Investigation of relationship between vitamin D status and reproductive fitness in Scottish hill sheep

There is a growing interest in the influence of vitamin D on ovine non-skeletal health. The aim of this study was to explore the relationship between pre-mating vitamin D status, as assessed by serum concentrations of 25-Hydroxyvitamin D [25(OH)D; comprising D2 and D3] and subsequent reproductive performance of genetically unimproved Scottish Blackface (UBF), genetically improved Scottish Blackface (IBF) and Lleyn ewes kept under Scottish hill conditions. 25-Hydroxyvitamin D2 (25(OH)D2) and 25-Hydroxyvitamin D3 (25(OH)D3) concentrations were determined in serum samples harvested in November from ewes grazed outdoors. There were no significant differences in 25(OH)D2concentrations amongst the 3 genotypes. Lleyn ewes had significantly higher 25(OH)D3 and 25(OH)D concentrations than both Scottish Blackface ewe genotypes, whereas these vitamin D parameters did not differ significantly between the UBF and IBF ewes. Concentrations of 25(OH)D3 and 25(OH)D were positively associated with subsequent birth weights of singleton and of twin lamb litters. No significant associations between vitamin D status and number of lambs born or weaned per ewe were found. This study demonstrates that concentrations of cutaneously-derived 25(OH)D3, but not of orally consumed 25(OH)D2, differed between breeds. The positive association between ewe vitamin D status and offspring birth weight highlights the need for further investigations

Preexisting Japanese Encephalitis Virus Neutralizing Antibodies and Increased Symptomatic Dengue Illness in a School-Based Cohort in Thailand

Dengue viruses (DENVs) and Japanese encephalitis virus (JEV) have significant cross-reactivity in serological assays, but the possible clinical implications of this remain poorly understood. Interactions between these flaviviruses are potentially important for public health because wild-type JEV continues to co-circulate with DENV in Southeast Asia, the area with the highest burden of DENV illness, and JEV vaccination coverage in this region is high. In this study, we examined how preexisting JEV neutralizing antibodies (NAbs) influenced the clinical severity of subsequent DENV infection using data from a prospective school-based cohort study in Thailand that captured a wide range of clinical severities, including asymptomatic, non-hospitalized, and hospitalized DENV infections. We found that the prior existence of JEV NAbs was associated with an increased occurrence of symptomatic versus asymptomatic DENV infection. This association was most notable in DENV-naives, in whom the presence of JEV NAbs was also associated with an illness of longer duration. These findings suggest that the issue of heterologous flavivirus immunity and DENV infection merits renewed attention and interest and that DENV vaccine developers might incorporate detailed assessments of preexisting immunity to non-DENV flaviviruses and histories of vaccination against non-DENV flaviviruses in evaluating DENV vaccine safety and efficacy

Anemia of Inflammation Is Related to Cognitive Impairment among Children in Leyte, The Philippines

Past studies have demonstrated that iron deficiency anemia is related to deficits in cognitive fucntioning in children, and treating iron deficiency anemia with iron supplementation can improve cognition. Anemia of inflammation is another type of anemia caused by many diseases of lesser-developed countries including bacterial and parasitic infections. Anemia of inflammation is characterized by disordered iron metabolism, such that iron is sequestered in storage forms, preventing its use from tissues that require it. We hypothesized that decreased iron delivery to the brain in the context of anemia of inflammation might lead to decreased cognitive performance. This study found that children with anemia of inflammation had decreased cognitive performance in specific domains, compared to subjects with no anemia. True total body iron deficiency anemia was related to lower performance in the same domains. The only treatment option for anemia of inflammation is treatment of the underlying disease. Iron supplementation will not prevent cognitive deficits in children with anemia of inflammation. Interventions aimed towards maximizing the cognitive development of children in lesser-developed countries will need to focus on the prevention and treatment of bacterial and parasitic infections

It is time to talk about people: a human-centered healthcare system

Examining vulnerabilities within our current healthcare system we propose borrowing two tools from the fields of engineering and design: a) Reason's system approach [1] and b) User-centered design [2,3]. Both approaches are human-centered in that they consider common patterns of human behavior when analyzing systems to identify problems and generate solutions. This paper examines these two human-centered approaches in the context of healthcare. We argue that maintaining a human-centered orientation in clinical care, research, training, and governance is critical to the evolution of an effective and sustainable healthcare system

The WD-repeat protein superfamily in Arabidopsis: conservation and divergence in structure and function

BACKGROUND: The WD motif (also known as the Trp-Asp or WD40 motif) is found in a multitude of eukaryotic proteins involved in a variety of cellular processes. Where studied, repeated WD motifs act as a site for protein-protein interaction, and proteins containing WD repeats (WDRs) are known to serve as platforms for the assembly of protein complexes or mediators of transient interplay among other proteins. In the model plant Arabidopsis thaliana, members of this superfamily are increasingly being recognized as key regulators of plant-specific developmental events. RESULTS: We analyzed the predicted complement of WDR proteins from Arabidopsis, and compared this to those from budding yeast, fruit fly and human to illustrate both conservation and divergence in structure and function. This analysis identified 237 potential Arabidopsis proteins containing four or more recognizable copies of the motif. These were classified into 143 distinct families, 49 of which contained more than one Arabidopsis member. Approximately 113 of these families or individual proteins showed clear homology with WDR proteins from the other eukaryotes analyzed. Where conservation was found, it often extended across all of these organisms, suggesting that many of these proteins are linked to basic cellular mechanisms. The functional characterization of conserved WDR proteins in Arabidopsis reveals that these proteins help adapt basic mechanisms for plant-specific processes. CONCLUSIONS: Our results show that most Arabidopsis WDR proteins are strongly conserved across eukaryotes, including those that have been found to play key roles in plant-specific processes, with diversity in function conferred at least in part by divergence in upstream signaling pathways, downstream regulatory targets and /or structure outside of the WDR regions

Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease-causing variants in 21% of cases, with the proportion increasing to 34% (23/68) for mendelian disorders and 57% (8/14) in family trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis but also highlight many outstanding challenges

Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease-causing variants in 21% of cases, with the proportion increasing to 34% (23/68) for mendelian disorders and 57% (8/14) in family trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis but also highlight many outstanding challenges