The endothelium isolated as an intact tube of cells offers a powerful approach to study endothelial cell function.
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Chemical signals can provide useful information to potential mates and rivals. The production mechanisms of these signals are poorly understood in birds, despite emerging evidence that volatile compounds from preen oil may serve as chemosignals. Steroid hormones, including testosterone (T), may influence the production of these signals, yet variation in circulating T only partly accounts for this variation. We hypothesized that odor is a T-mediated signal of an individual's phenotype, regulated in part by androgen sensitivity in the uropygial gland. We quantified natural variation in chemosignals, T, uropygial gland androgen sensitivity, and aggressive behavior in dark-eyed juncos (Junco hyemalis). The interaction between circulating T and androgen receptor transcript abundance significantly correlated with volatile concentrations in male, but not female, preen oil. In both sexes, odorant variables correlated with aggressive response to an intruder. Our results suggest that preen oil volatiles could function as signals of aggressive intent, and, at least in males, may be regulated by local androgen receptor signaling in the uropygial gland. Because these behavioral and chemical traits have been linked with reproductive success, local regulation of androgen sensitivity in the periphery has the potential to be a target of selection in the evolution of avian olfactory signaling.
The genetic trait of lactase persistence (LP) is associated with at least five independent functional single nucleotide variants in a regulatory region about 14 kb upstream of the lactase gene [−13910*T (rs4988235), −13907*G (rs41525747), −13915*G (rs41380347), −14009*G (rs869051967) and −14010*C (rs145946881)]. These alleles have been inferred to have spread recently and present-day frequencies have been attributed to positive selection for the ability of adult humans to digest lactose without risk of symptoms of lactose intolerance. One of the inferential approaches used to estimate the level of past selection has been to determine the extent of haplotype homozygosity (EHH) of the sequence surrounding the SNP of interest. We report here new data on the frequencies of the known LP alleles in the 'Old World' and their haplotype lineages. We examine and confirm EHH of each of the LP alleles in relation to their distinct lineages, but also show marked EHH for one of the older haplotypes that does not carry any of the five LP alleles. The region of EHH of this (B) haplotype exactly coincides with a region of suppressed recombination that is detectable in families as well as in population data, and the results show how such suppression may have exaggerated haplotype-based measures of past selection.
Ivermectin (IVM) is an antiparasitic drug that is used worldwide and rescues hundreds of millions of people from Onchocerciasis and lymphatic filariasis. It was discovered by Dr. Omura and Dr. Campbell, to whom the 2015 Nobel Prize in Physiology or Medicine was awarded. IVM kills parasites by activating glutamate-gated Cl− channels, and it also targets several ligand-gated ion channels and receptors, including Cys-loop receptors, P2X4 receptors and fernesoid X receptors. Recently, we found that IVM also activates a novel target, the G-protein-gated inwardly rectifying K+ channel, and also identified the structural determinant for the activation. In this review, we aim to update and summarize the information from recent progress in the identification of IVM targets, as well as their modulation mechanisms, through molecular structures, chimeras and site-directed mutagenesis, and molecular docking and modelling studies.
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Genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B; rs1229984, His48Arg) and aldehyde dehydrogenase-2 (ALDH2; rs671, Glu504Lys) affect body weight, body fat, and lipid metabolism in individuals with alcohol dependence, and the aim of this study was to identify their determinants in relation to the development of fatty liver.
We evaluated associations between the presence of fatty liver and ADH1B and ALDH2 genotypes and other factors in 1604 Japanese men who had been admitted for treatment of alcohol dependence.
Fatty liver was diagnosed when ultrasonography showed both hepatorenal contrast and liver brightness. Age-adjusted usual alcohol intake did not differ according to ADH1B or ALDH2 genotypes. A multivariate analysis showed that the adjusted odds ratio (OR, 95% confidence interval) of slow-metabolizing ADH1B Arg/Arg carriers was 1.61 (1.27–2.03) for fatty liver and 1.82 (1.37–2.41) for fatty liver with deep attenuation in comparison with the ADH1B His/Arg or His/His carriers, and that the OR of inactive heterozygous ALDH2 Glu/Lys carriers was 1.43 (1.08–1.91) for fatty liver and 1.84 (1.31–2.59) for fatty liver with deep attenuation in comparison with the ALDH2 Glu/Glu carriers. Younger age, shorter interval between the last drink and the ultrasound examination, larger body mass index, and absence of cirrhosis were identified as other positive determinants for fatty liver.
