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Background: Chagas disease remains a persistent vector-borne neglected tropical disease throughout the Americas and threatens both human and animal health. Diverse control methods have been used to target triatomine vector populations, with household insecticides being the most common. As an alternative to environmental sprays, host-targeted systemic insecticides (or endectocides) allow for application of chemicals to vertebrate hosts, resulting in toxic blood meals for arthropods (xenointoxication). In this study, we evaluated three systemic insecticide products for their ability to kill triatomines. Methods: Chickens were fed the insecticides orally, following which triatomines were allowed to feed on the treated chickens. The insecticide products tested included: Safe-Guard® Aquasol (fenbendazole), Ivomec® Pour-On (ivermectin) and Bravecto® (fluralaner). Triatoma gerstaeckeri nymphs were allowed to feed on insecticide-live birds at 0, 3, 7, 14, 28 and 56 days post-treatment. The survival and feeding status of the T. gerstaeckeri insects were recorded and analyzed using Kaplan–Meier curves and logistic regression. Results: Feeding on fluralaner-treated chickens resulted 50–100% mortality in T. gerstaeckeri over the first 14 days post-treatment but not later; in contrast, all insects that fed on fenbendazole- and ivermectin-treated chickens survived. Liquid chromatography tandem mass spectrometry (LC-QQQ) analysis, used to detect the concentration of fluralaner and fenbendazole in chicken plasma, revealed the presence of fluralaner in plasma at 3, 7, and 14 days post-treatment but not later, with the highest concentrations found at 3 and 7 days post-treatment. However, fenbendazole concentration was below the limit of detection at all time points. Conclusions: Xenointoxication using fluralaner in poultry is a potential new tool for integrated vector control to reduce risk of Chagas disease. [ABSTRACT FROM AUTHOR]

Background: Hypertensive disorders of pregnancy, including hypertension, are a leading cause of maternal mortality in Nigeria. However, there is a paucity of data on pregnant women with hypertension who receive care in primary health care facilities. This study presents the results from a cross-sectional analysis of pregnant women enrolled in the Hypertension Treatment in Nigeria Program which is aimed at integrating and strengthening hypertension care in primary health care centres. Methods: A descriptive analysis of the baseline results from the Hypertension Treatment in Nigeria Program was performed. Baseline blood pressures, treatment and control rates of pregnant women were analysed and compared to other adult women of reproductive age. A complete case analysis was performed, and a two-sided p value < 0.05 was considered statistically significant. Results: Between January 2020 to October 2022, 5972 women of reproductive age were enrolled in the 60 primary healthcare centres participating in the Hypertension Treatment in Nigeria Program and 112 (2%) were pregnant. Overall mean age (SD) was 39.6 years (6.3). Co-morbidities were rare in both groups, and blood pressures were similar amongst pregnant and non-pregnant women (overall mean (SD) first systolic and diastolic blood pressures were 157.4 (20.6)/100.7 (13.6) mm Hg and overall mean (SD) second systolic and diastolic blood pressures were 151.7 (20.1)/98.4 (13.5) mm Hg). However, compared to non-pregnant women, pregnant women had a higher rate of newly diagnosed hypertension (65.2% versus 54.4% p = 0.02) and lower baseline walk-in treatment (32.1% versus 42.1%, p = 0.03). The control rate was numerically lower among pregnant patients (6.3% versus 10.2%, p = 0.17), but was not statistically significant. Some pregnant patients (8.3%) were on medications contraindicated in pregnancy, and none of the pregnant women were on aspirin for primary prevention of preeclampsia. Conclusions: These findings indicate significant gaps in care and important areas for future studies to improve the quality of care and outcomes for pregnant women with hypertension in Nigeria, a country with the highest burden of maternal mortality globally. [ABSTRACT FROM AUTHOR]

