrol leads to increased anti-tumor activity, but causes profound changes in the mode of action

    International Nuclear Information System (INIS)

    Scherzberg, Maria-Christina; Kiehl, Andreas; Zivkovic, Aleksandra; Stark, Holger; Stein, Jürgen; Fürst, Robert; Steinhilber, Dieter; Ulrich-Rückert, Sandra

    2015-01-01

    (Z)-3,5,4′-Trimethoxystilbene (Z-TMS) is a resveratrol analog with increased antiproliferative activity towards a number of cancer cell lines compared to resveratrol, which has been shown to inhibit tubulin polymerization in vitro. The purpose of this study was to investigate if Z-TMS still shows potential for the prevention of metabolic diseases as known for resveratrol. Cell growth inhibition was determined with IC 50 values for Z-TMS between 0.115 μM and 0.473 μM (resveratrol: 110.7 μM to 190.2 μM). Flow cytometric analysis revealed a G 2 /M arrest after Z-TMS treatment, whereas resveratrol caused S phase arrest. Furthermore, Z-TMS was shown to impair microtubule polymerization. Beneficial effects on lipid accumulation were observed for resveratrol, but not for Z-TMS in an in vitro steatosis model. (E)-Resveratrol was confirmed to elevate cAMP levels, and knockdown of AMPK attenuated the antiproliferative activity, while Z-TMS did not show significant effects in these experiments. SIRT1 and AMPK activities were further measured indirectly via induction of the target gene small heterodimer partner (SHP). Thereby, (E)-resveratrol, but not Z-TMS, showed potent induction of SHP mRNA levels in an AMPK- and SIRT1-dependent manner, as confirmed by knockdown experiments. We provide evidence that Z-TMS does not show beneficial metabolic effects, probably due to loss of activity towards resveratrol target genes. Moreover, our data support previous findings that Z-TMS acts as an inhibitor of tubulin polymerization. These findings confirm that the methylation of resveratrol leads to profound changes in the mode of action, which should be taken into consideration when conducting lead structure optimization approaches. - Highlights: • Methylation of resveratrol leads to profound changes in biologic activity. • Z-TMS does not prevent hepatic steatosis, but inhibits tubulin polymerization. • Resveratrol analog Z-TMS does not influence known targets like PDEs, SIRT1

  18. Structural modification of resveratrol leads to increased anti-tumor activity, but causes profound changes in the mode of action

    Energy Technology Data Exchange (ETDEWEB)

    Scherzberg, Maria-Christina; Kiehl, Andreas; Zivkovic, Aleksandra; Stark, Holger [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Stein, Jürgen [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Department of Internal Medicine, Sachsenhausen Hospital, Frankfurt am Main (Germany); Fürst, Robert [Institute of Pharmaceutical Biology, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Steinhilber, Dieter [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Ulrich-Rückert, Sandra, E-mail: sandra.ulrich@em.uni-frankfurt.de [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany)

    2015-08-15

    (Z)-3,5,4′-Trimethoxystilbene (Z-TMS) is a resveratrol analog with increased antiproliferative activity towards a number of cancer cell lines compared to resveratrol, which has been shown to inhibit tubulin polymerization in vitro. The purpose of this study was to investigate if Z-TMS still shows potential for the prevention of metabolic diseases as known for resveratrol. Cell growth inhibition was determined with IC{sub 50} values for Z-TMS between 0.115 μM and 0.473 μM (resveratrol: 110.7 μM to 190.2 μM). Flow cytometric analysis revealed a G{sub 2}/M arrest after Z-TMS treatment, whereas resveratrol caused S phase arrest. Furthermore, Z-TMS was shown to impair microtubule polymerization. Beneficial effects on lipid accumulation were observed for resveratrol, but not for Z-TMS in an in vitro steatosis model. (E)-Resveratrol was confirmed to elevate cAMP levels, and knockdown of AMPK attenuated the antiproliferative activity, while Z-TMS did not show significant effects in these experiments. SIRT1 and AMPK activities were further measured indirectly via induction of the target gene small heterodimer partner (SHP). Thereby, (E)-resveratrol, but not Z-TMS, showed potent induction of SHP mRNA levels in an AMPK- and SIRT1-dependent manner, as confirmed by knockdown experiments. We provide evidence that Z-TMS does not show beneficial metabolic effects, probably due to loss of activity towards resveratrol target genes. Moreover, our data support previous findings that Z-TMS acts as an inhibitor of tubulin polymerization. These findings confirm that the methylation of resveratrol leads to profound changes in the mode of action, which should be taken into consideration when conducting lead structure optimization approaches. - Highlights: • Methylation of resveratrol leads to profound changes in biologic activity. • Z-TMS does not prevent hepatic steatosis, but inhibits tubulin polymerization. • Resveratrol analog Z-TMS does not influence known targets like

  19. Terpene metabolic engineering via nuclear or chloroplast genomes profoundly and globally impacts off-target pathways through metabolite signalling.

    Science.gov (United States)

    Pasoreck, Elise K; Su, Jin; Silverman, Ian M; Gosai, Sager J; Gregory, Brian D; Yuan, Joshua S; Daniell, Henry

    2016-09-01

    The impact of metabolic engineering on nontarget pathways and outcomes of metabolic engineering from different genomes are poorly understood questions. Therefore, squalene biosynthesis genes FARNESYL DIPHOSPHATE SYNTHASE (FPS) and SQUALENE SYNTHASE (SQS) were engineered via the Nicotiana tabacum chloroplast (C), nuclear (N) or both (CN) genomes to promote squalene biosynthesis. SQS levels were ~4300-fold higher in C and CN lines than in N, but all accumulated ~150-fold higher squalene due to substrate or storage limitations. Abnormal leaf and flower phenotypes, including lower pollen production and reduced fertility, were observed regardless of the compartment or level of transgene expression. Substantial changes in metabolomes of all lines were observed: levels of 65-120 unrelated metabolites, including the toxic alkaloid nicotine, changed by as much as 32-fold. Profound effects of transgenesis on nontarget gene expression included changes in the abundance of 19 076 transcripts by up to 2000-fold in CN; 7784 transcripts by up to 1400-fold in N; and 5224 transcripts by as much as 2200-fold in C. Transporter-related transcripts were induced, and cell cycle-associated transcripts were disproportionally repressed in all three lines. Transcriptome changes were validated by qRT-PCR. The mechanism underlying these large changes likely involves metabolite-mediated anterograde and/or retrograde signalling irrespective of the level of transgene expression or end product, due to imbalance of metabolic pools, offering new insight into both anticipated and unanticipated consequences of metabolic engineering. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  20. COPD: Definition and Phenotypes

    DEFF Research Database (Denmark)

    Vestbo, J.

    2014-01-01

    particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients. The evolution of this definition and the diagnostic criteria currently in use are discussed. COPD is increasingly divided in subgroups or phenotypes based on specific features and association...

  1. Phenotypic Resistance to Antibiotics

    Directory of Open Access Journals (Sweden)

    Jose L. Martinez

    2013-04-01

    Full Text Available The development of antibiotic resistance is usually associated with genetic changes, either to the acquisition of resistance genes, or to mutations in elements relevant for the activity of the antibiotic. However, in some situations resistance can be achieved without any genetic alteration; this is called phenotypic resistance. Non-inherited resistance is associated to specific processes such as growth in biofilms, a stationary growth phase or persistence. These situations might occur during infection but they are not usually considered in classical susceptibility tests at the clinical microbiology laboratories. Recent work has also shown that the susceptibility to antibiotics is highly dependent on the bacterial metabolism and that global metabolic regulators can modulate this phenotype. This modulation includes situations in which bacteria can be more resistant or more susceptible to antibiotics. Understanding these processes will thus help in establishing novel therapeutic approaches based on the actual susceptibility shown by bacteria during infection, which might differ from that determined in the laboratory. In this review, we discuss different examples of phenotypic resistance and the mechanisms that regulate the crosstalk between bacterial metabolism and the susceptibility to antibiotics. Finally, information on strategies currently under development for diminishing the phenotypic resistance to antibiotics of bacterial pathogens is presented.

  2. Reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia: sugammadex versus neostigmine.

    Directory of Open Access Journals (Sweden)

    Lemmens Hendrikus JM

    2010-09-01

    Full Text Available Abstract Background Acetylcholinesterase inhibitors cannot rapidly reverse profound neuromuscular block. Sugammadex, a selective relaxant binding agent, reverses the effects of rocuronium and vecuronium by encapsulation. This study assessed the efficacy of sugammadex compared with neostigmine in reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia. Methods Patients aged ≥18 years, American Society of Anesthesiologists class 1-4, scheduled to undergo surgery under general anesthesia were enrolled in this phase III, multicenter, randomized, safety-assessor blinded study. Sevoflurane anesthetized patients received vecuronium 0.1 mg/kg for intubation, with maintenance doses of 0.015 mg/kg as required. Patients were randomized to receive sugammadex 4 mg/kg or neostigmine 70 μg/kg with glycopyrrolate 14 μg/kg at 1-2 post-tetanic counts. The primary efficacy variable was time from start of study drug administration to recovery of the train-of-four ratio to 0.9. Safety assessments included physical examination, laboratory data, vital signs, and adverse events. Results Eighty three patients were included in the intent-to-treat population (sugammadex, n = 47; neostigmine, n = 36. Geometric mean time to recovery of the train-of-four ratio to 0.9 was 15-fold faster with sugammadex (4.5 minutes compared with neostigmine (66.2 minutes; p Conclusions Recovery from profound vecuronium-induced block is significantly faster with sugammadex, compared with neostigmine. Neostigmine did not rapidly reverse profound neuromuscular block (Trial registration number: NCT00473694.

  3. Speech timing and working memory in profoundly deaf children after cochlear implantation

    OpenAIRE

    Burkholder, Rose A.; Pisoni, David B.

    2003-01-01

    Thirty-seven profoundly deaf children between 8- and 9-years-old with cochlear implants and a comparison group of normal-hearing children were studied to measure speaking rates, digit spans, and speech timing during digit span recall. The deaf children displayed longer sentence durations and pauses during recall and shorter digit spans compared to the normal-hearing children. Articulation rates, measured from sentence durations, were strongly correlated with immediate memory span in both norm...

  4. Epidemiology of fractures in people with severe and profound developmental disabilities

    Science.gov (United States)

    Glick, N.R.; Fischer, M.H.; Heisey, D.M.; Leverson, G.E.; Mann, D.C.

    2005-01-01

    Fractures are more prevalent among people with severe and profound developmental disabilities than in the general population. In order to characterize the tendency of these people to fracture, and to identify features that may guide the development of preventive strategies, we analyzed fracture epidemiology in people with severe and profound developmental disabilities who lived in a stable environment. Data from a 23-year longitudinal cohort registry of 1434 people with severe and profound developmental disabilities were analyzed to determine the effects of age, gender, mobility, bone fractured, month of fracture, and fracture history upon fracture rates. Eighty-five percent of all fractures involved the extremities. The overall fracture rate increased as mobility increased. In contrast, femoral shaft fracture risk was substantially higher in the least mobile [relative risk (RR), 10.36; 95% confidence interval (CI), 3.29-32.66] compared with the most mobile group. Although the overall fracture rate was not associated with age, the femoral shaft fractures decreased but hand/foot fractures increased with age. Overall fracture risk declined in August and September (RR, 0.70; 95% CI, 0.55-0.89), being especially prominent for tibial/fibular fractures (RR, 0.31; 95% CI, 0.13-0.70). Gender was not a factor in fracture risk. Two primary fracture mechanisms are apparent: one, largely associated with lack of weight-bearing in people with the least mobility, is exemplified by femoral fractures during non-traumatic events as simple as diapering or transfers; the other, probably due to movement- or fall-related trauma, is exemplified by hand/foot fractures in people who ambulate. The fracture experience of people with severe and profound developmental disabilities is unique and, because it differs qualitatively from postmenopausal osteoporosis, may require population-specific methods for assessing risk, for improving bone integrity, and for reduction of falls and accidents

  5. Like cognitive function, decision making across the life span shows profound age-related changes.

    Science.gov (United States)

    Tymula, Agnieszka; Rosenberg Belmaker, Lior A; Ruderman, Lital; Glimcher, Paul W; Levy, Ifat

    2013-10-15

    It has long been known that human cognitive function improves through young adulthood and then declines across the later life span. Here we examined how decision-making function changes across the life span by measuring risk and ambiguity attitudes in the gain and loss domains, as well as choice consistency, in an urban cohort ranging in age from 12 to 90 y. We identified several important age-related patterns in decision making under uncertainty: First, we found that healthy elders between the ages of 65 and 90 were strikingly inconsistent in their choices compared with younger subjects. Just as elders show profound declines in cognitive function, they also show profound declines in choice rationality compared with their younger peers. Second, we found that the widely documented phenomenon of ambiguity aversion is specific to the gain domain and does not occur in the loss domain, except for a slight effect in older adults. Finally, extending an earlier report by our group, we found that risk attitudes across the life span show an inverted U-shaped function; both elders and adolescents are more risk-averse than their midlife counterparts. Taken together, these characterizations of decision-making function across the life span in this urban cohort strengthen the conclusions of previous reports suggesting a profound impact of aging on cognitive function in this domain.

  6. D-2-hydroxyglutaric aciduria: a case with an intermediate phenotype and prenatal diagnosis of two affected fetuses.

    Science.gov (United States)

    Clarke, Nigel F; Andrews, Ian; Carpenter, Kevin; Jakobs, Cornelis; van der Knaap, Marjo S; Kirk, Edwin P

    2003-08-01

    D-2-hydroxyglutaric aciduria (D2HGA) is a rare autosomal recessive disorder with variable clinical expression. The biochemical defect is unknown at present. Previously reported cases have either followed a severe clinical course characterized by neonatal epileptic encephalopathy, cortical blindness, and profound developmental delay, or a mild course characterized by mild developmental delay, manageable epilepsy, and mild hypotonia. To date there has been a clear distinction between these two groups. We report the second case of a child with D2HGA who has followed an intermediate course. She presented in infancy with hypotonia, manageable epilepsy and developed moderate to severe developmental delay, and cortical visual impairment. The proposita had a coarse facial appearance, flat face, broad nasal bridge, up-turned nose, and simple, anteverted ears. These facial anomalies have been noted in other children with D2HGA and this case strengthens the proposed association between this facial phenotype and D2HGA. We also report the third and fourth instances of prenatal diagnosis for D2HGA. At each prenatal diagnosis, an affected fetus was diagnosed on the basis of markedly increased levels of D-2-hydroxyglutaric acid in amniotic fluid. Copyright 2003 Wiley-Liss, Inc.

  7. Clinical phenotype-based gene prioritization: an initial study using semantic similarity and the human phenotype ontology.

    Science.gov (United States)

    Masino, Aaron J; Dechene, Elizabeth T; Dulik, Matthew C; Wilkens, Alisha; Spinner, Nancy B; Krantz, Ian D; Pennington, Jeffrey W; Robinson, Peter N; White, Peter S

    2014-07-21

    Exome sequencing is a promising method for diagnosing patients with a complex phenotype. However, variant interpretation relative to patient phenotype can be challenging in some scenarios, particularly clinical assessment of rare complex phenotypes. Each patient's sequence reveals many possibly damaging variants that must be individually assessed to establish clear association with patient phenotype. To assist interpretation, we implemented an algorithm that ranks a given set of genes relative to patient phenotype. The algorithm orders genes by the semantic similarity computed between phenotypic descriptors associated with each gene and those describing the patient. Phenotypic descriptor terms are taken from the Human Phenotype Ontology (HPO) and semantic similarity is derived from each term's information content. Model validation was performed via simulation and with clinical data. We simulated 33 Mendelian diseases with 100 patients per disease. We modeled clinical conditions by adding noise and imprecision, i.e. phenotypic terms unrelated to the disease and terms less specific than the actual disease terms. We ranked the causative gene against all 2488 HPO annotated genes. The median causative gene rank was 1 for the optimal and noise cases, 12 for the imprecision case, and 60 for the imprecision with noise case. Additionally, we examined a clinical cohort of subjects with hearing impairment. The disease gene median rank was 22. However, when also considering the patient's exome data and filtering non-exomic and common variants, the median rank improved to 3. Semantic similarity can rank a causative gene highly within a gene list relative to patient phenotype characteristics, provided that imprecision is mitigated. The clinical case results suggest that phenotype rank combined with variant analysis provides significant improvement over the individual approaches. We expect that this combined prioritization approach may increase accuracy and decrease effort for

  8. Speech and language therapists' approaches to communication intervention with children and adults with profound and multiple learning disability.

    Science.gov (United States)

    Goldbart, Juliet; Chadwick, Darren; Buell, Susan

    2014-11-01

    People with profound intellectual and multiple disabilities (PMLD) have communication impairments as one defining characteristic. To explore speech and language therapists' (SLTs) decision making in communication interventions for people with PMLD, in terms of the intervention approaches used, the factors informing the decisions to use specific interventions and the extent to which the rationales underpinning these decisions related to the components of evidence based practice (EBP), namely empirical evidence, clinical experience and client/carer views and values. A questionnaire on communication assessment and intervention for people with PMLD was sent to SLTs in the UK to elicit information on: the communication intervention approaches they used; their rationales for their intervention choices; their use of published evidence to inform decision making. Intensive interaction and objects of reference were the communication interventions most often used with people with PMLD, with some differences between children and adults evident. Rationales provided conformed somewhat to the EBP framework though extension of the existing framework and addition of practical and organizational considerations led to a revised typology of rationale for decision making. Rationales most frequently related to the empowerment, development and behavioural preferences of the person with PMLD. Empirical research evidence was seldom mentioned by SLTs as informing intervention decision making leading to very diverse practice. There is a need for further research on the effectiveness of commonly used but under-evaluated interventions. There is also a need to alert SLTs to the evidence base supporting other approaches, particularly switch-based, cause and effect approaches. © 2014 Royal College of Speech and Language Therapists.

  9. The duplication 17p13.3 phenotype

    DEFF Research Database (Denmark)

    Curry, Cynthia J; Rosenfeld, Jill A; Grant, Erica

    2013-01-01

    . Older patients were often overweight. Three variant phenotypes included cleft lip/palate (CLP), split hand/foot with long bone deficiency (SHFLD), and a connective tissue phenotype resembling Marfan syndrome. The duplications in patients with clefts appear to disrupt ABR, while the SHFLD phenotype......Chromosome 17p13.3 is a gene rich region that when deleted is associated with the well-known Miller-Dieker syndrome. A recently described duplication syndrome involving this region has been associated with intellectual impairment, autism and occasional brain MRI abnormalities. We report 34...... was associated with duplication of BHLHA9 as noted in two recent reports. The connective tissue phenotype did not have a convincing critical region. Our experience with this large cohort expands knowledge of this diverse duplication syndrome....

  10. Depletion of 4-hydroxynonenal in hGSTA4-transfected HLE B-3 cells results in profound changes in gene expression

    International Nuclear Information System (INIS)

    Patrick, Brad; Li Jie; Jeyabal, Prince V.S.; Reddy, Prasada M.R.V.; Yang Yusong; Sharma, Rajendra; Sinha, Mala; Luxon, Bruce; Zimniak, Piotr; Awasthi, Sanjay; Awasthi, Yogesh C.

    2005-01-01

    Previously, we have shown that overexpression of 4-hydroxy-2-nonenal (HNE)-detoxifying enzyme glutathione S-transferase A4-4 (hGSTA4-4) in human lens epithelial cells (HLE B-3) leads to pro-carcinogenic phenotypic transformation of these cells [R. Sharma, et al. Eur. J. Biochem. 271 (2004) 1960-1701]. We now demonstrate that hGSTA4-transfection also causes a profound change in the expression of genes involved in cell adhesion, cell cycle control, proliferation, cell growth, and apoptosis, which is consistent with phenotypic changes of the transformed cells. The expression of p53, p21, p16, fibronectin 1, laminin γ1, connexin 43, Fas, integrin α6, TGFα, and c-jun was down-regulated, while the expression of protein kinase C beta II (PKCβII), c-myc, cyclin-dependent kinase 2 (CDK2), and TGFβ was up-regulated in transfected cells. These results demonstrate that HNE serves as a crucial signaling molecule and, by modulating the expression of genes, can influence cellular functions

  11. Correlation between audiovestibular function tests and hearing outcomes in severe to profound sudden sensorineural hearing loss.

    Science.gov (United States)

    Wang, Chi-Te; Huang, Tsung-Wei; Kuo, Shih-Wei; Cheng, Po-Wen

    2009-02-01

    This study investigated whether audiovestibular function tests, namely auditory brain stem response (ABR) and vestibular-evoked myogenic potential (VEMP) tests were correlated to hearing outcomes after controlling the effects of other potential confounding factors in severe to profound sudden sensorineural hearing loss (SSHL). Eighty-eight patients with severe to profound SSHL were enrolled in this study. Pretreatment hearing levels, results of audiovestibular function tests, and final hearing outcomes were recorded from retrospective chart reviews. Other factors, including age, gender, delay of treatment, vertigo, diabetes mellitus, and hypertension, were collected as well. Comparative analysis between multiple variables and hearing outcomes was conducted using the cumulative logits model in overall subjects. Further, multivariate analysis of prognostic factors was conducted in the stratified groups of severe (70 dB HL 90 dB HL) SSHL. Multivariate analysis showed that pretreatment hearing levels, presence of vertigo, and results of ABR and VEMP testing were significant outcome predictors in the overall subjects. Stratification analysis demonstrated that both the presence of ABR and VEMP waveforms were significantly correlated with better hearing outcomes in the group of severe SSHL [ABR: adjusted odds ratio (aOR) = 14.7, 95% confidence interval (CI) = 1.78 to 122, p = 0.01; VEMP: aOR = 5.91, 95% CI = 1.18 to 29.5, p = 0.03], whereas the presence of vertigo was the only significant negative prognostic factor in the group of profound SSHL (aOR = 0.24, 95% CI = 0.06 to 0.95, p = 0.04). Other variables, including age, gender, diabetes mellitus, hypertension, and delay of treatment, were not significantly related to hearing outcomes in both groups (p > 0.05). A predictive hearing recovery table with the combined ABR and VEMP results was proposed for the group of severe SSHL. ABR and VEMP tests should be included in the battery of neurootological examinations in

  12. Spider Silk Violin Strings with a Unique Packing Structure Generate a Soft and Profound Timbre

    Science.gov (United States)

    Osaki, Shigeyoshi

    2012-04-01

    We overcome the difficulties in pulling long draglines from spiders, twist bundles of dragline filaments, and succeed in preparing violin strings. The twisting is found to change the cross section shapes of filaments from circular to polygonal and to optimize the packing structure with no openings among filaments providing mechanically strong and elastic strings. The spider string signal peaks of overtones for the violin are relatively large at high frequencies, generating a soft and profound timbre. Such a preferable timbre is considered to be due to the unique polygonal packing structure which provides valuable knowledge for developing new types of materials.

  13. Dissecting phenotypic variation among AIS patients

    International Nuclear Information System (INIS)

    Wang Minghua; Wang Jiucun; Zhang Zhen; Zhao Zhimin; Zhang Rongmei; Hu Xiaohua; Tan Tao; Luo Shijing; Luo Zewei

    2005-01-01

    We have created genital skin fibroblast cell lines directly from three patients in a Chinese family affected by androgen insensitivity syndrome (AIS). All patients in the family share an identical AR Arg 840 Cys mutant but show different disease phenotypes. By using the cell lines, we find that the mutation has not influenced a normal androgen-binding capacity at 37 deg C but has reduced the affinity for androgens and may cause thermolability of the androgen-receptor complex. The impaired nuclear trafficking of the androgen receptor in the cell lines is highly correlated with the severity of donors' disease phenotype. The transactivity of the mutant is substantially weakened and the extent of the reduced transactivity reflects severity of the donors' disease symptom. Our data reveal that although etiology of AIS is monogenic and the mutant may alter the major biological functions of its wild allele, the function of the mutant AR can also be influenced by the different genetic backgrounds and thus explains the divergent disease phenotypes

  14. Enabling Access to Digital Media for the Profoundly Disabled, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The system proposed in this effort will allow the handicapped individual with hand/arm motor impairment to use the computer and access digital libraries on the...

  15. Amyloid-beta aggregates cause alterations of astrocytic metabolic phenotype: impact on neuronal viability.

    Science.gov (United States)

    Allaman, Igor; Gavillet, Mathilde; Bélanger, Mireille; Laroche, Thierry; Viertl, David; Lashuel, Hilal A; Magistretti, Pierre J

    2010-03-03

    Amyloid-beta (Abeta) peptides play a key role in the pathogenesis of Alzheimer's disease and exert various toxic effects on neurons; however, relatively little is known about their influence on glial cells. Astrocytes play a pivotal role in brain homeostasis, contributing to the regulation of local energy metabolism and oxidative stress defense, two aspects of importance for neuronal viability and function. In the present study, we explored the effects of Abeta peptides on glucose metabolism in cultured astrocytes. Following Abeta(25-35) exposure, we observed an increase in glucose uptake and its various metabolic fates, i.e., glycolysis (coupled to lactate release), tricarboxylic acid cycle, pentose phosphate pathway, and incorporation into glycogen. Abeta increased hydrogen peroxide production as well as glutathione release into the extracellular space without affecting intracellular glutathione content. A causal link between the effects of Abeta on glucose metabolism and its aggregation and internalization into astrocytes through binding to members of the class A scavenger receptor family could be demonstrated. Using astrocyte-neuron cocultures, we observed that the overall modifications of astrocyte metabolism induced by Abeta impair neuronal viability. The effects of the Abeta(25-35) fragment were reproduced by Abeta(1-42) but not by Abeta(1-40). Finally, the phosphoinositide 3-kinase (PI3-kinase) pathway appears to be crucial in these events since both the changes in glucose utilization and the decrease in neuronal viability are prevented by LY294002, a PI3-kinase inhibitor. This set of observations indicates that Abeta aggregation and internalization into astrocytes profoundly alter their metabolic phenotype with deleterious consequences for neuronal viability.

  16. Whole exome sequencing identifies mutations in Usher syndrome genes in profoundly deaf Tunisian patients.

    Science.gov (United States)

    Riahi, Zied; Bonnet, Crystel; Zainine, Rim; Lahbib, Saida; Bouyacoub, Yosra; Bechraoui, Rym; Marrakchi, Jihène; Hardelin, Jean-Pierre; Louha, Malek; Largueche, Leila; Ben Yahia, Salim; Kheirallah, Moncef; Elmatri, Leila; Besbes, Ghazi; Abdelhak, Sonia; Petit, Christine

    2015-01-01

    Usher syndrome (USH) is an autosomal recessive disorder characterized by combined deafness-blindness. It accounts for about 50% of all hereditary deafness blindness cases. Three clinical subtypes (USH1, USH2, and USH3) are described, of which USH1 is the most severe form, characterized by congenital profound deafness, constant vestibular dysfunction, and a prepubertal onset of retinitis pigmentosa. We performed whole exome sequencing in four unrelated Tunisian patients affected by apparently isolated, congenital profound deafness, with reportedly normal ocular fundus examination. Four biallelic mutations were identified in two USH1 genes: a splice acceptor site mutation, c.2283-1G>T, and a novel missense mutation, c.5434G>A (p.Glu1812Lys), in MYO7A, and two previously unreported mutations in USH1G, i.e. a frameshift mutation, c.1195_1196delAG (p.Leu399Alafs*24), and a nonsense mutation, c.52A>T (p.Lys18*). Another ophthalmological examination including optical coherence tomography actually showed the presence of retinitis pigmentosa in all the patients. Our findings provide evidence that USH is under-diagnosed in Tunisian deaf patients. Yet, early diagnosis of USH is of utmost importance because these patients should undergo cochlear implant surgery in early childhood, in anticipation of the visual loss.

  17. Profound microcephaly, primordial dwarfism with developmental brain malformations: a new syndrome.

    Science.gov (United States)

    Abdel-Salam, Ghada M H; Abdel-Hamid, Mohamed S; Saleem, Sahar N; Ahmed, Mahmoud K H; Issa, Mahmoud; Effat, Laila K; Kayed, Hisham F; Zaki, Maha S; Gaber, Khaled R

    2012-08-01

    We describe two sibs with a lethal form of profound congenital microcephaly, intrauterine and postnatal growth retardation, subtle skeletal changes, and poorly developed brain. The sibs had striking absent cranial vault with sloping of the forehead, large beaked nose, relatively large ears, and mandibular micro-retrognathia. Brain magnetic resonance imaging (MRI) revealed extremely simplified gyral pattern, large interhemispheric cyst and agenesis of corpus callosum, abnormally shaped hippocampus, and proportionately affected cerebellum and brainstem. In addition, fundus examination showed foveal hypoplasia with optic nerve atrophy. No abnormalities of the internal organs were found. This profound form of microcephaly was identified at 17 weeks gestation by ultrasound and fetal brain MRI helped in characterizing the developmental brain malformations in the second sib. Molecular analysis excluded mutations in potentially related genes such as RNU4ATAC, SLC25A19, and ASPM. These clinical and imaging findings are unlike that of any recognized severe forms of microcephaly which is believed to be a new microcephalic primordial dwarfism (MPD) with developmental brain malformations with most probably autosomal recessive inheritance based on consanguinity and similarly affected male and female sibs. Copyright © 2012 Wiley Periodicals, Inc.

  18. Profound neonatal hypoglycemia and lactic acidosis caused by pyridoxine-dependent epilepsy.

    Science.gov (United States)

    Mercimek-Mahmutoglu, Saadet; Horvath, Gabriella A; Coulter-Mackie, Marion; Nelson, Tanya; Waters, Paula J; Sargent, Michael; Struys, Eduard; Jakobs, Cornelis; Stockler-Ipsiroglu, Sylvia; Connolly, Mary B

    2012-05-01

    Pyridoxine-dependent epilepsy (PDE) was first described in 1954. The ALDH7A1 gene mutations resulting in α-aminoadipic semialdehyde dehydrogenase deficiency as a cause of PDE was identified only in 2005. Neonatal epileptic encephalopathy is the presenting feature in >50% of patients with classic PDE. We report the case of a 13-month-old girl with profound neonatal hypoglycemia (0.6 mmol/L; reference range >2.4), lactic acidosis (11 mmol/L; reference range A (p.Val278Val), and a novel putative pathogenic missense mutation c.1192G>C (p.Gly398Arg) in the ALDH7A1 gene. She has been seizure-free since 1.5 months of age on treatment with pyridoxine alone. She has motor delay and central hypotonia but normal language and social development at the age of 13 months. This case is the first description of a patient with PDE due to mutations in the ALDH7A1 gene who presented with profound neonatal hypoglycemia and lactic acidosis masquerading as a neonatal-onset gluconeogenesis defect. PDE should be included in the differential diagnosis of hypoglycemia and lactic acidosis in addition to medically refractory neonatal seizures.

  19. Quantification of structural changes in the corpus callosumin children with profound hypoxic-ischaemic brain injury

    Energy Technology Data Exchange (ETDEWEB)

    Stivaros, Stavros M. [Manchester Academic Health Science Centre, Academic Unit of Paediatric Radiology, Royal Manchester Children' s Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester (United Kingdom); University of Manchester, Centre for Imaging Sciences, Institute of Population Health, Manchester (United Kingdom); Radon, Mark R. [The Walton Centre NHS Foundation Trust, Department of Neuroradiology, Liverpool (United Kingdom); Mileva, Reneta; Gledson, Ann; Keane, John A. [University of Manchester, School of Computer Science, Manchester (United Kingdom); Connolly, Daniel J.A.; Batty, Ruth [Sheffield Children' s Hospital NHS Foundation Trust, Department of Neuroradiology, Sheffield (United Kingdom); Cowell, Patricia E. [University of Sheffield, Department of Human Communication Sciences, Sheffield (United Kingdom); Hoggard, Nigel; Griffiths, Paul D. [University of Sheffield, Academic Unit of Radiology, Sheffield (United Kingdom); Wright, Neville B.; Tang, Vivian [Manchester Academic Health Science Centre, Academic Unit of Paediatric Radiology, Royal Manchester Children' s Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester (United Kingdom)

    2016-01-15

    Birth-related acute profound hypoxic-ischaemic brain injury has specific patterns of damage including the paracentral lobules. To test the hypothesis that there is anatomically coherent regional volume loss of the corpus callosum as a result of this hemispheric abnormality. Study subjects included 13 children with proven acute profound hypoxic-ischaemic brain injury and 13 children with developmental delay but no brain abnormalities. A computerised system divided the corpus callosum into 100 segments, measuring each width. Principal component analysis grouped the widths into contiguous anatomical regions. We conducted analysis of variance of corpus callosum widths as well as support vector machine stratification into patient groups. There was statistically significant narrowing of the mid-posterior body and genu of the corpus callosum in children with hypoxic-ischaemic brain injury. Support vector machine analysis yielded over 95% accuracy in patient group stratification using the corpus callosum centile widths. Focal volume loss is seen in the corpus callosum of children with hypoxic-ischaemic brain injury secondary to loss of commissural fibres arising in the paracentral lobules. Support vector machine stratification into the hypoxic-ischaemic brain injury group or the control group on the basis of corpus callosum width is highly accurate and points towards rapid clinical translation of this technique as a potential biomarker of hypoxic-ischaemic brain injury. (orig.)

  20. Validation of the Spanish version of the Baylor Profound Mental Status Examination.

    Science.gov (United States)

    Salmerón, Sergio; Huedo, Isabel; López-Utiel, Melisa; Soler-Moratalla, Isabel; Flores-Ruano, Teresa; Fernández-Sánchez, Miguel; Noguerón, Alicia; Doody, Rachelle S; Abizanda, Pedro

    2016-01-01

    There are no short valid instruments to evaluate cognitive status in severe Alzheimer's disease (AD) patients in the Spanish language. To validate the Spanish version of the Baylor Profound Mental Status Examination (BPMSE-Sp). The Baylor Profound Mental Status Examination (BPMSE) was translated to Spanish and back translated. Validation was conducted in 100 patients with severe probable AD with a Mini-Mental State Examination (MMSE) reliability. The mean age of patients was 84.9; 74% were female; 64% were institutionalized. The mean MMSE was 5.6; the mean BPMSE-Sp was 13.6; the mean BPMSE-Sp behavior was 1.2; the mean SIB was 42.2; and the mean NPI-Q was 4.7. BPMSE-Sp presented good internal consistency (Cronbach α= 0.84). There were significant correlations between the BPMSE-Sp and MMSE (r = 0.86, p reliability were in both cases excellent, ranging between 0.96 and 0.99 (p <  0.001). BPMSE-Sp had fewer floor and ceiling effects than the MMSE. The BPMSE-Sp is a valid tool for use in daily practice and research in the evaluation of cognitive function of patients with severe AD.

  1. Loss of CIB2 Causes Profound Hearing Loss and Abolishes Mechanoelectrical Transduction in Mice

    Directory of Open Access Journals (Sweden)

    Yanfei Wang

    2017-12-01

    Full Text Available Calcium and integrin-binding protein 2 (CIB2 belongs to a protein family with four known members, CIB1 through CIB4, which are characterized by multiple calcium-binding EF-hand domains. Among the family members, the Cib1 and Cib2 genes are expressed in mouse cochlear hair cells, and mutations in the human CIB2 gene have been associated with nonsyndromic deafness DFNB48 and syndromic deafness USH1J. To further explore the function of CIB1 and CIB2 in hearing, we established Cib1 and Cib2 knockout mice using the clustered regularly interspaced short palindromic repeat (CRISPR-associated Cas9 nuclease (CRISPR/Cas9 genome editing technique. We found that loss of CIB1 protein does not affect auditory function, whereas loss of CIB2 protein causes profound hearing loss in mice. Further investigation revealed that hair cell stereocilia development is affected in Cib2 knockout mice. Noticeably, loss of CIB2 abolishes mechanoelectrical transduction (MET currents in auditory hair cells. In conclusion, we show here that although both CIB1 and CIB2 are readily detected in the cochlea, only loss of CIB2 results in profound hearing loss, and that CIB2 is essential for auditory hair cell MET.

  2. Whole exome sequencing identifies mutations in Usher syndrome genes in profoundly deaf Tunisian patients.

    Directory of Open Access Journals (Sweden)

    Zied Riahi

    Full Text Available Usher syndrome (USH is an autosomal recessive disorder characterized by combined deafness-blindness. It accounts for about 50% of all hereditary deafness blindness cases. Three clinical subtypes (USH1, USH2, and USH3 are described, of which USH1 is the most severe form, characterized by congenital profound deafness, constant vestibular dysfunction, and a prepubertal onset of retinitis pigmentosa. We performed whole exome sequencing in four unrelated Tunisian patients affected by apparently isolated, congenital profound deafness, with reportedly normal ocular fundus examination. Four biallelic mutations were identified in two USH1 genes: a splice acceptor site mutation, c.2283-1G>T, and a novel missense mutation, c.5434G>A (p.Glu1812Lys, in MYO7A, and two previously unreported mutations in USH1G, i.e. a frameshift mutation, c.1195_1196delAG (p.Leu399Alafs*24, and a nonsense mutation, c.52A>T (p.Lys18*. Another ophthalmological examination including optical coherence tomography actually showed the presence of retinitis pigmentosa in all the patients. Our findings provide evidence that USH is under-diagnosed in Tunisian deaf patients. Yet, early diagnosis of USH is of utmost importance because these patients should undergo cochlear implant surgery in early childhood, in anticipation of the visual loss.

  3. Quantification of structural changes in the corpus callosumin children with profound hypoxic-ischaemic brain injury

    International Nuclear Information System (INIS)

    Stivaros, Stavros M.; Radon, Mark R.; Mileva, Reneta; Gledson, Ann; Keane, John A.; Connolly, Daniel J.A.; Batty, Ruth; Cowell, Patricia E.; Hoggard, Nigel; Griffiths, Paul D.; Wright, Neville B.; Tang, Vivian

    2016-01-01

    Birth-related acute profound hypoxic-ischaemic brain injury has specific patterns of damage including the paracentral lobules. To test the hypothesis that there is anatomically coherent regional volume loss of the corpus callosum as a result of this hemispheric abnormality. Study subjects included 13 children with proven acute profound hypoxic-ischaemic brain injury and 13 children with developmental delay but no brain abnormalities. A computerised system divided the corpus callosum into 100 segments, measuring each width. Principal component analysis grouped the widths into contiguous anatomical regions. We conducted analysis of variance of corpus callosum widths as well as support vector machine stratification into patient groups. There was statistically significant narrowing of the mid-posterior body and genu of the corpus callosum in children with hypoxic-ischaemic brain injury. Support vector machine analysis yielded over 95% accuracy in patient group stratification using the corpus callosum centile widths. Focal volume loss is seen in the corpus callosum of children with hypoxic-ischaemic brain injury secondary to loss of commissural fibres arising in the paracentral lobules. Support vector machine stratification into the hypoxic-ischaemic brain injury group or the control group on the basis of corpus callosum width is highly accurate and points towards rapid clinical translation of this technique as a potential biomarker of hypoxic-ischaemic brain injury. (orig.)

  4. Epigenetics: A Fascinating Field with Profound Research, Clinical, & Public Health Implications

    Science.gov (United States)

    Stein, Richard A.; Davis, Devra Lee

    2012-01-01

    Epigenetics is emerging as one of the most dynamic and vibrant biomedical areas. Multiple lines of evidence confirm that inherited genetic changes alone cannot fully explain all phenotypic characteristics of live organisms, and additional factors, which are not encoded in the DNA sequence, are involved. The contribution of non-genetic factors is…

  5. Cortical visual impairment

    OpenAIRE

    Koželj, Urša

    2013-01-01

    In this thesis we discuss cortical visual impairment, diagnosis that is in the developed world in first place, since 20 percent of children with blindness or low vision are diagnosed with it. The objectives of the thesis are to define cortical visual impairment and the definition of characters suggestive of the cortical visual impairment as well as to search for causes that affect the growing diagnosis of cortical visual impairment. There are a lot of signs of cortical visual impairment. ...

  6. Mice lacking collapsin response mediator protein 1 manifest hyperactivity, impaired learning and memory, and impaired prepulse inhibition

    Directory of Open Access Journals (Sweden)

    Naoya eYamashita

    2013-12-01

    Full Text Available Collapsin response mediator protein 1 (CRMP1 is one of the CRMP family members that are involved in various aspects of neuronal development such as axonal guidance and neuronal migration. Here we provide evidence that crmp1-/- mice exhibited behavioral abnormalities related to schizophrenia. The crmp1-/- mice exhibited hyperactivity and/or impaired emotional behavioral phenotype. These mice also exhibited impaired context-dependent memory and long-term memory retention. Furthermore, crmp1-/- mice exhibited decreased prepulse inhibition, and this phenotype was rescued by administration of chlorpromazine, a typical antipsychotic drug. In addition, in vivo microdialysis revealed that the methamphetamine-induced release of dopamine in prefrontal cortex was exaggerated in crmp1-/- mice, suggesting that enhanced mesocortical dopaminergic transmission contributes to their hyperactivity phenotype. These observations suggest that impairment of CRMP1 function may be involved in the pathogenesis of schizophrenia. We propose that crmp1-/- mouse may model endophenotypes present in this neuropsychiatric disorder.

  7. Developing a questionnaire on physical activity support of people with (profound) intellectual (and multiple) disabilities : Experiences from the Netherlands

    NARCIS (Netherlands)

    Bossink, Leontien; van der Putten, Annette; Vlaskamp, Carla

    2017-01-01

    Introduction: People with intellectual disabilities (ID) undertake extremely low levels of physical activity, which is even more true in people with profound intellectual and multiple disabilities (PIMD). Physical activity approaches, particularly for people with PIMD, are more likely to be

  8. Early reversal of profound rocuronium-induced neuromuscular blockade by sugammadex in a randomized multicenter study - Efficacy, safety, and pharmacokinetics

    NARCIS (Netherlands)

    Sparr, Harald J.; Vermeyen, Karel M.; Beaufort, Anton M.; Rietbergen, Henk; Proost, Johannes H.; Saldien, Vera; Velik-Salchner, Corinna; Wierda, J. Mark K. H.

    Background: Sugammadex reverses the neuromuscular blocking effects of rocuronium by chemical encapsulation. The efficacy, safety, and pharmacokinetics of sugammadex for reversal of profound rocuronium-induced neuromuscular blockade were evaluated. Methods: Ninety-eight male adult patients were

  9. Examining relationships between staff attributions of soundscapes and core affect in people with severe or profound intellectual and visual disabilities

    NARCIS (Netherlands)

    van den Bosch, Kirsten A.; Vlaskamp, Carla; Andringa, Tjeerd C.; Post, Wendy J.; Ruijssenaars, Wied A.J.J.M.

    Background: People with profound intellectual disabilities experience a high prevalence of visual disabilities, making them more dependent on sound. However, research addressing the influence of the auditory environment is scarce. Method: Observations of the auditory environments (soundscapes) and

  10. An atypical case of successful resuscitation of an accidental profound hypothermia patient, occurring in a temperate climate.

    LENUS (Irish Health Repository)

    Coleman, E

    2010-03-01

    Cases of accidental profound hypothermia occur most frequently in cold, northern climates. We describe an atypical case, occurring in a temperate climate, where a hypothermic cardiac-arrested patient was successfully resuscitated using extracorporeal circulation (ECC).

  11. Informal social networks of people with profound intellectual and multiple disabilities : Relationship with age, communicative abilities and current living arrangements

    NARCIS (Netherlands)

    Kamstra, A.; van der Putten, A.A.J.; Post, W.J.; Vlaskamp, C.

    2015-01-01

    BACKGROUND: People with profound intellectual and multiple disabilities (PIMD) have limited informal social contacts. Research to determine the factors which can positively influence establishing sound informal social contacts is required. MATERIALS AND METHODS: Regression analysis for 200 people

  12. Family matters: The experiences and opinions of family members of persons with (severe) or profound intellectual disabilities

    OpenAIRE

    Luijkx, Jorien

    2016-01-01

    “I love my sister, but sometimes I don’t”. This is one of the statements made in the study focused on the experiences of family members of people with (profound) intellectual (and multiple) disabilities (both of individuals living in a residential facility as persons living at home). In recent years, there has been greater recognition of the important position of parents and siblings of people with (profound) intellectual (and multiple) disabilities and the importance of the wellbeing of all ...

  13. Phenotype determination guides swift genotyping of a DFNA2/KCNQ4 family with a hot spot mutation (W276S).

    NARCIS (Netherlands)

    Topsakal, V.; Pennings, R.J.E.; Brinke, H. te; Hamel, B.C.J.; Huygen, P.L.M.; Kremer, J.M.J.; Cremers, C.W.R.J.

    2005-01-01

    OBJECTIVE: Genotype a family trait with autosomal dominant nonsyndromic sensorineural hearing impairment guided only by the phenotype. STUDY DESIGN: Family study. SETTING: Tertiary referral center. PATIENTS: Fifteen family members. METHODS: In the first phase, sequence analysis was performed on DNA

  14. Auditory hallucinations in adults with hearing impairment: a large prevalence study.

    Science.gov (United States)

    Linszen, M M J; van Zanten, G A; Teunisse, R J; Brouwer, R M; Scheltens, P; Sommer, I E

    2018-03-20

    Similar to visual hallucinations in visually impaired patients, auditory hallucinations are often suggested to occur in adults with hearing impairment. However, research on this association is limited. This observational, cross-sectional study tested whether auditory hallucinations are associated with hearing impairment, by assessing their prevalence in an adult population with various degrees of objectified hearing impairment. Hallucination presence was determined in 1007 subjects aged 18-92, who were referred for audiometric testing to the Department of ENT-Audiology, University Medical Center Utrecht, the Netherlands. The presence and severity of hearing impairment were calculated using mean air conduction thresholds from the most recent pure tone audiometry. Out of 829 participants with hearing impairment, 16.2% (n = 134) had experienced auditory hallucinations in the past 4 weeks; significantly more than the non-impaired group [5.8%; n = 10/173; p impairment, with rates up to 24% in the most profoundly impaired group (p impairment in the best ear. Auditory hallucinations mostly consisted of voices (51%), music (36%), and doorbells or telephones (24%). Our findings reveal that auditory hallucinations are common among patients with hearing impairment, and increase with impairment severity. Although more research on potential confounding factors is necessary, clinicians should be aware of this phenomenon, by inquiring after hallucinations in hearing-impaired patients and, conversely, assessing hearing impairment in patients with auditory hallucinations, since it may be a treatable factor.

  15. Profound hypoglycemia-ınduced by vaccinium corymbosum juice and laurocerasus fruit.

    Science.gov (United States)

    Aktan, Ahmet Hamdi; Ozcelik, Abdullah; Cure, Erkan; Cure, Medine Cumhur; Yuce, Suleyman

    2014-01-01

    An emergency intervention was performed in a 75-year-old male patient with hypoglycemic attack and blackout. Although he was diagnosed with prediabetes before 2 years, he did not take any anti-diabetic drug or follow dietary advice. He drank Vaccinium corymbosum L (VC) juice daily with a belief that it increases sexual potency. Before the development of hypoglycemia, the patient had consumed about 500 ml VC juice in addition to eating 200-300 gram of Laurocerasus officinalis (LO) fruit. The measured plasma glucose (PG) level during loss of consciousness was 30 mg/dl. The profound hypoglycemia may be an unexpected side effect of an interaction between the chemical compositions of the two plants, occurred as a result of LO fruit intake that may have a strong PG-lowering effect or related to excessive intake of VC juice. Both plants may be considered in the alternative treatment of diabetes.

  16. Basic life support and children with profound and multiple learning disabilities.

    Science.gov (United States)

    Cash, Stefan; Shinnick-Page, Andrea

    2008-10-01

    Nurses and other carers of people with learning disabilities must be able to manage choking events and perform basic life support effectively. UK guidelines for assessment of airway obstruction and for resuscitation do not take account of the specific needs of people with profound multiple learning disability. For example, they fail to account for inhibited gag and coughing reflexes, limited body movements or chest deformity. There are no national guidelines to assist in clinical decisions and training for nurses and carers. Basic life support training for students of learning disability nursing at Birmingham City University is supplemented to address these issues. The authors ask whether such training should be provided for all nurses including those caring for children and young people. They also invite comment and discussion on questions related to chest compression and training in basic life support for a person in a seated position.

