Fetal Bowel Abnormalities Suspected by Ultrasonography in Microvillus Inclusion Disease:Prevalence and Clinical Significance

Microvillus inclusion disease (MVID) is a rare, inherited, congenital, diarrheal disorder that is invariably fatal if left untreated. Within days after birth, MVID presents as a life-threatening emergency characterized by severe dehydration, metabolic acidosis, and weight loss. Diagnosis is cumbersome and can take a long time. Whether MVID could be diagnosed before birth is not known. Anecdotal reports of MVID-associated fetal bowel abnormalities suspected by ultrasonography (that is, dilated bowel loops and polyhydramnios) have been published. These are believed to be rare, but their prevalence in MVID has not been investigated. Here, we have performed a comprehensive retrospective study of 117 published MVID cases spanning three decades. We find that fetal bowel abnormalities in MVID occurred in up to 60% of cases of MVID for which prenatal ultrasonography or pregnancy details were reported. Suspected fetal bowel abnormalities appeared in the third trimester of pregnancy and correlated with postnatal, early-onset diarrhea and case-fatality risk during infancy. Fetal bowel dilation correlated with MYO5B loss-of-function variants. In conclusion, MVID has already started during fetal life in a significant number of cases. Genetic testing for MVID-causing gene variants in cases where fetal bowel abnormalities are suspected by ultrasonography may allow for the prenatal diagnosis of MVID in a significant percentage of cases, enabling optimal preparation for neonatal intensive care

Age differences in the association between sleep and Alzheimer\u27s disease biomarkers in the EPAD cohort

INTRODUCTION: We aimed to determine the independent association between sleep quality and Alzheimer\u27s disease (AD) biomarkers, and whether the associations differ with age. METHODS: We included 1240 individuals aged ≥50, without dementia from the RESULTS: For the youngest age tertile, shorter sleep duration and higher sleep efficiency were associated with greater p-tau/Aβ42 ratio. For the oldest tertile, longer sleep latency was associated with greater p-tau/Aβ42. DISCUSSION: Differential relationships between sleep and AD pathology depend on age. Short sleep duration and sleep efficiency are relevant in middle age whereas time taken to fall asleep is more closely linked to AD biomarkers in later life. HIGHLIGHTS: This study shows age differences in the link between sleep and AD biomarkers.Shorter sleep was associated with greater p-tau/Aβ42 ratio in middle age.The association was independent of genetic, vascular, and neuroimaging markers of AD

Screening A Trinucleotide Repeat Expansion: How precise PCR can be?

ABSTRACT Background. Trinucleotide Repeat Expansion (TRE) in human DNA could lead to various diseases. An expanded CAG repeat (>31 or 37 repeats, depends on the ethnicity) in Androgen Receptor gene is suggested to be associated with the occurrence of isolated hypospadias. In an effort to identify the exact numbers of repeats, sequencing has been the most favored method to be conducted despite its cost. Objective. This study wished to investigate the possibilities of using Polymerase Chain Reaction (PCR) method to screen expanded repeats in isolated hypospadias, as one of the TRE diseases. Materials and Methods. Numbers of CAG repeat in twelve hypospadias patients and one normal male was first predicted from the visualization of PCR products in 3% agarose gel electrophoreses with 20 bp ladder marker before it was finally sequenced. Results. Two samples gave the same exact result, while the rest showed a range of 1-11 bp differences. Statistically, there was a significant difference between the mean of CAG repeats from PCR method (M=26.1667, SD=6.71272) and the mean of CAG repeats from sequencing (M=23.75, SD=5.70685); t(11)= 4.570, p=0.001. Furthermore, the sensitivity of PCR was 100% and the specificity was 83.33%. Conclusion. It can be concluded that PCR method could be used as a screening method in identifying TRE with large numbers of repeats. However, PCR in TRE disease with small numbers of expanded repeats needs to be followed by sequencing in order to obtain the exact numbers of repeats.   Keywords: Trinucleotide Repeat Expansion, Polymerase Chain Reaction, Sequencing, Isolated Hypospadia

Sleep duration and risk of fatal and nonfatal stroke: a prospective study and meta-analysis.