Background: The dilution effect is the reduction in vector-borne pathogen transmission associated with the presence of diverse potential host species, some of which are incompetent. It is popularized as the notion that increased biodiversity leads to decreased rates of disease. West Nile virus (WNV) is an endemic mosquito-borne virus in the United States that is maintained in a zoonotic cycle involving various avian host species. In Atlanta, Georgia, substantial WNV presence in the vector and host species has not translated into a high number of human cases. Methods: To determine whether a dilution effect was contributing to this reduced transmission, we characterized the host species community composition and performed WNV surveillance of hosts and vectors in urban Atlanta between 2010 and 2011. We tested the relationship between host diversity and both host seroprevalence and vector infection rates using a negative binomial generalized linear mixed model. Results: Regardless of how we measured host diversity or whether we considered host seroprevalence and vector infection rates as predictor variables or outcome variables, we did not detect a dilution effect. Rather, we detected an amplification effect, in which increased host diversity resulted in increased seroprevalence or infection rates; this is the first empirical evidence for this effect in a mosquito-borne system. Conclusions: We suggest that this effect may be driven by an over-abundance of moderately-to poorly-competent host species, such as northern cardinals and members of the Mimid family, which cause optimal hosts to become rarer and present primarily in species-rich areas. Our results support the notion that dilution or amplification effects depend more on the identities of the species comprising the host community than on the absolute diversity of hosts. [ABSTRACT FROM AUTHOR]

Background: In low-income countries (LICs), HIV sentinel surveillance surveys (HIV-SSS) are recommended in between two demographic and health surveys, due to low-cost than the latter. Using the classical unlinked anonymous testing (UAT), HIV-SSS among pregnant women raised certain ethical and financial challenges. We therefore aimed at evaluating how to use prevention of mother-to-child transmission of HIV (PMTCT) routine data as an alternative approach for HIV-SSS in LICs.Methods: A survey conducted through 2012 among first antenatal-care attendees (ANC1) in the ten regions of Cameroon. HIV testing was performed at PMTCT clinics as-per the national serial algorithm (rapid test), and PMTCT site laboratory (PMTCT-SL) performances were evaluated by comparison with results of the national reference laboratory (NRL), determined as the reference standard.Results: Acceptance rate for HIV testing was 99%, for a total of 6521 ANC1 (49 · 3% aged 15-24) enrolled nationwide. Among 6103 eligible ANC1, sensitivity (using NRL testing as the reference standard) was 81 · 2%, ranging from 58 · 8% (South region) to 100% (West region); thus implying that 18 · 8% HIV-infected ANC1 declared HIV-negative at the PMTCT-SL were positive from NRL-results. Specificity was 99 · 3%, without significant disparity across sites. At population-level, this implies that every year in Cameroon, ~2,500 HIV-infected women are wrongly declared seronegative, while ~1,000 are wrongly declared seropositive. Only 44 · 4% (16/36) of evaluated laboratories reached the quality target of 80%.Conclusions: The study identified weaknesses in routine PMTCT HIV testing. As Cameroon transitions to using routine PMTCT data for HIV-SSS among pregnant women, there is need in optimizing quality system to ensure robust routine HIV testing for programmatic and surveillance purposes. [ABSTRACT FROM AUTHOR]

Background: SCLC has limited treatment options and inadequate preclinical models. Promising activity of arsenic trioxide (ASO) recorded in conventional preclinical models of SCLC supported the clinical evaluation of ASO in patients. We assessed the efficacy of ASO in relapsed SCLC patients and in corresponding patient-derived xenografts (PDX).Methods: Single arm, Simon 2-stage, phase II trial to enroll patients with relapsed SCLC who have failed at least one line of therapy. ASO was administered as an intravenous infusion over 1-2 h daily for 4 days in week 1 and for 2 days in weeks 2-6 of an 8-week cycle. Treatment continued until disease progression. Pretreatment tumor biopsy was employed for PDX generation through direct implantation into subcutaneous pockets of SCID mice without in vitro manipulation and serially propagated for five generations. Ex vivo efficacy of cisplatin (3 mg/kg i.p. weekly) and ASO (3.75 mg/kg i.p. every other day) was tested in PDX representative of platinum sensitive and platinum refractory SCLC.Results: The best response in 17 evaluable patients was stable disease in 2 (12 %), progressive disease in 15 (88 %) patients and median time-to-progression of seven (range 1-7) weeks. PDX was successfully grown in 5 of 9 (56 %) transplanted biopsy samples. Serially-propagated PDXs preserved characteristic small cell histology and genomic stability confirmed by immunohistochemistry, short tandem repeat (STR) profiling and targeted sequencing. ASO showed in vitro cytotoxicity but lacked in vivo efficacy against SCLC PDX tumor growth.Conclusions: Cisplatin inhibited growth of PDX derived from platinum-sensitive SCLC but was ineffective against PDX from platinum-refractory SCLC. Strong concordance between clinical and ex vivo effects of ASO and cisplatin in SCLC supports the use of PDX models to prescreen promising anticancer agents prior to clinical testing in SCLC patients. Trial Registration The study was registered at http://www.clinicaltrials.gov (NCT01470248). [ABSTRACT FROM AUTHOR]

