Prevalence of Paid Sex and Associated Factors Among Women and Men Attending HIV Voluntary Counseling and Testing in Kinshasa, Democratic Republic of the Congo: A Prospective Cohort.

Paid sex is associated with HIV and other sexually transmitted infections, which are highly prevalent in Sub-Saharan Africa (SSA). However, few data exist on this sexual practice among the general population in SSA, including the Democratic Republic of the Congo, where data on paid sex mainly comes from sex workers. In the DRC, most HIV Voluntary Counseling and Testing (VCT) centers do not discuss paid sex as a risk factor. Thus, we aimed to analyze the prevalence of paid sex, its associated factors and association with HIV among women and men attending HIV VCT at a reference hospital in Kinshasa. From 2016 to 2018, the Observational Kinshasa AIDS Initiative cohort analyzed the impact of HIV VCT on changes in HIV knowledge, attitudes, and sexual behaviors at follow-up. Participants aged 15-69 years were HIV tested and interviewed at baseline and at 6- and 12-month follow-ups. At baseline, participants were asked about their history of "ever" having had exchanged sex for money. At both follow-ups, the frequency of this practice was referred to as "the previous 6 months." Descriptive, bivariate, and multivariate logistic regression analyses were carried out to evaluate the prevalence of paid sex, its associated factors, and the association between paid sex and HIV. Statistical analyses were performed with Stata 15.1. Among 797 participants at baseline, 10% of those sexually experienced reported having ever had paid sex (18% men and 4% women, p < 0.001). At 6 and 12-month follow-ups, 5% and 2%, respectively. Paid sex was significantly and independently associated with being male (aOR = 2.7; 95% CI = 1.4-5.2), working or studying (aOR = 2.8; 95% CI = 1.5-5.0), daily newspaper reading (aOR = 4.4; 95% CI = 1.7-11.2); daily/weekly alcohol consumption (aOR = 3.3; 95% CI = 1.8-6.1), first sexual intercourse before age 15 years (aOR = 2.3; 95% CI = 1.1-5.0), multiple sexual partners (aOR = 4.1; 95% CI = 2.2-7.7), and extragenital sexual practices (aOR = 2.4; 95% CI = 1.3-4.4). A high religiosity (daily/weekly church attendance and praying) was inversely associated with paid sex (aOR = 0.1; 95% CI = 0.0-0.4). The high prevalence of paid sex among people attending HIV VCT in Kinshasa, associated with other sexual and consumption risk behaviors, highlights the need to include paid sex among the risk factors mentioned in HIV prevention counseling.

Determination of the androgen receptor status of disseminated tumor cells in primary breast cancer patients.

PURPOSE: Androgen receptor (AR) can serve as a new therapeutic target since it was shown to play a proliferative role in several breast cancer (BC) subtypes. Moreover, AR positivity has been suggested to reflect the metastatic potential of tumor cells in some BC subtypes. The aim of this study was to determine the AR expression on disseminated tumor cells (DTCs) as a surrogate marker of minimal residual disease (MRD) and potential precursor of metastasis in early BC. METHODS: Bone marrow (BM) aspirates from 62 DTC-positive early BC patients were included into this study and analyzed by immunofluorescence staining for the presence of AR-positive DTCs. CK-positive, CD45-negative cells containing an intact nucleus (DAPI positive) were identified as DTCs. AR expression of the primary tumor (PT) was assessed by immunohistochemistry on formalin-fixed, paraffin-embedded (FFPE) tumor sections from core biopsies and surgical specimens. RESULTS: AR status of DTCs could be determined in 21 patients. We detected AR-positive DTCs in nine samples (43%). AR expression of DTCs and corresponding PT showed a concordance rate of 33%. The DTC-AR status did not correlate with clinicopathological factors, nor did we observe a significant correlation between the AR status of the PT and other established prognostic factors for BC. CONCLUSION: AR-positive DTCs can be detected in BM of early BC patients with a marked discordance of the AR status between DTCs and corresponding PTs. The clinical significance of these findings needs further investigation.

Diagnosis of Potomac horse fever (syn. equine neorickettsiosis) in 2 foals in southwestern Ontario.

