Unidirectional cross-activation of GRPR by MOR1D uncouples itch and analgesia induced by opioids.

Spinal opioid-induced itch, a prevalent side effect of pain management, has been proposed to result from pain inhibition. We now report that the µ-opioid receptor (MOR) isoform MOR1D is essential for morphine-induced scratching (MIS), whereas the isoform MOR1 is required only for morphine-induced analgesia (MIA). MOR1D heterodimerizes with gastrin-releasing peptide receptor (GRPR) in the spinal cord, relaying itch information. We show that morphine triggers internalization of both GRPR and MOR1D, whereas GRP specifically triggers GRPR internalization and morphine-independent scratching. Providing potential insight into opioid-induced itch prevention, we demonstrate that molecular and pharmacologic inhibition of PLCß3 and IP3R3, downstream effectors of GRPR, specifically block MIS but not MIA. In addition, blocking MOR1D-GRPR association attenuates MIS but not MIA. Together, these data suggest that opioid-induced itch is an active process concomitant with but independent of opioid analgesia, occurring via the unidirectional cross-activation of GRPR signaling by MOR1D heterodimerization.

COVID-19 and Kidney Disease.

COVID-19 can cause acute kidney injury and may cause or exacerbate chronic kidney diseases, including glomerular diseases. SARS-CoV-2 infection of kidney cells has been reported, but it remains unclear if viral infection of kidney cells causes disease. The most important causes of kidney injury in patients with COVID-19 include impaired renal perfusion and immune dysregulation. Chronic kidney disease, especially kidney failure with kidney replacement therapy and kidney transplant, is associated with markedly increased COVID-19 mortality. Persons with severe kidney disease have been excluded from most clinical trials of COVID-19 therapies, so therapeutic approaches must be extrapolated from studies of patients without kidney disease. Some medications used to treat COVID-19 should be avoided or used at reduced dosages in patients with severe kidney disease and in kidney transplant recipients. Additional research is needed to determine the optimal strategies to prevent and treat COVID-19 in patients with kidney disease.

Political leadership has limited impact on fossil fuel taxes and subsidies.

For countries to rapidly decarbonize, they need strong leadership, according to both academic studies and popular accounts. But leadership is difficult to measure, and its importance is unclear. We use original data to investigate the role of presidents, prime ministers, and monarchs in 155 countries from 1990 to 2015 in changing their countries' gasoline taxes and subsidies. Our findings suggest that the impact of leaders on fossil fuel taxes and subsidies is surprisingly limited and often ephemeral. This holds true regardless of the leader's age, gender, education, or political ideology. Rulers who govern during an economic crisis perform no better or worse than other rulers. Even presidents and prime ministers who were recognized by the United Nations for environmental leadership had no more success than other leaders in reducing subsidies or raising fuel taxes. Where leaders appear to play an important role-primarily in countries with large subsidies-their reforms often failed, with subsidies returning to prereform levels within the first 12 mo 62% of the time, and within 5 y 87% of the time. Our findings suggest that leaders of all types find it exceptionally hard to raise the cost of fossil fuels for consumers. To promote deep decarbonization, leaders are likely to have more success with other types of policies, such as reducing the costs and increasing the availability of renewable energy.

Long-term impact of immediate versus deferred antiretroviral therapy on kidney health in people with HIV.

People with human immunodeficiency virus (HIV) are at risk for chronic kidney disease (CKD) due to HIV and antiretroviral therapy (ART) nephrotoxicity. Immediate ART initiation reduces mortality and is now the standard of care, but the long-term impact of prolonged ART exposure on CKD is unknown. To evaluate this, the Strategic Timing of Antiretroviral Treatment (START) trial randomized 4,684 ART-naïve adults with CD4 cell count under 500 cells/mm3 to immediate versus deferred ART. We previously reported a small but statistically significantly greater decline in estimated glomerular filtration rate (eGFR) over a median of 2.1 years in participants randomized to deferred versus immediate ART. Here, we compare the incidence of CKD events and changes in eGFR and urine albumin/creatinine ratio (UACR) in participants randomized to immediate versus deferred ART during extended follow-up. Over a median of 9.3 years, eight participants experienced kidney failure or kidney-related death, three in the immediate and five in the deferred ART arms, respectively. Over a median of five years of more comprehensive follow-up, the annual rate of eGFR decline was 1.19 mL/min/1.73m2/year, with no significant difference between treatment arms (difference deferred - immediate arm 0.055; 95% confidence interval -0.106, 0.217 mL/min/1.73m2). Results were similar in models adjusted for baseline covariates associated with CKD, including UACR and APOL1 genotype. Similarly, there was no significant difference between treatment arms in incidence of confirmed UACR 30 mg/g or more (odds ratio 1.13; 95% confidence interval 0.85, 1.51). Thus, our findings provide the most definitive evidence to date in support of the long-term safety of early ART with respect to kidney health.