Background: Various ecological and physiological mechanisms might influence the probability that two or more pathogens may simultaneously or sequentially infect a host individual. Concurrent infections can have important consequences for host condition and fitness, including elevated mortality risks. In addition, interactions between coinfecting pathogens may have important implications for transmission dynamics. Methods: Here, we explore patterns of association between two common avian pathogens (West Nile virus and avian malaria parasites) among a suburban bird community in Chicago, IL, USA that share mosquito vectors. We surveyed 1714 individual birds across 13 species for both pathogens through established molecular protocols. Results: Field investigations of haemosporidian and West Nile virus (WNV) infections among sampled birds yielded an inverse association between WNV serostatus and Plasmodium infection status. This relationship occurred in adult birds but not in juveniles. There was no evidence for a relationship between Haemoproteus infection and WNV serostatus. We detected similar prevalence of Plasmodium among birds captured with active WNV infections and spatiotemporally paired WNV-naïve individuals of the same species, demonstrating that the two pathogens can co-infect hosts. Conclusions: Mechanisms explaining the negative association between WNV serostatus and Plasmodium infection status remain unclear and must be resolved through experimental infection procedures. However, our results highlight potential interactions between two common avian pathogens that may influence their transmission among hosts. This is especially relevant considering that West Nile virus is a common zoonotic pathogen with public health implications. Moreover, both pathogens are instructive models in infectious disease ecology, and infection with either has fitness consequences for their avian hosts. [ABSTRACT FROM AUTHOR]

Background Krüppel-like Factor 2 (KLF2) plays an important role in vessel maturation during embryonic development. In adult mice, KLF2 regulates expression of the tight junction protein occludin, which may allow KLF2 to maintain vascular integrity. Adult tamoxifen-inducible Krüppel-like Factor 4 (KLF4) knockout mice have thickened arterial intima following vascular injury. The role of KLF4, and the possible overlapping functions of KLF2 and KLF4, in the developing vasculature are not well-studied. Results Endothelial breaks are observed in a major vessel, the primary head vein (PHV), in KLF2-/-KLF4-/- embryos at E9.5. KLF2-/-KLF4-/- embryos die by E10.5, which is earlier than either single knockout. Gross hemorrhaging of multiple vessels may be the cause of death. E9.5 KLF2-/-KLF4+/- embryos do not exhibit gross hemorrhaging, but crosssections display disruptions of the endothelial cell layer of the PHV, and these embryos generally also die by E10.5. Electron micrographs confirm that there are gaps in the PHV endothelial layer in E9.5 KLF2-/-KLF4-/- embryos, and show that the endothelial cells are abnormally bulbous compared to KLF2-/- and wild-type (WT). The amount of endothelial Nitric Oxide Synthase (eNOS) mRNA, which encodes an endothelial regulator, is reduced by 10-fold in E9.5 KLF2-/-KLF4-/- compared to KLF2-/- and WT embryos. VEGFR2, an eNOS inducer, and occludin, a tight junction protein, gene expression are also reduced in E9.5 KLF2-/-KLF4-/- compared to KLF2-/- and WT embryos. Conclusions This study begins to define the roles of KLF2 and KLF4 in the embryonic development of blood vessels. It indicates that the two genes interact to maintain an intact endothelial layer. KLF2 and KLF4 positively regulate the eNOS, VEGFR2 and occludin genes. Downregulation of these genes in KLF2-/-KLF4-/- embryos may result in the observed loss of vascular integrity. [ABSTRACT FROM AUTHOR]

