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Background: E-pharmacy has gained popularity as an increasingly utilized platform for accessing healthcare services online. However, its adoption exhibits regional variations and necessitates improvement in certain aspects. Guided by the Theory of Reasoned Action (TRA) and Trust theory, this research explores the pivotal role of information literacy in influencing attitudes, perceived control, word of mouth, and trust. The overarching aim is to understand how these factors collectively impact the adoption of E-pharmacy services., Methods: The study employed Structural Equation Modeling to assess data collected from 473 participants in Nigeria. This methodology allowed for a comprehensive evaluation of the intricate relationships between information literacy, attitudes, perceived control, word of mouth, trust, and E-pharmacy adoption. By utilizing statistical tests within this framework, the research sought to provide a robust analysis of the data and derive meaningful insights., Results: The findings of the research underscore the significance of information literacy in shaping individuals' attitudes towards E-pharmacy. Higher information literacy levels were associated with more positive attitudes, an enhanced sense of perceived control, and increased positive word-of-mouth regarding the use of E-pharmacy services. Additionally, the study revealed that trust plays a crucial intermediary role between word-of-mouth communication and the actual adoption of E-pharmacy., Conclusions: In summary, this research offers a novel and comprehensive explanation of the relationship between information literacy and the adoption of E-pharmacy services. The study's outcomes contribute valuable insights to the ongoing discourse on E-pharmacy adoption, emphasizing its potential to enhance healthcare accessibility and efficiency within the evolving landscape of digital healthcare. The implications of the findings extend to policymakers, healthcare providers, and other stakeholders interested in optimizing the adoption and integration of E-pharmacy services., (© 2024. The Author(s).)

Metabolism in males and females is distinct. Differences are usually linked to sexual reproduction, with circulating signals (e.g. hormones) playing major roles. In contrast, sex differences prior to sexual maturity and intrinsic to individual metabolic tissues are less understood. We analyzed Drosophila melanogaster larvae and find that males store more fat than females, the opposite of the sexual dimorphism in adults. We show that metabolic differences are intrinsic to the major fat storage tissue, including many differences in the expression of metabolic genes. Our previous work identified fat storage roles for Spenito (Nito), a conserved RNA-binding protein and regulator of sex determination. Nito knockdown specifically in the fat storage tissue abolished fat differences between males and females. We further show that Nito is required for sex-specific expression of the master regulator of sex determination, Sex-lethal (Sxl). "Feminization" of fat storage cells via tissue-specific overexpression of a Sxl target gene made larvae lean, reduced the fat differences between males and females, and induced female-like metabolic gene expression. Altogether, this study supports a model in which Nito autonomously controls sexual dimorphisms and differential expression of metabolic genes in fat cells in part through its regulation of the sex determination pathway., Competing Interests: Conflicts of interest statement The authors declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Trichogramma wasps are egg parasitoids of agricultural lepidopteran pests. The sex of Trichogramma is determined by its ploidy as well as certain sex ratio distorters, such as the endosymbiotic bacteria Wolbachia spp. and the paternal sex ratio (PSR) chromosome. The sex determination systems of hymenopterans, such as Trichogramma spp., involve cascades of the genes transformer ( tra ), transformer - 2 ( tra2 ), and doublesex ( dsx ) and are associated with sex-specific tra and dsx splicing. First, these genes and their sex-specific variants must be identified to elucidate the interactions between the sex ratio disorders and the sex determination mechanism of Trichogramma . Methods: Here, we characterized the sex determination genes tra , tra2 , and dsx in Trichogramma dendrolimi . Sex-specific tra and dsx variants were detected in cDNA samples obtained from both male and female Trichogramma wasps. They were observed in the early embryos (1-10 h), late embryos (12-20 h), larvae (32 h and 48 h), pre-pupae (96 h), and pupae (144 h, 168 h, 192 h, and 216 h) of both male and female T. dendrolimi offspring. Results: We detected female-specific tra variants throughout the entire early female offspring stage. The male-specific variant began to express at 9-10 h as the egg was not fertilized. However, we did not find any maternally derived, female-specific tra variant in the early male embryo. This observation suggests that the female-specific tra variant expressed in the female embryo at 1-9 h may not have originated from the maternal female wasp. Discussion: The present study might be the first to identify the sex determination genes and sex-specific gene splicing in Trichogramma wasps. The findings of this study lay the foundation for investigating the sex determination mechanisms of Trichogramma and other wasps. They also facilitate sex identification in immature T. dendrolimi and the application of this important egg parasitoid in biological insect pest control programs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ning, Huo, Lv, Wang, Zhang, Che, Dong and Zhou.)

