Favorably skewed X‐inactivation accounts for neurological sparing in female carriers of Menkes disease

Desai V, Donsante A, Swoboda KJ, Martensen M, Thompson J, Kaler SG. Favorably skewed X‐inactivation accounts for neurological sparing in female carriers of Menkes disease. Classical Menkes disease is an X‐linked recessive neurodegenerative disorder caused by mutations in ATP7A, which is located at Xq13.1‐q21. ATP7A encodes a copper‐transporting P‐type ATPase and plays a critical role in development of the central nervous system. With rare exceptions involving sex chromosome aneuploidy or X‐autosome translocations, female carriers of ATP7A mutations are asymptomatic except for subtle hair and skin abnormalities, although the mechanism for this neurological sparing has not been reported. We studied a three‐generation family in which a severe ATP7A mutation, a 5.5‐kb genomic deletion spanning exons 13 and 14, segregated. The deletion junction fragment was amplified from the proband by long‐range polymerase chain reaction and sequenced to characterize the breakpoints. We screened at‐risk females in the family for this junction fragment and analyzed their X‐inactivation patterns using the human androgen‐receptor (HUMARA) gene methylation assay. We detected the junction fragment in the proband, two obligate heterozygotes, and four of six at‐risk females. Skewed inactivation of the X chromosome harboring the deletion was noted in all female carriers of the deletion (n = 6), whereas random X‐inactivation was observed in all non‐carriers (n = 2). Our results formally document one mechanism for neurological sparing in female carriers of ATP7A mutations. Based on review of X‐inactivation patterns in female carriers of other X‐linked recessive diseases, our findings imply that substantial expression of a mutant ATP7A at the expense of the normal allele could be associated with neurologic symptoms in female carriers of Menkes disease and its allelic variants, occipital horn syndrome, and ATP7A‐related distal motor neuropathy.     

Hunger and associated harms among injection drug users in an urban Canadian setting

Background  

Food insufficiency is often associated with health risks and adverse outcomes among marginalized populations. However, little is known about correlates of food insufficiency among injection drug users (IDU).     

Methamphetamine use and malnutrition among street-involved youth

We sought to explore the effect of crystal methamphetamine use on the risk of experiencing malnutrition among street-involved youth in Vancouver, Canada. Risk of malnutrition was defined as being hungry but not having enough money to buy food. Socio-demographic and drug use factors associated with risk of malnutrition were investigated using univariate and multivariate analysis among a prospective cohort of street-involved youth known as the At-Risk Youth Study (ARYS). Between September 2005 and December 2006, 509 street-involved youth were enrolled in ARYS, among whom 21% reported being at risk of malnutrition as defined above in the previous six months. In multivariate analysis, only non-injection crystal methamphetamine was significantly associated with being at risk of malnutrition among this cohort (Adjusted Odds Ratio [AOR] = 1.60, 95% Confidence Interval [CI]: 1.03 - 2.48, p = 0.036). Interventions seeking to address food insecurity among street youth may benefit from considering drug use patterns since methamphetamine use predicted higher risk in this setting.     

Castleman's disease in childhood: report of three cases and review of the literature

Background

Diarrhoea disease which has been attributed to poverty constitutes a major cause of morbidity and mortality in children aged five and below in most low-and-middle income countries. This study sought to examine the contribution of individual and neighbourhood socio-economic characteristics to caregiver's treatment choices for managing childhood diarrhoea at household level in sub-Saharan Africa.

Methods

Multilevel multinomial logistic regression analysis was applied to Demographic and Health Survey data conducted in 11 countries in sub-Saharan Africa. The unit of analysis were the 12,988 caregivers of children who were reported to have had diarrhoea two weeks prior to the survey period.

Results

There were variability in selecting treatment options based on several socioeconomic characteristics. Multilevel-multinomial regression analysis indicated that higher level of education of both the caregiver and that of the partner, as well as caregivers occupation were associated with selection of medical centre, pharmacies and home care as compared to no treatment. In contrast, caregiver's partners' occupation was negatively associated with selection medical centre and home care for managing diarrhoea. In addition, a low-level of neighbourhood socio-economic disadvantage was significantly associated with selection of both medical centre and pharmacy stores and medicine vendors.

Conclusion

In the light of the findings from this study, intervention aimed at improving on care seeking for managing diarrhoea episode and other childhood infectious disease should jointly consider the influence of both individual SEP and the level of economic development of the communities in which caregivers of these children resides.     

010 中年男性广泛性缺血性心脏病的自然病程

从英国24家综合医疗机构随机抽取年龄为40～59岁的7 735例病人(均为男性),依据调查表和心电图结果分为以下7个病组：Ⅰ组：已确诊的心肌梗死病人;Ⅱ组：隐匿性心肌梗死病人;Ⅲ组：已确诊的心绞痛病人;Ⅳ组：有心绞痛症侯群的病人;V组：有可疑心肌梗死症侯群的病人;Ⅵ组：心电图示心肌缺血或可能心肌梗死的病人,Ⅶ组：无缺血性心脏病(IHD)证据的病人。对以上各组病人进行15年随访,将这期间调查对象发生的一系列致命及非致命的并发症分别与相应病组加以联系评估。     

Psychotherapeutengesetz / Arztregistereintragung

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