  17. Hypothalamic obesity in patients with craniopharyngioma: Profound changes of several weight regulatory circuits

    Directory of Open Access Journals (Sweden)

    Christian eRoth

    2011-10-01

    Full Text Available One of the most striking examples of dysfunctional hypothalamic signaling of energy homeostasis is observed in patients with hypothalamic lesions leading to hypothalamic obesity (HO. This drastic condition is frequently seen in patients with craniopharyngioma (CP, an embryological tumor located in the hypothalamic and/or pituitary region, frequently causing not only hypopituitarism, but also leading to damage of medial hypothalamic nuclei due to the tumor and its treatment. HO syndrome in CP patients is characterized by fatigue, decreased physical activity, uncontrolled appetite, and morbid obesity, and is associated with insulin and leptin resistance. Mechanisms leading to the profoundly disturbed energy homeostasis are complex. This review summarizes different aspects of important clinical studies as well as data obtained in rodent studies. In addition a model is provided describing how medial hypothalamic lesion can interact simultaneously with several weight regulating circuitries.

  18. Profound Endothelial Damage Predicts Impending Organ Failure and Death in Sepsis

    DEFF Research Database (Denmark)

    Johansen, Maria E; Johansson, Pär I.; Ostrowski, Sisse R

    2015-01-01

    levels at enrollment predicted risk of multiple organ failure during follow-up (HR [> 14 ng/mL vs. organ failure and death in septic......Endothelial damage contributes to organ failure and mortality in sepsis, but the extent of the contribution remains poorly quantified. Here, we examine the association between biomarkers of superficial and profound endothelial damage (syndecan-1 and soluble thrombomodulin [sTM], respectively......), organ failure, and death in sepsis. The data from a clinical trial, including critically ill patients predominantly suffering sepsis (Clinicaltrials.gov: NCT00271752) were studied. Syndecan-1 and sTM levels at the time of study enrollment were determined. The predictive ability of biomarker levels...

  19. From metabolome to phenotype

    DEFF Research Database (Denmark)

    Khakimov, Bekzod; Rasmussen, Morten Arendt; Kannangara, Rubini Maya

    2017-01-01

    for ideal vegetable protein production and for augmented β-glucan production. Seeds from three barley lines (Bomi, lys3.a and lys5.f) were sampled eight times during grain filling and analysed for metabolites using gas chromatography-mass spectrometry (GC-MS). The lys3.a mutation disrupts a regulator gene...... their successful application to link genetic and environmental factors with the seed phenotype of unique and agro-economically important barley models for optimal vegetable protein and dietary fibre production......., causing an increase in proteins rich in the essential amino acid lysine, while lys5.f carries a mutation in an ADP-glucose transporter gene leading to a significant increase in production of mixed-linkage β-glucan at the expense of α-glucan. Unique metabolic patterns associated with the tricarboxylic acid...

  20. Deep Learning for Plant Phenotyping

    OpenAIRE

    Mori, Matteo

    2016-01-01

    Plant Phenotyping is an emerging science which provides us the knowledge to better understand plants. Indeed, the study of the link between genetic background and environment in which plants develop can help us to determine cures for plants’ sicknesses and new ways to improve yields using limited resources. In this regard, one of the main aspects of Plant Phenotyping that were studied in the past, was Root Phenotyping, which is based on the study of the root architectures. In particular, toda...

  1. Delineation of C12orf65-related phenotypes: a genotype-phenotype relationship.

    Science.gov (United States)

    Spiegel, Ronen; Mandel, Hanna; Saada, Ann; Lerer, Issy; Burger, Ayala; Shaag, Avraham; Shalev, Stavit A; Jabaly-Habib, Haneen; Goldsher, Dorit; Gomori, John M; Lossos, Alex; Elpeleg, Orly; Meiner, Vardiella

    2014-08-01

    C12orf65 participates in the process of mitochondrial translation and has been shown to be associated with a spectrum of phenotypes, including early onset optic atrophy, progressive encephalomyopathy, peripheral neuropathy, and spastic paraparesis.We used whole-genome homozygosity mapping as well as exome sequencing and targeted gene sequencing to identify novel C12orf65 disease-causing mutations in seven affected individuals originating from two consanguineous families. In four family members affected with childhood-onset optic atrophy accompanied by slowly progressive peripheral neuropathy and spastic paraparesis, we identified a homozygous frame shift mutation c.413_417 delAACAA, which predicts a truncated protein lacking the C-terminal portion. In the second family, we studied three affected individuals who presented with early onset optic atrophy, peripheral neuropathy, and spastic gait in addition to moderate intellectual disability. Muscle biopsy in two of the patients revealed decreased activities of the mitochondrial respiratory chain complexes I and IV. In these patients, we identified a homozygous splice mutation, g.21043 T>A (c.282+2 T>A) which leads to skipping of exon 2. Our study broadens the phenotypic spectrum of C12orf65 defects and highlights the triad of optic atrophy, axonal neuropathy and spastic paraparesis as its key clinical features. In addition, a clear genotype-phenotype correlation is anticipated in which deleterious mutations which disrupt the GGQ-containing domain in the first coding exon are expected to result in a more severe phenotype, whereas down-stream C-terminal mutations may result in a more favorable phenotype, typically lacking cognitive impairment.

  2. Propositional Density in Spoken and Written Language of Czech-Speaking Patients with Mild Cognitive Impairment

    Science.gov (United States)

    Smolík, Filip; Stepankova, Hana; Vyhnálek, Martin; Nikolai, Tomáš; Horáková, Karolína; Matejka, Štepán

    2016-01-01

    Purpose Propositional density (PD) is a measure of content richness in language production that declines in normal aging and more profoundly in dementia. The present study aimed to develop a PD scoring system for Czech and use it to compare PD in language productions of older people with amnestic mild cognitive impairment (aMCI) and control…

  3. Does visual impairment lead to additional disability in adults with intellectual disabilities?

    NARCIS (Netherlands)

    Sjoukes, L.; Koot, H. M.; Kooijman, A. C.; Evenhuis, H.

    This study addresses the question to what extent visual impairment leads to additional disability in adults with intellectual disabilities (ID). In a multi-centre cross-sectional study of 269 adults with mild to profound ID, social and behavioural functioning was assessed with observant-based

  4. Does visual impairment lead to additional disability in adults with intellectual disabilities?

    NARCIS (Netherlands)

    Evenhuis, H.M.; Sjoukes, L.; Koot, H.M.; Kooijman, A.C.

    2009-01-01

    Background: This study addresses the question to what extent visual impairment leads to additional disability in adults with intellectual disabilities (ID). Method: In a multi-centre cross-sectional study of 269 adults with mild to profound ID, social and behavioural functioning was assessed with

  5. Subtle variation in shade avoidance responses may have profound consequences for plant competitiveness.

    Science.gov (United States)

    Bongers, Franca J; Pierik, Ronald; Anten, Niels P R; Evers, Jochem B

    2017-12-21

    Although phenotypic plasticity has been shown to be beneficial for plant competitiveness for light, there is limited knowledge on how variation in these plastic responses plays a role in determining competitiveness. A combination of detailed plant experiments and functional-structural plant (FSP) modelling was used that captures the complex dynamic feedback between the changing plant phenotype and the within-canopy light environment in time and 3-D space. Leaf angle increase (hyponasty) and changes in petiole elongation rates in response to changes in the ratio between red and far-red light, two important shade avoidance responses in Arabidopsis thaliana growing in dense population stands, were chosen as a case study for plant plasticity. Measuring and implementing these responses into an FSP model allowed simulation of plant phenotype as an emergent property of the underlying growth and response mechanisms. Both the experimental and model results showed that substantial differences in competitiveness may arise between genotypes with only marginally different hyponasty or petiole elongation responses, due to the amplification of plant growth differences by small changes in plant phenotype. In addition, this study illustrated that strong competitive responses do not necessarily have to result in a tragedy of the commons; success in competition at the expense of community performance. Together, these findings indicate that selection pressure could probably have played a role in fine-tuning the sensitive shade avoidance responses found in plants. The model approach presented here provides a novel tool to analyse further how natural selection could have acted on the evolution of plastic responses.

  6. Gender Differences and the Risk of Falls in Individuals with Profound Vision Loss

    Science.gov (United States)

    Ray, Christopher T.; Wolf, Steven L.

    2010-01-01

    Adults with visual impairments experience a loss of balance and mobility, which presents a barrier to independence and is associated with the fear of falling. The purpose of this study was to determine the extent to which visual status, age, gender, body mass index (BMI), and the strength of quadriceps and hamstrings contribute to compromised…

  7. Differentiating characteristics of deafblindness and autism in people with congenital deafblindness and profound intellectual disability

    NARCIS (Netherlands)

    Hoevenaars-van den Boom, M.A.A.; Antonissen, A.C.F.M.; Knoors, H.E.T.; Vervloed, M.P.J.

    2009-01-01

    In persons with deafblindness, it is hard to distinguish autism spectrum disorders from several deafblind specific behaviours caused by the dual sensory impairments, especially when these persons are also intellectually disabled. As a result, there is an over-diagnosis of autism in persons who are

  8. Insulin sensitivity, insulin release and glucagon-like peptide-1 levels in persons with impaired fasting glucose and/or impaired glucose tolerance in the EUGENE2 study

    DEFF Research Database (Denmark)

    Laakso, M; Zilinskaite, J; Hansen, T

    2008-01-01

    AIMS/HYPOTHESIS: We examined the phenotype of individuals with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) with regard to insulin release and insulin resistance. METHODS: Non-diabetic offspring (n=874; mean age 40+/-10.4 years; BMI 26.6+/-4.9 kg/m(2)) of type 2 diabetic...

  9. A vascular mechanism to explain thermally mediated variations in deep-body cooling rates during the immersion of profoundly hyperthermic individuals.

    Science.gov (United States)

    Caldwell, Joanne N; van den Heuvel, Anne M J; Kerry, Pete; Clark, Mitchell J; Peoples, Gregory E; Taylor, Nigel A S

    2018-04-01

    What is the central question of this study? Does the cold-water immersion (14°C) of profoundly hyperthermic individuals induce reductions in cutaneous and limb blood flow of sufficient magnitude to impair heat loss relative to the size of the thermal gradient? What is the main finding and its importance? The temperate-water cooling (26°C) of profoundly hyperthermic individuals was found to be rapid and reproducible. A vascular mechanism accounted for that outcome, with temperature-dependent differences in cutaneous and limb blood flows observed during cooling. Decisions relating to cooling strategies must be based upon deep-body temperature measurements that have response dynamics consistent with the urgency for cooling. Physiologically trivial time differences for cooling the intrathoracic viscera of hyperthermic individuals have been reported between cold- and temperate-water immersion treatments. One explanation for that observation is reduced convective heat delivery to the skin during cold immersion, and this study was designed to test both the validity of that observation, and its underlying hypothesis. Eight healthy men participated in four head-out water immersions: two when normothermic, and two after exercise-induced, moderate-to-profound hyperthermia. Two water temperatures were used within each thermal state: temperate (26°C) and cold (14°C). Tissue temperatures were measured at three deep-body sites (oesophagus, auditory canal and rectum) and eight skin surfaces, with cutaneous vascular responses simultaneously evaluated from both forearms (laser-Doppler flowmetry and venous-occlusion plethysmography). During the cold immersion of normothermic individuals, oesophageal temperature decreased relative to baseline (-0.31°C over 20 min; P immersed in cold rather than in temperate water (P immersion, whereas pronounced constriction was evident during both immersions when subjects were hyperthermic, with the colder water eliciting a greater vascular

  10. Mild Cognitive Impairment (MCI)

    Science.gov (United States)

    Mild cognitive impairment (MCI) Overview Mild cognitive impairment (MCI) is an intermediate stage between the expected cognitive decline of normal aging and the more-serious decline of dementia. It ...

  11. Adapting for Impaired Patrons.

    Science.gov (United States)

    Schuyler, Michael

    1999-01-01

    Describes how a library, with an MCI Corporation grant, approached the process of setting up computers for the visually impaired. Discusses preparations, which included hiring a visually-impaired user as a consultant and contacting the VIP (Visually Impaired Persons) group; equipment; problems with the graphical user interface; and training.…

  12. Plant Phenotype Characterization System

    Energy Technology Data Exchange (ETDEWEB)

    Daniel W McDonald; Ronald B Michaels

    2005-09-09

    This report is the final scientific report for the DOE Inventions and Innovations Project: Plant Phenotype Characterization System, DE-FG36-04GO14334. The period of performance was September 30, 2004 through July 15, 2005. The project objective is to demonstrate the viability of a new scientific instrument concept for the study of plant root systems. The root systems of plants are thought to be important in plant yield and thus important to DOE goals in renewable energy sources. The scientific study and understanding of plant root systems is hampered by the difficulty in observing root activity and the inadequacy of existing root study instrumentation options. We have demonstrated a high throughput, non-invasive, high resolution technique for visualizing plant root systems in-situ. Our approach is based upon low-energy x-ray radiography and the use of containers and substrates (artificial soil) which are virtually transparent to x-rays. The system allows us to germinate and grow plant specimens in our containers and substrates and to generate x-ray images of the developing root system over time. The same plant can be imaged at different times in its development. The system can be used for root studies in plant physiology, plant morphology, plant breeding, plant functional genomics and plant genotype screening.

  13. Sex hormone binding globulin phenotypes

    DEFF Research Database (Denmark)

    Cornelisse, M M; Bennett, Patrick; Christiansen, M

    1994-01-01

    Human sex hormone binding globulin (SHBG) is encoded by a normal and a variant allele. The resulting SHBG phenotypes (the homozygous normal SHBG, the heterozygous SHBG and the homozygous variant SHBG phenotype) can be distinguished by their electrophoretic patterns. We developed a novel detection....... This method of detection was used to determine the distribution of SHBG phenotypes in healthy controls of both sexes and in five different pathological conditions characterized by changes in the SHBG level or endocrine disturbances (malignant and benign ovarian neoplasms, hirsutism, liver cirrhosis...... on the experimental values. Differences in SHBG phenotypes do not appear to have any clinical significance and no sex difference was found in the SHBG phenotype distribution....

  14. Age at onset and Parkinson disease phenotype

    Science.gov (United States)

    Pagano, Gennaro; Ferrara, Nicola; Brooks, David J.

    2016-01-01

    Objective: To explore clinical phenotype and characteristics of Parkinson disease (PD) at different ages at onset in recently diagnosed patients with untreated PD. Methods: We have analyzed baseline data from the Parkinson's Progression Markers Initiative database. Four hundred twenty-two patients with a diagnosis of PD confirmed by DaTSCAN imaging were divided into 4 groups according to age at onset (onset younger than 50 years, 50–59 years, 60–69 years, and 70 years or older) and investigated for differences in side, type and localization of symptoms, occurrence/severity of motor and nonmotor features, nigrostriatal function, and CSF biomarkers. Results: Older age at onset was associated with a more severe motor and nonmotor phenotype, a greater dopaminergic dysfunction on DaTSCAN, and reduction of CSF α-synuclein and total tau. The most common presentation was the combination of 2 or 3 motor symptoms (bradykinesia, resting tremor, and rigidity) with rigidity being more common in the young-onset group. In about 80% of the patients with localized onset, the arm was the most affected part of the body, with no difference across subgroups. Conclusions: Although the presentation of PD symptoms is similar across age subgroups, the severity of motor and nonmotor features, the impairment of striatal binding, and the levels of CSF biomarkers increase with age at onset. The variability of imaging and nonimaging biomarkers in patients with PD at different ages could hamper the results of future clinical trials. PMID:26865518

  15. Catalase deletion promotes prediabetic phenotype in mice.

    Science.gov (United States)

    Heit, Claire; Marshall, Stephanie; Singh, Surrendra; Yu, Xiaoqing; Charkoftaki, Georgia; Zhao, Hongyu; Orlicky, David J; Fritz, Kristofer S; Thompson, David C; Vasiliou, Vasilis

    2017-02-01

    Hydrogen peroxide is produced endogenously and can be toxic to living organisms by inducing oxidative stress and cell damage. However, it has also been identified as a signal transduction molecule. By metabolizing hydrogen peroxide, catalase protects cells and tissues against oxidative damage and may also influence signal transduction mechanisms. Studies suggest that acatalasemic individuals (i.e., those with very low catalase activity) have a higher risk for the development of diabetes. We now report catalase knockout (Cat -/- ) mice, when fed a normal (6.5% lipid) chow, exhibit an obese phenotype that manifests as an increase in body weight that becomes more pronounced with age. The mice demonstrate altered hepatic and muscle lipid deposition, as well as increases in serum and hepatic triglycerides (TGs), and increased hepatic transcription and protein expression of PPARγ. Liver morphology revealed steatosis with inflammation. Cat -/- mice also exhibited pancreatic morphological changes that correlated with impaired glucose tolerance and increased fasting serum insulin levels, conditions consistent with pre-diabetic status. RNA-seq analyses revealed a differential expression of pathways and genes in Cat -/- mice, many of which are related to metabolic syndrome, diabetes, and obesity, such as Pparg and Cidec. In conclusion, the results of the present study show mice devoid of catalase develop an obese, pre-diabetic phenotype and provide compelling evidence for catalase (or its products) being integral in metabolic regulation. Copyright © 2016. Published by Elsevier Inc.

  16. Simultaneous versus Sequential Intratympanic Steroid Treatment for Severe-to-Profound Sudden Sensorineural Hearing Loss.

    Science.gov (United States)

    Yoo, Myung Hoon; Lim, Won Sub; Park, Joo Hyun; Kwon, Joong Keun; Lee, Tae-Hoon; An, Yong-Hwi; Kim, Young-Jin; Kim, Jong Yang; Lim, Hyun Woo; Park, Hong Ju

    2016-01-01

    Severe-to-profound sudden sensorineural hearing loss (SSNHL) has a poor prognosis. We aimed to compare the efficacy of simultaneous and sequential oral and intratympanic steroids for this condition. Fifty patients with severe-to-profound SSNHL (>70 dB HL) were included from 7 centers. The simultaneous group (27 patients) received oral and intratympanic steroid injections for 2 weeks. The sequential group (23 patients) was treated with oral steroids for 2 weeks and intratympanic steroids for the subsequent 2 weeks. Pure-tone averages (PTA) and word discrimination scores (WDS) were compared before treatment and 2 weeks and 1 and 2 months after treatment. Treatment outcomes according to the modified American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) criteria were also analyzed. The improvement in PTA and WDS at the 2-week follow-up was 23 ± 21 dB HL and 20 ± 39% in the simultaneous group and 31 ± 29 dB HL and 37 ± 42% in the sequential group; this was not statistically significant. Complete or partial recovery at the 2-week follow-up was observed in 26% of the simultaneous group and 30% of the sequential group; this was also not significant. The improvement in PTA and WDS at the 2-month follow-up was 40 ± 20 dB HL and 37 ± 35% in the simultaneous group and 41 ± 25 dB HL and 48 ± 41% in the sequential group; this was not statistically significant. Complete or partial recovery at the 2-month follow-up was observed in 33% of the simultaneous group and 35% of the sequential group; this was also not significant. Seven patients in the sequential group did not need intratympanic steroid injections for sufficient improvement after oral steroids alone. Simultaneous oral/intratympanic steroid treatment yielded a recovery similar to that produced by sequential treatment. Because the addition of intratympanic steroids can be decided upon based on the improvement after an oral steroid, the sequential regimen can be recommended to avoid unnecessary

  17. Phenotype of normal spirometry in an aging population.

    Science.gov (United States)

    Vaz Fragoso, Carlos A; McAvay, Gail; Van Ness, Peter H; Casaburi, Richard; Jensen, Robert L; MacIntyre, Neil; Gill, Thomas M; Yaggi, H Klar; Concato, John

    2015-10-01

    In aging populations, the commonly used Global Initiative for Chronic Obstructive Lung Disease (GOLD) may misclassify normal spirometry as respiratory impairment (airflow obstruction and restrictive pattern), including the presumption of respiratory disease (chronic obstructive pulmonary disease [COPD]). To evaluate the phenotype of normal spirometry as defined by a new approach from the Global Lung Initiative (GLI), overall and across GOLD spirometric categories. Using data from COPDGene (n = 10,131; ages 45-81; smoking history, ≥10 pack-years), we evaluated spirometry and multiple phenotypes, including dyspnea severity (Modified Medical Research Council grade 0-4), health-related quality of life (St. George's Respiratory Questionnaire total score), 6-minute-walk distance, bronchodilator reversibility (FEV1 % change), computed tomography-measured percentage of lung with emphysema (% emphysema) and gas trapping (% gas trapping), and small airway dimensions (square root of the wall area for a standardized airway with an internal perimeter of 10 mm). Among 5,100 participants with GLI-defined normal spirometry, GOLD identified respiratory impairment in 1,146 (22.5%), including a restrictive pattern in 464 (9.1%), mild COPD in 380 (7.5%), moderate COPD in 302 (5.9%), and severe COPD in none. Overall, the phenotype of GLI-defined normal spirometry included normal adjusted mean values for dyspnea grade (0.8), St. George's Respiratory Questionnaire (15.9), 6-minute-walk distance (1,424 ft [434 m]), bronchodilator reversibility (2.7%), % emphysema (0.9%), % gas trapping (10.7%), and square root of the wall area for a standardized airway with an internal perimeter of 10 mm (3.65 mm); corresponding 95% confidence intervals were similarly normal. These phenotypes remained normal for GLI-defined normal spirometry across GOLD spirometric categories. GLI-defined normal spirometry, even when classified as respiratory impairment by GOLD, included adjusted mean values in the

  18. Does visual impairment lead to additional disability in adults with intellectual disabilities?

    Science.gov (United States)

    Evenhuis, H M; Sjoukes, L; Koot, H M; Kooijman, A C

    2009-01-01

    This study addresses the question to what extent visual impairment leads to additional disability in adults with intellectual disabilities (ID). In a multi-centre cross-sectional study of 269 adults with mild to profound ID, social and behavioural functioning was assessed with observant-based questionnaires, prior to expert assessment of visual function. With linear regression analysis the percentage of variance, explained by levels of visual function, was calculated for the total population and per ID level. A total of 107/269 participants were visually impaired or blind (WHO criteria). On top of the decrease by ID visual impairment significantly decreased daily living skills, communication & language, recognition/communication. Visual impairment did not cause more self-absorbed and withdrawn behaviour or anxiety. Peculiar looking habits correlated with visual impairment and not with ID. In the groups with moderate and severe ID this effect seems stronger than in the group with profound ID. Although ID alone impairs daily functioning, visual impairment diminishes the daily functioning even more. Timely detection and treatment or rehabilitation of visual impairment may positively influence daily functioning, language development, initiative and persistence, social skills, communication skills and insecure movement.

  19. Memory Impairment in Children with Language Impairment

    Science.gov (United States)

    Baird, Gillian; Dworzynski, Katharina; Slonims, Vicky; Simonoff, Emily

    2010-01-01

    Aim: The aim of this study was to assess whether any memory impairment co-occurring with language impairment is global, affecting both verbal and visual domains, or domain specific. Method: Visual and verbal memory, learning, and processing speed were assessed in children aged 6 years to 16 years 11 months (mean 9y 9m, SD 2y 6mo) with current,…

  20. Targeting superoxide dismutase to endothelial caveolae profoundly alleviates inflammation caused by endotoxin.

    Science.gov (United States)

    Shuvaev, Vladimir V; Kiseleva, Raisa Yu; Arguiri, Evguenia; Villa, Carlos H; Muro, Silvia; Christofidou-Solomidou, Melpo; Stan, Radu V; Muzykantov, Vladimir R

    2018-02-28

    Inflammatory mediators binding to Toll-Like receptors (TLR) induce an influx of superoxide anion in the ensuing endosomes. In endothelial cells, endosomal surplus of superoxide causes pro-inflammatory activation and TLR4 agonists act preferentially via caveolae-derived endosomes. To test the hypothesis that SOD delivery to caveolae may specifically inhibit this pathological pathway, we conjugated SOD with antibodies (Ab/SOD, size ~10nm) to plasmalemmal vesicle-associated protein (Plvap) that is specifically localized to endothelial caveolae in vivo and compared its effects to non-caveolar target CD31/PECAM-1. Plvap Ab/SOD bound to endothelial cells in culture with much lower efficacy than CD31 Ab/SOD, yet blocked the effects of LPS signaling with higher efficiency than CD31 Ab/SOD. Disruption of cholesterol-rich membrane domains by filipin inhibits Plvap Ab/SOD endocytosis and LPS signaling, implicating the caveolae-dependent pathway(s) in both processes. Both Ab/SOD conjugates targeted to Plvap and CD31 accumulated in the lungs after IV injection in mice, but the former more profoundly inhibited LPS-induced pulmonary inflammation and elevation of plasma level of interferon-beta and -gamma and interleukin-27. Taken together, these results indicate that targeted delivery of SOD to specific cellular compartments may offer effective, mechanistically precise interception of pro-inflammatory signaling mediated by reactive oxygen species. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Smoking cessation induces profound changes in the composition of the intestinal microbiota in humans.

    Directory of Open Access Journals (Sweden)

    Luc Biedermann

    Full Text Available BACKGROUND: The human intestinal microbiota is a crucial factor in the pathogenesis of various diseases, such as metabolic syndrome or inflammatory bowel disease (IBD. Yet, knowledge about the role of environmental factors such as smoking (which is known to influence theses aforementioned disease states on the complex microbial composition is sparse. We aimed to investigate the role of smoking cessation on intestinal microbial composition in 10 healthy smoking subjects undergoing controlled smoking cessation. METHODS: During the observational period of 9 weeks repetitive stool samples were collected. Based on abundance of 16S rRNA genes bacterial composition was analysed and compared to 10 control subjects (5 continuing smokers and 5 non-smokers by means of Terminal Restriction Fragment Length Polymorphism analysis and high-throughput sequencing. RESULTS: Profound shifts in the microbial composition after smoking cessation were observed with an increase of Firmicutes and Actinobacteria and a lower proportion of Bacteroidetes and Proteobacteria on the phylum level. In addition, after smoking cessation there was an increase in microbial diversity. CONCLUSIONS: These results indicate that smoking is an environmental factor modulating the composition of human gut microbiota. The observed changes after smoking cessation revealed to be similar to the previously reported differences in obese compared to lean humans and mice respectively, suggesting a potential pathogenetic link between weight gain and smoking cessation. In addition they give rise to a potential association of smoking status and the course of IBD.

  2. Partial neuroprotection by nNOS inhibition during profound asphyxia in preterm fetal sheep.

    Science.gov (United States)

    Drury, Paul P; Davidson, Joanne O; van den Heuij, Lotte G; Tan, Sidhartha; Silverman, Richard B; Ji, Haitao; Blood, Arlin B; Fraser, Mhoyra; Bennet, Laura; Gunn, Alistair Jan

    2013-12-01

    Preterm brain injury is partly associated with hypoxia-ischemia starting before birth. Excessive nitric oxide production during HI may cause nitrosative stress, leading to cell membrane and mitochondrial damage. We therefore tested the hypothesis that therapy with a new, selective neuronal nitric oxide synthase (nNOS) inhibitor, JI-10 (0.022mg/kg bolus, n=8), given 30min before 25min of complete umbilical cord occlusion was protective in preterm fetal sheep at 101-104day gestation (term is 147days), compared to saline (n=8). JI-10 had no effect on fetal blood pressure, heart rate, carotid and femoral blood flow, total EEG power, nuchal activity, temperature or intracerebral oxygenation on near-infrared spectroscopy during or after occlusion. JI-10 was associated with later onset of post-asphyxial seizures compared with saline (p<0.05), and attenuation of the subsequent progressive loss of cytochrome oxidase (p<0.05). After 7days recovery, JI-10 was associated with improved neuronal survival in the caudate nucleus (p<0.05), but not the putamen or hippocampus, and more CNPase positive oligodendrocytes in the periventricular white matter (p<0.05). In conclusion, prophylactic nNOS inhibition before profound asphyxia was associated with delayed onset of seizures, slower decline of cytochrome oxidase and partial white and gray matter protection, consistent with protection of mitochondrial function. © 2013.

  3. Attentional processes in interactions between people with profound intellectual and multiple disabilities and direct support staff.

    Science.gov (United States)

    Hostyn, Ine; Ine, Hostyn; Neerinckx, Heleen; Heleen, Neerinckx; Maes, Bea; Bea, Maes

    2011-01-01

    Few studies have examined joint attention in interactions with persons with profound intellectual and multiple disabilities (PIMD), despite its important role in high-quality interaction. The purpose of this study is to describe the attention-directing behaviours of persons with PIMD and their direct support staff and the attention episodes resulting from their interactions, and to understand how these variables relate to each other. Video observations of 17 staff-client dyads were coded using partial interval recording. The results showed considerable variation across individuals and dyads. In general, persons with PIMD directed the attention of staff members infrequently. The staff members frequently directed their clients' attention towards a topic of interest but did not often use the tactile modality. Within the staff-client dyad, there was not much joint attention; however, shared attention episodes occurred frequently. Shared attention and joint attention are strongly correlated. A negative correlation was found between clients not using attention-directing behaviours and staff members using tactile methods to direct the attention, and joint attention episodes. This study presents both directions for future research and practical implications. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. The current status of audiologic rehabilitation for profound unilateral sensorineural hearing loss.

    Science.gov (United States)

    Bishop, Charles E; Eby, Thomas L

    2010-03-01

    Audiologic rehabilitation of individuals with profound unilateral sensorineural hearing loss (USNHL) has traditionally been limited to the use of air-conduction contralateral routing of sound (CROS) hearing aids. Treatment for these individuals has expanded with new applications of the bone-anchored hearing aid (BAHA), transcranial hearing aid (t-CROS), and the cochlear implant. In this article, the authors review the literature that addresses these various treatment options. Contemporary review Historical information is available that describes the limited efficacy of air-conduction CROS hearing aids in lifting hearing handicap associated with USNHL. Current investigations on providing cross hearing are generally focused on use of the BAHA. Little is known at present whether new developments in hearing aid technology can improve on conventional air-conduction CROS or t-CROS approaches. Interestingly, the cochlear implant seems to be a viable option for individuals with USNHL and tinnitus who also have intact auditory nerve pathways. There is indication in the literature that BAHA provides greater relief of hearing handicap associated with USNHL than CROS hearing aids; however, both have been found to provide limited patient satisfaction and seemingly fall short of restoring true sound localization. Adequate trials have not been performed comparing BAHA with the best CROS hearing aid technology. Transcranial hearing aids and cochlear implants are experimental methods to treat USNHL and hold promise, although there remains a lack of studies available to fully support this.

  5. Driving to learn in a powered wheelchair: the process of learning joystick use in people with profound cognitive disabilities.

    Science.gov (United States)

    Nilsson, Lisbeth; Eklund, Mona; Nyberg, Per; Thulesius, Hans

    2011-01-01

    The Driving to Learn project explored ways to help people with profound cognitive disabilities practice operating a joystick-operated powered wheelchair. The project used a grounded theory approach with constant comparative analysis and was carried out over 12 yr. The participants were 45 children and adults with profound cognitive disabilities. Reference groups included 17 typically developing infants and 64 participants with lesser degrees of cognitive disability. The data sources included video recordings, field notes, open interviews, and a rich mixture of literature. The findings that emerged yielded strategies for facilitating achievements, an 8-phase learning process, an assessment tool, and a grounded theory of deplateauing explaining the properties necessary for participants to exceed expected limitations and plateaus. Eight participants with profound cognitive disabilities reached goal-directed driving or higher. Participants were empowered by attaining increased control over tool use, improving their autonomy and quality of life.

  6. Detection of phenazepam in impaired driving.

    Science.gov (United States)

    Kerrigan, Sarah; Mellon, Monica Brady; Hinners, Paige

    2013-10-01

    Phenazepam is a potent 1,4-benzodiazepine that has gained notoriety among recreational drug users. First synthesized in Ukraine in the 1970s, it is one of the most commonly prescribed benzodiazepines in Russia and other commonwealth of independent state nations, where it is used therapeutically as a prescription drug. Reports of abuse are widespread and several European countries have taken steps to control its use. However, in the USA, phenazepam is not approved for use by the Food and Drug Administration, nor scheduled under the Federal Controlled Substances Act. Phenazepam is widely available on the Internet, and recreational drug users report a potency 10-fold greater than that of nordiazepam. We report a case of a 24-year-old male driver who was apprehended for impaired driving following a two-vehicle crash. The subject exhibited slurred speech and profound psychomotor impairment. Toxicology testing revealed phenazepam at a concentration of 76 ng/mL in blood, with no other drugs detected. This case report not only demonstrates the potential for adverse traffic safety consequences following the misuse of phenazepam, but also highlights the importance of analytical factors such as immunoassay cutoff concentration, cross-reactivity and comprehensive screening using chromatographic-based techniques for impaired driving investigations.

  7. Mimicry in Heliconius and Ithomiini butterflies: The profound consequences of an adaptation

    Directory of Open Access Journals (Sweden)

    Elias Marianne

    2015-01-01

    Full Text Available Prey populations have evolved multiple strategies to escape predation. Camouflage is a strategy resting on avoiding detection by potential predators, whereas aposematism relies on advertising chemical defences with conspicuous warning signals. While camouflaged phenotypes are subject to negative frequency-dependent selection, aposematic preys are under positive frequency-dependence, where the efficiency of a signal increases with its own local abundance. Because of his “strength-in-number” effect, multiple chemically-defended species exposed to the same suite of predators gain a selective advantage from converging on the same warning signals. Convergence in warning signals is called Müllerian mimicry. Here, we review the results of recent genetic and ecological research on two well-studied groups of neotropical Müllerian mimetic butterflies, the genus Heliconius and the tribe Ithomiini, which advertise their unpalatability through conspicuous wing colour patterns. Mimicry represents a major adaptation in these groups, where the effects of selection extend well beyond mere phenotypic resemblance. Selection acts on other traits used as mating cues, on the genetic architecture of colour pattern and even on the ecological niche of species. The origin of mimicry itself and the coexistence of multiple mimicry patterns are well understood, but the ultimate drivers of mimicry diversity remain unclear.

  8. Phenotypic plasticity, costs of phenotypes, and costs of plasticity

    DEFF Research Database (Denmark)

    Callahan, Hilary S; Maughan, Heather; Steiner, Uli

    2008-01-01

    Why are some traits constitutive and others inducible? The term costs often appears in work addressing this issue but may be ambiguously defined. This review distinguishes two conceptually distinct types of costs: phenotypic costs and plasticity costs. Phenotypic costs are assessed from patterns...... of covariation, typically between a focal trait and a separate trait relevant to fitness. Plasticity costs, separable from phenotypic costs, are gauged by comparing the fitness of genotypes with equivalent phenotypes within two environments but differing in plasticity and fitness. Subtleties associated with both...... types of costs are illustrated by a body of work addressing predator-induced plasticity. Such subtleties, and potential interplay between the two types of costs, have also been addressed, often in studies involving genetic model organisms. In some instances, investigators have pinpointed the mechanistic...

  9. Deep Phenotyping: Deep Learning For Temporal Phenotype/Genotype Classification

    OpenAIRE

    Najafi, Mohammad; Namin, Sarah; Esmaeilzadeh, Mohammad; Brown, Tim; Borevitz, Justin

    2017-01-01

    High resolution and high throughput, genotype to phenotype studies in plants are underway to accelerate breeding of climate ready crops. Complex developmental phenotypes are observed by imaging a variety of accessions in different environment conditions, however extracting the genetically heritable traits is challenging. In the recent years, deep learning techniques and in particular Convolutional Neural Networks (CNNs), Recurrent Neural Networks (RNNs) and Long-Short Term Memories (LSTMs), h...

  10. Multiple sclerosis with predominant, severe cognitive impairment

    Science.gov (United States)

    Staff, Nathan P.; Lucchinetti, Claudia F.; Keegan, B. Mark

    2009-01-01

    Objective To describe the characteristics of multiple sclerosis (MS) presenting with severe cognitive impairment as its primary disabling manifestation. Design Retrospective case series. Setting Tertiary referral center. Patients Patients were identified through the Mayo Clinic data retrieval system (1996–2008) with definite MS (McDonald criteria) and severe cognitive impairment as their primary neurological symptom without accompanying significant MS-related impairment or alternative diagnosis for cognitive dysfunction. Twenty-three patients meeting inclusion criteria were compared regarding demographics, clinical course and radiological features. Main Outcome Measures Demographic, clinical, and radiological characteristics of the disease. Results Twelve patients were men. The median age of the first clinical symptom suggestive of CNS demyelination was 33 years, and severe MS-related cognitive impairment developed at a median of 39 years. Cognitive impairment could be dichotomized as subacute fulminant (n=9) or chronic progressive (n=14) in presentation, which corresponded to subsequent relapsing or progressive MS courses. Study patients commonly exhibited psychiatric (65%), mild cerebellar (57%) and cortical symptoms and signs (e.g. seizure, aphasia, apraxia) (39%). Fourteen of 21 (67%), where documented, smoked cigarettes. Brain MRI demonstrated diffuse cerebral atrophy in 16 and gadolinium enhancing lesions in 11. Asymptomatic spinal cord MRI lesions were present in 12 of 16 patients (75%). Immunomodulatory therapies were generally ineffective in improving these patients. Conclusions We describe patients with MS whose clinical phenotype is characterized by severe cognitive dysfunction and prominent cortical and psychiatric signs presenting as a subacute fulminant or chronic progressive clinical course. Cigarette smokers may be over represented in this phenotype. PMID:19752304

  11. A Glance on Diagnosis and Ttreatment of Profound Fatigue in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Mojtaba Azimian

    2007-09-01

    Full Text Available Multiple Sclerosis (M.S is one of the prevalent diseases of the central nervous system which cause disability in young adults. This appears as neural signs in different parts and various times. The main defect is local deterioration or destruction of myelin tissue in the brain and spinal cord. Profound fatigue is one the most common symptoms of this disease. Because MS is prevalent in middle ages, so the presence of this symptom affects the life and activity of the patient In these ages people have high amount of activities and this functional disorder creates many difficulties for daily works in patient. For this reason, fatigue problem in patients, always, have caught the attention of researchers. Despite numerous studies, still the exact reason for producing fatigue have not been mentioned But several mechanisms have been discussed, such as: autoimmune mechanism of the disease, Involvement and disorder of endocrine system, involvement of central nervous system and de-synchronization of autonom system. Among these, autoimmune mechanism is considered as a main role in producing fatigue. Lack of proper knowledge regarding exact fatigue mechanism several problems in its treatment. Evaluation is the first step for controlling fatigue, which is done through various tests. Clear and proper evaluation can be obtained by these tests. After evaluation, non-drug and finally drug procedures are helpful. In non-drug treatment the focus is on: sport exercises, suitable diet program, identification and improvement of the patient psychotic disorders, energy conservation methods. Finally, the use of drugs such as Amantadine, Pemoline and Modafini is recommended for fatigue treatment.

  12. Profound tumor-specific Th2 bias in patients with malignant glioma

    International Nuclear Information System (INIS)

    Shimato, Shinji; Maier, Lisa M; Maier, Richard; Bruce, Jeffrey N; Anderson, Richard CE; Anderson, David E

    2012-01-01

    Vaccination against tumor-associated antigens is one promising approach to immunotherapy against malignant gliomas. While previous vaccine efforts have focused exclusively on HLA class I-restricted peptides, class II-restricted peptides are necessary to induce CD4 + helper T cells and sustain effective anti-tumor immunity. In this report we investigated the ability of five candidate peptide epitopes derived from glioma-associated antigens MAGE and IL-13 receptor α2 to detect and characterize CD4 + helper T cell responses in the peripheral blood of patients with malignant gliomas. Primary T cell responses were determined by stimulating freshly isolated PBMCs from patients with primary glioblastoma (GBM) (n = 8), recurrent GBM (n = 5), meningioma (n = 7), and healthy controls (n = 6) with each candidate peptide, as well as anti-CD3 monoclonal antibody (mAb) and an immunodominant peptide epitope derived from myelin basic protein (MBP) serving as positive and negative controls, respectively. ELISA was used to measure IFN-γ and IL-5 levels, and the ratio of IFN-γ/IL-5 was used to determine whether the response had a predominant Th1 or Th2 bias. We demonstrate that novel HLA Class-II restricted MAGE-A3 and IL-13Rα2 peptides can detect T cell responses in patients with GBMs as well as in healthy subjects. Stimulation with a variety of peptide antigens over-expressed by gliomas is associated with a profound reduction in the IFN-γ/IL-5 ratio in GBM patients relative to healthy subjects. This bias is more pronounced in patients with recurrent GBMs. Therapeutic vaccine strategies to shift tumor antigen-specific T cell response to a more immunostimulatory Th1 bias may be needed for immunotherapeutic trials to be more successful clinically

  13. Cochlear implantation: is hearing preservation necessary in severe to profound hearing loss?

    Science.gov (United States)

    Derinsu, Ufuk; Serin, Gediz Murat; Akdaş, Ferda; Batman, Çağlar

    2011-03-01

    The goal of the cochlear implant surgery is to place the electrode array with minimal damage to preserve the residual hearing. Round-window insertion can be performed in a manner that is potentially less traumatic than the standard cochleostomy. The purpose of the study was to investigate audiological results of the round-window approach using standard electrode. A retrospective study was performed to evaluate our experience in patients with implanted through round window between January 2007 and March 2009. Sixty patients had undergone cochlear implant surgery through the round window with full insertion of a standard electrode array. Preoperative and postoperative pure-tone thresholds were measured for implanted ears in the range of 250 to 4000 Hz. Within these 60 cases, 31 patients had been evaluated. The population comprised 16 women and 15 men. The mean age was 15.96 years (range, 4-64 years). Follow-up times ranged from 6 to 26 months. Preservation of low-frequency hearing (250 and 500 Hz) was achieved in 27 (87%) of 31 patients. Complete hearing preservation (all frequencies) was accomplished in 11 patients (35.48%). No hearing could be determined postoperatively in 4 patients (12.9%), having preoperative thresholds of 120 dB at 250, 500, and 1000 Hz. Round-window approach has been widely used for preservation of residual hearing. In our patients with severe to profound hearing loss, we preserved residual hearing. Although the residual hearing cannot be sufficient for using additional acoustic stimulation, the preserved residual hearing means minimal damage and a more convenient cochlea, so this is promising for future development.

  14. Recurrent Vestibular Migraine Vertigo Attacks Associated With the Development of Profound Bilateral Vestibulopathy: A Case Series.

    Science.gov (United States)

    Wester, Jacob L; Ishiyama, Akira; Ishiyama, Gail

    2017-09-01

    Bilateral vestibulopathy (BVP) is a debilitating condition characterized by gait ataxia, oscillopsia, and imbalance. Case series of patients with migraine-linked vertigo spells and profound BVP. PATIENT 1:: A 69-year-old man presented with a history of recurrent severe vertigo spells lasting up to 3 days in duration associated with prostrating migraine headaches starting at age 60. His symptoms were misdiagnosed as an anxiety syndrome. At age 68, electronystagmography (ENG) revealed bilaterally absent caloric responses and complete BVP. His hearing was normal. PATIENT 2:: A 51-year-old man presented with a history of "earthquake-like" vertigo, sharp head pain, and phonophobia. These episodes occurred a handful of times over a 7-year period. Previous ENG testing at age 43 was normal. However, his ENG at age 48 revealed complete BVP. He was started on acetazolamide and noted improved balance, although subsequent ENG was unchanged. PATIENT 3:: A 49-year-old woman presented with a history of recurrent migraines with visual aura associated with vertigo lasting 1 hour. ENG at age 50 revealed complete BVP. Subjectively, she noted improved balance with acetazolamide and subsequent ENG demonstrated mild improvement. PATIENT 4:: A 43-year-old man presented with a 5-year history of optical migraines and recurrent vertigo spells, lasting 30 seconds, which was misdiagnosed as positional vertigo. He additionally had a 10-year history of oscillopsia. ENG at age 61 revealed complete BVP. In these cases, vestibular migraine was linked to recurrent vertigo spells that eventually led to complete bilateral vestibulopathy.

  15. The notochord in Atlantic salmon (Salmo salar L.) undergoes profound morphological and mechanical changes during development.

    Science.gov (United States)

    Kryvi, Harald; Rusten, Iselin; Fjelldal, Per Gunnar; Nordvik, Kari; Totland, Geir K; Karlsen, Tine; Wiig, Helge; Long, John H

    2017-11-01

    We present the development of the notochord of the Atlantic salmon (Salmo salar L.), from early embryo to sexually mature fish. Over the salmon's lifespan, profound morphological changes occur. Cells and gross structures of the notochord reorganize twice. In the embryo, the volume of the notochord is dominated by large, vacuolated chordocytes; each cell can be modeled as a hydrostat organized into a larger cellular-hydrostat network, structurally bound together with desmosomes. After the embryo hatches and grows into a fry, vacuolated chordocytes disappear, replaced by extracellular lacunae. The formation of mineralized, segmental chordacentra stiffens the notochord and creates intervertebral joints, where tissue strain during lateral bending is now focused. As development proceeds towards the parr stage, a process of devacuolization and intracellular filament accumulation occur, forming highly dense, non-vacuolated chordocytes. As extracellular lacunae enlarge, they are enclosed by dense filamentous chordocytes that form transverse intervertebral septa, which are connected to the intervertebral ligaments, and a longitudinal notochordal strand. In the vertebral column of pelagic adults, large vacuolated chordocytes reappear; cells of this secondary population have a volume up to 19 000 times larger than the primary vacuolated chordocytes of the early notochord. In adults the lacunae have diminished in relative size. Hydrostatic pressure within the notochord increases significantly during growth, from 525 Pa in the alevins to 11 500 Pa in adults, at a rate of increase with total body length greater than that expected by static stress similarity. Pressure and morphometric measurements were combined to estimate the stress in the extracellular material of the notochordal sheath and intervertebral ligaments and the flexural stiffness of the axial skeleton. The functional significance of the morphological changes in the axial skeleton is discussed in relation to the

  16. NATURE FACILITATES CONNECTION WITH THE PROFOUND SELF: NEEDS, GOALS AND RESOURCE AWARENESS

    Directory of Open Access Journals (Sweden)

    Nicoleta Răban-Motounu

    2014-11-01

    Full Text Available The present study is based on Kaplan and Kaplan’s (1989 theory explaining the restorative effects that nature has on a person’s psychic. According to this theory, nature exerts a “soft fascination” combining the activation of involuntary attention mechanisms with the reflexive awareness, allowing a spontaneous detachment from stress factors and automatic functioning, and also the feeling of compatibility between personal purposes, and the possibilities for action offered by the environment (a sense of meaning. Our objective was to investigate the effects of nature on Self awareness: the immediate, emotional experience; needs awareness and organization; plans for action, and availability of resources, both personal, and external. We conducted an experiment with an experimental group (persons watching a video with life in nature and an active control group (involved in a psychotherapeutic technique focused on confronting and solving personal difficulties by creative means, accompanied by a short psychological analysis. The effects were assessed in terms of “here and now” emotions and available resources according to a self-evaluation scale, and with open-ended questions regarding personal needs and goals. The results showed that, for the experimental group, the relaxation effects and the awareness of long term goals were stronger, while all the other effects were the same as for the control group. The results suggest that indeed, nature helps a person get in contact with her profound Self, allowing the access to both “here and now” basic needs, and also long term goals (inner sources of meaning, the sense of connection between internal tendencies, personal, and external resources, resulting in increased positive emotions, and decreased negative emotions. Nature contemplation may facilitate a meditative state whit all its positive effects.

