Plasma phospholipid fatty acid profile confirms compliance to a novel saturated fat-reduced, monounsaturated fat-enriched dairy product intervention in adults at moderate cardiovascular risk: a randomized controlled trial

$\textbf{Background:}$ Dairy products are a major contributor to dietary SFA. Partial replacement of milk SFA with unsaturated fatty acids (FAs) is possible through oleic-acid rich supplementation of the dairy cow diet. To assess adherence to the intervention of SFA-reduced, MUFA-enriched dairy product consumption in the RESET (REplacement of SaturatEd fat in dairy on Total cholesterol) study using 4-d weighed dietary records, in addition to plasma phospholipid FA (PL-FA) status. $\textbf{Methods:}$ In a randomised, controlled, crossover design, free-living UK participants identified as moderate risk for CVD (n = 54) were required to replace habitually consumed dairy foods (milk, cheese and butter), with study products with a FA profile typical of retail products (control) or SFA-reduced, MUFA-enriched profile (modified), for two 12-week periods, separated by an 8-week washout period. A flexible food-exchange model was used to implement each isoenergetic high-fat, high-dairy diet (38% of total energy intake (%TE) total fat): control (dietary target: 19%TE SFA; 11%TE MUFA) and modified (16%TE SFA; 14%TE MUFA). $\textbf{Results:}$ Following the modified diet, there was a smaller increase in SFA (17.2%TE vs. 19.1%TE; p < 0.001) and greater increase in MUFA intake (15.4%TE vs. 11.8%TE; p < 0.0001) when compared with the control. PL-FA analysis revealed lower total SFAs (p = 0.006), higher total cis-MUFAs and trans-MUFAs (both p < 0.0001) following the modified diet. $\textbf{Conclusion:}$ The food-exchange model was successfully used to achieve RESET dietary targets by partial replacement of SFAs with MUFAs in dairy products, a finding reflected in the PL-FA profile and indicative of objective dietary compliance. $\textbf{Trial registration:}$ ClinicalTrials.gov Identifier: NCT02089035 , date 05-01-2014.This work was supported by funding from the Medical Research Council (United Kingdom; Ref: MR/K020218/1)

Radiation induced angiosarcoma a sequela of radiotherapy for breast cancer following conservative surgery

Radiation induced angiosarcomas (RIA) can affect breast cancer patients who had radiotherapy following conservative breast surgery. They are very rare tumors and often their diagnosis is delayed due to their benign appearance and difficulty in differentiation from radiation induced skin changes. Therefore it is very important that clinicians are aware of their existence. We report here a case of RIA followed by discussion and review of literature

Analysis of genome-wide structure, diversity and fine mapping of Mendelian traits in traditional and village chickens

Extensive phenotypic variation is a common feature among village chickens found throughout much of the developing world, and in traditional chicken breeds that have been artificially selected for traits such as plumage variety. We present here an assessment of traditional and village chicken populations, for fine mapping of Mendelian traits using genome-wide single-nucleotide polymorphism (SNP) genotyping while providing information on their genetic structure and diversity. Bayesian clustering analysis reveals two main genetic backgrounds in traditional breeds, Kenyan, Ethiopian and Chilean village chickens. Analysis of linkage disequilibrium (LD) reveals useful LD (r(2)⩾0.3) in both traditional and village chickens at pairwise marker distances of ∼10 Kb; while haplotype block analysis indicates a median block size of 11–12 Kb. Association mapping yielded refined mapping intervals for duplex comb (Gga 2:38.55–38.89 Mb) and rose comb (Gga 7:18.41–22.09 Mb) phenotypes in traditional breeds. Combined mapping information from traditional breeds and Chilean village chicken allows the oocyan phenotype to be fine mapped to two small regions (Gga 1:67.25–67.28 Mb, Gga 1:67.28–67.32 Mb) totalling ∼75 Kb. Mapping the unmapped earlobe pigmentation phenotype supports previous findings that the trait is sex-linked and polygenic. A critical assessment of the number of SNPs required to map simple traits indicate that between 90 and 110K SNPs are required for full genome-wide analysis of haplotype block structure/ancestry, and for association mapping in both traditional and village chickens. Our results demonstrate the importance and uniqueness of phenotypic diversity and genetic structure of traditional chicken breeds for fine-scale mapping of Mendelian traits in the species, with village chicken populations providing further opportunities to enhance mapping resolutions

Population-Specific Responses to Interspecific Competition in the Gut Microbiota of Two Atlantic Salmon (Salmo salar) Populations