Potomac horse fever (PHF) is characterized by fever, depression, anorexia, ileus, diarrhea, and occasionally, laminitis. The disease is caused by infection with Neorickettsia risticii and/or N. findlayensis. Equids of all ages may be affected; however, the condition has not been well-characterized in foals. This report describes clinical signs, laboratory findings, and treatment of 2 foals diagnosed with PHF in southwestern Ontario. Feces submitted for an equine PCR panel tested positive for Neorickettsia spp. and were subsequently confirmed to be N. risticii (Case 1) and N. findlayensis (Case 2). Both foals recovered following hospitalization and intensive care. Key clinical message: The purpose of this report is to make veterinarians aware that foals may develop PHF. During summer (July to September), when encountering foals in endemic areas with clinical signs compatible with PHF, veterinarians should consider PHF as a diagnostic rule-out. For confirmation of the diagnosis, blood and feces should be submitted for PCR testing for Neorickettsia spp.

Diagnostic de la fièvre équine du Potomac (syn. néorickettsiose équine) chez 2 poulains dans le sud-ouest de l'Ontario. La fièvre équine du Potomac (PHF) se caractérise par de la fièvre, une dépression, de l'anorexie, un iléus, de la diarrhée et, occasionnellement, une fourbure. La maladie est causée par une infection par Neorickettsia risticii et/ou N. findlayensis. Les équidés de tous âges peuvent être atteints; cependant, cette pathologie n'a pas été bien caractérisée chez les poulains. Ce rapport décrit les signes cliniques, les résultats de laboratoire et le traitement de 2 poulains diagnostiqués avec PHF dans le sud-ouest de l'Ontario. Les matières fécales soumises à un panel PCR équin se sont révélées positives pour Neorickettsia spp. et ont ensuite été confirmées comme étant positives pour N. risticii (cas 1) et N. findlayensis (cas 2). Les deux poulains se sont rétablis après une hospitalisation et des soins intensifs.Message clinique clé :Le but de ce rapport est de sensibiliser les vétérinaires au fait que les poulains peuvent développer une PHF. Pendant l'été (juillet à septembre), lorsqu'ils rencontrent des poulains dans des zones d'endémie présentant des signes cliniques compatibles avec le PHF, les vétérinaires doivent considérer le PHF comme une exclusion diagnostique. Pour confirmer le diagnostic, du sang et des selles doivent être soumis à un test PCR pour Neorickettsia spp.(Traduit par Dr Serge Messier).

Second messenger signalling bypasses CGRP receptor blockade to provoke migraine attacks in humans.

There are several endogenous molecules that can trigger migraine attacks when administered to humans. Notably, calcitonin gene-related peptide (CGRP) has been identified as a key player in a signalling cascade involved in migraine attacks, acting through the second messenger cyclic adenosine monophosphate (cAMP) in various cells, including intracranial vascular smooth muscle cells. However, it remains unclear whether intracellular cAMP signalling requires CGRP receptor activation during a migraine attack in humans. To address this question, we conducted a randomized, double-blind, placebo-controlled, parallel trial using a human provocation model involving the administration of CGRP and cilostazol in individuals with migraine pretreated with erenumab or placebo. Our study revealed that migraine attacks can be provoked in patients by cAMP-mediated mechanisms using cilostazol, even when the CGRP receptor is blocked by erenumab. Furthermore, the dilation of cranial arteries induced by cilostazol was not influenced by the CGRP receptor blockade. These findings provide clinical evidence that cAMP-evoked migraine attacks do not require CGRP receptor activation. This discovery opens up new possibilities for the development of mechanism-based drugs for the treatment of migraine.

Rationale for the selection of dual primary endpoints in prevention studies of cognitively unimpaired individuals at genetic risk for developing symptoms of Alzheimer's disease.

BACKGROUND: There is a critical need for novel primary endpoints designed to detect early and subtle changes in cognition in clinical trials targeting the asymptomatic (preclinical) phase of Alzheimer's disease (AD). The Alzheimer's Prevention Initiative (API) Generation Program, conducted in cognitively unimpaired individuals at risk of developing AD (e.g., enriched by the apolipoprotein E (APOE) genotype), used a novel dual primary endpoints approach, whereby demonstration of treatment effect in one of the two endpoints is sufficient for trial success. The two primary endpoints were (1) time to event (TTE)-with an event defined as a diagnosis of mild cognitive impairment (MCI) due to AD and/or dementia due to AD-and (2) change from baseline to month 60 in the API Preclinical Composite Cognitive (APCC) test score. METHODS: Historical observational data from three sources were used to fit models to describe the TTE and the longitudinal APCC decline, both in people who do and do not progress to MCI or dementia due to AD. Clinical endpoints were simulated based on the TTE and APCC models to assess the performance of the dual endpoints versus each of the two single endpoints, with the selected treatment effect ranging from a hazard ratio (HR) of 0.60 (40% risk reduction) to 1 (no effect). RESULTS: A Weibull model was selected for TTE, and power and linear models were selected to describe the APCC score for progressors and non-progressors, respectively. Derived effect sizes in terms of reduction of the APCC change from baseline to year 5 were low (0.186 for HR = 0.67). The power for the APCC alone was consistently lower compared to the power of TTE alone (58% [APCC] vs 84% [TTE] for HR = 0.67). Also, the overall power was higher for the 80%/20% distribution (82%) of the family-wise type 1 error rate (alpha) between TTE and APCC compared to 20%/80% (74%). CONCLUSIONS: Dual endpoints including TTE and a measure of cognitive decline perform better than the cognitive decline measure as a single primary endpoint in a cognitively unimpaired population at risk of AD (based on the APOE genotype). Clinical trials in this population, however, need to be large, include older age, and have a long follow-up period of at least 5 years to be able to detect treatment effects.

