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Nursing education includes a constant challenge regarding the competencies that nurses must possess to provide high-quality nursing care. One of these competencies is critical thinking (CT), and motivation for critical thinking (MCT) has been identified as an element necessary to develop CT. Expectancy and value are important components of the MCT. This study aimed to analyze sociodemographic and academic factors related to MCT in Chilean nursing students. This study is an analytical-correlational, cross-sectional study conducted with 478 nursing students in Chile. The data were collected using an online questionnaire. The Critical Thinking Motivation Scale was used to measure MCT. Pearson's square, Chi-square, means comparison test, and binomial logistic regression were used to analyze the data. The expectancy component of the MCT had the lowest scores on the scale. Age was associated with the cost subcomponent ( p < .03), and high school was associated with the interest subcomponent ( p < .01). Academic factors contributing to MCT were problem-based learning, professor motivation, and the inclusion of MCT in nursing disciplinary subjects. Strategies that improve CT and MCT should be implemented and evaluated periodically from the beginning of a nursing career. Faculty should be trained to motivate students to think critically.

Background and Objective: Chronic intermittent hypoxia (CIH), one of the main features of obstructive sleep apnea (OSA), enhances carotid body-mediated chemoreflex and induces hypertension and breathing disorders. The carbamylated form of erythropoietin (cEpo) may have beneficial effects as it retains its antioxidant/anti-inflammatory and neuroprotective profile without increasing red blood cells number. However, no studies have evaluated the potential therapeutic effect of cEpo on CIH-related cardiorespiratory disorders. We aimed to determine whether cEpo normalized the CIH-enhanced carotid body ventilatory chemoreflex, the hypertension and ventilatory disorders in rats., Methods: Male Sprague-Dawley rats (250 g) were exposed to CIH (5% O2, 12/h, 8 h/day) for 28 days. cEPO (20 μg/kg, i.p) was administrated from day 21 every other day for one more week. Cardiovascular and respiratory function were assessed in freely moving animals., Results: Twenty-one days of CIH increased carotid body-mediated chemoreflex responses as evidenced by a significant increase in the hypoxic ventilatory response (FiO2 10%) and triggered irregular eupneic breathing, active expiration, and produced hypertension. cEpo treatment significantly reduced the carotid body--chemoreflex responses, normalizes breathing patterns and the hypertension in CIH. In addition, cEpo treatment effectively normalized carotid body chemosensory responses evoked by acute hypoxic stimulation in CIH rats., Conclusion: Present results strongly support beneficial cardiorespiratory therapeutic effects of cEpo during CIH exposure., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Literature shows that sexual activity remains important at older age and is a valued part of life. However, little is known about the intimate partner relationships (IPR) among minority older women living with Human Immunodeficiency Virus (HIV). The purpose of this study is to explore the effect HIV diagnosis had on the intimate partner relationships (IPR) among minority older women living with HIV (MOWH)., Methods: Qualitative descriptive study. A total of 28 MOWH (Black and Latinas) aged 50 years and older participated in face to face semi-structured in-depth interviews. Interviews were analyzed using content analysis., Results: Three themes emerged from the analysis: (a)" Intimate partner relationships before HIV diagnosis" that revealed sexual practices increasing the risk for HIV in their intimate relationships; (b)" Facing relationship consequences of HIV disclosure after diagnosis" explored the consequences of HIV disclosure, and how disclosure determined the future of their intimate relationships; and (c) "Intimate partner relationships after HIV diagnosis" described the quality of intimate partner relationships and changes after HIV diagnosis., Conclusions: Results from this study contribute to understanding and increasing awareness of the effect of HIV on the intimacy of MOWH., Clinical Implications: Education provided by health care workers and interventions targeting MOWH should address the effect of HIV in IPR, address MOWH's concerns about it, and help them to improve their overall health.

Paraquat (PQT) herbicide is widely used in agricultural practices despite being highly toxic to humans. It has been proposed that PQT exposure may promote cardiorespiratory impairment. However, the physiological mechanisms involved in cardiorespiratory dysfunction following PQT exposure are poorly known. We aimed to determine the effects of PQT on ventilatory chemoreflex control, cardiac autonomic control, and cardiac function in rats. Male Sprague-Dawley rats received two injections/week of PQT (5 mg·kg -1 ip) for 4 wk. Cardiac function was assessed through echocardiography and pressure-volume loops. Ventilatory function was evaluated using whole body plethysmography. Autonomic control was indirectly evaluated by heart rate variability (HRV). Cardiac electrophysiology (EKG) and exercise capacity were also measured. Four weeks of PQT administration markedly enlarged the heart as evidenced by increases in ventricular volumes and induced cardiac diastolic dysfunction. Indeed, end-diastolic pressure was significantly higher in PQT rats compared with control (2.42 ± 0.90 vs. 4.01 ± 0.92 mmHg, PQT vs. control, P < 0.05). In addition, PQT significantly reduced both the hypercapnic and hypoxic ventilatory chemoreflex response and induced irregular breathing. Also, PQT induced autonomic imbalance and reductions in the amplitude of EKG waves. Finally, PQT administration impaired exercise capacity in rats as evidenced by a ∼2-fold decrease in times-to-fatigue compared with control rats. Our results showed that 4 wk of PQT treatment induces cardiorespiratory dysfunction in rats and suggests that repetitive exposure to PQT may induce harmful mid/long-term cardiovascular, respiratory, and cardiac consequences. NEW & NOREWORTHY Paraquat herbicide is still employed in agricultural practices in several countries. Here, we showed for the first time that 1 mo paraquat administration results in cardiac adverse remodeling, blunts ventilatory chemoreflex drive, and promotes irregular breathing at rest in previously healthy rats. In addition, paraquat exposure induced cardiac autonomic imbalance and cardiac electrophysiology alterations. Lastly, cardiac diastolic dysfunction was overt in rats following 1 mo of paraquat treatment.

The development of smart nanoparticles (NPs) became a trend to enhance the delivery of drugs. In the present work, Tobramycin (TB), an aminoglycoside antibiotic that displays several undesirable side effects, has been encapsulated into cationic Eudragit®E100 (E100) NPs for the treatment of infections caused by Pseudomonas aeruginosa. Combination with neutral Eudragit®NE30D (NE30D) NPs containing resveratrol (RSV), a strong natural antioxidant, increased the antimicrobial activity of TB (75% higher than free TB). NPs were stabilized with 1.0% (w/v) poloxamer 188 (P188) or poloxamer 407 (P407) as surfactants. E100 NPs showed 83.3 ± 8.5%, and 70.1 ± 2.7 encapsulation efficiency (EE) of TB with P188 and P407 coatings, respectively. The presence of NPs was confirmed by DLS and TEM studies. TB was controlled released from NPs for 6 h. Hemotoxicity tests of NPs in the range of MIC values on human blood gave negative results. Analysis of Surface Plasmon Resonance verified that NE30D/P407/RSV does not interact with plasma proteins BSA, IgG or fibrinogen, besides E100/P188/TB interact with BSA, findings that are compatible with a negligible in vivo clearance of the nanovehicles. The obtained results show a potential binary fluid composed of two NPs to highly improve the effectiveness of conventional antibiotics., (Copyright © 2021 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: In addition to providing millions of men with lifelong lower risk for HIV infection, voluntary medical male circumcision (VMMC) also provides female partners with health benefits including decreased risk for human papillomavirus (HPV) and resultant cervical cancer (CC)., Setting: We modeled potential impacts of VMMC on CC incidence and mortality in Uganda as an additional benefit beyond HIV prevention., Methods: HPV and CC outcomes were modeled using the CC model from the Spectrum policy tool suite, calibrated for Uganda, to estimate HPV infection incidence and progression to CC, using a 50-year (2018-2067) time horizon. 2016 Demographic Health Survey data provided baseline VMMC coverage. The baseline (no VMMC scale-up beyond current coverage, minimal HPV vaccination coverage) was compared with multiple scenarios to assess the varying impact of VMMC according to different implementations of HPV vaccination and HPV screening programs., Results: Without further intervention, annual CC incidence was projected to rise from 16.9 to 31.2 per 100,000 women in 2067. VMMC scale-up alone decreased 2067 annual CC incidence to 25.3, averting 13,000 deaths between 2018 and 2067. With rapidly-achieved 90% HPV9 vaccination coverage for adolescent girls and young women, 2067 incidence dropped below 10 per 100,000 with or without a VMMC program. With 45% vaccine coverage, the addition of VMMC scaleup decreased incidence by 2.9 per 100,000 and averted 8000 additional deaths. Similarly, with HPV screen-and-treat without vaccination, the addition of VMMC scaleup decreased incidence by 5.1 per 100,000 and averted 10,000 additional deaths., Conclusions: Planned VMMC scale-up to 90% coverage from current levels could prevent a substantial number of CC cases and deaths in the absence of rapid scale-up of HPV vaccination to 90% coverage., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Introduction & Objectives: The independent effect of liver biochemistries as a prognostic factor in patients with COVID-19 has not been completely addressed. We aimed to evaluate the prognostic value of abnormal liver tests on admission of hospitalized patients with COVID-19., Materials & Methods: We performed a prospective cohort study including 1611 hospitalized patients with confirmed SARS-CoV-2 infection from April 15, 2020 through July 31, 2020 in 38 different Hospitals from 11 Latin American countries. We registered clinical and laboratory parameters, including liver function tests, on admission and during hospitalization. All patients were followed until discharge or death. We fit multivariable logistic regression models, further post-estimation effect through margins and inverse probability weighting., Results: Overall, 57.8% of the patients were male with a mean age of 52.3 years, 8.5% had chronic liver disease and 3.4% had cirrhosis. Abnormal liver tests on admission were present on 45.2% (CI 42.7-47.7) of the cohort (n = 726). Overall, 15.1% (CI 13.4-16.9) of patients died (n = 244). Patients with abnormal liver tests on admission presented higher mortality 18.7% (CI 15.9-21.7), compared to those with normal liver biochemistries 12.2% (CI 10.1-14.6); P < .0001). After excluding patients with history of chronic liver disease, abnormal liver tests on admission were independently associated with death [OR 1.5 (CI 1.1-2.0); P = 0.01], and severe COVID-19 (2.6 [2.0-3.3], P < .0001), both adjusted by age, gender, diabetes, pneumonia and body mass index >30., Conclusions: The presence of abnormal liver tests on admission is independently associated with mortality and severe COVID-19 in hospitalized patients with COVID-19 infection and may be used as surrogate marker of inflammation. CLINICALTRIALS.GOV: NCT04358380., (Copyright © 2020 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Voluntary medical male circumcision (VMMC) is an HIV prevention strategy recommended to partially protect men from heterosexually acquired HIV. From 2015 to 2019, the President's Emergency Plan for AIDS Relief (PEPFAR) has supported approximately 14.9 million VMMCs in 15 African countries. Urethrocutaneous fistulas, abnormal openings between the urethra and penile skin through which urine can escape, are rare, severe adverse events (AEs) that can occur with VMMC. This analysis describes fistula cases, identifies possible risks and mechanisms of injury, and offers mitigation actions., Methods: Demographic and clinical program data were reviewed from all reported fistula cases during 2015 to 2019, descriptive analyses were performed, and an odds ratio was calculated by patient age group., Results: In total, 41 fistula cases were reported. Median patient age for fistula cases was 11 years and 40/41 (98%) occurred in patients aged < 15 years. Fistulas were more often reported among patients < 15 compared to ≥ 15 years old (0.61 vs. 0.01 fistulas per 100,000 VMMCs, odds ratio 50.9 (95% confidence interval [CI] = 8.6-2060.0)). Median time from VMMC surgery to appearance of fistula was 20 days (interquartile range (IQR) 14-27)., Conclusions: Urethral fistulas were significantly more common in patients under age 15 years. Thinner tissue overlying the urethra in immature genitalia may predispose boys to injury. The delay between procedure and symptom onset of 2-3 weeks indicates partial thickness injury or suture violation of the urethral wall as more likely mechanisms of injury than intra-operative urethral transection. This analysis helped to inform PEPFAR's recent decision to change VMMC eligibility policy in 2020, raising the minimum age to 15 years.

