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71.
I. Filges E. Nosova E. Bruder S. Tercanli K. Townsend W.T. Gibson B. Röthlisberger K. Heinimann J.G. Hall C.Y. Gregory‐Evans W.W. Wasserman P. Miny J.M. Friedman 《Clinical genetics》2014,86(3):220-228
Gene discovery using massively parallel sequencing has focused on phenotypes diagnosed postnatally such as well‐characterized syndromes or intellectual disability, but is rarely reported for fetal disorders. We used family‐based whole‐exome sequencing in order to identify causal variants for a recurrent pattern of an undescribed lethal fetal congenital anomaly syndrome. The clinical signs included intrauterine growth restriction (IUGR), severe microcephaly, renal cystic dysplasia/agenesis and complex brain and genitourinary malformations. The phenotype was compatible with a ciliopathy, but not diagnostic of any known condition. We hypothesized biallelic disruption of a gene leading to a defect related to the primary cilium. We identified novel autosomal recessive truncating mutations in KIF14 that segregated with the phenotype. Mice with autosomal recessive mutations in the same gene have recently been shown to have a strikingly similar phenotype. Genotype–phenotype correlations indicate that the function of KIF14 in cell division and cytokinesis can be linked to a role in primary cilia, supported by previous cellular and model organism studies of proteins that interact with KIF14. We describe the first human phenotype, a novel lethal ciliary disorder, associated with biallelic inactivating mutations in KIF14. KIF14 may also be considered a candidate gene for allelic viable ciliary and/or microcephaly phenotypes. 相似文献
72.
Eye misalignment, called strabismus, is amongst the most common phenotypes observed, occurring in up to 5% of individuals in a studied population. While misalignment is frequently observed in rare complex syndromes, the majority of strabismus cases are non‐syndromic. Over the past decade, genes and pathways associated with syndromic forms of strabismus have emerged, but the genes contributing to non‐syndromic strabismus remain elusive. Genetic testing for strabismus risk may allow for earlier diagnosis and treatment, as well as decreased frequency of surgery. We review human and model organism literature describing non‐syndromic strabismus, including family, twin, linkage, and gene expression studies. Recent advances in the genetics of Duane retraction syndrome are considered, as relatives of those impacted show elevated familial rates of non‐syndromic strabismus. As whole genome sequencing efforts are advancing for the discovery of the elusive strabismus genes, this overview is intended to support the interpretation of the new findings. 相似文献
73.
Heidi Hjelmeland Tore C. Stiles Unni Bille-brahe Aini Ostamo Ellinor Salander Renberg Danuta Wasserman 《Archives of Suicide Research》2013,17(3):209-225
Abstract The main aim of the study was to examine whether various aspects of suicidal intent or various motives for an index parasuicide can predict nonfatal or fatal repetition of suicidal behaviour. 776 parasuicide patients from 5 Nordic regions participating in the WHO/EURO Multicentre Study on Parasuicide were followed for one year. The Suicide Intent Scale (SIS) and the Motives for Parasuicide Questionnaire (MPQ) were used as predictor variables. A low level of suicidal intent predicted nonfatal repetition. The motive “make things easier for someone” differentiated female repeaters From male repeaters. The report of an unclear motive was the only significant predictor of fatal repetition. Suicidal intent and various motives for a parasuicide have some value in predicting repetition of suicidal behaviour. but should, perhaps. in future studies be combined with other variables in order to increase the predictive value. 相似文献
74.
Katz AR Komeya AY Soge OO Kiaha MI Lee MV Wasserman GM Maningas EV Whelen AC Kirkcaldy RD Shapiro SJ Bolan GA Holmes KK 《Clinical infectious diseases》2012,54(6):841-843
We report on the first Neisseria gonorrhoeae isolate in the United States identified with high-level resistance to azithromycin. This report discusses the epidemiologic case investigation, the molecular studies of resistance-associated mutations and N. gonorrhoeae multiantigen sequence typing, and challenges posed by emerging gonococcal antimicrobial resistance. 相似文献
75.
76.
Aledort L Bullinger M von Mackensen S Wasserman J Young NL Globe D;Health Related Quality of Life Expert Working Group of the International Prophylaxis Study Group 《Haemophilia》2012,18(3):e154-e157
The very high cost of haemophilia care, including the increase in use of factor prophylaxis in both children and adults requires that funders of clotting factor concentrates require objective measures of health, such as joint status and quality of life (QOL). Many clinical trials, especially those for licensing of new products, are including QOL instruments in their protocols to evaluate the patients' perspective of wellbeing before and during therapy. This article gives a perspective on QOL the importance of QOL measurement in the field of haemophilia and its impact on patient outcome. 相似文献
77.