Accurate computational design of three-dimensional protein crystals.

Protein crystallization plays a central role in structural biology. Despite this, the process of crystallization remains poorly understood and highly empirical, with crystal contacts, lattice packing arrangements and space group preferences being largely unpredictable. Programming protein crystallization through precisely engineered side-chain-side-chain interactions across protein-protein interfaces is an outstanding challenge. Here we develop a general computational approach for designing three-dimensional protein crystals with prespecified lattice architectures at atomic accuracy that hierarchically constrains the overall number of degrees of freedom of the system. We design three pairs of oligomers that can be individually purified, and upon mixing, spontaneously self-assemble into >100 µm three-dimensional crystals. The structures of these crystals are nearly identical to the computational design models, closely corresponding in both overall architecture and the specific protein-protein interactions. The dimensions of the crystal unit cell can be systematically redesigned while retaining the space group symmetry and overall architecture, and the crystals are extremely porous and highly stable. Our approach enables the computational design of protein crystals with high accuracy, and the designed protein crystals, which have both structural and assembly information encoded in their primary sequences, provide a powerful platform for biological materials engineering.

Association of same-sex criminalisation laws and national HIV policies with HIV testing in African MSM: an ecological single-level and multilevel cross-sectional study of sub-Saharan African countries.

BACKGROUND: HIV incidence among men who have sex with men (MSM) in sub-Saharan Africa (SSA) remains high compared with the general population. Many countries in the region still criminalise consensual homosexual relationships, and some are yet to adopt WHO-recommended interventions for MSM into national HIV policies. This study examines how HIV testing of adult MSM in SSA varies according to the legal climate and presence of targeted HIV policy using data from the cross-sectional 2019 Global LGBTI Internet Survey study. METHODS: Using data from 3191 MSM in 44 SSA countries, we assessed associations of legal climate and HIV policy with ever and recent HIV testing using linear ecological and logistic multilevel analyses. From the single-level analysis, we can compare our findings to previously reported data, then, extending to a two-level multilevel analysis, we account for the hierarchical structure of the population and simultaneously adjust for differences in context and composition in each country. We then test the sensitivity of our analyses to excluding countries from the model. RESULTS: We find evidence that legalised same-sex relationships were associated with increased odds of ever testing (OR=2.00, 95% CI 1.04, 3.82) in multilevel analyses. We also find evidence of an association of targeted HIV policies with increased odds of ever testing (OR=2.49, 95% CI 1.12, 5.52). We did not find evidence of an association of the legal climate (OR=1.01, 95% CI 0.69, 1.46) and targeted HIV policies (OR=1.26, 95% CI 0.78, 2.04) with recent testing. CONCLUSIONS: This study suggests elimination of discriminatory laws and policies might be important for increasing HIV status awareness of MSM, an important first step in epidemic control. Additionally, we highlight heterogeneity between South Africa and other SSA countries, which has implications for studying SSA countries as a homogeneous group.

Sexual Behavior and Perceived Risk for Oropharyngeal Cancer Among Men Who Have Sex With Men: A Psychometric Scale Validation.