Increased quality of life in patients with breakthrough cancer pain after individualized therapy: the CAVIDIOM study.

Aim: To evaluate the quality of life (QoL) in patients with breakthrough cancer pain (BTcP) in Spanish medical oncology departments. Patients & methods: In a prospective, observational, multicenter study, we assessed QoL using the EQ-5D-5L instrument at baseline and after 15 and 30 days of individualized BTcP therapy, as well as BTcP characteristics and treatment. Results: Patients (n = 118) were mainly women, over 64 years old and with advanced cancer. QoL improved at 15 (p = 0.013) and 30 days (p = 0.011) versus baseline. Individualized BTcP therapy consisted mostly of rapid-onset opioids (transmucosal fentanyl at doses of 67-800 µg) according to the physician evaluation. BTcP improved, including statistically significant reductions in intensity, duration, number of episodes in the last 24 h and time to onset of BTcP relief. Conclusion: QoL increased after individualized pain therapy in patients with advanced cancer and BTcP in medical oncology departments.

Cancer patients can experience flares of pain, called breakthrough pain (BTcP), despite treatment with painkillers. Although BTcP can be excruciating, its intensity and other characteristics depend on several factors, including its treatment. However, even if treated, BTcP can impair quality of life for cancer patients. We assessed quality of life in 118 patients with advanced cancer and BTcP treated in 13 medical oncology departments across Spain. We treated BTcP with individualized therapy, taking into account both pain-related and patient-related factors. We also measured quality of life using a specific, widely-used questionnaire at the study visits: at onset of individualized pain therapy and after 3, 15 and 30 days' treatment. At each visit, flare-up pain therapy was adjusted or maintained as necessary. Throughout the study, quality of life and sleep quality improved for all participants. Furthermore, there was a greater reduction in intensity, duration and frequency of BTcP. The most common treatments for flare-ups were low doses of rapid-onset opioids (fentanyl given by sublingual, buccal or nasal administration), which were much better tolerated than high-dose opioids. Overall, the study showed that quality of life in patients with advanced cancer and BTcP increased after individualized pain therapy, mainly with low doses of rapid-onset opioids.

A Delphi Consensus on Patient Reported Outcomes for Registries and Trials Including Patients with Intermittent Claudication: Recommendations and Reporting Standard.

OBJECTIVE: This study aimed to develop a core set of patient reported outcome quality indicators (QIs) for the treatment of patients with intermittent claudication (IC), that allow a broad international implementation across different vascular registries and within trials. METHODS: A rigorous modified two stage Delphi technique was used to promote consensus building on patient reported outcome QIs among an expert panel consisting of international vascular specialists, patient representatives, and registry members of the VASCUNET and the International Consortium of Vascular Registries. Potential QIs identified through an extensive literature search or additionally proposed by the panel were validated by the experts in a preliminary survey and included for evaluation. Consensus was reached if ≥ 80% of participants agreed that an item was both clinically relevant and practical. RESULTS: Participation rates in two Delphi rounds were 66% (31 participants of 47 invited) and 90% (54 of 60), respectively. Initially, 145 patient reported outcome QIs were documented. Following the two Delphi rounds, 18 quality indicators remained, all of which reached consensus regarding clinical relevance. The VascuQoL questionnaire (VascuQoL-6), currently the most common patient reported outcome measurement (PROM) used within vascular registries, includes a total of six items. Five of these six items also matched with high rated indicators identified in the Delphi study. Consequently, the panel recommends the use of the VascuQoL-6 survey as a preferred core PROM QI set as well as an optional extension of 12 additional patient reported QIs that were also identified in this study. CONCLUSION: The current recommendation based on the Delphi consensus building approach, strengthens the international harmonisation of registry data collection in relation to patient reported outcome quality. Continuous and standardised quality assurance will ensure that registry data may be used for future quality benchmarking studies and, ultimately, positively impact the overall quality of care provided to patients with peripheral arterial occlusive disease.