HIV infection during pregnancy, may present risk of developing depression during pregnancy and postpartum. This psychiatric mood disorder, and many others such as anxiety and HIV-related post-traumatic stress disorder (PTSD) have been reported prevalent among pregnant and non-pregnant women living with HIV (WLWH). Multiple studies have found associations between social determinants of health and depressive symptoms in this population. However, despite deleterious effects on mother and child which may include suicidal ideations and infant death, only very few studies have examined this phenomenon for peripartum women, particularly Black women- a population prone to living in poor social and economic environments. Therefore, guided by the socio-ecologic model, this study examined predictors of peripartum depressive symptoms among Black peripartum WLWH. The study was a secondary data analysis of 143 Black women seen at special prenatal and women's health clinics in Miami, South Florida, USA. More than half of the women who experienced peripartum depressive symptoms (PDS) (n = 81, 57%) were of low socio-economic status. Low income was associated with increased odds of experiencing PDS. Women who endorsed intimate partner violence/abuse (IPV/A) were 6.5 times more likely to experience PDS; and compared to women with 1 or no childcare burden, women with 2 children-care burden were 4.6 times more likely to experience PDS. These findings demonstrate the negative impact of social factors on the psychological health of Black peripartum WLWH. Burdensome interpersonal relationships may have deleterious effects and trigger PDS among these women. Implications for nursing practice, education and research are also discussed., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Recent evidence shows that chronic activation of catecholaminergic neurons of the rostral ventrolateral medulla is crucial in promoting autonomic imbalance and cardiorespiratory dysfunction in high output heart failure (HF). Brainstem endoplasmic reticulum stress (ERS) is known to promote cardiovascular dysfunction; however, no studies have addressed the potential role of brainstem ERS in cardiorespiratory dysfunction in high output HF. In this study, we assessed the presence of brainstem ERS and its potential role in cardiorespiratory dysfunction in an experimental model of HF induced by volume overload. High output HF was surgically induced via creation of an arterio-venous fistula in adult male Sprague-Dawley rats. Tauroursodeoxycholic acid (TUDCA), an inhibitor of ERS, or vehicle was administered intracerebroventricularly for 4 weeks post-HF induction. Compared with vehicle treatment, TUDCA improved cardiac autonomic balance (LF HRV /HF HRV ratio, 3.02±0.29 versus 1.14±0.24), reduced cardiac arrhythmia incidence (141.5±26.7 versus 35.67±12.5 events/h), and reduced abnormal respiratory patterns (Apneas: 11.83±2.26 versus 4.33±1.80 events/h). TUDCA administration (HF+Veh versus HF+TUDCA, P <0.05) attenuated cardiac hypertrophy (HW/BW 4.4±0.3 versus 4.0±0.1 mg/g) and diastolic dysfunction. Analysis of rostral ventrolateral medulla gene expression confirmed the presence of ERS, inflammation, and activation of renin-angiotensin system pathways in high output HF and showed that TUDCA treatment completely abolished ERS and ERS-related signaling. Taken together, these results support the notion that ERS plays a role in cardiorespiratory dysfunction in high output HF and more importantly that reducing brain ERS with TUDCA treatment has a potent salutary effect on cardiac function in this model.

Purpose: This study aimed (1) to explore the validity and reliability of a new and specific change-of-direction (COD) test that requires dribbling skills to classify international footballers with cerebral palsy (CP) and compare it with another valid and reliable COD test without ball dribbling and (2) to probe whether both tests can discriminate between the new CP football classes (ie, FT1, FT2, and FT3) established worldwide in 2018., Methods: This study involved 180 international para-footballers with CP from 23 national teams at the 3 regional competitions held in 2018. They performed 2 COD tests, the modified agility test (no dribbling skills) and the dribbling speed test (DST)., Results: Reliability was excellent for both the modified agility test (intraclass correlation coefficient [ICC]2,1 = .91, SEM = 5.75%) and the DST (ICC2,1 = .92, SEM = 4.66%). The modified agility test and DST results were highly to very highly correlated to one another for the whole group and considering the sport classes (r = .60-.80; P < .001). A 1-way analysis of variance showed significant differences between sport classes in both tests (P < .001). However, among classes, there were significant differences between FT1 and FT2 and FT3 (P < .01, effect size = large) and low to moderate effect sizes between FT2 and FT3 for either test., Conclusion: The DST appears to be valid and reliable to classify CP football players within the new classification system. Regression analysis revealed that 18.2% of the variance in the new sport classes could be explained by the 2 examined tests.

Abstract: Male circumcision reduces men's risk of acquiring HIV through heterosexual sex, and voluntary medical male circumcision (VMMC) is central to HIV prevention strategies in 15 sub-Saharan African countries. Nurses have emerged as primary VMMC providers; however, barriers remain to institutionalizing nurse-led VMMC. Patient safety concerns have hindered task sharing, and regulations governing nurse-performed VMMC are not always supportive or clear. We performed a systematic review on VMMC safety by provider cadre and a desk review of national policies governing the VMMC roles of nurses and midwives. Also, VMMC by nurses is safe and has become standard practice. Countries had multiple policy combinations among different documents, with only one disallowing VMMC by these cadres. Countries with alignment between policies often ensured that nursing workforces were equipped with clinical competencies through national certification. Regulatory clarity and formalized certification for nurse-performed VMMC can increase program sustainability and build nursing capacity to meet other critical basic surgical needs., (Copyright © 2020 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Andrade, DC, Manzo, O, Beltrán, AR, Álvarez, C, Del Rio, R, Toledo, C, Moran, J, and Ramirez-Campillo, R. Kinematic and neuromuscular measures of intensity during plyometric jumps. J Strength Cond Res 34(12): 3395-3402, 2020-The aim of this study was to assess jumping performance and neuromuscular activity in lower limb muscles after drop jumps (DJs) from different drop heights (intensity) and during continuous jumping (fatigue), using markers such as reactive strength, jump height, mechanical power and surface electromyography (sEMG). The eccentric (EC) and concentric (CON) sEMG from the medial gastrocnemius (MG), biceps femoris (BF), and rectus (R) muscles were assessed during all tests. In a cross-sectional, randomized study, 11 volleyball players (age 24.4 ± 3.2 years) completed 20-90-cm (DJ20 to DJ90) DJs and a 60-second continuous jump test. A 1-way analysis of variance test was used for comparisons, with Sidak post hoc. The α level was <0.05. Reactive strength was greater for DJ40 compared with DJ90 (p ≤ 0.05; effect size (ES): 1.27). In addition, jump height was greater for DJ40 and DJ60 compared with DJ20 (p ≤ 0.05; ES: 1.26 and 1.27, respectively). No clear pattern of neuromuscular activity appeared during DJ20 to DJ90: some muscles showed greater, lower, or no change with increasing heights for both agonist and antagonist muscles, as well as for EC and CON activity. Mechanical power, but not reactive strength, was reduced in the 60-second jump test (p ≤ 0.05; ES: 3.46). No changes were observed in sEMG for any muscle during the EC phase nor for the R muscle during the CON phase of the 60-second jump test. However, for both MG and BF, CON sEMG was reduced during the 60-second jump test (p ≤ 0.05; ES: 5.10 and 4.61, respectively). In conclusion, jumping performance and neuromuscular markers are sensitive to DJ height (intensity), although not in a clear dose-response fashion. In addition, markers such as mechanical power and sEMG are, especially sensitive to the effects of continuous jumping (fatigue). Therefore, increasing the drop height during DJ does not ensure a greater training intensity and a combination of different drop heights may be required to elicit adaptations.

