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181.
Pascal Molenberghs Cline R. Gillebert Hanne Schoofs Patrick Dupont Ronald Peeters Rik Vandenberghe 《Neuropsychologia》2009,47(13):2866-2875
The Sustained Attention to Response task is a classical neuropsychological test that has been used by many centres to characterize the attentional deficits in traumatic brain injury, ADHD, autism and other disorders. During the SART a random series of digits 1–9 is presented repeatedly and subjects have to respond to each digit (go trial) except the digit ‘3’ (no-go trial). Using voxel-based lesion symptom mapping (VLSM) in a consecutive series of 44 ischemic unifocal non-lacunar hemispheric stroke patients we determined the neuroanatomy of 4 SART parameters: commission and omission error rate, reaction time variability and post-error slowing. Lesions of the right inferior frontal gyrus significantly increased commission error rate. Lesions of the middle third of the right inferior frontal sulcus (IFS) reduced post-error slowing, a measure of how well subjects can utilize errors to adjust cognitive resource allocation. Omissions and reaction time variability had less localising value in our sample. To conclude, commission errors and post-error slowing in the SART mainly probe right inferior frontal integrity. 相似文献
182.
Fleur S Van Dijk Isabel M Nesbitt Peter G J Nikkels Ann Dalton Ernie M H F Bongers Jiddeke M van de Kamp Yvonne Hilhorst-Hofstee Nicolette S Den Hollander Augusta M A Lachmeijer Carlo L Marcelis Gita M B Tan-Sindhunata Rick R van Rijn Hanne Meijers-Heijboer Jan M Cobben Gerard Pals 《European journal of human genetics : EJHG》2009,17(12):1560-1569
Autosomal recessive lethal and severe osteogenesis imperfecta (OI) is caused by the deficiency of cartilage-associated protein (CRTAP) and prolyl-3-hydroxylase 1 (P3H1) because of CRTAP and LEPRE1 mutations. We analyzed five families in which 10 individuals had a clinical diagnosis of lethal and severe OI with an overmodification of collagen type I on biochemical testing and without a mutation in the collagen type I genes. CRTAP mutations not described earlier were identified in the affected individuals. Although it seems that one important feature of autosomal recessive OI due to CRTAP mutations is the higher consistency of radiological features with OI type II-B/III, differentiation between autosomal dominant and autosomal recessive OI on the basis of clinical, radiological and biochemical investigations proves difficult in the affected individuals reported here. These observations confirm that once a clinical diagnosis of OI has been made in an affected individual, biochemical testing for overmodification of collagen type I should always be combined with molecular genetic analysis of the collagen type I genes. If no mutations in the collagen type I genes are found, additional molecular genetic analysis of the CRTAP and LEPRE1 genes should follow. This approach will allow proper identification of the genetic cause of lethal or severe OI, which is important in providing prenatal diagnosis, preimplantation genetic diagnosis and estimating recurrence risk. 相似文献
183.
184.