Reproduction-manipulating bacteria like Wolbachia can shift sex ratios in insects towards females, but skewed sex ratios may also arise from genetic conflicts. The flea beetle Altica lythri harbors three main mtDNA strains that are coupled to three different Wolbachia infections. Depending on the mtDNA types, the females produce either offspring with a balanced sex ratio or exclusively daughters. To obtain markers that can monitor when sex bias arises in the beetle's ontogeny, we elucidated the sex determination cascade of A. lythri. We established a RT-PCR method based on length variants of dsx (doublesex) transcripts to determine the sex of morphologically indistinguishable eggs and larvae. In females of one mtDNA type (HT1/HT1*) known to produce only daughters, male offspring were already missing at the egg stage while for females of another type (HT2), the dsx splice variants revealed a balanced sex ratio among eggs and larvae. Our data suggest that the sex determination cascade in A. lythri is initiated by maternally transmitted female-specific tra (transformer) mRNA as primary signal. This tra mRNA seems to be involved in a positive feedback loop that maintains the production of the female splice variant, as known for female offspring in Tribolium castaneum. The translation of the maternally transmitted female tra mRNA must be inhibited in male offspring, but the underlying primary genetic signal remains to be identified. We discuss which differences between the mtDNA types can influence sex determination and lead to the skewed sex ratio of HT1., (© 2023. The Author(s).)

The European Joint Programme HBM4EU coordinated and advanced human biomonitoring (HBM) in Europe in order to provide science-based evidence for chemical policy development and improve chemical management. Arsenic (As) was selected as a priority substance under the HBM4EU initiative for which open, policy relevant questions like the status of exposure had to be answered. Internal exposure to inorganic arsenic (iAs), measured as Toxic Relevant Arsenic (TRA) (the sum of As(III), As(V), MMA, DMA) in urine samples of teenagers differed among the sampling sites (BEA (Spain) > Riksmaten adolescents (Sweden), ESTEBAN (France) > FLEHS IV (Belgium), SLO CRP (Slovenia)) with geometric means between 3.84 and 8.47 μg/L. The ratio TRA to TRA + arsenobetaine or the ratio TRA to total arsenic varied between 0.22 and 0.49. Main exposure determinants for TRA were the consumption of rice and seafood. When all studies were combined, Pearson correlation analysis showed significant associations between all considered As species. Higher concentrations of DMA, quantitatively a major constituent of TRA, were found with increasing arsenobetaine concentrations, a marker for organic As intake, e.g. through seafood, indicating that other sources of DMA than metabolism of inorganic As exist, e.g. direct intake of DMA or via the intake of arsenosugars or -lipids. Given the lower toxicity of DMA(V) versus iAs, estimating the amount of DMA not originating from iAs, or normalizing TRA for arsenobetaine intake could be useful for estimating iAs exposure and risk. Comparing urinary TRA concentrations with formerly derived biomonitoring equivalent (BE) for non-carcinogenic effects (6.4 μg/L) clearly shows that all 95th percentile exposure values in the different studies exceeded this BE. This together with the fact that cancer risk may not be excluded even at lower iAs levels, suggests a possible health concern for the general population of Europe., (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)