  17. Achieving and sustaining profound institutional change in healthcare: case study using neo-institutional theory.

    Science.gov (United States)

    Macfarlane, Fraser; Barton-Sweeney, Cathy; Woodard, Fran; Greenhalgh, Trisha

    2013-03-01

    Change efforts in healthcare sometimes have an ambitious, whole-system remit and seek to achieve fundamental changes in norms and organisational culture rather than (or as well as) restructuring the service. Long-term evaluation of such initiatives is rarely undertaken. We report a secondary analysis of data from an evaluation of a profound institutional change effort in London, England, using a mixed-method longitudinal case study design. The service had received £15 million modernisation funding in 2004, covering multiple organisations and sectors and overseen by a bespoke management and governance infrastructure that was dismantled in 2008. In 2010-11, we gathered data (activity statistics, documents, interviews, questionnaires, site visits) and compared these with data from 2003 to 2008. Data analysis was informed by neo-institutional theory, which considers organisational change as resulting from the material-resource environment and three 'institutional pillars' (regulative, normative and cultural-cognitive), enacted and reproduced via the identities, values and activities of human actors. Explaining the long-term fortunes of the different components of the original programme and their continuing adaptation to a changing context required attention to all three of Scott's pillars and to the interplay between macro institutional structures and embedded human agency. The paper illustrates how neo-institutional theory (which is typically used by academics to theorise macro-level changes in institutional structures over time) can also be applied at a more meso level to inform an empirical analysis of how healthcare organisations achieve change and what helps or hinders efforts to sustain those changes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. What parents find important in the support of a child with profound intellectual and multiple disabilities.

    Science.gov (United States)

    Jansen, S L G; van der Putten, A A J; Vlaskamp, C

    2013-05-01

    The importance of a partnership between parents and professionals in the support of children with disabilities is widely acknowledged and is one of the key elements of 'family-centred care'. To what extent family-centred principles are also applied to the support of persons with profound intellectual and multiple disabilities (PIMD) is not yet known. The purpose of this exploratory study was to examine what parents with a child with PIMD find important in the support of their child. In addition, we examined which child or parent characteristics influence these parental opinions. In total, 100 parents completed an adapted version of the Measure of Processes of Care. Mean unweighted and weighted scale scores were computed. Non-parametric tests were used to examine differences in ratings due to child (gender, age, type and number of additional disabilities, type of services used and duration of service use) and parent characteristics (gender, involvement with support and educational level). Parents rated situations related to 'Respectful and Supportive Care' and 'Enabling and Partnership' with averages of 7.07 and 6.87 respectively on a scale from 1 to 10. They were generally satisfied with the services provided, expressed in a mean score of 6.88 overall. The age of the child significantly affected the scores for 'Providing Specific Information about the Child'. Parents of children in the '6-12 years' age group gave significantly higher scores on this scale than did parents of children in the '≥17 years' age group (U = 288, r = -0.34). This study shows that parents with children with PIMD find family-centred principles in the professional support of their children important. Although the majority of parents are satisfied with the support provided for their children, a substantial minority of the parents indicated that they did not receive the support they find important. © 2012 Blackwell Publishing Ltd.

  19. Time use of parents raising children with severe or profound intellectual and multiple disabilities.

    Science.gov (United States)

    Luijkx, J; van der Putten, A A J; Vlaskamp, C

    2017-07-01

    Raising children with severe or profound intellectual and multiple disabilities (PIMD) is expected to put extreme pressure on parental time use patterns. The aim of this study was to examine the total time use of mothers and fathers raising children with PIMD and compare it with the time use of parents of typically developing children. Twenty-seven fathers and 30 mothers raising children with PIMD completed a time use diary on a mobile phone or tablet app, as did 66 fathers and 109 mothers of typically developing children. Independent t-tests and Mann-Whitney tests were performed to compare mean time use. There are no differences in the time use of parents of children with PIMD on contracted time (paid work and educational activities) and necessary time (personal care, eating and drinking and sleeping) when compared with parents of typically developing children. There are significant differences between the parents of children with PIMD and the parents of typically developing children in terms of committed time (time for domestic work and the care and supervision of their children) and free time. The mothers of children with PIMD spend significantly less time on domestic work and more time on care and supervision than mothers of typically developing children. This study shows that the parents of children with PIMD have to spend a significant amount of time on care tasks and have on average 1.5 h less free time per day than parents of typically developing children. This is a striking difference, because leisure time can substantially contribute to well-being. Therefore, it is important not only to consider a child with PIMD's support needs but also to identify what parents need to continue their children's daily care and supervision. © 2017 John Wiley & Sons Ltd.

  20. PHENOTYPIC CORRELATIONS AND BODY WEIGHTS ...

    African Journals Online (AJOL)

    Dr Osondu

    Ethiopian Journal of Environmental Studies and Management Vol. 4 No.3 2011. PHENOTYPIC ... because of its high meat quality and acceptance by her populace. The meat is ... commands high price in the restaurants and markets than other ...

  1. Localization of A Novel Autosomal Recessive Non-Syndromic Hearing Impairment Locus (DFNB38) to 6q26–q27 in a Consanguineous Kindred from Pakistan

    OpenAIRE

    Ansar, Muhammad; Ramzan, Mohammad; Pham, Thanh L.; Yan, Kai; Jamal, Syed Muhammad; Haque, Sayedul; Ahmad, Wasim; Leal, Suzanne M.

    2003-01-01

    For autosomal recessive nonsyndromic hearing impairment over 30 loci have been mapped and 19 genes have been identified. DFNB38, a novel locus for autosomal recessive nonsyndromic hearing impairment, was localized in a consanguineous Pakistani kindred to 6q26–q27. The affected family members present with profound prelingual sensorineural hearing impairment and use sign language for communications. Linkage was established to microsatellite markers located on chromosome 6q26–q27 (Multipoint lod...

  2. The genetic basis of hair whorl, handedness, and other phenotypes

    Science.gov (United States)

    Hatfield, J.S.

    2006-01-01

    Evidence is presented that RHO, RHCE, and other RH genes, may be interesting candidates to consider when searching for the genetic basis of hair whorl rotation (i.e., clockwise or counterclockwise), handedness (i.e., right handed, left handed or ambidextrous), speech laterality (i.e., right brained or left brained), speech dyslexia (e.g., stuttering), sexual orientation (i.e., heterosexual, homosexual, bisexual, or transsexual), schizophrenia, bipolar disorder, and autism spectrum disorder. Such evidence involves the need for a genetic model that includes maternal immunization to explain some of the empirical results reported in the literature. The complex polymorphisms present among the maternally immunizing RH genes can then be used to explain other empirical results. Easily tested hypotheses are suggested, based upon genotypic (but not phenotypic) frequencies of the RH genes. In particular, homozygous dominant individuals are expected to be less common or lacking entirely among the alternative phenotypes. If it is proven that RH genes are involved in brain architecture, it will have a profound effect upon our understanding of the development and organization of the asymmetrical vertebrate brain and may eventually lead to a better understanding of the developmental processes which occur to produce the various alternative phenotypes discussed here. In addition, if RH genes are shown to be involved in the production of these phenotypes, then the evolutionary studies can be performed to demonstrate the beneficial effect of the recessive alleles of RHO and RHCE, and why human evolution appears to be selecting for the recessive alleles even though an increase in the frequency of such alleles may imply lower average fecundity among some individuals possessing them.

  3. Profound loss of general knowledge in retrograde amnesia: Evidence from an amnesic artist

    Directory of Open Access Journals (Sweden)

    Emma eGregory

    2014-05-01

    Full Text Available Studies of retrograde amnesia have focused on autobiographical memory, with fewer studies examining how non-autobiographical memory is affected. Those that have done so have focused primarily on memory for famous people and public events—relatively limited aspects of memory that are tied to learning during specific times of life and do not deeply tap into the rich and extensive knowledge structures that are developed over a lifetime. To assess whether retrograde amnesia can also cause impairments to other forms of general world knowledge, we explored losses across a broad range of knowledge domains in a newly-identified amnesic. LSJ is a professional artist, amateur musician and history buff with extensive bilateral medial temporal and left anterior temporal damage. We examined LSJ's knowledge across a range of everyday domains (e.g., sports and domains for which she had premorbid expertise (e.g., famous paintings. Across all domains tested, LSJ showed losses of knowledge at a level of breadth and depth never before documented in retrograde amnesia. These results show that retrograde amnesia can involve broad and deep deficits across a range of general world knowledge domains. Thus, losses that have already been well-documented (famous people and public events may severely underestimate the nature of human knowledge impairment that can occur in retrograde amnesia.

  4. Improving Social Skills in Adolescents and Adults with Autism and Severe to Profound Intellectual Disability: A Review of the Literature

    Science.gov (United States)

    Walton, Katherine M.; Ingersoll, Brooke R.

    2013-01-01

    Social skills are important treatment targets for individuals with autism spectrum disorders (ASD) across the lifespan. However, few treatments are available for adolescents and adults with ASD who also have severe to profound intellectual disability (S/PID). Several social skill interventions have been described that may improve social skills in…

  5. The Hands with Eyes and Nose in the Palm: As Effective Communication Alternatives for Profoundly Deaf People in Zimbabwe

    Science.gov (United States)

    Mutswanga, Phillipa

    2017-01-01

    Drawing from the experiences and testimonies of people with profound deafness, the study qualitatively explored the use of the hands with eyes and nose in the palm as communication alternatives in the field of deafness. The study was prompted by the 27 year old lady, Leah Katz-Hernandez who is deaf who got engaged in March 2015 as the 2016…

  6. How to Facilitate Transition to Adulthood? Innovative Solutions from Parents of Young Adults with Profound Intellectual Disability

    Science.gov (United States)

    Gauthier-Boudreault, Camille; Couture, Mélanie; Gallagher, Frances

    2018-01-01

    Background: At age 21, access to specialised services for youth with profound intellectual disability is reduced. Few studies have focused on parents' views concerning potential solutions to ease the transition to adulthood, and most existing solutions target young adults with less severe intellectual disability. The aim of this study is to…

  7. Reliability of assessing the sensory perception of children with profound intellectual and multiple disabilities : a case study

    NARCIS (Netherlands)

    Vlaskamp, C.; Cuppen-Fonteine, H.

    Background This study describes preliminary stages of developing a checklist to enable practitioners to determine the behavioural responses of children with profound intellectual and multiple disabilities to sensory stimuli. Reliability of currently used checklists is low, with a focus on the

  8. Motor activation in people with profound intellectual and multiple disabilities: research in daily practice in residential facilities

    NARCIS (Netherlands)

    Bossink, Leontien; van der Putten, Annette; Vlaskamp, Carla

    2014-01-01

    Aim: The total study aims at generating knowledge about the best way to motor activate persons with profound intellectual and multiple disabilities (PIMD) in residential facilities. The purpose of the current poster presentation is to present the results of the first step executed in this project

  9. Parental Adaptation to Out-of-Home Placement of a Child with Severe or Profound Developmental Disabilities

    Science.gov (United States)

    Jackson, Jeffrey B.; Roper, Susanne Olsen

    2014-01-01

    Utilizing grounded theory qualitative research methods, a model was developed for describing parental adaptation after voluntary placement of a child with severe or profound developmental disabilities in out-of-home care. Interviews of parents from 20 families were analyzed. Parents' cognitive appraisals of placement outcomes were classified…

  10. The documentation of health problems in relation to prescribed medication in people with profound intellectual and multiple disabilities

    NARCIS (Netherlands)

    van der Heide, D. C.; van der Putten, A. A. J.; van den Berg, P. B.; Taxis, K.; Vlaskamp, C.

    Persons with profound intellectual and multiple disabilities (PIMD) suffer from a wide range of health problems and use a wide range of different drugs. This study investigated for frequently used medication whether there was a health problem documented in the medical notes for the drug prescribed.

  11. You Should be Dancin:! The Role of Performing Arts in the Lives of the Severely and Profoundly Handicapped.

    Science.gov (United States)

    Barringer, Mary Dean

    The manual presents a program planning framework and teaching units for teaching dance and movement to severely and profoundly handicapped individuals. The planning framework contains four components: (1) aesthetic perception/multisensory integration; (2) creative expression; (3) dance heritage/historical and cultural; and (4) aesthetic…

  12. Domains of quality of life of people with profound multiple disabilities : The perspective of parents and direct support staff

    NARCIS (Netherlands)

    Petry, K; Maes, B; Vlaskamp, C

    Background This study considered the general validity of the basic domains of quality of life that appear in theoretical models, in relation to people with profound multiple disabilities. The authors examined how parents and direct support staff operationalized these basic domains for people with

  13. Camera-based microswitch technology to monitor mouth, eyebrow, and eyelid responses of children with profound multiple disabilities

    NARCIS (Netherlands)

    Lancioni, G.E.; Bellini, D.; Oliva, D.; Singh, N.N.; O'Reilly, M.F.; Sigafoos, J.; Lang, R.B.; Didden, H.C.M.

    2011-01-01

    A camera-based microswitch technology was recently used to successfully monitor small eyelid and mouth responses of two adults with profound multiple disabilities (Lancioni et al., Res Dev Disab 31:1509-1514, 2010a). This technology, in contrast with the traditional optic microswitches used for

  14. Informal Social Networks of People with Profound Intellectual and Multiple Disabilities: Relationship with Age, Communicative Abilities and Current Living Arrangements

    Science.gov (United States)

    Kamstra, A.; van der Putten, A. A. J.; Post, W. J.; Vlaskamp, C.

    2015-01-01

    Background: People with profound intellectual and multiple disabilities (PIMD) have limited informal social contacts. Research to determine the factors which can positively influence establishing sound informal social contacts is required. Materials and Methods: Regression analysis for 200 people with PIMD was used to analyse how age,…

  15. Family matters : The experiences and opinions of family members of persons with (severe) or profound intellectual disabilities

    NARCIS (Netherlands)

    Luijkx, Jorien

    2016-01-01

    “I love my sister, but sometimes I don’t”. This is one of the statements made in the study focused on the experiences of family members of people with (profound) intellectual (and multiple) disabilities (both of individuals living in a residential facility as persons living at home). In recent

  16. An Evaluation of Social and Adaptive Skills in Adults with Bipolar Disorder and Severe/Profound Intellectual Disability

    Science.gov (United States)

    Matson, Johnny L.; Terlonge, Cindy; Gonzalez, Melissa L.; Rivet, Tessa

    2006-01-01

    The purpose of this study was to explore the interrelationship of social and adaptive skills in adults with bipolar disorder and severe or profound intellectual disability. A bipolar group (N=14), a severe psychopathology group without bipolar disorder (N=14), and a control group with no DSM-IV Axis I diagnosis (N=14) were compared on the…

  17. Therapeutic interventions in the Netherlands and Belgium in support of people with profound intellectual and multiple disabilities

    NARCIS (Netherlands)

    Vlaskamp, Carla; Nakken, Han

    For several reasons, people with profound and multiple disabilities may be offered a variety of therapeutic interventions. Thus far, researchers have shown a limited interest in providing an empirical base for these interventions. Research is needed on the theoretical rationale (if any), the

  18. The Role of the External Personal Assistants for Children with Profound Intellectual and Multiple Disabilities Working in the Children's Home

    Science.gov (United States)

    Axelsson, Anna Karin

    2015-01-01

    Background: Children with profound intellectual and multiple disabilities need support to function in an optimal way. However, there is a limited knowledge about the role of external personal assistants working in the children's home. Materials and Methods: A mixed method study was performed including qualitative data from interviews with 11…

  19. Catch the wave! Time-window sequential analysis of alertness stimulation in individuals with profound intellectual and multiple disabilities

    NARCIS (Netherlands)

    Munde, V. S.; Vlaskamp, C.; Maes, B.; Ruijssenaars, A. J. J. M.

    BackgroundWhile optimally activities are provided at those moments when the individual with profound intellectual and multiple disabilities (PIMD) is focused on the environment' or alert', detailed information about the impact that the design and timing of the activity has on alertness is lacking.

  20. Quality-Enhancing Interventions for People with Profound Intellectual and Multiple Disabilities: A Review of the Empirical Research Literature

    Science.gov (United States)

    Maes, Bea; Lambrechts, Greet; Hostyn, Ine; Petry, Katja

    2007-01-01

    Background: This study provides an overview of empirical research on the effectiveness of quality-enhancing interventions for people with profound intellectual and multiple disabilities (PIMD). Method: Through computerised searches of the PsycINFO and ERIC databases, and using several search criteria specifically relating to the target group and…

  1. Staff attributions of the causes of challenging behaviour in children and adults with profound intellectual and multiple disabilities

    NARCIS (Netherlands)

    Poppes, P.; van der Putten, A.A.J.; ten Brug, A.; Vlaskamp, C.

    A study has shown that staff do not generally perceive challenging behaviour in people with profound intellectual and multiple disabilities (PIMD) as being of serious consequence. In this study we aimed to gain a better understanding of the causal explanations that direct care and support staff give

  2. Prenatal stress produces anxiety prone female offspring and impaired maternal behaviour in the domestic pig.

    Science.gov (United States)

    Rutherford, Kenneth M D; Piastowska-Ciesielska, Agnieszka; Donald, Ramona D; Robson, Sheena K; Ison, Sarah H; Jarvis, Susan; Brunton, Paula J; Russell, John A; Lawrence, Alistair B

    2014-04-22

    Numerous studies have shown that prenatal stress (PNS) can have profound effects on postnatal well-being. Here, the domestic pig (Sus scrofa) was used to investigate PNS effects owing to the direct relevance for farm animal welfare and the developing status of the pig as a large animal model in translational research. Pregnant primiparous sows were exposed, in mid-gestation, to either a social stressor (mixing with unfamiliar conspecifics) or were kept in stable social groups. The ratio of levels of mRNAs for corticotropin releasing hormone (CRH) receptors 1 and 2 in the amygdala, measured for the first time in the pig, was substantially increased in 10-week-old female, but not male, PNS progeny indicating a neurobiological propensity for anxiety-related behaviour. Mature female offspring were observed at parturition in either a behaviourally restrictive crate or open pen. Such PNS sows showed abnormal maternal behaviour in either environment, following the birth of their first piglet. They spent more time lying ventrally, more time standing and showed a higher frequency of posture changes. They were also more reactive towards their piglets, and spent longer visually attending to their piglets compared to controls. Associated with this abnormal maternal care, piglet mortality was increased in the open pen environment, where protection for piglets is reduced. Overall, these data indicate that PNS females have their brain development shifted towards a pro-anxiety phenotype and that PNS can be causally related to subsequent impaired maternal behaviour in adult female offspring. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Story retelling skills in Persian speaking hearing-impaired children.

    Science.gov (United States)

    Jarollahi, Farnoush; Mohamadi, Reyhane; Modarresi, Yahya; Agharasouli, Zahra; Rahimzadeh, Shadi; Ahmadi, Tayebeh; Keyhani, Mohammad-Reza

    2017-05-01

    Since the pragmatic skills of hearing-impaired Persian-speaking children have not yet been investigated particularly through story retelling, this study aimed to evaluate some pragmatic abilities of normal-hearing and hearing-impaired children using a story retelling test. 15 normal-hearing and 15 profound hearing-impaired 7-year-old children were evaluated using the story retelling test with the content validity of 89%, construct validity of 85%, and reliability of 83%. Three macro structure criteria including topic maintenance, event sequencing, explicitness, and four macro structure criteria including referencing, conjunctive cohesion, syntax complexity, and utterance length were assessed. The test was performed with live voice in a quiet room where children were then asked to retell the story. The tasks of the children were recorded on a tape, transcribed, scored and analyzed. In the macro structure criteria, utterances of hearing-impaired students were less consistent, enough information was not given to listeners to have a full understanding of the subject, and the story events were less frequently expressed in a rational order than those of normal-hearing group (P hearing students who obtained high scores, hearing-impaired students failed to gain any scores on the items of this section. These results suggest that Hearing-impaired children were not able to use language as effectively as their hearing peers, and they utilized quite different pragmatic functions. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Genomic analysis of a heterogeneous Mendelian phenotype: multiple novel alleles for inherited hearing loss in the Palestinian population

    OpenAIRE

    Walsh Tom; Rayan Amal; Sa'ed Judeh; Shahin Hashem; Shepshelovich Jeanne; Lee Ming K; Hirschberg Koret; Tekin Mustafa; Salhab Wa'el; Avraham Karen B; King Mary-Claire; Kanaan Moien

    2006-01-01

    Abstract Recessively inherited phenotypes are frequent in the Palestinian population, as the result of a historical tradition of marriages within extended kindreds, particularly in isolated villages. In order to characterise the genetics of inherited hearing loss in this population, we worked with West Bank schools for the deaf to identify children with prelingual, bilateral, severe to profound hearing loss not attributable to infection, trauma or other known environmental exposure. Of 156 fa...

  5. Binaural auditory outcomes in patients with postlingual profound unilateral hearing loss: 3 years after cochlear implantation.

    Science.gov (United States)

    Mertens, Griet; Kleine Punte, Andrea; De Bodt, Marc; Van de Heyning, Paul

    2015-01-01

    The value of cochlear implants (CI) in patients with profound unilateral hearing loss (UHL) and tinnitus has recently been investigated. The authors previously demonstrated the feasibility of CI in a 12- month outcome study in a prospective UHL cohort. The aim of this study was to investigate the binaural auditory outcomes in this cohort 36 months after CI surgery. The 36-month outcome was evaluated in 22 CI users with postlingual UHL and severe tinnitus. Twelve subjects had contralateral normal hearing (single-sided deafness - SSD group) and 10 subjects had a contralateral, mild to moderate hearing loss and used a hearing aid (asymmetric hearing loss - AHL group). Speech perception in noise was assessed in two listening conditions: the CIoff and the CIon condition. The binaural summation effect (S0N0), binaural squelch effect (S0NCI) and the combined head shadow effect (SCIN0) were investigated. Subjective benefit in daily life was assessed by means of the Speech, Spatial and Qualities of Hearing Scale (SSQ). At 36 months, a significant binaural summation effect was observed for the study cohort (2.00, SD 3.82 dB; p binaural effect was not significant 12 months after CI surgery. A binaural squelch effect was significant for the AHL subgroup at 12 months (2.00, SD 4.38 dB; p < 0.05). A significant combined head shadow and squelch effect was also noted in the spatial configuration SCIN0 for the study cohort (4.00, SD 5.89 dB; p < 0.01) and for the AHL subgroup (5.67, SD 6.66 dB; p < 0.05). The SSQ data show that the perceived benefit in daily life after CI surgery remains stable up to 36 months at CIon. CI can significantly improve speech perception in noise in patients with UHL. The positive effects of CIon speech perception in noise increase over time up to 36 months after CI surgery. Improved subjective benefit in daily life was also shown to be sustained in these patients. © 2015 S. Karger AG, Basel.

  6. Criteria for driver impairment

    NARCIS (Netherlands)

    Brookhuis, K.A.; De Waard, D.; Fairclough, S.H

    2003-01-01

    Most traffic accidents can be attributed to driver impairment, e.g. inattention, fatigue, intoxication, etc. It is now technically feasible to monitor and diagnose driver behaviour with respect to impairment with the aid of a limited number of in-vehicle sensors. However, a valid framework for the

  7. Childhood asthma-predictive phenotype.

    Science.gov (United States)

    Guilbert, Theresa W; Mauger, David T; Lemanske, Robert F

    2014-01-01

    Wheezing is a fairly common symptom in early childhood, but only some of these toddlers will experience continued wheezing symptoms in later childhood. The definition of the asthma-predictive phenotype is in children with frequent, recurrent wheezing in early life who have risk factors associated with the continuation of asthma symptoms in later life. Several asthma-predictive phenotypes were developed retrospectively based on large, longitudinal cohort studies; however, it can be difficult to differentiate these phenotypes clinically as the expression of symptoms, and risk factors can change with time. Genetic, environmental, developmental, and host factors and their interactions may contribute to the development, severity, and persistence of the asthma phenotype over time. Key characteristics that distinguish the childhood asthma-predictive phenotype include the following: male sex; a history of wheezing, with lower respiratory tract infections; history of parental asthma; history of atopic dermatitis; eosinophilia; early sensitization to food or aeroallergens; or lower lung function in early life. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  8. Phenotypic characteristics of early Wolfram syndrome.

    Science.gov (United States)

    Marshall, Bess A; Permutt, M Alan; Paciorkowski, Alexander R; Hoekel, James; Karzon, Roanne; Wasson, Jon; Viehover, Amy; White, Neil H; Shimony, Joshua S; Manwaring, Linda; Austin, Paul; Hullar, Timothy E; Hershey, Tamara

    2013-04-27

    Wolfram Syndrome (WFS:OMIM 222300) is an autosomal recessive, progressive, neurologic and endocrinologic degenerative disorder caused by mutations in the WFS1 gene, encoding the endoplasmic reticulum (ER) protein wolframin, thought to be involved in the regulation of ER stress. This paper reports a cross section of data from the Washington University WFS Research Clinic, a longitudinal study to collect detailed phenotypic data on a group of young subjects in preparation for studies of therapeutic interventions. Eighteen subjects (ages 5.9-25.8, mean 14.2 years) with genetically confirmed WFS were identified through the Washington University International Wolfram Registry. Examinations included: general medical, neurologic, ophthalmologic, audiologic, vestibular, and urologic exams, cognitive testing and neuroimaging. Seventeen (94%) had diabetes mellitus with the average age of diabetes onset of 6.3 ± 3.5 years. Diabetes insipidus was diagnosed in 13 (72%) at an average age of 10.6 ± 3.3 years. Seventeen (94%) had optic disc pallor and defects in color vision, 14 (78%) had hearing loss and 13 (72%) had olfactory defects, eight (44%) had impaired vibration sensation. Enuresis was reported by four (22%) and nocturia by three (17%). Of the 11 tested for bladder emptying, five (45%) had elevated post-void residual bladder volume. WFS causes multiple endocrine and neurologic deficits detectable on exam, even early in the course of the disease. Defects in olfaction have been underappreciated. The proposed mechanism of these deficits in WFS is ER stress-induced damage to neuronal and hormone-producing cells. This group of subjects with detailed clinical phenotyping provides a pool for testing proposed treatments for ER stress. Longitudinal follow-up is necessary for establishing the natural history and identifying potential biomarkers of progression.

  9. Does visual impairment lead to additional disability in adults with intellectual disabilities? A cross-sectional study

    NARCIS (Netherlands)

    Evenhuis, H.M.; Sjoukes, L.; Koot, H.M.; Kooijman, A.C.

    2009-01-01

    Background: This study addresses the question to what extent visual impairment leads to additional disability in adults with intellectual disabilities (ID). Method: In a multi-centre cross-sectional study of 269 adults with mild to profound ID, social and behavioural functioning was assessed with

  10. Homozygous SLC6A17 Mutations Cause Autosomal-Recessive Intellectual Disability with Progressive Tremor, Speech Impairment, and Behavioral Problems

    NARCIS (Netherlands)

    Iqbal, Z.; Willemsen, M.H.; Papon, M.A.; Musante, L.; Benevento, M.; Hu, H; Venselaar, H.; Wissink-Lindhout, W.M.; Silfhout, A.T. van; Vissers, L.E.L.M.; Brouwer, A.P.M. de; Marouillat, S.; Wienker, T.F.; Ropers, H.H.; Kahrizi, K.; Nadif Kasri, N.; Najmabadi, H.; Laumonnier, F.; Kleefstra, T.; Bokhoven, H. van

    2015-01-01

    We report on Dutch and Iranian families with affected individuals who present with moderate to severe intellectual disability and additional phenotypes including progressive tremor, speech impairment, and behavioral problems in certain individuals. A combination of exome sequencing and homozygosity

  11. Cantonese tone production performance of mainstream school children with hearing impairment.

    Science.gov (United States)

    Cheung, Karen K L; Lau, Ada H Y; Lam, Joffee H S; Lee, Kathy Y S

    2014-12-01

    This study investigated the Cantonese tone production ability of children with hearing impairment studying in mainstream schools. The participants were 87 Cantonese-speaking children with mild-to-profound degrees of hearing loss aged 5.92-13.58 in Hong Kong. Most of the children were fitted with hearing aids (n = 65); 17 of them had profound hearing impairment, one who had severe hearing loss had cochlear implantation, and four who had mild hearing loss were without any hearing device. The Hong Kong Cantonese Articulation Test was administered, and the tones produced were rated by two of the authors and a speech-language pathologist. Group effects of tones, hearing loss level, and also an interaction of the two were found to be significant. The children with profound hearing impairment performed significantly worse than most of the other children. Tone 1 was produced most accurately, whereas tone 6 productions were the poorest. No relationship was found between the number of years of mainstreaming and tone production ability. Tone production error pattern revealed that confusion patterns in tone perception coincided with those in production. Tones having a similar fundamental frequency (F0) at the onset also posed difficulty in tone production for children with hearing impairment.

  12. Heterogeneity in Phenotype of Usher-Congenital Hyperinsulinism Syndrome

    Science.gov (United States)

    Al Mutair, Angham N.; Brusgaard, Klaus; Bin-Abbas, Bassam; Hussain, Khalid; Felimban, Naila; Al Shaikh, Adnan; Christesen, Henrik T.

    2013-01-01

    OBJECTIVE To evaluate the phenotype of 15 children with congenital hyperinsulinism (CHI) and profound hearing loss, known as Homozygous 11p15-p14 Deletion syndrome (MIM #606528). RESEARCH DESIGN AND METHODS Prospective clinical follow-up and genetic analysis by direct sequencing, multiplex ligation-dependent probe amplification, and microsatellite markers. RESULTS Genetic testing identified the previous described homozygous deletion in 11p15, USH1C:c.(90+592)_ABCC8:c.(2694–528)del. Fourteen patients had severe CHI demanding near-total pancreatectomy. In one patient with mild, transient neonatal hypoglycemia and nonautoimmune diabetes at age 11 years, no additional mutations were found in HNF1A, HNF4A, GCK, INS, and INSR. Retinitis pigmentosa was found in two patients aged 9 and 13 years. No patients had enteropathy or renal tubular defects. Neuromotor development ranged from normal to severe delay with epilepsy. CONCLUSIONS The phenotype of Homozygous 11p15-p14 Deletion syndrome, or Usher-CHI syndrome, includes any severity of neonatal-onset CHI and severe, sensorineural hearing loss. Retinitis pigmentosa and nonautoimmune diabetes may occur in adolescence. PMID:23150283

  13. Prominent scapulae mimicking an inherited myopathy expands the phenotype of CHD7-related disease

    NARCIS (Netherlands)

    O'Grady, Gina L.; Ma, Alan; Sival, Deborah; Wong, Monica T. Y.; Peduto, Tony; Menezes, Manoj P.; Young, Helen; Waddell, Leigh; Ghaoui, Roula; Needham, Merrilee; Lek, Monkol; North, Kathryn N.; MacArthur, Daniel G.; van Ravenswaaij-Arts, Conny M. A.; Clarke, Nigel F.

    CHD7 variants are a well-established cause of CHARGE syndrome, a disabling multi-system malformation disorder that is often associated with deafness, visual impairment and intellectual disability. Less severe forms of CHD7-related disease are known to exist, but the full spectrum of phenotypes

  14. Tension and Transformation in Pancreas Cancer: Can Phenotype Break Free from the Chrysalis of Genotype?

    Science.gov (United States)

    DuFort, Christopher C; Hingorani, Sunil R

    2016-06-13

    A recent study finds that impaired TGFβ signaling can initiate a positive feedback loop between increasing ECM stiffness and epithelial cell contractility in pancreas cancer. Even more surprising is the possibility that this phenotype can liberate the epithelium from dependence on the genetic events that transformed it. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Abnormalities of lymphocyte function and phenotypic pattern in a case of toxic epidermal necrolysis

    DEFF Research Database (Denmark)

    Hagdrup, H; Tønnesen, E; Clemmensen, O

    1992-01-01

    We examined the blood lymphocyte function and phenotypic pattern in a patient with toxic epidermal necrolysis after taking salazopyrin. We studied cell surface markers, natural killer cell activity and mitogen-induced lymphocyte transformation. Our results point to temporary immunosuppression...... as evidenced by lymphopenia with a large "null cell" population, reduced natural killer cell activity, and impaired lymphocyte response to mitogens....

  16. The causal effect of profound organizational change when job insecurity is low – a quasi-experiment analysing municipal mergers

    DEFF Research Database (Denmark)

    Bhatti, Yosef; Gørtz, Mette; Pedersen, Lene Holm

    2015-01-01

    The present article finds that the causal effect of profound organizational change on employee health can be very low, if job insecurity is mitigated. We demonstrate this by investigating a rare case of a large-scale radical public sector reform with low job insecurity, in which a large number...... and job insecurity may explain the divergence from previous results. An important strength of our study is that the reform investigated can be considered a quasi-experiment, as it was exogenous and implemented simultaneously by the affected local governments. We also have access to an objective measure...... of robustness tests are performed, including propensity score matching and in-depth analysis of particular sub-groups of public sector employees. The results indicate that profound organizational change per se does not necessarily lead to decreased health, if job insecurity is low. However, a very modest effect...

  17. Profound, prelingual nonsyndromic deafness maps to chromosome 10q21 and is caused by a novel missense mutation in the Usher syndrome type IF gene PCDH15.

    Science.gov (United States)

    Doucette, Lance; Merner, Nancy D; Cooke, Sandra; Ives, Elizabeth; Galutira, Dante; Walsh, Vanessa; Walsh, Tom; MacLaren, Linda; Cater, Tracey; Fernandez, Bridget; Green, Jane S; Wilcox, Edward R; Shotland, Lawrence I; Shotland, Larry; Li, Xiaoyan Cindy; Li, X C; Lee, Ming; King, Mary-Claire; Young, Terry-Lynn

    2009-05-01

    We studied a consanguineous family (Family A) from the island of Newfoundland with an autosomal recessive form of prelingual, profound, nonsyndromic sensorineural hearing loss. A genome-wide scan mapped the deafness trait to 10q21-22 (max LOD score of 4.0; D10S196) and fine mapping revealed a 16 Mb ancestral haplotype in deaf relatives. The PCDH15 gene was mapped within the critical region and was an interesting candidate because truncating mutations cause Usher syndrome type IF (USH1F) and two missense mutations have been previously associated with isolated deafness (DFNB23). Sequencing of the PCDH15 gene revealed 33 sequencing variants. Three of these variants were homozygous exclusively in deaf siblings but only one of them was not seen in ethnically matched controls. This novel c.1583 T>A transversion predicts an amino-acid substitution of a valine with an aspartic acid at codon 528 (V528D). Like the two DFNB23 mutations, the V528D mutation in Family A occurs in a highly conserved extracellular cadherin (EC) domain of PCDH15 and is predicted to be more deleterious than the previously identified DFNB23 missense mutations (R134G and G262D). Physical assessment, vestibular and visual function testing in deaf adults ruled out syndromic deafness because of Usher syndrome. This study validates the DFNB23 designation and supports the hypothesis that missense mutations in conserved motifs of PCDH15 cause nonsyndromic hearing loss. This emerging genotype-phenotype correlation in USH1F is similar to that in several other USH1 genes and cautions against a prognosis of a dual sensory loss in deaf children found to be homozygous for hypomorphic mutations at the USH1F locus.

  18. Exposing to cadmium stress cause profound toxic effect on microbiota of the mice intestinal tract.

    Directory of Open Access Journals (Sweden)

    Yehao Liu

    Full Text Available Cadmium (Cd, one of the heavy metals, is an important environmental pollutant and a potent toxicant to organism. It poses a severe threat to the growth of the organism, and also has been recognized as a human carcinogen. However, the toxicity of cadmium and its influences on microbiota in mammal's intestine are still unclear. In our experiment, the changes of intestinal microbiota in two groups of mice were investigated, which were supplied with 20 and 100 mg kg(-1 cadmium chloride respectively for 3 weeks. The control group was treated with water free from cadmium chloride only. This study demonstrated that Cd accumulated in some tissues of mice after Cd administration and the gut barrier was impaired. Cd exposure also significantly elevated the colonic level of TNF-α. On the other hand, Cd-treatment could slow down the growth of gut microbiota and reduced the abundance of total intestinal bacteria of the mice. Among them, the growth of Bacteroidetes was significantly suppressed while Firmicutes growth was not. The probiotics including Lactobacillus and Bifidobacterium were notably inhibited. We also observed that the copies of key genes involved in the metabolism of carbohydrates to short-chain fatty acids (SCFAs were lower in Cd-treated groups than control. As a result, the levels of short-chain fatty acids in colonic decreased significantly. In summary, this study provides valuable insight into the effects of Cd intake on mice gut microbiota.

  19. Managing Profound Suffering at the End-of-Life: Should expanding access to continuous deep sedation be the priority?

    Directory of Open Access Journals (Sweden)

    Kirby, Jeffrey

    2015-01-01

    Full Text Available This paper argues that in addressing and managing profound suffering at the end-of-life, the priority should not be the legalization of physician-assisted suicide or voluntary active euthanasia in jurisdictions where these practices are not currently available. Rather, concerted efforts should be made by society and the healthcare provider community to expand patient access to proportionate distress-relieving sedation and continuous deep sedation.

  20. The experience of black parents/caretakers with the births and care of a child with profound congenital defects

    Directory of Open Access Journals (Sweden)

    M.S. Mabaso

    1990-09-01

    Full Text Available The reaction of Black families to the birth and care of a baby with profound congenital defects was researched using twenty case studies. It was found that the families went through stages of the grieving process, that they shifted from the Western/Christian viewpoint to the traditional viewpoint in their struggle to cope and that they find the existing services grossly inadequate.

  1. Congenital hearing impairment

    Energy Technology Data Exchange (ETDEWEB)

    Robson, Caroline D. [Children' s Hospital and Harvard Medical School, Division of Neuroradiology, Department of Radiology, Boston, MA (United States)

    2006-04-15

    Establishing the etiology of congenital hearing impairment can significantly improve treatment for certain causes of hearing loss and facilitates genetic counseling. High-resolution CT and MRI have contributed to the evaluation and management of hearing impairment. In addition, with the identification of innumerable genetic loci and genetic defects involved in hearing loss, genetic testing has emerged as an invaluable tool in the assessment of hearing impairment. Some of the common forms of congenital hearing loss are reviewed and their imaging features illustrated. (orig.)

  2. Congenital hearing impairment

    International Nuclear Information System (INIS)

    Robson, Caroline D.

    2006-01-01

    Establishing the etiology of congenital hearing impairment can significantly improve treatment for certain causes of hearing loss and facilitates genetic counseling. High-resolution CT and MRI have contributed to the evaluation and management of hearing impairment. In addition, with the identification of innumerable genetic loci and genetic defects involved in hearing loss, genetic testing has emerged as an invaluable tool in the assessment of hearing impairment. Some of the common forms of congenital hearing loss are reviewed and their imaging features illustrated. (orig.)

  3. Undernutrition in children with profound intellectual and multiple disabilities (PIMD): its prevalence and influence on quality of life.

    Science.gov (United States)

    Holenweg-Gross, C; Newman, C J; Faouzi, M; Poirot-Hodgkinson, I; Bérard, C; Roulet-Perez, E

    2014-07-01

    To estimate the prevalence of undernutrition among children with profound intellectual and multiple disabilities (PIMD) and to explore its influence on quality of life. Seventy-two children with PIMD (47 male; 25 female; age range 2 to 15 years 4 months; mean age 8.6, SD 3.6) underwent an anthropometric assessment, including body weight, triceps skinfold thickness, segmental measures and recumbent length. Undernutrition was determined using tricipital skinfold percentile and z-scores of weight-for-height and height-for-age. The quality of life of each child was evaluated using the QUALIN questionnaire adapted for profoundly disabled children. Twenty-five children (34.7%) were undernourished and seven (9.7%) were obese. Among undernourished children only eight (32 %) were receiving food supplements and two (8%) had a gastrostomy, of which one was still on a refeeding programme. On multivariate analysis, undernutrition was one of the independent predictors of lower quality of life. Undernutrition remains a matter of concern in children with PIMD. There is a need to better train professionals in systematically assessing the nutritional status of profoundly disabled children in order to start nutritional management when necessary. © 2013 John Wiley & Sons Ltd.

  4. Demonstration of ipsilateral brain activation by noise in patients profoundly deaf with cochlear implant, or unilaterally deaf

    International Nuclear Information System (INIS)

    Herzog, H.; Wieler, H.; Morgenstern, C.; Lipman, J.; Langen, K.-J.; Schmid, A.; Rota, E.; Patton, D.; Feinendegen, L.F.

    1986-01-01

    Two groups of patients with hearing handicaps have been investigated with PET and F-18-2-FDG. Since these patients were unilaterally deaf or profoundly deaf with a cochlear implant installed, monaural stimulation was possible excluding any effects of bone conduction to the contralateral ear. White noise was used as acoustic stimulus in unilaterally deaf patients. The peripheral auditory nerve of cochlear implant patients was stimulated by electrical impulses which were encoded from music or a 4-tone mixture by an electronic speech processor. The non-music stimuli were chosen to avoid associative cortical reactions. In both groups response to the stimuli by increase of glucose consumption (LCMRglc) was found not only in the contralateral primary auditory cortex as expected from neuroanatomical knowledge, but also in the ipsilateral auditory cortex. Furthermore there was no correlation between the hemisphere showing increased LCMRglc and the side of stimulation or the type of stimulus. The similarity of results obtained in both groups by acoustical and electrical stimulation of the auditory nerve suggests that this kind of measurement might be a tool to predict or check the performance of a cochlear implant in a profoundly deaf patient. The finding of increased LCMRglc in the area of the normal auditory cortex in patients profoundly deaf since birth contradicts the hypothesis of degeneration of this cortical center in such patients. (Author)

  5. Protein energy malnutrition associates with different types of hearing impairments in toddlers: Anemia increases cochlear dysfunction.

    Science.gov (United States)

    Kamel, Terez Boshra; Deraz, Tharwat Ezzat; Elkabarity, Rasha H; Ahmed, Rasha K

    2016-06-01

    This work aimed to highlight a challenging asymptomatic problem which is early detection of hearing impairment in toddlers with protein energy malnutrition (PEM) as a neuro-cognitive effect of PEM on developing brain in relation to hemoglobin level. 100 toddlers, aged 6-24 months, fifty with moderate/severe PEM and fifty healthy children, were included in study. Both TEOAEs and ABR testing were used to assess auditory function. Study reported an association between malnutrition and hearing impairment, 26% of cases had conductive deafness secondary to otitis media with effusion using tympanometry; 84.6% showed type B and 15.4% type C which may suggest developing or resolving otitis media. Their ABR showed 46% mild and 53% moderate impairment. 32% of PEM cases had sensory neural hearing loss and with type (A) tympanometry. Those were assessed using ABR; 58% had mild, 34% moderate and 8% profound impairment. 10% of PEM cases had mixed hearing loss with 50% type B and 50% type C tympanometry and their ABR showed moderate to profound impairment. TEOAEs latencies at different frequencies correlate negatively with hemoglobin level. Toddlers with moderate/severe PEM had hearing impairments of different types and degrees. Neuro-physiological methods could be early and safe detectors of auditory disorders especially in high-risk toddlers. Anemia increases risk for auditory dysfunction. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Linking genotypes database with locus-specific database and genotype-phenotype correlation in phenylketonuria.

    Science.gov (United States)

    Wettstein, Sarah; Underhaug, Jarl; Perez, Belen; Marsden, Brian D; Yue, Wyatt W; Martinez, Aurora; Blau, Nenad

    2015-03-01

    The wide range of metabolic phenotypes in phenylketonuria is due to a large number of variants causing variable impairment in phenylalanine hydroxylase function. A total of 834 phenylalanine hydroxylase gene variants from the locus-specific database PAHvdb and genotypes of 4181 phenylketonuria patients from the BIOPKU database were characterized using FoldX, SIFT Blink, Polyphen-2 and SNPs3D algorithms. Obtained data was correlated with residual enzyme activity, patients' phenotype and tetrahydrobiopterin responsiveness. A descriptive analysis of both databases was compiled and an interactive viewer in PAHvdb database was implemented for structure visualization of missense variants. We found a quantitative relationship between phenylalanine hydroxylase protein stability and enzyme activity (r(s) = 0.479), between protein stability and allelic phenotype (r(s) = -0.458), as well as between enzyme activity and allelic phenotype (r(s) = 0.799). Enzyme stability algorithms (FoldX and SNPs3D), allelic phenotype and enzyme activity were most powerful to predict patients' phenotype and tetrahydrobiopterin response. Phenotype prediction was most accurate in deleterious genotypes (≈ 100%), followed by homozygous (92.9%), hemizygous (94.8%), and compound heterozygous genotypes (77.9%), while tetrahydrobiopterin response was correctly predicted in 71.0% of all cases. To our knowledge this is the largest study using algorithms for the prediction of patients' phenotype and tetrahydrobiopterin responsiveness in phenylketonuria patients, using data from the locus-specific and genotypes database.

  7. Particularities of COPD exacerbations in different phenotypes of the disease in Tunisia.

    Science.gov (United States)

    Zendah, Ines; Ayed, Khadija; Kwas, Hamida; Khattab, Amel; Ghédira, Habib

    2016-03-01

    Chronic Obstructive Pulmonary Disease is defined by a limitation of airflow. This disease is characterized by exacerbations that threaten the patient's life and worsens his prognosis. Moreover, COPD patients are different according to many parameters that define different phenotypes. Characteristics of exacerbations may depend on these phenotypes according to few recent studies. To determine the characteristics and the prognosis of the exacerbations in each phenotype of COPD patients phenotype in Tunisia. Retrospective study including 153 male patients hospitalized for COPD exacerbation from January 2009 to June 2012. Patients were classified into 4 phenotypes according to Burgel's classification. Patients were divided into four phenotypes: phenotype (PH)1: (n=68), PH2: (n=33), PH3: (n=25) and PH4: (n=27). Mean age for PH1, 2, 3 and 4 was: 61, 74, 56 and 72 years. The number of exacerbations per year was higher in PH1. Dyspnea was more important in PH1 and 4. Hypercapnia on admission was higher in PH4. Non invasive ventilation and transfer to resuscitation unit were more frequently mandatory in PH3 and 4.   Death occurred 2% of PH1 and 5% of PH4. Hospitalization duration was more important in PH4. COPD patients are heterogenous and belong to different phenotypes. The characteristics of the exacerbations and their prognosis widely differ according to these different groups. In Tunisia, it seems that patients who had moderate respiratory functional tests impairment are the lowest responders to treatment with a higher frequency of resuscitation unit transfer.

  8. Phenotypic spectrum of GABRA1

    DEFF Research Database (Denmark)

    Johannesen, Katrine; Marini, Carla; Pfeffer, Siona

    2016-01-01

    OBJECTIVE: To delineate phenotypic heterogeneity, we describe the clinical features of a cohort of patients with GABRA1 gene mutations. METHODS: Patients with GABRA1 mutations were ascertained through an international collaboration. Clinical, EEG, and genetic data were collected. Functional analy...

  9. Leaf segmentation in plant phenotyping

    NARCIS (Netherlands)

    Scharr, Hanno; Minervini, Massimo; French, Andrew P.; Klukas, Christian; Kramer, David M.; Liu, Xiaoming; Luengo, Imanol; Pape, Jean Michel; Polder, Gerrit; Vukadinovic, Danijela; Yin, Xi; Tsaftaris, Sotirios A.

    2016-01-01

    Image-based plant phenotyping is a growing application area of computer vision in agriculture. A key task is the segmentation of all individual leaves in images. Here we focus on the most common rosette model plants, Arabidopsis and young tobacco. Although leaves do share appearance and shape

  10. Delineating SPTAN1 associated phenotypes

    DEFF Research Database (Denmark)

    Syrbe, Steffen; Harms, Frederike L; Parrini, Elena

    2017-01-01

    De novo in-frame deletions and duplications in the SPTAN1 gene, encoding the non-erythrocyte αII spectrin, have been associated with severe West syndrome with hypomyelination and pontocerebellar atrophy. We aimed at comprehensively delineating the phenotypic spectrum associated with SPTAN1 mutati...