BACKGROUND: Men who have sex with men (MSM) are at increased risk for human papillomavirus-associated oropharyngeal cancer (HPV-OPC). The objective of this analysis was to create a psychometrically validated scale to measure perception of risk for HPV-OPC. METHODS: We conducted an exploratory and a confirmatory factor analysis to determine and confirm the latent factor structure. We used a path diagram to evaluate the relationship between the validated scale and perceived risk for HPV-OPC. The model was determined to be a good fit if it met all criteria: root mean square error of approximation ≤0.06, standardized root mean residual ≤0.08, Comparative Fit Index ≥0.90, and Tucker-Lewis Index ≥0.90. We report standardized estimates and 95% confidence intervals. RESULTS: This cross-sectional study recruited 1315 MSM. A majority (73.33%) of MSM had performed fellatio on ≥20 partners, 36.98% had rimmed ≥20 partners, and 5.31% had performed cunnilingus on ≥10 partners in their lifetime.Six sexual history survey items loaded onto 2 latent factors: sexual risk behaviors: class 1 and sexual risk behaviors: class 2. The final model statistics indicated good fit: root mean square error of approximation = 0.064, standardized root mean residual = 0.059, Comparative Fit Index = 0.996, and Tucker-Lewis Index = 0.993. Sexual risk behaviors: class 1 was associated with greater perceived risk for HPV-OPC (0.217; 95% confidence interval, 0.138-0.295). Age, HIV status, HPV vaccination status, and sexual risk behaviors: class 2 were not associated with perceived risk for HPV-OPC. CONCLUSION: Men who have sex with men assessed risk for HPV-OPC based on their lifetime number of cisgender male sexual partners, rimming partners, and fellatio partners but not other sexual behaviors. Men who have sex with men may be responsive to future HPV-OPC educational interventions and opportunities for screening.

Hypothalamic α7 nicotinic acetylcholine receptor (α7nAChR) is downregulated by TNFα-induced Let-7 overexpression driven by fatty acids.

The α7nAChR is crucial to the anti-inflammatory reflex, and to the expression of neuropeptides that control food intake, but its expression can be decreased by environmental factors. We aimed to investigate whether microRNA modulation could be an underlying mechanism in the α7nAchR downregulation in mouse hypothalamus following a short-term exposure to an obesogenic diet. Bioinformatic analysis revealed Let-7 microRNAs as candidates to regulate Chrna7, which was confirmed by the luciferase assay. Mice exposed to an obesogenic diet for 3 days had increased Let-7a and decreased α7nAChR levels, accompanied by hypothalamic fatty acids and TNFα content. Hypothalamic neuronal cells exposed to fatty acids presented higher Let-7a and TNFα levels and lower Chrna7 expression, but when the cells were pre-treated with TLR4 inhibitor, Let-7a, TNFα, and Chrna7 were rescued to normal levels. Thus, the fatty acids overload trigger TNFα-induced Let-7 overexpression in hypothalamic neuronal cells, which negatively regulates α7nAChR, an event that can be related to hyperphagia and obesity predisposition in mice.

A fluid relationship: Calcineurin inhibitors and pericardial effusions.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a common and effective treatment for multiple malignant and non-malignant pediatric conditions. Graft-versus-host disease (GVHD) is a common complication of HSCT that can be prevented with prophylactic use of calcineurin inhibitor (CNI) immunosuppressants. A complication of HSCT and CNI use is pericardial effusion (PEF), which is frequently treated by CNI discontinuation with or without surgical intervention. No studies to date have evaluated the management of PEF without CNI discontinuation as a means of preventing GVHD flares. METHODS: In this single-center retrospective study, we reviewed the management of PEF in pediatric patients post-HSCT who received conservative or surgical intervention with or without CNI discontinuation between May 2012 and June 2022. RESULTS: Of the patients found to have PEF, all were given tacrolimus for GVHD prophylaxis. Management of PEF included surgical intervention for 83% of patients, and CNI was not discontinued for 83%. None of the patients developed GVHD during the management of PEF. CONCLUSIONS: Our results demonstrate that continuation of CNI therapy for GVHD prophylaxis did not negatively impact the disease course of PEF in post-HSCT patients.

The need for and acceptability of a curriculum to train nursing and medical students in the sexual healthcare of clients with female genital mutilation/cutting in Tanzania.

