The role of HLA-G in human pregnancy

Pregnancy in mammals featuring hemochorial placentation introduces a major conflict with the mother's immune system, which is dedicated to repelling invaders bearing foreign DNA and RNA. Numerous and highly sophisticated strategies for preventing mothers from rejecting their genetically different fetus(es) have now been identified. These involve production of novel soluble and membrane-bound molecules by uterine and placental cells. In humans, the placenta-derived molecules include glycoproteins derived from the HLA class Ib gene, HLA-G. Isoforms of HLA-G saturate the maternal-fetal interface and circulate in mothers throughout pregnancy. Uteroplacental immune privilege for the fetus and its associated tissues is believed to result when immune cells encounter HLA-G. Unequivocally demonstration of this concept requires experiments in animal models. Both the monkey and the baboon express molecules that are similar but not identical to HLA-G, and may comprise suitable animal models for establishing a central role for these proteins in pregnancy

Breast cancer risk genes: association analysis in more than 113,000 women

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Brain tumour differentiation: rapid stratified serum diagnostics via attenuated total reflection Fourier-transform infrared spectroscopy

The ability to diagnose cancer rapidly with high sensitivity and specificity is essential to exploit advances in new treatments to lead significant reductions in mortality and morbidity. Current cancer diagnostic tests observing tissue architecture and specific protein expression for specific cancers suffer from inter-observer variability, poor detection rates and occur when the patient is symptomatic. A new method for the detection of cancer using 1 μl of human serum, attenuated total reflection - Fourier transform infrared spectroscopy and pattern recognition algorithms is reported using a 433 patient dataset (3897 spectra). To the best of our knowledge, we present the largest study on serum mid-infrared spectroscopy for cancer research. We achieve optimum sensitivities and specificities using a Radial Basis Function Support Vector Machine of between 80.0 and 100% for all strata and identify the major spectral features, hence biochemical components, responsible for the discrimination within each stratum. We assess feature fed-SVM analysis for our cancer versus non-cancer model and achieve 91.5 and 83.0% sensitivity and specificity respectively. We demonstrate the use of infrared light to provide a spectral signature from human serum to detect, for the first time, cancer versus non-cancer, metastatic cancer versus organ confined, brain cancer severity and the organ of origin of metastatic disease from the same sample enabling stratified diagnostics depending upon the clinical question asked. © 2016, The Author(s)

Effects of sprint interval training on ectopic lipids and tissue-specific insulin sensitivity in men with non-alcoholic fatty liver disease

Purpose: This study examined the feasibility of sprint interval exercise training (SIT) for men with non-alcoholic fatty liver disease (NAFLD) and its effects on intrahepatic triglyceride (IHTG), insulin sensitivity (hepatic and peripheral), visceral (VAT) and subcutaneous adipose tissue (ScAT). Methods: Nine men with NAFLD (age 41 ± 8 years; BMI 31.7 ± 3.1 kg m−2; IHTG 15.6 ± 8.3%) were assessed at: (1) baseline (2) after a control phase of no intervention (pre-training) and (3) after 6 weeks of SIT (4–6 maximal 30 s cycling intervals, three times per week). IHTG, VAT and ScAT were measured using magnetic resonance spectroscopy or imaging and insulin sensitivity was assessed via dual-step hyperinsulinaemic-euglycaemic clamp with [6,6-D2] glucose tracer. Results: Participants adhered to SIT, completing ≥ 96.7% of prescribed intervals. SIT increased peak oxygen uptake [ V O2peak: + 13.6% (95% CI 8.8–18.2%)] and elicited a relative reduction in IHTG [− 12.4% (− 31.6 to 6.7%)] and VAT [− 16.9% (− 24.4 to − 9.4%); n = 8], with no change in body weight or ScAT. Peripheral insulin sensitivity increased throughout the study (n = 8; significant main effect of phase) but changes from pre- to post-training were highly variable (range − 18.5 to + 58.7%) and not significant (P = 0.09), despite a moderate effect size (g* = 0.63). Hepatic insulin sensitivity was not influenced by SIT. Conclusions: SIT is feasible for men with NAFLD in a controlled laboratory setting and is able to reduce IHTG and VAT in the absence of weight loss

A comparison of methods for temporal analysis of aoristic crime

Objectives: To test the accuracy of various methods previously proposed (and one new method) to estimate offence times where the actual time of the event is not known. Methods: For 303 thefts of pedal cycles from railway stations, the actual offence time was determined from closed-circuit television and the resulting temporal distribution compared against commonly-used estimated distributions using circular statistics and analysis of residuals. Results: Aoristic analysis and allocation of a random time to each offence allow accurate estimation of peak offence times. Commonly-used deterministic methods were found to be inaccurate and to produce misleading results. Conclusions: It is important that analysts use the most accurate methods for temporal distribution approximation to ensure any resource decisions made on the basis of peak times are reliable

Repercussões da amniorrexe prematura no pré-termo sobre a morbimortalidade neonatal Repercussions of premature rupture of fetal membranes on neonatal morbidity and mortality

O objetivo foi analisar os fatores associados ao óbito e sobrevida com seqüela em neonatos egressos de gestações que cursaram com amniorrexe prematura. Estudo observacional do tipo coorte histórica analisou prontuários de pacientes que evoluíram com quadro de amniorrexe prematura < 34 semanas de gestação. As variáveis foram cotejadas com os desfechos óbito neonatal e sobrevida com seqüela. Em ambos os grupos os dados foram submetidos à análise bivariada, sendo os valores que exibem significância estatística submetidos à regressão logística. No modelo multivariado final em relação ao óbito fetal tiveram significância estatística: corioamnionite; índice de Apgar < 5 no 5º minuto; peso ao nascimento < 1.000g; e reanimação cardiopulmonar. Quanto à presença de seqüela entre os sobreviventes destacam se: a colonização cervical; persistência do canal arterial; índice de Apgar < 5 no 5º minuto; e peso ao nascimento < 1.000g. Processos infecciosos, extremo baixo peso ao nascer e asfixia periparto são as principais variáveis ligadas aos desfechos estudados entre neonatos egressos de gestações que cursaram com amniorrexe prematura.<br>The objective of this study was to analyze factors associated with death and survival with sequelae in neonates after premature rupture of fetal membranes (PROM). An observational historical cohort study analyzed charts of patients with PROM at < 34 weeks gestation. The variables were compared with neonatal death and survival with sequelae as the outcomes. In both groups, the data were submitted to bivariate analysis, and the variables showing significance were submitted to logistic regression. The final multivariate model for fetal death showed statistical significance for the following: chorioamnionitis; 5-minute Apgar score < 5; birth weight < 1,000g; and cardiopulmonary resuscitation. Survival with sequela was associated with: cervical colonization; patent ductus arteriosus; 5-minute Apgar score < 5; and birth weight < 1,000g. Infections, very low birth weight, and peripartum asphyxia were the principal variables associated with the target outcomes among newborns from gestations involving PROM