Plasma Levels of CGRP During a 2-h Infusion of VIP in Healthy Volunteers and Patients With Migraine: An Exploratory Study.

Introduction: The activation of perivascular fibers and the consequent release of vasoactive peptides, including the vasoactive intestinal polypeptide (VIP), play a role in migraine pathogenesis. A 2-h infusion of VIP provoked migraine, but the mechanisms remain unknown. We investigated whether 2-h infusion of VIP caused alterations in plasma levels of the calcitonin gene-related peptide (CGRP) and whether any changes might be related to the induced migraine attacks. Materials and Methods: We enrolled individuals with episodic migraine without aura and healthy participants to randomly receive a 2-h infusion of either VIP (8 pmol/kg/min) or placebo (sterile saline) in two randomized, placebo-controlled crossover trials. We collected clinical data and measured plasma levels of VIP and CGRP at fixed time points: at baseline (T0) and every 30 min until 180 min (T180) after the start of the infusion. Results: Blood samples were collected from patients with migraine (n = 19) and healthy individuals (n = 12). During VIP infusion, mixed effects analysis revealed a significant increase in plasma CGRP (p = 0.027) at T30 (vs. T180, adjusted p-value = 0.039) and T60 (vs. T180, adjusted p-value = 0.027) in patients with migraine. We found no increase in plasma CGRP during VIP-induced migraine attacks (p = 0.219). In healthy individuals, there was no increase in plasma CGRP during VIP (p = 0.205) or placebo (p = 0.428) days. Discussion: Plasma CGRP was elevated in patients with migraine during a prolonged infusion of VIP, but these alterations were not associated with VIP-induced migraine attacks. Given the exploratory design of our study, further investigations are needed to clarify the role of CGRP in VIP-induced migraine. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT03989817 and NCT04260035.

Low-dose sublingual fentanyl improves quality of life in patients with breakthrough cancer pain in palliative care.

Aim: This subanalysis of the CAVIDIOPAL study evaluated the impact of individualized management of breakthrough cancer pain (BTcP) with fentanyl on the quality of life (QoL) of advanced cancer patients in Spanish palliative care units. Patients & methods: This was a prospective, observational, multicenter study. The European Organization for Research and Treatment of Cancer's QLQ-C30 questionnaire was used at baseline (V0) and visit 28 (V28). Results: Ninety-five patients were mainly treated with 67-133 µg fentanyl, showing a notable reduction in intensity (visual analog scale: 8.0 [V0] to 4.6 [V28]), frequency and duration of BTcP episodes shortly after the first 1-2 weeks of treatment, with significantly improved QoL (global health status: 31.1 [V0] to 53.1 [V28]). Conclusion: Low-dose sublingual fentanyl effectively reduced BTcP in advanced cancer patients in palliative care units, significantly improving QoL. Clinical trial registration: NCT02840500 (ClinicalTrials.gov).

After the CAVIDIOPAL study, we carried out an additional analysis to evaluate the impact of individualized management of breakthrough cancer pain, using the analgesic drug fentanyl, on quality of life (QoL) of advanced cancer patients receiving palliative care in Spain. We performed a prospective, observational, multicenter study, in which patients' QoL was assessed using a validated questionnaire at baseline (day 0) and after 28 days of fentanyl treatment. Of the 95 patients included in the study, the majority were treated with low doses of fentanyl and showed significant pain relief. The intensity, frequency and duration of breakthrough cancer pain episodes were notably reduced shortly after the first 1­2 weeks of treatment. Moreover, patients' QoL significantly improved during fentanyl treatment from baseline to day 28. A global impression of improvement was reported by both patients and clinicians.

