Is there a role for glucocorticoid receptor beta in asthma?

Glucocorticoids (GCs) are routinely used as anti-inflammatory drugs in the treatment of asthma. They act through binding to glucocorticoid receptor α (GRα), which represses numerous genes encoding pro-inflammatory mediators. A hormone binding deficient GR isoform named GRβ has been isolated in humans. When overexpressed by transfection, GRβ may function as a dominant negative modulator of GRα. However, to act as such, GRβ has to be more abundant than GRα, and conflicting data have been obtained concerning the relative levels of the two isoforms in cell lines and freshly isolated cells. Moreover, the dominant negative effect was not confirmed by independent laboratories. In GC-resistant asthmatics, GRβ was expressed by an increased number of peripheral blood mononuclear cells (PBMCs), airway T cells, and cells found in skin biopsies of tuberculin responses. However, the relative amounts of GRα and GRβ in these cells were not determined. In GC-dependent asthmatics, PBMCs expressed GRα predominantly. No cells containing higher levels of GRβ than GRα have yet been reported in asthmatics. Even if the existence of such cells is demonstrated, the role of GRβ in asthma will remain a matter of controversy because functional studies have given discrepant data

The supernatural characters and powers of sacred trees in the Holy Land

This article surveys the beliefs concerning the supernatural characteristics and powers of sacred trees in Israel; it is based on a field study as well as a survey of the literature and includes 118 interviews with Muslims and Druze. Both the Muslims and Druze in this study attribute supernatural dimensions to sacred trees which are directly related to ancient, deep-rooted pagan traditions. The Muslims attribute similar divine powers to sacred trees as they do to the graves of their saints; the graves and the trees are both considered to be the abode of the soul of a saint which is the source of their miraculous powers. Any violation of a sacred tree would be strictly punished while leaving the opportunity for atonement and forgiveness. The Druze, who believe in the transmigration of souls, have similar traditions concerning sacred trees but with a different religious background. In polytheistic religions the sacred grove/forest is a centre of the community's official worship; any violation of the trees is regarded as a threat to the well being of the community. Punishments may thus be collective. In the monotheistic world (including Christianity, Islam and Druze) the pagan worship of trees was converted into the worship/adoration of saints/prophets; it is not a part of the official religion but rather a personal act and the punishments are exerted only on the violating individual

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Impact of Weight Loss on the Metabolic Syndrome

Objective:To evaluate the effects of weight loss on the risk of having metabolic syndrome after 1 year of treatment with lifestyle modification alone, pharmacotherapy alone (sibutramine) or the combination of the two. Design:Randomized, controlled, 1-year clinical trial. Patients:One hundred and eighty women and 44 men, 18–65 years of age, with a body mass index of 30–45 kg/m2, free of uncontrolled hypertension or type 1 or 2 diabetes. Intervention:Fifteen milligrams of sibutramine per day alone, lifestyle modification counseling alone, sibutramine plus lifestyle modification counseling or sibutramine plus brief lifestyle modification counseling. Measurements:The metabolic syndrome, as defined by the Adult Treatment Panel III. Results: Before treatment, 34.8% of the participants had the metabolic syndrome. Metabolic syndrome was more prevalent in Caucasians than African Americans (42.5 vs 20.3%; P44 years) than younger (less than or equal to44 years) participants (47.5 vs 20.8%; PConclusions: The metabolic syndrome was prevalent in over one-third of obese individuals who sought weight loss treatment, and the prevalence differed by age, sex and ethnicity. Moderate weight loss markedly reduced the odds of metabolic syndrome in this sample

Patterns of variation at a mitochondrial sequence-tagged-site locus provides new insights into the postglacial history of European Pinus sylvestris populations

Due to their maternal mode of inheritance, mitochondrial markers can be regarded as almost 'ideal' tools in evolutionary studies of conifer populations. In the present study, polymorphism was analysed at one mitochondrial intron (nad 1, exon B/C) in 23 native European Pinus sylvestris populations. In a preliminary screening for variation using a polymerase chain reaction-restriction fragment length polymorphism approach, two length variants were identified. By fully sequencing the 2.5 kb region, the observed length polymorphism was found to result from the insertion of a 31 bp sequence, with no other mutations observed within the intron. A set of primers was designed flanking the observed mutation, which identified a novel sequence-tagged-site mitochondrial marker for P. sylvestris. Analysis of 747 trees from the 23 populations using these primers revealed the occurrence of two distinct haplotypes in Europe. Within the Iberian Peninsula, the two haplotypes exhibited extensive population differentiation (Φ(ST) = 0.59; P ≤ 0.001) and a marked geographical structuring. In the populations of central and northern Europe, one haplotype largely predominated, with the second being found in only one individual of one population

Arching the back (lumbar curvature) as a female sexual proceptivity signal: an eye-tracking study

It is common in studies of human mate preference to have participants judge the attractiveness of photographs in which models adopt a neutral facial expression or a neutral body posture. However, it is unlikely that humans adopt neutral expressions and postures in normal social circumstances. One way in which posture can vary is in the curvature of the lower spine. In some non-human animals, a “lordotic” posture (in which the lower spine is curved towards the belly) is associated in females with readiness to mate. In humans, this posture may serve a similar function, attracting heterosexual men. In this study, participants were presented with computergenerated images of female bodies in which the back curvature was systematically manipulated. The result showed that small changes in lumbar curvature are associated with changes in the perception of attractiveness. Specifically, the result showed that there is a relationship between the range of the back curvatures used in this study and attractiveness, such that increasing the curvature increased the perception of attractiveness. Additionally, as the curvature increased, participants looked longer and fixated more on the hip region of the female bodies. This paper argues that the attractiveness of women in lordotic posture is due to a conserved mechanism across the taxa which signals proceptivity to men.This study was supported by the Portuguese Foundation for Science and Technology and the Portuguese Ministry of Science, Technology and Higher Education through national funds and co-financed by FEDER through COMPETE2020 under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007653). FP receives funding from FCT Portugal through grant SFRH/BD/114366/2016; AM receives funding from FCT Portugal through grants PTDC/DTP-EPI/0412/2012 and PEST-C/FIS/UI607/2011; JA receives funding from FCT Portugal through grant IF/01298/2014.info:eu-repo/semantics/publishedVersio