CMC Tiga Warna is one of the coastal area management for conservation and ecotourism in southern Malang, Indonesia. Despite fewer tourist visits, the COVID-19 pandemic did not dissuade locals from managing and protecting ecotourism in the coastal area. This study aims to: (a) to describe coastal ecosystem management; and (b) to analyze coastal ecotourist visit intention related to tourism knowledge, perceived health risk, and risk attitude in the post-COVID-19 era as a part of developing strategy for coastal ecosystem management in the study area from the perspective of ecotourists and destination management. CMC Tiga Warna management, community group supervisors, the local community, and a variety of experts were interviewed in order to gather data for the current strategy. Coastal ecotourist visit intention data from domestic ecotourists was gathered via online and offline surveys. Analyzing the visit intention data with Warp-PLS. Using the visit intention model and interview data, the coastline management strategy was described. This study found that the coastal environment management plan constantly involved ecotourists and locals. Tourism knowledge and risk attitude are positively related to the visit intention, however perceived health risk is negatively related to it. The significant positive relationship between tourism knowledge and ecotourist visit intention is mediated by perceived health risk and risk attitude. Development of the coastal ecosystem management plan could be supported by boosting visit intention, ecotourism visits, or economic incentive as a motive for sustaining the conservation program's consistency, and ecological and social rewards in a sustainable manner. This study added to the Theory of Reasoned Action by adding two additional factors, tourist knowledge and perceived health risk, in addition to the attitude to predict the visit intention. The ecotourism manager should provide varied tourist information and knowledge as needed, reduce COVID-19 exposure risk at tourist destinations, and increase risk attitude., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Sex determination pathways in insects are generally characterised by an upstream primary signal, which is highly variable across species, and that regulates the splicing of a suite of downstream but highly-conserved genes ( transformer , doublesex and fruitless ). In turn, these downstream genes then regulate the expression of sex-specific characteristics in males and females. Identification of sex determination pathways has and continues to be, a critical component of insect population suppression technologies. For example, "first-generation" transgenic technologies such as fsRIDL (Female-Specific Release of Insects carrying Dominant Lethals) enabled efficient selective removal of females from a target population as a significant improvement on the sterile insect technique (SIT). Second-generation technologies such as CRISPR/Cas9 homing gene drives and precision-guided SIT (pgSIT) have used gene editing technologies to manipulate sex determination genes in vivo . The development of future, third-generation control technologies, such as Y-linked drives, (female to male) sex-reversal, or X-shredding, will require additional knowledge of aspects of sexual development, including a deeper understanding of the nature of primary signals and dosage compensation. This review shows how knowledge of sex determination in target pest species is fundamental to all phases of the development of control technologies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Siddall, Harvey-Samuel, Chapman and Leftwich.)

Aim: Based on the Theory of Reasoned Action (TRA), we examined whether attitudes of nurses from different ethnic groups, subjective norms, behavioral intentions, assessments of relationships and communication were associated with their perceptions of the quality of perinatal care provided to lesbian women., Background: Nurses administer healthcare, provide pertinent information and consultation to lesbians from pregnancy planning through birth., Introduction: During the past few decades, worldwide, there has been a rise in lesbian-parenting. Despite the changes in Israeli society's public and legal reality, intolerance and discrimination to the homosexual population is still prevalent in Israel's healthcare system., Methods: A cross-sectional study conducted between 12/2015-4/2016. Of the 270 nurses approached, 184 completed a self-report anonymous questionnaire (a response rate of 74%)., Findings: This is an important and timely study reflecting nurses' perceptions of the quality of perinatal care provided to lesbians. The study findings reflect that attitudes, subjective norms, behavioral intentions, assessments of relationships and communication of nurses from different ethnic groups are associated with their perceptions of the quality of perinatal care provided to the lesbians. The hierarchical regression analysis demonstrated that attitudes, subjective norms, behavioral intentions, assessments of relationships and communication of nurses contributed 56% to the variance of nurses' perception of their own quality of perinatal care., Discussion: TRA conceptualization predicted the quality of care of nurses from different ethnic groups treating lesbians in a perinatal setting., Conclusion: TRA provides a useful framework for understanding and predicting the motivational effect of health care personnel with the lesbian population, being at risk for stigmatization and receiving less quality perinatal care., Implications for Nursing and Heath Policy: Our findings revealed the importance of formulating a recognized policy in the field of LGBT medicine at the national level. Further training of nurses as to the lesbians' unique health needs, might improve the nurses' relationships and communication as well as the quality of perinatal nursing care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tzur-Peled, Kushnir and Sarid.)

Radial artery pseudoaneurysm is a very rare complication. In the presented case, computed tomography 3 months post percutaneous coronary intervention demonstrated contrast extravasation, suggestive of radial artery pseudoaneurysm. This complication was managed with thrombin infusion at the distal radial artery.

Transfemoral access (TFA) is a widely used first-line approach for most peripheral vascular interventions. Since its introduction in cardiologic and neurointerventional procedures, several advantages of transradial access (TRA) over TFA have been demonstrated, such as patient preference, lower complication rates, early ambulation, and shorter hospital stay. However, studies reporting the safety and efficacy of this approach for peripheral vascular interventions performed by interventional radiologists are relatively few. This review aimed to summarize the technique and clinical applications of TRA in percutaneous transcatheter visceral artery embolization and the management of complications., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2021 The Korean Society of Radiology.)