Background: An important determinant of mosquito-borne pathogen transmission is the spatial distribution of vectors. The primary vectors of West Nile virus (WNV) in Illinois are Culex pipiens Linnaeus (Diptera: Culicidae) and Culex restuans Theobald. In urban environments, these mosquitoes commonly oviposit in roadside storm water catch basins. However, use of this habitat is inconsistent, with abundance of larvae varying significantly across catch basins at a fine spatial scale. Methods: We tested the hypothesis that attributes of the biotic and abiotic environment contribute to spatial and temporal variation in production of mosquito vectors, characterizing the relationship between terrestrial vegetation and aquatic chemistry and Culex abundance in Chicago, Illinois. Larvae were sampled from 60 catch basins from June 14 to October 3, 2009. Density of shrubs and 14 tree genera surrounding the basins were quantified, as well as aquatic chemistry content of each basin. Results: We demonstrate that the spatial pattern of Culex abundance in catch basins is strongly influenced by environmental characteristics, resulting in significant variation across the urban landscape. Using regression and machine learning techniques, we described landscape features and microhabitat characteristics of four Chicago neighborhoods and examined the implications of these measures for larval abundance in adjacent catch basins. The important positive predictors of high larval abundance were aquatic ammonia, nitrates, and area of shrubs of height <1 m surrounding the catch basins, whereas pH and area of flowering shrub were negatively correlated with larval abundance. Tree density, particularly of arborvitae, maple, and pear, also positively influenced the distribution of Culex during the fruit-bearing periods and early senescent periods in August and September. Conclusions: This study identifies environmental predictors of mosquito production in urban environments. Because an abundance of adult Culex is integral to efficient WNV transmission and mosquitoes are found in especially high densities near larval habitats, identifying aquatic sites for Culex and landscape features that promote larval production are important in predicting the spatial pattern of cases of human and veterinary illness. Thus, these data enable accurate assessment of regions at risk for exposure to WNV and aid in the prevention of vector-borne disease transmission. [ABSTRACT FROM AUTHOR]

Background: Models of the effects of environmental factors on West Nile virus disease risk have yielded conflicting outcomes. The role of precipitation has been especially difficult to discern from existing studies, due in part to habitat and behavior characteristics of specific vector species and because of differences in the temporal and spatial scales of the published studies. We used spatial and statistical modeling techniques to analyze and forecast fine scale spatial (2000 m grid) and temporal (weekly) patterns of West Nile virus mosquito infection relative to changing weather conditions in the urban landscape of the greater Chicago, Illinois, region for the years from 2004 to 2008. Results: Increased air temperature was the strongest temporal predictor of increased infection in Culex pipiens and Culex restuans mosquitoes, with cumulative high temperature differences being a key factor distinguishing years with higher mosquito infection and higher human illness rates from those with lower rates. Drier conditions in the spring followed by wetter conditions just prior to an increase in infection were factors in some but not all years. Overall, 80% of the weekly variation in mosquito infection was explained by prior weather conditions. Spatially, lower precipitation was the most important variable predicting stronger mosquito infection; precipitation and temperature alone could explain the pattern of spatial variability better than could other environmental variables (79% explained in the best model). Variables related to impervious surfaces and elevation differences were of modest importance in the spatial model. Conclusion: Finely grained temporal and spatial patterns of precipitation and air temperature have a consistent and significant impact on the timing and location of increased mosquito infection in the northeastern Illinois study area. The use of local weather data at multiple monitoring locations and the integration of mosquito infection data from numerous sources across several years are important to the strength of the models presented. The other spatial environmental factors that tended to be important, including impervious surfaces and elevation measures, would mediate the effect of rainfall on soils and in urban catch basins. Changes in weather patterns with global climate change make it especially important to improve our ability to predict how inter-related local weather and environmental factors affect vectors and vector-borne disease risk. Local impact of temperature and precipitation on West Nile virus infection in Culex species mosquitoes in northeast Illinois, USA. [ABSTRACT FROM AUTHOR]