Excelência no Handebol: o processo de desenvolvimento esportivo de atletas brasileiras campeãs do mundo / La excelencia en balonmano: el proceso de desarrollo deportivo de los atletas brasileños campeones del mundo / Handball excellence: the sport development process of world champion Brazilian athletes

O objetivo do estudo foi analisar o processo de desenvolvimento da carreira esportiva de atle-tas brasileiras campeãs do mundo de handebol. Estudo retrospectivo com foco nos principais episódios da iniciação ao esporte elite, na perspectiva das sete atletas. Os dados foram coleta-dos através de entrevistas semiestruturadas individuais, e analisados pelo método da Análise Temática. Os resultados revelam que a carreira das atletas foi marcada por: iniciação diversifi-cada no esporte; aumento de prática deliberada durante os anos de especialização; avanço precoce e rápido para os anos de investimento esportivo. Transições normativas e não normati-vas também foram identificadas, sendo mais evidentes a partir da transição para o esporte de elite. Além disso, o processo de desenvolvimento das atletas foi assistemático, expresso pela falta de organização e planejamento por parte de órgãos responsáveis pelo fomento da prática do handebol. Sendo o contexto escolar, um ambiente significativo para promover o acesso ini-cial ao handebol. (AU)

The objective was to analyze the development process of the sports career of Brazilian ath-letes who are handball world champions. A retrospective study was carried out with seven athletes, focusing onthe main episodes of the sports career, from initiation to elite sport. Da-ta were collected through individual semi-structured interviews and was analyzed using the Thematic Analysis method. The results revealed that the athletes’ careers were marked by: diversified initiation in the sport; increase in deliberate practice during the years of speciali-zation; early and rapid advance into the years of sports investment. Normative and non-normative transitions were also identified, being more evident from the transition to elite sport. In addition, the athletes’ development process was unsystematic, expressed by the lack of organization and planning by the bodies responsible for promoting handball practice. The school context represents a significant environment to promote access to handball. (AU)

Quantification and Isolation of Spontaneous Colony Growth Variants.

The appearance of colony growth sectors on solid medium plates has been described in many fungi. Although the molecular bases of this phenomenon remain largely unknown, possible relationships with genetic or epigenetic changes have been reported. Here we present a method to quantify the frequency of colony growth sectors in Fusarium oxysporum, which can be used to compare different fungal strains and to infer their genetic instability.

Adolescent Athletes' Perceptions of Both Their Coachs' Leadership and Their Personal Motivation.

Previous studies, framed within the full range leadership approach, have described how the coach's interpersonal behaviors affected athletic outcomes. However researchers have yet to explore how specific leadership behaviors (transformational vs transactional), as perceived by athletes, may affect athletes' motivation. The aim of this study was to further examine the link between coaches' leadership behaviors and athletes' motivation among high achieving adolescent athletes. Two-hundred and twenty-three elite youth athletes (M = 15.4 years; SD = 1.6; 53.4% male and 46.6% female) responded to questionnaires pertaining to their coaches' leadership and their individual motivation levels. We found a direct and linear relationship between transformational leadership and intrinsic motivation, and between transactional leadership and external regulation. None of the moderators we studied (age, gender, age group category, and sport skill level) moderated relations between coaches' leadership and personal motivation. This research re-emphasized the important interpersonal role that coaches play in athletes' sport development. We recommend that coaches include more interpersonally focused educational programs that emphasize transformational leadership.

Analysis of the sports career of brazilian international elite squash athletes / Análise da carreira esportiva de atletas brasileiros de squash com nível internacional

ABSTRACT The sports career is a process through which the athletes voluntarily seek to achieve high levels of sport performance, however, how the development of international elite squash athletes has occurred in different periods of their sports career is not known. This study aimed at describing and assessing the sport trajectory of Brazilian international elite squash athletes at different periods of their career, in light of dynamic elements, that is, personal engagement, quality relationships and appropriate settings. Semi-structured interviews were carried out based on the Personal Assets Framework (PAF). The interviews were applied to six athletes (three males and three females) and evaluated according to the Thematic Analysis (TA) method. The results showed that personality traits, interpersonal relationships and the sport practice settings enabled the squash players to develop their sports career. In conclusion, these three aspects when acting concurrently can favor the development of international elite squash athletes.

RESUMO A carreira esportiva é um processo onde o atleta, de forma voluntária, busca atingir níveis elevados de desempenho esportivo, entretanto não se conhece sobre como ocorreu o desenvolvimento da carreira esportiva em atletas de squash. O objetivo foi analisar a trajetória esportiva de atletas brasileiros de squash de nível internacional em diferentes momentos da carreira esportiva. Utilizando o Quadro de Desenvolvimento de Valores Pessoais no Esporte como base, realizamos entrevista semi-estruturada com seis atletas (três do sexo masculino e três do sexo feminino), e empregamos para a análise das entrevistas a Análise Temática. Os resultados encontrados foram que os temas características pessoais, relações interpessoais e o contexto de prática esportiva são temas que possibilitam o desenvolvimento da carreira esportiva de atletas de squash. De modo conclusivo os três aspectos, atuando de forma concomitante, possam ofertar, de modo favorável, o desenvolvimento de atletas de squash de nível internacional.