The availability of transparent zebrafish mutants (either TraNac : tra b6/b6 ; nac w2/w2 or casper: roy a9/a9 ; nac w2/w2 ) for live imaging studies together with the ease of generating transgenic lines are two of the strengths of the zebrafish model organism. The fact that transparent casper ( roy a9/a9 ;nac w2/w2 ) and silver nacre ( nac w2/w2 ) mutants are indistinguishable by eye at early stages (1-5 days post-fertilization; dpf) means many fish must be raised and later culled if they are not transparent. To identify translucent mutants early and easily at the early larval stage (≤5 dpf) before they are classified as protected animals, we developed a simple screening method using standard fluorescence microscopy. We estimate that this procedure could annually save 60,000 animals worldwide., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Wenz R et al.)

Background: Debate still occurs of the benefits of transradial access (TRA) versus transfemoral access (TFA), especially for complex percutaneous coronary interventions. Recent data has shown equivalent efficacy and improved safety outcomes with TRA., Objectives: To systematically review and perform a meta-analysis comparing procedural characteristics and clinical outcomes of TRA versus TFA in patients who underwent percutaneous coronary intervention (PCI) for left main (LM) disease., Methods: We conducted an electronic database search of all published data for studies that compared TRA with TFA in patients undergoing PCI of LM disease. Event rates were compared using the odds ratio (OR) as a measure of effect size. Random-effects models were used to account for interstudy heterogeneity., Results: A total of 12 observational studies including 17,258 patients (TRA n = 7,971; TFA n = 9,287) were included. Compared to TFA, TRA was associated with a significant reduction in access site bleeding (OR = 0.11; 95% confidence interval [CI] = 0.04-0.26; I 2 = 0%; p < .0001), major bleeding (OR = 0.44; 95% CI = 0.27-0.69; I 2 = 0%; p = .0005) or any bleeding episode (OR = 0.43; 95% CI = 0.27-0.69; I 2 = 12%; p = .0004). Rates of access site or vascular complications (OR = 0.26; 95% CI = 0.17-0.40; I 2 = 0%; p < .00001) and in-hospital mortality (OR = 0.49; 95% CI = 0.31-0.79: I 2 = 11%; p = .004) were also lower in the TRA group. There were no significant differences in procedural outcomes between TRA and TFA except for a significant reduction in the rate of long-term target vessel revascularization (TVR) in the TRA group (OR = 0.62; 95% CI = 0.41-0.94: I 2 = 0%: p = .02). We further performed a subgroup analysis for unprotected left main PCI only, which showed a significant reduction in rates of any bleeding episode, lower access site or vascular complications, and in-hospital mortality with TRA as compared to TFA., Conclusion: Patients undergoing PCI for LM disease via TRA have with less bleeding, reduced access site or vascular complications, reduced in-hospital mortality, comparable procedural success, and possibly better long-term clinical efficacy when compared to those undergoing the procedure via TFA., (© 2019 Wiley Periodicals, Inc.)