Background: Globally, disrespectful, and abusive childbirth practices negatively impact women's health, create barriers to accessing health facilities, and contribute to poor birth experiences and adverse outcomes for both mothers and newborns. However, the degree to which disrespectful maternity care is associated with complications during childbirth is poorly understood, particularly in Ethiopia., Aim: To determine the extent to which disrespectful maternity care is associated with maternal and neonatal-related complications in central Ethiopia., Methods: A multicentre cross-sectional study was conducted in the West Shewa Zone of Oromia, Ethiopia. The sample size was determined using the single population proportion formula. Participants (n = 440) were selected with a simple random sampling technique using computer-generated random numbers. Data were collected through face-to-face interviews with a pretested questionnaire and were entered into Epidata and subsequently exported to STATA version 17 for the final analysis. Analyses included descriptive statistics and binary logistic regression, with a 95% confidence interval (CI) and an odds ratio (OR) of 0.05. Co-founders were controlled by adjusting for maternal sociodemographic characteristics. The primary exposure was disrespectful maternity care; the main outcomes were maternal and neonatal-related complications., Results: Disrespectful maternity care was reported by 344 women (78.2%) [95% CI: 74-82]. Complications were recorded in one-third of mothers (33.4%) and neonates (30%). Disrespectful maternity care was significantly associated with maternal (AOR = 2.22, 95% CI: 1.29, 3.8) and neonatal-related complications (AOR = 2.78, 95% CI: 1.54, 5.04)., Conclusion: The World Health Organization advocates respectful maternal care during facility-based childbirth to improve the quality of care and outcomes. However, the findings of this study indicated high mistreatment and abuse during childbirth in central Ethiopia and a significant association between such mistreatment and the occurrence of both maternal and neonatal complications during childbirth. Therefore, healthcare professionals ought to prioritise respectful maternity care to achieve improved birth outcomes and alleviate mistreatment and abuse within the healthcare sector., (© 2024. The Author(s).)

Background: The Earth Biogenome Project has rapidly increased the number of available eukaryotic genomes, but most released genomes continue to lack annotation of protein-coding genes. In addition, no transcriptome data is available for some genomes., Results: Various gene annotation tools have been developed but each has its limitations. Here, we introduce GALBA, a fully automated pipeline that utilizes miniprot, a rapid protein-to-genome aligner, in combination with AUGUSTUS to predict genes with high accuracy. Accuracy results indicate that GALBA is particularly strong in the annotation of large vertebrate genomes. We also present use cases in insects, vertebrates, and a land plant. GALBA is fully open source and available as a docker image for easy execution with Singularity in high-performance computing environments., Conclusions: Our pipeline addresses the critical need for accurate gene annotation in newly sequenced genomes, and we believe that GALBA will greatly facilitate genome annotation for diverse organisms., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Respiratory distress is one of the most common afflictions of brachycephalic dogs. Dogs in respiratory distress usually present to the emergency service with a constellation of clinical signs including but not limited to: stertorous breathing, dyspnea, gagging, cyanotic mucus membranes, hyperthermia, and commonly a history of gastrointestinal signs. While Brachycephalic Obstructive Airway Syndrome is the most common cause of respiratory distress in dogs with brachycephalic conformation, any condition eliciting an inflammatory response in the oropharynx, can result in obstruction. There is no previous report of respiratory obstruction leading to emergency tonsillectomy caused by tonsillar polyps., Case Presentation: A 9-month-old male intact English bulldog presented to the emergency service in severe respiratory distress. Due to continued severe dyspnea and cyanosis the patient was induced with propofol (Propofol, Hospira) 4 mg/kg intravenously titrated to effect and tracheal intubation performed. Intubation was noted to be difficult due the presence of two, large, inflamed masses in the oropharynx region. The remainder of his physical exam was unremarkable. Minimum database blood work and chest radiographs revealed only minor abnormalities. The patient was placed under anesthesia and the masses were transected sharply using a carbon dioxide (CO2) laser (Aesculight, Bothell, WA, USA). Anesthesia and recovery were uneventful, and the patient was discharged the following day. Histopathology results of the masses revealed them to be benign lymphoglandular polyps., Conclusions: This is the first report of bilateral tonsillar polyps causing life-threatening respiratory obstruction in a dog. Both masses were excised safely and completely with the CO2 laser. Difficulties inherent to oropharyngeal surgery include the hemorrhage, small working space, tissue swelling and difficult visualization. Surgical excision of these polyps alleviated all emergent and chronic clinical signs, and the patient's remains healthy 12-months post-treatment., (© 2021. The Author(s).)