The ADH1B Arg/Arg genotype and the ALDH2 Glu/Lys genotype were positive determinants of fatty liver in the subjects. These results suggest that slow ethanol and acetaldehyde metabolism accelerates the development of alcoholic fatty liver in heavy drinkers.
Long-term resorbable mesh represents a promising technology for complex ventral and incisional hernia repair (VIHR). Preclinical studies indicate that poly-4-hydroxybutyrate (P4HB) resorbable mesh supports strength restoration of the abdominal wall. This study evaluated outcomes of high-risk subjects undergoing VIHR with P4HB mesh.
This was a prospective, multi-institutional study of subjects undergoing retrorectus or onlay VIHR. Inclusion criteria were CDC Class I, defect 10–350 cm2, ≤ 3 prior repairs, and ≥ 1 high-risk criteria (obesity (BMI: 30–40 kg/m2), active smoker, COPD, diabetes, immunosuppression, coronary artery disease, chronic corticosteroid use, hypoalbuminemia, advanced age, and renal insufficiency). Physical exam and/or quality of life surveys were performed at regular intervals through 18 months (to date) with longer-term, 36-month follow-up ongoing.
One hundred and twenty-one subjects (46M, 75F) with an age of 54.7 ± 12.0 years and BMI of 32.2 ± 4.5 kg/m2 (mean ± SD), underwent VIHR. Comorbidities included the following: obesity (n = 95, 78.5%), hypertension (n = 72, 59.5%), cardiovascular disease (n = 42, 34.7%), diabetes (n = 40, 33.1%), COPD (n = 34, 28.1%), malignancy (n = 30, 24.8%), active smoker (n = 28, 23.1%), immunosuppression (n = 10, 8.3%), chronic corticosteroid use (n = 6, 5.0%), advanced age (n = 6, 5.0%), hypoalbuminemia (n = 3, 2.5%), and renal insufficiency (n = 1, 0.8%). Hernia types included the following: primary ventral (n = 17, 14%), primary incisional (n = 54, 45%), recurrent ventral (n = 15, 12%), and recurrent incisional hernia (n = 35, 29%). Defect and mesh size were 115.7 ± 80.6 and 580.9 ± 216.1 cm2 (mean ± SD), respectively. Repair types included the following: retrorectus (n = 43, 36%), retrorectus with additional myofascial release (n = 45, 37%), onlay (n = 24, 20%), and onlay with additional myofascial release (n = 8, 7%). 95 (79%) subjects completed 18-month follow-up to date. Postoperative wound infection, seroma requiring intervention, and hernia recurrence occurred in 11 (9%), 7 (6%), and 11 (9%) subjects, respectively.
High-risk VIHR with P4HB mesh demonstrated positive outcomes and low incidence of hernia recurrence at 18 months. Longer-term 36-month follow-up is ongoing.
Biliary colic is a common diagnosis for patients presenting to the emergency department (ED). The purpose of this study is to examine the outcomes of patients coming to the ED with biliary colic.
The NYS longitudinal SPARCS database was used to identify patients presenting to the ED with biliary colic from 2005 to 2014. Through the use of a unique identifier, patients were followed in NYS across multiple institutions. Patients who were lost to follow-up, with duplicated records, and those that underwent percutaneous cholecystectomy tubes were excluded from the analysis.
Between 2005 and 2014, there were 72,376 patients who presented to an ED with biliary colic. The admission rate was 20.7–26.02%. Overall, most patients who presented to the ED did not undergo surgery (39,567, 54.7%), of which 35,204 (89%) had only one ED visit, while 4,363(11%) returned to the ED (≥ 2 visits). Only 3.23–5.51% of patients underwent cholecystectomy at the time of initial presentation. Most subsequent cholecystectomies were performed electively (27.38–52.51%) (See Table 1 in this article). Average time to surgery among patients with elective cholecystectomy was 178.4 days. From the patients who underwent cholecystectomy, 10.35% had cholecystectomy at their first ED visit, 77.7% had cholecystectomy following the first ED visit, and 12% had multiple ED visits prior to surgery. Among patients who were discharged from the ED, 32% had their surgery at a different hospital than index presentation.
A significant portion of patients (48.6%) who present to the ED with biliary colic will not return or have surgery within 5 years. A third of patients who eventually undergo cholecystectomy will go to another hospital for their surgery.