Background: The transradial artery (TRA) approach for neuroendovascular procedures continues to gain popularity, but neurointerventionalists still lag behind interventional cardiologists in the adoption of a TRA-first approach. This study compares the complications and efficiency of the TRA approach to the standard transfemoral artery (TFA) approach at our institution during our initial phase of adopting a TRA-first approach., Methods: A retrospective analysis was performed on all consecutive neuroangiographic procedures performed at a large cerebrovascular center from October 1, 2018 to June 30, 2019. The standard TFA approach was compared with TRA access, with the primary outcome of complications analyzed via a propensity-adjusted analysis., Results: A total of 1050 consecutive procedures were performed on 877 patients during this 9-month period; 206 (20%) procedures were performed via TRA and 844 (80%) via TFA. The overall complication rate was significantly higher with the TFA procedures than with the TRA procedures (7% (60/844) vs 2% (4/206), respectively; p=0.003). A propensity-adjusted analysis showed that the TFA approach was a significant risk factor for a complication (OR 3.6, 95% CI 1.3 to 10.2, p=0.01). However, the propensity analysis showed that fluoroscopy times were on average 4 min less for TFA procedures than for TRA procedures (p=0.003)., Conclusion: The TRA approach for neuroendovascular procedures appears to be safer than the TFA approach. Although a steep learning curve is initially encountered when adopting the TRA approach, the transition to a TRA-first practice can be performed safely for neurointerventional procedures and may reduce complications., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Transfemoral access is the traditional gold standard for uterine artery angiography; however, transradial access is gaining in popularity because of its decreased complication profile and patient preference. We present a case of a patient who underwent successful total abdominal hysterectomy for symptomatic uterine fibroids with ambiguous pelvic vasculature that would have been otherwise aborted if it were not for intraoperative transradial access angiography., Case Presentation: A 52-year-old Caucasian woman presented to her gynecologist for an elective total abdominal hysterectomy and bilateral salpingo-oophorectomy. During preoperative imaging, a 15-cm mass consistent with a uterine fibroid was identified, and the patient's gynecologist decided to treat her with surgical resection, given the fibroid's size. The procedure was halted upon discovery of a complicated vascular plexus at the fundus of the uterus, and an intraoperative vascular consult was requested. The vascular operator used a transradial access to perform pelvic angiography in real time to identify the complicated pelvic vasculature, which allowed the gynecologist to surgically resect the uterine fibroid. The patient was discharged on postoperative day 4 without any complications., Conclusions: Intraoperative imaging is a useful technique for the identification of complicated anatomical structures during surgical procedures. The successful outcome of this case demonstrates an additional unique benefit of transradial access and highlights an opportunity for interdisciplinary collaboration for management of complicated surgical interventions.

Niraparib is an investigational oral, once daily, selective poly(ADP-Ribose) polymerase (PARP)-1 and PARP-2 inhibitor. In the pivotal Phase 3 NOVA/ENGOT/OV16 study, niraparib met its primary endpoint of improving progression-free survival (PFS) for adult patients with recurrent, platinum sensitive, ovarian, fallopian tube, or primary peritoneal cancer in complete or partial response to platinum-based chemotherapy. Significant improvements in PFS were seen in all patient cohorts regardless of biomarker status. This study evaluates the absorption, metabolism and excretion (AME) of 14 C-niraparib, administered to six patients as a single oral dose of 300 mg with a radioactivity of 100 μCi. Total radioactivity (TRA) in whole blood, plasma, urine and faeces was measured using liquid scintillation counting (LSC) to obtain the mass balance of niraparib. Moreover, metabolite profiling was performed on selected plasma, urine and faeces samples using liquid chromatography - tandem mass spectrometry (LC-MS/MS) coupled to off-line LSC. Mean TRA recovered over 504 h was 47.5% in urine and 38.8% in faeces, indicating that both renal and hepatic pathways are comparably involved in excretion of niraparib and its metabolites. The elimination of 14 C-radioactivity was slow, with t 1/2 in plasma on average 92.5 h. Oral absorption of 14 C-niraparib was rapid, with niraparib concentrations peaking at 2.49 h, and reaching a mean maximum concentration of 540 ng/mL. Two major metabolites were found: the known metabolite M1 (amide hydrolysed niraparib) and the glucuronide of M1. Based on this study it was shown that niraparib undergoes hydrolytic, and conjugative metabolic conversions, with the oxidative pathway being minimal.

Objectives: This study sought to examine the relationship between access site practice and clinical outcomes in patients requiring percutaneous coronary intervention (PCI) following thrombolysis for ST-segment elevation myocardial infarction (STEMI)., Background: Transradial access (TRA) is associated with better outcomes in patients requiring PCI for STEMI. A significant proportion of STEMI patients may receive thrombolysis before undergoing PCI in many countries across the world. There are limited data around access site practice and its associated outcomes in this cohort of patients., Methods: The author used the British Cardiovascular Intervention Society dataset to investigate the outcomes of patients undergoing PCI following thrombolysis between 2007 and 2014. Patients were divided into TRA and transfemoral access groups depending on the access site used. Multiple logistic regression and propensity score matching were used to study the association of access site with in-hospital and long-term mortality, major bleeding, and access site-related complications., Results: A total of 10,209 patients received thrombolysis and PCI during the study time. TRA was used in 48% (n = 4,959) of patients; 3.3% (n = 336) patients died in hospital, 1.6% (n = 165) of patients experienced major bleeding, 4.2% (n = 437) experienced major adverse cardiac events (MACE), and 4.6% (n = 468) experienced 30-day mortality. After multivariate adjustment, TRA was associated with significantly reduced odds of in-hospital mortality (odds ratio [OR]: 0.59; 95% confidence interval [CI]: 0.42 to 0.83; p = 0.002), major bleeding (OR: 0.45; 95% CI: 0.31 to 0.66; p < 0.001), MACE (OR: 0.72; 95% CI: 0.55 to 0.94; p = 0.01), and 30-day mortality (OR: 0.72; 95% CI: 0.55 to 0.94; p = 0.01)., Conclusions: TRA is associated with decreased odds of bleeding complications, mortality, and MACE in patients undergoing PCI following thrombolysis and should be preferred access site choice in this cohort of patients., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