Background: BRAKER is a suite of automatic pipelines, BRAKER1 and BRAKER2, for the accurate annotation of protein-coding genes in eukaryotic genomes. Each pipeline trains statistical models of protein-coding genes based on provided evidence and, then predicts protein-coding genes in genomic sequences using both the extrinsic evidence and statistical models. For training and prediction, BRAKER1 and BRAKER2 incorporate complementary extrinsic evidence: BRAKER1 uses only RNA-seq data while BRAKER2 uses only a database of cross-species proteins. The BRAKER suite has so far not been able to reliably exceed the accuracy of BRAKER1 and BRAKER2 when incorporating both types of evidence simultaneously. Currently, for a novel genome project where both RNA-seq and protein data are available, the best option is to run both pipelines independently, and to pick one, likely better output. Therefore, one or another type of the extrinsic evidence would remain unexploited., Results: We present TSEBRA, a software that selects gene predictions (transcripts) from the sets generated by BRAKER1 and BRAKER2. TSEBRA uses a set of rules to compare scores of overlapping transcripts based on their support by RNA-seq and homologous protein evidence. We show in computational experiments on genomes of 11 species that TSEBRA achieves higher accuracy than either BRAKER1 or BRAKER2 running alone and that TSEBRA compares favorably with the combiner tool EVidenceModeler., Conclusion: TSEBRA is an easy-to-use and fast software tool. It can be used in concert with the BRAKER pipeline to generate a gene prediction set supported by both RNA-seq and homologous protein evidence., (© 2021. The Author(s).)

Background: Previous research examining the birth of the placenta has focussed on quantitative outcomes comparing active and expectant (physiological) management. However, it is also important to understand women's experiences of birthing the placenta., Methods: The participant group consisted of 11 women who had expectant management, eight who had active management and one who was unsure. Participants were interviewed in-depth and the data analysed using thematic analysis., Results: Seven themes were identified in the data relating to before, during and after the birth of the placenta. Before birth themes focused on making decisions and included 'doing the research' and 'natural birth'. During the birth of the placenta themes were 'boundaries of time', 'focusing on baby' and 'sensations'. After the birth themes consisted of 'looking' and 'keeping'., Conclusion: Most of the women considered a physiological birth of the placenta to be an intrinsic element of natural birth. Active management was considered to be an intervention used if complications occurred. In contrast, women who chose active management did not consider the placenta to be an important element of natural birth, and chose active management in order to prevent complications. Decisions about birthing the placenta were informed by Internet sources and previous personal experiences rather than care providers. During the birth of the placenta care providers managed the boundaries of time whilst women focused on their baby. The sensations women described were consistent across both types of management. Women valued seeing their placenta and having the opportunity to keep it, and placenta encapsulation was popular. The findings of this study contribute the experiences of women to the body of knowledge informing practice during the birth of the placenta.

