Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Assessment of eco-sustainability vis-à-vis zoo-technical attributes of soybean meal (SBM) replacement with varying levels of coated urea in Nellore sheep (Ovis aries).

The contemporary environmental-stewardship programmes primarily aimed at curbing the global warming potential by adopting a multidisciplinary approach. Manipulating the feeding strategies has great potential in reducing the environmental footprints of livestock production. This study intends to assess the effect of soybean meal (SBM) replacement with varying levels of coated urea (SRU) on both zoo-technical (nutrient digestibility, heat increment, and physio-biochemical parameters) and environmental attributes. The coated urea was used to replace the SBM at 0, 25, 50, and 75 percent levels. Eight adult rams (43.02 ± 0.76) maintained in a conventional shed were used in a replicated 4 x 4 Latin square design. Not all the physiological parameters viz. rectal temperature, pulse rate, and respiratory rate were affected (P>0.05)f by varying levels of SRU incorporation. The SRU fed animals had higher (P<0.05) crude protein digestibility compared to SBM fed animals; however, the replacements did not affect the nutrient digestibility coefficients of DM, OM, NFC, NDFap, ADF, and hemicellulose components. The SRU did not affect various biochemical parameters such as serum glucose, total protein, albumin, globulin, urea, creatinine, ALT, AST, Ca, P and T3, and T4 levels; however, post-prandial serum urea N (SUN) values showed a diurnal quadratic pattern (P<0.05) with a dose-dependent relationship. Further, the SBM replacements had no effect on the calcium excretion, while the SRU incorporation decreased the faecal phosphorous content, thereby abating the eutrophication phenomenon. Although the SBM replacements did not affect in vivo water variables and faecal solid fractions, they managed to decrease the land and virtual water requirement along with global warming potential (GWP) of the entire trial. The GWP-perceptual map unveils the fact that replacement of conventional feed ingredients with NPN compounds aids in eco-friendly livestock production. Further, the conjectural analysis of the carbon footprint methodology revealed that agricultural by-products consideration could cause a huge increase in the GWP share of feed consumed, thus compelling the importance of research pertaining to feed production perspective as equal as ruminal methane amelioration

Farming systems in sheep rearing: Impact on growth and reproductive performance, nutrient digestibility, disease incidence and heat stress indices.

The experiment was conducted with an intent to know the effect of different farming systems on the growth performance, nutrient digestibility coefficients, reproductive traits, disease incidence, heat stress indices, and cost economics of Nellore sheep. The study includes two parallel trials to prevent the influence of age on heat stress indices (panting score and erythrocyte osmotic fragility (EOF)). One hundred and twenty lambs (60 ram-lambs and 60 ewe-lambs) were allotted in a randomized block design under extensive, semi-intensive, and intensive systems for trial I, whereas trial II include eighteen rams assigned to the three respective farming systems in a completely randomised design. Both, season (summer) and grazing practice increased the panting score and EOF. The heat stress indices were positively correlated (P<0.01) with dry-bulb temperature and temperature-humidity index (THI) and inversely correlated (P<0.01) to relative humidity. Allotting the sheep to intensive system increased (P<0.001) weight gain and average daily gain with higher effect in males compared to females. The parameters of asymptotic weight (A), integration constant (B), and maturation rate were higher for intensive males. The male Nellore lambs had higher asymptotic weight and lower maturity rate than females, irrespective of the rearing system. Intensive sheep revealed a higher dry matter intake, digestibility coefficients, feed conversion ratio. The instantaneous bite mass (IBM) was higher for Commelina benghalensis, while instantaneous bite frequency (IBF), instantaneous intake rate (IIR) were higher for Cyanodon dactylon and amaranthus viridis, respectively. The proportion of intakes were highest for Stylo hemata followed by Cynodon dactylon and Tridax procumbens species. No differences were observed for the weight at puberty, oestrus cycle length, oestrus duration, conception percent, gestation period, and lambing percent in three rearing systems; however, the age at puberty was lower (P<0.001) and the birth weight was higher (P<0.001) for sheep reared under intensive farming system. Highest disease incidence was observed in rainy and winter seasons, particularly in sheep reared under extensive system. The capital expenditure was same for the three rearing systems, while the recurring expenditure was higher for Intensive farming system. The gross income and net income were higher for intensive system on account of higher weight gains. However, the higher returns per rupee of expenditure project the extensive farming as an ideal rearing system for small farmers and entrepreneurs with a low initial capital

Extended adipofascial wrap around radial forearm flap for hard palate reconstruction

Background: While using radial forearm free flap in palate reconstruction, the pedicle lies in the nasal floor, constantly exposed to the nasal secretions and turbulent air current. To overcome this problem, we have designed a procedure which utilises the adipofascial extension to wrap the pedicle and nasal side of the flap. Materials and Methods: The study was done during 2017 and 2018, 2 years’ period. Totally 13 consecutive patients with defect in the palate status post-oncological resection and those in whom local flaps were not enough to cover the defect were included into the study. These patients were divided into two groups. First group in whom adipofascial extension was not used to cover the pedicle and second group in whom adipofascial extension was used to cover the pedicle. The incidence of nasal crusting, secondary haemorrage, blow out and flap necrosis were analysed and compared. Results: In Group 1, we had 2 among 6 (33%) patients with secondary haemorrage. One patient had partial flap loss. On exploring, we noticed thrombosis of cephalic vein. We did not had any incidence of blow out of the pedicle. In Group 2, none of the patients had any secondary haemorrage. All flaps healed well. On doing nasal endoscopy at 6 months of follow-up, all flaps showed complete mucosalisation at the nasal side. Conclusion: Use of adipofascial extension while planning a radial forearm free flap to cover the nasal side of the flap and pedicle in the nasal floor helps to reduce the nasal crusting and secondary haemorrhage