T cells undergo positive and negative selection in the thymic cortex and medulla, respectively. A promiscuous expression of a wide array of self-antigens in the thymus is essential for the negative selection of self-reactive T cells and the establishment of central tolerance. Aire was originally thought to be the exclusive factor regulating the expression of tissue-restricted antigens, but Fezf2 recently emerged as a critical transcription factor in this regulatory activity. Fezf2 is selectively expressed in thymic medullary epithelial cells, regulates a large number of tissue-restricted antigens and suppresses the onset of autoimmune responses. Here, we discuss novel findings on the transcriptional mechanisms of tissue restricted-antigen expression in the medullary thymic epithelial cells and its effects on T cell selection., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction and Aim: Transradial (TRA) instead of transfemoral (TFA) approach strategy has been presented in research literature as superior access strategy especially for acute ST elevation myocardial infarction (STEMI) primary percutaneous coronary intervention (PCI). There is a paucity of registry-based data of outcomes from default TRA strategy compared to TFA., Materials and Methods: All-comers STEMI PCI institutional Registry identified 1808 consecutive patients in time-frame of 40 months from 2007 to 2010, without making any exclusions. Moreover, we applied Propensity Score Matching (PSM) to replace randomization, address the potential confounding and selection bias. PSM derived 565 congruent pairs of patients from the groups., Results: After 30 days the primary composite endpoint of major adverse cardiovascular events (MACE) was in favor of TRA 6.5% vs. 12.4% in TFA group, simultaneously secondary endpoints of death in TRA with rate of 4.8% and with rate of 10.1% in TFA. Moreover, the rate of major access related bleeding was 1.1% in TRA vs. 8.5% in TFA, in contrast the major non-access related bleeding was 1.8% and 2.4% respectively showed no significant difference. One year Kaplan Meier survival plots were in favor of TRA., Conclusions: Default transradial access strategy is associated with improved STEMI PCI outcomes.

Biofilms formed by nontypeable Haemophilus influenzae (NTHI) are central to the chronicity, recurrence, and resistance to treatment of multiple human respiratory tract diseases including otitis media, chronic rhinosinusitis, and exacerbations of both cystic fibrosis and chronic obstructive pulmonary disease. Extracellular DNA (eDNA) and associated DNABII proteins are essential to the overall architecture and structural integrity of biofilms formed by NTHI and all other bacterial pathogens tested to date. Although cell lysis and outer-membrane vesicle extrusion are possible means by which these canonically intracellular components might be released into the extracellular environment for incorporation into the biofilm matrix, we hypothesized that NTHI additionally used a mechanism of active DNA release. Herein, we describe a mechanism whereby DNA and associated DNABII proteins transit from the bacterial cytoplasm to the periplasm via an inner-membrane pore complex (TraC and TraG) with homology to type IV secretion-like systems. These components exit the bacterial cell through the ComE pore through which the NTHI type IV pilus is expressed. The described mechanism is independent of explosive cell lysis or cell death, and the release of DNA is confined to a discrete subpolar location, which suggests a novel form of DNA release from viable NTHI. Identification of the mechanisms and determination of the kinetics by which critical biofilm matrix-stabilizing components are released will aid in the design of novel biofilm-targeted therapeutic and preventative strategies for diseases caused by NTHI and many other human pathogens known to integrate eDNA and DNABII proteins into their biofilm matrix., Competing Interests: Conflict of interest statement: S.D.G. and L.O.B. are scientific advisors to and have equity in ProclaRx, LLC, to whom technology related to DNABII proteins has been licensed.