Yvonne B?ttcher Hanne Unbehauen Nora Kl?ting Karen Ruschke Antje K?rner Dorit Schleinitz Anke T?njes Beate Enigk Sara Wolf Kerstin Dietrich Moritz Koriath Gerhard Harry Scholz Yu-Hua Tseng Arne Dietrich Michael R. Sch?n Wieland Kiess Michael Stumvoll Matthias Blüher Peter Kovacs 《Diabetes》2009,58(9):2119-2128
OBJECTIVE
Members of the family of bone morphogenetic proteins (BMPs) are important regulators of adipogenesis. We examined the role of the BMP receptor 1A gene (BMPR1A) in the pathophysiology of human obesity.RESEARCH DESIGN AND METHODS
We measured BMPR1A mRNA expression in paired samples of visceral and subcutaneous adipose tissue from 297 subjects and sequenced the BMPR1A in 48 nonrelated white subjects. Twenty-one representative variants including HapMap tagging single nucleotide polymorphisms (SNPs) were then genotyped for association studies in German whites (n = 1,907). For replication analyses, we used a population of Sorbs from Germany (n = 900) and German childhood cohorts (n = 1,029 schoolchildren and 270 obese children).RESULTS
mRNA expression of the BMPR1A was significantly increased in both visceral and subcutaneous adipose tissue of overweight and obese subjects compared with lean subjects (P < 0.05). In a case-control study, four SNPs (rs7095025, rs11202222, rs10788528, and rs7922846) were nominally associated with obesity (adjusted P < 0.05). For three SNPs (rs7095025, rs11202222, and rs10788528), the association with obesity was confirmed in the independent cohort of Sorbs (adjusted P < 0.005). Consistent with this, BMPR1A SNPs were nominally associated with obesity-related quantitative traits in nondiabetic subjects in both adult cohorts. Furthermore, homozygous carriers of the obesity risk alleles had higher BMPR1A mRNA expression in fat than noncarriers.CONCLUSIONS
Our data suggest that genetic variation in the BMPR1A may play a role in the pathophysiology of human obesity, possibly mediated through effects on mRNA expression.Recent advances in the field of genetics of complex diseases succeeded in identification of novel genes associated with human obesity (1–6). However, in contrast to fat mass and obesity associated (FTO) that turned out to be the first robustly replicated susceptibility signal for polygenic obesity (1,2), several other genes such as GAD2 and INSIG2 failed to “survive” replication efforts following initial studies (7,8). Therefore, along with the highly powered genome-wide association studies highlighting both expected and unexpected genes/variants, the candidate gene approach focusing on genes with plausible functional relevance can still substantially contribute to a better understanding of the etiology of complex disorders such as obesity and its sequelae.Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β (TGF-β) superfamily and are involved in control of multiple key steps of embryonic development and differentiation (9–11). BMPs have been shown to have different roles in adipogenesis depending on the differentiation stage, the concentrations of BMP, as well as the presence of other extracellular and intracellular factors (12–15). Cellular responses to BMPs have been shown to be mediated by the formation of a hetero-oligomeric complex of the type 1 and type 2 BMP receptors (16–18). Among different isoforms, three type 1 receptors (BMPR1A/ALK3, BMPR1B/ALK6, and ACVR1A/ALK2) and three type 2 receptors (BMPR2, ACTR2A, and ACTR2B) mediate most of the effects of BMPs (9). Of the different BMPR isoforms, BMPR1A is particularly interesting to adipocyte biology since it has been shown to specialize in adipocyte differentiation in vitro (19). Therefore, BMPR1A seems to be a convincing candidate gene possibly involved in the pathogenesis of human obesity and type 2 diabetes.Here, we examined the role of BMPR1A in the pathophysiology of human obesity. We measured mRNA expression of BMPR1A in paired samples of visceral and subcutaneous adipose tissue and examined its relation with anthropometric traits such as BMI, waist-to-hip ratio (WHR), and measures of glucose metabolism. Further, we investigated whether genetic variation within the BMPR1A might affect adipose tissue BMPR1A mRNA expression. Twenty-one representative variants including HapMap tagging single nucleotide polymorphisms (SNPs) were initially genotyped for association studies in German whites. For replication analyses, we used a population of Sorbs from Germany and German children cohorts (schoolchildren and obese children). 相似文献185.