The bovine viral diarrhea virus (BVDV-1) is a pathogen with the capacity to modulate the interferon type I system. To further investigate the effects of BVDV-1 on the production of the immune response, the Madin-Darby bovine kidney cell line was infected with the cytopathic CH001 field isolate of BVDV-1, and the IFNbeta expression profiles were analyzed. The results showed that cpBVDV-1 was able to induce the production of IFNbeta in a way similar to polyinosinic-polycytidylic acid, but with less intensity. Interestingly, all cpBVDV-1 activities were blocked by pharmacological inhibitors of the IRF-1, IRF-7, and NF-κB signaling pathway, and the level of IFNbeta decreased at the level of transcript and protein. These results, together with in silico analyses showing the presence of several regulatory consensus target motifs, suggest that cpBVDV-1 regulates IFNbeta expression in bovines through the activation of several key transcription factors. Collectively, the results suggest that during cpBVDV-1 infection, cross talk is evident between various signaling pathways involved in transcriptional activation of IFNbeta in cattle., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: With the global population aging and life expectancy increasing, dementia has turned a priority in the health care system. In Chile, dementia is one of the most important causes of disability in the elderly and the most rapidly growing cause of death in the last 20 years. Cognitive complaint is considered a predictor for cognitive and functional decline, incident mild cognitive impairment, and incident dementia. The GERO cohort is the Chilean core clinical project of the Geroscience Center for Brain Health and Metabolism (GERO). The objective of the GERO cohort is to analyze the rate of functional decline and progression to clinical dementia and their associated risk factors in a community-dwelling elderly with subjective cognitive complaint, through a population-based study. We also aim to undertake clinical research on brain ageing and dementia disorders, to create data and biobanks with the appropriate infrastructure to conduct other studies and facilitate to the national and international scientific community access to the data and samples for research., Methods: The GERO cohort aims the recruitment of 300 elderly subjects (> 70 years) from Santiago (Chile), following them up for at least 3 years. Eligible people are adults not diagnosed with dementia with subjective cognitive complaint, which are reported either by the participant, a proxy or both. Participants are identified through a household census. The protocol for evaluation is based on a multidimensional approach including socio-demographic, biomedical, psychosocial, neuropsychological, neuropsychiatric and motor assessments. Neuroimaging, blood and stool samples are also obtained. This multidimensional evaluation is carried out in a baseline and 2 follow-ups assessments, at 18 and 36 months. In addition, in months 6, 12, 24, and 30, a telephone interview is performed in order to keep contact with the participants and to assess general well-being., Discussion: Our work will allow us to determine multidimensional risks factors associated with functional decline and conversion to dementia in elderly with subjective cognitive complain. The aim of our GERO group is to establish the capacity to foster cutting edge and multidisciplinary research on aging in Chile including basic and clinical research., Trial Registration: NCT04265482 in ClinicalTrials.gov. Registration Date: February 11, 2020. Retrospectively Registered.

Background: Sexually transmitted infections (STIs) and Human immunodeficiency virus (HIV) share a complex bidirectional relationship, however, population prevalence and the association between the presence of STIs and HIV in a high HIV burden district in KwaZulu-Natal, South Africa is not known., Methods: A total of 9812 participants aged 15-49 years were enrolled in a cross-sectional population-based household survey. Participants completed a structured questionnaire and provided first-pass urine (males) or self-collected vulvo-vaginal swabs (females) for the detection of STIs., Results: Prevalence of herpes simplex virus type-2 (HSV-2) was 57.8%, syphilis was 1.6%, Neisseria gonorrhoeae was 2.8%, Chlamydia trachomatis was 7.1%, Trichomonas vaginalis was 9.0%, Mycoplasma genitalium was 5.5% and HIV was 36.3%. HIV positive status was associated with an increased probability of having M. genitalium (aPR = 1.49, 95% CI 1.02-2.19) among males and syphilis (aPR = 2.54, 95% CI 1.32-4.86), N. gonorrhoeae (aPR = 2.39, 95% CI 1.62-3.52), T. vaginalis (aPR = 1.70, 95% CI 1.43-2.01) and M. genitalium (aPR = 1.60, 95% CI 1.15-2.22) among females. HIV viral load ≥400 copies per mL was associated with an increased probability of N. gonorrhoeae (aPR = 1.91, 95% CI 1.36-2.70), C. trachomatis (aPR = 1.52, 95% CI 1.12-2.05) and M. genitalium (aPR = 1.83, 95% CI 1.27-2.63)., Conclusions: The high prevalence of STIs and the association between STIs and HIV, and HIV viral load underscores the public health implications of sustained transmission risk of STIs and HIV. These findings highlight the urgent need for expanding STI surveillance and implementing interventions to monitor and reduce the STI burden., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

An increased abundance of antibiotic resistance genes (ARGs) in aquatic environments has been linked to environmental pollution. Mining polluted sites with high concentration of metals could favor the in situ coselection of ARGs, whereas wastewater discharges release fecal antibiotic resistant bacteria in the environment. To study the effect of human fecal contamination and mining pollution, water and sediment samples affected by mining activities and sewage discharges were collected from three lakes in Bolivia, the pristine Andean lake Pata Khota, the Milluni Chico lake directly impacted by acid mine drainage, and the Uru-Uru lake located close to Oruro city and highly polluted by mining activities and human wastewater discharges. Physicochemical parameters, including metal composition, were analyzed in water and sediment samples. ARGs were screened for and verified by quantitative polymerase chain reaction (PCR) together with the mobile element class 1 integron ( intl1 ), as well as crAssphage, a marker of human fecal pollution. The gene intl1 was positively correlated with sul1 , sul2 , tetA , and bla OXA-2 . CrAssphage was only detected in the Uru-Uru lake, and its tributaries and significantly higher abundance of ARGs were found in these sites. Multivariate analysis showed that crAssphage abundance, electrical conductivity, and pH were positively correlated with higher levels of intl1 and ARGs. Taken together, our results suggest that fecal pollution is the major driver of higher levels of ARGs and intl1 in environments contaminated by wastewater and mining activities.

Background: Male circumcision confers partial protection against heterosexual HIV acquisition among men. The President's Emergency Plan for AIDS Relief (PEPFAR) has supported > 18,900,000 voluntary medical male circumcisions (VMMC). Glans injuries (GIs) are rare but devastating adverse events (AEs) that can occur during circumcision. To address this issue, PEPFAR has supported multiple interventions in the areas of surveillance, policy, education, training, supply chain, and AE management., Methods: Since 2015, PEPFAR has conducted surveillance of GIs including rapid investigation by the in-country PEPFAR team. This information is collected on standardized forms, which were reviewed for this analysis., Results: Thirty-six GIs were reported from 2015 to 2018; all patients were < 15 years old (~ 0·7 per 100,000 VMMCs in this age group) with a decreasing annual rate (2015: 0.7 per 100,000 VMMCs; 2018: 0.4 per 100,000 VMMC; p = 0.02). Most (64%) GIs were partial or complete amputations. All amputations among 10-14 year-olds occurred using the forceps-guided (FG) method, as opposed to the dorsal-slit (DS) method, and three GIs among infants occurred using a Mogen clamp. Of 19 attempted amputation repairs, reattached tissue was viable in four (21%) in the short term. In some cases, inadequate DS method training and being overworked, were found., Conclusion: Following numerous interventions by PEPFAR and other stakeholders, GIs are decreasing; however, they have not been eliminated and remain a challenge for the VMMC program. Preventing further cases of complete and partial amputation will likely require additional interventions that prevent use of the FG method in young patients and the Mogen clamp in infants. Improving management of GIs is critical to optimizing outcomes.

Alterations in connexins and specifically in 43 isoform (Cx43) in the heart have been associated with a high incidence of arrhythmogenesis and sudden death in several cardiac diseases. We propose to determine salutary effect of Cx43 mimetic peptide Gap27 in the progression of heart failure. High-output heart failure was induced by volume overload using the arterio-venous fistula model (AV-Shunt) in adult male rats. Four weeks after AV-Shunt surgery, the Cx43 mimetic peptide Gap27 or scrambled peptide, were administered via osmotic minipumps (AV-Shunt Gap27 or AV-Shunt Scr ) for 4 weeks. Cardiac volumes, arrhythmias, function and remodeling were determined at 8 weeks after AV-Shunt surgeries. At 8 th week, AV-Shunt Gap27 showed a marked decrease in the progression of cardiac deterioration and showed a significant improvement in cardiac functions measured by intraventricular pressure-volume loops. Furthermore, AV-Shunt Gap27 showed less cardiac arrhythmogenesis and cardiac hypertrophy index compared to AV-Shunt Scr . Gap27 treatment results in no change Cx43 expression in the heart of AV-Shunt rats. Our results strongly suggest that Cx43 play a pivotal role in the progression of cardiac dysfunction and arrhythmogenesis in high-output heart failure; furthermore, support the use of Cx43 mimetic peptide Gap27 as an effective therapeutic tool to reduce the progression of cardiac dysfunction in high-output heart failure.