  11. Small changes in climate can profoundly alter the dynamics and ecosystem services of tropical crater lakes.

    Directory of Open Access Journals (Sweden)

    Émilie Saulnier-Talbot

    Full Text Available African tropical lakes provide vital ecosystem services including food and water to some of the fastest growing human populations, yet they are among the most understudied ecosystems in the world. The consequences of climate change and other stressors on the tropical lakes of Africa have been informed by long-term analyses, but these studies have largely focused on the massive Great Rift Valley lakes. Our objective was to evaluate how recent climate change has altered the functioning and services of smaller tropical lakes, which are far more abundant on the landscape. Based on a paired analysis of 20 years of high-resolution water column data and a paleolimnological record from a small crater lake in western Uganda, we present evidence that even a modest warming of the air (∼0.9°C increase over 20 years and changes in the timing and intensity of rainfall can have significant consequences on the dynamics of this common tropical lake type. For example, we observed a significant nonlinear increase (R(2 adj  = 0.23, e.d.f. = 7, p<0.0001 in thermal stability over the past 20 years. This resulted in the expansion of anoxic waters and consequent deterioration of fish habitat and appears to have abated primary production; processes that may impair ecosystem services for a vulnerable human population. This study on a system representative of small tropical crater lakes highlights the far-reaching effects of global climatic change on tropical waters. Increased research efforts into tropical aquatic ecosystem health and the development of sound management practices are necessary in order to strengthen adaptive capabilities in tropical regions.

  12. Small changes in climate can profoundly alter the dynamics and ecosystem services of tropical crater lakes.

    Science.gov (United States)

    Saulnier-Talbot, Émilie; Gregory-Eaves, Irene; Simpson, Kyle G; Efitre, Jackson; Nowlan, Tobias E; Taranu, Zofia E; Chapman, Lauren J

    2014-01-01

    African tropical lakes provide vital ecosystem services including food and water to some of the fastest growing human populations, yet they are among the most understudied ecosystems in the world. The consequences of climate change and other stressors on the tropical lakes of Africa have been informed by long-term analyses, but these studies have largely focused on the massive Great Rift Valley lakes. Our objective was to evaluate how recent climate change has altered the functioning and services of smaller tropical lakes, which are far more abundant on the landscape. Based on a paired analysis of 20 years of high-resolution water column data and a paleolimnological record from a small crater lake in western Uganda, we present evidence that even a modest warming of the air (∼0.9°C increase over 20 years) and changes in the timing and intensity of rainfall can have significant consequences on the dynamics of this common tropical lake type. For example, we observed a significant nonlinear increase (R(2) adj  = 0.23, e.d.f. = 7, pdeterioration of fish habitat and appears to have abated primary production; processes that may impair ecosystem services for a vulnerable human population. This study on a system representative of small tropical crater lakes highlights the far-reaching effects of global climatic change on tropical waters. Increased research efforts into tropical aquatic ecosystem health and the development of sound management practices are necessary in order to strengthen adaptive capabilities in tropical regions.

  13. Impairments to Vision

    Science.gov (United States)

    ... an external Non-Government web site. Impairments to Vision Normal Vision Diabetic Retinopathy Age-related Macular Degeneration In this ... pictures, fixate on the nose to simulate the vision loss. In diabetic retinopathy, the blood vessels in ...

  14. Stormwater Impaired Watersheds

    Data.gov (United States)

    Vermont Center for Geographic Information — Stormwater impaired watersheds occuring on both the Priority Waters (Part D - Completed TMDL) and 303(d) list of waters (Part A - need TMDL) The Vermont State...

  15. Interoperability between phenotype and anatomy ontologies.

    Science.gov (United States)

    Hoehndorf, Robert; Oellrich, Anika; Rebholz-Schuhmann, Dietrich

    2010-12-15

    Phenotypic information is important for the analysis of the molecular mechanisms underlying disease. A formal ontological representation of phenotypic information can help to identify, interpret and infer phenotypic traits based on experimental findings. The methods that are currently used to represent data and information about phenotypes fail to make the semantics of the phenotypic trait explicit and do not interoperate with ontologies of anatomy and other domains. Therefore, valuable resources for the analysis of phenotype studies remain unconnected and inaccessible to automated analysis and reasoning. We provide a framework to formalize phenotypic descriptions and make their semantics explicit. Based on this formalization, we provide the means to integrate phenotypic descriptions with ontologies of other domains, in particular anatomy and physiology. We demonstrate how our framework leads to the capability to represent disease phenotypes, perform powerful queries that were not possible before and infer additional knowledge. http://bioonto.de/pmwiki.php/Main/PheneOntology.

  16. Canine Distemper Virus Infection Leads to an Inhibitory Phenotype of Monocyte-Derived Dendritic Cells In Vitro with Reduced Expression of Co-Stimulatory Molecules and Increased Interleukin-10 Transcription

    Science.gov (United States)

    Herder, Vanessa; Stein, Veronika M.; Tipold, Andrea; Urhausen, Carola; Günzel-Apel, Anne-Rose; Rohn, Karl; Baumgärtner, Wolfgang; Beineke, Andreas

    2014-01-01

    Canine distemper virus (CDV) exhibits a profound lymphotropism that causes immunosuppression and increased susceptibility of affected dogs to opportunistic infections. Similar to human measles virus, CDV is supposed to inhibit terminal differentiation of dendritic cells (DCs), responsible for disturbed repopulation of lymphoid tissues and diminished antigen presenting function in dogs. In order to testify the hypothesis that CDV-infection leads to an impairment of professional antigen presenting cells, canine DCs have been generated from peripheral blood monocytes in vitro and infected with CDV. Virus infection was confirmed and quantified by transmission electron microscopy, CDV-specific immunofluorescence, and virus titration. Flow cytometric analyses revealed a significant down-regulation of the major histocompatibility complex class II and co-stimulatory molecules CD80 and CD86 in CDV-infected DCs, indicative of disturbed antigen presenting capacity. Molecular analyses revealed an increased expression of the immune inhibitory cytokine interleukin-10 in DCs following infection. Results of the present study demonstrate that CDV causes phenotypical changes and altered cytokine expression of DCs, which represent potential mechanisms to evade host immune responses and might contribute to immune dysfunction and virus persistence in canine distemper. PMID:24769532

  17. Canine distemper virus infection leads to an inhibitory phenotype of monocyte-derived dendritic cells in vitro with reduced expression of co-stimulatory molecules and increased interleukin-10 transcription.

    Directory of Open Access Journals (Sweden)

    Visar Qeska

    Full Text Available Canine distemper virus (CDV exhibits a profound lymphotropism that causes immunosuppression and increased susceptibility of affected dogs to opportunistic infections. Similar to human measles virus, CDV is supposed to inhibit terminal differentiation of dendritic cells (DCs, responsible for disturbed repopulation of lymphoid tissues and diminished antigen presenting function in dogs. In order to testify the hypothesis that CDV-infection leads to an impairment of professional antigen presenting cells, canine DCs have been generated from peripheral blood monocytes in vitro and infected with CDV. Virus infection was confirmed and quantified by transmission electron microscopy, CDV-specific immunofluorescence, and virus titration. Flow cytometric analyses revealed a significant down-regulation of the major histocompatibility complex class II and co-stimulatory molecules CD80 and CD86 in CDV-infected DCs, indicative of disturbed antigen presenting capacity. Molecular analyses revealed an increased expression of the immune inhibitory cytokine interleukin-10 in DCs following infection. Results of the present study demonstrate that CDV causes phenotypical changes and altered cytokine expression of DCs, which represent potential mechanisms to evade host immune responses and might contribute to immune dysfunction and virus persistence in canine distemper.

  18. Canine distemper virus infection leads to an inhibitory phenotype of monocyte-derived dendritic cells in vitro with reduced expression of co-stimulatory molecules and increased interleukin-10 transcription.

    Science.gov (United States)

    Qeska, Visar; Barthel, Yvonne; Herder, Vanessa; Stein, Veronika M; Tipold, Andrea; Urhausen, Carola; Günzel-Apel, Anne-Rose; Rohn, Karl; Baumgärtner, Wolfgang; Beineke, Andreas

    2014-01-01

    Canine distemper virus (CDV) exhibits a profound lymphotropism that causes immunosuppression and increased susceptibility of affected dogs to opportunistic infections. Similar to human measles virus, CDV is supposed to inhibit terminal differentiation of dendritic cells (DCs), responsible for disturbed repopulation of lymphoid tissues and diminished antigen presenting function in dogs. In order to testify the hypothesis that CDV-infection leads to an impairment of professional antigen presenting cells, canine DCs have been generated from peripheral blood monocytes in vitro and infected with CDV. Virus infection was confirmed and quantified by transmission electron microscopy, CDV-specific immunofluorescence, and virus titration. Flow cytometric analyses revealed a significant down-regulation of the major histocompatibility complex class II and co-stimulatory molecules CD80 and CD86 in CDV-infected DCs, indicative of disturbed antigen presenting capacity. Molecular analyses revealed an increased expression of the immune inhibitory cytokine interleukin-10 in DCs following infection. Results of the present study demonstrate that CDV causes phenotypical changes and altered cytokine expression of DCs, which represent potential mechanisms to evade host immune responses and might contribute to immune dysfunction and virus persistence in canine distemper.

  19. Fried frailty phenotype assessment components as applied to geriatric inpatients

    Directory of Open Access Journals (Sweden)

    Bieniek J

    2016-04-01

    Full Text Available Joanna Bieniek, Krzysztof Wilczynski, Jan Szewieczek Department of Geriatrics, School of Health Sciences in Katowice, Medical University of Silesia, Katowice, Poland Background: Management of geriatric patients would be simplified if a universally accepted definition of frailty for clinical use was defined. Among definitions of frailty, Fried frailty phenotype criteria constitute a common reference frame for many geriatric studies. However, this reference frame has been tested primarily in elderly patients presenting with relatively good health status. Objective: The aim of this article was to assess the usefulness and limitations of Fried frailty phenotype criteria in geriatric inpatients, characterized by comorbidity and functional impairments, and to estimate the frailty phenotype prevalence in this group. Patients and methods: Five hundred consecutive patients of the university hospital subacute geriatric ward, aged 79.0±8.4 years (67% women and 33% men, participated in this cross-sectional study. Comprehensive geriatric assessment and Fried frailty phenotype component evaluation were performed in all patients. Results: Multimorbidity (6.0±2.8 diseases characterized our study group, with a wide range of clinical conditions and functional states (Barthel Index of Activities of Daily Living 72.2±28.2 and Mini-Mental State Examination 23.6±7.1 scores. All five Fried frailty components were assessed in 65% of patients (95% confidence interval [CI] =60.8–69.2 (diagnostic group. One or more components were not feasible to be assessed in 35% of the remaining patients (nondiagnostic group because of lack of past patient’s body mass control and/or cognitive or physical impairment. Patients from the nondiagnostic group, as compared to patients from the diagnostic group, presented with more advanced age, higher prevalence of dementia, lower prevalence of hypertension, lower systolic and diastolic blood pressure, body mass index, Mini

  20. Psychopaths are impaired in social exchange and precautionary reasoning.

    Science.gov (United States)

    Ermer, Elsa; Kiehl, Kent A

    2010-10-01

    Psychopaths show a profound lack of morality and behavioral controls in the presence of intact general intellectual functioning. Two hallmarks of psychopathy are the persistent violation of social contracts (i.e., cheating) and chronic, impulsive risky behavior. These behaviors present a puzzle: Can psychopaths understand and reason about what counts as cheating or risky behavior in a particular situation? We tested incarcerated psychopaths' and incarcerated nonpsychopaths' reasoning about social contract rules, precautionary rules, and descriptive rules using the Wason selection task. Results were consistent with our hypotheses: Psychopaths (compared with matched nonpsychopaths) showed significant impairment on social contract rules and precautionary rules, but not on descriptive rules. These results cannot be accounted for by differences in intelligence, motivation, or general antisocial tendency. These findings suggest that examination of evolutionarily identified reasoning processes can be a fruitful research approach for identifying which specific mechanisms are impaired in psychopathy.

  1. Facial identity recognition in the broader autism phenotype.

    Directory of Open Access Journals (Sweden)

    C Ellie Wilson

    Full Text Available BACKGROUND: The 'broader autism phenotype' (BAP refers to the mild expression of autistic-like traits in the relatives of individuals with autism spectrum disorder (ASD. Establishing the presence of ASD traits provides insight into which traits are heritable in ASD. Here, the ability to recognise facial identity was tested in 33 parents of ASD children. METHODOLOGY AND RESULTS: In experiment 1, parents of ASD children completed the Cambridge Face Memory Test (CFMT, and a questionnaire assessing the presence of autistic personality traits. The parents, particularly the fathers, were impaired on the CFMT, but there were no associations between face recognition ability and autistic personality traits. In experiment 2, parents and probands completed equivalent versions of a simple test of face matching. On this task, the parents were not impaired relative to typically developing controls, however the proband group was impaired. Crucially, the mothers' face matching scores correlated with the probands', even when performance on an equivalent test of matching non-face stimuli was controlled for. CONCLUSIONS AND SIGNIFICANCE: Components of face recognition ability are impaired in some relatives of ASD individuals. Results suggest that face recognition skills are heritable in ASD, and genetic and environmental factors accounting for the pattern of heritability are discussed. In general, results demonstrate the importance of assessing the skill level in the proband when investigating particular characteristics of the BAP.

  2. Constitutional bone impairment in Noonan syndrome.

    Science.gov (United States)

    Baldassarre, Giuseppina; Mussa, Alessandro; Carli, Diana; Molinatto, Cristina; Ferrero, Giovanni Battista

    2017-03-01

    Noonan syndrome (NS) is an autosomal dominant trait characterized by genotypic and phenotypic variability. It belongs to the Ras/MAPK pathway disorders collectively named Rasopathies or neurocardiofaciocutaneous syndromes. Phenotype is characterized by short stature, congenital heart defects, facial dysmorphisms, skeletal and ectodermal anomalies, cryptorchidism, mild to moderate developmental delay/learning disability, and tumor predisposition. Short stature and skeletal dysmorphisms are almost constant and several studies hypothesized a role for the RAS pathway in regulating bone metabolism. In this study, we investigated the bone quality assessed by phalangeal quantitative ultrasound (QUS) and the metabolic bone profiling in a group of patients with NS, to determine whether low bone mineralization is primary or secondary to NS characteristics. Thirty-five patients were enrolled, including 20 males (55.6%) and 15 females (44.5%) aged 1.0-17.8 years (mean 6.4 ± 4.5, median 4.9 years). Each patients was submitted to clinical examination, estimation of the bone age, laboratory assays, and QUS assessment. Twenty-five percent of the cohort shows reduced QUS values for their age based on bone transmission time. Bone measurement were adjusted for multiple factors frequently observed in NS patients, such as growth retardation, delayed bone age, retarded puberty, and reduced body mass index, potentially affecting bone quality or its appraisal. In spite of the correction attempts, QUS measurement indicates that bone impairment persists in nearly 15% of the cohort studied. Our results indicate that bone impairment in NS is likely primary and not secondary to any of the phenotypic traits of NS, nor consistent with metabolic disturbances. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  3. Phenotypic instability of Saos-2 cells in long-term culture

    International Nuclear Information System (INIS)

    Hausser, Heinz-Juergen; Brenner, Rolf E.

    2005-01-01

    The human osteosarcoma cell line Saos-2 is widely used as a model system for human osteoblastic cells, though its phenotypic stability has not been ascertained. We therefore propagated these cells over 100 passages and compared relevant phenotypic properties. In general, higher passage cells exhibited higher proliferation rates and lower specific alkaline phosphatase activities, though mineralization was significantly more pronounced in cultures of late passage cells. Whereas expression of most genes investigated did not vary profoundly, some genes exhibited remarkable differences. Decorin, for instance, that has been discussed as a regulator of proliferation and mineralization, is strongly expressed only in early passage cells, and two receptors for pleiotrophin and midkine exhibited an almost mutually exclusive expression pattern in early and late passage cells, respectively. Our observations indicate that special care is required when results obtained with Saos-2 cells with different culture history are to be compared

  4. Audiological and vestibular features in affected subjects with USH3: a genotype/phenotype correlation.

    Science.gov (United States)

    Sadeghi, Mehdi; Cohn, Edward S; Kimberling, William J; Tranebjaerg, Lisbeth; Möller, Claes

    2005-05-01

    The aims were to compare the genotype/phenotype relationship between USH3 mutations and the consequent hearing and vestibular phenotype; and to compare hearing loss (HL) progression between Usher syndrome types IB, IIA and USH3. Genetic, audiometric and vestibular examinations were performed in 28 subjects with USH3. Five different mutations in USH3 were identified. Severe HL was present from an early age (4 to 6 years) in 35% of subjects with USH3. Progression of HL begins in the first decade, and approximately 50% of subjects with USH3 become profoundly deaf by age 40. Various vestibular abnormalities were found in about half (10/22) of the tested subjects with USH3. Depending on the severity of HL, subjects with USH3 might be misdiagnosed as either Usher type IB or IIA. The results from this study can be used as discriminatory features in differential diagnosis of this syndrome.

  5. Impaired fasting glucose and impaired glucose tolerance in children and adolescents with overweight/obesity.

    Science.gov (United States)

    Di Bonito, P; Pacifico, L; Chiesa, C; Valerio, G; Miraglia Del Giudice, E; Maffeis, C; Morandi, A; Invitti, C; Licenziati, M R; Loche, S; Tornese, G; Franco, F; Manco, M; Baroni, M G

    2017-04-01

    To investigate in a large sample of overweight/obese (OW/OB) children and adolescents the prevalence of prediabetic phenotypes such as impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), and to assess their association with cardiometabolic risk (CMR) factors including hepatic steatosis (HS). Population data were obtained from the CARdiometabolic risk factors in children and adolescents in ITALY study. Between 2003 and 2013, 3088 youths (972 children and 2116 adolescents) received oral glucose tolerance test (OGTT) and were included in the study. In 798 individuals, abdominal ultrasound for identification of HS was available. The prevalence of IFG (3.2 vs. 3.3%) and IGT (4.6 vs. 5.0%) was similar between children and adolescents. Children with isolated IGT had a 2-11 fold increased risk of high LDL-C, non-HDL-C, Tg/HDL-C ratio, and low insulin sensitivity, when compared to those with normal glucose tolerance (NGT). No significant association of IFG with any CMR factor was found in children. Among adolescents, IGT subjects, and to a lesser extent those with IFG, showed a worse CMR profile compared to NGT subgroup. In the overall sample, IGT phenotype showed a twofold increased risk of HS compared to NGT subgroup. Our study shows an unexpected similar prevalence of IFG and IGT between children and adolescents with overweight/obesity. The IGT phenotype was associated with a worse CMR profile in both children and adolescents. Phenotyping prediabetes conditions by OGTT should be done as part of prediction and prevention of cardiometabolic diseases in OW/OB youth since early childhood.

  6. The Effect of Parkinson Disease Tremor Phenotype on Cepstral Peak Prominence and Transglottal Airflow in Vowels and Speech.

    Science.gov (United States)

    Burk, Brittany R; Watts, Christopher R

    2018-02-19

    The physiological manifestations of Parkinson disease are heterogeneous, as evidenced by disease subtypes. Dysphonia has been well documented as an early and progressively significant impairment associated with the disease. The purpose of this study was to investigate how acoustic and aerodynamic measures of vocal function were affected by Parkinson tremor subtype (phenotype) in an effort to better understand the heterogeneity of voice impairment severity in Parkinson disease. This is a prospective case-control study. Thirty-two speakers with Parkinson disease assigned to tremor and nontremor phenotypes and 10 healthy controls were recruited. Sustained vowels and connected speech were recorded from each speaker. Acoustic measures of cepstral peak prominence (CPP) and aerodynamic measures of transglottal airflow (TAF) were calculated from the recorded acoustic and aerodynamic waveforms. Speakers with a nontremor dominant phenotype exhibited significantly (P Parkinson tremor phenotype in mild to moderate stages of the disease. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  7. Race is gendered: how covarying phenotypes and stereotypes bias sex categorization.

    Science.gov (United States)

    Johnson, Kerri L; Freeman, Jonathan B; Pauker, Kristin

    2012-01-01

    We argue that race and sex categories are psychologically and phenotypically confounded, affecting social categorizations and their efficiency. Sex categorization of faces was facilitated when the race category shared facial phenotypes or stereotypes with the correct sex category (e.g., Asian women and Black men) but was impaired when the race category shared incompatible phenotypes or stereotypes with the correct sex category (e.g., Asian men and Black women). These patterns were evident in the disambiguation of androgynous faces (Study 1) and the efficiency of judgments (Studies 1, 2, 4, and 5). These patterns emerged due to common facial phenotypes for the categories Black and men (Studies 3 and 5) and due to shared stereotypes among the categories Black and men and the categories Asian and women (Studies 4 and 5). These findings challenge the notion that social categories are perceived independent of one another and show, instead, that race is gendered.

  8. Automated phenotyping of permanent crops

    Science.gov (United States)

    McPeek, K. Thomas; Steddom, Karl; Zamudio, Joseph; Pant, Paras; Mullenbach, Tyler

    2017-05-01

    AGERpoint is defining a new technology space for the growers' industry by introducing novel applications for sensor technology and data analysis to growers of permanent crops. Serving data to a state-of-the-art analytics engine from a cutting edge sensor platform, a new paradigm in precision agriculture is being developed that allows growers to understand the unique needs of each tree, bush or vine in their operation. Autonomous aerial and terrestrial vehicles equipped with multiple varieties of remote sensing technologies give AGERpoint the ability to measure key morphological and spectral features of permanent crops. This work demonstrates how such phenotypic measurements combined with machine learning algorithms can be used to determine the variety of crops (e.g., almond and pecan trees). This phenotypic and varietal information represents the first step in enabling growers with the ability to tailor their management practices to individual plants and maximize their economic productivity.

  9. Phenotypic deconstruction of gene circuitry.

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    2013-06-01

    It remains a challenge to obtain a global perspective on the behavioral repertoire of complex nonlinear gene circuits. In this paper, we describe a method for deconstructing complex systems into nonlinear sub-systems, based on mathematically defined phenotypes, which are then represented within a system design space that allows the repertoire of qualitatively distinct phenotypes of the complex system to be identified, enumerated, and analyzed. This method efficiently characterizes large regions of system design space and quickly generates alternative hypotheses for experimental testing. We describe the motivation and strategy in general terms, illustrate its use with a detailed example involving a two-gene circuit with a rich repertoire of dynamic behavior, and discuss experimental means of navigating the system design space.

  10. Phenotypic deconstruction of gene circuitry

    Science.gov (United States)

    Lomnitz, Jason G.; Savageau, Michael A.

    2013-06-01

    It remains a challenge to obtain a global perspective on the behavioral repertoire of complex nonlinear gene circuits. In this paper, we describe a method for deconstructing complex systems into nonlinear sub-systems, based on mathematically defined phenotypes, which are then represented within a system design space that allows the repertoire of qualitatively distinct phenotypes of the complex system to be identified, enumerated, and analyzed. This method efficiently characterizes large regions of system design space and quickly generates alternative hypotheses for experimental testing. We describe the motivation and strategy in general terms, illustrate its use with a detailed example involving a two-gene circuit with a rich repertoire of dynamic behavior, and discuss experimental means of navigating the system design space.

  11. Wine Expertise Predicts Taste Phenotype.

    Science.gov (United States)

    Hayes, John E; Pickering, Gary J

    2012-03-01

    Taste phenotypes have long been studied in relation to alcohol intake, dependence, and family history, with contradictory findings. However, on balance - with appropriate caveats about populations tested, outcomes measured and psychophysical methods used - an association between variation in taste responsiveness and some alcohol behaviors is supported. Recent work suggests super-tasting (operationalized via propylthiouracil (PROP) bitterness) not only associates with heightened response but also with more acute discrimination between stimuli. Here, we explore relationships between food and beverage adventurousness and taste phenotype. A convenience sample of wine drinkers (n=330) were recruited in Ontario and phenotyped for PROP bitterness via filter paper disk. They also filled out a short questionnaire regarding willingness to try new foods, alcoholic beverages and wines as well as level of wine involvement, which was used to classify them as a wine expert (n=110) or wine consumer (n=220). In univariate logisitic models, food adventurousness predicted trying new wines and beverages but not expertise. Likewise, wine expertise predicted willingness to try new wines and beverages but not foods. In separate multivariate logistic models, willingness to try new wines and beverages was predicted by expertise and food adventurousness but not PROP. However, mean PROP bitterness was higher among wine experts than wine consumers, and the conditional distribution functions differed between experts and consumers. In contrast, PROP means and distributions did not differ with food adventurousness. These data suggest individuals may self-select for specific professions based on sensory ability (i.e., an active gene-environment correlation) but phenotype does not explain willingness to try new stimuli.

  12. From plant genomes to phenotypes

    OpenAIRE

    Bolger, Marie; Gundlach, Heidrun; Scholz, Uwe; Mayer, Klaus; Usadel, Björn; Schwacke, Rainer; Schmutzer, Thomas; Chen, Jinbo; Arend, Daniel; Oppermann, Markus; Weise, Stephan; Lange, Matthias; Fiorani, Fabio; Spannagl, Manuel

    2017-01-01

    Recent advances in sequencing technologies have greatly accelerated the rate of plant genome and applied breeding research. Despite this advancing trend, plant genomes continue to present numerous difficulties to the standard tools and pipelines not only for genome assembly but also gene annotation and downstream analysis.Here we give a perspective on tools, resources and services necessary to assemble and analyze plant genomes and link them to plant phenotypes.

  13. Phenotypic covariance at species' borders.

    Science.gov (United States)

    Caley, M Julian; Cripps, Edward; Game, Edward T

    2013-05-28

    Understanding the evolution of species limits is important in ecology, evolution, and conservation biology. Despite its likely importance in the evolution of these limits, little is known about phenotypic covariance in geographically marginal populations, and the degree to which it constrains, or facilitates, responses to selection. We investigated phenotypic covariance in morphological traits at species' borders by comparing phenotypic covariance matrices (P), including the degree of shared structure, the distribution of strengths of pair-wise correlations between traits, the degree of morphological integration of traits, and the ranks of matricies, between central and marginal populations of three species-pairs of coral reef fishes. Greater structural differences in P were observed between populations close to range margins and conspecific populations toward range centres, than between pairs of conspecific populations that were both more centrally located within their ranges. Approximately 80% of all pair-wise trait correlations within populations were greater in the north, but these differences were unrelated to the position of the sampled population with respect to the geographic range of the species. Neither the degree of morphological integration, nor ranks of P, indicated greater evolutionary constraint at range edges. Characteristics of P observed here provide no support for constraint contributing to the formation of these species' borders, but may instead reflect structural change in P caused by selection or drift, and their potential to evolve in the future.

  14. Adaptive evolution of molecular phenotypes

    International Nuclear Information System (INIS)

    Held, Torsten; Nourmohammad, Armita; Lässig, Michael

    2014-01-01

    Molecular phenotypes link genomic information with organismic functions, fitness, and evolution. Quantitative traits are complex phenotypes that depend on multiple genomic loci. In this paper, we study the adaptive evolution of a quantitative trait under time-dependent selection, which arises from environmental changes or through fitness interactions with other co-evolving phenotypes. We analyze a model of trait evolution under mutations and genetic drift in a single-peak fitness seascape. The fitness peak performs a constrained random walk in the trait amplitude, which determines the time-dependent trait optimum in a given population. We derive analytical expressions for the distribution of the time-dependent trait divergence between populations and of the trait diversity within populations. Based on this solution, we develop a method to infer adaptive evolution of quantitative traits. Specifically, we show that the ratio of the average trait divergence and the diversity is a universal function of evolutionary time, which predicts the stabilizing strength and the driving rate of the fitness seascape. From an information-theoretic point of view, this function measures the macro-evolutionary entropy in a population ensemble, which determines the predictability of the evolutionary process. Our solution also quantifies two key characteristics of adapting populations: the cumulative fitness flux, which measures the total amount of adaptation, and the adaptive load, which is the fitness cost due to a population's lag behind the fitness peak. (paper)

  15. Comparison of Irrational Believes between Mothers of Severe or Profound Mentally Handicapped Children with Healthy Children Mothers

    Directory of Open Access Journals (Sweden)

    Behrouz Hivadi

    2007-10-01

    Full Text Available Objective: The purpose of present research was the comparison of mothers irrational believes with severe or profound mentally handicapped child and mothers with normal child from 6 to14 years old in Tehran city. Materials & Methods: This study was an analytical, cross – sectional and comparative (case – control research. From mothers with severe or profound mentally handicapped child who had refered to Tehran welfare services centers, 80 mothers were selected by regular randomized sampling from two rehabilitation centers and 80 mothers with normal child were selected for peering with the group of testimonial from schools areas of east, west, south, north and center of Tehran, through multi - stage cluster sampling in for variables of: age of mothers, educational levels, the location of living and the number of children. They answered to questionnaire of irrational believes of jons (IBT. Analysis of data was done by descriptive and infringing statistics methods (Independent T test, U Mann Whitney, Chi-square and fisher. Results: The findings showed that: there are significantly differences in total irrational believes and irrational believes of blame proneness, frustration reactive, anxious over concern, problem avoiding and dependency, perfectionism between two groups of mothers (P<0/05. There was no significant difference in irrational believes between mothers who had mental handicap daughter and mothers who had mental handicap son (P=0/314. There was no significantly difference between two groups of mothers in four believes of demand for approval (P=0/737, high-self expectation (P=0/126, emotional irresponsibility (P=0/727, helplessness for change (p=0/283. Conclusion: Irrational believes and many its sub scales. In mothers of severe or profound mental handicap children were more than mothers with normal child. But believes of demand for approval, high self expectation, emotional irresponsibility, helplessness for change in mothers with

  16. Vascular cognitive impairment

    Directory of Open Access Journals (Sweden)

    N.V. Vakhnina

    2014-01-01

    Full Text Available Vascular pathology of the brain is the second most common cause of cognitive impairment after Alzheimer's disease. The article describes the modern concepts of etiology, pathogenetic mechanisms, clinical features and approaches to diagnosis and therapy of vascular cognitive impairment (VCI. Cerebrovascular accident, chronic cerebral circulatory insufficiency and their combination, sometimes in combination with a concomitant neurodegenerative process, are shown to be the major types of brain lesions leading to VCI. The clinical presentation of VCI is characterized by the neuropsychological status dominated by impairment of the executive frontal functions (planning, control, attention in combination with focal neurological symptoms. The diagnosis is based on comparing of the revealed neuropsychological and neurological features with neuroimaging data. Neurometabolic, acetylcholinergic, glutamatergic, and other vasoactive drugs and non-pharmacological methods are widely used to treat VCI. 

  17. Lithium and Renal Impairment

    DEFF Research Database (Denmark)

    Nielsen, René Ernst; Kessing, Lars Vedel; Nolen, Willem A

    2018-01-01

    INTRODUCTION: Lithium is established as an effective treatment of mania, of depression in bipolar and unipolar disorder, and in maintenance treatment of these disorders. However, due to the necessity of monitoring and concerns about irreversible adverse effects, in particular renal impairment......, after long-term use, lithium might be underutilized. METHODS: This study reviewed 6 large observational studies addressing the risk of impaired renal function associated with lithium treatment and methodological issues impacting interpretation of results. RESULTS: An increased risk of renal impairment...... associated with lithium treatment is suggested. This increased risk may, at least partly, be a result of surveillance bias. Additionally, the earliest studies pointed toward an increased risk of end-stage renal disease associated with lithium treatment, whereas the later and methodologically most sound...

  18. Language ability in children with permanent hearing impairment: the influence of early management and family participation.

    Science.gov (United States)

    Watkin, Peter; McCann, Donna; Law, Catherine; Mullee, Mark; Petrou, Stavros; Stevenson, Jim; Worsfold, Sarah; Yuen, Ho Ming; Kennedy, Colin

    2007-09-01

    The goal was to examine the relationships between management after confirmation, family participation, and speech and language outcomes in the same group of children with permanent childhood hearing impairment. Speech, oral language, and nonverbal abilities, expressed as z scores and adjusted in a regression model, and Family Participation Rating Scale scores were assessed at a mean age of 7.9 years for 120 children with bilateral permanent childhood hearing impairment from a 1992-1997 United Kingdom birth cohort. Ages at institution of management and hearing aid fitting were obtained retrospectively from case notes. Compared with children managed later (> 9 months), those managed early (early did not have significantly higher scores for these outcomes. Family Participation Rating Scale scores showed significant positive correlations with language and speech intelligibility scores only for those with confirmation after 9 months and were highest for those with late confirmed, severe/profound, permanent childhood hearing impairment. Early management of permanent childhood hearing impairment results in improved language. Family participation is also an important factor in cases that are confirmed late, especially for children with severe or profound permanent childhood hearing impairment.

  19. Social communication impairments: pragmatics.

    Science.gov (United States)

    Russell, Robert L

    2007-06-01

    Social communication or pragmatic impairments are characterized and illustrated as involving inappropriate or ineffective use of language and gesture in social contexts. Three clinical vignettes illustrate different pragmatic impairments and the wealth of diagnostic information that can be garnered from observation of a child's social communication behavior. Definitions of, and developmental milestones in, domains of pragmatic competence are provided. Several screening instruments are suggested for use in assessing pragmatic competence within the time-frame of a pediatric examination. Frequent comorbid psychiatric conditions are described and a sample of current neurobiologic research is briefly summarized.

  20. Early phenotypical diagnoses in Trembler-J mice model.

    Science.gov (United States)

    Rosso, Gonzalo; Cal, Karina; Canclini, Lucía; Damián, Juan Pablo; Ruiz, Paul; Rodríguez, Héctor; Sotelo, José Roberto; Vazquez, Cristina; Kun, Alejandra

    2010-06-30

    Pmp-22 mutant mice (Trembler-J: B6.D2-Pmp22/J), are used as a model to study Charcot-Marie-Tooth type 1A (CMT1A). The identification of individual genotypes is a routine in the management of the Tr(J) colony. The earliest phenotypic manifestation of the pmp-22 mutation is just about 20th postnatal days, when pups begin to tremble. In this study, a rapid and simple diagnostic method was developed by modifying the Tail Suspension Test (MTST) to determine the difference between the Tr(J) and the wild-type mice phenotype. The animal behavioral phenotypes generated during the test were consistent with the specific genotype of each animal. The MTST allowed us to infer the heterozygous genotype in early postnatal stages, at 11 days after birth. The motor impairment of Tr(J) mice was also analyzed by a Fixed Bar Test (FBT), which revealed the disease evolution according to age. The main advantages of MTST are its objectivity, simplicity, and from the viewpoint of animal welfare, it is a non-invasive technique that combined with his rapidity show its very well applicability for use from an early age in these mice. Copyright 2010 Elsevier B.V. All rights reserved.

  1. Clinical features of Friedreich's ataxia: classical and atypical phenotypes.

    Science.gov (United States)

    Parkinson, Michael H; Boesch, Sylvia; Nachbauer, Wolfgang; Mariotti, Caterina; Giunti, Paola

    2013-08-01

    One hundred and fifty years since Nikolaus Friedreich's first description of the degenerative ataxic syndrome which bears his name, his description remains at the core of the classical clinical phenotype of gait and limb ataxia, poor balance and coordination, leg weakness, sensory loss, areflexia, impaired walking, dysarthria, dysphagia, eye movement abnormalities, scoliosis, foot deformities, cardiomyopathy and diabetes. Onset is typically around puberty with slow progression and shortened life-span often related to cardiac complications. Inheritance is autosomal recessive with the vast majority of cases showing an unstable intronic GAA expansion in both alleles of the frataxin gene on chromosome 9q13. A small number of cases are caused by a compound heterozygous expansion with a point mutation or deletion. Understanding of the underlying molecular biology has enabled identification of atypical phenotypes with late onset, or atypical features such as retained reflexes. Late-onset cases tend to have slower progression and are associated with smaller GAA expansions. Early-onset cases tend to have more rapid progression and a higher frequency of non-neurological features such as diabetes, cardiomyopathy, scoliosis and pes cavus. Compound heterozygotes, including those with large deletions, often have atypical features. In this paper, we review the classical and atypical clinical phenotypes of Friedreich's ataxia. © 2013 International Society for Neurochemistry.

  2. Phenotype expression in women with CMT1X.

    LENUS (Irish Health Repository)

    Siskind, Carly E

    2011-06-01

    Charcot-Marie-Tooth disease type 1X (CMT1X) is the second most common inherited peripheral neuropathy. Women with CMT1X typically have a less severe phenotype than men, perhaps because of X-inactivation patterns. Our objective was to determine the phenotype of women with CMT1X and whether X-inactivation patterns in white blood cells (WBCs) differ between females with CMT1X and controls. Thirty-one women with CMT1X were evaluated using the CMT neuropathy score (CMTNS) and the CMT symptom score in cross-sectional and longitudinal analyses. Lower scores correspond to less disability. WBCs were analyzed for X-inactivation pattern by androgen receptor X-inactivation assay in 14 patients and 23 controls. The 31 women\\'s mean CMTNS was 8.35. Two-thirds of the cohort had a mild CMTNS (mean 4.85) and one-third had a moderate CMTNS (mean 14.73). Three patients had a CMTNS of 0. The pattern of X-inactivation did not differ between the affected and control groups. Women with CMT1X presented with variable impairment independent of age, type of mutation, or location of mutation. No evidence supported the presence of a gap junction beta-1 (GJB1) mutation affecting the pattern of X-inactivation in blood. Further studies are planned to determine whether X-inactivation is the mechanism for CMT1X females\\' variable phenotypes.

  3. Impaired Interoceptive Accuracy in Semantic Variant Primary Progressive Aphasia

    Directory of Open Access Journals (Sweden)

    Charles R. Marshall

    2017-11-01

    Full Text Available BackgroundInteroception (the perception of internal bodily sensations is strongly linked to emotional experience and sensitivity to the emotions of others in healthy subjects. Interoceptive impairment may contribute to the profound socioemotional symptoms that characterize frontotemporal dementia (FTD syndromes, but remains poorly defined.MethodsPatients representing all major FTD syndromes and healthy age-matched controls performed a heartbeat counting task as a measure of interoceptive accuracy. In addition, patients had volumetric MRI for voxel-based morphometric analysis, and their caregivers completed a questionnaire assessing patients’ daily-life sensitivity to the emotions of others.ResultsInteroceptive accuracy was impaired in patients with semantic variant primary progressive aphasia relative to healthy age-matched individuals, but not in behavioral variant frontotemporal dementia and nonfluent variant primary progressive aphasia. Impaired interoceptive accuracy correlated with reduced daily-life emotional sensitivity across the patient cohort, and with atrophy of right insula, cingulate, and amygdala on voxel-based morphometry in the impaired semantic variant group, delineating a network previously shown to support interoceptive processing in the healthy brain.ConclusionInteroception is a promising novel paradigm for defining mechanisms of reduced emotional reactivity, empathy, and self-awareness in neurodegenerative syndromes and may yield objective measures for these complex symptoms.

  4. Cortical activation in profoundly deaf patients during cochlear implant stimulation demonstrated by H2(15)O PET

    International Nuclear Information System (INIS)

    Herzog, H.; Lamprecht, A.; Kuehn, A.R.; Roden, W.; Vosteen, K.H.; Feinendegen, L.E.

    1991-01-01

    Cochlear implants (CIs) are used to provide sensations of sound to profoundly deaf patients. The performance of the CI is assessed mainly by the subjective reports of patients. The aim of this study was to look for objective cortical responses to the stimulation of the CI. Two postlingually and two prelingually deaf patients were investigated by positron emission tomography (PET) using 15 O-labeled water (H 2 15 O) to determine the regional cerebral blood flow (rCBF). Instead of quantifying rCBF in absolute terms, it was estimated by referring the regional tissue concentration of H 2 15 O to the mean whole brain concentration. CI stimulation encoded from white noise and sequential words led to an increased rCBF in the primary and secondary (Wernicke) auditory cortex. Relative elevations of up to 33% were observed bilaterally, although they were higher contralateral to the CI. These results were obtained not only in the postlingually deaf patients but also in two patients who had never been able to hear. Thus, it could be demonstrated that PET measurements of cerebral H 2 15 O distribution yield objective responses of the central auditory system during electrical stimulation by CIs in profoundly deaf patients

  5. Knowledge-based analysis of phenotypes

    KAUST Repository

    Hoendorf, Robert

    2016-01-27

    Phenotypes are the observable characteristics of an organism, and they are widely recorded in biology and medicine. To facilitate data integration, ontologies that formally describe phenotypes are being developed in several domains. I will describe a formal framework to describe phenotypes. A formalized theory of phenotypes is not only useful for domain analysis, but can also be applied to assist in the diagnosis of rare genetic diseases, and I will show how our results on the ontology of phenotypes is now applied in biomedical research.

  6. Highly variable penetrance of abnormal phenotypes in embryonic lethal knockout mice

    Science.gov (United States)

    Wilson, Robert; Geyer, Stefan H.; Reissig, Lukas; Rose, Julia; Szumska, Dorota; Hardman, Emily; Prin, Fabrice; McGuire, Christina; Ramirez-Solis, Ramiro; White, Jacqui; Galli, Antonella; Tudor, Catherine; Tuck, Elizabeth; Mazzeo, Cecilia Icoresi; Smith, James C.; Robertson, Elizabeth; Adams, David J.; Mohun, Timothy; Weninger, Wolfgang J.

    2017-01-01

    Background: Identifying genes that are essential for mouse embryonic development and survival through term is a powerful and unbiased way to discover possible genetic determinants of human developmental disorders. Characterising the changes in mouse embryos that result from ablation of lethal genes is a necessary first step towards uncovering their role in normal embryonic development and establishing any correlates amongst human congenital abnormalities. Methods: Here we present results gathered to date in the Deciphering the Mechanisms of Developmental Disorders (DMDD) programme, cataloguing the morphological defects identified from comprehensive imaging of 220 homozygous mutant and 114 wild type embryos from 42 lethal and subviable lines, analysed at E14.5. Results: Virtually all mutant embryos show multiple abnormal phenotypes and amongst the 42 lines these affect most organ systems. Within each mutant line, the phenotypes of individual embryos form distinct but overlapping sets. Subcutaneous edema, malformations of the heart or great vessels, abnormalities in forebrain morphology and the musculature of the eyes are all prevalent phenotypes, as is loss or abnormal size of the hypoglossal nerve. Conclusions: Overall, the most striking finding is that no matter how profound the malformation, each phenotype shows highly variable penetrance within a mutant line. These findings have challenging implications for efforts to identify human disease correlates. PMID:27996060

  7. NIH Mouse Metabolic Phenotyping Centers: the power of centralized phenotyping.

    Science.gov (United States)

    Laughlin, Maren R; Lloyd, K C Kent; Cline, Gary W; Wasserman, David H

    2012-10-01

    The Mouse Metabolic Phenotyping Centers (MMPCs) were founded in 2001 by the National Institutes of Health (NIH) to advance biomedical research by providing the scientific community with standardized, high-quality phenotyping services for mouse models of diabetes, obesity, and their complications. The intent is to allow researchers to take optimum advantage of the many new mouse models produced in labs and in high-throughput public efforts. The six MMPCs are located at universities around the country and perform complex metabolic tests in intact mice and hormone and analyte assays in tissues on a fee-for-service basis. Testing is subsidized by the NIH in order to reduce the barriers for mouse researchers. Although data derived from these tests belong to the researcher submitting mice or tissues, these data are archived after publication in a public database run by the MMPC Coordinating and Bioinformatics Unit. It is hoped that data from experiments performed in many mouse models of metabolic diseases, using standard protocols, will be useful in understanding the nature of these complex disorders. The current areas of expertise include energy balance and body composition, insulin action and secretion, whole-body and tissue carbohydrate and lipid metabolism, cardiovascular and renal function, and metabolic pathway kinetics. In addition to providing services, the MMPC staff provides expertise and advice to researchers, and works to develop and refine test protocols to best meet the community's needs in light of current scientific developments. Test technology is disseminated by publications and through annual courses.

  8. Medications and impaired driving.

    Science.gov (United States)

    Hetland, Amanda; Carr, David B

    2014-04-01

    To describe the association of specific medication classes with driving outcomes and provide clinical recommendations. The MEDLINE and EMBASE databases were searched for articles published from January 1973 to June 2013 on classes of medications associated with driving impairment. The search included outcome terms such as automobile driving, motor vehicle crash, driving simulator, and road tests. Only English-language articles that contained findings from observational or interventional designs with ≥ 10 participants were included in this review. Cross-sectional studies, case series, and case reports were excluded. Driving is an important task and activity for the majority of adults. Some commonly prescribed medications have been associated with driving impairment measured by road performance, driving simulation, and/or motor vehicle crashes. This review of 30 studies identified findings with barbiturates, benzodiazepines, hypnotics, antidepressants, opioid and nonsteroidal analgesics, anticonvulsants, antipsychotics, antiparkinsonian agents, skeletal muscle relaxants, antihistamines, anticholinergic medications, and hypoglycemic agents. Additional studies of medication impact on sedation, sleep latency, and psychomotor function, as well as the role of alcohol, are also discussed. Psychotropic agents and those with central nervous system side effects were associated with measures of impaired driving performance. It is difficult to determine if such associations are actually a result of medication use or the medical diagnosis itself. Regardless, clinicians should be aware of the increased risk of impaired driving with specific classes of medications, educate their patients, and/or consider safer alternatives.

  9. The Human Phenotype Ontology in 2017

    International Nuclear Information System (INIS)

    Köhler, Sebastian; Vasilevsky, Nicole A.; Engelstad, Mark; Foster, Erin; McMurry, Julie

    2016-01-01

    Deep phenotyping has been defined as the precise and comprehensive analysis of phenotypic abnormalities in which the individual components of the phenotype are observed and described. The three components of the Human PhenotypeOntology (HPO; www.human-phenotype-ontology.org) project are the phenotype vocabulary, disease-phenotype annotations and the algorithms that operate on these. These components are being used for computational deep phenotyping and precision medicine as well as integration of clinical data into translational research. The HPO is being increasingly adopted as a standard for phenotypic abnormalities by diverse groups such as international rare disease organizations, registries, clinical labs, biomedical resources, and clinical software tools and will thereby contribute toward nascent efforts at global data exchange for identifying disease etiologies. This update article reviews the progress of the HPO project since the debut Nucleic Acids Research database article in 2014, including specific areas of expansion such as common (complex) disease, new algorithms for phenotype driven genomic discovery and diagnostics, integration of cross-species mapping efforts with the Mammalian Phenotype Ontology, an improved quality control pipeline, and the addition of patient-friendly terminology.

  10. Rescue of Impaired Fear Extinction and Normalization of Cortico-Amygdala Circuit Dysfunction in a Genetic Mouse Model by Dietary Zinc Restriction

    OpenAIRE

    Whittle, Nigel; Hauschild, Markus; Lubec, Gert; Holmes, Andrew; Singewald, Nicolas

    2010-01-01

    Fear extinction is impaired in neuropsychiatric disorders, including posttraumatic stress disorder. Identifying drugs that facilitate fear extinction in animal models provides leads for novel pharmacological treatments for these disorders. Zinc (Zn) is expressed in neurons in a cortico-amygdala circuit mediating fear extinction, and modulates neurotransmitter systems regulating extinction. We previously found that the 129S1/SvImJ mouse strain (S1) exhibited a profound impairment in fear extin...

  11. Phenotypic variability in Meesmann's dystrophy

    DEFF Research Database (Denmark)

    Ehlers, Niels; Hjortdal, Jesper; Nielsen, Kim

    2008-01-01

    symptoms often include blurred vision and ocular irritation. Typical cases may be entirely free of complaints. Intermittent pain episodes, such as occur in recurrent erosion syndrome, are not the rule. Genetic sequencing indicated a familial relationship with the originally described Meesmann family......'s dystrophy occurs worldwide. The largest family described is the original German one, now supplemented with a Danish branch. Despite the presence of an identical genetic defect, the clinical phenotype varies. This suggests that non-KRT12-related mechanisms are responsible for the variation....

  12. The thrifty phenotype hypothesis revisited

    DEFF Research Database (Denmark)

    Vaag, A A; Grunnet, L G; Arora, G P

    2012-01-01

    Twenty years ago, Hales and Barker along with their co-workers published some of their pioneering papers proposing the 'thrifty phenotype hypothesis' in Diabetologia (4;35:595-601 and 3;36:62-67). Their postulate that fetal programming could represent an important player in the origin of type 2...... of the underlying molecular mechanisms. Type 2 diabetes is a multiple-organ disease, and developmental programming, with its idea of organ plasticity, is a plausible hypothesis for a common basis for the widespread organ dysfunctions in type 2 diabetes and the metabolic syndrome. Only two among the 45 known type 2...