Drosophila females are larger than males. In this article, we describe how X -chromosome dosage drives sexual dimorphism of body size through two means: first, through unbalanced expression of a key X -linked growth-regulating gene, and second, through female-specific activation of the sex-determination pathway. X -chromosome dosage determines phenotypic sex by regulating the genes of the sex-determining pathway. In the presence of two sets of X -chromosome signal elements (XSEs), Sex-lethal ( Sxl ) is activated in female ( XX ) but not male ( XY ) animals. Sxl activates transformer ( tra ), a gene that encodes a splicing factor essential for female-specific development. It has previously been shown that null mutations in the tra gene result in only a partial reduction of body size of XX animals, which shows that other factors must contribute to size determination. We tested whether X dosage directly affects animal size by analyzing males with duplications of X -chromosomal segments. Upon tiling across the X chromosome, we found four duplications that increase male size by >9%. Within these, we identified several genes that promote growth as a result of duplication. Only one of these, Myc , was found not to be dosage compensated. Together, our results indicate that both Myc dosage and tra expression play crucial roles in determining sex-specific size in Drosophila larvae and adult tissue. Since Myc also acts as an XSE that contributes to tra activation in early development, a double dose of Myc in females serves at least twice in development to promote sexual size dimorphism., (Copyright © 2017 by the Genetics Society of America.)

Insulin self-tolerance is, to a large extent, assured by the expression of small quantities of insulin by medullary thymic epithelial cells (mTECs). Regulation of thymic insulin expression differs from that in pancreas and its therapeutic manipulation could play an important role in the prevention of type 1 diabetes (T1D). Knowledge of the transcriptional regulators involved in the mTEC nuclear environment is essential for the development of such therapeutics. The yeast one-hybrid (Y1H) approach was used in order to identify such mTEC-specific nuclear proteins. We used a target composed of the human insulin gene promoter joined to the upstream class III VNTR allele, which is associated with both protection from T1D and higher thymic insulin expression, and a cDNA library from our insulin-producing mouse mTEC line. The Y1H screening allowed the identification of eleven proteins. An in vitro assay was used to confirm and quantify protein-DNA binding to the human insulin gene promoter alone or joined to a class I or class III VNTR allele, and identified the transcription factors ZBTB7A, JUN and EWSR1 as strong interacting partners. All three proteins could induce insulin expression in transfected HEK-293 cells, but ZBTB7A provided the most robust results especially in the presence of AIRE, with an additional 11-fold increase of the insulin mRNA levels from a co-transfected reporter driven by the class III VNTR allele. Thus, ZBTB7A is identified as a strong candidate for regulation of thymic insulin expression., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: To study the causes of and to develop a risk score for failure of transradial approach (TRA) for percutaneous coronary intervention (PCI)., Background: TRA-PCI failure has been reported in 5% to 10% of cases., Methods: TRA-PCI failure was categorized as primary (clinical reasons) or crossover failure. Multivariate analysis was performed to determine independent predictors of TRA-PCI failure, and an integer risk score was developed., Results: From January to June 2010, TRA-PCI was attempted in 1,609 (97.3%) consecutive patients, whereas 45 (2.7%) had primary TRA-PCI failure. Crossover TRA-PCI failure occurred in 30 (1.8%) patients. Causes of primary TRA-PCI failure included chronic radial artery occlusion (11%), previous coronary artery bypass graft (27%), and cardiogenic shock (20%). Causes for crossover TRA-PCI failure included: inadequate puncture in 17 patients (57%); radial artery spasm in 5 (17%); radial loop in 4 (13%); subclavian tortuosity in 2 (7%); and inadequate guide catheter support in 2 (7%) patients. Female sex (odds ratio [OR]: 3.2; 95% confidence interval [CI]: 1.95 to 5.26, p < 0.0001), previous coronary artery bypass graft (OR: 6.1; 95% CI: 3.63 to 10.05, p < 0.0001), and cardiogenic shock (OR: 11.2; 95% CI: 2.78 to 41.2, p = 0.0011) were independent predictors of TRA-PCI failure. Risk score values from 0 to 7 predicted a TRA-PCI failure rate from 2% to 80%., Conclusions: In a high-volume radial center, 2.7% of patients undergoing PCI are excluded from initial TRA on clinical grounds, whereas crossover to femoral approach is required in only 1.8% of the cases. A new simple clinical risk score is developed to predict TRA-PCI failure., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Until recently, little was known about the importance of CD8+ T effectors in promoting and preventing autoimmune disease development. CD8+ T cells can oppose or promote autoimmune disease through activities as suppressor cells and as cytotoxic effectors. Studies in several distinct autoimmune models and data from patient samples are beginning to establish the importance of CD8+ T cells in these diseases and to define the mechanisms by which these cells influence autoimmunity. CD8+ effectors can promote disease via dysregulated secretion of inflammatory cytokines, skewed differentiation profiles and inappropriate apoptosis induction of target cells, and work to block disease by eliminating self-reactive cells and self-antigen sources, or as regulatory T cells. Defining the often major contribution of CD8+ T cells to autoimmune disease and identifying the mechanisms by which they alter the pathogenesis of disease is a rapidly expanding area of study and will add valuable information to our understanding of the kinetics, pathology and biology of autoimmune disease., (Published by Elsevier Ltd.)

