Expression of Integrin α6β4 in Junctional Epidermolysis Bullosa

The integrin α6β4 is a member of the integrin family of adhesion receptors. The integrin α6β4 is preferentially expressed in stratified squamous epithelia, where it is localized in hemidesmosomes. A reduced number of rudimentary he- midesmosomes is often found in skin from patients with junctional epidermolysis bullosa (JEB). In this study we have investigated the expression of α6β4 in skin specimens of patients with junctional (one non-lethal, two lethal) and dystrophic (two) epidermolysis bullosa, using immunofluorescent (IF) staining with five different monoclonal antibodies against the α6 and β4 subunits. The intensity of IF staining of the integrin α6β4 and bullous pemphigoid antigen (BPA) was unreduced along the epidermal basement membrane zone (EBMZ) of all EB patients, compared to that in skin of healthy human controls. However, in the skin of two patients with lethal (Herlitz) JEB, who did not express GB3, IF staining of integrin α6β4 and BPA showed a “stitchy” discontinuous linear pattern along the EBMZ with interruptions at the borders of adjoining basal keratinocytes. The same results were obtained by immunoelectron microscopy. They corresponded with freeze-induced partial cell detachment from the basement membrane at the ultimate baso-lateral edge ot the basal keratinocytes in lethal JEB skin. The basal lamellipodia at that location almost completely lacked tonofilaments and hemidesmosomes. Furthermore, in JEB there was a split between the intra- and extracellular epitopes of the integrin α6β4 receptor, whereas the integrin remains intact in salt-split skin. This suggests that the defect is in α6β4 itself or perhaps its ligand

Adolescents in conflict: Intercultural contact attitudes of mothers and adolescents as predictors of family conflicts

Recent research demonstrates that intergenerational differences in immigrant families' adaptation can be detrimental for family functioning. However, most of the findings originate from immigrant groups in North America who face different situations compared with European Diaspora returnees. This comparative study investigated whether ethnic German Diaspora immigrant adolescents' and mothers' disagreement about the desirability of adolescents' intercultural contact with native peers relates to more conflict in the family domain. In addition, we accounted for general developmental factors predicting family conflict by considering adolescents' background in terms of prosocial behaviour and hyperactivity. Participants comprised 185 Diaspora immigrant mother–adolescent dyads from the former Soviet Union living in Germany (adolescents: mean age 15.7 years, 60% female) and 197 native German mother–adolescent dyads (adolescents: mean age 14.7 years, 53% female). Results indicated a similar level of family conflict in immigrant and native families. However, conflict was elevated in those immigrant families disagreeing on intercultural contact attitudes, independent of the significant effects of adolescents' background of prosocial behaviour or hyperactivity. Our study highlights potential side effects in the family domain, if immigrant adolescents and parents disagree in their attitude regarding adaptation to the host culture's life domains, such as contact with native peers

T helper cell subsets specific for pseudomonas aeruginosa in healthy individuals and patients with cystic fibrosis

Background: We set out to determine the magnitude of antigen-specific memory T helper cell responses to Pseudomonas aeruginosa in healthy humans and patients with cystic fibrosis. Methods: Peripheral blood human memory CD4+ T cells were co-cultured with dendritic cells that had been infected with different strains of Pseudomonas aeruginosa. The T helper response was determined by measuring proliferation, immunoassay of cytokine output, and immunostaining of intracellular cytokines. Results: Healthy individuals and patients with cystic fibrosis had robust antigen-specific memory CD4+ T cell responses to Pseudomonas aeruginosa that not only contained a Th1 and Th17 component but also Th22 cells. In contrast to previous descriptions of human Th22 cells, these Pseudomonal-specific Th22 cells lacked the skin homing markers CCR4 or CCR10, although were CCR6+. Healthy individuals and patients with cystic fibrosis had similar levels of Th22 cells, but the patient group had significantly fewer Th17 cells in peripheral blood. Conclusions: Th22 cells specific to Pseudomonas aeruginosa are induced in both healthy individuals and patients with cystic fibrosis. Along with Th17 cells, they may play an important role in the pulmonary response to this microbe in patients with cystic fibrosis and other conditions

Obesity or diet? Levels and determinants of phthalate body burden – A case study on Portuguese children