BACKGROUND: Female genital mutilation/cutting (FGM/C) is tied to one of the most conservative cultures in the Mediterranean and Sub-Saharan Africa. More than 200 million girls and women in 30 African, Asian and the middle Eastern countries have undergone FGM/C. However, healthcare professionals are not adequately trained to prevent and manage FGM/C-related complications including sexual health problems. This study aimed to assess the need and acceptability of a curriculum to train nursing and medical students in the sexual healthcare of clients with FGM/C in Tanzania. METHODS: We used a descriptive and cross sectional study design to collect and analyse information from 271 medical and 137 nursing students in Tanzania. A Qualtrics online survey was used to obtain quantitative data on training interest, previous training received, and the curriculum delivery method. Open-ended questions were used to explore their insights on significance to obtain the necessary competencies to treat and prevent FGM/C. Descriptive statistics were used to analyze quantitative data while qualitative data were analyzed using a thematic approach. RESULTS: Almost half of the participants reported they had little to no training in sexual healthcare for women with FGM/C (47%). In all, 82.4% reported the training to be acceptable. Following thematic analysis of open-ended questions, participants expressed a desire to improve their competencies to meet the current and future sexual and psychological health needs of women and girls who have undergone FGM/C. CONCLUSION: It is a necessary and acceptable to develop a curriculum to train healthcare students to diagnose, treat and prevent sexual health complications related to FGM/C. In our study, designing a culturally sensitive curriculum and its delivery method, that includes practical sessions with simulated patients, was considered the most beneficial and favorable.

The feasibility of emergency department observation units in the management of mild to moderate hyponatremia.

OBJECTIVE: To describe the feasibility of managing hyponatremia patients under outpatient observation status in an academic medical center, and compare outcomes based on the use of an emergency department observation unit (EDOU). METHODS: This is a retrospective cohort study of emergency department hyponatremic patients managed in four hospitals within a large urban academic medical center over 27 months. All patients had an admit-to-observation order, ICD-10 codes for hyponatremia, and mild (130-135 mmol/L) to moderate (121-129 mmol/L) hyponatremia. Observation settings were divided into two groups: EDOU and Non-Observation Unit (NOU) inpatient beds. Severe hyponatremia (≤120 mmol/L) was excluded. Primary clinical outcomes were inpatient admit rate, length of stay (LOS), total direct cost, the rate of adverse events and 30-day recidivism. RESULTS: 188 patients were managed as an observation patient, with 64 managed in an EDOU setting (age 74.0 yr, 70.3% female) and 124 managed in a NOU setting (age 71.5 yr, 64.5% female). Patient subgroups were similar in terms of presenting complaints, comorbidities, and medication histories. Initial and final sodium levels were similar between settings: EDOU (125.1 to 132.6 mmol/L) vs NOU (123.5 to 132.0 mmol/L). However, outcomes differed by setting for observation to inpatient admit rate (EDOU 28.1% vs NOU 37.9%, adjusted effect 0.70), overall length of stay (EDOU 19.2 h vs NOU 31.9 h; adjusted effect -10.5 h and total direct cost ($1230 vs $1531; adjusted effect -$167). EDOU sodium correction rates were faster (EDOU 0.44 mmol/L/h vs 0.24 mmol/L/h; adjusted effect 0.15 mmol/L/h) and 30-day recidivism rate was similar (EDOU 13% vs NOU 15%). There were no index visit deaths or intensive care unit admissions. CONCLUSION: Management of selected hyponatremia patients under observation status is feasible, with the EDOU setting demonstrating lower admit rates, shorter length of stay, and lower total direct costs with similar clinical outcomes.

Addressing sexual health concerns in Tanzania: perceived barriers among healthcare professionals and students in the "training for health professionals" study.