Primary lymphocytic hypophysitis is an autoimmune disease characterized by lymphocytic infiltration of the pituitary gland, with a higher incidence during late pregnancy and the postpartum period. It causes glandular destruction, mass effect and symptoms such headache, visual field defects, ophthalmoplegia and symptoms of hypopituitarism. We report a 38-year-old postpartum woman who, after giving birth presented decreased left visual acuity associated with a non ictal headache. Magnetic resonance imaging demonstrated a sellar mass associated with decreased free thyroxine and cortisol levels. Suspecting a primary lymphocytic hypophysitis, she was treated with prednisone 60 mg/day and hormonal replacement therapy. One month later, size of the pituitary gland decreased, and the visual field defect improved. Steroidal treatment was maintained for 36 months and progressively tapered. After two years of follow-up, the imaging studies show a normal sized pituitary gland.

Heart failure (HF) is a complex clinical syndrome affecting roughly 26 million people worldwide. Increased sympathetic drive is a hallmark of HF and is associated with disease progression and higher mortality risk. Several mechanisms contribute to enhanced sympathetic activity in HF, but these pathways are still incompletely understood. Previous work suggests that inflammation and activation of the renin-angiotensin system (RAS) increases sympathetic drive. Importantly, chronic inflammation in several brain regions is commonly observed in aged populations, and a growing body of evidence suggests neuroinflammation plays a crucial role in HF. In animal models of HF, central inhibition of RAS and pro-inflammatory cytokines normalizes sympathetic drive and improves cardiac function. The precise molecular and cellular mechanisms that lead to neuroinflammation and its effect on HF progression remain undetermined. This review summarizes the most recent advances in the field of neuroinflammation and autonomic control in HF. In addition, it focuses on cellular and molecular mediators of neuroinflammation in HF and in particular on brain regions involved in sympathetic control. Finally, we will comment on what is known about neuroinflammation in the context of preserved vs. reduced ejection fraction HF., (© 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society.)

The article Association of Male Circumcision with Women's Knowledge of its Biomedical Effects and With Their Sexual Satisfaction and Function: A Systematic Review, written by Jonathan M. Grund, Tyler S. Bryant, Carlos Toledo, Inimfon Jackson, Kelly Curran, Sheng Zhou, Jorge Martin del Campo, Ling Yang, Apollo Kivumbi, Peizi Li, Naomi Bock, Joanna Taliano, Stephanie M. Davis was originally published electronically on the publisher's internet portal (currently SpringerLink) on 24 October 2018 without open access.

Enhanced central chemoreflex (CC) gain is observed in volume overload heart failure (HF) and is correlated with autonomic dysfunction and breathing disorders. The aim of this study was to determine the role of the CC in the development of respiratory and autonomic dysfunction in HF. Volume overload was surgically created to induce HF in male Sprague-Dawley rats. Radiotelemetry transmitters were implanted for continuous monitoring of blood pressure and heart rate. After recovering from surgery, conscious unrestrained rats were exposed to episodic hypercapnic stimulation [EHS; 10 cycles/5 min, inspiratory fraction of carbon dioxide ( F I CO 2 ) 7%] in a whole body plethysmograph for recording of cardiorespiratory function. To determine the contribution of CC to cardiorespiratory variables, selective ablation of chemoreceptor neurons within the retrotrapezoid nucleus (RTN) was performed via injection of saporin toxin conjugated to substance P (SSP-SAP). Vehicle-treated rats (HF+Veh and Sham+Veh) were used as controls for SSP-SAP experiments. Sixty minutes post-EHS, minute ventilation was depressed in sham animals relative to HF animals (ΔV̇e: -5.55 ± 2.10 vs. 1.24 ± 1.35 mL/min 100 g, P < 0.05; Sham+Veh vs. HF+Veh). Furthermore, EHS resulted in autonomic imbalance, cardiorespiratory entrainment, and ventilatory disturbances in HF+Veh but not Sham+Veh rats, and these effects were significantly attenuated by SSP-SAP treatment. Also, the apnea-hypopnea index (AHI) was significantly lower in HF+SSP-SAP rats compared with HF+Veh rats (AHI: 5.5 ± 0.8 vs. 14.4 ± 1.3 events/h, HF+SSP-SAP vs. HF+Veh, respectively, P < 0.05). Finally, EHS-induced respiratory-cardiovascular coupling in HF rats depends on RTN chemoreceptor neurons because it was reduced by SSP-SAP treatment. Overall, EHS triggers ventilatory plasticity and elicits cardiorespiratory abnormalities in HF that are largely dependent on RTN chemoreceptor neurons.

Heart failure (HF) is a major public health issue affecting more than 26 million people worldwide. HF is the most common cardiovascular disease in elder population; and it is associated with neurocognitive function decline, which represent underlying brain pathology diminishing learning and memory faculties. Both HF and neurocognitive impairment are associated with recurrent hospitalization episodes and increased mortality rate in older people, but particularly when they occur simultaneously. Overall, the published studies seem to confirm that HF patients display functional impairments relating to attention, memory, concentration, learning, and executive functioning compared with age-matched controls. However, little is known about the molecular mechanisms underpinning neurocognitive decline in HF. The present review round step recent evidence related to the possible molecular mechanism involved in the establishment of neurocognitive disorders during HF. We will make a special focus on cerebral ischemia, neuroinflammation and oxidative stress, Wnt signaling, and mitochondrial DNA alterations as possible mechanisms associated with cognitive decline in HF. Also, we provide an integrative mechanism linking pathophysiological hallmarks of altered cardiorespiratory control and the development of cognitive dysfunction in HF patients. Graphical Abstract Main molecular mechanisms involved in the establishment of cognitive impairment during heart failure. Heart failure is characterized by chronic activation of brain areas responsible for increasing cardiac sympathetic load. In addition, HF patients also show neurocognitive impairment, suggesting that the overall mechanisms that underpin cardiac sympathoexcitation may be related to the development of cognitive disorders in HF. In low cardiac output, HF cerebral infarction due to cardiac mural emboli and cerebral ischemia due to chronic or intermittent cerebral hypoperfusion has been described as a major mechanism related to the development of CI. In addition, while acute norepinephrine (NE) release may be relevant to induce neural plasticity in the hippocampus, chronic or tonic release of NE may exert the opposite effects due to desensitization of the adrenergic signaling pathway due to receptor internalization. Enhanced chemoreflex drive is a major source of sympathoexcitation in HF, and this phenomenon elevates brain ROS levels and induces neuroinflammation through breathing instability. Importantly, both oxidative stress and neuroinflammation can induce mitochondrial dysfunction and vice versa. Then, this ROS inflammatory pathway may propagate within the brain and potentially contribute to the development of cognitive impairment in HF through the activation/inhibition of key molecular pathways involved in neurocognitive decline such as the Wnt signaling pathway.

Key Points: A strong association between disordered breathing patterns, elevated sympathetic activity, and enhanced central chemoreflex drive has been shown in experimental and human heart failure (HF). The aim of this study was to determine the contribution of catecholaminergic rostral ventrolateral medulla catecholaminergic neurones (RVLM-C1) to both haemodynamic and respiratory alterations in HF. Apnoea/hypopnoea incidence (AHI), breathing variability, respiratory-cardiovascular coupling, cardiac autonomic control and cardiac function were analysed in HF rats with or without selective ablation of RVLM-C1 neurones. Partial lesion (∼65%) of RVLM-C1 neurones reduces AHI, respiratory variability, and respiratory-cardiovascular coupling in HF rats. In addition, the deleterious effects of central chemoreflex activation on cardiac autonomic balance and cardiac function in HF rats was abolished by ablation of RVLM-C1 neurones. Our findings suggest that RVLM-C1 neurones play a pivotal role in breathing irregularities in volume overload HF, and mediate the sympathetic responses induced by acute central chemoreflex activation., Abstract: Rostral ventrolateral medulla catecholaminergic neurones (RVLM-C1) modulate sympathetic outflow and breathing under normal conditions. Heart failure (HF) is characterized by chronic RVLM-C1 activation, increased sympathetic activity and irregular breathing patterns. Despite studies showing a relationship between RVLM-C1 and sympathetic activity in HF, no studies have addressed a potential contribution of RVLM-C1 neurones to irregular breathing in this context. Thus, the aim of this study was to determine the contribution of RVLM-C1 neurones to irregular breathing patterns in HF. Sprague-Dawley rats underwent surgery to induce volume overload HF. Anti-dopamine β-hydroxylase-saporin toxin (DβH-SAP) was used to selectively lesion RVLM-C1 neurones. At 8 weeks post-HF induction, breathing pattern, blood pressures (BP), respiratory-cardiovascular coupling (RCC), central chemoreflex function, cardiac autonomic control and cardiac function were studied. Reduction (∼65%) of RVLM-C1 neurones resulted in attenuation of irregular breathing, decreased apnoea-hypopnoea incidence (11.1 ± 2.9 vs. 6.5 ± 2.5 events h -1 ; HF+Veh vs. HF+DβH-SAP; P < 0.05) and improved cardiac autonomic control in HF rats. Pathological RCC was observed in HF rats (peak coherence >0.5 between breathing and cardiovascular signals) and was attenuated by DβH-SAP treatment (coherence: 0.74 ± 0.12 vs. 0.54 ± 0.10, HF+Veh vs. HF+DβH-SAP rats; P < 0.05). Central chemoreflex activation had deleterious effects on cardiac function and cardiac autonomic control in HF rats that were abolished by lesion of RVLM-C1 neurones. Our findings reveal that RVLM-C1 neurones play a major role in irregular breathing patterns observed in volume overload HF and highlight their contribution to cardiac dysautonomia and deterioration of cardiac function during chemoreflex activation., (© 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society.)