  13. Exploring the motor development of young children with possible severe to profound cognitive and motor developmental delay by means of a questionnaire

    NARCIS (Netherlands)

    Schalen, Gertruud Henrike; van der Putten, Annette; Maes, Bea; Vlaskamp, Carla

    Aim: Early motor stimulation may be valuable for children with profound intellectual and multiple disabilities (PIMD), however limited knowledge of their typical motor developmental trajectory may be currently restraining the efficacy and specificity of this intervention. Research on young children

  14. Reversal of rocuronium-induced (1.2 mg/kg) profound neuromuscular block by sugammadex: a multicenter, dose-finding and safety study.

    NARCIS (Netherlands)

    Boer, H.D. de; Driessen, J.J.; Marcus, M.A.; Kerkkamp, H.E.M.; Heeringa, M.; Klimek, M.

    2007-01-01

    BACKGROUND: Reversal of rocuronium-induced neuromuscular blockade can be accomplished by chemical encapsulation of rocuronium by sugammadex, a modified gamma-cyclodextrin derivative. This study investigated the efficacy and safety of sugammadex in reversing rocuronium-induced profound neuromuscular

  15. IGF-1 deficiency impairs cerebral myogenic autoregulation in hypertensive mice.

    Science.gov (United States)

    Toth, Peter; Tucsek, Zsuzsanna; Tarantini, Stefano; Sosnowska, Danuta; Gautam, Tripti; Mitschelen, Matthew; Koller, Akos; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

    2014-12-01

    Aging impairs autoregulatory protection in the brain, exacerbating hypertension-induced cerebromicrovascular injury, neuroinflammation, and development of vascular cognitive impairment. Despite the importance of the age-related decline in circulating insulin-like growth factor-1 (IGF-1) levels in cerebrovascular aging, the effects of IGF-1 deficiency on functional adaptation of cerebral arteries to high blood pressure remain elusive. To determine whether IGF-1 deficiency impairs autoregulatory protection, hypertension was induced in control and IGF-1-deficient mice (Igf1(f/f)+TBG-iCre-AAV8) by chronic infusion of angiotensin-II. In hypertensive control mice, cerebral blood flow (CBF) autoregulation was extended to higher pressure values and the pressure-induced tone of middle cerebral arteries (MCAs) was increased. In hypertensive IGF-1-deficient mice, autoregulation was markedly disrupted, and MCAs did not show adaptive increases in myogenic tone. In control mice, the mechanism of adaptation to hypertension involved upregulation of TRPC channels in MCAs and this mechanism was impaired in hypertensive IGF-1-deficient mice. Likely downstream consequences of cerebrovascular autoregulatory dysfunction in hypertensive IGF-1-deficient mice included exacerbated disruption of the blood-brain barrier and neuroinflammation (microglia activation and upregulation of proinflammatory cytokines and chemokines), which were associated with impaired hippocampal cognitive function. Collectively, IGF-1 deficiency impairs autoregulatory protection in the brain of hypertensive mice, potentially exacerbating cerebromicrovascular injury and neuroinflammation mimicking the aging phenotype.

  16. Targeting MEK5 Enhances Radiosensitivity of Human Prostate Cancer and Impairs Tumor-Associated Angiogenesis

    Science.gov (United States)

    2016-09-01

    analysis of tumor necrosis factor - alpha resistant human breast cancer cells reveals a MEK5/Erk5-mediated epithelial-mesenchymal transition phenotype...AWARD NUMBER: W81XWH-15-1-0296 TITLE: Targeting MEK5 Enhances Radiosensitivity of Human Prostate Cancer and Impairs Tumor - Associated...Cancer and Impairs Tumor -Associated Angiogenesis 5b. GRANT NUMBER W81XWH-15-1-0296 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER

  17. ACE phenotyping in Gaucher disease.

    Science.gov (United States)

    Danilov, Sergei M; Tikhomirova, Victoria E; Metzger, Roman; Naperova, Irina A; Bukina, Tatiana M; Goker-Alpan, Ozlem; Tayebi, Nahid; Gayfullin, Nurshat M; Schwartz, David E; Samokhodskaya, Larisa M; Kost, Olga A; Sidransky, Ellen

    2018-04-01

    Gaucher disease is characterized by the activation of splenic and hepatic macrophages, accompanied by dramatically increased levels of angiotensin-converting enzyme (ACE). To evaluate the source of the elevated blood ACE, we performed complete ACE phenotyping using blood, spleen and liver samples from patients with Gaucher disease and controls. ACE phenotyping included 1) immunohistochemical staining for ACE; 2) measuring ACE activity with two substrates (HHL and ZPHL); 3) calculating the ratio of the rates of substrate hydrolysis (ZPHL/HHL ratio); 4) assessing the conformational fingerprint of ACE by evaluating the pattern of binding of monoclonal antibodies to 16 different ACE epitopes. We show that in patients with Gaucher disease, the dramatically increased levels of ACE originate from activated splenic and/or hepatic macrophages (Gaucher cells), and that both its conformational fingerprint and kinetic characteristics (ZPHL/HHL ratio) differ from controls and from patients with sarcoid granulomas. Furthermore, normal spleen was found to produce high levels of endogenous ACE inhibitors and a novel, tightly-bound 10-30 kDa ACE effector which is deficient in Gaucher spleen. The conformation of ACE is tissue-specific. In Gaucher disease, ACE produced by activated splenic macrophages differs from that in hepatic macrophages, as well as from macrophages and dendritic cells in sarcoid granulomas. The observed differences are likely due to altered ACE glycosylation or sialylation in these diseased organs. The conformational differences in ACE may serve as a specific biomarker for Gaucher disease. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Grammatical Impairments in PPA.

    Science.gov (United States)

    Thompson, Cynthia K; Mack, Jennifer E

    2014-09-01

    Grammatical impairments are commonly observed in the agrammatic subtype of primary progressive aphasia (PPA-G), whereas grammatical processing is relatively preserved in logopenic (PPA-L) and semantic (PPA-S) subtypes. We review research on grammatical deficits in PPA and associated neural mechanisms, with discussion focused on production and comprehension of four aspects of morphosyntactic structure: grammatical morphology, functional categories, verbs and verb argument structure, and complex syntactic structures. We also address assessment of grammatical deficits in PPA, with emphasis on behavioral tests of grammatical processing. Finally, we address research examining the effects of treatment for progressive grammatical impairments. PPA-G is associated with grammatical deficits that are evident across linguistic domains in both production and comprehension. PPA-G is associated with damage to regions including the left inferior frontal gyrus (IFG) and dorsal white matter tracts, which have been linked to impaired comprehension and production of complex sentences. Detailing grammatical deficits in PPA is important for estimating the trajectory of language decline and associated neuropathology. We, therefore, highlight several new assessment tools for examining different aspects of morphosyntactic processing in PPA. Individuals with PPA-G present with agrammatic deficit patterns distinct from those associated with PPA-L and PPA-S, but similar to those seen in agrammatism resulting from stroke, and patterns of cortical atrophy and white matter changes associated with PPA-G have been identified. Methods for clinical evaluation of agrammatism, focusing on comprehension and production of grammatical morphology, functional categories, verbs and verb argument structure, and complex syntactic structures are recommended and tools for this are emerging in the literature. Further research is needed to investigate the real-time processes underlying grammatical impairments in

  19. The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 2: the evolving clinical phenotype.

    Science.gov (United States)

    Kölker, Stefan; Valayannopoulos, Vassili; Burlina, Alberto B; Sykut-Cegielska, Jolanta; Wijburg, Frits A; Teles, Elisa Leão; Zeman, Jiri; Dionisi-Vici, Carlo; Barić, Ivo; Karall, Daniela; Arnoux, Jean-Baptiste; Avram, Paula; Baumgartner, Matthias R; Blasco-Alonso, Javier; Boy, S P Nikolas; Rasmussen, Marlene Bøgehus; Burgard, Peter; Chabrol, Brigitte; Chakrapani, Anupam; Chapman, Kimberly; Cortès I Saladelafont, Elisenda; Couce, Maria L; de Meirleir, Linda; Dobbelaere, Dries; Furlan, Francesca; Gleich, Florian; González, Maria Julieta; Gradowska, Wanda; Grünewald, Stephanie; Honzik, Tomas; Hörster, Friederike; Ioannou, Hariklea; Jalan, Anil; Häberle, Johannes; Haege, Gisela; Langereis, Eveline; de Lonlay, Pascale; Martinelli, Diego; Matsumoto, Shirou; Mühlhausen, Chris; Murphy, Elaine; de Baulny, Hélène Ogier; Ortez, Carlos; Pedrón, Consuelo C; Pintos-Morell, Guillem; Pena-Quintana, Luis; Ramadža, Danijela Petković; Rodrigues, Esmeralda; Scholl-Bürgi, Sabine; Sokal, Etienne; Summar, Marshall L; Thompson, Nicholas; Vara, Roshni; Pinera, Inmaculada Vives; Walter, John H; Williams, Monique; Lund, Allan M; Garcia-Cazorla, Angeles; Garcia Cazorla, Angeles

    2015-11-01

    The disease course and long-term outcome of patients with organic acidurias (OAD) and urea cycle disorders (UCD) are incompletely understood. To evaluate the complex clinical phenotype of OAD and UCD patients at different ages. Acquired microcephaly and movement disorders were common in OAD and UCD highlighting that the brain is the major organ involved in these diseases. Cardiomyopathy [methylmalonic (MMA) and propionic aciduria (PA)], prolonged QTc interval (PA), optic nerve atrophy [MMA, isovaleric aciduria (IVA)], pancytopenia (PA), and macrocephaly [glutaric aciduria type 1 (GA1)] were exclusively found in OAD patients, whereas hepatic involvement was more frequent in UCD patients, in particular in argininosuccinate lyase (ASL) deficiency. Chronic renal failure was often found in MMA, with highest frequency in mut(0) patients. Unexpectedly, chronic renal failure was also observed in adolescent and adult patients with GA1 and ASL deficiency. It had a similar frequency in patients with or without a movement disorder suggesting different pathophysiology. Thirteen patients (classic OAD: 3, UCD: 10) died during the study interval, ten of them during the initial metabolic crisis in the newborn period. Male patients with late-onset ornithine transcarbamylase deficiency were presumably overrepresented in the study population. Neurologic impairment is common in OAD and UCD, whereas the involvement of other organs (heart, liver, kidneys, eyes) follows a disease-specific pattern. The identification of unexpected chronic renal failure in GA1 and ASL deficiency emphasizes the importance of a systematic follow-up in patients with rare diseases.

  20. Efforts to increase social contact in persons with profound intellectual and multiple disabilities: Analysing individual support plans in the Netherlands.

    Science.gov (United States)

    Kamstra, Aafke; van der Putten, Annette Aj; Vlaskamp, Carla

    2017-06-01

    Most people with profound intellectual and multiple disabilities (PIMD) have limited social contact and it is unclear what is done to maintain or increase these contacts. Individual support planning (ISP) can be used in the systematic enhancement of social contacts. This study analyses the content of ISPs with respect to the social contacts of people with PIMD. ISPs for 60 persons with PIMD in the Netherlands were inductively coded and illustrated with quotations. It turned out that every ISP contained information about social contacts. Of all the quotations extracted, 71.2% were about current conditions, 6.2% were about the future and less than 1% concerned actual goals. The social contacts of people with PIMD are mentioned in their ISPs, but this is rarely translated into goals. The results of the current study suggest that attention should be paid to ensuring that professionals understand the importance of social contacts and their application in practice.

  1. An ecological method for the sampling of nonverbal signalling behaviours of young children with profound and multiple learning disabilities (PMLD).

    Science.gov (United States)

    Atkin, Keith; Lorch, Marjorie Perlman

    2016-08-01

    Profound and multiple learning disabilities (PMLD) are a complex range of disabilities that affect the general health and well-being of the individual and their capacity to interact and learn. We developed a new methodology to capture the non-symbolic signalling behaviours of children with PMLD within the context of a face-to-face interaction with a caregiver to provide analysis at a micro-level of descriptive detail incorporating the use of the ELAN digital video software. The signalling behaviours of participants in a natural, everyday interaction can be better understood with the use of this innovation in methodology, which is predicated on the ecology of communication. Recognition of the developmental ability of the participants is an integral factor within that ecology. The method presented establishes an advanced account of the modalities through which a child affected by PMLD is able to communicate.

  2. A Case of Profound Soft Tissue Infection of Lower Limb Contained Maggots after IV Abuse of Iranian

    Directory of Open Access Journals (Sweden)

    Majid Heidary

    2016-07-01

    Full Text Available Background: Infections include soft tissue infections are notable reason for hospital admission among IDUs, owing to unsterile injection techniques and equipment, contamination of drugs with organisms, and poor hygiene. In present case report a patient with profound limb infection is introduced. Case: A 32 years old man was transferred to the emergency department. He was IDU with Iranian for 3 years. Gangrenous deformity of left lower extremity below the knee was seen. Live maggots were moving around the limb freely. The patient underwent before knee amputation (BKA to remove the infected tissues of the limb. Conclusion: In order to evaluate and treat the serious infectious disease problems, drug abuse treatment programs will need to develop appropriate procedures. It is important that physicians, nurses, and other health care providers become better educated about drug abuse. Workers in drug abuse treatment should be well informed about infectious diseases and other complications of drug abuse.

  3. Tyr120Asp mutation alters domain flexibility and dynamics of MeCP2 DNA binding domain leading to impaired DNA interaction: Atomistic characterization of a Rett syndrome causing mutation.

    Science.gov (United States)

    D'Annessa, Ilda; Gandaglia, Anna; Brivio, Elena; Stefanelli, Gilda; Frasca, Angelisa; Landsberger, Nicoletta; Di Marino, Daniele

    2018-05-01

    Mutations in the X-linked MECP2 gene represent the main origin of Rett syndrome, causing a profound intellectual disability in females. MeCP2 is an epigenetic transcriptional regulator containing two main functional domains: a methyl-CpG binding domain (MBD) and a transcription repression domain (TRD). Over 600 pathogenic mutations were reported to affect the whole protein; almost half of missense mutations affect the MBD. Understanding the impact of these mutations on the MBD structure and interaction with DNA will foster the comprehension of their pathogenicity and possibly genotype/phenotype correlation studies. Herein, we use molecular dynamics simulations to obtain a detailed view of the dynamics of WT and mutated MBD in the presence and absence of DNA. The pathogenic mutation Y120D is used as paradigm for our studies. Further, since the Y120 residue was previously found to be a phosphorylation site, we characterize the dynamic profile of the MBD also in the presence of Y120 phosphorylation (pY120). We found that addition of a phosphate group to Y120 or mutation in aspartic acid affect domain mobility that samples an alternative conformational space with respect to the WT, leading to impaired ability to interact with DNA. Experimental assays showing a significant reduction in the binding affinity between the mutated MBD and the DNA confirmed our predictions. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Working with impairments

    OpenAIRE

    Maroesjka Versantvoort; Patricia van Echtelt

    2012-01-01

    Original title: Belemmerd aan het werk The Netherlands was long known as a country with high sickness absenteeism rates and a burgeoning group of people who were unfit for work. In response to this, many policy measures have been introduced in recent decades which attempt to limit the benefit volume and foster the reintegration of people with health impairments. What is the position of the Netherlands today in this regard? The main trends in sickness absenteeism, degree of incapacity for work...

  5. Age-Related Sensory Impairments and Risk of Cognitive Impairment

    Science.gov (United States)

    Fischer, Mary E; Cruickshanks, Karen J.; Schubert, Carla R; Pinto, Alex A; Carlsson, Cynthia M; Klein, Barbara EK; Klein, Ronald; Tweed, Ted S.

    2016-01-01

    Background/Objectives To evaluate the associations of sensory impairments with the 10-year risk of cognitive impairment. Previous work has primarily focused on the relationship between a single sensory system and cognition. Design The Epidemiology of Hearing Loss Study (EHLS) is a longitudinal, population-based study of aging in the Beaver Dam, WI community. Baseline examinations were conducted in 1993 and follow-up exams have been conducted every 5 years. Setting General community Participants EHLS members without cognitive impairment at EHLS-2 (1998–2000). There were 1,884 participants (mean age = 66.7 years) with complete EHLS-2 sensory data and follow-up information. Measurements Cognitive impairment was a Mini-Mental State Examination score of impairment was a pure-tone average of hearing thresholds (0.5, 1, 2 and 4 kHz) of > 25 decibel Hearing Level in either ear. Visual impairment was Pelli-Robson contrast sensitivity of impairment was a San Diego Odor Identification Test score of impairment were independently associated with cognitive impairment risk [Hearing: Hazard Ratio (HR) = 1.90, 95% Confidence Interval (C.I.) = 1.11, 3.26; Vision: HR = 2.05, 95% C.I. = 1.24, 3.38; Olfaction: HR = 3.92, 95% C.I. = 2.45, 6.26]. However, 85% with hearing impairment, 81% with visual impairment, and 76% with olfactory impairment did not develop cognitive impairment during follow-up. Conclusion The relationship between sensory impairment and cognitive impairment was not unique to one sensory system suggesting sensorineural health may be a marker of brain aging. The development of a combined sensorineurocognitive measure may be useful in uncovering mechanisms of healthy brain aging. PMID:27611845

  6. Does Visual Impairment Affect Social Ties in Late Life? Findings of a Multicenter Prospective Cohort Study in Germany.

    Science.gov (United States)

    Hajek, A; Brettschneider, C; Lühmann, D; Eisele, M; Mamone, S; Wiese, B; Weyerer, S; Werle, J; Pentzek, M; Fuchs, A; Stein, J; Luck, T; Bickel, H; Weeg, D; Heser, K; Jessen, F; Maier, W; Scherer, M; Riedel-Heller, S G; König, H-H

    2017-01-01

    To investigate how visual impairment affects social ties in late life longitudinally. Population-based prospective cohort study. Individuals in old age were recruited via general practitioners' offices (at six study centers) in Germany. They were interviewed every 18 months. Individuals aged 75 years and above at baseline. Follow-up wave 2 (36 months after baseline, n=2,443) and wave 4 (72 months after baseline, n=1,618) were used for the analyses presented here. Social ties were assessed using the 14-item form of the questionnaire for social support (F-SozU K-14). Visual impairment was self-rated on a three level Likert scale (no impairment, mild visual impairment, or severe/profound visual impairment). Adjusting for sociodemographic factors, hearing impairment and comorbidity, fixed effects regressions revealed that the onset of mild visual impairment decreased the social support score, in particular the emotional support score. Additionally, the onset of mild hearing impairment decreased the social support score in men. Moreover, increasing age decreased the social support score in the total sample and in both sexes. Loss of spouse and increasing comorbidity did not affect the social support score. Our results highlight the importance of visual impairment for social ties in late life. Consequently, appropriate strategies in order to delay visual impairment might help to maintain social ties in old age.

  7. Examination of the communication interface between students with severe to profound and multiple intellectual disability and educational staff during structured teaching sessions.

    Science.gov (United States)

    Bunning, K; Smith, C; Kennedy, P; Greenham, C

    2013-01-01

    Individuals with severe to profound and multiple intellectual disability (S-PMID) tend to function at the earlier stages of communication development. Variable and highly individual means of communicating may present challenges to the adults providing support in everyday life. The current study aimed to examine the communication interface between students with S-PMID and educational staff. An in-depth, observational study of dyadic interaction in a class within the secondary part of a special school was conducted. The designated educational level was Key Stage 3 under the National Curriculum of England, which is typically for children from age 11 to 14 years attending a state school. There were four student-teacher dyads in the class. The students had multiple impairments with severely limited communication skills. Video capture of dyadic interaction was conducted during five English lessons and sampled to 2.5 min per dyad per lesson. The video footage was transcribed into standard orthography, detailing the vocal and non-vocal aspects. A coding framework guided by the principles of structural-functional linguistics was used to determine the nature of dyadic interaction, comprising linguistic moves, functions and communicative modalities. The relative contributions of student and teacher to the interaction were examined. Significant differences were found between the students and educational staff on the majority of the measures. The teachers dominated the interaction, occupying significantly more turns than the students. Teacher turns contained significantly more initiations and follow-up moves than the students, who used more response moves. Teacher communication mainly served the functions of requesting and information giving. Feedback and scripted functions were also significantly greater among teacher turns, with only limited occurrence among the students. Self- or shared-expression was greatest among the students. The modalities of speech, touch, singing and

  8. Assessment of Hearing Impaired Youth.

    Science.gov (United States)

    Hicks, Doin E., Ed.; And Others

    1980-01-01

    The issue of Directions contains 11 articles on assessment of hearing impaired individuals. Entries have the following titles and authors: "Classroom Assessment Techniques for Hearing Impaired Students--A Literature Review" (B. McKee, M. Hausknecht); "Informal Assessment of Hearing Impaired Students In the Classroom" (B. Culhane, R. Hein);…

  9. Refined Phenotyping of Modic Changes

    Science.gov (United States)

    Määttä, Juhani H.; Karppinen, Jaro; Paananen, Markus; Bow, Cora; Luk, Keith D.K.; Cheung, Kenneth M.C.; Samartzis, Dino

    2016-01-01

    Abstract Low back pain (LBP) is the world's most disabling condition. Modic changes (MC) are vertebral bone marrow changes adjacent to the endplates as noted on magnetic resonance imaging. The associations of specific MC types and patterns with prolonged, severe LBP and disability remain speculative. This study assessed the relationship of prolonged, severe LBP and back-related disability, with the presence and morphology of lumbar MC in a large cross-sectional population-based study of Southern Chinese. We addressed the topographical and morphological dimensions of MC along with other magnetic resonance imaging phenotypes (eg, disc degeneration and displacement) on the basis of axial T1 and sagittal T2-weighted imaging of L1-S1. Prolonged severe LBP was defined as LBP lasting ≥30 days during the past year, and a visual analog scale severest pain intensity of at least 6/10. An Oswestry Disability Index score of 15% was regarded as significant disability. We also assessed subject demographics, occupation, and lifestyle factors. In total, 1142 subjects (63% females, mean age 53 years) were assessed. Of these, 282 (24.7%) had MC (7.1% type I, 17.6% type II). MC subjects were older (P = 0.003), had more frequent disc displacements (P disability. The strength of the associations increased with the number of MC. This large-scale study is the first to definitively note MC types and specific morphologies to be independently associated with prolonged severe LBP and back-related disability. This proposed refined MC phenotype may have direct implications in clinical decision-making as to the development and management of LBP. Understanding of these imaging biomarkers can lead to new preventative and personalized therapeutics related to LBP. PMID:27258491

  10. The phenotypic variance gradient - a novel concept.

    Science.gov (United States)

    Pertoldi, Cino; Bundgaard, Jørgen; Loeschcke, Volker; Barker, James Stuart Flinton

    2014-11-01

    Evolutionary ecologists commonly use reaction norms, which show the range of phenotypes produced by a set of genotypes exposed to different environments, to quantify the degree of phenotypic variance and the magnitude of plasticity of morphometric and life-history traits. Significant differences among the values of the slopes of the reaction norms are interpreted as significant differences in phenotypic plasticity, whereas significant differences among phenotypic variances (variance or coefficient of variation) are interpreted as differences in the degree of developmental instability or canalization. We highlight some potential problems with this approach to quantifying phenotypic variance and suggest a novel and more informative way to plot reaction norms: namely "a plot of log (variance) on the y-axis versus log (mean) on the x-axis, with a reference line added". This approach gives an immediate impression of how the degree of phenotypic variance varies across an environmental gradient, taking into account the consequences of the scaling effect of the variance with the mean. The evolutionary implications of the variation in the degree of phenotypic variance, which we call a "phenotypic variance gradient", are discussed together with its potential interactions with variation in the degree of phenotypic plasticity and canalization.

  11. Can the genotype or phenotype of two polymorphic drug metabolising cytochrome P450-enzymes identify oral lichenoid drug eruptions?

    DEFF Research Database (Denmark)

    Kragelund, Camilla; Hansen, Claus; Reibel, Jesper

    2010-01-01

    Lichenoid drug eruptions (LDE) in the oral cavity are adverse drug reactions (ADR) that are impossible to differentiate from oral lichen planus (OLP) as no phenotypic criteria exist. Impaired function of polymorphic cytochrome 450-enzymes (CYPs) may cause increased plasma concentration of some...

  12. The Broader Autism Phenotype and Its Implications on the Etiology and Treatment of Autism Spectrum Disorders

    OpenAIRE

    Gerdts, Jennifer; Bernier, Raphael

    2011-01-01

    The presence of autism-related traits has been well documented in undiagnosed family members of individuals with autism spectrum disorder (ASD). The most common finding is mild impairments in social and communication skills that are similar to those shown by individuals with autism, but exhibited to a lesser degree. Termed the broader autism phenotype (BAP), these traits suggest a genetic liability for autism-related traits in families. Genetic influence in autism is strong, with identical tw...

  13. Hereditary spastic paraplegia with cerebellar ataxia: a complex phenotype associated with a new SPG4 gene mutation

    DEFF Research Database (Denmark)

    Nielsen, Jørgen Erik; Johnson, B; Koefoed, Pernille

    2004-01-01

    Complex forms of hereditary spastic paraplegia (HSP) are rare and usually transmitted in an autosomal recessive pattern. A family of four generations with autosomal dominant hereditary spastic paraplegia (AD-HSP) and a complex phenotype with variably expressed co-existing ataxia, dysarthria......, unipolar depression, epilepsy, migraine, and cognitive impairment was investigated. Genetic linkage analysis and sequencing of the SPG4 gene was performed and electrophysiologic investigations were carried out in six individuals and positron emission tomography (PET) in one patient. The disease was linked...... in those individuals who were clinically affected by a complex phenotype consisting of HSP and cerebellar ataxia. Other features noted in this kindred including epilepsy, cognitive impairment, depression, and migraine did not segregate with the HSP phenotype or mutation, and therefore the significance...

  14. Characterisation of Physical Frailty and Associated Physical and Functional Impairments in Mild Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Ma Shwe Zin Nyunt

    2017-12-01

    Full Text Available ObjectiveTo characterize the physical frailty phenotype and its associated physical and functional impairments in mild cognitive impairment (MCI.MethodParticipants with MCI (N = 119, normal low cognition (NLC, N = 138, and normal high cognition (NHC, N = 1,681 in the Singapore Longitudinal Ageing Studies (SLAS-2 were compared on the prevalence of physical frailty, low lean body mass, weakness, slow gait, exhaustion and low physical activity, and POMA balance and gait impairment and fall risk.ResultsThere were significantly higher prevalence of frailty in MCI (18.5%, than in NLC (8.0% and NHC (3.9%, and pre-frailty in MCI (54.6%, NLC (52.9% than in NHC (48.0%. Age, sex, and ethnicity-adjusted OR (95% CI of association with MCI (versus NHC for frailty were 4.65 (2.40–9.04 and for pre-frailty, 1.67 (1.07–2.61. Similar significantly elevated prevalence and adjusted ORs of association with MCI were observed for frailty-associated physical and functional impairments. Further adjustment for education, marital status, living status, comorbidities, and GDS significantly reduced the OR estimates. However, the OR estimates remained elevated for frailty: 3.86 (1.83–8.17, low body mass: 1.70 (1.08–2.67, slow gait: 1.84 (1.17–2.89, impaired gait: 4.17 (1.98–8.81, and elevated fall risk 3.42 (1.22–9.53.ConclusionTwo-thirds of MCI were physically frail or pre-frail, most uniquely due to low lean muscle mass, slow gait speed, or balance and gait impairment. The close associations of frailty and physical and functional impairment with MCI have important implications for improving diagnostic acuity of MCI and targetting interventions among cognitively frail individuals to prevent dementia and disability.

  15. Gamma c-signaling cytokines induce a regulatory T cell phenotype in malignant CD4+ T lymphocytes

    DEFF Research Database (Denmark)

    Kasprzycka, Monika; Zhang, Qian; Witkiewicz, Agnieszka

    2008-01-01

    In this study, we demonstrate that malignant mature CD4(+) T lymphocytes derived from cutaneous T cell lymphomas (CTCL) variably display some aspects of the T regulatory phenotype. Whereas seven cell lines representing a spectrum of primary cutaneous T cell lymphoproliferative disorders expressed...... that FOXP3-expressing cells were common among the CD7-negative enlarged atypical and small lymphocytes at the early skin patch and plaque stages. Their frequency was profoundly diminished at the tumor stage and in the CTCL lymph node lesions with or without large cell transformation. These results indicate...

  16. Cattle phenotypes can disguise their maternal ancestry.

    Science.gov (United States)

    Srirattana, Kanokwan; McCosker, Kieren; Schatz, Tim; St John, Justin C

    2017-06-26

    Cattle are bred for, amongst other factors, specific traits, including parasite resistance and adaptation to climate. However, the influence and inheritance of mitochondrial DNA (mtDNA) are not usually considered in breeding programmes. In this study, we analysed the mtDNA profiles of cattle from Victoria (VIC), southern Australia, which is a temperate climate, and the Northern Territory (NT), the northern part of Australia, which has a tropical climate, to determine if the mtDNA profiles of these cattle are indicative of breed and phenotype, and whether these profiles are appropriate for their environments. A phylogenetic tree of the full mtDNA sequences of different breeds of cattle, which were obtained from the NCBI database, showed that the mtDNA profiles of cattle do not always reflect their phenotype as some cattle with Bos taurus phenotypes had Bos indicus mtDNA, whilst some cattle with Bos indicus phenotypes had Bos taurus mtDNA. Using D-loop sequencing, we were able to contrast the phenotypes and mtDNA profiles from different species of cattle from the 2 distinct cattle breeding regions of Australia. We found that 67 of the 121 cattle with Bos indicus phenotypes from NT (55.4%) had Bos taurus mtDNA. In VIC, 92 of the 225 cattle with Bos taurus phenotypes (40.9%) possessed Bos indicus mtDNA. When focusing on oocytes from cattle with the Bos taurus phenotype in VIC, their respective oocytes with Bos indicus mtDNA had significantly lower levels of mtDNA copy number compared with oocytes possessing Bos taurus mtDNA (P cattle with a Bos taurus phenotype. The phenotype of cattle is not always related to their mtDNA profiles. MtDNA profiles should be considered for breeding programmes as they also influence phenotypic traits and reproductive capacity in terms of oocyte quality.

  17. Clinical-pathologic correlations in vascular cognitive impairment and dementia.

    Science.gov (United States)

    Flanagan, Margaret; Larson, Eric B; Latimer, Caitlin S; Cholerton, Brenna; Crane, Paul K; Montine, Kathleen S; White, Lon R; Keene, C Dirk; Montine, Thomas J

    2016-05-01

    The most common causes of cognitive impairment and dementia are Alzheimer's disease (AD) and vascular brain injury (VBI), either independently, in combination, or in conjunction with other neurodegenerative disorders. The contribution of VBI to cognitive impairment and dementia, particularly in the context of AD pathology, has been examined extensively yet remains difficult to characterize due to conflicting results. Describing the relative contribution and mechanisms of VBI in dementia is important because of the profound impact of dementia on individuals, caregivers, families, and society, particularly the stability of health care systems with the rapidly increasing age of our population. Here we discuss relationships between pathologic processes of VBI and clinical expression of dementia, specific subtypes of VBI including microvascular brain injury, and what is currently known regarding contributions of VBI to the development and pathogenesis of the dementia syndrome. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. 20 CFR 220.184 - If the annuitant becomes disabled by another impairment(s).

    Science.gov (United States)

    2010-04-01

    ... impairment(s). 220.184 Section 220.184 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE... Activity or Medical Improvement § 220.184 If the annuitant becomes disabled by another impairment(s). If a new severe impairment(s) begins in or before the month in which the last impairment(s) ends, the Board...

  19. Severe Affective and Behavioural Dysregulation Is Associated with Significant Psychosocial Adversity and Impairment

    Science.gov (United States)

    Jucksch, Viola; Salbach-Andrae, Harriet; Lenz, Klaus; Goth, Kirstin; Dopfner, Manfred; Poustka, Fritz; Freitag, Christine M.; Lehmkuhl, Gerd; Lehmkuhl, Ulrike; Holtmann, Martin

    2011-01-01

    Background: Recently, a highly heritable behavioral phenotype of simultaneous deviance on the Anxious/Depressed, Attention Problems, and Aggressive Behavior syndrome scales has been identified on the Child Behavior Checklist (CBCL-Dysregulation Profile, CBCL-DP). This study aims to investigate psychosocial adversity and impairment of the CBCL-DP.…

  20. Cognitive impairments in epilepsy

    Directory of Open Access Journals (Sweden)

    Aleksandr Anatolyevich Kostylev

    2013-01-01

    Full Text Available Cognitive impairments in epilepsy are a current problem in neurology. The basis of the idea on the pathogenesis of higher nervous system dysfunctions is the interaction of a few factors that include the form and duration of the disease, gender differences, and the impact of antiepileptic therapy. The role of interattack epileptiform changes in the development of cognitive deficit in adults and epileptic encephalopathies in children is discussed. Up-to-date neurophysiological and neuroimaging diagnostic methods allow the detection of new features in the course and progression of higher nervous system dysfunctions in epilepsy.

  1. Cognitive impairment and pragmatics.

    Science.gov (United States)

    Gutiérrez-Rexach, Javier; Schatz, Sara

    2016-01-01

    One of the most important ingredients of felicitous conversation exchanges is the adequate expression of illocutionary force and the achievement of perlocutionary effects, which can be considered essential to the functioning of pragmatic competence. The breakdown of illocutionary and perlocutionary functions is one of the most prominent external features of cognitive impairment in Alzheimer's Disease, with devastating psychological and social consequences for patients, their family and caregivers. The study of pragmatic functions is essential for a proper understanding of the linguistic and communicative aspects of Alzheimer's disease.

  2. The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data

    NARCIS (Netherlands)

    Kohler, S.; Doelken, S.C.; Mungall, C.J.; Bauer, S.; Firth, H.V.; Bailleul-Forestier, I.; Black, G.C.M.; Brown, D.L.; Brudno, M.; Campbell, J.; FitzPatrick, D.R.; Eppig, J.T.; Jackson, A.P.; Freson, K.; Girdea, M.; Helbig, I.; Hurst, J.A.; Jahn, J.; Jackson, L.G.; Kelly, A.M.; Ledbetter, D.H.; Mansour, S.; Martin, C.L.; Moss, C.; Mumford, A.; Ouwehand, W.H.; Park, S.M.; Riggs, E.R.; Scott, R.H.; Sisodiya, S.; Vooren, S. van der; Wapner, R.J.; Wilkie, A.O.; Wright, C.F.; Silfhout, A.T. van; Leeuw, N. de; Vries, B. de; Washingthon, N.L.; Smith, C.L.; Westerfield, M.; Schofield, P.; Ruef, B.J.; Gkoutos, G.V.; Haendel, M.; Smedley, D.; Lewis, S.E.; Robinson, P.N.

    2014-01-01

    The Human Phenotype Ontology (HPO) project, available at http://www.human-phenotype-ontology.org, provides a structured, comprehensive and well-defined set of 10,088 classes (terms) describing human phenotypic abnormalities and 13,326 subclass relations between the HPO classes. In addition we have

  3. Language impairments in youths with traumatic brain injury: implications for participation in criminal proceedings.

    Science.gov (United States)

    Wszalek, Joseph A; Turkstra, Lyn S

    2015-01-01

    As many as 30% of incarcerated juveniles have a history of traumatic brain injury (TBI). Moderate or severe TBI is associated with a high risk of impairment in language comprehension and expression, which may have profound effects on juveniles' ability to understand and express themselves in criminal proceedings. In this article, we review common language impairments in youths with TBI and discuss potential effects of these impairments on 3 stages of US criminal proceedings: (1) initial encounter with law enforcement; (2) interrogation and Miranda rights; and (3) competence to undergo trial proceedings. We then describe language assessment tools and procedures that may be helpful in legal contexts. Our aim was to inform clinicians and legal staff working with juvenile defendants with TBI, with the long-term goal of developing empirically based guidelines to ensure that juvenile defendants with TBI can fully and effectively participate in criminal proceedings.

  4. Making a difference? A comparison between multi-sensory and regular storytelling for persons with profound intellectual and multiple disabilities.

    Science.gov (United States)

    Ten Brug, A; Van der Putten, A A J; Penne, A; Maes, B; Vlaskamp, C

    2016-11-01

    Multi-sensory storytelling (MSST) was developed to include persons with profound intellectual and multiple disabilities in storytelling culture. In order to increase the listeners' attention, MSST stories are individualised and use multiple sensory stimuli to support the verbal text. In order to determine the value of MSST, this study compared listeners' attention under two conditions: (1) being read MSST books and (2) being read regular stories. A non-randomised control study was executed in which the intervention group read MSST books (n = 45) and a comparison group (n = 31) read regular books. Books were read 10 times during a 5-week period. The 1st, 5th and 10th storytelling sessions were recorded on video in both groups, and the percentage of attention directed to the book and/or stimuli and to the storyteller was scored by a trained and independent rater. Two repeated measure analyses (with the storytelling condition as a between-subject factor and the three measurements as factor) were performed to determine the difference between the groups in terms of attention directed to the book/stimuli (first analysis) and storyteller (second analysis). A further analysis established whether the level of attention changed between the reading sessions and whether there was an interaction effect between the repetition of the book and the storytelling condition. The attention directed to the book and/or the stimuli was significantly higher in the MSST group than in the comparison group. No significant difference between the two groups was found in the attention directed to the storyteller. For MSST stories, most attention was observed during the fifth reading session, while for regular stories, the fifth session gained least attentiveness from the listener. The persons with profound intellectual and multiple disabilities paid more attention to the book and/or stimuli in the MSST condition compared with the regular story telling group. Being more attentive towards

  5. Mild Cognitive Impairment in Parkinson's Disease-What Is It?

    Science.gov (United States)

    Weil, Rimona S; Costantini, Alyssa A; Schrag, Anette E

    2018-03-10

    Mild cognitive impairment is a common feature of Parkinson's disease, even at the earliest disease stages, but there is variation in the nature and severity of cognitive involvement and in the risk of conversion to Parkinson's disease dementia. This review aims to summarise current understanding of mild cognitive impairment in Parkinson's disease. We consider the presentation, rate of conversion to dementia, underlying pathophysiology and potential biomarkers of mild cognitive impairment in Parkinson's disease. Finally, we discuss challenges and controversies of mild cognitive impairment in Parkinson's disease. Large-scale longitudinal studies have shown that cognitive involvement is important and common in Parkinson's disease and can present early in the disease course. Recent criteria for mild cognitive impairment in Parkinson's provide the basis for further study of cognitive decline and for the progression of different cognitive phenotypes and risk of conversion to dementia. Improved understanding of the underlying pathology and progression of cognitive change are likely to lead to opportunities for early intervention for this important aspect of Parkinson's disease.

  6. IGF-1 deficiency impairs neurovascular coupling in mice: implications for cerebromicrovascular aging.

    Science.gov (United States)

    Toth, Peter; Tarantini, Stefano; Ashpole, Nicole M; Tucsek, Zsuzsanna; Milne, Ginger L; Valcarcel-Ares, Noa M; Menyhart, Akos; Farkas, Eszter; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

    2015-12-01

    Aging is associated with marked deficiency in circulating IGF-1, which has been shown to contribute to age-related cognitive decline. Impairment of moment-to-moment adjustment of cerebral blood flow (CBF) via neurovascular coupling is thought to play a critical role in the genesis of age-related cognitive impairment. To establish the link between IGF-1 deficiency and cerebromicrovascular impairment, neurovascular coupling mechanisms were studied in a novel mouse model of IGF-1 deficiency (Igf1(f/f) -TBG-Cre-AAV8) and accelerated vascular aging. We found that IGF-1-deficient mice exhibit neurovascular uncoupling and show a deficit in hippocampal-dependent spatial memory test, mimicking the aging phenotype. IGF-1 deficiency significantly impaired cerebromicrovascular endothelial function decreasing NO mediation of neurovascular coupling. IGF-1 deficiency also impaired glutamate-mediated CBF responses, likely due to dysregulation of astrocytic expression of metabotropic glutamate receptors and impairing mediation of CBF responses by eicosanoid gliotransmitters. Collectively, we demonstrate that IGF-1 deficiency promotes cerebromicrovascular dysfunction and neurovascular uncoupling mimicking the aging phenotype, which are likely to contribute to cognitive impairment. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  7. Daddy issues: paternal effects on phenotype.

    Science.gov (United States)

    Rando, Oliver J

    2012-11-09

    The once popular and then heretical idea that ancestral environment can affect the phenotype of future generations is coming back into vogue due to advances in the field of epigenetic inheritance. How paternal environmental conditions influence the phenotype of progeny is now a tractable question, and researchers are exploring potential mechanisms underlying such effects. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Phenotypes of organ involvement in sarcoidosis

    NARCIS (Netherlands)

    Schupp, Jonas Christian; Freitag-Wolf, Sandra; Bargagli, Elena; Mihailović-Vučinić, Violeta; Rottoli, Paola; Grubanovic, Aleksandar; Müller, Annegret; Jochens, Arne; Tittmann, Lukas; Schnerch, Jasmin; Olivieri, Carmela; Fischer, Annegret; Jovanovic, Dragana; Filipovic, Snežana; Videnovic-Ivanovic, Jelica; Bresser, Paul; Jonkers, René; O'Reilly, Kate; Ho, Ling-Pei; Gaede, Karoline I.; Zabel, Peter; Dubaniewicz, Anna; Marshall, Ben; Kieszko, Robert; Milanowski, Janusz; Günther, Andreas; Weihrich, Anette; Petrek, Martin; Kolek, Vitezslav; Keane, Michael P.; O'Beirne, Sarah; Donnelly, Seamas; Haraldsdottir, Sigridur Olina; Jorundsdottir, Kristin B.; Costabel, Ulrich; Bonella, Francesco; Wallaert, Benoît; Grah, Christian; Peroš-Golubičić, Tatjana; Luisetti, Mauritio; Kadija, Zamir; Pabst, Stefan; Grohé, Christian; Strausz, János; Vašáková, Martina; Sterclova, Martina; Millar, Ann; Homolka, Jiří; Slováková, Alena; Kendrick, Yvonne; Crawshaw, Anjali; Wuyts, Wim; Spencer, Lisa; Pfeifer, Michael; Valeyre, Dominique; Poletti, Venerino; Wirtz, Hubertus; Prasse, Antje; Schreiber, Stefan; Krawczak, Michael; Müller-Quernheim, Joachim

    2018-01-01

    Sarcoidosis is a highly variable, systemic granulomatous disease of hitherto unknown aetiology. The GenPhenReSa (Genotype-Phenotype Relationship in Sarcoidosis) project represents a European multicentre study to investigate the influence of genotype on disease phenotypes in sarcoidosis. The baseline

  9. Emerging semantics to link phenotype and environment

    Directory of Open Access Journals (Sweden)

    Anne E. Thessen

    2015-12-01

    Full Text Available Understanding the interplay between environmental conditions and phenotypes is a fundamental goal of biology. Unfortunately, data that include observations on phenotype and environment are highly heterogeneous and thus difficult to find and integrate. One approach that is likely to improve the status quo involves the use of ontologies to standardize and link data about phenotypes and environments. Specifying and linking data through ontologies will allow researchers to increase the scope and flexibility of large-scale analyses aided by modern computing methods. Investments in this area would advance diverse fields such as ecology, phylogenetics, and conservation biology. While several biological ontologies are well-developed, using them to link phenotypes and environments is rare because of gaps in ontological coverage and limits to interoperability among ontologies and disciplines. In this manuscript, we present (1 use cases from diverse disciplines to illustrate questions that could be answered more efficiently using a robust linkage between phenotypes and environments, (2 two proof-of-concept analyses that show the value of linking phenotypes to environments in fishes and amphibians, and (3 two proposed example data models for linking phenotypes and environments using the extensible observation ontology (OBOE and the Biological Collections Ontology (BCO; these provide a starting point for the development of a data model linking phenotypes and environments.

  10. Haptoglobin Phenotypes and Hypertension in Indigenous Zambians ...

    African Journals Online (AJOL)

    Haptoglobin Phenotypes and Hypertension in Indigenous Zambians at the University Teaching Hospital, Lusaka, Zambia. MM Phiri, T Kaile, FM Goma. Abstract. Objectives: The aim of the study was to investigate the association between presence of haptoglobin phenotypes and hypertension in indigenous Zambian patients ...

  11. Knowledge-based analysis of phenotypes

    KAUST Repository

    Hoendorf, Robert

    2016-01-01

    a formal framework to describe phenotypes. A formalized theory of phenotypes is not only useful for domain analysis, but can also be applied to assist in the diagnosis of rare genetic diseases, and I will show how our results on the ontology

  12. The Neuroanatomy of the Autistic Phenotype

    Science.gov (United States)

    Fahim, Cherine; Meguid, Nagwa A.; Nashaat, Neveen H.; Yoon, Uicheul; Mancini-Marie, Adham; Evans, Alan C.

    2012-01-01

    The autism phenotype is associated with an excess of brain volume due in part to decreased pruning during development. Here we aimed at assessing brain volume early in development to further elucidate previous findings in autism and determine whether this pattern is restricted to idiopathic autism or shared within the autistic phenotype (fragile X…

  13. Modeling lineage and phenotypic diversification in the New World monkey (Platyrrhini, Primates) radiation.

    Science.gov (United States)

    Aristide, Leandro; Rosenberger, Alfred L; Tejedor, Marcelo F; Perez, S Ivan

    2015-01-01

    Adaptive radiations that have taken place in the distant past can now be more thoroughly studied with the availability of large molecular phylogenies and comparative data drawn from extant and fossil species. Platyrrhines are a good example of a major mammalian evolutionary radiation confined to a single continent, involving a relatively large temporal scale and documented by a relatively small but informative fossil record. Here, we present comparative evidence using data on extant and fossil species to explore alternative evolutionary models in an effort to better understand the process of platyrrhine lineage and phenotypic diversification. Specifically, we compare the likelihood of null models of lineage and phenotypic diversification versus various models of adaptive evolution. Moreover, we statistically explore the main ecological dimension behind the platyrrhine diversification. Contrary to the previous proposals, our study did not find evidence of a rapid lineage accumulation in the phylogenetic tree of extant platyrrhine species. However, the fossil-based diversity curve seems to show a slowdown in diversification rates toward present times. This also suggests an early high rate of extinction among lineages within crown Platyrrhini. Finally, our analyses support the hypothesis that the platyrrhine phenotypic diversification appears to be characterized by an early and profound differentiation in body size related to a multidimensional niche model, followed by little subsequent change (i.e., stasis). Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Fertility impairment in radiotherapy

    Directory of Open Access Journals (Sweden)

    Marta Biedka

    2016-02-01

    Full Text Available Infertility as a result of antineoplastic therapy is becoming a very important issue due to the growing incidence of neoplastic diseases. Routinely applied antineoplastic treatments and the illness itself lead to fertility disorders. Therapeutic methods used in antineoplastic treatment may cause fertility impairment or sterilization due to permanent damage to reproductive cells. The risk of sterilization depends on the patient’s sex, age during therapy, type of neoplasm, radiation dose and treatment area. It is known that chemotherapy and radiotherapy can lead to fertility impairment and the combination of these two gives an additive effect. The aim of this article is to raise the issue of infertility in these patients. It is of growing importance due to the increase in the number of children and young adults who underwent radiotherapy in the past. The progress in antineoplastic therapy improves treatment results, but at the same time requires a deeper look at existential needs of the patient. Reproductive function is an integral element of self-esteem and should be taken into account during therapy planning.