In this study we analyzed one of the most comprehensive sets of 21 urinary phthalate metabolites representing exposure to 11 parent phthalates (DEP, DMP, DiBP, DnBP, BBzP, DEHP, DiNP, DiDP, DCHP, DnPeP, DnOP) in first morning urine samples of 112 Portuguese children (4-18 years) sampled in 2014/15. The study population consisted of two groups: group 1 with normal weight/underweight children (N = 43) following their regular diet and group 2 with obese/overweight children (N = 69) following a healthy diet (with nutritional counselling). Most of the metabolites were above the limits quantification (81-100%) except for MCHP, MnPEP and MnOP. Metabolite levels were generally comparable to other recent child and general populations sampled worldwide, confirming the steady decline in exposures to most phthalates. Compared to Portuguese children sampled in 2011/2012, median urinary metabolite levels decreased by approximately 50% for DEHP, DnBP, DiBP and BBzP. Risk assessments for individual phthalates and the sum of the anti-androgenic phthalates did not indicate to attributable health risks, also at the upper percentiles of exposure. In the healthy diet group the median concentration of the DEHP metabolites was significant lower, while all phthalate metabolites except MEP tended to be lower compared to the regular diet group. Multiple log-linear regression analyses revealed significantly lower daily intakes (DIs) for all phthalates in the healthy diet group compared to the regular diet group (geometric mean ratios (gMR) between 0.510-0.618; p ≤ 0.05), except for DEP (gMR: 0.811; p = 0.273). The same analyses with the continuous variable body mass index instead of the diet groups also showed effects on the DIs (gMRs between 0.926-0.951; p ≤ 0.05), however much smaller than the effects of the diet. The results indicate that obese children following a healthy diet composed of fresh and less packaged/processed food can considerably reduce their intake for most phthalates and can have lower phthalate intakes than regular weight/regular diet children.Luísa Correia-Sá is grateful to Fundação para a Ciência e a Tecnologia (FCT) by the grant (SFRH/BD/87019/2012), financed by POCH, subsidized by Fundo Social Europeu and Ministério da Ciência, Tecnologia e Ensino Superior. The authors are thankful to the project Qualidade e Segurança Alimentar – uma abordagem (nano)tecnológica, reference NORTE-01-0145-FEDER-000011.info:eu-repo/semantics/publishedVersio

Genome sequence of the button mushroom Agaricus bisporus reveals mechanisms governing adaptation to a humic-rich ecological niche

Agaricus bisporus is the model fungus for the adaptation, persistence, and growth in the humic-rich leaf-litter environment. Aside from its ecological role, A. bisporus has been an important component of the human diet for over 200 y and worldwide cultivation of the "button mushroom" forms a multibillion dollar industry. We present two A. bisporus genomes, their gene repertoires and transcript profiles on compost andduringmushroomformation.The genomes encode a full repertoire of polysaccharide-degrading enzymes similar to that of wood-decayers. Comparative transcriptomics of mycelium grown on defined medium, casing-soil, and compost revealed genes encoding enzymes involved in xylan, cellulose, pectin, and protein degradation aremore highly expressed in compost. The striking expansion of heme-thiolate peroxidases and β-etherases is distinctive from Agaricomycotina wood-decayers and suggests a broad attack on decaying lignin and related metabolites found in humic acid-rich environment. Similarly, up-regulation of these genes together with a lignolytic manganese peroxidase, multiple copper radical oxidases, and cytochrome P450s is consistent with challenges posed by complex humic-rich substrates. The gene repertoire and expression of hydrolytic enzymes in A. bisporus is substantially different from the taxonomically related ectomycorrhizal symbiont Laccaria bicolor. A common promoter motif was also identified in genes very highly expressed in humic-rich substrates. These observations reveal genetic and enzymatic mechanisms governing adaptation to the humic-rich ecological niche formed during plant degradation, further defining the critical role such fungi contribute to soil structure and carbon sequestration in terrestrial ecosystems. Genome sequence will expedite mushroom breeding for improved agronomic characteristics

Development of a Framework Structuring Themes in the Course of Adverse Drug Reactions from a Patient's Perspective