Importance: In Africa, the persistently high HIV incidence rate among young women is the major obstacle to achieving the goal of epidemic control., Objective: To determine trends in coverage of HIV prevention and treatment programs and HIV incidence., Design, Setting, and Participants: This cohort study consisted of 2 sequential, community-based longitudinal studies performed in the Vulindlela and Greater Edendale area in KwaZulu-Natal, South Africa. Participants enrolled from June 11, 2014, to June 22, 2015 (2014 survey), with a single follow-up visit from June 24, 2016, to April 3, 2017 (2016 cohort), or enrolled from July 8, 2015, to June 7, 2016 (2015 survey), with a single follow-up visit from November 7, 2016, to August 30, 2017 (2017 cohort). Men and women aged 15 to 49 years were enrolled in the 2014 and 2015 surveys, and HIV-seronegative participants aged 15 to 35 years were followed up in the 2016 and 2017 cohorts. Analysis was conducted from January 1 through December 31, 2018., Exposures: HIV prevention and treatment programs in a real-world, nontrial setting., Main Outcomes and Measures: Trends in sex- and age-specific HIV incidence rates, condom use, voluntary medical male circumcision, knowledge of HIV-seropositive status, uptake of antiretroviral therapy, and viral suppression., Results: A total of 9812 participants (6265 women [63.9%]; median age, 27 years [interquartile range, 20-36 years]) from 11 289 households were enrolled in the 2014 survey, and 10 236 participants (6341 women [61.9%]; median age, 27 years [interquartile range, 20-36 years]) from 12 247 households were enrolled in the 2015 survey. Of these, 3536 of 4539 (annual retention rate of 86.7%) completed follow-up in the 2016 cohort, and 3907 of 5307 (annual retention rate of 81.4%) completed follow-up in the 2017 cohort. From 2014 to 2015, condom use with last sex partner decreased by 10% from 24.0% (n = 644 of 3547) to 21.6% (n = 728 of 3895; P = .12) in men and by 17% from 19.6% (n = 1039 of 6265) to 16.2% (n = 871 of 6341; P = .002) in women. Voluntary medical male circumcision increased by 13% from 31.9% (1102 of 3547) to 36.1% (n = 1472 of 3895); P = .007) in men, and the proportion of women reporting that their partner was circumcised increased by 35% from 35.7% (n = 1695 of 4766) to 48.2% (n = 2519 of 5207; P < .001). Knowledge of HIV-seropositive status increased by 21% from 51.8% (n = 504 of 3547) to 62.9% (n = 570 of 3895; P < .001) in men and by 14% from 64.6% (n = 1833 of 6265) to 73.4% (n = 2182 of 6341; P < .001) in women. Use of antiretroviral therapy increased by 32% from 36.7% (n = 341 of 3547) to 48.6% (n = 432 of 3895; P < .001) in men and by 29% from 45.6% (n = 1251 of 6265) to 58.8% (n = 1743 of 6341; P < .001) in women; HIV viral suppression increased by 20% from 41.9% (n = 401 of 3547) to 50.3% (n = 456 of 3895; P = .005) in men and by 13% from 54.8% (n = 1547 of 6265) to 61.9% (n = 1828 of 6341; P < .001) in women. Incidence of HIV declined in women aged 15 to 19 years from 4.63 (95% CI, 3.29-6.52) to 2.74 (95% CI, 1.84-4.09) per 100 person-years (P = .04) but declined marginally or remained unchanged among men and women in other age groups., Conclusions and Relevance: This study showed a significant decline in HIV incidence in young women; however, to further reduce HIV incidence, HIV prevention and treatment program coverage must be intensified and scaled up.

Introduction: Our aim was to determine the difference between measuring blood pressure (BP) with the mean of three determinations versus the mean of the second and the third determinations in a random general population sample., Methods: Epidemiological study of the general population aged ≥ 18 from the Health Area of Toledo (Spain), based on the health card database. Three readings of systolic and diastolic BP were taken with validated oscillometric devices OMRON HEM-907. The mean of the three readings was compared with the mean of the second and third readings after discarding the first measurement. We analyzed age, sex, BMI, abdominal obesity, dyslipidemia, diabetes mellitus, smoking and sedentary lifestyle. A descriptive study was conducted, as well as the agreement in the diagnosis of hypertension., Results: 1532 subjects were analyzed (mean age 49.01 ± 15.79 years old, 55.5% women). Response rate 36.3%. The mean systolic BP with three readings was 125.39 ± 17.43 mmHg, versus 124.33 ± 17.07 mmHg with the mean of the second and third readings (mean difference 1.01 ± 4.31; Cohen's D = 0.059). The mean diastolic BP was 73.93 ± 10.89 versus 73.71 ± 10.93 mmHg with both methods (mean difference 0.19 ± 2.11; Cohen's D = 0.017). Differences by age, sex, BMI, abdominal obesity, dyslipidemia, diabetes, smoking and sedentary lifestyle were all small (Cohen's D < 0.08). The agreement between both models for classifying subjects as hypertensive/non-hypertensive showed a Kappa value = 0.936 (McNemar's test p < 0.001)., Conclusions: Determining the mean of three readings of BP does not make a significant difference in relation to the reading of the second and third measurements in a sample of general population.

Introduction: Since 2011, Kenya has been evaluating ShangRing device for use in its voluntary medical male circumcision (VMMC) program according to World Health Organization (WHO) guidelines. Compared to conventional surgical circumcision, the ShangRing procedure is shorter, does not require suturing and gives better cosmetic outcomes. After a pilot evaluation of ShangRing in 2011, Kenya conducted an active surveillance for adverse events associated with its use from 2016-2018 to further assess its safety, uptake and to identify any operational bottlenecks to its widespread use based on data from a larger pool of procedures in routine health care settings., Methods: From December 2017 to August 2018, HIV-negative VMMC clients aged 13 years or older seeking VMMC at six sites across five counties in Kenya were offered ShangRing under injectable local anesthetic as an alternative to conventional surgical circumcision. Providers described both procedures to clients before letting them make a choice. Outcome measures recorded for clients who chose ShangRing included the proportions who were clinically eligible, had successful device placement, experienced adverse events (AEs), or failed to return for device removal. Clients failing to return for follow up were sought through phone calls, text messages or home visits to ensure removal and complete information on adverse events., Results: Out of 3,692 eligible clients 1,079 (29.2%) chose ShangRing; of these, 11 (1.0%) were excluded due to ongoing clinical conditions, 17 (1.6%) underwent conventional surgery due to lack of appropriate device size at the time of the procedure, 97.3% (1051/1079) had ShangRing placement. Uptake of ShangRing varied from 11% to 97% across different sites. There was one severe AE, a failed ShangRing placement (0.1%) managed by conventional wound suturing, plus two moderate AEs (0.2%), post removal wound dehiscence and bleeding, that resolved without sequelae. The overall AE rate was 0.3%. All clients returned for device removal from fifth to eleventh day after placement., Conclusion: ShangRing circumcision is effective and safe in the Kenyan context but its uptake varies widely in different settings. It should be rolled out under programmatic implementation for eligible males to take advantage of its unique benefits and the freedom of choice beyond conventional surgical MMC. Public education on its availability and unique advantages is necessary to optimize its uptake and to actualize the benefit of its inclusion in VMMC programs., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To report the diagnosis, histological findings, and treatment of a patient who developed epithelial ingrowth after Descemet membrane endothelial keratoplasty (DMEK)., Methods: We present the case of a type 2 diabetic 60-year-old man who underwent DMEK for Fuchs dystrophy. Two months after surgery, an epithelial ingrowth in the graft-host interface was suspected. After a 3-month follow-up period in which progressive and centrifugal growth of the epithelial cells in the interface was documented, penetrating keratoplasty (PK) was performed to remove all areas of epithelial ingrowth. No evidence of recurrence was observed 1 year later., Results: Histopathologic evaluation of the corneal button obtained in the PK procedure confirmed the epithelial ingrowth in the interface between the Descemet membrane graft and the host cornea., Conclusions: Epithelial ingrowth may occur after a corneal endothelium transplant. There have been multiple reports of epithelial ingrowth after Descemet stripping automated endothelial keratoplasty, but this particular case report suggests that epithelial ingrowth may also occur after DMEK. In this case, PK solved the complication.

Age represents the highest risk factor for death due to cardiovascular disease. Heart failure (HF) is the most common cardiovascular disease in elder population and it is associated with cognitive impairment (CI), diminishing learning and memory process affecting life quality and mortality in these patients. In HF, CI has been associated with inadequate O 2 supply to the brain; however, an important subset of HF patients displays CI with almost no alteration in cerebral blood flow. Importantly, nothing is known about the pathophysiological mechanisms underpinning CI in HF with no change in brain tissue perfusion. Here, we aimed to study memory performance and learning function in a rodent model of HF that shows no change in blood flow going to the brain. We found that HF rats presented learning impairments and memory loss. In addition, HF rats displayed a decreased level of Wnt/β-catenin signaling downstream elements in the hippocampus, one pathway implicated largely in aging diseases. Taken together, our results suggest that in HF rats CI is associated with dysfunction of the Wnt/β-catenin signaling pathway. The mechanisms involved in the alterations of Wnt/β-catenin signaling in HF and its contribution to the development/maintenance of CI deserves future investigations.