Little is known about the factors that may prevent healthcare professionals as key stakeholders from exploring sexual health issues in Tanzania. This study examined healthcare professionals' perspectives on the barriers to addressing sexual health concerns in practice. In June 2019, we conducted an exploratory qualitative study involving 18 focus group discussions among healthcare professionals (n = 60) and students (n = 61) in the health professions (midwifery, nursing, medicine) in Dar es Salaam, Tanzania. Study participants and design were purposively selected and stratified. We used a focus group discussion guide in Kiswahili. Data were transcribed in Kiswahili and translated into English. A thematic analysis approach was used for data analysis. Two themes were developed: (1) differences between health care professional and patient socio-demographic characteristics; (2) health care system and patients' backgrounds, such as communication barriers, lack of confidentiality and privacy within health facilities, type of clinical presentation and complaint, patient behaviours, and their clinical background. Several key barriers prevented sexual health communication between healthcare professionals and patients, affecting the quality of sexual health service delivery. Additional sexual health clinical training is warranted for health professions students and professionals to optimise sexual health care delivery in a culturally conservative country like Tanzania.

Healthcare professional students' skills in sexual health communication and history taking: inter-rater reliability of standardized patients and faculty ratings in dar es Salaam, tanzania- a cross-sectional study.

BACKGROUND: Low- and middle-income countries face a disproportionate impact of sexual health problems compared to high-income countries. To address this situation proper interpersonal communication skills are essential for clinician to gather necessary information during medical history-taking related to sexual health. This study aimed to evaluate the interrater reliability of ratings on sexual health-related interpersonal communication and medical history-taking between SPs and trained HCP faculty for health care professional students. METHODS: We conducted a cross-sectional comparative study to evaluate the interrater reliability of ratings for sexual health-related interpersonal communication and medical history-taking. The data were collected from medical and nursing students at Muhimbili University of Health and Allied Sciences, who interviewed 12 Standardized Patients (SPs) presenting with sexual health issues. The video-recorded interviews rated by SPs, were compared to the one rated by 5 trained Health Care Professional (HCP) faculty members. Inter-rater reliability was evaluated using percent agreement (PA) and kappa statistics (κ). RESULTS: A total of 412 students (mean age 24) were enrolled in the study to conduct interviews with two SPs presenting with sexual health concerns. For interpersonal communication (IC), the overall median agreement between raters was slight (κ2 0.0095; PA 48.9%) while the overall median agreement for medical sexual history-taking was deemed fair (κ2 0.139; PA 75.02%). CONCLUSION: The use of SPs for training and evaluating medical and nursing students in Tanzania is feasible only if they undergo proper training and have sufficient time for practice sessions, along with providing feedback to the students.

The need for and acceptability of a cancer training course for medical and nursing students in Tanzania: a convergent mixed methods study.

BACKGROUND: The cancer burden in Africa is on the rise. A Cancer Training Course on screening, prevention, care, and community education is crucial for addressing a wide range of cancer health issues. When appropriately educated healthcare providers on cancer provide care, patient care improves, and healthcare costs decrease. However, in Tanzania, doctors and nurses receive little or no training in primary cancer care in their bachelor's program. AIM: This study assessed the need and acceptability of a cancer training course for nursing and medical doctor students at the Muhimbili University of Health and Allied Sciences (MUHAS) in Dar es Salaam, Tanzania. METHODS: This study was a cross-sectional parallel mixed method study during the 3-month follow-up within the larger study on sexual health training for health professionals. The study was a randomized controlled (RCT), single-blind, parallel trial of sexual health training versus a waitlist control among health students at MUHAS in Tanzania. Descriptive analysis was performed to analyze the participants' demographic information, need, and acceptability of the cancer training courseto determine the frequencies and percentages of their distribution between disciplines. In addition, inductive thematic analysis was performed for the qualitative data. The RCT study was registered at Clinical Trial.gov (NCT03923582; 01/05/2021). RESULTS: Data were collected from 408 students (272 medical doctors and 136 nursing students). The median age of the participants was 23 years. Most (86.0%) medical and 78.1% of nursing students reported receiving little to no cancer training. On the other hand, most (92.3%) medical and nursing (92.0%) students were interested in receiving cancer training. Furthermore, 94.1% of medical and 92.0% of nursing students needed a cancer training course in their undergraduate program. In addition, participants said a cancer training course would be important because it would help them improve the quality of cancer care and enhance the quality of life for patients by ensuring early diagnosis and treatment. CONCLUSION: A cancer training course is both highly needed and acceptable to medical and nursing students. Implementation of this cancer training course will improve students' knowledge and skills and eventually improve the quality of cancer care and patients' quality of life by ensuring early diagnosis and management.