INTRODUCTION: There is a need for more extensive information about adverse drug reactions (ADRs) for patients than currently available, including information on the course of ADRs. Aspects characterising the course of ADRs from the patient perspective have not been identified before.OBJECTIVE: We aimed to develop a framework based on common themes in the course of ADRs identified from patient descriptions in patient-reported ADRs.METHODS: In this qualitative study, patient descriptions of the course of patient-reported ADRs were analysed by a thematic analysis with an inductive approach using three different existing datasets containing patient-reported ADRs. Two datasets included patient-reported ADRs from cohort event monitoring of biologics and direct oral anticoagulants and one dataset included spontaneous reports from patients concerning medication for lower urinary tract symptoms. A conceptual framework was developed from the identified main themes and subthemes.RESULTS: Patient-reported data concerning 3888 ADRs were analysed. Six main themes with multiple subthemes were identified from patient descriptions of the course of ADRs. Four themes were descriptive: frequency of an ADR episode, duration of an ADR episode, moment or period of ADR occurrence, and development in the intensity of the ADR. Two themes concerned factors influencing the course of ADRs: triggering factors and improving factors.CONCLUSIONS: The presented framework illustrates that patients describe extensive details on the course and timeframe of ADRs. The identified themes provide a basis for improving the systematic data collection of more extensive details about ADRs from patients as a first step towards the provision of more comprehensive ADR information to patients.</p

Male Circumcision and STI Acquisition in Britain: Evidence from a National Probability Sample Survey.

BACKGROUND: It is well-established that male circumcision reduces acquisition of HIV, herpes simplex virus 2, chancroid, and syphilis. However, the effect on the acquisition of non-ulcerative sexually transmitted infections (STIs) remains unclear. We examined the relationship between circumcision and biological measures of three STIs: human papillomavirus (HPV), Chlamydia trachomatis and Mycoplasma genitalium. METHODS: A probability sample survey of 15,162 men and women aged 16-74 years (including 4,060 men aged 16-44 years) was carried out in Britain between 2010 and 2012. Participants completed a computer-assisted personal interview, including a computer-assisted self-interview, which asked about experience of STI diagnoses, and circumcision. Additionally, 1,850 urine samples from sexually-experienced men aged 16-44 years were collected and tested for STIs. Multivariable logistic regression was used to calculate adjusted odds ratios (AOR) to quantify associations between circumcision and i) self-reporting any STI diagnosis and ii) presence of STIs in urine, in men aged 16-44 years, adjusting for key socio-demographic and sexual behavioural factors. RESULTS: The prevalence of circumcision in sexually-experienced men aged 16-44 years was 17.4% (95%CI 16.0-19.0). There was no association between circumcision and reporting any previous STI diagnoses, and specifically previous chlamydia or genital warts. However, circumcised men were less likely to have any HPV type (AOR 0.26, 95% confidence interval (CI) 0.13-0.50) including high-risk HPV types (HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and/or 68) (AOR 0.14, 95% CI 0.05-0.40) detected in urine. CONCLUSIONS: Circumcised men had reduced odds of HPV detection in urine. These findings have implications for improving the precision of models of STI transmission in populations with different circumcision prevalence and in designing interventions to reduce STI acquisition

Examining the association between male circumcision and sexual function: evidence from a British probability survey.

OBJECTIVE: Despite biological advantages of male circumcision in reducing HIV/sexually transmitted infection acquisition, concern is often expressed that it may reduce sexual enjoyment and function. We examine the association between circumcision and sexual function among sexually active men in Britain using data from Britain's third National Survey of Sexual Attitudes and Lifestyles (Natsal-3). Natsal-3 asked about circumcision and included a validated measure of sexual function, the Natsal-SF, which takes into account not only sexual difficulties but also the relationship context and overall level of satisfaction. METHODS: A stratified probability survey of 6293 men and 8869 women aged 16-74 years, resident in Britain, undertaken 2010-2012, using computer-assisted face-to-face interviewing with computer-assisted self-interview for the more sensitive questions. Logistic regression was used to calculate odds ratios (ORs) to examine the association between reporting male circumcision and aspects of sexual function among sexually active men (n = 4816). RESULTS: The prevalence of male circumcision in Britain was 20.7% [95% confidence interval (CI): 19.3-21.8]. There was no association between male circumcision and, being in the lowest quintile of scores for the Natsal-SF, an indicator of poorer sexual function (adjusted OR: 0.95, 95% CI: 0.76-1.18). Circumcised men were as likely as uncircumcised men to report the specific sexual difficulties asked about in Natsal-3, except that a larger proportion of circumcised men reported erectile difficulties. This association was of borderline statistical significance after adjusting for age and relationship status (adjusted OR: 1.27, 95% CI: 0.99-1.63). CONCLUSION: Data from a large, nationally representative British survey suggest that circumcision is not associated with men's overall sexual function at a population level