Background: Studies have shown significant benefits of exercise therapy in heart failure (HF) with a reduced ejection fraction (HFrEF) and HF with a preserved ejection fraction (HFpEF). The mechanisms responsible for the beneficial effect of exercise in HFrEF and HFpEF are still unclear. We hypothesized that the effect of exercise on myocardial remodeling may explain its beneficial effect., Methods: IMAGING-REHAB-HF is a single-center, randomized, controlled clinical trial using cardiac magnetic resonance imaging, vasomotor endothelial function, cardiac sympathetic activity imaging and serum biomarkers to compare the effect of exercise therapy in HFpEF (LVEF ≥ 45%) and HFrEF (LVEF < 45%). Subjects will be assessed at baseline and after 4 months. The exercise program will consist of three 60-min exercise sessions/week. The primary endpoints are the effect of exercise on myocardial extracellular volume (ECV), left ventricular (LV) systolic function, LV mass, LV mass-to-volume and LV cardiomyocyte volume. Secondary endpoints include the effect of exercise on vasomotor endothelial function, cardiac sympathetic activity and plasmatic biomarkers. Patients will be allocated in a 2:1 fashion to supervised exercise program or usual care. A total sample size of 90 patients, divided into two groups according to LVEF:HFpEF group (45 patients:30 in the intervention arm and 15 in the control arm) and HFrEF group (45 patients:30 in the intervention arm and 15 in the control arm) - will be necessary to achieve adequate power., Conclusion: This will be the first study to evaluate the benefits of a rehabilitation program on cardiac remodeling in HF patients. The unique design of our study may provide unique data to further elucidate the mechanisms involved in reverse cardiac remodeling after exercise in HFpEF and HFrEF patients., Competing Interests: Conflict of interest statement: The author(s) declared following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Neilan reports consultancy for Parexel, Intrinsic Imaging, BMS and Aprea Therapeutics unrelated to the contents of this article. The other authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Background: Hypertonia is characterized by increased resting muscle tone. Previous studies have shown that adult patients with hypertonia displayed autonomic imbalance. However, cardiac sympatho-vagal control in infants with hypertonia have not been explored. The main aim was to estimate cardiac autonomic control in infants with hypertonia using heart rate variability (HRV)., Methods: Thirty infants (0-2 years old) were studied. Heart rate (HR) and R-R interval time series were obtained in 15 Control and 15 Hypertonia infants. HRV was analyzed in time and frequency domains. Additionally, non-linear analysis and entropy measurements were performed., Results: Infants with hypertonia showed cardiac autonomic imbalance as evidenced by alterations in HRV, characterized by an increased power spectral density of low frequency (LF) over high frequency (HF) components of HRV. Indeed, a ∼7% increase in LF, and ∼30% reduction in HF, were found in infants with hypertonia vs. control infants. In addition, time domain and non-linear HRV analysis (Root-mean-square of successive normal sinus R-R interval difference, entropy, and R-R interval variability) were all significantly decreased in hypertonia vs. control subjects., Conclusions: Our results showed that hypertonia infants displayed HRV disturbances, which suggest an alteration in overall autonomic cardiac modulation in infants with hypertonia compared with healthy condition.

Introduction: Male circumcision (MC) confers partial protection to men against HIV and, in research settings, some sexually transmitted infections (STIs). It is also associated with protection from some STIs among female partners. However, real-world data on changes in STI transmission associated with large-scale public African medical male circumcision (MMC) conducted for HIV prevention are lacking and would improve estimates of the health impact of MMC., Methods: The HIV Incidence Provincial Surveillance System is a community-based surveillance platform for HIV prevalence, incidence and intervention coverage trends in KwaZulu-Natal province, South Africa. HIPPS collected cross-sectional self-reported data on circumcision status (from men), partner circumcision status for past three partners (from women) and demographic characteristics and behavioural risk factors; and tested participants for HIV, herpes simplex virus type 2 (HSV-2), syphilis, hepatitis B, N eisseria gonorrhoeae , C hlamydia trachomatis , Trichomonas vaginalis and Mycoplasma genitalium . Bivariable and multivariable analyses were performed on associations between own (men) or partner's (women) circumcision status and each STI. Multivariable analyses adjusted for age, demographic characteristics and behavioural risk factors, and incorporated false discovery rate (FDR) correction., Results: Among men, MMC had a protective association with HSV-2 (OR 0.66, 95% CI 0.50 to 0.86), hepatitis B (OR 0.53, 95% CI 0.30 to 0.95), HIV (OR 0.50, 95% CI 0.38 to 0.65) and M. genitalium (OR 0.53, 95% CI 0.32 to 0.88). Among women, partner circumcision had a protective association with HSV-2 (OR 0.71, 95% CI 0.53 to 0.95) and HIV (OR 0.66, 95% CI 0.49 to 0.90). Associations with HIV and HSV-2 remained significant for men and all women after FDR correction., Conclusion: These real-world data, supporting protective associations between MMC conducted for HIV prevention and STIs in men and women, can help clarify the full impact of MMC and support a role in broader sexual health programming., Competing Interests: Competing interests: None declared.

Male circumcision (MC) is a key HIV prevention intervention for men in countries with high HIV prevalence. Women's understanding of MC is important but poorly understood. We conducted a systematic review including women's knowledge of MC's biomedical impacts and its association with female sexual satisfaction and function through October 2017. Thirty-eight articles were identified: thirty-two with knowledge outcomes, seven with sexual satisfaction, and four with sexual function (N = 38). Respondent proportions aware MC protects men from HIV were 9.84-91.8% (median 60.0%). Proportions aware MC protects men from STIs were 14.3-100% (72.6%). Proportions aware MC partially protects men from HIV were 37.5-82% (50.7%). Proportions aware MC is not proven to protect women from infection by an HIV-positive partner were 90.0-96.8% (93.0%). No increases over time were noted. Women's MC knowledge is variable. Education could help women support MC and make better-informed sexual decisions.

Background & Aims: Bacterial infections are common and life-threatening in patients with cirrhosis. Little is known about the epidemiology of bacterial infections in different regions. We performed a multicenter prospective intercontinental study to assess the prevalence and outcomes of bacterial and fungal infections in patients with cirrhosis., Methods: We collected data from 1302 hospitalized patients with cirrhosis and bacterial or fungal infections at 46 centers (15 in Asia, 15 in Europe, 11 in South America, and 5 in North America) from October 2015 through September 2016. We obtained demographic, clinical, microbiology, and treatment data at time of diagnosis of infection and during hospitalization. Patients were followed until death, liver transplantation, or discharge., Results: The global prevalence of multidrug-resistant (MDR) bacteria was 34% (95% confidence interval 31%-37%). The prevalence of MDR bacteria differed significantly among geographic areas, with the greatest prevalence in Asia. Independent risk factors for infection with MDR bacteria were infection in Asia (particularly in India), use of antibiotics in the 3 months before hospitalization, prior health care exposure, and site of infection. Infections caused by MDR bacteria were associated with a lower rate of resolution of infection, a higher incidence of shock and new organ failures, and higher in-hospital mortality than those caused by non-MDR bacteria. Administration of adequate empirical antibiotic treatment was independently associated with improved in-hospital and 28-day survival., Conclusions: In a worldwide study of hospitalized patients, we found a high prevalence of infection with MDR bacteria in patients with cirrhosis. Differences in the prevalence of MDR bacterial infections in different global regions indicate the need for different empirical antibiotic strategies in different continents and countries. While we await new antibiotics, effort should be made to decrease the spread of MDR bacteria in patients with cirrhosis., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Focus group methods were used to explore heterosexual women's receptive anal sex attitudes and motivations. Behaviors under investigation included penile-anal intercourse (PAI), manual-anal stimulation, oral-anal contact, and the use of sex toys. A total of 33 self-identified heterosexual women ages 18 to 30 recruited from two metropolitan areas in the Midwestern United States participated in one of six focus groups. The findings suggest that women viewed heterosexual anal sex as an emerging norm. Attitudes and motivations were complex and varied by behavior. Dominant themes included curiosity, pain, pleasure, and stigma. Relational factors, including acquiescence, coercion, and consent, were also salient among participants. Factors that influence anal sexual behaviors may not be entirely distinct from those that influence other sexual behaviors; however, factors that influence anal intercourse may be distinct from those that influence nonintercourse anal sex. Improved understanding will allow scientists to better understand the integration of anal sex behaviors into the broader sexual repertoire.

To increase the overall rate of breastfeeding initiation and duration, factors involved in a mother's decision to breastfeed must be identified. Self-objectification in the context of breastfeeding was a concept selected for exploring factors associated with negative views of breastfeeding. A concept analysis following the eight-step Walker & Avant method provides clarity and context to the concept of self-objectification in the context of breastfeeding. The antecedents of self-objectification in the context of breastfeeding include living in a culture of sexualization and objectification of women and the internalization of the values of objectification. Attributes of self-objectification in the context of breastfeeding are a prioritization of physical appearance attributes of the breast over the health benefits of breastfeeding and a preoccupation with physical appearance. Consequences include negative views toward breastfeeding initiation, duration, and public breastfeeding. A concept analysis on self-objectification in the context of breastfeeding will provide definition and clarity to this phenomenon, lend to theory and measurement, and add literature to the sociocultural factors impacting breastfeeding decisions., (© 2018 Wiley Periodicals, Inc.)