Despite caregivers' impact on suicidal patients' compliance with treatment and suicide prevention, little is known about mental-health professionals' perceptions of work with suicidal patients. The roles of psychiatric staff's training and supervision in the care of suicidal patients were investigated by means of a postal questionnaire sent to a random sample of 1543 psychiatric staff members. The response rates were 71% for psychiatrists and 57% for nurses and assistant nurses. The responses of 53 psychiatrists, 164 nurses and 333 assistant nurses working with suicidal patients on a regular basis were compared and analysed using the Kruskal-Wallis test. Thirty-five per cent of the assistant nurses, 43% of the nurses and 74% of the psychiatrists who worked with suicidal patients on a regular basis perceived that they were sufficiently trained for this work, while 75% of the assistant nurses, 72% of the nurses and 34% of the psychiatrists received supervision in their work with suicidal patients. In spite of receiving supervision, nursing staff who perceived that they lacked training reported uncertainties in their work with suicidal patients to a larger extent than those who perceived that their training was sufficient. Uncertainties were significantly more prevalent among nursing staff than among psychiatrists. Basic and specific training in suicidology is needed and cannot be replaced solely by supervision, since psychiatric staff often have to deal with suicidal patients in emergency situations and must be able to rely on their own skills. 相似文献
78.
To promote implementation of suicide-preventive activities, the Swedish National Centre for Suicide Research and Prevention of Mental Ill-Health (NASP) introduced a 200-h academic, postgraduate educational programme (based on the training-of-trainers model) in suicide prevention. This programme was provided at Karolinska Institute, Stockholm, for key persons in psychiatric care. Twenty-nine key persons from 11 psychiatric intervention clinics in Stockholm County attended the first course. Preconditions for implementing suicide-preventive activities were assessed by means of semi-structured interviews with all course participants still working in the intervention clinics (n=10). In all but one of these 10 clinics, a wide range of suicide-preventive activities had been implemented as a result of the NASP course. Activities varied in scope, but the key persons seemed to have succeeded in pinpointing the key elements in suicide prevention – the need for specific knowledge about the suicidal process and for well-defined suicide-preventive routines. However, organizational factors and staff turnover were obstacles to maintaining and making the activities routine. There is a need to strengthen the course participants’ formal roles as implementers and encourage the clinical management in their continuous implementation of suicide-preventive activities. 相似文献
79.
David I. Wasserman Haoran G. Wang Asim J. Rashid Sheena A. Josselyn John S. Yeomans 《The European journal of neuroscience》2013,38(5):2774-2785
M5 muscarinic acetylcholine receptors expressed on ventral tegmental dopamine (DA) neurons are needed for opioid activation of DA outputs. Here, the M5 receptor gene was bilaterally transfected into neurons in the ventral tegmental area (VTA) or the adjacent rostromedial tegmental nucleus (RMTg) in mice by means of a Herpes simplex viral vector (HSV) to increase the effect of endogenous acetylcholine. Three days after HSV‐M5 gene infusion in VTA sites, morphine‐induced locomotion more than doubled at two doses, while saline‐induced locomotion was unaffected. When the HSV‐M5 gene was infused into the adjacent RMTg, morphine‐induced locomotion was strongly inhibited. The sharp boundary between these opposing effects was found where tyrosine hydroxylase (TH) and cholinesterase labelling decreases (?4.00 mm posterior to bregma). The same HSV‐M5 gene transfections in M5 knockout mice induced even stronger inhibitory behavioural effects in RMTg but more variability in VTA sites due to stereotypy. The VTA sites where HSV‐M5 increased morphine‐induced locomotion receive direct inputs from many RMTg GAD‐positive neurons, and from pontine ChAT‐positive neurons, as shown by cholera‐toxin B retrograde tracing. Therefore, morphine‐induced locomotion was decreased by M5 receptor gene expression in RMTg GABA neurons that directly inhibit VTA DA neurons. Conversely, enhancing M5 receptor gene expression on VTA DA neurons increased morphine‐induced locomotion via cholinergic inputs. 相似文献
80.
Kenneth N. Levy Joseph E. Beeney Rachel H. Wasserman John F. Clarkin 《Psychotherapy research》2013,23(4):413-422
This study evaluated the psychometric properties of the 4 scales of the Behavioral Health Questionnaire-20 (BHQ-20): Global Mental Health, Well-Being, Symptoms, and Life Functioning. Four samples were used: community adults, college students, college students in counseling, and adults in outpatient psychotherapy. Support was found for internal consistency and 2-week test-retest reliability. For construct validity, the BHQ-20 scales distinguished levels of pathology among the samples and were sensitive to improvement across 3 psychotherapy sessions. Concurrent validity correlations with the scales of established measures were at least moderately high. Higher correlations were also found between the BHQ-20 scales and the nonanalogous scales of the established measures. These results, along with high correlations among the BHQ-20 scales, indicated the presence of 1 primary mental health dimension accounting for the variance. The BHQ-20 was proven to be a generally reliable, valid questionnaire that is distinguished by the efficiency with which it assesses mental health. 相似文献