Vita W Jongen Thijs Reyniers Zorah MH Ypma Maarten F Schim van der Loeff Udi Davidovich Hanne ML Zimmermann Liza Coyer Mark AM van den Elshout Henry JC de Vries Kristien Wouters Tom Smekens Bea Vuylsteke Maria Prins Marie Laga Elske Hoornenborg 《Journal of the International AIDS Society》2021,24(8)
IntroductionDaily and event‐driven PrEP are both efficacious in reducing the risk for HIV infection. However, the practice of event‐driven PrEP (edPrEP) is less well studied, in particular when provided as an alternative to daily PrEP. We studied regimen preferences and switches, and sexually transmitted infection (STI) incidence.MethodsWe analysed pooled data from two prospective cohort studies among MSM: Be‐PrEP‐ared, Belgium and AMPrEP, the Netherlands. In both projects, participants could choose between daily and edPrEP at three‐monthly study visits, when they were also screened for sexually transmitted infections including hepatitis C (HCV). We assessed the proportion choosing each regimen, and the determinants of choosing edPrEP at baseline. Additionally, we compared the incidence rates (IRs) of HCV, syphilis and chlamydia or gonorrhoea between regimens using Poisson regression. The study period was from 3 August 2015 until 24 September 2018.Results and discussionWe included 571 MSM, of whom 148 (25.9%) chose edPrEP at baseline. 31.7% of participants switched regimen at least once. After 28 months, 23.5% used edPrEP. Older participants (adjusted odds ratio (aOR) = 1.38 per 10 years, 95% confidence interval (CI) = 1.15 to 1.64) and those unemployed (aOR = 1.68, 95% CI = 1.03 to 1.75) were more likely to initially choose edPrEP. IR of HCV and syphilis did not differ between regimens, but the IR of chlamydia/gonorrhoea was higher among daily users (adjusted incidence rate ratio = 1.61, 95% CI = 1.35 to 1.94).ConclusionsA quarter of participants chose edPrEP at baseline and at 28 months this proportion was similar. Although the IR of HCV and syphilis were similar in the two regimens, the lower incidence of chlamydia and gonorrhoea among edPrEP users may suggest that less frequent STI testing of this group could be considered. 相似文献
186.
Developmental dyslexia is strongly associated with a phonological deficit. Yet, implicit phonological processing (in)capacities in dyslexia remain relatively unexplored. Here we use a neurophysiological response sensitive to experience-dependent auditory memory traces, the mismatch negativity (MMN), to investigate implicit phonological processing of natural speech in dyslexic and normally reading children. In a modified passive oddball design that minimizes the contribution of acoustic processes, we presented non-words that differed by the degree of phonotactic probability, i.e. the distributional frequency of phoneme combinations in a given language. Overall morphology of ERP responses to the non-words indicated comparable processing of acoustic-phonetic stimulus differences in both children groups. Consistent with previous findings in adults, normally reading children showed a significantly stronger MMN response to the non-word with high phonotactic probability (notsel) as compared to the non-word with low phonotactic probability (notkel), suggesting auditory cortical tuning to statistical regularities of phoneme combinations. In contrast, dyslexic children did not show this sensitivity to phonotactic probability. These findings indicate that the phonological problems often reported in dyslexia relate to a subtle deficit in the implicit phonetic-phonological processing of natural speech. 相似文献
187.
Contrast sensitivity is one of several factors necessary to obtain good visual quality. The aim of this study was to develop normal data on the Cambridge Low Contrast Gratings test in children and to compare these data with data from a group of children with developmental delay. Ninety-nine normal children (aged 2-14 years) and 146 children with developmental delay were tested with the contrast sensitivity test. All children had normal visual acuity and stereopsis. The normal children had an age-dependent development in contrast sensitivity, and adult level was reached after the age of 10 years. A significantly lower score was found in children with developmental delay compared to normal children. The Cambridge Low Contrast Gratings test is suitable for preschool children and children with developmental delay because of its simplicity, and it might be a valuable tool in diagnosing ophthalmologic diseases in children with developmental delay. 相似文献
188.
Common variable immune deficiency and lung transplantation 总被引:1,自引:0,他引:1
Burton CM Milman N Andersen CB Marquart H Iversen M 《Scandinavian journal of infectious diseases》2007,39(4):362-367
We report on a male patient with bronchiectasis secondary to common variable immune deficiency (CVID) receiving lung transplantation. The patient had been diagnosed with CVID many y prior to right-sided single lung transplantation and was receiving appropriate immunoglobulin substitution therapy. He received antithymocyte globulin induction and maintenance triple therapy with cyclosporine, azathioprine and prednisolone. The early post-operative course was complicated by the development of severe acute cellular rejection and organizing pneumonia. Despite immunoglobulin replacement and antifungal prophylaxis and treatment, Aspergillus fumigatus was repeatedly cultured from bronchoalveolar lavage fluid, 18 months after transplantation. The patient died following a protracted period of repeated hospital admissions, 46 months after transplantation. A review of the literature suggests that many CVID patients appear to have had a complicated post-operative course after lung- and other solid-organ transplantation, and highlights the need for the establishment of international registries for transplanted patients with uncommon conditions. 相似文献
189.