Activation of the sympathetic nervous system is a hallmark of heart failure (HF) and is positively correlated with disease progression. Catecholaminergic (C1) neurons located in the rostral ventrolateral medulla (RVLM) are known to modulate sympathetic outflow and are hyperactivated in volume overload HF. However, there is no conclusive evidence showing a contribution of RVLM-C1 neurons to the development of cardiac dysfunction in the setting of HF. Therefore, the aim of this study was to determine the role of RVLM-C1 neurons in cardiac autonomic control and deterioration of cardiac function in HF rats. A surgical arteriovenous shunt was created in adult male Sprague-Dawley rats to induce HF. RVLM-C1 neurons were selectively ablated using cell-specific immunotoxin (dopamine-β hydroxylase saporin [DβH-SAP]) and measures of cardiac autonomic tone, function, and arrhythmia incidence were evaluated. Cardiac autonomic imbalance, arrhythmogenesis and cardiac dysfunction were present in HF rats and improved after DβH-SAP toxin treatment. Most importantly, the progressive decline in fractional shortening observed in HF rats was reduced by DβH-SAP toxin. Our results unveil a pivotal role played by RVLM-C1 neurons in cardiac autonomic imbalance, arrhythmogenesis and cardiac dysfunction in volume overload-induced HF., (© 2019 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Obstructive sleep apnea (OSA) is the most common form of sleep disordered breathing and is associated with wide array of cardiovascular morbidities. It has been proposed that during OSA, the respiratory control center (RCC) is affected by exaggerated afferent signals coming from peripheral/central chemoreceptors which leads to ventilatory instability and may perpetuate apnea generation. Treatments focused on decreasing hyperactivity of peripheral/central chemoreceptors may be useful to improving ventilatory instability in OSA patients. Previous studies indicate that oxidative stress and inflammation are key players in the increased peripheral/central chemoreflex drive associated with OSA. Recent data suggest that erythropoietin (Epo) could also be involved in modulating chemoreflex activity as functional Epo receptors are constitutively expressed in peripheral and central chemoreceptors cells. Additionally, there is some evidence that Epo has anti-oxidant/anti-inflammatory effects. Accordingly, we propose that Epo treatment during OSA may reduce enhanced peripheral/central chemoreflex drive and normalize the activity of the RCC which in turn may help to abrogate ventilatory instability. In this perspective article we discuss the potential beneficial effects of Epo administration on ventilatory regulation in the setting of OSA.

Plyometric training performed at sea level enhance explosive and endurance performance at sea level. However, its effects on explosive and endurance performance at high altitude had not been studied. Therefore, the aim of this study was to determine the effects of a sea level short-term (i.e., 4-week) plyometric training program on explosive and endurance performance at sea level and at high altitude (i.e., 3,270 m above sea level). Participants were randomly assigned to a control group ( n = 12) and a plyometric training group ( n = 11). Neuromuscular (reactive strength index - RSI) and endurance (2-km time-trial; running economy [RE]; maximal oxygen uptake - VO 2 max) measurements were performed at sea level before, at sea level after intervention (SL +4 week), and at high altitude 24-h post SL +4 week. The ANOVA revealed that at SL +4 week the VO 2 max was not significantly changed in any group, although RE, RSI and 2-km time trial were significantly ( p < 0.05) improved in the plyometric training group. After training, when both groups were exposed to high altitude, participants from the plyometric training group showed a greater RSI ( p < 0.05) and were able to maintain their 2-km time trial (11.3 ± 0.5 min vs. 10.7 ± 0.6 min) compared to their pre-training sea level performance. In contrast, the control group showed no improvement in RSI, with a worse 2-km time trial performance (10.3 ± 0.8 min vs. 9.02 ± 0.64 min; p < 0.05; ES = 0.13). Moreover, after training, both at sea level and at high altitude the plyometric training group demonstrated a greater ( p < 0.05) RSI and 2-km time trial performance compared to the control group. The oxygen saturation was significantly decreased after acute exposure to high altitude in the two groups ( p < 0.05). These results confirm the beneficial effects of sea level short-term plyometric training on explosive and endurance performance at sea level. Moreover, current results indicates that plyometric training may also be of value for endurance athletes performing after an acute exposure to high altitude.

Objective: This article provides an overview and interpretation of the performance of the US President's Emergency Plan for AIDS Relief's (PEPFAR's) male circumcision programme which has supported the majority of voluntary medical male circumcisions (VMMCs) performed for HIV prevention, from its 2007 inception to 2017, and client characteristics in 2017., Design: Longitudinal collection of routine programme data and disaggregations., Setting: 14 countries in sub-Saharan Africa with low baseline male circumcision coverage, high HIV prevalence and PEPFAR-supported VMMC programmes., Participants: Clients of PEPFAR-supported VMMC programmes directed at males aged 10 years and above., Main Outcome Measures: Numbers of circumcisions performed and disaggregations by age band, result of HIV test offer, procedure technique and follow-up visit attendance., Results: PEPFAR supported a total of 15 269 720 circumcisions in 14 countries in Southern and Eastern Africa. In 2017, 45% of clients were under 15 years of age, 8% had unknown HIV status, 1% of those tested were HIV+ and 84% returned for a follow-up visit within 14 days of circumcision., Conclusions: Over 15 million VMMCs have been supported by PEPFAR since 2007. VMMC continues to attract primarily young clients. The non-trivial proportion of clients not testing for HIV is expected, and may be reassuring that testing is not being presented as mandatory for access to circumcision, or in some cases reflect test kit stockouts or recent testing elsewhere. While VMMC is extremely safe, achieving the highest possible follow-up rates for early diagnosis and intervention on complications is crucial, and programmes continue to work to raise follow-up rates. The VMMC programme has achieved rapid scale-up but continues to face challenges, and new approaches may be needed to achieve the new Joint United Nations Programme on HIV/AIDS goal of 27 million additional circumcisions through 2020., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In high HIV burden settings, maximising the coverage of prevention strategies is crucial to achieving epidemic control. However, little is known about the reach and effect of these strategies in some communities., Methods: We did a cross-sectional community survey in the adjacent Greater Edendale and Vulindlela areas in the uMgungundlovu district, KwaZulu-Natal, South Africa. Using a multistage cluster sampling method, we randomly selected enumeration areas, households, and individuals. One household member (aged 15-49 years) selected at random was invited for survey participation. After obtaining consent, questionnaires were administered to obtain sociodemographic, psychosocial, and behavioural information, and exposure to HIV prevention and treatment programmes. Clinical samples were collected for laboratory measurements. Statistical analyses were done accounting for multilevel sampling and weighted to represent the population. A multivariable logistic regression model assessed factors associated with HIV infection., Findings: Between June 11, 2014, and June 22, 2015, we enrolled 9812 individuals. The population-weighted HIV prevalence was 36·3% (95% CI 34·8-37·8, 3969 of 9812); 44·1% (42·3-45·9, 2955 of 6265) in women and 28·0% (25·9-30·1, 1014 of 3547) in men (p<0·0001). HIV prevalence in women aged 15-24 years was 22·3% (20·2-24·4, 567 of 2224) compared with 7·6% (6·0-9·3, 124 of 1472; p<0·0001) in men of the same age. Prevalence peaked at 66·4% (61·7-71·2, 517 of 760) in women aged 35-39 years and 59·6% (53·0-66·3, 183 of 320) in men aged 40-44 years. Consistent condom use in the last 12 months was 26·5% (24·1-28·8, 593 of 2356) in men and 22·7% (20·9-24·4, 994 of 4350) in women (p=0·0033); 35·7% (33·4-37·9, 1695 of 5447) of women's male partners and 31·9% (29·5-34·3, 1102 of 3547) of men were medically circumcised (p<0·0001), and 45·6% (42·9-48·2, 1251 of 2955) of women and 36·7% (32·3-41·2, 341 of 1014) of men reported antiretroviral therapy (ART) use (p=0·0003). HIV viral suppression was achieved in 54·8% (52·0-57·5, 1574 of 2955) of women and 41·9% (37·1-46·7, 401 of 1014) of men (p<0·0001), and 87·2% (84·6-89·8, 1086 of 1251) of women and 83·9% (78·5-89·3, 284 of 341; p=0·3670) of men on ART. Age, incomplete secondary schooling, being single, having more than one lifetime sex partner (women), sexually transmitted infections, and not being medically circumcised were associated with HIV-positive status., Interpretation: The HIV burden in specific age groups, the suboptimal differential coverage, and uptake of HIV prevention strategies justifies a location-based approach to surveillance with finer disaggregation by age and sex. Intensified and customised approaches to seek, identify, and link individuals to HIV services are crucial to achieving epidemic control in this community., Funding: The President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Male circumcision provides men with approximately 60% protection from acquiring HIV infection via heterosexual sex, and has become a key component of HIV prevention efforts in sub-Saharan Africa. Possible mechanisms for this protection include removal of the inflammatory anaerobic sub-preputial environment and the high concentration of Langerhans cells on the inside of the foreskin, both believed to promote local vulnerability to HIV infection. In people who do acquire HIV, viral load is partially determined by infecting partner viral load, potentially mediated by size of infecting inoculum. By removing a portal for virion entry, prior male circumcision could decrease infecting inoculum and thus viral load in men who become HIV-infected, conferring the known associated benefits of slower progression to disease and decreased infectiousness., Methods: We performed an as-treated analysis of plasma samples collected under a randomized controlled trial of male circumcision for HIV prevention, comparing men based on their circumcision status at the time of HIV acquisition, to determine whether circumcision is associated with lower viral load. Eligible men were seroconverters who had at least one plasma sample available drawn at least 6 months after infection, reported no potential exposures other than vaginal sex and, for those who were circumcised, were infected more than 6 weeks after circumcision, to eliminate the open wound as a confounder. Initial viral load testing indicated that quality of pre-2007 samples might have been compromised during storage and they were excluded, as were those with undetectable or unquantifiable results. Log viral loads were compared between groups using univariable and multivariable linear regression, adjusting for sample age and sexually transmitted infection diagnosis with 3.5 months of seroconversion, with a random effect for intra-individual clustering for samples from the same man. A per-protocol analysis was also performed., Results: There were no viral load differences between men who were circumcised and uncircumcised at the time of HIV infection (means 4.00 and 4.03 log 10 copies/mL respectively, p = .88) in any analysis., Conclusion: Circumcision status at the time of HIV infection does not affect viral load in men., Trial Registration: The original RCT which provided the samples was ClinicalTrials.gov trial NCT00059371 .