OBJECTIVE: To study the association between sleep duration and stroke incidence in a British population and to synthesize our findings with published results through a meta-analysis. METHODS: The prospective study included 9,692 stroke-free participants aged 42-81 years from the European Prospective Investigation into Cancer-Norfolk cohort. Participants reported sleep duration in 1998-2000 and 2002-2004, and all stroke cases were recorded until March 31, 2009. For the meta-analysis, we searched Ovid Medline, EMBASE, and the Cochrane Library for prospective studies published until May 2014, and pooled effect estimates using a weighted random-effect model. RESULTS: After 9.5 years of follow-up, 346 cases of stroke occurred. Long sleep was significantly associated with an increased risk of stroke (hazard ratio [HR] = 1.46 [95% confidence interval (CI) 1.08, 1.98]) after adjustment for all covariates. The association remained robust among those without preexisting diseases and those who reported sleeping well. The association for short sleep was smaller (and not statistically significant) (HR = 1.18 [95% CI 0.91, 1.53]). There was a higher stroke risk among those who reported persistently long sleep or a substantial increase in sleep duration over time, compared to those reporting persistently average sleep. These were compatible with the pooled HRs from an updated meta-analysis, which were 1.15 (1.07, 1.24) and 1.45 (1.30, 1.62) for short and long sleep duration, respectively. CONCLUSIONS: This prospective study and meta-analysis identified prolonged sleep as a potentially useful marker of increased future stroke risk in an apparently healthy aging population.The design and conduct of the EPIC-Norfolk study was supported by program grants from the Medical Research Council of the United Kingdom (grants G9502233 and G1000143) and Cancer Research UK (grants SP2024/0204 and C864/A14136). Ms. Leng is supported by Cambridge Commonwealth, European & International Trusts. Prof. Cappuccio leads the Sleep Health & Society Programme at the University of Warwick supported, in part, by the University of Warwick RDF and IAS. It has received funding by the NHS National Workforce Projects and the Economic & Social Research Council (ES/K002910/1).This is the final published version. It first appeared at http://www.neurology.org/content/early/2015/02/25/WNL.0000000000001371.short

Interpreting long chain n-alkyl lipids in lake sediments: A critical evaluation of their sources and isotope signals

Stable carbon and hydrogen isotopic values of n-alkyl lipids extracted from lake sediments have been widely used for the reconstruction of ancient vegetation, climate, altitude, hydrology, etc. Compound-specific isotope analysis has taken the advantage of source-specific environmental signals from both autochthonous and allochthonous lipids, assuming that long chain n-alkyl lipids are primary derived from terrestrial plants. In recent years, substantial progresses have been made toward lipids produced by lacustrine macrophytes (aquatic plants and macro-algae) regarding their abundance, metabolism, chain length distribution, and isotope values. Accumulating evidence indicates that long chain (C26– C31) n-alkyl lipids in lacustrine sediments are derived from diverse sources, including terrestrial plants, aquatic macrophytes, and microbes; some emerged aquatic plants and macro-algae produce similar or even higher concentrations of long chain n-alkyl lipids as they are from terrestrial plants. Abundant long chain n-alkyl lipids from submerged aquatic plants with C4-like metabolism suggested an underlying cause for the large discrepancies of δ13C values and uniformed δD value variations among homologous lipids with different chain lengths, complicating the estimate of ancient C3/C4 vegetation and the reconstruction of paleohydrology. The significant correlations between δD values of long-chain nalkyl lipids from aquatic macrophytes and lake water (vs δD values of precipitation) found in lakes at the Tibetan Plateau further highlight both challenges and opportunities for paleohydological reconstructions. The assessment of relative contributions of long-chain nalkyl lipids from various sources in a particular lacustrine site becomes a critical prerequisite for the application of their isotope values as proxies. To discriminate the sources of these lipids, we found that some traditional indicators, such as Paq, ACL, and CPI, are of limited values, while inter-molecular isotope offsets among n-alkyl lipids with different chain lengths show promising results. Knowledge gaps exist regarding factors that influence lipid biomass from aquatic macrophytes, their molecular isotope behaviors, and implications as lacustrine environmental proxies