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Skeletal muscle wasting results from numerous pathological conditions affecting both the musculoskeletal and nervous systems. A unifying feature of these pathologies is the upregulation of members of the E3 ubiquitin ligase family, resulting in increased proteolytic degradation of target proteins. Despite the critical role of E3 ubiquitin ligases in regulating muscle mass, the specific proteins they target for degradation and the mechanisms by which they regulate skeletal muscle homeostasis remain ill-defined. Here, using zebrafish loss-of-function models combined with in vivo cell biology and proteomic approaches, we reveal a role of atrogin-1 in regulating the levels of the endoplasmic reticulum chaperone BiP. Loss of atrogin-1 resulted in an accumulation of BiP, leading to impaired mitochondrial dynamics and a subsequent loss in muscle fiber integrity. We further implicated a disruption in atrogin-1-mediated BiP regulation in the pathogenesis of Duchenne muscular dystrophy. We revealed that BiP was not only upregulated in Duchenne muscular dystrophy, but its inhibition using pharmacological strategies, or by upregulating atrogin-1, significantly ameliorated pathology in a zebrafish model of Duchenne muscular dystrophy. Collectively, our data implicate atrogin-1 and BiP in the pathogenesis of Duchenne muscular dystrophy and highlight atrogin-1's essential role in maintaining muscle homeostasis.

Background: The US President's Emergency Plan for AIDS Relief aims to address the higher risk of cervical cancer among women living with HIV by offering high-quality screening services in the highest burden regions of the world., Methods: We analyzed the US President's Emergency Plan for AIDS Relief Monitoring, Evaluation, and Reporting data from Centers for Disease Control and Prevention-supported sites in 13 countries in sub-Saharan Africa for women living with HIV aged older than 15 years who accessed cervical cancer screening services (mostly visual inspection, with ablative or excisional treatment offered for precancerous lesions), April 2018-March 2022. We calculated the positivity by age, country, and clinical visit type (first lifetime screen or routine rescreening). We fitted negative binomial random coefficient models of log-linear trends in time to estimate the probabilities of testing positive and any temporal trends in positivity., Results: Among the 2.8 million completed cancer screens, 5.4% identified precancerous lesions, and 0.8% were positive for suspected invasive cervical cancers (6.1% overall). The positivity rates declined over the study period among those women screening for cervical cancer for the first time and among those women presenting to antiretroviral therapy clinics for routine rescreening., Conclusions: These positivity rates are lower than expectations set by the published literature. Further research is needed to determine whether these lower rates are attributable to the high level of consistent antiretroviral therapy use among these populations, and systematic program monitoring and quality assurance activities are essential to ensure women living with HIV have access to the highest possible quality prevention services., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Sharks occupy diverse ecological niches and play critical roles in marine ecosystems, often acting as apex predators. They are considered a slow-evolving lineage and have been suggested to exhibit exceptionally low cancer rates. These two features could be explained by a low nuclear mutation rate. Here, we provide a direct estimate of the nuclear mutation rate in the epaulette shark (Hemiscyllium ocellatum). We generate a high-quality reference genome, and resequence the whole genomes of parents and nine offspring to detect de novo mutations. Using stringent criteria, we estimate a mutation rate of 7×10 -10 per base pair, per generation. This represents one of the lowest directly estimated mutation rates for any vertebrate clade, indicating that this basal vertebrate group is indeed a slowly evolving lineage whose ability to restore genetic diversity following a sustained population bottleneck may be hampered by a low mutation rate., (© 2023. Springer Nature Limited.)