Male circumcision reduces the risk for female-to-male human immunodeficiency virus (HIV) transmission by approximately 60% (1) and has become a key component of global HIV prevention programs in countries in Eastern and Southern Africa where HIV prevalence is high and circumcision coverage is low. Through September 2017, the President's Emergency Plan for AIDS Relief (PEPFAR) had supported 15.2 million voluntary medical male circumcisions (VMMCs) in 14 priority countries in Eastern and Southern Africa (2). Like any surgical intervention, VMMC carries a risk for complications or adverse events. Adverse events during circumcision of males aged ≥10 years occur in 0.5% to 8% of procedures, though the majority of adverse events are mild (3,4). To monitor safety and service quality, PEPFAR tracks and reports qualifying notifiable adverse events. Data reported from eight country VMMC programs during 2015-2016 revealed that bleeding resulting in hospitalization for ≥3 days was the most commonly reported qualifying adverse event. In several cases, the bleeding adverse event revealed a previously undiagnosed or undisclosed bleeding disorder. Bleeding adverse events in men with potential bleeding disorders are serious and can be fatal. Strategies to improve precircumcision screening and performance of circumcisions on clients at risk in settings where blood products are available are recommended to reduce the occurrence of these adverse events or mitigate their effects (5)., Competing Interests: No conflicts of interest were reported.

Heart failure (HF) is a global public health problem that, independent of its etiology [reduced (HFrEF) or preserved ejection fraction (HFpEF)], is characterized by functional impairments of cardiac function, chemoreflex hypersensitivity, baroreflex sensitivity (BRS) impairment, and abnormal autonomic regulation, all of which contribute to increased morbidity and mortality. Exercise training (ExT) has been identified as a nonpharmacological therapy capable of restoring normal autonomic function and improving survival in patients with HFrEF. Improvements in autonomic function after ExT are correlated with restoration of normal peripheral chemoreflex sensitivity and BRS in HFrEF. To date, few studies have addressed the effects of ExT on chemoreflex control, BRS, and cardiac autonomic control in HFpEF; however, there are some studies that have suggested that ExT has a beneficial effect on cardiac autonomic control. The beneficial effects of ExT on cardiac function and autonomic control in HF may have important implications for functional capacity in addition to their obvious importance to survival. Recent studies have suggested that the peripheral chemoreflex may also play an important role in attenuating exercise intolerance in HFrEF patients. The role of the central/peripheral chemoreflex, if any, in mediating exercise intolerance in HFpEF has not been investigated. The present review focuses on recent studies that address primary pathophysiological mechanisms of HF (HFrEF and HFpEF) and the potential avenues by which ExT exerts its beneficial effects.

The carotid body (CB) is the main arterial chemoreceptor involved in oxygen sensing. Upon hypoxic stimulation, CB chemoreceptor cells release neurotransmitters, which increase the frequency of action potentials in sensory nerve fibers of the carotid sinus nerve. The identity of the molecular entity responsible for oxygen sensing is still a matter of debate; however several ion channels have been shown to be involved in this process. Connexin-based ion channels are expressed in the CB; however a definitive role for these channels in mediating CB oxygen sensitivity has not been established. To address the role of these channels, we studied the effect of blockers of connexin-based ion channels on oxygen sensitivity of the CB. A connexin43 (Cx43) hemichannel blocking agent (CHBa) was applied topically to the CB and the CB-mediated hypoxic ventilatory response (F i O 2 21, 15, 10 and 5%) was measured in adult male Sprague-Dawley rats (~250 g). In normoxic conditions, CHBa had no effect on tidal volume or respiratory rate, however Cx43 hemichannels inhibition by CHBa significantly impaired the CB-mediated chemoreflex response to hypoxia. CHBa reduced both the gain of the hypoxic ventilatory response (HVR) and the maximum HVR by ~25% and ~50%, respectively. Our results suggest that connexin43 hemichannels contribute to the CB chemoreflex response to hypoxia in rats. Our results suggest that CB connexin43 hemichannels may be pharmacological targets in disease conditions characterized by CB hyperactivity.

Countries in Southern and Eastern Africa have the highest prevalence of human immunodeficiency virus (HIV) infection in the world; in 2015, 52% (approximately 19 million) of all persons living with HIV infection resided in these two regions.* Voluntary medical male circumcision (VMMC) reduces the risk for heterosexually acquired HIV infection among males by approximately 60% (1). As such, it is an essential component of the Joint United Nations Programme on HIV/AIDS (UNAIDS) strategy for ending acquired immunodeficiency syndrome (AIDS) by 2030 (2). Substantial progress toward achieving VMMC targets has been made in the 10 years since the World Health Organization (WHO) and UNAIDS recommended scale-up of VMMC for HIV prevention in 14 Southern and Eastern African countries with generalized HIV epidemics and low male circumcision prevalence (3). † This has been enabled in part by nearly $2 billion in cumulative funding through the President's Emergency Plan for AIDS Relief (PEPFAR), administered through multiple U.S. governmental agencies, including CDC, which has supported nearly half of all PEPFAR-supported VMMCs to date. Approximately 14.5 million VMMCs were performed globally during 2008-2016, which represented 70% of the original target of 20.8 million VMMCs in males aged 15-49 years through 2016 (4). Despite falling short of the target, these VMMCs are projected to avert 500,000 HIV infections by the end of 2030 (4). However, UNAIDS has estimated an additional 27 million VMMCs need to be performed by 2021 to meet the Fast Track targets (2). This report updates a previous report covering the period 2010-2012, when VMMC implementing partners supported by CDC performed approximately 1 million VMMCs in nine countries (5). During 2013-2016, these implementing partners performed nearly 5 million VMMCs in 12 countries. Meeting the global target will require redoubling current efforts and introducing novel strategies that increase demand among subgroups of males who have historically been reluctant to undergo VMMC.

Background: Male circumcision reduces men's risk of acquiring HIV and some sexually transmitted infections from heterosexual exposure, and is essential for HIV prevention in sub-Saharan Africa. Studies have also investigated associations between male circumcision and risk of acquisition of HIV and sexually transmitted infections in women. We aimed to review all evidence on associations between male circumcision and women's health outcomes to benefit women's health programmes., Methods: In this systematic review we searched for peer-reviewed and grey literature publications reporting associations between male circumcision and women's health outcomes up to April 11, 2016. All biomedical (not psychological or social) outcomes in all study types were included. Searches were not restricted by year of publication, or to sub-Saharan Africa. Publications without primary data and not in English were excluded. We extracted data and assessed evidence on each outcome as high, medium, or low consistency on the basis of agreement between publications; outcomes found in fewer than three publications were indeterminate consistency., Findings: 60 publications were included in our assessment. High-consistency evidence was found for five outcomes, with male circumcision protecting against cervical cancer, cervical dysplasia, herpes simplex virus type 2, chlamydia, and syphilis. Medium-consistency evidence was found for male circumcision protecting against human papillomavirus and low-risk human papillomavirus. Although the evidence shows a protective association with HIV, it was categorised as low consistency, because one trial showed an increased risk to female partners of HIV-infected men resuming sex early after male circumcision. Seven outcomes including HIV had low-consistency evidence and six were indeterminate., Interpretation: Scale-up of male circumcision in sub-Saharan Africa has public health implications for several outcomes in women. Evidence that female partners are at decreased risk of several diseases is highly consistent. Synergies between male circumcision and women's health programmes should be explored., Funding: US Centers for Disease Control and Prevention and Jhpiego., (Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Chronic heart failure is characterized by autonomic imbalance, cardiac dysfunction, and arrhythmogenesis. It has been shown that exercise training (ExT) improves central nervous system oxidative stress, autonomic control, and cardiac function in heart failure with reduced ejection fraction; however, to date no comprehensive studies have addressed the effects of ExT, if any, on oxidative stress in brain stem cardiovascular areas, cardiac autonomic balance, arrhythmogenesis, and cardiac function in heart failure with preserved ejection fraction (HFpEF). We hypothesize that ExT reduces brain stem oxidative stress, improves cardiac autonomic control and cardiac function, and reduces arrhythmogenesis in HFpEF rats. Rats underwent sham treatment or volume overload to induce HFpEF. ExT (60 min/day, 25 m/min, 10% inclination) was performed for 6 wk starting at the second week after HFpEF induction. Rats were randomly allocated into Sham+sedentary (Sed) ( n = 8), Sham+ExT ( n = 6), HFpEF+Sed ( n = 8), and HFpEF+ExT ( n = 8) groups. Compared with the HFpEF+Sed condition, HFpEF+ExT rats displayed reduced NAD(P)H oxidase activity and oxidative stress in the rostral ventrolateral medulla (RVLM), improved cardiac autonomic balance, and reduced arrhythmogenesis. Furthermore, a threefold improvement in cardiac function was observed in HFpEF+ExT rats. These novel findings suggest that moderate-intensity ExT is an effective means to attenuate the progression of HFpEF through improvement in RVLM redox state, cardiac autonomic control, and cardiac function. NEW & NOTEWORTHY In the present study, we found that exercise reduced oxidative stress in key brain stem areas related to autonomic control, improved sympathovagal control of the heart, reduced cardiac arrhythmias, and delayed deterioration of cardiac function in rats with heart failure with preserved ejection fraction (HFpEF). Our results provide strong evidence for the therapeutic efficacy of exercise training in HFpEF., (Copyright © 2017 the American Physiological Society.)