  15. Evolving phenotypic networks in silico.

    Science.gov (United States)

    François, Paul

    2014-11-01

    Evolved gene networks are constrained by natural selection. Their structures and functions are consequently far from being random, as exemplified by the multiple instances of parallel/convergent evolution. One can thus ask if features of actual gene networks can be recovered from evolutionary first principles. I review a method for in silico evolution of small models of gene networks aiming at performing predefined biological functions. I summarize the current implementation of the algorithm, insisting on the construction of a proper "fitness" function. I illustrate the approach on three examples: biochemical adaptation, ligand discrimination and vertebrate segmentation (somitogenesis). While the structure of the evolved networks is variable, dynamics of our evolved networks are usually constrained and present many similar features to actual gene networks, including properties that were not explicitly selected for. In silico evolution can thus be used to predict biological behaviours without a detailed knowledge of the mapping between genotype and phenotype. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

  16. Adjusting phenotypes by noise control.

    Directory of Open Access Journals (Sweden)

    Kyung H Kim

    2012-01-01

    Full Text Available Genetically identical cells can show phenotypic variability. This is often caused by stochastic events that originate from randomness in biochemical processes involving in gene expression and other extrinsic cellular processes. From an engineering perspective, there have been efforts focused on theory and experiments to control noise levels by perturbing and replacing gene network components. However, systematic methods for noise control are lacking mainly due to the intractable mathematical structure of noise propagation through reaction networks. Here, we provide a numerical analysis method by quantifying the parametric sensitivity of noise characteristics at the level of the linear noise approximation. Our analysis is readily applicable to various types of noise control and to different types of system; for example, we can orthogonally control the mean and noise levels and can control system dynamics such as noisy oscillations. As an illustration we applied our method to HIV and yeast gene expression systems and metabolic networks. The oscillatory signal control was applied to p53 oscillations from DNA damage. Furthermore, we showed that the efficiency of orthogonal control can be enhanced by applying extrinsic noise and feedback. Our noise control analysis can be applied to any stochastic model belonging to continuous time Markovian systems such as biological and chemical reaction systems, and even computer and social networks. We anticipate the proposed analysis to be a useful tool for designing and controlling synthetic gene networks.

  17. Federated Tensor Factorization for Computational Phenotyping

    Science.gov (United States)

    Kim, Yejin; Sun, Jimeng; Yu, Hwanjo; Jiang, Xiaoqian

    2017-01-01

    Tensor factorization models offer an effective approach to convert massive electronic health records into meaningful clinical concepts (phenotypes) for data analysis. These models need a large amount of diverse samples to avoid population bias. An open challenge is how to derive phenotypes jointly across multiple hospitals, in which direct patient-level data sharing is not possible (e.g., due to institutional policies). In this paper, we developed a novel solution to enable federated tensor factorization for computational phenotyping without sharing patient-level data. We developed secure data harmonization and federated computation procedures based on alternating direction method of multipliers (ADMM). Using this method, the multiple hospitals iteratively update tensors and transfer secure summarized information to a central server, and the server aggregates the information to generate phenotypes. We demonstrated with real medical datasets that our method resembles the centralized training model (based on combined datasets) in terms of accuracy and phenotypes discovery while respecting privacy. PMID:29071165

  18. Nordic research infrastructures for plant phenotyping

    Directory of Open Access Journals (Sweden)

    Kristiina Himanen

    2018-03-01

    Full Text Available Plant phenomics refers to the systematic study of plant phenotypes. Together with closely monitored, controlled climates, it provides an essential component for the integrated analysis of genotype-phenotype-environment interactions. Currently, several plant growth and phenotyping facilities are under establishment globally, and numerous facilities are already in use. Alongside the development of the research infrastructures, several national and international networks have been established to support shared use of the new methodology. In this review, an overview is given of the Nordic plant phenotyping and climate control facilities. Since many areas of phenomics such as sensor-based phenotyping, image analysis and data standards are still developing, promotion of educational and networking activities is especially important. These facilities and networks will be instrumental in tackling plant breeding and plant protection challenges. They will also provide possibilities to study wild species and their ecological interactions under changing Nordic climate conditions.

  19. Update on neuroimaging phenotypes of mid-hindbrain malformations

    Energy Technology Data Exchange (ETDEWEB)

    Jissendi-Tchofo, Patrice [University Hospital of Lille (CHRU), Department of Neuroradiology, MRI 3T Research, Plateforme Imagerie du vivant, IMPRT-IFR 114, Lille-Cedex (France); CHU Saint-Pierre, Radiology Department, Pediatric Neuroradiology Section, Brussels (Belgium); Severino, Mariasavina [Istituto Giannina Gaslini, Neuroradiology Unit, Genoa (Italy); Nguema-Edzang, Beatrice; Toure, Cisse; Soto Ares, Gustavo [University Hospital of Lille (CHRU), Department of Neuroradiology, MRI 3T Research, Plateforme Imagerie du vivant, IMPRT-IFR 114, Lille-Cedex (France); Barkovich, Anthony James [University of California, Neuroradiology Section, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States)

    2014-10-23

    Neuroimaging techniques including structural magnetic resonance imaging (MRI) and functional positron emission tomography (PET) are useful in categorizing various midbrain-hindbrain (MHB) malformations, both in allowing diagnosis and in helping to understand the developmental processes that were disturbed. Brain imaging phenotypes of numerous malformations are characteristic features that help in guiding the genetic testing in case of direct neuroimaging-genotype correlation or, at least, to differentiate among MHB malformations entities. The present review aims to provide the reader with an update of the use of neuroimaging applications in the fine analysis of MHB malformations, using a comprehensive, recently proposed developmental and genetic classification. We have performed an extensive systematic review of the literature, from the embryology main steps of MHB development through the malformations entities, with regard to their molecular and genetic basis, conventional MRI features, and other neuroimaging characteristics. We discuss disorders in which imaging features are distinctive and how these features reflect the structural and functional impairment of the brain. Recognition of specific MRI phenotypes, including advanced imaging features, is useful to recognize the MHB malformation entities, to suggest genetic investigations, and, eventually, to monitor the disease outcome after supportive therapies. (orig.)

  20. Communication strategies and intensive interaction therapy meet the theology of the body: bioethics in dialogue with people with profound disabilities.

    Science.gov (United States)

    Matthews, Pia

    2013-01-01

    Academic bioethics does not appear to be interested in communication and its ethical concerns unless communication is to do with issues such as capacity, consent, truth telling and confidentiality. In contrast practitioners are interested in actually communicating with their patients and they are often particularly perplexed when it comes to people with profound disabilities where communication appears disrupted. Although some new and not so new communication strategies, and especially intensive interaction, are available, little has been written on either the ethical concerns these may present or the deeper concepts that underpin them. This article explores the practical applications of some of these communication strategies. By engaging these strategies with theology, and specifically Pope John Paul's Theology of the Body, this article identifies and addresses some significant ethical issues that may arise, notably the risk of dualism and of objectifying the human person. Moreover it provides communication strategies with a rationale that goes beyond practicalities to one based on respect for human dignity, justice and solidarity.

  1. Systematic Moiety Variations of Ultrashort Peptides Produce Profound Effects on Self-Assembly, Nanostructure Formation, Hydrogelation, and Phase Transition

    KAUST Repository

    Chan, Kiat Hwa

    2017-10-04

    Self-assembly of small biomolecules is a prevalent phenomenon that is increasingly being recognised to hold the key to building complex structures from simple monomeric units. Small peptides, in particular ultrashort peptides containing up to seven amino acids, for which our laboratory has found many biomedical applications, exhibit immense potential in this regard. For next-generation applications, more intricate control is required over the self-assembly processes. We seek to find out how subtle moiety variation of peptides can affect self-assembly and nanostructure formation. To this end, we have selected a library of 54 tripeptides, derived from systematic moiety variations from seven tripeptides. Our study reveals that subtle structural changes in the tripeptides can exert profound effects on self-assembly, nanostructure formation, hydrogelation, and even phase transition of peptide nanostructures. By comparing the X-ray crystal structures of two tripeptides, acetylated leucine-leucine-glutamic acid (Ac-LLE) and acetylated tyrosine-leucine-aspartic acid (Ac-YLD), we obtained valuable insights into the structural factors that can influence the formation of supramolecular peptide structures. We believe that our results have major implications on the understanding of the factors that affect peptide self-assembly. In addition, our findings can potentially assist current computational efforts to predict and design self-assembling peptide systems for diverse biomedical applications.

  2. Macroevolutionary consequences of profound climate change on niche evolution in marine molluscs over the past three million years

    Science.gov (United States)

    Saupe, E.E.; Hendricks, J.R.; Portell, R.W.; Dowsett, Harry J.; Haywood, A. M.; Hunter, S.J.; Lieberman, B.S.

    2014-01-01

    In order to predict the fate of biodiversity in a rapidly changing world, we must first understand how species adapt to new environmental conditions. The long-term evolutionary dynamics of species' physiological tolerances to differing climatic regimes remain obscure. Here, we unite palaeontological and neontological data to analyse whether species' environmental tolerances remain stable across 3 Myr of profound climatic changes using 10 phylogenetically, ecologically and developmentally diverse mollusc species from the Atlantic and Gulf Coastal Plains, USA. We additionally investigate whether these species' upper and lower thermal tolerances are constrained across this interval. We find that these species' environmental preferences are stable across the duration of their lifetimes, even when faced with significant environmental perturbations. The results suggest that species will respond to current and future warming either by altering distributions to track suitable habitat or, if the pace of change is too rapid, by going extinct. Our findings also support methods that project species' present-day environmental requirements to future climatic landscapes to assess conservation risks.

  3. Comparison of swallowing outcomes of laryngotracheal separation versus total laryngectomy in a validated ovine model of profound oropharyngeal dysphagia.

    Science.gov (United States)

    Venkatesan, N N; Johnson, C M; Siddiqui, M T; Cates, D J; Kuhn, M A; Postma, G N; Belafsky, P C

    2017-04-01

    To validate the ovine model of profound oropharyngeal dysphagia and compare swallowing outcomes of laryngotracheal separation with those of total laryngectomy. Under real-time fluoroscopy, swallowing trials were conducted using the head and neck of two Dorper cross ewes and one human cadaver, secured in lateral fluoroscopic orientation. Barium trials were administered at baseline, pre- and post-laryngohyoid suspension, following laryngotracheal separation, and following laryngectomy in the ovine model. Mean pre-intervention Penetration Aspiration Scale and National Institutes of Health Swallow Safety Scale scores were 8 ± 0 and 6 ± 0 respectively in sheep and human cadavers, with 100 per cent intra- and inter-species reproducibility. These scores improved to 1 ± 0 and 2 ± 0 post-laryngohyoid suspension (p < 0.01). Aerodigestive tract residue was 18.6 ± 2.4 ml at baseline, 15.4 ± 3.8 ml after laryngotracheal separation and 3.0 ± 0.7 ml after total laryngectomy (p < 0.001). The ovine model displayed perfect intra- and inter- species reliability for the Penetration Aspiration Scale and Swallow Safety Scale. Less aerodigestive tract residue after narrow-field laryngectomy suggests that swallowing outcomes after total laryngectomy are superior to those after laryngotracheal separation.

  4. Butyrate induces profound changes in gene expression related to multiple signal pathways in bovine kidney epithelial cells

    Directory of Open Access Journals (Sweden)

    Li CongJun

    2006-09-01

    Full Text Available Abstract Background Global gene expression profiles of bovine kidney epithelial cells regulated by sodium butyrate were investigated with high-density oligonucleotide microarrays. The bovine microarray with 86,191 distinct 60mer oligonucleotides, each with 4 replicates, was designed and produced with Maskless Array Synthesizer technology. These oligonucleotides represent approximately 45,383 unique cattle sequences. Results 450 genes significantly regulated by butyrate with a median False Discovery Rate (FDR = 0 % were identified. The majority of these genes were repressed by butyrate and associated with cell cycle control. The expression levels of 30 selected genes identified by the microarray were confirmed using real-time PCR. The results from real-time PCR positively correlated (R = 0.867 with the results from the microarray. Conclusion This study presented the genes related to multiple signal pathways such as cell cycle control and apoptosis. The profound changes in gene expression elucidate the molecular basis for the pleiotropic effects of butyrate on biological processes. These findings enable better recognition of the full range of beneficial roles butyrate may play during cattle energy metabolism, cell growth and proliferation, and possibly in fighting gastrointestinal pathogens.

  5. JAK inhibition induces silencing of T Helper cytokine secretion and a profound reduction in T regulatory cells.

    Science.gov (United States)

    Keohane, Clodagh; Kordasti, Shahram; Seidl, Thomas; Perez Abellan, Pilar; Thomas, Nicholas S B; Harrison, Claire N; McLornan, Donal P; Mufti, Ghulam J

    2015-10-01

    CD4(+) T cells maintain cancer surveillance and immune tolerance. Chronic inflammation has been proposed as a driver of clonal evolution in myeloproliferative neoplasms (MPN), suggesting that T cells play an important role in their pathogenesis. Treatment with JAK inhibitors (JAKi) results in improvements in MPN-associated constitutional symptoms as well as reductions in splenomegaly. However, effects of JAKi on T cells in MPN are not well established and the baseline immune signature remains unclear. We investigated the frequency and function of CD4(+) T cell subsets in 50 MPN patients at baseline as well as during treatment with either ruxolitinib or fedratinib in a subset. We show that CD4(+)  CD127(low)  CD25(high)  FOXP3(+) T regulatory cells are reduced in MPN patients compared to healthy controls and that this decrease is even more pronounced following JAKi therapy. Moreover, we show that after 6 months of treatment the number of T helper (Th)-17 cells increased. We also describe a functional 'silencing' of T helper cells both in vivo and in vitro and a blockade of pro-inflammatory cytokines from these cells. This profound effect of JAKi on T cell function may underlay augmented rates of atypical infections that have been reported with use of these drugs. © 2015 John Wiley & Sons Ltd.

  6. Developing and Implementing School for Highly Gifted, Exceptionally Gifted, and Profoundly Gifted Students: An Interview with Lynette Breedlove

    Directory of Open Access Journals (Sweden)

    Engin KARADUMAN

    2013-12-01

    Full Text Available According to research, while moderately gifted students can often fit in the regular classrooms with differentiated instructions, pull-out programs, or acceleration options, highly gifted students do better when they are grouped with other intellectually-advanced peers in accordance with their strengths, interests, and background knowledge of a topic. Each of these students requires special attention and management strategies to develop better cognitive, social, emotional, and physical skills. Thanks to the grouping strategy, highly gifted students can study concepts at the appropriate pace, depth, and complexity so that these students feel valued and normal (Neville, 2007; Rogers, 2007. In order to fully meet these students’ needs, creating a school for highly, exceptionally, and profoundly gifted students would be a more beneficial plan compared to requiring them to stay within the regular classroom, accelerating, or grade skipping. Rogers (2002 pointed out that these students showed more academic growth by studying with other intellectual peers in separate classrooms. According to VanTassel-Baska (2006, identification, curriculum, program design, staff development, parental involvement assessment, and evaluation areas were essential for gifted program development. In accordance with the program development guidelines noted above, in this presentation, the process of developing and implementing a program for highly gifted students in Science, Math, Reading, and Social Studies will be provided based on an interview with Lynette Breedlove, Ph.D. who is the director of Advanced Academic Studies & Secondary Counseling at Spring Branch Independent School District in Houston, TX.

  7. Are Auditory Steady-State Responses Useful to Evaluate Severe-to-Profound Hearing Loss in Children?

    Science.gov (United States)

    Grasel, Signe Schuster; de Almeida, Edigar Rezende; Beck, Roberto Miquelino de Oliveira; Goffi-Gomez, Maria Valéria Schmidt; Ramos, Henrique Faria; Rossi, Amanda Costa; Koji Tsuji, Robinson; Bento, Ricardo Ferreira; de Brito, Rubens

    2015-01-01

    To evaluate Auditory Steady-State Responses (ASSR) at high intensities in pediatric cochlear implant candidates and to compare the results to behavioral tests responses. This prospective study evaluated 42 children with suspected severe-to-profound hearing loss, aged from 3 to 72 months. All had absent ABR and OAE responses. ASSR were evoked using binaural single frequency stimuli at 110 dB HL with a 10 dB down-seeking procedure. ASSR and behavioral test results were compared. Forty-two subjects completed both ASSR and behavioral evaluation. Eleven children (26.2%) had bilateral responses. Four (9.5%) showed unilateral responses in at least two frequencies, all confirmed by behavioral results. Overall 61 ASSR responses were obtained, most (37.7%) in 500 Hz. Mean thresholds were between 101.3 and 104.2 dB HL. Among 27 subjects with absent ASSR, fifteen had no behavioral responses. Seven subjects showed behavioral responses with absent ASSR responses. No spurious ASSR responses were observed at 100 or 110 dB HL. ASSR is a valuable tool to detect residual hearing. No false-positive ASSR results were observed among 42 children, but in seven cases with absent ASSR, the test underestimated residual hearing as compared to the behavioral responses.

  8. Are Auditory Steady-State Responses Useful to Evaluate Severe-to-Profound Hearing Loss in Children?

    Directory of Open Access Journals (Sweden)

    Signe Schuster Grasel

    2015-01-01

    Full Text Available Objective. To evaluate Auditory Steady-State Responses (ASSR at high intensities in pediatric cochlear implant candidates and to compare the results to behavioral tests responses. Methods. This prospective study evaluated 42 children with suspected severe-to-profound hearing loss, aged from 3 to 72 months. All had absent ABR and OAE responses. ASSR were evoked using binaural single frequency stimuli at 110 dB HL with a 10 dB down-seeking procedure. ASSR and behavioral test results were compared. Results. Forty-two subjects completed both ASSR and behavioral evaluation. Eleven children (26.2% had bilateral responses. Four (9.5% showed unilateral responses in at least two frequencies, all confirmed by behavioral results. Overall 61 ASSR responses were obtained, most (37.7% in 500 Hz. Mean thresholds were between 101.3 and 104.2 dB HL. Among 27 subjects with absent ASSR, fifteen had no behavioral responses. Seven subjects showed behavioral responses with absent ASSR responses. No spurious ASSR responses were observed at 100 or 110 dB HL. Conclusion. ASSR is a valuable tool to detect residual hearing. No false-positive ASSR results were observed among 42 children, but in seven cases with absent ASSR, the test underestimated residual hearing as compared to the behavioral responses.

  9. Communication training for centre-based carers of children with severe or profound disabilities in the Western Cape, South Africa

    Directory of Open Access Journals (Sweden)

    Martha Geiger

    2012-09-01

    Full Text Available The purpose of this paper is to provide a preliminary, qualitative review of an approach to training centre-based carers in supporting basic communication development and providing communication opportunities for the children with severe and profound disabilities in their care. In South Africa, these children are often the most neglected in terms of planning and providing appropriate interventions. For those with severe communication disabilities, an additional lack is in the area of the basic human right to meaningful interactions and communication. Sustainable strategies to provide opportunities for basic communication development of these children are urgently sought. Several effective international and local parent training programmes have been developed, but the urgent need remains to train centre-based carers who are taking care of groups of diversely disabled children in severely under-resourced settings. Non-profit organisations (NPOs have been exploring practical centre-based approaches to skills sharing in physical rehabilitation, activities for daily living, feeding and support for basic communication development. As a freelance speech therapist contracted by four NPOs to implement hands-on training in basic communication for centre-based carers of non-verbal children, the author describes a training approach that evolved over three years, in collaboration with the carers and centre managements. Implications for training (for speech therapists and for community-based rehabilitation workers and for further research are identified.

  10. Triangulated Proxy Reporting: a technique for improving how communication partners come to know people with severe cognitive impairment.

    Science.gov (United States)

    Lyons, Gordon; De Bortoli, Tania; Arthur-Kelly, Michael

    2017-09-01

    This paper explains and demonstrates the pilot application of Triangulated Proxy Reporting (TPR); a practical technique for enhancing communication around people who have severe cognitive impairment (SCI). An introduction explains SCI and how this impacts on communication; and consequently on quality of care and quality of life. This is followed by an explanation of TPR and its origins in triangulation research techniques. An illustrative vignette explicates its utility and value in a group home for a resident with profound multiple disabilities. The Discussion and Conclusion sections propose the wider application of TPR for different cohorts of people with SCIs, their communication partners and service providers. TPR presents as a practical technique for enhancing communication interactions with people who have SCI. The paper demonstrates the potential of the technique for improving engagement amongst those with profound multiple disabilities, severe acquired brain injury and advanced dementia and their partners in and across different care settings. Implications for Rehabilitation Triangulated Proxy Reporting (TPR) shows potential to improve communications between people with severe cognitive impairments and their communication partners. TPR can lead to improved quality of care and quality of life for people with profound multiple disabilities, very advanced dementia and severe acquired brain injury, who otherwise are very difficult to support. TPR is a relatively simple and inexpensive technique that service providers can incorporate into practice to improving communications between clients with severe cognitive impairments, their carers and other support professionals.

  11. Autosomal dominant SCN8A mutation with an unusually mild phenotype.

    Science.gov (United States)

    Anand, G; Collett-White, F; Orsini, A; Thomas, S; Jayapal, S; Trump, N; Zaiwalla, Z; Jayawant, S

    2016-09-01

    Mutations in SCN8A, coding for the voltage-gated sodium channel Nav 1.6, have been described in relation to infantile onset epilepsy with developmental delay and cognitive impairment, in particular early onset epileptic encephalopathy (EIEE) type 13. Here we report an infant and his father with early onset focal epileptic seizures but without cognitive or neurological impairment in whom next generation sequence analysis identified a heterozygous mutation (c.5630A > G, p. (Asn1877Ser)) in the SCN8A gene. This mutation, confirmed by Sanger sequence analysis, affects a highly conserved amino acid and in silico tools predicts that it may be pathogenic. The reported infant has a normal developmental profile at 16-month follow-up. His father also had normal development and has no cognitive impairment at 42 years. This is the second known SCN8A mutation associated with a phenotype of benign familial infantile epilepsy. Good seizure control was achieved in our patients with sodium channel blockers. Based on our proband and a recently described group of families with benign familial infantile epilepsy and SCN8A variant we suggest expanding testing to patients with infantile epilepsy and no cognitive impairment. In addition, the same SCN8A variant (c.5630A > G, p. (Asn1877Ser)) is also found in patients with epilepsy and developmental delay highlighting the phenotypic variability and the possible role of other protective genetic factors. Copyright © 2016. Published by Elsevier Ltd.

  12. Semantic Disease Gene Embeddings (SmuDGE): phenotype-based disease gene prioritization without phenotypes

    KAUST Repository

    AlShahrani, Mona; Hoehndorf, Robert

    2018-01-01

    In the past years, several methods have been developed to incorporate information about phenotypes into computational disease gene prioritization methods. These methods commonly compute the similarity between a disease's (or patient's) phenotypes and a database of gene-to-phenotype associations to find the phenotypically most similar match. A key limitation of these methods is their reliance on knowledge about phenotypes associated with particular genes which is highly incomplete in humans as well as in many model organisms such as the mouse. Results: We developed SmuDGE, a method that uses feature learning to generate vector-based representations of phenotypes associated with an entity. SmuDGE can be used as a trainable semantic similarity measure to compare two sets of phenotypes (such as between a disease and gene, or a disease and patient). More importantly, SmuDGE can generate phenotype representations for entities that are only indirectly associated with phenotypes through an interaction network; for this purpose, SmuDGE exploits background knowledge in interaction networks comprising of multiple types of interactions. We demonstrate that SmuDGE can match or outperform semantic similarity in phenotype-based disease gene prioritization, and furthermore significantly extends the coverage of phenotype-based methods to all genes in a connected interaction network.

  13. Semantic Disease Gene Embeddings (SmuDGE): phenotype-based disease gene prioritization without phenotypes

    KAUST Repository

    Alshahrani, Mona

    2018-04-30

    In the past years, several methods have been developed to incorporate information about phenotypes into computational disease gene prioritization methods. These methods commonly compute the similarity between a disease\\'s (or patient\\'s) phenotypes and a database of gene-to-phenotype associations to find the phenotypically most similar match. A key limitation of these methods is their reliance on knowledge about phenotypes associated with particular genes which is highly incomplete in humans as well as in many model organisms such as the mouse. Results: We developed SmuDGE, a method that uses feature learning to generate vector-based representations of phenotypes associated with an entity. SmuDGE can be used as a trainable semantic similarity measure to compare two sets of phenotypes (such as between a disease and gene, or a disease and patient). More importantly, SmuDGE can generate phenotype representations for entities that are only indirectly associated with phenotypes through an interaction network; for this purpose, SmuDGE exploits background knowledge in interaction networks comprising of multiple types of interactions. We demonstrate that SmuDGE can match or outperform semantic similarity in phenotype-based disease gene prioritization, and furthermore significantly extends the coverage of phenotype-based methods to all genes in a connected interaction network.

  14. Neutral lipid-storage disease with myopathy and extended phenotype with novel PNPLA2 mutation.

    Science.gov (United States)

    Massa, Roberto; Pozzessere, Simone; Rastelli, Emanuele; Serra, Laura; Terracciano, Chiara; Gibellini, Manuela; Bozzali, Marco; Arca, Marcello

    2016-04-01

    Neutral lipid-storage disease with myopathy is caused by mutations in PNPLA2, which produce skeletal and cardiac myopathy. We report a man with multiorgan neutral lipid storage and unusual multisystem clinical involvement, including cognitive impairment. Quantitative brain MRI with voxel-based morphometry and extended neuropsychological assessment were performed. In parallel, the coding sequences and intron/exon boundaries of the PNPLA2 gene were screened by direct sequencing. Neuropsychological assessment revealed global cognitive impairment, and brain MRI showed reduced gray matter volume in the temporal lobes. Molecular characterization revealed a novel homozygous mutation in exon 5 of PNPLA2 (c.714C>A), resulting in a premature stop codon (p.Cys238*). Some PNPLA2 mutations, such as the one described here, may present with an extended phenotype, including brain involvement. In these cases, complete neuropsychological testing, combined with quantitative brain MRI, may help to characterize and quantify cognitive impairment. © 2016 Wiley Periodicals, Inc.

  15. Metabolic mechanisms behind the type 2 diabetes susceptible phenotype in low birth weight individuals

    DEFF Research Database (Denmark)

    Ribel-Madsen, Amalie

    Background and aims: Low birth weight (LBW) individuals have an increased risk of developing insulin resistance and type 2 diabetes compared with normal birth weight (NBW) individuals. Accordingly, young, healthy, LBW men of the study population examined in the present plasma metabolome studies...... show impaired hepatic insulin sensitivity and, in contrast to NBW men, develop impaired peripheral insulin sensitivity in response to a 5-day high-fat overfeeding. However, the metabolic mechanisms behind the type 2 diabetes susceptible phenotype in LBW individuals are not clear. Our primary aim...... available for lipogenesis, including the synthesis of lipotoxic lipids such as ceramides and diacylglycerols that impair insulin signalling. In the second study, we demonstrated that LBW men had higher plasma alanine, proline, methionine, citrulline, and total amino acid levels after the HFHC diet compared...

  16. Current Concept and Update of the Macrophage Plasticity Concept: Intracellular Mechanisms of Reprogramming and M3 Macrophage “Switch” Phenotype

    Science.gov (United States)

    Malyshev, Igor; Malyshev, Yuri

    2015-01-01

    Macrophages play a key role in immunity. In this review, we consider the traditional notion of macrophage plasticity, data that do not fit into existing concepts, and a hypothesis for existence of a new switch macrophage phenotype. Depending on the microenvironment, macrophages can reprogram their phenotype toward the proinflammatory M1 phenotype or toward the anti-inflammatory M2 phenotype. Macrophage reprogramming involves well-coordinated changes in activities of signalling and posttranslational mechanisms. Macrophage reprogramming is provided by JNK-, PI3K/Akt-, Notch-, JAK/STAT-, TGF-β-, TLR/NF-κB-, and hypoxia-dependent pathways. Posttranscriptional regulation is based on micro-mRNA. We have hypothesized that, in addition to the M1 and M2 phenotypes, an M3 switch phenotype exists. This switch phenotype responds to proinflammatory stimuli with reprogramming towards the anti-inflammatory M2 phenotype or, contrarily, it responds to anti-inflammatory stimuli with reprogramming towards the proinflammatory M1 phenotype. We have found signs of such a switch phenotype in lung diseases. Understanding the mechanisms of macrophage reprogramming will assist in the selection of new therapeutic targets for correction of impaired immunity. PMID:26366410

  17. Post-stroke cognitive impairments

    Directory of Open Access Journals (Sweden)

    Elena Anatolyevna Katunina

    2013-01-01

    Full Text Available Post-stroke cognitive impairments are common effects of stroke. Vascular cognitive impairments are characterized by the heterogeneity of the neuropsychological profile in relation to the site and pattern of stroke. Their common trait is the presence of dysregulation secondary to frontal dysfunction. The treatment of vascular cognitive impairments should be multimodality and aimed at stimulating neuroplasticity processes, restoring neurotransmitter imbalance, and preventing recurrent vascular episodes.

  18. Impairments in Skin Integrity.

    Science.gov (United States)

    Murphree, Rose W

    2017-09-01

    Altered skin integrity increases the chance of infection, impaired mobility, and decreased function and may result in the loss of limb or, sometimes, life. Skin is affected by both intrinsic and extrinsic factors. Intrinsic factors can include altered nutritional status, vascular disease issues, and diabetes. Extrinsic factors include falls, accidents, pressure, immobility, and surgical procedures. Ensuring skin integrity in the elderly requires a team approach and includes the individual, caregivers, and clinicians. The twenty-first century clinician has several online, evidence-based tools to assist with optimal treatment plans. Understanding best practices in addressing skin integrity issues can promote positive outcomes with the elderly. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. [Multilingualism and specific language impairment].

    Science.gov (United States)

    Arkkila, Eva; Smolander, Sini; Laasonen, Marja

    2013-01-01

    Specific language impairment is one of the most common developmental disturbances in childhood. With the increase of the foreign language population group an increasing number of children assimilating several languages and causing concern in language development attend clinical examinations. Knowledge of factors underlying the specific language impairment and the specific impairment in general, special features of language development of those learning several languages, as well as the assessment and support of the linguistic skills of a multilingual child is essential. The risk of long-term problems and marginalization is high for children having specific language impairment.

  20. Integrating phenotype ontologies with PhenomeNET

    KAUST Repository

    Rodriguez-Garcia, Miguel Angel

    2017-12-19

    Background Integration and analysis of phenotype data from humans and model organisms is a key challenge in building our understanding of normal biology and pathophysiology. However, the range of phenotypes and anatomical details being captured in clinical and model organism databases presents complex problems when attempting to match classes across species and across phenotypes as diverse as behaviour and neoplasia. We have previously developed PhenomeNET, a system for disease gene prioritization that includes as one of its components an ontology designed to integrate phenotype ontologies. While not applicable to matching arbitrary ontologies, PhenomeNET can be used to identify related phenotypes in different species, including human, mouse, zebrafish, nematode worm, fruit fly, and yeast. Results Here, we apply the PhenomeNET to identify related classes from two phenotype and two disease ontologies using automated reasoning. We demonstrate that we can identify a large number of mappings, some of which require automated reasoning and cannot easily be identified through lexical approaches alone. Combining automated reasoning with lexical matching further improves results in aligning ontologies. Conclusions PhenomeNET can be used to align and integrate phenotype ontologies. The results can be utilized for biomedical analyses in which phenomena observed in model organisms are used to identify causative genes and mutations underlying human disease.

  1. Redefining Aging in HIV Infection Using Phenotypes.

    Science.gov (United States)

    Stoff, David M; Goodkin, Karl; Jeste, Dilip; Marquine, Maria

    2017-10-01

    This article critically reviews the utility of "phenotypes" as behavioral descriptors in aging/HIV research that inform biological underpinnings and treatment development. We adopt a phenotypic redefinition of aging conceptualized within a broader context of HIV infection and of aging. Phenotypes are defined as dimensions of behavior, closely related to fundamental mechanisms, and, thus, may be more informative than chronological age. Primary emphasis in this review is given to comorbid aging and cognitive aging, though other phenotypes (i.e., disability, frailty, accelerated aging, successful aging) are also discussed in relation to comorbid aging and cognitive aging. The main findings that emerged from this review are as follows: (1) the phenotypes, comorbid aging and cognitive aging, are distinct from each other, yet overlapping; (2) associative relationships are the rule in HIV for comorbid and cognitive aging phenotypes; and (3) HIV behavioral interventions for both comorbid aging and cognitive aging have been limited. Three paths for research progress are identified for phenotype-defined aging/HIV research (i.e., clinical and behavioral specification, biological mechanisms, intervention targets), and some important research questions are suggested within each of these research paths.

  2. Evolution of molecular phenotypes under stabilizing selection

    International Nuclear Information System (INIS)

    Nourmohammad, Armita; Schiffels, Stephan; Lässig, Michael

    2013-01-01

    Molecular phenotypes are important links between genomic information and organismic functions, fitness, and evolution. Complex phenotypes, which are also called quantitative traits, often depend on multiple genomic loci. Their evolution builds on genome evolution in a complicated way, which involves selection, genetic drift, mutations and recombination. Here we develop a coarse-grained evolutionary statistics for phenotypes, which decouples from details of the underlying genotypes. We derive approximate evolution equations for the distribution of phenotype values within and across populations. This dynamics covers evolutionary processes at high and low recombination rates, that is, it applies to sexual and asexual populations. In a fitness landscape with a single optimal phenotype value, the phenotypic diversity within populations and the divergence between populations reach evolutionary equilibria, which describe stabilizing selection. We compute the equilibrium distributions of both quantities analytically and we show that the ratio of mean divergence and diversity depends on the strength of selection in a universal way: it is largely independent of the phenotype’s genomic encoding and of the recombination rate. This establishes a new method for the inference of selection on molecular phenotypes beyond the genome level. We discuss the implications of our findings for the predictability of evolutionary processes. (paper)

  3. Phenotype of CNTNAP1: a study of patients demonstrating a specific severe congenital hypomyelinating neuropathy with survival beyond infancy.

    Science.gov (United States)

    Low, K J; Stals, K; Caswell, R; Wakeling, M; Clayton-Smith, J; Donaldson, A; Foulds, N; Norman, A; Splitt, M; Urankar, K; Vijayakumar, K; Majumdar, A; Study, Ddd; Ellard, S; Smithson, S F

    2018-06-01

    CHN is genetically heterogeneous and its genetic basis is difficult to determine on features alone. CNTNAP1 encodes CASPR, integral in the paranodal junction high molecular mass complex. Nineteen individuals with biallelic variants have been described in association with severe congenital hypomyelinating neuropathy, respiratory compromise, profound intellectual disability and death within the first year. We report 7 additional patients ascertained through exome sequencing. We identified 9 novel CNTNAP1 variants in 6 families: three missense variants, four nonsense variants, one frameshift variant and one splice site variant. Significant polyhydramnios occurred in 6/7 pregnancies. Severe respiratory compromise was seen in 6/7 (tracheostomy in 5). A complex neurological phenotype was seen in all patients who had marked brain hypomyelination/demyelination and profound developmental delay. Additional neurological findings included cranial nerve compromise: orobulbar dysfunction in 5/7, facial nerve weakness in 4/7 and vocal cord paresis in 5/7. Dystonia occurred in 2/7 patients and limb contractures in 5/7. All had severe gastroesophageal reflux, and a gastrostomy was required in 5/7. In contrast to most previous reports, only one patient died in the first year of life. Protein modelling was performed for all detected CNTNAP1 variants. We propose a genotype-phenotype correlation, whereby hypomorphic missense variants partially ameliorate the phenotype, prolonging survival. This study suggests that biallelic variants in CNTNAP1 cause a distinct recognisable syndrome, which is not caused by other genes associated with CHN. Neonates presenting with this phenotype will benefit from early genetic definition to inform clinical management and enable essential genetic counselling for their families.

  4. Predicting impaired extinction of traumatic memory and elevated startle.

    Directory of Open Access Journals (Sweden)

    Rebecca Nalloor

    Full Text Available Emotionally traumatic experiences can lead to debilitating anxiety disorders, such as phobias and Post-Traumatic Stress Disorder (PTSD. Exposure to such experiences, however, is not sufficient to induce pathology, as only up to one quarter of people exposed to such events develop PTSD. These statistics, combined with findings that smaller hippocampal size prior to the trauma is associated with higher risk of developing PTSD, suggest that there are pre-disposing factors for such pathology. Because prospective studies in humans are limited and costly, investigating such pre-dispositions, and thus advancing understanding of the genesis of such pathologies, requires the use of animal models where predispositions are identified before the emotional trauma. Most existing animal models are retrospective: they classify subjects as those with or without a PTSD-like phenotype long after experiencing a traumatic event. Attempts to create prospective animal models have been largely unsuccessful.Here we report that individual predispositions to a PTSD-like phenotype, consisting of impaired rate and magnitude of extinction of an emotionally traumatic event coupled with long-lasting elevation of acoustic startle responses, can be revealed following exposure to a mild stressor, but before experiencing emotional trauma. We compare, in rats, the utility of several classification criteria and report that a combination of criteria based on acoustic startle responses and behavior in an anxiogenic environment is a reliable predictor of a PTSD-like phenotype.There are individual predispositions to developing impaired extinction and elevated acoustic startle that can be identified after exposure to a mildly stressful event, which by itself does not induce such a behavioral phenotype. The model presented here is a valuable tool for studying the etiology and pathophysiology of anxiety disorders and provides a platform for testing behavioral and pharmacological

  5. Phenotyping animal models of diabetic neuropathy

    DEFF Research Database (Denmark)

    Biessels, G J; Bril, V; Calcutt, N A

    2014-01-01

    NIDDK, JDRF, and the Diabetic Neuropathy Study Group of EASD sponsored a meeting to explore the current status of animal models of diabetic peripheral neuropathy. The goal of the workshop was to develop a set of consensus criteria for the phenotyping of rodent models of diabetic neuropathy...... with a discussion on the merits and limitations of a unified approach to phenotyping rodent models of diabetic neuropathy and a consensus formed on the definition of the minimum criteria required for establishing the presence of the disease. A neuropathy phenotype in rodents was defined as the presence...

  6. Impairment of adolescent hippocampal plasticity in a mouse model for Alzheimer's disease precedes disease phenotype.

    Directory of Open Access Journals (Sweden)

    Daniela Hartl

    Full Text Available The amyloid precursor protein (APP was assumed to be an important neuron-morphoregulatory protein and plays a central role in Alzheimer's disease (AD pathology. In the study presented here, we analyzed the APP-transgenic mouse model APP23 using 2-dimensional gel electrophoresis technology in combination with DIGE and mass spectrometry. We investigated cortex and hippocampus of transgenic and wildtype mice at 1, 2, 7 and 15 months of age. Furthermore, cortices of 16 days old embryos were analyzed. When comparing the protein patterns of APP23 with wildtype mice, we detected a relatively large number of altered protein spots at all age stages and brain regions examined which largely preceded the occurrence of amyloid plaques. Interestingly, in hippocampus of adolescent, two-month old mice, a considerable peak in the number of protein changes was observed. Moreover, when protein patterns were compared longitudinally between age stages, we found that a large number of proteins were altered in wildtype mice. Those alterations were largely absent in hippocampus of APP23 mice at two months of age although not in other stages compared. Apparently, the large difference in the hippocampal protein patterns between two-month old APP23 and wildtype mice was caused by the absence of distinct developmental changes in the hippocampal proteome of APP23 mice. In summary, the absence of developmental proteome alterations as well as a down-regulation of proteins related to plasticity suggest the disturption of a normally occurring peak of hippocampal plasticity during adolescence in APP23 mice. Our findings are in line with the observation that AD is preceded by a clinically silent period of several years to decades. We also demonstrate that it is of utmost importance to analyze different brain regions and different age stages to obtain information about disease-causing mechanisms.

  7. Disruption of Var2csa Gene Impairs Placental Malaria Associated Adhesion Phenotype

    OpenAIRE

    Viebig, Nicola K.; Levin, Emily; Dechavanne, Sébastien; Rogerson, Stephen J.; Gysin, Jürg; Smith, Joseph D.; Scherf, Artur; Gamain, Benoit

    2007-01-01

    Infection with Plasmodium falciparum during pregnancy is one of the major causes of malaria related morbidity and mortality in newborn and mothers. The complications of pregnancy-associated malaria result mainly from massive adhesion of Plasmodium falciparum-infected erythrocytes (IE) to chondroitin sulfate A (CSA) present in the placental intervillous blood spaces. Var2CSA, a member of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family is the predominant parasite ligand mediati...

  8. Cytokine and Phenotypic Cell Profiles of Leishmania infantum Infection in the Dog

    Directory of Open Access Journals (Sweden)

    Carla Maia

    2012-01-01

    Full Text Available Leishmaniasis has reemerged in recent years showing a wider geographic distribution and increased global incidence of human and canine disease than previously known. Dogs are the main domestic/peridomestic reservoir hosts of zoonotic visceral leishmaniasis caused by Leishmania infantum. Since the evolution of leishmaniasis and clinical appearance is a consequence of complex interactions between the parasite and host immune response, a profound knowledge about the immune profile developed in dog's infection is crucial for vaccine and immunomodulatory therapy design. The main goal of this paper is to compile the recent advances made on cytokine and phenotypic cell profiles in different tissues and organs of dogs infected with L. infantum. This paper also stressed that the knowledge of the immune responses developed, namely, in liver, lymph node, and spleen is very limited. All data emphasizes that more research on canine leishmaniasis is necessary for the development of new and efficacious tools to control zoonotic leishmaniasis.

  9. Fast-food-based hyper-alimentation can induce rapid and profound elevation of serum alanine aminotransferase in healthy subjects.

    Science.gov (United States)

    Kechagias, S; Ernersson, A; Dahlqvist, O; Lundberg, P; Lindström, T; Nystrom, F H

    2008-05-01

    To study the effect of fast-food-based hyper-alimentation on liver enzymes and hepatic triglyceride content (HTGC). Prospective interventional study with parallel control group. University Hospital of Linköping, Sweden. 12 healthy men and six healthy women with a mean (SD) age of 26 (6.6) years and a matched control group. Subjects in the intervention group aimed for a body weight increase of 5-15% by eating at least two fast-food-based meals a day with the goal to double the regular caloric intake in combination with adoption of a sedentary lifestyle for 4 weeks. Weekly changes of serum aminotransferases and HTGC measured by proton nuclear magnetic resonance spectroscopy at baseline and after the intervention. Subjects in the intervention group increased from 67.6 (9.1) kg to 74.0 (11) kg in weight (p19 U/l, men >30 U/l) during the intervention. Sugar (mono- and disaccharides) intake during week 3 correlated with the maximal ALT/baseline ALT ratio (r = 0.62, p = 0.006). HTGC increased from 1.1 (1.9)% to 2.8 (4.8)%, although this was not related to the increase in ALT levels. ALT levels were unchanged in controls. Hyper-alimentation per se can induce profound ALT elevations in less than 4 weeks. Our study clearly shows that in the evaluation of subjects with elevated ALT the medical history should include not only questions about alcohol intake but also explore whether recent excessive food intake has occurred.

  10. Amide-linked Ethanolamine Conjugate of Gemfibrozil as a Profound HDL Enhancer: Design, Synthesis, Pharmacological Screening and Docking Study.

    Science.gov (United States)

    Rai, Himanshu; Dhaneshwar, Suneela S

    2015-01-01

    Elevated concentration of any or all types of lipids in the plasma including hypertriglyceridemia and hypercholesterolemia leads to atherosclerotic cardiovascular disease. Effective medication needs multiple drug therapy as recommended cholesterol and triglyceride levels are difficult to achieve by monotherapy and frequently require the use of more than one lipid-lowering medication. Gemfibrozil lowers plasma triglyceride-rich lipoproteins mainly VLDL and increases HDL. It is associated with short plasma half-life (1.5h) and GIT distress on long term use. In a study it was found that ethanolamine decreases serum cholesterol, especially VLDL cholesterol and LDL cholesterol in rats fed an HF/HC diet. In the present work, we thought of exploring the effect of co-drug of gemfibrozil with ethanolamine (GE-I) as a potential combination therapy for the management of mixed hyperlipidemia. Synthesis of GE-I was effected by CDI coupling. Structure was confirmed spectrally. Interestingly kinetic studies revealed that GE-I resisted chemical and enzymatic hydrolysis. In tritoninduced hyperlipidemia, significant lowering of serum lipid levels was observed. The hallmark of GEI was its profound effect on HDL level which was raised above the normal level by 15%. Docking study also supported modulatory effect of GE-I (docking score -7.012) on PPAR-α which was comparable to docking score of gemfibrozil (-9.432). These preliminary observations prompt us to consider GE-I as a novel, serendipitous, hybrid anti-hyperlipidemic new chemical entity which needs be studied extensively to prove it as an HDL enhancing anti-hyperlipidemic agent.

  11. 20 CFR 416.998 - If you become disabled by another impairment(s).

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false If you become disabled by another impairment... Disability Or Blindness § 416.998 If you become disabled by another impairment(s). If a new severe impairment(s) begins in or before the month in which your last impairment(s) ends, we will find that your...

  12. 20 CFR 404.1598 - If you become disabled by another impairment(s).

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false If you become disabled by another impairment... Disability § 404.1598 If you become disabled by another impairment(s). If a new severe impairment(s) begins in or before the month in which your last impairment(s) ends, we will find that your disability is...

  13. Negative affect impairs associative memory but not item memory.

    Science.gov (United States)

    Bisby, James A; Burgess, Neil

    2013-12-17

    The formation of associations between items and their context has been proposed to rely on mechanisms distinct from those supporting memory for a single item. Although emotional experiences can profoundly affect memory, our understanding of how it interacts with different aspects of memory remains unclear. We performed three experiments to examine the effects of emotion on memory for items and their associations. By presenting neutral and negative items with background contexts, Experiment 1 demonstrated that item memory was facilitated by emotional affect, whereas memory for an associated context was reduced. In Experiment 2, arousal was manipulated independently of the memoranda, by a threat of shock, whereby encoding trials occurred under conditions of threat or safety. Memory for context was equally impaired by the presence of negative affect, whether induced by threat of shock or a negative item, relative to retrieval of the context of a neutral item in safety. In Experiment 3, participants were presented with neutral and negative items as paired associates, including all combinations of neutral and negative items. The results showed both above effects: compared to a neutral item, memory for the associate of a negative item (a second item here, context in Experiments 1 and 2) is impaired, whereas retrieval of the item itself is enhanced. Our findings suggest that negative affect impairs associative memory while recognition of a negative item is enhanced. They support dual-processing models in which negative affect or stress impairs hippocampal-dependent associative memory while the storage of negative sensory/perceptual representations is spared or even strengthened.