Background: Our previous studies demonstrated that growth and migration of medulloblastoma (MB), the most common malignant brain tumor in children, are stimulated by 17β-estradiol. The growth stimulating effects of estrogens are mediated through ERβ and insulin-like growth factor 1 signaling to inhibit caspase 3 activity and reduce tumor cell apoptosis. The objective of this study was to determine whether estrogens decreased sensitivity of MB cells to cytotoxic actions of chemotherapeutic drugs., Methods: Using in vitro cell viability and clonogenic survival assays, concentration response analysis was used to determine whether the cytoprotective effects of estradiol protected human D283 Med MB cells from the cytotoxic actions of the MB chemotherapeutic drugs cisplatin, vincristine, or lomustine. Additional experiments were done to determine whether the ER antagonist fulvestrant or the selective ER modulator tamoxifen blocked the cytoprotective actions of estradiol. ER-selective agonists and antagonists were used to define receptor specificity, and the impacts of the soy-derived phytoestrogens genistein, daidzein, and s-equol on chemosensitivity were evaluated., Results: In D283 Med cells the presence of 10 nM estradiol increased the IC 50 for cisplatin-induced inhibition of viability 2-fold from ~5 μM to >10 μM. In clonogenic survival assays estradiol decreased the chemosensitivity of D283 Med cells exposed to cisplatin, lomustine and vincristine. The ERβ selective agonist DPN and low physiological concentrations of the soy-derived phytoestrogens genistein, daidzein, and s-equol also decreased sensitivity of D283 Med cells to cisplatin. The protective effects of estradiol were blocked by the antiestrogens 4-hydroxytamoxifen, fulvestrant (ICI 182,780) and the ERβ selective antagonist PPHTP. Whereas estradiol also decreased chemosensitivity of PFSK-1 cells, estradiol increased sensitivity of Daoy cell to cisplatin, suggesting that ERβ mediated effects may vary in different MB celltypes., Conclusions: These findings demonstrate that E2 and environmental estrogens decrease sensitivity of MB to cytotoxic chemotherapeutics, and that ERβ selective and non-selective inhibition of estrogen receptor activity blocks these cytoprotective actions. These findings support the therapeutic potential of antiestrogen adjuvant therapies for MB, and findings that soy phytoestrogens also decrease sensitivity of MB cells to cytotoxic chemotherapeutics suggest that decreased exposure to environmental estrogens may benefit MB patient responses to chemotherapy.

Background: NICE guidelines state cognitive behavioural therapy (CBT) is a front-line psychological treatment for people presenting with depression in primary care. Counselling for Depression (CfD), a form of Person-Centred Experiential therapy, is also offered within Improving Access to Psychological Therapies (IAPT) services for moderate depression but its effectiveness for severe depression has not been investigated. A full-scale randomised controlled trial to determine the efficacy and cost-effectiveness of CfD is required., Methods: PRaCTICED is a two-arm, parallel group, non-inferiority randomised controlled trial comparing CfD against CBT. It is embedded within the local IAPT service using a stepped care service delivery model where CBT and CfD are routinely offered at step 3. Trial inclusion criteria comprise patients aged 18 years or over, wishing to work on their depression, judged to require a step 3 intervention, and meeting an ICD-10 diagnosis of moderate or severe depression. Patients are randomised using a centralised, web-based system to CfD or CBT with each treatment being delivered up to a maximum 20 sessions. Both interventions are manualised with treatment fidelity tested via supervision and random sampling of sessions using adherence/competency scales. The primary outcome measure is the Patient Health Questionnaire-9 collected at baseline, 6 and 12 months. Secondary outcome measures tap depression, generic psychological distress, anxiety, functioning and quality of life. Cost-effectiveness is determined by a patient service receipt questionnaire. Exit interviews are conducted with patients by research assessors blind to treatment allocation. The trial requires 500 patients (250 per arm) to test the non-inferiority hypothesis of -2 PHQ-9 points at the one-sided, 2.5% significance level with 90% power, assuming no underlying difference and a standard deviation of 6.9. The primary analysis will be undertaken on all patients randomised (intent to treat) alongside per-protocol and complier-average causal effect analyses as recommended by the extension to the CONSORT statement for non-inferiority trials., Discussion: This large-scale trial utilises routinely collected outcome data as well as specific trial data to provide evidence of the comparative efficacy and cost-effectiveness of Counselling for Depression compared with Cognitive Behaviour Therapy as delivered within the UK government's Improving Access to Psychological Therapies initiative., Trial Registration: Controlled Trials ISRCTN Registry, ISRCTN06461651 . Registered on 14 September 2014.