Introduction: Pregnant and lactating people (PLP) experience heightened risk of acquiring HIV, which adversely impacts their health and increases the risk for vertical HIV transmission. Preexposure prophylaxis (PrEP), as part of a combination prevention package, including condoms, sexually transmitted infection prevention, and regular HIV testing, is a safe, efficacious method to prevent HIV infections among PLP and their infants. This article examines the evolution of strategies and guidance on PrEP services for PLP from 18 countries supported by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR)., Methods: The 18 countries implement PEPFAR-supported prevention of vertical transmission of HIV and PrEP programs. We reviewed a total of 18 national HIV strategic plans, 28 national HIV guidelines, and 54 PEPFAR country operational plans (COPs) published in 2013-2020. We compared documents from 2013 to 2017 to those from 2017 to 2020 to assess for differences after the release of the 2017 World Health Organization recommendations supporting the use of PrEP by PLP at substantial risk of acquiring HIV., Results: National HIV guidelines and PEPFAR COPs that endorsed PrEP for PLP through any categorization increased from 41% to 73% and 11% to 83%, respectively, in the pre-2017 and post-2017 periods. While many documents approved PrEP but not specifically for PLP (10 national strategic plans, 6 national guidelines, and 28 COPs), none of the documents explicitly prohibited PrEP for PLP., Conclusion: National HIV guidelines and PEPFAR COPs expanded inclusion of PLP in PrEP eligibility when comparing the pre-2017 and the post-2017 groups. However, policy gaps remain as only 36% (4/11) of the post-2017 national HIV guidelines included PLP as a specific priority population for PrEP. Inclusive national HIV strategic plans and guidelines on PrEP for PLP, together with effective program implementation, remain critical for reducing new infections in PLP and eliminating vertical transmission of HIV., (© Abadan et al.)

The recently uncovered role of Fukutin-related protein (FKRP) in fibronectin glycosylation has challenged our understanding of the basis of disease pathogenesis in the muscular dystrophies. FKRP is a Golgi-resident glycosyltransferase implicated in a broad spectrum of muscular dystrophy (MD) pathologies that are not fully attributable to the well-described α-Dystroglycan hypoglycosylation. By revealing a new role for FKRP in the glycosylation of fibronectin, a modification critical for the development of the muscle basement membrane (MBM) and its associated muscle linkages, new possibilities for understanding clinical phenotype arise. This modification involves an interaction between FKRP and myosin-10, a protein involved in the Golgi organization and function. These observations suggest a FKRP nexus exists that controls two critical aspects to muscle fibre integrity, both fibre stability at the MBM and its elastic properties. This review explores the new potential disease axis in the context of our current knowledge of muscular dystrophies., (© 2022 Wiley Periodicals LLC.)

Homeostatic renal filtration relies on the integrity of podocytes, which function in glomerular filtration. These highly specialized cells are damaged in 90% of chronic kidney disease, representing the leading cause of end-stage renal failure. Although modest podocyte renewal has been documented in adult mice, the mechanisms regulating this process remain largely unknown and controversial. Using a mouse model of Adriamycin-induced nephropathy, we find that the recovery of filtration function requires up-regulation of the endogenous telomerase component TERT. Previous work has shown that transient overexpression of catalytically inactive TERT (i-TERT ci mouse model) has an unexpected role in triggering dramatic podocyte proliferation and renewal. We therefore used this model to conduct specific and stochastic lineage-tracing strategies in combination with high throughput sequencing methods. These experiments provide evidence that TERT drives the activation and clonal expansion of podocyte progenitor cells. Our findings demonstrate that the adult kidney bears intrinsic regenerative capabilities involving the protein component of telomerase, paving the way for innovative research toward the development of chronic kidney disease therapeutics., (© 2022. The Author(s).)