Gut microbiota composition and development of atopic manifestations in infancy: the KOALA Birth Cohort Study 总被引:1,自引:0,他引:1
Penders J Thijs C van den Brandt PA Kummeling I Snijders B Stelma F Adams H van Ree R Stobberingh EE 《Gut》2007,56(5):661-667
BACKGROUND AND AIMS: Perturbations in intestinal microbiota composition due to lifestyle changes may be involved in the development of atopic diseases. We examined gut microbiota composition in early infancy and the subsequent development of atopic manifestations and sensitisation. METHODS: The faeces of 957 infants aged 1 month and participating in the KOALA Birth Cohort Study were analysed using quantitative real-time PCR. Information on atopic symptoms (eczema, wheeze) and potential confounders was acquired through repeated questionnaires. Total and specific IgE were measured in venous blood samples collected during home visits when the infant was 2 years old. During these home visits a clinical diagnosis of atopic dermatitis was made according to the UK-Working Party criteria. RESULTS: The presence of Escherichia coli was associated with a higher risk of developing eczema (OR(adj) = 1.87; 95% CI 1.15 to 3.04), this risk being increased with increasing numbers of E coli (p(for trend) = 0.016). Infants colonised with Clostridium difficile were at higher risk of developing eczema (OR(adj) = 1.40; 95% CI 1.02 to 1.91), recurrent wheeze (OR(adj) = 1.75; 95% CI 1.09 to 2.80) and allergic sensitisation (OR(adj) = 1.54; 95% CI 1.02 to 2.31). Furthermore, the presence of C difficile was also associated with a higher risk of a diagnosis of atopic dermatitis during the home visit (OR(adj) = 1.73; 95% CI 1.08 to 2.78). CONCLUSION: This study demonstrates that differences in gut microbiota composition precede the development of atopy. Since E coli was only associated with eczema and C difficile was associated with all atopic outcomes, the underlying mechanisms explaining these association may be different. 相似文献
190.
Bilde L Rud Svenning A Dollerup J Baekke Borgeskov H Lange P 《Respiratory medicine》2007,101(3):539-546
This paper describes a population-based study of health care resource use of patients with chronic obstructive pulmonary disease (COPD) compared to non-COPD controls. Through a screening of the Danish Patient Registry for patients admitted with COPD diagnoses for a 5-year period, 1998-2002, 66,000 individuals with COPD still alive at the beginning of 2002 were identified. Their use of health care resources in 2002 were compared with equivalent data, stratified for age, sex and mortality rates, for a control population without COPD based on data for the 300,000 remaining patients on the Danish Patient Registry in 2002. Results indicated that the gross cost of treating patients with COPD in the Danish somatic hospital and primary health care sector corresponded to 10% of the total cost of treating patients of 40 years or more. The net cost for COPD patients was 1.9 billion DKK (256 million euro), 6% of the total annual costs of treating the population of 40 years or more. The gross cost related to any disease and the net cost reflected the resource use which could be attributed to COPD and its related diagnoses. The incidence of inpatient hospital admissions was almost four times higher in the COPD population than in the control group. COPD patients contacted their general practitioner 12 times more per year than non-COPD controls, but for specialist and paramedic treatment in the primary care sector there was no significant difference between COPD patients and non-COPD controls. Only one third of the COPD costs were due to treatment of COPD as the primary diagnosis. The remaining two-thirds of the COPD-related costs were mainly due to admissions for other diseases such as cardio-vascular diseases, other respiratory diseases, and cancer. 相似文献