Asymmetric Polymerization-Induced Crystallization-Driven Self-Assembly of Helical, Rod-Coil Poly(aryl isocyanide) Block Copolymers.

Polymerization-induced crystallization-driven self-assembly (PI-CDSA) is combined, for the first time, with helical, rod-coil block copolymer (BCP) self-assembly to enable scalable and controllable in situ synthesis of chiral nanostructures of variable shape, size, and dimensionality. Herein, we report newly developed asymmetric PI-CDSA (A-PI-CDSA) methodologies in the synthesis and in situ self-assembly of chiral, rod-coil BCPs composed of poly(aryl isocyanide) (PAIC) rigid-rod and poly(ethylene glycol) (PEG) random-coil components. Using PEG-based nickel(II) macroinitiators, the construction of PAIC-BCP nanostructures with variable chiral morphologies is accomplished at solids contents ranging 5.0-10 wt %. At low core-to-corona ratios for PAIC-BCPs, we demonstrate the scalable formation of chiral one-dimensional (1D) nanofibers via "living" A-PI-CDSA whose contour lengths can be tuned through alterations to unimer-to-1D seed particle ratio. At high core-to-corona ratios, A-PI-CDSA was implemented for the rapid fabrication of molecularly thin, uniform hexagonal nanosheets via spontaneous nucleation and growth aided by vortex agitation. Investigations into 2D seeded, living A-PI-CDSA revealed a brand-new paradigm in the context of CDSA where hierarchically chiral, M helical spirangle morphologies (i.e., hexagonal helicoids) are size-tuned in three dimensions (i.e., heights and areas) via alterations to unimer-to-seed ratio. These unique nanostructures are formed in situ at scalable solids contents up to 10 wt % via rapid crystallization about screw dislocation defect sites in an enantioselective fashion. The liquid crystalline nature of PAIC blocks dictates the hierarchical assembly of these BCPs, with chirality translated across length scales and in multiple dimensions affording large amplifications in chiroptical activity with g-factors reaching -0.030 for spirangle nanostructures.

Association of HIV and viral suppression status with hospital acute kidney injury in the era of antiretroviral therapy.

In the modern era, it is unknown if people that are virally suppressed with HIV (PWH) are at increased risk for acute kidney injury (AKI) compared to people without HIV and no studies have compared the risk of AKI by viral suppression status. Here, we determined the associations of HIV status and AKI among PWH with and without viral suppression compared to people without HIV. An observational cohort study of PWH and people without HIV hospitalized in a large New York City health system between 2010-2019 was conducted. Multivariable Cox proportional hazards models were used to determine associations between HIV status and risk of AKI, severe AKI and development of chronic kidney disease (CKD). Among 173,884 hospitalized patients, 4,718 had HIV; 2,532 (53.7%) were virally suppressed and 2,186 (46.3%) were not suppressed. Compared to people without HIV, PWH with and without viral suppression were at increased risk of AKI (adjusted hazard ratio 1.27, 95% confidence interval 1.15, 1.40 and 1.73, 1.58, 1.90, respectively) and AKI requiring kidney replacement therapy (1.89, 1.27, 2.84 and 1.87, 1.23, 2.84, respectively). Incremental, graded associations were observed between HIV status and Stage 2 or 3 AKI, and among AKI survivors, and incident CKD. The elevated risk of AKI across ages of PWH was similar in magnitude to older people without HIV. Thus, regardless of virologic control, HIV is an independent risk factor for AKI among hospitalized patients. Future studies should determine the mechanisms by which HIV increases susceptibility to AKI and identify strategies to prevent AKI in PWH.

Unrecognized sexual dysfunction in gay and bisexual men after prostate cancer treatment: the antecedents and impact of anodyspareunia.