Background: Knowledge of the characteristics of patients co-infected with tuberculosis (TB) and human immunodeficiency virus (HIV) when TB treatment is initiated would allow clinicians to improve care and help policy-makers develop relevant and realistic guidelines. The aim of this study was to describe socio-demographic, clinical, and laboratory characteristics of TB/HIV co-infected patients starting inpatient TB treatment in Yaoundé, Cameroon., Methods: We conducted a retrospective cross-sectional study, collecting data from medical records of HIV-infected patients with TB, aged 15 years old or more, hospitalized in the Infectious Diseases Unit of the Yaoundé Central Hospital, Cameroon from January 1, 2006 to June 30, 2013., Results: The mean age of 337 patients meeting study inclusion criteria was 39.3 years. More than half were female (53.4%). Most (89.3%) resided in urban areas, 44.2% had a secondary education, and 46.0% were married. The majority was receiving co-trimoxazole prophylaxis (79.5%), and two thirds were taking antiretroviral therapy (67.4%). The mean duration of known HIV infection before TB treatment was 8.4 months. Most (88.1%) had newly diagnosed TB, rather than relapsed disease. Smear-positive pulmonary TB was documented in a third, (35.3%). Laboratory data revealed a median white blood cell count of 5,100 cells/mm(3) (IQR 3,300-7,990 cells/mm(3)), a median hemoglobin level of 8 g/dl (IQR 7-10 g/dl), and a median CD4 cell count of 102 cells/mm(3) (IQR 33-178 cells/mm(3)). Sex differences in our study included older age in the men (p < 0.001), more of whom were married (p < 0.001) and had achieved a higher level of education (p = 0.042). Men had fewer diagnoses of smear-positive pulmonary TB (p = 0.020). They weighed more than the women (p = 0.001) and had higher hemoglobin levels (p = 0.003)., Conclusions: Suboptimal adherence to WHO treatment recommendations in our Cameroonian study reinforces the importance of prescribing co-trimoxazole in HIV infection and ART for all TB/HIV co-infected persons. We urge that Ministries of Health continue implementing and disseminating guidelines for management of TB/HIV co-infected patients, and we call for measures ensuring that healthcare facilities' stocks of ART and co-trimoxazole are sufficient to meet the need for both.

Background: In July 2011, the Malawi national HIV program implemented the integrated antiretroviral therapy (ART) and prevention of mother-to-child transmission (PMTCT) guidelines. Among the principle goals of the guidelines were increasing ART uptake among TB/HIV co-infected patients and treating TB/HIV patients with a different drug regimen. We, therefore, assessed the effects of the new guidelines on ART uptake, the factors associated with ART uptake and the frequency of ARV-related adverse events in TB/HIV co-infected patients., Methods: This was an observational cohort study using routine program data. All ART-naïve adult TB/HIV co-infected patients starting TB treatment over the six months preceding and following implementation of 2011 integrated ART/PMTCT guidelines were included., Results: A total of 685 adult TB/HIV co-infected patients were registered in the study; 377 (55%) before and 308 (45%) after the implementation of the new guidelines. ART uptake increased from 70% (240/308) before implementation of the new guidelines to 78% (262/377) after the inception of the new guidelines (P=0.013). The proportion of TB patients initiating ART within two weeks of starting TB treatment increased from 30% before implementation of the new guidelines to 46% after implementation of the new guidelines (p <0.001). The median time from the start of TB treatment to ART initiation dropped from 16 days (IQR 14-31) before the new guidelines to 14 days (IQR 9-20; p = 0.004) after implementing the new guidelines. Factors associated with ART uptake were enrolment in HIV care before starting TB treatment and being a retreatment TB patient. The overall frequency of ARV-related adverse events was higher in patients on d4T/3TC/NVP (35%) than those on TDF/3TC/EFV (25%) but not significantly different (P=0.052)., Conclusion: Implementation of the 2011 Malawi Integrated ART/PMTCT guidelines was associated with an overall increase in ART uptake among TB/HIV patients and with an increase in the number of patients initiating ART within two weeks of starting their TB treatment. However, the reduction in time between initiating TB treatment and starting ART was small suggesting that further measures must be implemented to facilitate ART uptake. Early enrolment in HIV care provides opportunities for timely ART initiation among TB patients.