IL-17A induces Pendrin expression and chloride-bicarbonate exchange in human bronchial epithelial cells

The epithelium plays an active role in the response to inhaled pathogens in part by responding to signals from the immune system. Epithelial responses may include changes in chemokine expression, increased mucin production and antimicrobial peptide secretion, and changes in ion transport. We previously demonstrated that interleukin-17A (IL-17A), which is critical for lung host defense against extracellular bacteria, significantly raised airway surface pH in vitro, a finding that is common to a number of inflammatory diseases. Using microarray analysis of normal human bronchial epithelial (HBE) cells treated with IL-17A, we identified the electroneutral chloride-bicarbonate exchanger Pendrin (SLC26A4) as a potential mediator of this effect. These data were verified by real-time, quantitative PCR that demonstrated a time-dependent increase in Pendrin mRNA expression in HBE cells treated with IL-17A up to 48 h. Using immunoblotting and immunofluorescence, we confirmed that Pendrin protein expression is increased in IL-17 treated HBE cells and that it is primarily localized to the mucosal surface of the cells. Functional studies using live-cell fluorescence to measure intracellular pH demonstrated that IL-17A induced chloride-bicarbonate exchange in HBE cells that was not present in the absence of IL-17A. Furthermore, HBE cells treated with short interfering RNA against Pendrin showed substantially reduced chloride-bicarbonate exchange. These data suggest that Pendrin is part of IL-17A-dependent epithelial changes and that Pendrin may therefore be a therapeutic target in IL-17A-dependent lung disease. © 2014 Adams et al

Predicting participation in group parenting education in an Australian sample: The role of attitudes, norms, and control factors

We examined the theory of planned behavior (TPB) in predicting intentions to participate in group parenting education. One hundred and seventy-six parents (138 mothers and 38 fathers) with a child under 12 years completed TPB items assessing attitude, subjective norms, perceived behavioral control (PBC), and two additional social influence variables (self-identity and group norm). Regression analyses supported the TPB predictors of participation intentions with self-identity and group norm also significantly predicting intentions. These findings offer preliminary support for the TPB, along with additional sources of social influence, as a useful predictive model of participation in parenting education

Antimicrobial Peptides and Skin: A Paradigm of Translational Medicine

Antimicrobial peptides (AMPs) are small, cationic, amphiphilic peptides with broad-spectrum microbicidal activity against both bacteria and fungi. In mammals, AMPs form the first line of host defense against infections and generally play an important role as effector agents of the innate immune system. The AMP era was born more than 6 decades ago when the first cationic cyclic peptide antibiotics, namely polymyxins and tyrothricin, found their way into clinical use. Due to the good clinical experience in the treatment of, for example, infections of mucus membranes as well as the subsequent understanding of mode of action, AMPs are now considered for treatment of inflammatory skin diseases and for improving healing of infected wounds. Based on the preclinical findings, including pathobiochemistry and molecular medicine, targeted therapy strategies are developed and first results indicate that AMPs influence processes of diseased skin. Importantly, in contrast to other antibiotics, AMPs do not seem to propagate the development of antibiotic-resistant micro-organisms. Therefore, AMPs should be tested in clinical trials for their efficacy and tolerability in inflammatory skin diseases and chronic wounds. Apart from possible fields of application, these peptides appear suited as an example of the paradigm of translational medicine for skin diseases which is today seen as a `two-way road' - from bench to bedside and backwards from bedside to bench. Copyright (c) 2012 S. Karger AG, Base

Understanding why adult participants at the World Senior Games choose a healthy diet

BACKGROUND: Identifying those seniors most likely to adopt a healthy diet, the relative importance they place on certain perceived benefits associated with a healthy diet, and whether these perceived benefits are associated with selected demographic, lifestyle, and health history variables is important for directing effective dietary health promotion programs. METHODS: Analyses are based on a cross-sectional convenience sample of 670 seniors aged 50 years and older at the 2002 World Senior Games in St. George, Utah. Data are assessed using frequencies, bivariate analysis, analysis of variance, and multiple logistic regression analysis. RESULTS: Fruit and vegetable consumption was significantly higher in individuals aged 70–79, in women, in those not overweight or obese, and in those with excellent overall health. Dietary fiber consumption was significantly higher in former or never smokers, current and previous alcohol drinkers, in those not overweight or obese, and in those with excellent health. The strongest motivating factors identified for adopting a healthy diet were to improve the quality of life, to increase longevity, and to prevent disease. Of intermediate importance were the need to feel a sense of control and to satisfy likes or dislikes. Least important were the desire to experience a higher level of spirituality, social reasons, and peer acceptance. CONCLUSION: Seniors who have adopted a healthy diet are more likely to have chosen that behavior because of perceived health benefits than for personal and social benefits. Overweight or obese individuals and those in poor health were less likely to be engaged in healthy eating behavior and require special attention by dieticians and public health professionals

FcRn-mediated antibody transport across epithelial cells revealed by electron tomography