BACKGROUND: Anodyspareunia may be an adverse outcome of prostate cancer (PCa) treatment for gay, bisexual, and other men who have sex with men (GBM). AIM: The aims of this study were to (1) describe the clinical symptoms of painful receptive anal intercourse (RAI) in GBM following PCa treatment, (2) estimate the prevalence of anodyspareunia, and (3) identify clinical and psychosocial correlates. METHODS: This was a secondary analysis of baseline and 24-month follow-up data from the Restore-2 randomized clinical trial of 401 GBM treated for PCa. The analytic sample included only those participants who attempted RAI during or since their PCa treatment (N = 195). OUTCOMES: Anodyspareunia was operationalized as moderate to severe pain during RAI for ≥6 months that resulted in mild to severe distress. Additional quality-of-life outcomes included the Expanded Prostate Cancer Index Composite (bowel function and bother subscales), the Brief Symptom Inventory-18, and the Functional Assessment of Cancer Therapy-Prostate. RESULTS: Overall 82 (42.1%) participants reported pain during RAI since completing PCa treatment. Of these, 45.1% experienced painful RAI sometimes or frequently, and 63.0% indicated that the pain was persistent. The pain at its worst was moderate to very severe for 79.0%. The experience of pain was at least mildly distressing for 63.5%. Painful RAI worsened for a third (33.4%) of participants after completing PCa treatment. Of the 82 GBM, 15.4% were classified as meeting criteria for anodyspareunia. Antecedents of anodyspareunia included a lifelong history of painful RAI and bowel dysfunction following PCa treatment. Those reporting symptoms of anodyspareunia were more likely to avoid RAI due to pain (adjusted odds ratio, 4.37), which was negatively associated with sexual satisfaction (mean difference, -2.77) and self-esteem (mean difference, -3.33). The model explained 37.2% of the variance in overall quality of life. CLINICAL IMPLICATIONS: Culturally responsive PCa care should include the assessment of anodyspareunia among GBM and explore treatment options. STRENGTHS AND LIMITATIONS: This is the largest study to date focused on anodyspareunia among GBM treated for PCa. Anodyspareunia was assessed with multiple items characterizing the intensity, duration, and distress related to painful RAI. The external validity of the findings is limited by the nonprobability sample. Furthermore, the cause-and-effect relationships between the reported associations cannot be established by the research design. CONCLUSIONS: Anodyspareunia should be considered a sexual dysfunction in GBM and investigated as an adverse outcome of PCa treatment.

The Impact of Virtual Care in an Emergency Department Observation Unit.

STUDY OBJECTIVE(S): We report the impact of telemedicine virtual rounding in emergency department observation units (EDOU) on the effectiveness, safety, and cost relative to traditional observation care. METHODS: In this retrospective diff-in-diff study, we compared observation visit outcomes from 2 EDOUs before (pre) and after (post) full adoption of telemedicine rounding tele-observation (tele-obs) with usual care in control EDOU and care in a hospital bed in an integrated health system without tele-obs. Tele-obs physicians did not work at the control hospital. Outcomes were the length of stay, total direct costs, admission status, and adverse events (ICU and death). Difference-in-differences modeling evaluated outcomes with covariates including age, sex, payer type, and clinical classification software diagnostic category. Data from a system data warehouse and a cost accounting database were used. RESULTS: Of the 20,861 EDOU visits, 15,630 (74.9%) were seen in the preperiod and 6,657 (31.9%) in control EDOU. Of 23,055 non-EDOU inpatient visits assigned to observation status (nonobservation unit), 76% were seen in the preperiod. Adjusted length of stay was not significantly different for tele-obs and control EDOUs (26.4 hours versus 23.5 hours), which remained lower than in hospital settings (37.9 hours). The pre-post diff-in-diff was not significant (P=.78). Inpatient admission status was similar for tele-obs and control EDOUs (20.9% versus 22.4.%) and lower than in hospital settings (30.3%). Prepost odds ratios for inpatient admission and adverse outcomes did not change significantly for all study groups. Adjusted costs increased over time for all settings; however, the prepost median cost change was not significantly different between tele-obs EDOUs and control EDOUs ($162.5 versus $235) and was lower than the change for control hospital settings ($783). Median tele-obs EDOU cost over both periods ($1,541) remained significantly lower than hospital costs ($2,413). CONCLUSION: Using tele-obs to manage observation patients in an ED observation unit was not associated with significant differences in length of stay, admission status, measured adverse events, or total direct cost.