Objectives: This study sought to investigate the influence of access site utilization on mortality, major adverse cardiac and cardiovascular events (MACCE), bleeding, and vascular complications in a large number of patients treated by primary percutaneous coronary intervention (PPCI) in the United Kingdom over a 5-year period, through analysis of the British Cardiovascular Intervention Society database., Background: Despite advances in antithrombotic and antiplatelet therapy, bleeding complications remain an important cause of morbidity and mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing PPCI. A significant proportion of such bleeding complications are related to the access site, and adoption of radial access may reduce these complications. These benefits have not previously been studied in a large unselected national population of PPCI patients., Methods: Mortality (30-day), MACCE (a composite of 30-day mortality and in-hospital myocardial re-infarction, target vessel revascularization, and cerebrovascular events), and bleeding and access site complications were studied based on transfemoral access (TFA) and transradial access (TRA) site utilization in PPCI STEMI patients. The influence of access site selection was studied in 46,128 PPCI patients; TFA was used in 28,091 patients and TRA in 18,037. Data were adjusted for potential confounders using Cox regression that accounted for the propensity to undergo radial or femoral approach., Results: TRA was independently associated with a lower 30-day mortality (hazard ratio [HR]: 0.71, 95% confidence interval [CI]: 0.52 to 0.97; p < 0.05), in-hospital MACCE (HR: 0.73, 95% CI: 0.57 to 0.93; p < 0.05), major bleeding (HR: 0.37, 95% CI: 0.18 to 0.74; p < 0.01), and access site complications (HR: 0.38, 95% CI: 0.19 to 0.75; p < 0.01)., Conclusions: This analysis of a large number of PPCI procedures demonstrates that utilization of TRA is independently associated with major reductions in mortality, MACCE, major bleeding, and vascular complication rates., (Copyright © 2013. Published by Elsevier Inc.)

When XX animals homozygous for the temperature-sensitive mutation vir ts of virilizer (2-103.9) are raised at the restrictive temperature of 29° C, they are transformed into sterile intersexes with a morphology comparable to XX flies mutant at the sex-determining gene doublesex (dsx). The gonads of the vir ts intersexes are ovaries in which the germ cells undergo abortive oogenesis. At the permissive temperature of 25° C or below, XX vir ts animals develop into marginally fertile females. The temperature-sensitive period of vir ts is within the third larval instar. XY males are not affected by the mutation. Animals that are homozygous for vir ts and either transformer (tra) or tra2 develop as pseudomales; on the other hand, constitutive expression of a female-specific tra product rescues XX animals from the effect of vir ts , but these females are sterile. The data show that tra and tra2 are epistatic to vir. Animals with only one wildtype copy of either tra or tra2 and mutant for vir ts are already transformed into intersexes at 25° C. Conversely, the presence of three copies of the tra + gene largely prevents the effect of vir ts at 29° C; such flies are practically female, but sterile. Animals homozygous for vir ts and heterozygous for dsx D /+, raised at 29° C, are transformed into severely masculinized intersexes or almost pseudomales. The observations suggest that vir acts above and via tra and tra2 to achieve proper female-specific expression of the dsx gene in XX zygotes.