The gut microbial community in vertebrates plays a role in nutrient digestion and absorption, development of intestine and immune systems, resistance to infection, regulation of bone mass and even host behavior and can thus impact host fitness. Atlantic salmon (Salmo salar) reintroduction efforts into Lake Ontario, Canada, have been unsuccessful, likely due to competition with non-native salmonids. In this study, we explored interspecific competition effects on the gut microbiota of two Atlantic salmon populations (LaHave and Sebago) resulting from four non-native salmonids. After 10 months of rearing in semi-natural stream tanks under six interspecific competition treatments, we characterized the gut microbiota of 178 Atlantic salmon by parallel sequencing the 16S rRNA gene. We found 3978 bacterial OTUs across all samples. Microbiota alpha diversity and abundance of 27 OTUs significantly differed between the two populations. Interspecific competition reduced relative abundance of potential beneficial bacteria (six genera of lactic acid bacteria) as well as 13 OTUs, but only in the LaHave population, indicating population-specific competition effects. The pattern of gut microbiota response to interspecific competition may reflect local adaptation of the host-microbiota interactions and can be used to select candidate populations for improved species reintroduction success

Selective Cholinergic Depletion in Medial Septum Leads to Impaired Long Term Potentiation and Glutamatergic Synaptic Currents in the Hippocampus

Cholinergic depletion in the medial septum (MS) is associated with impaired hippocampal-dependent learning and memory. Here we investigated whether long term potentiation (LTP) and synaptic currents, mediated by alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors in the CA1 hippocampal region, are affected following cholinergic lesions of the MS. Stereotaxic intra-medioseptal infusions of a selective immunotoxin, 192-saporin, against cholinergic neurons or sterile saline were made in adult rats. Four days after infusions, hippocampal slices were made and LTP, whole cell, and single channel (AMPA or NMDA receptor) currents were recorded. Results demonstrated impairment in the induction and expression of LTP in lesioned rats. Lesioned rats also showed decreases in synaptic currents from CA1 pyramidal cells and synaptosomal single channels of AMPA and NMDA receptors. Our results suggest that MS cholinergic afferents modulate LTP and glutamatergic currents in the CA1 region of the hippocampus, providing a potential synaptic mechanism for the learning and memory deficits observed in the rodent model of selective MS cholinergic lesioning

BRAFV600E mutation is highly prevalent in thyroid carcinomas in the young population in Fukushima: a different oncogenic profile from Chernobyl

After the accident at the Fukushima Daiichi Nuclear Power Plant, the thyroid ultrasound screening program for children aged 0-18 at the time of the accident was started from October 2011. The prevalence of thyroid carcinomas in that population has appeared to be very high (84 cases per 296,253). To clarify the pathogenesis, we investigated the presence of driver mutations in these tumours. 61 classic papillary thyroid carcinomas (PTCs), two follicular variant PTCs, four cribriform-morular variant PTCs and one poorly-differentiated thyroid carcinoma were analysed. We detected BRAF V600E in 43 cases (63.2%), RET/PTC1 in six (8.8%), RET/PTC3 in one (1.5%) and ETV6/NTRK3 in four (5.9%). Among classic and follicular variant PTCs, BRAF V600E was significantly associated with the smaller size. The genetic pattern was completely different from post-Chernobyl PTCs, suggesting non-radiogenic etiology of these cancers. This is the first study demonstrating the oncogene profile in the thyroid cancers discovered by large mass screening, which probably reflects genetic status of all sporadic and latent tumours in the young Japanese population. It is assumed that BRAF V600E may not confer growth advantage on paediatric PTCs, and many of these cases grow slowly, suggesting that additional factors may be important for tumour progression in paediatric PTCs

State of the Art Review: Emerging Therapies: The Use of Insulin Sensitizers in the Treatment of Adolescents with Polycystic Ovary Syndrome (PCOS)

PCOS, a heterogeneous disorder characterized by cystic ovarian morphology, androgen excess, and/or irregular periods, emerges during or shortly after puberty. Peri- and post-pubertal obesity, insulin resistance and consequent hyperinsulinemia are highly prevalent co-morbidities of PCOS and promote an ongoing state of excess androgen. Given the relationship of insulin to androgen excess, reduction of insulin secretion and/or improvement of its action at target tissues offer the possibility of improving the physical stigmata of androgen excess by correction of the reproductive dysfunction and preventing metabolic derangements from becoming entrenched. While lifestyle changes that concentrate on behavioral, dietary and exercise regimens should be considered as first line therapy for weight reduction and normalization of insulin levels in adolescents with PCOS, several therapeutic options are available and in wide use, including oral contraceptives, metformin, thiazolidenediones and spironolactone. Overwhelmingly, the data on the safety and efficacy of these medications derive from the adult PCOS literature. Despite the paucity of randomized control trials to adequately evaluate these modalities in adolescents, their use, particularly that of metformin, has gained popularity in the pediatric endocrine community. In this article, we present an overview of the use of insulin sensitizing medications in PCOS and review both the adult and (where available) adolescent literature, focusing specifically on the use of metformin in both mono- and combination therapy