Impact of Migration and Acculturation on Turkish Men Who Have Sex with Men in Germany: Results from the 2010 European MSM Internet Survey.

To examine the impact of migration and acculturation of Turkish men who have sex with men (MSM) to Germany, using data from the European MSM Internet Survey (EMIS-2010), on measures of acculturation including circumcision status, internalized homonegativity (IH), HIV/STI knowledge, sexual orientation, outness, HIV-testing, and sexual behaviors. We compared four groups of MSM: MSM born and residing in Germany who had completed the questionnaire in German (n = 38,915), MSM born and residing in Germany, with a father or mother born in Turkey (n = 97), MSM residing in Germany who were born in Turkey or whose parents were born in Turkey (n = 262), and MSM who were born and residing in Turkey and who completed the questionnaire in Turkish (n = 1,717). Data showed that there were significant dose-response curves between level of migration and several outcome variables. As exposure to Germany increased, MSM had lower IH, higher HIV/STI knowledge, increased outness, and were less likely to be circumcised. There were similar significant findings with regard to sexual HIV risk behavior (condomless anal intercourse with partners of unknown (or sero-discordant) HIV status). Data were consistent with acculturation over generations in immigrant groups in MSM migrating from Turkey to Germany. Integration includes both cultural aspects (circumcision) and integration into a more homopositive gay environment (IH, outness, increased HIV/STI knowledge), and sexual HIV risk behavior. Migration and associated acculturation may constitute a risk change for HIV/STI and mental health issues associated with IH and outness.

Prevention of fetal brain injury in category II tracings.

INTRODUCTION: With category II fetal heart rate tracings, the preferred timing of interventions to prevent fetal hypoxic brain damage while limiting operative interventions remains unclear. We aimed to estimate fetal extracellular base deficit (BDecf ) during labor with category II tracings to quantify the timing of potential interventions to prevent severe fetal metabolic acidemia. MATERIAL AND METHODS: A longitudinal study was conducted using the database of the Recurrence Prevention Committee, Japan Obstetric Compensation System for Cerebral Palsy, including infants with severe cerebral palsy born at ≥34 weeks' gestation between 2009 and 2014. Cases included those presumed to have an intrapartum onset of hypoxic-ischemic insult based on the fetal heart rate pattern evolution from reassuring to an abnormal pattern during delivery, in association with category II tracings marked by recurrent decelerations and an umbilical arterial BDecf ≥ 12 mEq/L. BDecf changes during labor were estimated based on stages of labor and the frequency/severity of fetal heart rate decelerations using the algorithm of Ross and Gala. The times from the onset of recurrent decelerations to BDecf 8 and 12 mEq/L (Decels-to-BD8, Decels-to-BD12) and to delivery were determined. Cases were divided into two groups (rapid and slow progression) based upon the rate of progression of acidosis from onset of decelerations to BDecf 12 mEq/L, determined by a finite-mixture model. RESULTS: The median Decels-to-BD8 (28 vs. 144 min, p < 0.01) and Decels-to-BD12 (46 vs. 177 min, p < 0.01) times were significantly shorter in the rapid vs slow progression. In rapid progression cases, physicians' decisions to deliver the fetus occurred at ~BDecf 8 mEq/L, whereas the "decisions" did not occur until BDecf reached 12 mEq/L in slow progression cases. CONCLUSIONS: Fetal BDecf reached 12 mEq/L within 1 h of recurrent fetal heart rate decelerations in the rapid progression group and within 3 h in the slow progression group. These findings suggest that cases with category II tracings marked by recurrent decelerations (i.e., slow progression) may benefit from operative intervention if persisting for longer than 2 h. In contrast, cases with sudden bradycardia (i.e., rapid progression) represent a challenge to prevent severe acidosis and hypoxic brain injury due to the limited time opportunity for emergent delivery.