The neonatal Fc receptor (FcRn) transports maternal IgG across epithelial barriers, thereby providing the fetus or newborn with humoral immunity before its immune system is fully functional. In newborn rats, FcRn transfers IgG from milk to blood by apical-to-basolateral transcytosis across intestinal epithelial cells. The pH difference between the apical (pH 6.0–6.5) and basolateral (pH 7.4) sides of intestinal epithelial cells facilitates the efficient unidirectional transport of IgG, because FcRn binds IgG at pH 6.0–6.5 but not at pH 7 or more. As milk passes through the neonatal intestine, maternal IgG is removed by FcRn-expressing cells in the proximal small intestine (duodenum and jejunum); remaining proteins are absorbed and degraded by FcRn-negative cells in the distal small intestine (ileum). Here we use electron tomography to make jejunal transcytosis visible directly in space and time, developing new labelling and detection methods to map individual nanogold-labelled Fc within transport vesicles and simultaneously to characterize these vesicles by immunolabelling. Combining electron tomography with a nonperturbing endocytic label allowed us to conclusively identify receptor-bound ligands, resolve interconnecting vesicles, determine whether a vesicle was microtubule-associated, and accurately trace FcRn-mediated transport of IgG. Our results present a complex picture in which Fc moves through networks of entangled tubular and irregular vesicles, only some of which are microtubule-associated, as it migrates to the basolateral surface. New features of transcytosis are elucidated, including transport involving multivesicular body inner vesicles/tubules and exocytosis through clathrin-coated pits. Markers for early, late and recycling endosomes each labelled vesicles in different and overlapping morphological classes, revealing spatial complexity in endo-lysosomal trafficking

Determinants of Habitat Selection by Hatchling Australian Freshwater Crocodiles

Animals almost always use habitats non-randomly, but the costs and benefits of using specific habitat types remain unknown for many types of organisms. In a large lake in northwestern Australia (Lake Argyle), most hatchling (<12-month-old) freshwater crocodiles (Crocodylus johnstoni) are found in floating vegetation mats or grassy banks rather than the more widely available open banks. Mean body sizes of young crocodiles did not differ among the three habitat types. We tested four potential explanations for non-random habitat selection: proximity to nesting sites, thermal conditions, food availability, and exposure to predation. The three alternative habitat types did not differ in proximity to nesting sites, or in thermal conditions. Habitats with higher food availability harboured more hatchlings, and feeding rates (obtained by stomach-flushing of recently-captured crocodiles) were highest in such areas. Predation risk may also differ among habitats: we were twice as likely to capture a crocodile after seeing it in open-bank sites than in the other two habitat types. Thus, habitat selection of hatchling crocodiles in this system may be driven both by prey availability and by predation risk

Predicting intention to treat HIV-infected patients among Tanzanian and Sudanese medical and dental students using the theory of planned behaviour - a cross sectional study

<p>Abstract</p> <p>Background</p> <p>The HIV epidemic poses significant challenges to the low income countries in sub Saharan Africa (SSA), affecting the attrition rate among health care workers, their level of motivation, and absenteeism from work. Little is known about how to deal with deterioration of human resources in the health care systems. This study aimed to predict the intention to provide surgical treatment to HIV infected patients among medical- and dental students in Tanzania and Sudan using an extended version of the Theory of Planned Behaviour (TPB).</p> <p>Methods</p> <p>Four hundred and seventy five medical- and dental students at the University of Dar es Salaam (mean age, 25 yr) and 642 dental students attending 6 public and private dental faculties in Khartoum (mean age 21.7 yr) completed self-administered TPB questionnaires in 2005 and 2007, respectively.</p> <p>Results</p> <p>Both Tanzanian and Sudanese students demonstrated strong intentions to provide care for people with HIV and AIDS. Stepwise linear regression revealed that the TPB accounted for 51% (43% in Tanzania and Sudan) of the variance in intention across study sites. After having controlled for country and past behaviour, the TPB in terms of attitudes, subjective norms and perceived behavioural control accounted for 34% and moral norms for an additional 2,3% of the explainable variance in intention. Across both study sites, attitudes were the strongest predictor of intention followed in descending order by subjective norms, moral norms and perceived behavioural control.</p> <p>Conclusion</p> <p>The TPB is applicable to students' care delivery intentions in the context of HIV and AIDS across the two SSA countries investigated. It is suggested that attitudes, subjective norms, moral norms and perceived behavioural control are key factors in students' willingness to treat AIDS and HIV infected patients and should be targets of interventions aimed at improving the quality of health care delivery in this context.</p

Positive association between mammographic breast density and bone mineral density in the Postmenopausal Estrogen/Progestin Interventions Study

INTRODUCTION: Mammographic breast density is a strong independent risk factor for breast cancer. We hypothesized that demonstration of an association between mammographic breast density and bone mineral density (BMD) would suggest a unifying underlying mechanism influencing both breast density and BMD. METHODS: In a cross-sectional analysis of baseline data from the Postmenopausal Estrogen/Progestin Interventions Study (PEPI), participants were aged 45 to 64 years and were at least 1 year postmenopausal. Mammographic breast density (percentage of the breast composed of dense tissue), the outcome, was assessed with a computer-assisted percentage-density method. BMD, the primary predictor, was measured with dual-energy X-ray absorptiometry. Women quitting menopausal hormone therapy to join PEPI were designated recent hormone users. RESULTS: The mean age of the 594 women was 56 years. The average time since menopause was 5.6 years. After adjustment for age, body mass index, and cigarette smoking, in women who were not recent hormone users before trial enrollment (n = 415), mammographic density was positively associated with total hip (P = 0.04) and lumbar (P = 0.08) BMD. Mammographic density of recent hormone users (n = 171) was not significantly related to either total hip (P = 0.51) or lumbar (P = 0.44) BMD. In participants who were not recent hormone users, mammographic density was 4% greater in the highest quartile of total hip BMD than in the lowest. In participants who were not recent hormone users, mammographic density was 5% greater in the highest quartile of lumbar spine BMD than in the lowest. CONCLUSION: Mammographic density and BMD are positively associated in women who have not recently used postmenopausal hormones. A unifying biological mechanism may link mammographic density and BMD. Recent exogenous postmenopausal hormone use may obscure the association between mammographic density and BMD by having a persistent effect on breast tissue