Analysis of the Athletic Career and Retirement Depending on the Type of Sport: A Comparison between Individual and Team Sports.

The type of sport practiced may shape the athletic career, considered as the period in which an athlete is dedicated to obtaining their maximum performance in one or more sports. The aim of this study was to compare athletic careers and retirement in individual and team sports. Four hundred and ten former elite athletes (38.5 ± 7.6 years) answered an ad hoc questionnaire; 61.5% were men and 38.5% women; 45.1% were from individual sports, while 54.9% were from team sports. It emerged that the age of maximum sports performance and the retirement age occurred significantly later in team sports than in individual sports (U = 15,042 and U = 12,624.5, respectively p < 0.001). Team sports athletes combined their athletic career with work to a greater extent than those from individual sports (χ2 (3, N = 408) = 14.2; p = 0.003; Cv = 0.187). Individual sports athletes trained more hours per week (30.0 ± 11.7 h) than those involved in team sports (19.2 ± 10.7 h; U = 9682; p < 0.001). These athletes (team sports) were in a better economic and working situation at retirement transition (χ2 (3, N = 406) = 23.9; p < 0.001; Cv = 0.242). Individual sports athletes perform physical activity more frequently than team sports athletes (U = 16,267.5; p = 0.045), while team sports athletes participate more actively in veteran competitions (χ2 (1, N = 390) = 3.9; p = 0.047; Cv = 0.104) and more frequently attend events as spectators (χ2 (1, N = 390) = 8.4; p = 0.004; Cv = 0.151). dual career support providers should be aware that team sports athletes enjoy a longer athletic career, and they are in a better position to face the retirement transition than individual sports athletes.

A Cluster-Randomized Trial of Hydroxychloroquine as Prevention of Covid-19 Transmission and Disease

BackgroundCurrent strategies for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are limited to non-pharmacological interventions. Hydroxychloroquine (HCQ) has been proposed as a postexposure therapy to prevent Coronavirus disease 2019 (Covid-19) but definitive evidence is lacking. MethodsWe conducted an open-label, cluster-randomized trial including asymptomatic contacts exposed to a PCR-positive Covid-19 case in Catalonia, Spain. Clusters were randomized to receive no specific therapy (control arm) or HCQ 800mg once, followed by 400mg daily for 6 days (intervention arm). The primary outcome was PCR-confirmed symptomatic Covid-19 within 14 days. The secondary outcome was SARS-CoV-2 infection, either symptomatically compatible or a PCR-positive result regardless of symptoms. Adverse events (AEs) were assessed up to 28 days. ResultsThe analysis included 2,314 healthy contacts of 672 Covid-19 index cases identified between Mar 17 and Apr 28, 2020. A total of 1,198 were randomly allocated to usual care and 1,116 to HCQ therapy. There was no significant difference in the primary outcome of PCR-confirmed, symptomatic Covid-19 disease (6.2% usual care vs. 5.7% HCQ; risk ratio 0.89 [95% confidence interval 0.54-1.46]), nor evidence of beneficial effects on prevention of SARS-CoV-2 transmission (17.8% usual care vs. 18.7% HCQ). The incidence of AEs was higher in the intervention arm than in the control arm (5.9% usual care vs 51.6% HCQ), but no treatment-related serious AEs were reported. ConclusionsPostexposure therapy with HCQ did not prevent SARS-CoV-2 disease and infection in healthy individuals exposed to a PCR-positive case. Our findings do not support HCQ as postexposure prophylaxis for Covid-19. ClinicalTrials.gov registration numberNCT04304053

Two-hour infusion of vasoactive intestinal polypeptide induces delayed headache and extracranial vasodilation in healthy volunteers.