  14. Hybrid marriages and phenotypic heterosis in offspring: Evidence from China.

    Science.gov (United States)

    Zhu, Chen; Zhang, Xiaohui; Zhao, Qiran; Chen, Qihui

    2018-02-19

    In genetics, heterosis refers to the phenomenon that cross-breeding within species leads to offspring that are genetically fitter than their parents and exhibit improved phenotypic characteristics. Based on the theory of heterosis and existing genetic evidence, offspring of "hybrid" marriages (spouses originating from different states/provinces/countries/areas), though relatively rare due to physical boundaries, may exhibit greater genetic fitness in terms of intelligence, height, or physical attractiveness (the "distance-performance" hypothesis). This study explores whether heterosis is a contributing factor to offspring's educational attainment in China by applying a high-dimensional fixed effects (HDFE) modelling framework to the unique 0.1% micro-sample of the 2000 Chinese Population Census data. Concerning potential endogeneity of hybrid marriages, we conduct a series of robustness checks. Reassuringly, the estimated heterosis effect remains significantly positive across various measurements, after controlling for parental educational attainments/height, environmental influences, and over a thousand region and region-by-year fixed effects. The effects in male and higher-educated offspring are found to be stronger. Results are replicated when analyzing body height using data from the China Health and Nutrition Survey. Although endogeneity of "hybrid marriages" may not be completely ruled out, the current study sheds light on the potentially beneficial effects of interprovincial migration on population-level human capital accumulation, and we hope that this paper can intrigue future studies that further address endogeneity. The implied heterosis effect could, therefore, be profound for Homo sapiens as a species from an evolutionary point of view. An additional important implication is that the overall genetic influences of parents on offspring's performance may be further decomposed into a conventional heredity effect and a heterosis effect that has been

  15. The molecular and phenotypic spectrum of IQSEC2-related epilepsy.

    Science.gov (United States)

    Zerem, Ayelet; Haginoya, Kazuhiro; Lev, Dorit; Blumkin, Lubov; Kivity, Sara; Linder, Ilan; Shoubridge, Cheryl; Palmer, Elizabeth Emma; Field, Michael; Boyle, Jackie; Chitayat, David; Gaillard, William D; Kossoff, Eric H; Willems, Marjolaine; Geneviève, David; Tran-Mau-Them, Frederic; Epstein, Orna; Heyman, Eli; Dugan, Sarah; Masurel-Paulet, Alice; Piton, Ame'lie; Kleefstra, Tjitske; Pfundt, Rolph; Sato, Ryo; Tzschach, Andreas; Matsumoto, Naomichi; Saitsu, Hirotomo; Leshinsky-Silver, Esther; Lerman-Sagie, Tally

    2016-11-01

    IQSEC2 is an X-linked gene associated with intellectual disability (ID) and epilepsy. Herein we characterize the epilepsy/epileptic encephalopathy of patients with IQSEC2 pathogenic variants. Forty-eight patients with IQSEC2 variants were identified worldwide through Medline search. Two patients were recruited from our early onset epileptic encephalopathy cohort and one patient from personal communication. The 18 patients who have epilepsy in addition to ID are the subject of this study. Information regarding the 18 patients was ascertained by questionnaire provided to the treating clinicians. Six affected individuals had an inherited IQSEC2 variant and 12 had a de novo one (male-to-female ratio, 12:6). The pathogenic variant types were as follows: missense (8), nonsense (5), frameshift (1), intragenic duplications (2), translocation (1), and insertion (1). An epileptic encephalopathy was diagnosed in 9 (50%) of 18 patients. Seizure onset ranged from 8 months to 4 years; seizure types included spasms, atonic, myoclonic, tonic, absence, focal seizures, and generalized tonic-clonic (GTC) seizures. The electroclinical syndromes could be defined in five patients: late-onset epileptic spasms (three) and Lennox-Gastaut or Lennox-Gastaut-like syndrome (two). Seizures were pharmacoresistant in all affected individuals with epileptic encephalopathy. The epilepsy in the other nine patients had a variable age at onset from infancy to 18 years; seizure types included GTC and absence seizures in the hereditary cases and GTC and focal seizures in de novo cases. Seizures were responsive to medical treatment in most cases. All 18 patients had moderate to profound intellectual disability. Developmental regression, autistic features, hypotonia, strabismus, and white matter changes on brain magnetic resonance imaging (MRI) were prominent features. The phenotypic spectrum of IQSEC2 disorders includes epilepsy and epileptic encephalopathy. Epileptic encephalopathy is a main clinical

  16. Supporting End of Life Decision Making: Case Studies of Relational Closeness in Supported Decision Making for People with Severe or Profound Intellectual Disability

    Science.gov (United States)

    Watson, Joanne; Wilson, Erin; Hagiliassis, Nick

    2017-01-01

    Background: The United Nations Convention on the Rights of Persons with Disabilities (UNCRPD) promotes the use of supported decision making in lieu of substitute decision making. To date, there has been a lack of focus on supported decision making for people with severe or profound intellectual disability, including for end of life decisions.…

  17. Secrets for Survival: The Training Program for Teachers of the Severely/Profoundly Handicapped (S/PH). Description of Teacher Inservice Education Materials.

    Science.gov (United States)

    National Education Association, Washington, DC. Project on Utilization of Inservice Education R & D Outcomes.

    As a description of a "survival kit" for teachers confronted with the instruction of severely/profoundly handicapped children, complete information with regard to purposes of the kit, printed and audiovisual contents, scope and sequencing of topics for the six training modules, and activities and resources involved in the use of the kit is…

  18. Feasibility, Test-Retest Reliability, and Interrater Reliability of the Modified Ashworth Scale and Modified Tardieu Scale in Persons with Profound Intellectual and Multiple Disabilities

    Science.gov (United States)

    Waninge, A.; Rook, R. A.; Dijkhuizen, A.; Gielen, E.; van der Schans, C. P.

    2011-01-01

    Caregivers of persons with profound intellectual and multiple disabilities (PIMD) often describe the quality of the daily movements of these persons in terms of flexibility or stiffness. Objective outcome measures for flexibility and stiffness are muscle tone or level of spasticity. Two instruments used to grade muscle tone and spasticity are the…

  19. Feasibility, test-retest reliability, and interrater reliability of the Modified Ashworth Scale and Modified Tardieu Scale in persons with profound intellectual and multiple disabilities

    NARCIS (Netherlands)

    Waninge, A.; Rook, R.A.; Dijkhuizen, A.; Gielen, E.; van der Schans, C.P.

    2011-01-01

    Caregivers of persons with profound intellectual and multiple disabilities (PIMD) often describe the quality of the daily movements of these persons in terms of flexibility or stiffness. Objective outcome measures for flexibility and stiffness are muscle tone or level of spasticity. Two instruments

  20. Reversal of rocuronium-induced (1.2 mg kg-1) profound neuromuscular block by accidental high dose of sugammadex (40 mg kg-1).

    NARCIS (Netherlands)

    Molina, A.L.; Boer, H.D. de; Klimek, M.; Heeringa, M.; Klein, J.

    2007-01-01

    Sugammadex is the first selective relaxant binding agent and reverses rocuronium-induced neuromuscular block. A case is reported in which a patient accidentally received a high dose of sugammadex (40 mg kg-1) to reverse a rocuronium-induced (1.2 mg kg-1) profound neuromuscular block. A fast and

  1. A good read : A study into the use and effects of multi-sensory storytelling; a storytelling method for persons with profound intellectual and multiple disabilities.

    NARCIS (Netherlands)

    ten Brug, Annet

    2015-01-01

    In order to include persons with profound intellectual and multiple disabilities (PIMD) into our storytelling culture, multi-sensory storytelling (MSST) has been developed. In a multi-sensory book, verbal text is supported by sensory stimuli, the form and content of the book are adjusted to the

  2. Do Theory of Mind and Executive Function Deficits Underlie the Adverse Outcomes Associated with Profound Early Deprivation?: Findings from the English and Romanian Adoptees Study

    Science.gov (United States)

    Colvert, Emma; Rutter, Michael; Kreppner, Jana; Beckett, Celia; Castle, Jenny; Groothues, Christine; Hawkins, Amanda; Stevens, Suzanne; Sonuga-Barke, Edmund J. S.

    2008-01-01

    Theory of Mind (ToM) and Executive Function (EF) have been associated with autism and with attention-deficit hyperactivity disorder (ADHD), and hence might play a role in similar syndromes found following profound early institutional deprivation. In order to examine this possibility the current study included a group of 165 Romanian adoptees, of…

  3. Relabelling behaviour : The effects of psycho-education on the perceived severity and causes of challenging behaviour in people with profound intellectual and multiple disabilities

    NARCIS (Netherlands)

    Poppes, P.; Putten, van der Annette; Post, W.; Frans, N.; ten Brug, A.; van Es, A.; Vlaskamp, C.

    2016-01-01

    BackgroundPrevalence rates of challenging behaviour are high in children and adults with profound intellectual and multiple disabilities (PIMD). Moreover, many of these behaviours are observed daily. Direct support staff report that most challenging behaviour identified has little impact on the

  4. Relabelling Behaviour. The Effects of Psycho-Education on the Perceived Severity and Causes of Challenging Behaviour in People with Profound Intellectual and Multiple Disabilities

    Science.gov (United States)

    Poppes, P.; van der Putten, A.; Post, W.; Frans, N.; ten Brug, A.; van Es, A.; Vlaskamp, C.

    2016-01-01

    Background: Prevalence rates of challenging behaviour are high in children and adults with profound intellectual and multiple disabilities (PIMD). Moreover, many of these behaviours are observed daily. Direct support staff report that most challenging behaviour identified has little impact on the person with PIMD and attribute challenging…

  5. Efforts in enhancing social contacts of persons with severe of profound intellectual and multiple disabilities : Analysing individual support plans in the Netherlands

    NARCIS (Netherlands)

    Kamstra, Aafke; van der Putten, Annette; Vlaskamp, Carla

    2017-01-01

    Most people with profound intellectual and multiple disabilities (PIMD) have limited social contact and it is unclear what is done to maintain or increase these contacts. Individual support planning (ISP) can be used in the systematic enhancement of social contacts. This study analyses the content

  6. Implementation of an Initial Training Program for New Employees in a Profoundly Mentally and Physically Handicapped Children and Adult Residential Facility.

    Science.gov (United States)

    Hoeft, Linda A.

    A project was designed to reduce the turnover of direct care staff in a community-based residential facility that provides a home and educational or adult day training services for 54 severely or profoundly mentally and physically handicapped children and adults. The project sought to reduce total staff turnover by 40%, reduce employee…

  7. Look closer : The alertness of people with profound intellectual and multiple disabilities during multi-sensory storytelling, a time sequential analysis

    NARCIS (Netherlands)

    Ten Brug, Annet; Munde, Vera S.; van der Putten, Annette A. J.; Vlaskamp, Carla

    2015-01-01

    Introduction: Multi-sensory storytelling (MSST) is a storytelling method designed for individuals with profound intellectual and multiple disabilities (PIMD). It is essential that listeners be alert during MSST, so that they become familiar with their personalised stories. Repetition and the

  8. A Micro-Ethnographic Study of the Communication/Language Development in a Japanese Child with Profound Hearing Loss before and after Cochlear Implantation

    Science.gov (United States)

    Kretschmer, Richard R.; Kretschmer, Laura; Kuwahara, Katsura; Truax, Roberta

    2010-01-01

    This study described the communication and spoken language development of a Japanese girl with profound hearing loss who used a cochlear implant from 19 months of age. The girl, Akiko, was born in Belgium where her family was living at that time. After she was identified as deaf at birth, she and her parents were provided with support services.…

  9. Look Closer: The Alertness of People with Profound Intellectual and Multiple Disabilities during Multi-Sensory Storytelling, a Time Sequential Analysis

    Science.gov (United States)

    Ten Brug, Annet; Munde, Vera S.; van der Putten, Annette A.J.; Vlaskamp, Carla

    2015-01-01

    Introduction: Multi-sensory storytelling (MSST) is a storytelling method designed for individuals with profound intellectual and multiple disabilities (PIMD). It is essential that listeners be alert during MSST, so that they become familiar with their personalised stories. Repetition and the presentation of stimuli are likely to affect the…

  10. Phenotypic profiles of Armenian grape cultivars

    Directory of Open Access Journals (Sweden)

    Aroutiounian Rouben

    2015-01-01

    Full Text Available The conservation and sustainable use of grapevine biodiversity in Armenia is particularly important due to the large number of traditional local varieties. Being partially different from European grapevine gene pool, the material of Armenian local cultivars significantly contributes to the understanding of the genetic variation and is valuable source for target selection. During last years many Armenian grapevine cultivars have been already described and their genotypes determined, but some local varieties and wild accessions remain unidentified and their phenotypic characteristics overlooked. The comprehensive analysis of phenotypes is essential for research, including genetic association studies, cultivar evaluation and selection. The goal of our research was the phenotyping on the base of reproductive, carpological and analytical characteristics of 80 Armenian aboriginal and new grape cultivars. Description of phenotypic profiles is important step towards identification and conservation of genetic resources of Armenian grapes. In future, these data can be applied for breeding of improved grape varieties targeted to fresh consumption and wine production.

  11. Phenotypic diversity and phylogenetic relationship between the ...

    African Journals Online (AJOL)

    Phenotypic diversity and phylogenetic relationship between the Bakosi/Baweri and other pig breeds ( Sus scrofa Domesticus ) in the humid forest with monomodal rainfall agro-ecological zone of Cameroon.

  12. Mining skeletal phenotype descriptions from scientific literature.

    Directory of Open Access Journals (Sweden)

    Tudor Groza

    Full Text Available Phenotype descriptions are important for our understanding of genetics, as they enable the computation and analysis of a varied range of issues related to the genetic and developmental bases of correlated characters. The literature contains a wealth of such phenotype descriptions, usually reported as free-text entries, similar to typical clinical summaries. In this paper, we focus on creating and making available an annotated corpus of skeletal phenotype descriptions. In addition, we present and evaluate a hybrid Machine Learning approach for mining phenotype descriptions from free text. Our hybrid approach uses an ensemble of four classifiers and experiments with several aggregation techniques. The best scoring technique achieves an F-1 score of 71.52%, which is close to the state-of-the-art in other domains, where training data exists in abundance. Finally, we discuss the influence of the features chosen for the model on the overall performance of the method.

  13. Integrating phenotype ontologies with PhenomeNET

    KAUST Repository

    Rodriguez-Garcia, Miguel Angel; Gkoutos, Georgios V.; Schofield, Paul N.; Hoehndorf, Robert

    2017-01-01

    in clinical and model organism databases presents complex problems when attempting to match classes across species and across phenotypes as diverse as behaviour and neoplasia. We have previously developed PhenomeNET, a system for disease gene prioritization

  14. Wiedemann-Rautenstrauch syndrome: A phenotype analysis

    NARCIS (Netherlands)

    Paolacci, Stefano; Bertola, Debora; Franco, José; Mohammed, Shehla; Tartaglia, Marco; Wollnik, Bernd; Hennekam, Raoul C.

    2017-01-01

    Wiedemann-Rautenstrauch syndrome (WRS) is a neonatal progeroid disorder characterized by growth retardation, lipodystrophy, a distinctive face, and dental anomalies. Patients reported to date demonstrate a remarkable variability in phenotype, which hampers diagnostics. We performed a literature

  15. REVIEW ARTICLE One gene, many phenotypes

    African Journals Online (AJOL)

    salah

    Phenotype descriptions are valuable information right at the interface of medi- cine and biology. ... the interaction of alleles at different loci. Modifier genes. 5. ... the amount of normal protein is called ..... Institute, using computer simulations,.

  16. The spatial patterns of directional phenotypic selection

    KAUST Repository

    Siepielski, Adam M.; Gotanda, Kiyoko M.; Morrissey, Michael B.; Diamond, Sarah E.; DiBattista, Joseph; Carlson, Stephanie Marie

    2013-01-01

    the spatial patterns of selection, namely the extent of variation among populations in the strength and direction of selection. Here, we analyse a data set of spatially replicated studies of directional phenotypic selection from natural populations. The data

  17. Phenotypic variability among strains of Pasteurella multocida ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-05-02

    May 2, 2008 ... Available online at http://www.academicjournals.org/AJB. ISSN 1684–5315 ... extended phenotypic characterization methods supported by DNA ... septicaemia African (Obudu) strain (E:2) which are currently employed as ...

  18. Specific needs of families of young adults with profound intellectual disability during and after transition to adulthood: What are we missing?

    Science.gov (United States)

    Gauthier-Boudreault, Camille; Gallagher, Frances; Couture, Mélanie

    2017-07-01

    At the age of 21, the trajectory of services offered to youth with profound intellectual disability (ID) change significantly since access to specialised services is more limited. Despite the desire of parents to avoid any impact on their child, several factors can influence the course of this transition. However, there is little research on facilitators and obstacles to the transition to adulthood, and impacts on people with a profound ID. It is therefore difficult to provide solutions that meet their specific needs. The study aimed to document the needs of parents and young adults with profound ID during and after the transition to adulthood by exploring their transitioning experience and factors that influenced it. Using a descriptive qualitative design, two individual semi-structured interviews were conducted with fourteen (14) parents of young adults aged between 18 and 26 with a profound ID. At this point, many material, informative, cognitive and emotional needs of young adults and their parents are not met. Obstacles, mainly organisational, persist and result in a particularly difficult transition to adulthood experience. By knowing the specific needs of these families, it is possible to develop and implement solutions tailored to their reality. WHAT THE PAPERS ADDS?: The transition to adulthood is a critical period for families with young adults with an intellectual disability (ID), a reality observed internationally. Current literature on all levels of ID suggests some barriers to transition that lead to negative impacts on both parents and young adults with ID. However, presently, very little research exists on the reality of families of young adults with profound ID and factors influencing transition to adult life. Most of studies target people with mild to moderate ID. Considering the significant disabilities of people with profound ID, it is possible to imagine that their experience of transition will be even more difficult and they will present

  19. Atypical disease phenotypes in pediatric ulcerative colitis

    DEFF Research Database (Denmark)

    Levine, Arie; de Bie, Charlotte I; Turner, Dan

    2013-01-01

    Definitive diagnosis of pediatric ulcerative colitis (UC) may be particularly challenging since isolated colitis with overlapping features is common in pediatric Crohn's disease (CD), while atypical phenotypes of UC are not uncommon. The Paris classification allows more accurate phenotyping...... of atypical inflammatory bowel disease (IBD) patients. Our aim was to identify the prevalence of atypical disease patterns in new-onset pediatric UC using the Paris classification....

  20. A Regulatory RNA Inducing Transgenerationally Inherited Phenotypes

    DEFF Research Database (Denmark)

    Jensen, Lea Møller

    . The variation in Arabidopsis enables different regulatory networks and mechanisms to shape the phenotypic characteristics. The thesis describes the identification of regulatory RNA encoded by an enzyme encoding gene. The RNA regulates by inducing transgenerationally inherited phenotypes. The function of the RNA...... is dependent on the genetic background illustrating that polymorphisms are found in either interactors or target genes of the RNA. Furthermore, the RNA provides a mechanistic link between accumulation of glucosinolate and onset of flowering....

  1. Cognitive Impairment Associated with Cancer

    Science.gov (United States)

    Pendergrass, J. Cara; Harrison, John E.

    2018-01-01

    This brief review explores the areas of cognitive impairment that have been observed in cancer patients and survivors, the cognitive assessment tools used, and the management of the observed cognitive changes. Cognitive changes and impairment observed in patients with cancer and those in remission can be related to the direct effects of cancer itself, nonspecific factors or comorbid conditions that are independent of the actual disease, and/or the treatments or combination of treatments administered. Attention, memory, and executive functioning are the most frequently identified cognitive domains impacted by cancer. However, the prevalence and extent of impairment remains largely unknown due to marked differences in methodology, definitions of cognitive impairment, and the assessment measures used. Assessment of cognitive functioning is an important and necessary part of a comprehensive oncological care plan. Research is needed to establish a better understanding of cognitive changes and impairments associated with cancer so that optimal patient outcomes can be achieved. PMID:29497579

  2. Association Between Frailty and Cognitive Impairment: Cross-Sectional Data From Toulouse Frailty Day Hospital.

    Science.gov (United States)

    Fougère, Bertrand; Daumas, Matthieu; Lilamand, Matthieu; Sourdet, Sandrine; Delrieu, Julien; Vellas, Bruno; Abellan van Kan, Gabor

    2017-11-01

    A consensus panel, based on epidemiologic evidence, argued that physical frailty is often associated with cognitive impairment, possibly because of common underlying pathophysiological mechanisms. The concepts of cognitive frailty and motoric cognitive risk were recently proposed in literature and may represent a prodromal stage for neurodegenerative diseases. The purpose of this study was to analyze the relationship between cognition and the components of the physical phenotype of frailty. Participants admitted to the Toulouse frailty day hospital aged 65 years or older were included in this cross-sectional study. Cognitive impairment was identified using the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating (CDR). Frailty was assessed using the physical phenotype as defined by Fried's criteria. We divided the participants into 2 groups: participants with normal cognition (CDR = 0) and participants who had cognitive impairment (CDR = 0.5). Participants with CDR >0.5 were excluded. Data from 1620 participants, mean age 82 years and 63% of women were analyzed. Cognitive impairment was identified in 52.5% of the participants. Frailty was identified in 44.7% of the sample. There were more frail subjects in the impaired group than the normal cognitive group (51% vs 38%, P impairment [adjusted odds ratio (OR) 1.66, 95% confidence interval (CI) 1.12-2.46]. Subsequent analysis showed that the association between cognitive impairment and frailty was only observed considering one of the 5 frailty criteria: gait speed (adjusted OR 1.89, 95% CI 1.55-2.32). Physical frailty and in particular slow gait speed were associated with cognitive impairment. Future research including longitudinal studies should exploit the association between cognitive impairment and frailty. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  3. Phenex: ontological annotation of phenotypic diversity.

    Directory of Open Access Journals (Sweden)

    James P Balhoff

    2010-05-01

    Full Text Available Phenotypic differences among species have long been systematically itemized and described by biologists in the process of investigating phylogenetic relationships and trait evolution. Traditionally, these descriptions have been expressed in natural language within the context of individual journal publications or monographs. As such, this rich store of phenotype data has been largely unavailable for statistical and computational comparisons across studies or integration with other biological knowledge.Here we describe Phenex, a platform-independent desktop application designed to facilitate efficient and consistent annotation of phenotypic similarities and differences using Entity-Quality syntax, drawing on terms from community ontologies for anatomical entities, phenotypic qualities, and taxonomic names. Phenex can be configured to load only those ontologies pertinent to a taxonomic group of interest. The graphical user interface was optimized for evolutionary biologists accustomed to working with lists of taxa, characters, character states, and character-by-taxon matrices.Annotation of phenotypic data using ontologies and globally unique taxonomic identifiers will allow biologists to integrate phenotypic data from different organisms and studies, leveraging decades of work in systematics and comparative morphology.

  4. Phenex: ontological annotation of phenotypic diversity.

    Science.gov (United States)

    Balhoff, James P; Dahdul, Wasila M; Kothari, Cartik R; Lapp, Hilmar; Lundberg, John G; Mabee, Paula; Midford, Peter E; Westerfield, Monte; Vision, Todd J

    2010-05-05

    Phenotypic differences among species have long been systematically itemized and described by biologists in the process of investigating phylogenetic relationships and trait evolution. Traditionally, these descriptions have been expressed in natural language within the context of individual journal publications or monographs. As such, this rich store of phenotype data has been largely unavailable for statistical and computational comparisons across studies or integration with other biological knowledge. Here we describe Phenex, a platform-independent desktop application designed to facilitate efficient and consistent annotation of phenotypic similarities and differences using Entity-Quality syntax, drawing on terms from community ontologies for anatomical entities, phenotypic qualities, and taxonomic names. Phenex can be configured to load only those ontologies pertinent to a taxonomic group of interest. The graphical user interface was optimized for evolutionary biologists accustomed to working with lists of taxa, characters, character states, and character-by-taxon matrices. Annotation of phenotypic data using ontologies and globally unique taxonomic identifiers will allow biologists to integrate phenotypic data from different organisms and studies, leveraging decades of work in systematics and comparative morphology.

  5. Highly variable penetrance of abnormal phenotypes in embryonic lethal knockout mice [version 2; referees: 1 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Robert Wilson

    2017-02-01

    Full Text Available Background: Identifying genes that are essential for mouse embryonic development and survival through term is a powerful and unbiased way to discover possible genetic determinants of human developmental disorders. Characterising the changes in mouse embryos that result from ablation of lethal genes is a necessary first step towards uncovering their role in normal embryonic development and establishing any correlates amongst human congenital abnormalities. Methods: Here we present results gathered to date in the Deciphering the Mechanisms of Developmental Disorders (DMDD programme, cataloguing the morphological defects identified from comprehensive imaging of 220 homozygous mutant and 114 wild type embryos from 42 lethal and subviable lines, analysed at E14.5. Results: Virtually all mutant embryos show multiple abnormal phenotypes and amongst the 42 lines these affect most organ systems. Within each mutant line, the phenotypes of individual embryos form distinct but overlapping sets. Subcutaneous edema, malformations of the heart or great vessels, abnormalities in forebrain morphology and the musculature of the eyes are all prevalent phenotypes, as is loss or abnormal size of the hypoglossal nerve. Conclusions: Overall, the most striking finding is that no matter how profound the malformation, each phenotype shows highly variable penetrance within a mutant line. These findings have challenging implications for efforts to identify human disease correlates.

  6. Nutrition and cognitive impairment

    Science.gov (United States)

    Hernando-Requejo, Virgilio

    2016-07-12

    Dementia, closely linked to environmental predisposing factors such as diet, is a public health problem of increasing magnitude: currently there are more than 35 million patients with Alzheimer´s disease, and is expected to exceed 135 million by 2050. If we can delay the development of dementia 5 years will reduce its prevalence by 50%. Patients with dementia modify their diet, and it has been reported in them deficits, among others, of folic acid, vitamin B12, B6, C, E, A, D, K, beta carotene and omega 3 fatty acids, that must be resolved with proper diet and with extra contributions if needed in some cases. But to reduce, or at least delay, the prevalence of dementia we advocate prevention through proper diet from the beginning of life, an idea that is reinforced given that cardiovascular risk factors are related directly to the development of dementia. A lot of literature are available that, although with limits, allows us to make nutritional recommendations for preventing cognitive impairment. Better results are achieved when complete diets have been studied and considered over specific nutrients separately. Particularly, the Mediterranean diet has great interest in this disease, since it ensures a high intake of vegetables, fruits, nuts, legumes, cereals, fish and olive oil, and moderate intake of meat, dairy products and alcohol. We will focus more on this article in this type of diet.

  7. Multimodal MR-imaging reveals large-scale structural and functional connectivity changes in profound early blindness

    Science.gov (United States)

    Bauer, Corinna M.; Hirsch, Gabriella V.; Zajac, Lauren; Koo, Bang-Bon; Collignon, Olivier

    2017-01-01

    In the setting of profound ocular blindness, numerous lines of evidence demonstrate the existence of dramatic anatomical and functional changes within the brain. However, previous studies based on a variety of distinct measures have often provided inconsistent findings. To help reconcile this issue, we used a multimodal magnetic resonance (MR)-based imaging approach to provide complementary structural and functional information regarding this neuroplastic reorganization. This included gray matter structural morphometry, high angular resolution diffusion imaging (HARDI) of white matter connectivity and integrity, and resting state functional connectivity MRI (rsfcMRI) analysis. When comparing the brains of early blind individuals to sighted controls, we found evidence of co-occurring decreases in cortical volume and cortical thickness within visual processing areas of the occipital and temporal cortices respectively. Increases in cortical volume in the early blind were evident within regions of parietal cortex. Investigating white matter connections using HARDI revealed patterns of increased and decreased connectivity when comparing both groups. In the blind, increased white matter connectivity (indexed by increased fiber number) was predominantly left-lateralized, including between frontal and temporal areas implicated with language processing. Decreases in structural connectivity were evident involving frontal and somatosensory regions as well as between occipital and cingulate cortices. Differences in white matter integrity (as indexed by quantitative anisotropy, or QA) were also in general agreement with observed pattern changes in the number of white matter fibers. Analysis of resting state sequences showed evidence of both increased and decreased functional connectivity in the blind compared to sighted controls. Specifically, increased connectivity was evident between temporal and inferior frontal areas. Decreases in functional connectivity were observed

  8. A framework for communication between visually impaired, hearing impaired and speech impaired using arduino

    Science.gov (United States)

    Sujatha, R.; Khandelwa, Prakhar; Gupta, Anusha; Anand, Nayan

    2017-11-01

    A long time ago our society accepted the notion of treating people with disabilities not as unviable and disabled but as differently-abled, recognizing their skills beyond their disabilities. The next step has to be taken by our scientific community, that is, to normalize lives of the people with disabilities and make it so as if they are no different to us. The primary step in this direction would be to normalize communication between people. People with an impaired speech or impaired vision or impaired hearing face difficulties while having a casual conversation with others. Any form of communication feels so strenuous that the impaired end up communicating just the important information and avoid a casual conversation. To normalize conversation between the impaired we need a simple and compact device which facilitates the conversation by providing the information in the desired form.

  9. Single prolonged stress impairs social and object novelty recognition in rats.

    Science.gov (United States)

    Eagle, Andrew L; Fitzpatrick, Chris J; Perrine, Shane A

    2013-11-01

    Posttraumatic stress disorder (PTSD) results from exposure to a traumatic event and manifests as re-experiencing, arousal, avoidance, and negative cognition/mood symptoms. Avoidant symptoms, as well as the newly defined negative cognitions/mood, are a serious complication leading to diminished interest in once important or positive activities, such as social interaction; however, the basis of these symptoms remains poorly understood. PTSD patients also exhibit impaired object and social recognition, which may underlie the avoidance and symptoms of negative cognition, such as social estrangement or diminished interest in activities. Previous studies have demonstrated that single prolonged stress (SPS), models PTSD phenotypes, including impairments in learning and memory. Therefore, it was hypothesized that SPS would impair social and object recognition memory. Male Sprague Dawley rats were exposed to SPS then tested in the social choice test (SCT) or novel object recognition test (NOR). These tests measure recognition of novelty over familiarity, a natural preference of rodents. Results show that SPS impaired preference for both social and object novelty. In addition, SPS impairment in social recognition may be caused by impaired behavioral flexibility, or an inability to shift behavior during the SCT. These results demonstrate that traumatic stress can impair social and object recognition memory, which may underlie certain avoidant symptoms or negative cognition in PTSD and be related to impaired behavioral flexibility. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Age is associated with asthma phenotypes.

    Science.gov (United States)

    Ponte, Eduardo V; Lima, Aline; Almeida, Paula C A; de Jesus, Juliana P V; Lima, Valmar B; Scichilone, Nicola; Souza-Machado, Adelmir; Cruz, Álvaro A

    2017-11-01

    The relationship between age and asthma phenotypes is important as population is ageing, asthma is becoming common in older ages and recently developed treatments for asthma are guided by phenotypes. The aim of this study is to evaluate whether age is associated with specific asthma phenotypes. This is a cross-sectional study. We included subjects with asthma of varied degrees of severity. Subjects underwent spirometry, skin prick test to aeroallergens, answered the Asthma Control Questionnaire and had blood samples collected. We performed binary logistic regression analysis to evaluate whether age is associated with asthma phenotypes. We enrolled 868 subjects. In comparison with subjects ≤ 40 years, older subjects had high odds of irreversible airway obstruction (from 41 to 64 years, OR: 1.83 (95% CI: 1.32-2.54); ≥65 years, OR: 3.45 (2.12-5.60)) and severe asthma phenotypes (from 41 to 64 years, OR: 3.23 (2.26-4.62); ≥65 years, OR: 4.55 (2.39-8.67)). Older subjects had low odds of atopic (from 41 to 64 years, OR: 0.56 (0.39-0.79); ≥65 years, OR: 0.47 (0.27-0.84)) and eosinophilic phenotypes (from 41 to 64 years, OR: 0.63 (0.46-0.84); ≥65 years, OR: 0.39 (0.24-0.64)). Older subjects with asthma have low odds of atopic and eosinophilic phenotypes, whereas they present high odds of irreversible airway obstruction and severe asthma. © 2017 Asian Pacific Society of Respirology.

  11. Cognitive impairment in elderly women

    DEFF Research Database (Denmark)

    Rasmussen, Henrik Berg; Bagger, Yu Z; Tankó, László B

    2006-01-01

    BACKGROUND: A variety of factors contribute to the development of cognitive impairment in elderly people. Previous studies have focused upon a single or a few risk factors. In this study we assessed and compared the significance of a wide variety of potential risk factors for cognitive impairment...... in postmenopausal women. METHODS: A total of 208 pairs of elderly women (mean age = 73.2 years) were examined in a cross-sectional case-control study. Each pair consisted of a case (with impaired cognition) and a control subject matched by age and educational status. Cognitive functions were determined using...

  12. Impaired reasoning and problem-solving in individuals with language impairment due to aphasia or language delay

    Science.gov (United States)

    Baldo, Juliana V.; Paulraj, Selvi R.; Curran, Brian C.; Dronkers, Nina F.

    2015-01-01

    The precise nature of the relationship between language and thought is an intriguing and challenging area of inquiry for scientists across many disciplines. In the realm of neuropsychology, research has investigated the inter-dependence of language and thought by testing individuals with compromised language abilities and observing whether performance in other cognitive domains is diminished. One group of such individuals is patients with aphasia who have an impairment in speech and language arising from a brain injury, such as a stroke. Our previous research has shown that the degree of language impairment in these individuals is strongly associated with the degree of impairment on complex reasoning tasks, such as the Wisconsin Card Sorting Task (WCST) and Raven’s Matrices. In the current study, we present new data from a large group of individuals with aphasia that show a dissociation in performance between putatively non-verbal tasks on the Wechsler Adult Intelligence Scale (WAIS) that require differing degrees of reasoning (Picture Completion vs. Picture Arrangement tasks). We also present an update and replication of our previous findings with the WCST showing that individuals with the most profound core language deficits (i.e., impaired comprehension and disordered language output) are particularly impaired on problem-solving tasks. In the second part of the paper, we present findings from a neurologically intact individual known as “Chelsea” who was not exposed to language due to an unaddressed hearing loss that was present since birth. At the age of 32, she was fitted with hearing aids and exposed to spoken and signed language for the first time, but she was only able to acquire a limited language capacity. Chelsea was tested on a series of standardized neuropsychological measures, including reasoning and problem-solving tasks. She was able to perform well on a number of visuospatial tasks but was disproportionately impaired on tasks that required

  13. Brain visual impairment in childhood: mini review

    OpenAIRE

    Kozeis, N

    2010-01-01

    Cerebral visual impairment (CVI) is one of the leading causes of severe visual impairment in childhood. This article was written to highlight any new knowledge related to cerebral visual impairment in childhood.

  14. Impaired TCA cycle flux in mitochondria in skeletal muscle from type 2 diabetic subjects

    DEFF Research Database (Denmark)

    Gaster, Michael; Nehlin, Jan O; Minet, Ariane D

    2012-01-01

    The diabetic phenotype is complex, requiring elucidation of key initiating defects. Recent research has shown that diabetic myotubes express a primary reduced tricarboxylic acid (TCA) cycle flux. A reduced TCA cycle flux has also been shown both in insulin resistant offspring of T2D patients...... and exercising T2D patients in vivo. This review will discuss the latest advances in the understanding of the molecular mechanisms regulating the TCA cycle with focus on possible underlying mechanism which could explain the impaired TCA flux in insulin resistant human skeletal muscle in type 2 diabetes....... A reduced TCA is both a marker and a maker of the diabetic phenotype....

  15. Impaired cholesterol esterification in primary brain cultures of the lysosomal cholesterol storage disorder (LCSD) mouse mutant

    International Nuclear Information System (INIS)

    Patel, S.C.; Suresh, S.; Weintroub, H.; Brady, R.O.; Pentchev, P.G.

    1987-01-01

    Esterification of cholesterol was investigated in primary neuroglial cultures obtained from newborn lysosomal cholesterol storage disorder (LCSD) mouse mutants. An impairment in 3 H-oleic acid incorporation into cholesteryl esters was demonstrated in cultures of homozygous LCSD brain. Primary cultures derived from other phenotypically normal pups of the carrier breeders esterified cholesterol at normal levels or at levels which were intermediary between normal and deficient indicating a phenotypic expression of the LCSD heterozygote genotype. These observations on LCSD mutant brain cells indicate that the defect in cholesterol esterification is closely related to the primary genetic defect and is expressed in neuroglial cells in culture

  16. Overeating phenotypes in overweight and obese children.

    Science.gov (United States)

    Boutelle, Kerri N; Peterson, Carol B; Crosby, Ross D; Rydell, Sarah A; Zucker, Nancy; Harnack, Lisa

    2014-05-01

    The purpose of this study was to identify overeating phenotypes and their correlates in overweight and obese children. One hundred and seventeen treatment-seeking overweight and obese 8-12year-old children and their parents completed the study. Children completed an eating in the absence of hunger (EAH) paradigm, the Eating Disorder Examination interview, and measurements of height and weight. Parents and children completed questionnaires that evaluated satiety responsiveness, food responsiveness, negative affect eating, external eating and eating in the absence of hunger. Latent profile analysis was used to identify heterogeneity in overeating phenotypes in the child participants. Latent classes were then compared on measures of demographics, obesity status and nutritional intake. Three latent classes of overweight and obese children were identified: High Satiety Responsive, High Food Responsive, and Moderate Satiety and Food Responsive. Results indicated that the High Food Responsive group had higher BMI and BMI-Z scores compared to the High Satiety Responsive group. No differences were found among classes in demographics or nutritional intake. This study identified three overeating phenotypes, supporting the heterogeneity of eating patterns associated with overweight and obesity in treatment-seeking children. These finding suggest that these phenotypes can potentially be used to identify high risk groups, inform prevention and intervention targets, and develop specific treatments for these behavioral phenotypes. Copyright © 2014. Published by Elsevier Ltd.

  17. The Quantitative Nature of Autistic Social Impairment

    Science.gov (United States)

    Constantino, John N.

    2011-01-01

    Autism, like intellectual disability, represents the severe end of a continuous distribution of developmental impairments that occur in nature, that are highly inherited, and that are orthogonally related to other parameters of development. A paradigm shift in understanding the core social abnormality of autism as a quantitative trait rather than as a categorically-defined condition has key implications for diagnostic classification, the measurement of change over time, the search for underlying genetic and neurobiologic mechanisms, and public health efforts to identify and support affected children. Here a recent body of research in genetics and epidemiology is presented to examine a dimensional reconceptualization of autistic social impairment—as manifested in clinical autistic syndromes, the broader autism phenotype, and normal variation in the general population. It illustrates how traditional categorical approaches to diagnosis may lead to misclassification of subjects (especially girls and mildly affected boys in multiple-incidence autism families), which can be particularly damaging to biological studies, and proposes continued efforts to derive a standardized quantitative system by which to characterize this family of conditions. PMID:21289537

  18. The phenotypic manifestations of rare genic CNVs in autism spectrum disorder.

    Science.gov (United States)

    Merikangas, A K; Segurado, R; Heron, E A; Anney, R J L; Paterson, A D; Cook, E H; Pinto, D; Scherer, S W; Szatmari, P; Gill, M; Corvin, A P; Gallagher, L

    2015-11-01

    Significant evidence exists for the association between copy number variants (CNVs) and Autism Spectrum Disorder (ASD); however, most of this work has focused solely on the diagnosis of ASD. There is limited understanding of the impact of CNVs on the 'sub-phenotypes' of ASD. The objective of this paper is to evaluate associations between CNVs in differentially brain expressed (DBE) genes or genes previously implicated in ASD/intellectual disability (ASD/ID) and specific sub-phenotypes of ASD. The sample consisted of 1590 cases of European ancestry from the Autism Genome Project (AGP) with a diagnosis of an ASD and at least one rare CNV impacting any gene and a core set of phenotypic measures, including symptom severity, language impairments, seizures, gait disturbances, intelligence quotient (IQ) and adaptive function, as well as paternal and maternal age. Classification analyses using a non-parametric recursive partitioning method (random forests) were employed to define sets of phenotypic characteristics that best classify the CNV-defined groups. There was substantial variation in the classification accuracy of the two sets of genes. The best variables for classification were verbal IQ for the ASD/ID genes, paternal age at birth for the DBE genes and adaptive function for de novo CNVs. CNVs in the ASD/ID list were primarily associated with communication and language domains, whereas CNVs in DBE genes were related to broader manifestations of adaptive function. To our knowledge, this is the first study to examine the associations between sub-phenotypes and CNVs genome-wide in ASD. This work highlights the importance of examining the diverse sub-phenotypic manifestations of CNVs in ASD, including the specific features, comorbid conditions and clinical correlates of ASD that comprise underlying characteristics of the disorder.

  19. Pseudomonas aeruginosa infection alters the macrophage phenotype switching process during wound healing in diabetic mice.

    Science.gov (United States)

    Chen, Sinuo; Li, Renren; Cheng, Chun; Xu, Jing-Ying; Jin, Caixia; Gao, Furong; Wang, Juan; Zhang, Jieping; Zhang, Jingfa; Wang, Hong; Lu, Lixia; Xu, Guo-Tong; Tian, Haibin

    2018-03-07

    Macrophages play critical roles in wound healing process. They switch from "classically activated" (M1) phenotype in the early inflammatory phase to "alternatively activated" (M2) phenotype in the later healing phase. However, the dynamic process of macrophage phenotype switching in diabetic wounds burdened with bacteria is unclear. In this report, Pseudomonas aeruginosa, frequently detected in diabetic foot ulcers, was inoculated into cutaneous wounds of db/db diabetic mice to mimic bacterium-infected diabetic wound healing. We observed that P. aeruginosa infection impaired diabetic wound healing and quickly promoted the expression of pro-inflammatory genes (M1 macrophage markers) tumor necrosis factor-α (tnf-α), interleukin-1β (il-1β) and il-6 in wounds. The expression of markers of M2 macrophages, including il-10, arginase-1, and ym1 were also upregulated. In addition, similar gene expression patterns were observed in macrophages isolated directly from wounds. Immunostaining showed that P. aeruginosa infection increased both the ratios of M1 and M2 macrophages in wounds compared with that in control groups, which was further confirmed by in vitro culturing macrophages with P. aeruginosa and skin fibroblast conditioned medium. However, the ratios of the expression levels of pro-inflammatory genes to anti-inflammatory gene il-10 was increased markedly in P. aeruginosa infected wounds and macrophages compared with that in control groups, and P. aeruginosa prolonged the presence of M1 macrophages in the wounds. These data demonstrated that P. aeruginosa in diabetic wounds activates a mixed M1/M2 macrophage phenotype with an excessive activation of M1 phenotype or relatively inadequate activation of M2 phenotype. © 2018 International Federation for Cell Biology.

  20. Electrophysiology in visually impaired children

    NARCIS (Netherlands)

    Genderen, Maria Michielde van

    2006-01-01

    Inherited retinal disorders and posterior visual pathway abnormalities are important causes of visual impairment in children. Visual electrophysiology often is indispensable in diagnosing these conditions. This thesis shows the wide range of use of pediatric electro-ophthalmology, and demonstrates

  1. Abscisic acid ameliorates the systemic sclerosis fibroblast phenotype in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Bruzzone, Santina, E-mail: santina.bruzzone@unige.it [Department of Experimental Medicine, Section of Biochemistry, University of Genova, Viale Benedetto XV 1, 16132 Genova (Italy); Centre of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 9, 16132 Genova (Italy); Advanced Biotechnology Center, Largo Rosanna Benzi 10, 16132 Genova (Italy); Battaglia, Florinda [Centre of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 9, 16132 Genova (Italy); Mannino, Elena [Department of Experimental Medicine, Section of Biochemistry, University of Genova, Viale Benedetto XV 1, 16132 Genova (Italy); Parodi, Alessia [Centre of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 9, 16132 Genova (Italy); Fruscione, Floriana [Department of Experimental Medicine, Section of Biochemistry, University of Genova, Viale Benedetto XV 1, 16132 Genova (Italy); Advanced Biotechnology Center, Largo Rosanna Benzi 10, 16132 Genova (Italy); Basile, Giovanna [Department of Experimental Medicine, Section of Biochemistry, University of Genova, Viale Benedetto XV 1, 16132 Genova (Italy); Salis, Annalisa; Sturla, Laura [Department of Experimental Medicine, Section of Biochemistry, University of Genova, Viale Benedetto XV 1, 16132 Genova (Italy); Centre of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 9, 16132 Genova (Italy); Negrini, Simone; Kalli, Francesca; Stringara, Silvia [Centre of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 9, 16132 Genova (Italy); Filaci, Gilberto [Centre of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 9, 16132 Genova (Italy); Department of Internal Medicine, Viale Benedetto XV 6, 16132 Genova (Italy); and others

    2012-05-25

    Highlights: Black-Right-Pointing-Pointer ABA is an endogenous hormone in humans, regulating different cell responses. Black-Right-Pointing-Pointer ABA reverts some of the functions altered in SSc fibroblasts to a normal phenotype. Black-Right-Pointing-Pointer UV-B irradiation increases ABA content in SSc cultures. Black-Right-Pointing-Pointer SSc fibroblasts could benefit from exposure to ABA and/or to UV-B. -- Abstract: The phytohormone abscisic acid (ABA) has been recently identified as an endogenous hormone in humans, regulating different cell functions, including inflammatory processes, insulin release and glucose uptake. Systemic sclerosis (SSc) is a chronic inflammatory disease resulting in fibrosis of skin and internal organs. In this study, we investigated the effect of exogenous ABA on fibroblasts obtained from healthy subjects and from SSc patients. Migration of control fibroblasts induced by ABA was comparable to that induced by transforming growth factor-{beta} (TGF-{beta}). Conversely, migration toward ABA, but not toward TGF-{beta}, was impaired in SSc fibroblasts. In addition, ABA increased cell proliferation in fibroblasts from SSc patients, but not from healthy subjects. Most importantly, presence of ABA significantly decreased collagen deposition by SSc fibroblasts, at the same time increasing matrix metalloproteinase-1 activity and decreasing the expression level of tissue inhibitor of metalloproteinase (TIMP-1). Thus, exogenously added ABA appeared to revert some of the functions altered in SSc fibroblasts to a normal phenotype. Interestingly, ABA levels in plasma from SSc patients were found to be significantly lower than in healthy subjects. UV-B irradiation induced an almost 3-fold increase in ABA content in SSc cultures. Altogether, these results suggest that the fibrotic skin lesions in SSc patients could benefit from exposure to high(er) ABA levels.

  2. Abscisic acid ameliorates the systemic sclerosis fibroblast phenotype in vitro

    International Nuclear Information System (INIS)

    Bruzzone, Santina; Battaglia, Florinda; Mannino, Elena; Parodi, Alessia; Fruscione, Floriana; Basile, Giovanna; Salis, Annalisa; Sturla, Laura; Negrini, Simone; Kalli, Francesca; Stringara, Silvia; Filaci, Gilberto

    2012-01-01

    Highlights: ► ABA is an endogenous hormone in humans, regulating different cell responses. ► ABA reverts some of the functions altered in SSc fibroblasts to a normal phenotype. ► UV-B irradiation increases ABA content in SSc cultures. ► SSc fibroblasts could benefit from exposure to ABA and/or to UV-B. -- Abstract: The phytohormone abscisic acid (ABA) has been recently identified as an endogenous hormone in humans, regulating different cell functions, including inflammatory processes, insulin release and glucose uptake. Systemic sclerosis (SSc) is a chronic inflammatory disease resulting in fibrosis of skin and internal organs. In this study, we investigated the effect of exogenous ABA on fibroblasts obtained from healthy subjects and from SSc patients. Migration of control fibroblasts induced by ABA was comparable to that induced by transforming growth factor-β (TGF-β). Conversely, migration toward ABA, but not toward TGF-β, was impaired in SSc fibroblasts. In addition, ABA increased cell proliferation in fibroblasts from SSc patients, but not from healthy subjects. Most importantly, presence of ABA significantly decreased collagen deposition by SSc fibroblasts, at the same time increasing matrix metalloproteinase-1 activity and decreasing the expression level of tissue inhibitor of metalloproteinase (TIMP-1). Thus, exogenously added ABA appeared to revert some of the functions altered in SSc fibroblasts to a normal phenotype. Interestingly, ABA levels in plasma from SSc patients were found to be significantly lower than in healthy subjects. UV-B irradiation induced an almost 3-fold increase in ABA content in SSc cultures. Altogether, these results suggest that the fibrotic skin lesions in SSc patients could benefit from exposure to high(er) ABA levels.

  3. [Social cognition disorders in Klinefelter syndrome: A specific phenotype? (KS)].

    Science.gov (United States)

    Babinet, M-N; Rigard, C; Peyroux, É; Dragomir, A-R; Plotton, I; Lejeune, H; Demily, C

    2017-10-01

    The Klinefelter syndrome (KS) is a genetic condition characterized by an X supernumerary sex chromosome in males. The syndrome is frequently associated with cognitive impairment. Indeed, the different areas of the executive sphere can be affected such as inhibition, cognitive flexibility but also attentional and visual-spatial domain. Social cognition disorders, predominantly on emotional recognition processes, have also been documented. In addition, the syndrome may be associated with psychiatric symptoms. Our study aims to characterize of the various components of social cognition in the SK: facial emotional recognition, theory of mind and attributional style. For this two groups (SK group versus control group) of participants (n=16) matched for age and sociocultural level were recruited. Participants with intellectual disabilities, psychiatric or neurological disorders were excluded. Three social cognition tests were available: the TREF, the MASC, the AIHQ. Neurocognitive functions were assessed by the fNart, the subtest "logical memory" of the MEM-III, the subtests of the two VOSP battery, the d2, the TMT and the Stroop test. The SK group had specific social cognition disorders in comparison to the control group. Two emotions in particular were less well recognized: fear and contempt. In addition, the SK group had significantly lower results in theory of mind. Regarding the hostile attribution bias, no significant difference was found. Finally, the results showed correlations between specific attentional disorders and facial emotional recognition. Our study emphasizes social cognition disorders in SK. These disorders could be considered as a phenotypic trait in the syndrome. The interest of better characterizing the cognitive phenotype of genetic disorders that can affect the neurodevelopment is to offer specific cognitive remediation strategies. Copyright © 2016. Published by Elsevier Masson SAS.