BACKGROUND: In recent years, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptides (PACAPs) have gained special interest in headache science. VIP and PACAPs (two isoforms, PACAP27 and PACAP38) are related in structure and function, as are their receptors, but they show differences in vasodilating- and headache-inducing properties. Intravenous infusion of PACAP27 or PACAP38, but not VIP, induces a long-lasting dilation of cranial arteries and delayed headache. The relationship between the long-lasting cranial vasodilation and headache development is not fully clarified. METHODS: In a double-blinded, placebo-controlled, crossover study in 12 healthy volunteers, diameter changes of cranial arteries, occurrence of headache and the parasympathetic system were examined before, during and after a 2-hour continuous intravenous infusion of VIP and placebo. Primary endpoints were the differences in area under the curve for the superficial temporal artery diameter and headache intensity scores, as well as in headache incidence, between VIP and placebo. RESULTS: The superficial temporal artery diameter was significantly larger on the VIP day compared to placebo (p < 0.001) and the dilation lasted for more than 2 h. The incidence of headache was higher (p = 0.003) on the VIP day compared to the placebo day. The difference in headache intensity scores was more evident in the post-infusion period (120-200 min, p = 0.034) and in the post-hospital phase (4-12 h, p = 0.025). Cranial parasympathetic activity, measured through the production of tears, was higher during VIP compared to placebo (p = 0.033). CONCLUSION: Continuous intravenous infusion of VIP over 2 h induced a long-lasting cranial vasodilation, activation of the cranial parasympathetic system, and delayed mild headaches in healthy volunteers.Trial Registration: The study is registered at ClinicalTrials.gov (NCT03989817).

Evaluation of HER2 expression in urothelial carcinoma cells as a biomarker for circulating tumor cells.

BACKGROUND: Detection of circulating tumor cells (CTC) by techniques based on epithelial cell adhesion molecule (EpCAM) is suboptimal in urothelial carcinoma (UC). As HER2 is thought to be broadly expressed in UC, we explored its utility for CTC detection. METHODS: HER2 and EpCAM expression was analyzed in 18 UC cell lines (UCCs) by qRT-PCR, western blot and fluorescence-activated cell scanning (FACS) and compared to the strongly HER2-expressing breast cancer cell line SKBR3 and other controls. HER2 expression in UC patient tissues was measured by qRT PCR and correlated with data on survival and risk for metastasis. UCCs with high EpCAM and variable HER2 expression were used for spike-in experiments in the CellSearch system. Twenty-one blood samples from 13 metastatic UC patients were analyzed for HER2-positive CTCs with CellSearch. RESULTS: HER2 mRNA and protein were broadly expressed in UCC, with some heterogeneity, but at least 10-fold lower than in the HER-2+ SKBR3 cells. Variations were unrelated to cellular phenotype or clinicopathological characteristics. EpCAM expression was essentially restricted to UCCs with epitheloid phenotypes. Heterogeneity of EpCAM and HER2 expression was observed also in spike-in experiments. The 7 of 21 blood samples from 6 of 13 patients were enumerated as CTC positive via EpCAM, but only one sample stained weakly positive (1+) for HER2. CONCLUSIONS: Detection rate of CTCs by EpCAM in UC is poor, even in metastatic patients. Because of its widespread expression, particularly in patients with high risk of metastasis, detection of HER2 could improve identification of UC CTCs, which is why combined detection using antibodies for EpCAM and HER2 may be beneficial.

Genome Sequence of Metarhizium rileyi, a Microbial Control Agent for Lepidoptera.

Metarhizium rileyi (formerly known as Nomuraea rileyi) is a potential agent for microbial control of many insect pests from the order Lepidoptera, the damages of which can cause considerable loss of productivity in agriculture. We report the genome sequence and annotation of M. rileyi strain Cep018-CH2/ARSEF 7053.

Continuation of Unintended Pregnancy.

BACKGROUND: Forty-four percent of all pregnancies worldwide are unintended. Induced abortion has drawn a lot of attention from clinicians and policy makers, and the care for women requesting it has been covered in many publications. However, abortion challenges the values of many women, is associated with negative emotions, and has its own medical complications. Women have the right to discuss their unintended pregnancy with a clinician and receive elaborate information about other options to deal with it. Continuing an unintended pregnancy, and receiving the necessary care and support for it, is also a reproductive right of women. However, the provision of medical information and support required for the continuation of an unintended pregnancy has hardly been approached in the medical literature. OBJECTIVE: This review presents a clinical approach to unintentionally pregnant patients and describes the information and support that can be offered for the continuation of the unintended pregnancy. DISCUSSION: Clinicians should approach patients with an unintended pregnancy with a sympathetic tone in order to provide the most support and present the most complete options. A complete clinical history can help frame the problem and identify concerns related to the pregnancy. Any underlying medical or obstetric problems can be discussed. A social history, that includes the personal support from the patient's partner, parents, and siblings, can be taken. Doctors should also be alert of possible cases of violence from the partner or child abuse in adolescent patients. Finally, the clinician can provide the first information regarding the social care available and refer the patients for further support. For women who continue an unintended pregnancy, clinicians should start antenatal care immediately. CONCLUSION: Unintentionally pregnant women deserve a supportive and complete response from their clinicians, who should inform about, and sometimes activate, all the resources available for the continuation of unintended pregnancy. SUMMARY: Forty-four percent of all pregnancies worldwide are unintended. Induced abortion has drawn a lot of attention and the care for women requesting it has been covered in many publications. However, abortion challenges the values of many women, is associated with negative emotions, and has its own medical complications. Women have the right to discuss their unintended pregnancy with a clinician and receive elaborate information about other options to deal with it. Continuing an unintended pregnancy, and receiving the necessary care and support for it, is also a reproductive right of women. However, the provision of medical information and support required for the continuation of an unintended pregnancy has hardly been approached in the medical literature. This review presents a clinical approach to unintentionally pregnant patients and describes the information and support that can be offered for the continuation of the unintended pregnancy. Clinicians should approach patients with an unintended pregnancy with a sympathetic tone. A complete clinical history can help frame the problem and identify concerns related to the pregnancy. Any underlying medical or obstetric problems can be discussed. A social history, that includes the personal support from the patient's partner, parents, and siblings, can be taken. Doctors should also be alert of possible cases of violence from the partner or child abuse in adolescent patients. Finally, the clinician can provide the first information regarding the social care available and refer the patients for further support. For women who continue an unintended pregnancy, clinicians should start antenatal care immediately.

Análisis de la efectividad de los centros de rehabilitación psicosocial / Analysis of the effectiveness of psychosocial rehabilitation centers

Introducción: Los Centros de Rehabilitación Psicosocial para personas con trastorno mental grave son recursos de la red pública de atención social de la Comunidad de Madrid. A pesar de su larga tradición son pocos los estudios que intentan evaluar su efectividad. En el presente trabajo se analizan retrospectivamente los resultados obtenidos en tres dominios centrales en la recuperación: el funcionamiento psicosocial, la calidad de vida y la discapacidad. Material y método: Se analizan las 3173 puntuaciones de 1457 personas atendidas durante 5 años (2008-2012) en 10 Centros de Rehabilitación Psicosocial. Se utilizaron los siguientes instrumentos: cuestionario de datos sociodemográficos y clínicos de elaboración propia, Satisfaction with Life Domain Scale (SLDS), Escala de Evaluación del Funcionamiento Global (EEFG) y WHO Short Disability Assessment Schedule (WHO DAS-S). Resultados: Se observan correlaciones estadísticamente significativas entre todas las medidas de los diferentes instrumentos y la duración de la estancia en los centros, de tal forma que a más tiempo de intervención se obtienen mejores resultados, al menos durante los primeros 5 años. Desagregando los datos por sexo se constata que las mujeres mejoran más y más rápido que los hombres. Conclusiones: Las personas que son atendidas en los Centros de Rehabilitación Psicosocial mejoran en calidad de vida, funcionamientos psicosocial y discapacidad. Esa mejoría es más pronunciada en los primeros cinco a ocho años de intervención y es mayor en mujeres que en hombres (AU)

Introduction: Psychosocial Rehabilitation Centres for people with severe mental illness form part of the public network of social services in the Community of Madrid. Despite their long history in that region, few studies have attempted to evaluate their effectiveness. The present study retrospectively analyzes results obtained in three central domains of recovery: psychosocial functioning, quality of life and disability. Material and methods: 3173 scores of 1457 people who received treatment over 5 years (2008-2012) in 10 Psychosocial Rehabilitation Centres were analyzed. The following instruments were used: an in-house questionnaire of social, demographic and clinical data, the Satisfaction with Life Domain Scale (SLDS), the Global Assessment of Functioning Scale (GAF) and the World Health Organization’s Short Disability Assessment Schedule (WHO DAS-S). Results: Statistically significant correlations were drawn between the measures in all instruments and the total duration of treatment received at the centres. Longer time in treatment was associated with improved results at least over a five-year period. When the data were stratified by sex, women improved more overall and at a faster rate than men. Conclusion: People who received treatment at Psychosocial Rehabilitation Centres improved in terms of quality of life, psychosocial functioning and disability. This improvement was more pronounced within the first five to eight years of intervention and was greater in women than in men (AU)