  4. Metabolic phenotype in the mouse model of osteogenesis imperfecta.

    Science.gov (United States)

    Boraschi-Diaz, Iris; Tauer, Josephine T; El-Rifai, Omar; Guillemette, Delphine; Lefebvre, Geneviève; Rauch, Frank; Ferron, Mathieu; Komarova, Svetlana V

    2017-09-01

    Osteogenesis imperfecta (OI) is the most common heritable bone fragility disorder, usually caused by dominant mutations in genes coding for collagen type I alpha chains, COL1A1 or COL1A2 Osteocalcin (OCN) is now recognized as a bone-derived regulator of insulin secretion and sensitivity and glucose homeostasis. Since OI is associated with increased rates of bone formation and resorption, we hypothesized that the levels of undercarboxylated OCN are increased in OI. The objective of this study was to determine changes in OCN and to elucidate the metabolic phenotype in the Col1a1 Jrt/+ mouse, a model of dominant OI caused by a Col1a1 mutation. Circulating levels of undercarboxylated OCN were higher in 4-week-old OI mice and normal by 8 weeks of age. Young OI animals exhibited a sex-dependent metabolic phenotype, including increased insulin levels in males, improved glucose tolerance in females, lower levels of random glucose and low adiposity in both sexes. The rates of O 2 consumption and CO 2 production, as well as energy expenditure assessed using indirect calorimetry were significantly increased in OI animals of both sexes, whereas respiratory exchange ratio was significantly higher in OI males only. Although OI mice have significant physical impairment that may contribute to metabolic differences, we specifically accounted for movement and compared OI and WT animals during the periods of similar activity levels. Taken together, our data strongly suggest that OI animals have alterations in whole body energy metabolism that are consistent with the action of undercarboxylated osteocalcin. © 2017 Society for Endocrinology.

  5. A genetic code alteration is a phenotype diversity generator in the human pathogen Candida albicans.

    Directory of Open Access Journals (Sweden)

    Isabel Miranda

    Full Text Available BACKGROUND: The discovery of genetic code alterations and expansions in both prokaryotes and eukaryotes abolished the hypothesis of a frozen and universal genetic code and exposed unanticipated flexibility in codon and amino acid assignments. It is now clear that codon identity alterations involve sense and non-sense codons and can occur in organisms with complex genomes and proteomes. However, the biological functions, the molecular mechanisms of evolution and the diversity of genetic code alterations remain largely unknown. In various species of the genus Candida, the leucine CUG codon is decoded as serine by a unique serine tRNA that contains a leucine 5'-CAG-3'anticodon (tRNA(CAG(Ser. We are using this codon identity redefinition as a model system to elucidate the evolution of genetic code alterations. METHODOLOGY/PRINCIPAL FINDINGS: We have reconstructed the early stages of the Candida genetic code alteration by engineering tRNAs that partially reverted the identity of serine CUG codons back to their standard leucine meaning. Such genetic code manipulation had profound cellular consequences as it exposed important morphological variation, altered gene expression, re-arranged the karyotype, increased cell-cell adhesion and secretion of hydrolytic enzymes. CONCLUSION/SIGNIFICANCE: Our study provides the first experimental evidence for an important role of genetic code alterations as generators of phenotypic diversity of high selective potential and supports the hypothesis that they speed up evolution of new phenotypes.

  6. Constraints on the evolution of phenotypic plasticity

    DEFF Research Database (Denmark)

    Murren, Courtney J; Auld, Josh R.; Callahan, Hilary S

    2015-01-01

    Phenotypic plasticity is ubiquitous and generally regarded as a key mechanism for enabling organisms to survive in the face of environmental change. Because no organism is infinitely or ideally plastic, theory suggests that there must be limits (for example, the lack of ability to produce...... an optimal trait) to the evolution of phenotypic plasticity, or that plasticity may have inherent significant costs. Yet numerous experimental studies have not detected widespread costs. Explicitly differentiating plasticity costs from phenotype costs, we re-evaluate fundamental questions of the limits...... to the evolution of plasticity and of generalists vs specialists. We advocate for the view that relaxed selection and variable selection intensities are likely more important constraints to the evolution of plasticity than the costs of plasticity. Some forms of plasticity, such as learning, may be inherently...

  7. Semi-supervised Learning for Phenotyping Tasks.

    Science.gov (United States)

    Dligach, Dmitriy; Miller, Timothy; Savova, Guergana K

    2015-01-01

    Supervised learning is the dominant approach to automatic electronic health records-based phenotyping, but it is expensive due to the cost of manual chart review. Semi-supervised learning takes advantage of both scarce labeled and plentiful unlabeled data. In this work, we study a family of semi-supervised learning algorithms based on Expectation Maximization (EM) in the context of several phenotyping tasks. We first experiment with the basic EM algorithm. When the modeling assumptions are violated, basic EM leads to inaccurate parameter estimation. Augmented EM attenuates this shortcoming by introducing a weighting factor that downweights the unlabeled data. Cross-validation does not always lead to the best setting of the weighting factor and other heuristic methods may be preferred. We show that accurate phenotyping models can be trained with only a few hundred labeled (and a large number of unlabeled) examples, potentially providing substantial savings in the amount of the required manual chart review.

  8. End-of-life care: nurses' experiences in caring for dying patients with profound learning disabilities--a descriptive case study.

    Science.gov (United States)

    Li, S; Ng, J

    2008-12-01

    This qualitative study identifies areas of expertise and deficits in the specific knowledge and practical skills of nurses in the care of dying patients with profound learning disabilities in one NHS Primary Care Trust in the UK. In response to these findings, we have developed a simple observational checklist applicable to profound learning disability nursing to identify disease-related personality and physiological changes. The method consists of a descriptive case study of five nurses qualified in learning disabilities nursing, using semi-structured interviews. The disease trajectory was used as a framework of reference to guide the data analysis. Themes showed were 'certainty of knowing' about disease-related changes in patients' habits and behaviour and 'uncertainty and ambiguity' in the patho-physiology of advanced diseases and disease progression. This study interprets a lack of patho-physiological knowledge in both malignant and non-malignant diseases leading to delayed diagnosis and timely intervention. Timeliness of observation and intervention are emphasised.

  9. The health impacts of women's low control in their living environment: A theory-based systematic review of observational studies in societies with profound gender discrimination.

    Science.gov (United States)

    Pennington, Andy; Orton, Lois; Nayak, Shilpa; Ring, Adele; Petticrew, Mark; Sowden, Amanda; White, Martin; Whitehead, Margaret

    2018-05-01

    We conducted a systematic review of observational evidence on the health impacts of women's low control/autonomy in the living environment in societies with profound gender discrimination and gender bias. Thirty observational studies of varying methodological quality were included. Overall, the evidence suggests that women's lower control or autonomy (for example lack of freedom of movement outside the home, lack of authority to access healthcare for sick children) was associated with poorer mental and physical health for women and higher morbidity and mortality for their children, after adjusting for their socioeconomic circumstances. Further studies are needed to disentangle and understand the pathways between low control and health outcomes in contexts of profound gender discrimination. This systematic review has highlighted the general low quality of the evidence base on this research question. It identifies the pressing need for high quality, longitudinal studies in the future. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

  10. Restoration of hippocampal growth hormone reverses stress-induced hippocampal impairment

    Directory of Open Access Journals (Sweden)

    Caitlin M. Vander Weele

    2013-06-01

    Full Text Available Though growth hormone (GH is synthesized by hippocampal neurons, where its expression is influenced by stress exposure, its function is poorly characterized. Here, we show that a regimen of chronic stress that impairs hippocampal function in rats also leads to a profound decrease in hippocampal GH levels. Restoration of hippocampal GH in the dorsal hippocampus via viral-mediated gene transfer completely reversed stress-related impairment of two hippocampus-dependent behavioral tasks, auditory trace fear conditioning and contextual fear conditioning, without affecting hippocampal function in unstressed control rats. GH overexpression reversed stress-induced decrements in both fear acquisition and long-term fear memory. These results suggest that loss of hippocampal GH contributes to hippocampal dysfunction following prolonged stress and demonstrate that restoring hippocampal GH levels following stress can promote stress resilience.

  11. Does degree of gyrification underlie the phenotypic and genetic associations between cortical surface area and cognitive ability?

    Science.gov (United States)

    Docherty, Anna R; Hagler, Donald J; Panizzon, Matthew S; Neale, Michael C; Eyler, Lisa T; Fennema-Notestine, Christine; Franz, Carol E; Jak, Amy; Lyons, Michael J; Rinker, Daniel A; Thompson, Wesley K; Tsuang, Ming T; Dale, Anders M; Kremen, William S

    2015-02-01

    The phenotypic and genetic relationship between global cortical size and general cognitive ability (GCA) appears to be driven by surface area (SA) and not cortical thickness (CT). Gyrification (cortical folding) is an important property of the cortex that helps to increase SA within a finite space, and may also improve connectivity by reducing distance between regions. Hence, gyrification may be what underlies the SA-GCA relationship. In previous phenotypic studies, a 3-dimensional gyrification index (3DGI) has been positively associated with cognitive ability and negatively associated with mild cognitive impairment, Alzheimer's disease, and psychiatric disorders affecting cognition. However, the differential genetic associations of 3DGI and SA with GCA are still unclear. We examined the heritability of 3DGI, and the phenotypic, genetic, and environmental associations of 3DGI with SA and GCA in a large sample of adult male twins (N = 512). Nearly 85% of the variance in 3DGI was due to genes, and 3DGI had a strong phenotypic and genetic association with SA. Both 3DGI and total SA had positive phenotypic correlations with GCA. However, the SA-GCA correlation remained significant after controlling for 3DGI, but not the other way around. There was also significant genetic covariance between SA and GCA, but not between 3DGI and GCA. Thus, despite the phenotypic and genetic associations between 3DGI and SA, our results do not support the hypothesis that gyrification underlies the association between SA and GCA. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. A rare CYP21A2 mutation in a congenital adrenal hyperplasia kindred displaying genotype-phenotype nonconcordance.

    Science.gov (United States)

    Khattab, Ahmed; Yuen, Tony; Al-Malki, Sultan; Yau, Mabel; Kazmi, Diya; Sun, Li; Harbison, Madeleine; Haider, Shozeb; Zaidi, Mone; New, Maria I

    2016-01-01

    Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency is caused by the autosomal recessive inheritance of mutations in the gene CYP21A2. CYP21A2 mutations lead to variable impairment of the 21-hydroxylase enzyme, which, in turn, is associated with three clinical phenotypes, namely, salt wasting, simple virilizing, and nonclassical CAH. However, it is known that a given mutation can associate with different clinical phenotypes, resulting in a high rate of genotype-phenotype nonconcordance. We aimed to study the genotype-phenotype nonconcordance in a family with three siblings affected with nonclassical CAH. All had hormonal evidence of nonclassical CAH, but this phenotype could not be explained by the genotype obtained from commercial CYP21A2 genetic testing, which revealed heterozygosity for the maternal 30 kb deletion mutation. We performed Sanger sequencing of the entire CYP21A2 gene in this family to search for a rare mutation that was not covered by commercial testing and found in the three siblings a second, rare c.1097G>A (p.R366H) mutation in exon 8. Computational modeling confirmed that this was a mild mutation consistent with nonclassical CAH. We recommend that sequencing of entire genes for rare mutations should be carried out when genotype-phenotype nonconcordance is observed in patients with autosomal recessive monogenic disorders, including CAH. © 2015 New York Academy of Sciences.

  13. Relationship between endophenotype and phenotype in ADHD

    Directory of Open Access Journals (Sweden)

    Buitelaar Jan K

    2008-01-01

    Full Text Available Abstract Background It has been hypothesized that genetic and environmental factors relate to psychiatric disorders through the effect of intermediating, vulnerability traits called endophenotypes. The study had a threefold aim: to examine the predictive validity of an endophenotypic construct for the ADHD diagnosis, to test whether the magnitude of group differences at the endophenotypic and phenotypic level is comparable, and to investigate whether four factors (gender, age, IQ, rater bias have an effect (moderation or mediation on the relation between endophenotype and phenotype. Methods Ten neurocognitive tasks were administered to 143 children with ADHD, 68 non-affected siblings, and 120 control children (first-borns and 132 children with ADHD, 78 non-affected siblings, and 113 controls (second-borns (5 – 19 years. The task measures have been investigated previously for their endophenotypic viability and were combined to one component which was labeled 'the endophenotypic construct': one measure representative of endophenotypic functioning across several domains of functioning. Results The endophenotypic construct classified children with moderate accuracy (about 50% for each of the three groups. Non-affected children differed as much from controls at the endophenotypic as at the phenotypic level, but affected children displayed a more severe phenotype than endophenotype. Although a potentially moderating effect (age and several mediating effects (gender, age, IQ were found affecting the relation between endophenotypic construct and phenotype, none of the effects studied could account for the finding that affected children had a more severe phenotype than endophenotype. Conclusion Endophenotypic functioning is moderately predictive of the ADHD diagnosis, though findings suggest substantial overlap exists between endophenotypic functioning in the groups of affected children, non-affected siblings, and controls. Results suggest other

  14. Phenotypic Approaches to Drought in Cassava: Review

    Directory of Open Access Journals (Sweden)

    Emmanuel eOkogbenin

    2013-05-01

    Full Text Available Cassava is an important crop in Africa, Asia, Latin America and the Caribbean. Cassava can be produced adequately in drought conditions making it the ideal food security crop in marginal environments. Although cassava can tolerate drought stress, it can be genetically improved to enhance productivity in such environments. Drought adaptation studies in over three decades in cassava have identified relevant mechanisms which have been explored in conventional breeding. Drought is a quantitative trait and its multigenic nature makes it very challenging to effectively manipulate and combine genes in breeding for rapid genetic gain and selection process. Cassava has a long growth cycle of 12 - 18 months which invariably contributes to a long breeding scheme for the crop. Modern breeding using advances in genomics and improved genotyping, is facilitating the dissection and genetic analysis of complex traits including drought tolerance, thus helping to better elucidate and understand the genetic basis of such traits. A beneficial goal of new innovative breeding strategies is to shorten the breeding cycle using minimized, efficient or fast phenotyping protocols. While high throughput genotyping have been achieved, this is rarely the case for phenotyping for drought adaptation. Some of the storage root phenotyping in cassava are often done very late in the evaluation cycle making selection process very slow. This paper highlights some modified traits suitable for early-growth phase phenotyping that may be used to reduce drought phenotyping cycle in cassava. Such modified traits can significantly complement the high throughput genotyping procedures to fast track breeding of improved drought tolerant varieties. The need for metabolite profiling, improved phenomics to take advantage of next generation sequencing technologies and high throughput phenotyping are basic steps for future direction to improve genetic gain and maximize speed for drought tolerance

  15. Subdimensions of social-communication impairment in autism spectrum disorder.

    Science.gov (United States)

    Bishop, Somer L; Havdahl, Karoline Alexandra; Huerta, Marisela; Lord, Catherine

    2016-08-01

    neurodevelopmental disorders might be facilitated by separating the most basic (or proximal) social-communication impairments from those that could arise from a range of other phenotypic variables. Identification of social-communication subdimensions also highlights potential avenues for measuring different types of social-communication impairments for different purposes (e.g. for differential diagnosis vs. response to treatment). © 2016 Association for Child and Adolescent Mental Health.

  16. Triple-loop learning as foundation for profound change, individual cultivation, and radical innovation. Construction processes beyond scientific and rational knowledge.

    OpenAIRE

    Peschl, Markus F.

    2007-01-01

    Purpose: Ernst von Glasersfeld’s question concerning the relationship between scientific/ rational knowledge and the domain of wisdom and how these forms of knowledge come about is the starting point. This article aims at developing an epistemological as well as methodological framework that is capable of explaining how profound change can be brought about in various contexts, such as in individual cultivation, in organizations, in processes of radical innovation, etc. This fra...

  17. The tell-tale: what do heart rate; skin temperature and skin conductance reveal about emotions of people with severe and profound intellectual disabilities?

    Science.gov (United States)

    Vos, Pieter; De Cock, Paul; Munde, Vera; Petry, Katja; Van Den Noortgate, Wim; Maes, Bea

    2012-01-01

    Identifying emotions in people with severe and profound intellectual disabilities is a difficult challenge. Since self-reports are not available, behaviour is the most used source of information. Given the limitations and caveats associated with using behaviour as the sole source of information about their emotions, it is important to supplement behavioural information with information from another source. As it is accepted that emotions consist of language, behaviour and physiology, in this article we investigated if physiology could give information about the emotions of people with severe and profound intellectual disabilities. To this aim we tested hypotheses derived from the motivational model of Bradley, Codispoti, Cuthbert, and Lang (2001) about the relation between heart rate and the valence of emotions and between heart rate, skin conductance and skin temperature and behavioural expressions of emotions of people with severe and profound intellectual disability. We presented 27 participants with 4 staff-selected negative and 4 staff-selected positive stimuli. The situations were videotaped and their heart rate, skin conductance and skin temperature was measured. Each behaviour of the participant was coded using the observational method developed by Petry and Maes (2006). As hypothesized, we found a lower heart rate when participants were presented with negative stimuli than when they were presented with positive stimuli in the first 6s of stimuli presentation. Their skin temperature was higher for the expression of low intensity negative emotions compared to the expression of low intensity positive emotions. The results suggest that, as with people without disability, heart rate and skin temperature can give information about the emotions of persons with severe and profound ID. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Emergent Innovation—a Socio-Epistemological Innovation Technology. Creating Profound Change and Radically New Knowledge as Core Challenges in Knowledge Management

    OpenAIRE

    Peschl, Markus F.; Fundneider, Thomas

    2008-01-01

    This paper introduces an alternative approach to innovation: Emergent Innovation. As opposed to radical innovation Emergent Innovation finds a balance and integrates the demand both for radically new knowledge and at the same time for an organic development from within the organization. From a knowledge management perspective one can boil down this problem to the question of how to cope with the new and with profound change in knowledge. This question will be dealt with in the first part of t...

  19. The study of 1H-MRS on monkey of resuscitation after cerebral selection ultra-profound hypothermic blood flow occlusion

    International Nuclear Information System (INIS)

    Pu Jun; Xu Wei; Fang Shaolong; Zhao Xinxiang; Feng Zhongtang; Jiang Jiyao

    2005-01-01

    Objective: To investigate the appearance and feature of 1 H/protion magnetic resonance spectroscopy ( 1 H-MRS) on resuscitation after cerebral selective ultra-profound hypothermic and blood flow occlusion. To study effects of cerebral biochemical metabolism after cerebral selective ultra-profound hypothermia and blood flow occlusion and to explore the validity and feasibility of it. Methods: Bilateral carotid arteries and jugular veins were clipped about 10 minutes before perfusion. Then selective cerebral circulation was established by perfusion of cooling lingers liquid through right internal carotid artery and flow out of left jugular vein with clip of other carotid arteries and jugular veins. Brain temperature reached (15.1 ± 0.9) degree C, while the body temperature maintained (32.50 ± 0.58) degree C. Cerebral blood recovered after 60 minutes of cerebral ischemia and monkey came back. The cerebral MAI and DWI as well as 1 H-MRS were examined 4, 24, 72 h, 21 days before and after cerebral selective ultro-profound hypothermia and blood flow occlusion. The peak of N-acetyl-aspartate (NAA), Choline (Cho), creatine and phosphocreatine (Cr, PCr) of VOL were compare with those of control group in different time. Results: MRI T 1 WI, MRI T 2 WI and DWI is normal in different time in different region; there was not a significant difference in the ratio of NAA/(Cr+PCr), Cho/(Cr+PCr) in ROI in different time in the different region in the light of statistical analysis (P>0.05). Conclusion: The light of cerebral biochemical metabolism, selective ultra-profound hypothermia is safety and may provide effective protective effects and safety during cerebral ischemia. (authors)

  20. Understanding Fetal Alcohol Spectrum Disorders (FASDs: Toward Identification of a Behavioral Phenotype

    Directory of Open Access Journals (Sweden)

    Kelly Nash

    2008-01-01

    Full Text Available Fetal alcohol spectrum disorders (FASDs currently represent the leading cause of mental retardation in North America, ahead of Down syndrome and cerebral palsy. The damaging effects of alcohol on the developing brain have a cascading impact on the social and neurocognitive profiles of affected individuals. Researchers investigating the profiles of children with FASDs have found impairments in learning and memory, executive functioning, and language, as well as hyperactivity, impulsivity, poor communication skills, difficulties with social and moral reasoning, and psychopathology. The primary goal of this review paper is to examine current issues pertaining to the identification of a behavioral phenotype in FASDs, as well as to address related screening and diagnostic concerns. We conclude that future research initiatives comparing children with FASDs to nonalcohol-exposed children with similar cognitive and socioemotional profiles should aid in uncovering the unique behavioral phenotype for FASDs.

  1. Identification of differentiation-stage specific molecular markers for the osteoblastic phenotype

    DEFF Research Database (Denmark)

    Twine, Natalie; Chen, Li; Wilkins, Marc

    to age-matched control (n=4). Using RNA-seq and cluster analysis, we identified a set of stage-specific molecular markers that define the progression of OB phenotype during ex vivo culture of hMSC, predict in vivo bone formation capacity of hMSC and can be employed to study the mechanisms of impaired......The phenotype of osteoblastic (OB) cells in culture is currently defined using a limited number of markers of low sensitivity and specificity which belong mostly to extracellular matrix proteins. Also, for clinical use of human skeletal (mesenchymal) stem cells (hMSC) in bone regeneration......, there is a need to identify predictive markers for in vivo bone forming capacity. Thus, we employed Illumina RNA sequencing (RNASeq) to examine changes in gene expression across 8 time points between 0-12 days of ex vivo OB differentiation of hMSC. We identified a subset of expressed genes as potentially...

  2. Hyperphosphatasia with mental retardation syndrome, expanded phenotype of PIGL related disorders

    Directory of Open Access Journals (Sweden)

    Ruqaiah Altassan

    2018-06-01

    Full Text Available Hypomorphic mutations in six different genes involved in the glycosylphosphatidylinositol (GPI biogenesis pathway are linked to Mabry syndrome (hyperphosphatasia with mental retardation syndrome, HPMRS. This report on the third affected family with a HPMRS phenotype caused by mutations in PIGL, confirming the seventh GPI biogenesis gene linked to HPMRS. Two siblings presented with the main features of HPMRS; developmental delay, cognitive impairment, seizure disorder, skeletal deformities, and high alkaline phosphatase. We identified two heterozygous mutations in the PIGL gene (P.Trp20Ter and p.Arg88Cys. PIGL mutations have been linked to another distinctive neuroectodermal disorder: CHIME syndrome. The clinical picture of our patients expands the spectrum of PIGL-related phenotypes. Keywords: GPI biogenesis, Hyperphosphatasia mental retardation syndrome (HPMRS, Mabry syndrome, PIGL gene, CHIME syndrome

  3. Reversible Age-Related Phenotypes Induced during Larval Quiescence in C. elegans

    Science.gov (United States)

    Roux, Antoine E.; Langhans, Kelley; Huynh, Walter; Kenyon, Cynthia

    2017-01-01

    Summary Cells can enter quiescent states in which cell cycling and growth are suspended. We find that during a long developmental arrest (quiescence) induced by starvation, newly-hatched C. elegans acquire features associated with impaired proteostasis and aging: mitochondrial fission, ROS production, protein aggregation, decreased proteotoxic-stress resistance, and at the organismal level, decline of mobility and high mortality. All signs of aging but one, the presence of protein aggregates, were reversed upon return to development induced by feeding. The endoplasmic reticulum receptor IRE-1 is completely required for recovery, and the downstream transcription factor XBP-1, as well as a protein kinase, KGB-1, are partially required. Interestingly, kgb-1(−) mutants that do recover fail to reverse aging-like mitochondrial phenotypes and have a short adult lifespan. Our study describes the first pathway that reverses phenotypes of aging at the exit of prolonged quiescence. PMID:27304510

  4. Characterization of the Pediatric Acute-Onset Neuropsychiatric Syndrome Phenotype

    Science.gov (United States)

    Patel, Priyal D.; McGuire, Joseph F.; Kennel, Allison; Mutch, P. Jane; Parker-Athill, E. Carla; Hanks, Camille E.; Lewin, Adam B.; Storch, Eric A.; Toufexis, Megan D.; Dadlani, Gul H.; Rodriguez, Carina A.

    2015-01-01

    Abstract Objective: Pediatric acute-onset neuropsychiatric syndrome (PANS) is a subtype of obsessive compulsive disorder (OCD) marked by an abrupt onset or exacerbation of neuropsychiatric symptoms. We aim to characterize the phenotypic presentation of youth with PANS. Methods: Forty-three youth (ages 4–14 years) meeting criteria for PANS were assessed using self-report and clinician-administered measures, medical record reviews, comprehensive clinical evaluation, and laboratory measures. Results: Youth with PANS presented with an early age of OCD onset (mean=7.84 years) and exhibited moderate to severe obsessive compulsive symptoms upon evaluation. All had comorbid anxiety and emotional lability, and scored well below normative means on all quality of life subscales. Youth with elevated streptococcal antibody titers trended toward having higher OCD severity, and presented more frequently with dilated pupils relative to youth without elevated titers. A cluster analysis of core PANS symptoms revealed three distinct symptom clusters that included core characteristic PANS symptoms, streptococcal-related symptoms, and cytokine-driven/physiological symptoms. Youth with PANS who had comorbid tics were more likely to exhibit a decline in school performance, visuomotor impairment, food restriction symptoms, and handwriting deterioration, and they reported lower quality of life relative to youth without tics. Conclusions: The sudden, acute onset of neuropsychiatric symptoms, high frequency of comorbidities (i.e., anxiety, behavioral regression, depression, and suicidality), and poor quality of life capture the PANS subgroup as suddenly and severely impaired youth. Identifying clinical characteristics of youth with PANS will allow clinicians to diagnose and treat this subtype of OCD with a more strategized and effective approach. PMID:25314221

  5. Changing course in ageing research: The healthy ageing phenotype.

    Science.gov (United States)

    Franco, Oscar H; Karnik, Kavita; Osborne, Gabrielle; Ordovas, Jose M; Catt, Michael; van der Ouderaa, Frans

    2009-05-20

    Ageing is often associated with the aged and the diseased, nevertheless ageing is a process that starts in-uterus and is characterised by a progressive functional loss but not necessarily by the presence of disease and poor quality of life. How to meander through life without crossing the confines of major chronic disease and cognitive and physical impairment remains one of the most relevant challenges for science and humankind. Delimiting that 'immaculate' trajectory - that we dub as the 'Healthy Ageing Phenotype' - and exploring solutions to help the population to stay or return to this trajectory should constitute the core focus of scientific research. Nevertheless, current efforts on ageing research are mainly focused on developing animal models to disentangle the human ageing process, and on age-related disorders often providing merely palliative solutions. Therefore, to identify alternative perspectives in ageing research, Unilever and the Medical Research Council (MRC) UK convened a Spark workshop entitled 'The Healthy Ageing Phenotype'. In this meeting, international specialists from complementary areas related to ageing research, gathered to find clear attributes and definitions of the 'Healthy Ageing Phenotype', to identify potential mechanisms and interventions to improve healthy life expectancy of the population; and to highlight areas within ageing research that should be prioritised in the future. General agreement was reached in recognising ageing research as a disaggregated field with little communication between basic, epidemiological and clinical areas of research and limited translation to society. A more holistic, multi-disciplinary approach emanating from a better understanding of healthy ageing trajectories and centred along human biological resilience, its maintenance and the reversibility from early deviations into pathological trajectories, is urgently required. Future research should concentrate on understanding the mechanisms that permit

  6. How musical engagement promotes well-being in education contexts: The case of a young man with profound and multiple disabilities

    Science.gov (United States)

    McFerran, Katrina S.; Shoemark, Helen

    2013-01-01

    Students with profound intellectual disabilities disorders (IDDs) have the right to participate in educational opportunities that recognize their unique resources and needs, as do all children. Because of their specific communication challenges, positive relationships with attentive communication partners are critical for success. In fact, the power of positive relationships in schools is recognized to be connected to student well-being more broadly. This article examines the case of one young man with profound IDD and his relationship with his music therapist using a duo-ethnographic informed paradigmatic case study. Video analysis based on multi-voice perspectives is used to generate hermeneutic phenomenological findings to closely examine the relationship between a young man with profound IDD and a music therapist. The voices of four allied health researchers were also gathered to inform the authors’ construction of an informed commentary on the phenomenon. The results suggest that the essence lay in a combination of attentive, responsive and creative being with the other person over time. Four principles of musical engagement were identified in the video footage as critical to the meaningful relationships through music: the music therapist listens; the music therapist takes responsibility for structure; spontaneous initiation is sought from the young person; and the relationship is built over time. These concepts are contextualized within a discussion of student well-being that is underpinned by positive relationships and leads to students achieving their full potential within diverse school contexts. PMID:23930986

  7. Speech perception, production and intelligibility in French-speaking children with profound hearing loss and early cochlear implantation after congenital cytomegalovirus infection.

    Science.gov (United States)

    Laccourreye, L; Ettienne, V; Prang, I; Couloigner, V; Garabedian, E-N; Loundon, N

    2015-12-01

    To analyze speech in children with profound hearing loss following congenital cytomegalovirus (cCMV) infection with cochlear implantation (CI) before the age of 3 years. In a cohort of 15 children with profound hearing loss, speech perception, production and intelligibility were assessed before and 3 years after CI; variables impacting results were explored. Post-CI, median word recognition was 74% on closed-list and 48% on open-list testing; 80% of children acquired speech production; and 60% were intelligible for all listeners or listeners attentive to lip-reading and/or aware of the child's hearing loss. Univariate analysis identified 3 variables (mean post-CI hearing threshold, bilateral vestibular areflexia, and brain abnormality on MRI) with significant negative impact on the development of speech perception, production and intelligibility. CI showed positive impact on hearing and speech in children with post-cCMV profound hearing loss. Our study demonstrated the key role of maximizing post-CI hearing gain. A few children had insufficient progress, especially in case of bilateral vestibular areflexia and/or brain abnormality on MRI. This led us to suggest that balance rehabilitation and speech therapy should be intensified in such cases. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  8. How musical engagement promotes well-being in education contexts: the case of a young man with profound and multiple disabilities.

    Science.gov (United States)

    McFerran, Katrina S; Shoemark, Helen

    2013-08-07

    Students with profound intellectual disabilities disorders (IDDs) have the right to participate in educational opportunities that recognize their unique resources and needs, as do all children. Because of their specific communication challenges, positive relationships with attentive communication partners are critical for success. In fact, the power of positive relationships in schools is recognized to be connected to student well-being more broadly. This article examines the case of one young man with profound IDD and his relationship with his music therapist using a duo-ethnographic informed paradigmatic case study. Video analysis based on multi-voice perspectives is used to generate hermeneutic phenomenological findings to closely examine the relationship between a young man with profound IDD and a music therapist. The voices of four allied health researchers were also gathered to inform the authors' construction of an informed commentary on the phenomenon. The results suggest that the essence lay in a combination of attentive, responsive and creative being with the other person over time. Four principles of musical engagement were identified in the video footage as critical to the meaningful relationships through music: the music therapist listens; the music therapist takes responsibility for structure; spontaneous initiation is sought from the young person; and the relationship is built over time. These concepts are contextualized within a discussion of student well-being that is underpinned by positive relationships and leads to students achieving their full potential within diverse school contexts.

  9. Impaired fear extinction learning and cortico-amygdala circuit abnormalities in a common genetic mouse strain

    OpenAIRE

    Hefner, Kathryn; Whittle, Nigel; Juhasz, Jaynann; Norcross, Maxine; Karlsson, Rose-Marie; Saksida, Lisa M.; Bussey, Timothy J.; Singewald, Nicolas; Holmes, Andrew

    2008-01-01

    Fear extinction is a form of new learning that results in the inhibition of conditioned fear. Trait deficits in fear extinction are a risk factor for anxiety disorders. There are few examples of naturally-occurring animal models of impaired extinction. The present study compared fear extinction in a panel of inbred mouse strains. This strain survey revealed an impairment in fear extinction in 129/SvImJ (129S1). The phenotypic specificity of this deficit was evaluated by comparing 129S1 and C5...

  10. Dystypia: isolated typing impairment without aphasia, apraxia or visuospatial impairment.

    Science.gov (United States)

    Otsuki, Mika; Soma, Yoshiaki; Arihiro, Shoji; Watanabe, Yoshimasa; Moriwaki, Hiroshi; Naritomi, Hiroaki

    2002-01-01

    We report a 60-year-old right-handed Japanese man who showed an isolated persistent typing impairment without aphasia, agraphia, apraxia or any other neuropsychological deficit. We coined the term 'dystypia' for this peculiar neuropsychological manifestation. The symptom was caused by an infarction in the left frontal lobe involving the foot of the second frontal convolution and the frontal operculum. The patient's typing impairment was not attributable to a disturbance of the linguistic process, since he had no aphasia or agraphia. The impairment was not attributable to the impairment of the motor execution process either, since he had no apraxia. Thus, his typing impairment was deduced to be based on a disturbance of the intermediate process where the linguistic phonological information is converted into the corresponding performance. We hypothesized that there is a specific process for typing which branches from the motor programming process presented in neurolinguistic models. The foot of the left second frontal convolution and the operculum may play an important role in the manifestation of 'dystypia'. Copyright 2002 S. Karger AG, Basel

  11. Latent Cognitive Phenotypes in De Novo Parkinson's Disease: A Person-Centered Approach.

    Science.gov (United States)

    LaBelle, Denise R; Walsh, Ryan R; Banks, Sarah J

    2017-08-01

    Cognitive impairment is an important aspect of Parkinson's disease (PD), but there is considerable heterogeneity in its presentation. This investigation aims to identify and characterize latent cognitive phenotypes in early PD. Latent class analysis, a data-driven, person-centered, cluster analysis was performed on cognitive data from the Parkinson's Progressive Markers Initiative baseline visit. This analytic method facilitates identification of naturally occurring endophenotypes. Resulting classes were compared across biomarker, symptom, and demographic data. Six cognitive phenotypes were identified. Three demonstrated consistent performance across indicators, representing poor ("Weak-Overall"), average ("Typical-Overall"), and strong ("Strong-Overall") cognition. The remaining classes demonstrated unique patterns of cognition, characterized by "Strong-Memory," "Weak-Visuospatial," and "Amnestic" profiles. The Amnestic class evidenced greater tremor severity and anosmia, but was unassociated with biomarkers linked with Alzheimer's disease. The Weak-Overall class was older and reported more non-motor features associated with cognitive decline, including anxiety, depression, autonomic dysfunction, anosmia, and REM sleep behaviors. The Strong-Overall class was younger, more female, and reported less dysautonomia and anosmia. Classes were unrelated to disease duration, functional independence, or available biomarkers. Latent cognitive phenotypes with focal patterns of impairment were observed in recently diagnosed individuals with PD. Cognitive profiles were found to be independent of traditional biomarkers and motoric indices of disease progression. Only globally impaired class was associated with previously reported indicators of cognitive decline, suggesting this group may drive the effects reported in studies using variable-based analysis. Longitudinal and neuroanatomical characterization of classes will yield further insight into the evolution of cognitive

  12. Reflex impairment, physiological stress, and discard mortality of European plaice Pleuronectes platessa in an otter trawl fishery

    DEFF Research Database (Denmark)

    Methling, Caroline; Skov, Peter Vilhelm; Madsen, Niels

    2017-01-01

    whether reflex impairment can predict short-term mortality in commercially trawled European plaice upon landing and after air exposure of up to 90 min. Sub-lethal stress was assessed by a suite of physiological variables. Over a 10-day period, mortality was monitored for a total of 199 plaice following...... trawl and air exposure of varying duration, and for 50 control fish scored for reflex impairment on board the vessel. Mortality was only observed in fish exposed to air for >60 min, and averaged 11.1% (95% CI = 7.1–16.3%). Reflex impairment was found to be a significant (P ... of mortality in a generalized linear model, excluding other initially included variables by using a stepwise method. Plasma cortisol, haematocrit, and plasma osmolality all indicated a profound and increasing level of stress with air exposure, accompanied by a near depletion of muscle phosphocreatine...

  13. Arterial stiffness and cognitive impairment.

    Science.gov (United States)

    Li, Xiaoxuan; Lyu, Peiyuan; Ren, Yanyan; An, Jin; Dong, Yanhong

    2017-09-15

    Arterial stiffness is one of the earliest indicators of changes in vascular wall structure and function and may be assessed using various indicators, such as pulse-wave velocity (PWV), the cardio-ankle vascular index (CAVI), the ankle-brachial index (ABI), pulse pressure (PP), the augmentation index (AI), flow-mediated dilation (FMD), carotid intima media thickness (IMT) and arterial stiffness index-β. Arterial stiffness is generally considered an independent predictor of cardiovascular and cerebrovascular diseases. To date, a significant number of studies have focused on the relationship between arterial stiffness and cognitive impairment. To investigate the relationships between specific arterial stiffness parameters and cognitive impairment, elucidate the pathophysiological mechanisms underlying the relationship between arterial stiffness and cognitive impairment and determine how to interfere with arterial stiffness to prevent cognitive impairment, we searched PUBMED for studies regarding the relationship between arterial stiffness and cognitive impairment that were published from 2000 to 2017. We used the following key words in our search: "arterial stiffness and cognitive impairment" and "arterial stiffness and cognitive impairment mechanism". Studies involving human subjects older than 30years were included in the review, while irrelevant studies (i.e., studies involving subjects with comorbid kidney disease, diabetes and cardiac disease) were excluded from the review. We determined that arterial stiffness severity was positively correlated with cognitive impairment. Of the markers used to assess arterial stiffness, a higher PWV, CAVI, AI, IMT and index-β and a lower ABI and FMD were related to cognitive impairment. However, the relationship between PP and cognitive impairment remained controversial. The potential mechanisms linking arterial stiffness and cognitive impairment may be associated with arterial pulsatility, as greater arterial pulsatility

  14. Cone-rod dystrophy and amelogenesis imperfecta (Jalili syndrome): phenotypes and environs.

    Science.gov (United States)

    Jalili, I K

    2010-11-01

    To report a new phenotype with additional data on the oculo-dental syndrome of cone-rod dystrophy (CRD) and amelogenesis imperfecta (AI) caused by mutations on CNNM4, a metal transporter, with linkage at achromatopsia locus 2q11 (Jalili syndrome). Three siblings aged 5, 6, and 10 years from a six-generation Arab family in Gaza City underwent full systemic, ophthalmic, and dental examinations, investigations and detailed genealogy. Subjects presented at early childhood with visual impairment and abnormal dentition together with photophobia and fine nystagmus increasing under photopic conditions, in the presence of normal fundi. Electrophysiologically, photopic flicker responses were impaired; scotopic responses were extinguished at the age of 10 years. Anterior open bite accompanied AI in all siblings. The syndrome formed 83% of CRD cases in the Gaza Strip, which has a prevalence of 1 : 10,000. On the basis of clinical features and electrophysiology, two phenotypes exist: an infancy onset form with progressive macular lesion and an early childhood onset form with normal fundi. More prevalent than previously thought, Jalili syndrome presents a model of the effect of different mutations of the same genetic defect, observations of the same phenotype at different stages of the natural history of the disease, and the influence of epigenetic and tissue-specific factors as causes of phenotypic variability. The paper calls for action to tackle consanguinity in endogamous communities, addresses the possible role of high fluoride levels in groundwater as a trigger for genetic mutations, and the use of red-tinted filter in cone disorders.

  15. A broad phenotypic screen identifies novel phenotypes driven by a single mutant allele in Huntington's disease CAG knock-in mice.

    Directory of Open Access Journals (Sweden)

    Sabine M Hölter

    Full Text Available Huntington's disease (HD is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG trinucleotide repeat in the HTT gene encoding huntingtin. The disease has an insidious course, typically progressing over 10-15 years until death. Currently there is no effective disease-modifying therapy. To better understand the HD pathogenic process we have developed genetic HTT CAG knock-in mouse models that accurately recapitulate the HD mutation in man. Here, we describe results of a broad, standardized phenotypic screen in 10-46 week old heterozygous HdhQ111 knock-in mice, probing a wide range of physiological systems. The results of this screen revealed a number of behavioral abnormalities in HdhQ111/+ mice that include hypoactivity, decreased anxiety, motor learning and coordination deficits, and impaired olfactory discrimination. The screen also provided evidence supporting subtle cardiovascular, lung, and plasma metabolite alterations. Importantly, our results reveal that a single mutant HTT allele in the mouse is sufficient to elicit multiple phenotypic abnormalities, consistent with a dominant disease process in patients. These data provide a starting point for further investigation of several organ systems in HD, for the dissection of underlying pathogenic mechanisms and for the identification of reliable phenotypic endpoints for therapeutic testing.

  16. Audiometric Characteristics of a Dutch DFNA10 Family With Mid-Frequency Hearing Impairment.

    Science.gov (United States)

    van Beelen, Eline; Oonk, Anne M M; Leijendeckers, Joop M; Hoefsloot, Elisabeth H; Pennings, Ronald J E; Feenstra, Ilse; Dieker, Hendrik-Jan; Huygen, Patrick L M; Snik, Ad F M; Kremer, Hannie; Kunst, Henricus P M

    2016-01-01

    Mutations in EYA4 can cause nonsyndromic autosomal dominant sensorineural hearing impairment (DFNA10) or a syndromic variant with hearing impairment and dilated cardiomyopathy. A mutation in EYA4 was found in a Dutch family, causing DFNA10. This study is focused on characterizing the hearing impairment in this family. Whole exome sequencing was performed in the proband. In addition, peripheral blood samples were collected from 23 family members, and segregation analyses were performed. All participants underwent otorhinolaryngological examinations and pure-tone audiometry, and 12 participants underwent speech audiometry. In addition, an extended set of audiometric measurements was performed in five family members to evaluate the functional status of the cochlea. Vestibular testing was performed in three family members. Two individuals underwent echocardiography to evaluate the nonsyndromic phenotype. The authors present a Dutch family with a truncating mutation in EYA4 causing a mid-frequency hearing impairment. This mutation (c.464del) leads to a frameshift and a premature stop codon (p.Pro155fsX). This mutation is the most N-terminal mutation in EYA4 found to date. In addition, a missense mutation, predicted to be deleterious, was found in EYA4 in two family members. Echocardiography in two family members revealed no signs of dilated cardiomyopathy. Results of caloric and velocity step tests in three family members showed no abnormalities. Hearing impairment was found to be symmetric and progressive, beginning as a mid-frequency hearing impairment in childhood and developing into a high-frequency, moderate hearing impairment later in life. Furthermore, an extended set of audiometric measurements was performed in five family members. The results were comparable to those obtained in patients with other sensory types of hearing impairments, such as patients with Usher syndrome type IIA and presbyacusis, and not to those obtained in patients with (cochlear

  17. Patterns of Semantic Memory Impairment in Mild Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Sven Joubert

    2008-01-01

    Full Text Available Although the semantic memory impairment has been largely documented in Alzheimer's disease, little is known about semantic memory in the preclinical phase of the disease (Mild Cognitive Impairment. The purpose of this study was to document the nature of semantic breakdown using a battery of tests assessing different aspects of conceptual knowledge: knowledge about common objects, famous people and famous public events. Results indicate that all domains of semantic memory were impaired in MCI individuals but knowledge about famous people and famous events was affected to a greater extent than knowledge about objects. This pattern of results suggests that conceptual entities with distinctive and unique properties may be more prone to semantic breakdown in MCI. In summary, results of this study support the view that genuine semantic deficits are present in MCI. It could be useful to investigate the etiological outcome of patients failing or succeeding at such tests.

  18. Assumptions of Decision-Making Capacity: The Role Supporter Attitudes Play in the Realisation of Article 12 for People with Severe or Profound Intellectual Disability

    Directory of Open Access Journals (Sweden)

    Joanne Watson

    2016-02-01

    Full Text Available The United Nations Convention on the Rights of Persons with Disabilities (UNCRPD was the first legally binding instrument explicitly focused on how human rights apply to people with disability. Amongst their obligations, consistent with the social model of disability, the Convention requires signatory nations to recognise that “…persons with disabilities enjoy legal capacity on an equal basis with others in all aspects of life” and mandates signatory nations to develop “…appropriate measures to provide access by persons with disability to the support they may require in exercising their legal capacity”. The Convention promotes supported decision-making as one such measure. Although Australia ratified the UNCRPD in 2008, it retains an interpretative declaration in relation to Article 12 (2, 3, 4, allowing for the use of substituted decision-making in situations where a person is assessed as having no or limited decision-making capacity. Such an outcome is common for people with severe or profound intellectual disability because the assessments they are subjected to are focused on their cognition and generally fail to take into account the interdependent nature of human decision-making. This paper argues that Australia’s interpretative declaration is not in the spirit of the Convention nor the social model of disability on which it is based. It starts from the premise that the intention of Article 12 is to be inclusive of all signatory nations’ citizens, including those with severe or profound cognitive disability. From this premise, arises a practical need to understand how supported decision-making can be used with this group. Drawing from evidence from an empirical study with five people with severe or profound intellectual disability, this paper provides a rare glimpse on what supported decision-making can look like for people with severe or profound intellectual disability. Additionally, it describes the importance of

  19. Small amounts of functional ATP7A protein permit mild phenotype

    DEFF Research Database (Denmark)

    Møller, Lisbeth Birk

    2015-01-01

    concentrations, ATP7A shifts to the post-Golgi compartments or to the plasma membrane to export copper out of the cell. Impaired copper-regulation trafficking has been observed for ATP7A mutants, but its impact on the clinical outcome is not clear. The major problem in patients with MD seems to be insufficient...... of missense mutations on structural models of the ATP7A protein suggests that affected conserved residues generally lead to a severe phenotype. The ATP7A protein traffics within the cells. At low copper levels, ATP7A locates to the Trans-Golgi Network (TGN) to load cuproenzymes with copper, whereas at higher...

  20. Inactivating mutations in ESCO2 cause SC phocomelia and Roberts syndrome: no phenotype-genotype correlation.

    Science.gov (United States)

    Schüle, Birgitt; Oviedo, Angelica; Johnston, Kathreen; Pai, Shashidhar; Francke, Uta

    2005-12-01

    The rare, autosomal recessive Roberts syndrome (RBS) is characterized by tetraphocomelia, profound growth deficiency of prenatal onset, craniofacial anomalies, microcephaly, and mental deficiency. SC phocomelia (SC) has a milder phenotype, with a lesser degree of limb reduction and with survival to adulthood. Since heterochromatin repulsion (HR) is characteristic for both disorders and is not complemented in somatic-cell hybrids, it has been hypothesized that the disorders are allelic. Recently, mutations in ESCO2 (establishment of cohesion 1 homolog 2) on 8p21.1 have been reported in RBS. To determine whether ESCO2 mutations are also responsible for SC, we studied three families with SC and two families in which variable degrees of limb and craniofacial abnormalities, detected by fetal ultrasound, led to pregnancy terminations. All cases were positive for HR. We identified seven novel mutations in exons 3-8 of ESCO2. In two families, affected individuals were homozygous--for a 5-nucleotide deletion in one family and a splice-site mutation in the other. In three nonconsanguineous families, probands were compound heterozygous for a single-nucleotide insertion or deletion, a nonsense mutation, or a splice-site mutation. Abnormal splice products were characterized at the RNA level. Since only protein-truncating mutations were identified, regardless of clinical severity, we conclude that genotype does not predict phenotype. Having established that RBS and SC are caused by mutations in the same gene, we delineated the clinical phenotype of the tetraphocomelia spectrum that is associated with HR and ESCO2 mutations and differentiated it from other types of phocomelia that are negative for HR.