Background: Nigeria has low antiretroviral therapy (ART) coverage among HIV-positive pregnant women. In a previous cluster-randomized trial in Nigeria, Baby Shower events resulted in higher HIV testing coverage and linkage of pregnant women to ART; here, we assess outcomes of Baby Shower events in a non-research setting., Methods: Baby Shower events, including a prayer ceremony, group education, music, gifting of a "mama pack" with safe delivery supplies, and HIV testing with ART linkage support for HIV-positive pregnant women, were conducted in eighty sites in Benue State, Nigeria. Client questionnaires (including demographics, ANC attendance, and HIV testing history), HIV test results, and reported linkage to ART were analyzed. Descriptive data on HIV testing and ART linkage data for facility-based care at ANC clinics in Benue State were also analyzed for comparison., Results: Between July 2016 and October 2017, 10,056 pregnant women and 6,187 male partners participated in Baby Shower events; 61.5% of women attended with a male partner. Nearly half of female participants (n = 4515, 44.9%) were not enrolled in ANC for the current pregnancy, and 22.3% (n = 2,241) of female and 24.8% (n = 1,532) of male participants reported they had never been tested for HIV. Over 99% (n = 16,240) of participants had their HIV status ascertained, with 7.2% of females (n = 724) and 4.0% of males (n = 249) testing HIV-positive, and 2.9% of females (n = 274) and 2.3% of males (n = 138) receiving new HIV-positive diagnoses. The majority of HIV-positive pregnant women (93.0%, 673/724) were linked to ART. By comparison, at health facilities in Benue State during a similar time period, 99.7% of pregnant women had HIV status ascertained, 8.4% had a HIV-positive status, 2.1% were newly diagnosed HIV-positive, and 100% were linked to ART., Conclusion: Community-based programs such as the faith-based Baby Shower intervention complement facility-based approaches and can reach individuals who would not otherwise access facility-based care. Future Baby Showers implementation should incorporate enhanced support for ART linkage and retention to maximize the impact of this intervention on vertical HIV transmission., Competing Interests: No authors have competing interests.

Malawi faces challenges with retaining women in prevention of mother-to-child HIV transmission (PMTCT) services. We evaluated Cooperative for Assistance and Relief Everywhere, Inc. (CARE's) community score card (CSC) in 11 purposively selected health facilities, assessing the effect on: (1) retention in PMTCT services, (2) uptake of early infant diagnosis (EID), (3) collective efficacy among clients, and (4) self-efficacy among health care workers (HCWs) in delivering quality services. The CSC is a participatory community approach. In this study, HCWs and PMTCT clients identified issues impacting PMTCT service quality and uptake and implemented actions for improvement. A mixed-methods, pre- and post-intervention design was used to evaluate the intervention. We abstracted routine clinical data on retention in PMTCT services for HIV-positive clients attending their first antenatal care visit and EID uptake for their infants for 8-month periods before and after implementation. To assess collective efficacy and self-efficacy, we administered questionnaires and conducted focus group discussions (FGDs) pre- and post-intervention with PMTCT clients recruited from CSC participants, and HCWs providing HIV care from facilities. Retention of HIV-positive women in PMTCT services at three and six months and EID uptake was not significantly different pre- and post-implementation. For the clients, the collective efficacy scale average improved significantly post-intervention, (p = 0.003). HCW self-efficacy scale average did not improve. Results from the FGDs highlighted a strengthened relationship between HCWs and PMTCT clients, with clients reporting increased satisfaction with services. However, the data indicated continued challenges with stigma and fear of disclosure. While CSC may foster mutual trust and respect between HCWs and PMTCT clients, we did not find it improved PMTCT retention or EID uptake within the short duration of the study period. More research is needed on ways to improve service quality and decrease stigmatized behaviors, such as HIV testing and treatment services, as well as the longer-term impacts of interventions like the CSC on clinical outcomes., Competing Interests: The authors declare that they have no competing interests.

Skeletal muscle has a remarkable ability to regenerate following injury, which is driven by obligate tissue resident muscle stem cells. Following injury, the muscle stem cell is activated and undergoes cell proliferation to generate a pool of myoblasts, which subsequently differentiate to form new muscle fibers. In many muscle wasting conditions, including muscular dystrophy and ageing, this process is impaired resulting in the inability of muscle to regenerate. The process of muscle regeneration in zebrafish is highly conserved with mammalian systems providing an excellent system to study muscle stem cell function and regeneration, in muscle wasting conditions such as muscular dystrophy. Here, we present a method to examine muscle regeneration in zebrafish models of muscle disease. The first step involves the use of a genotyping platform that allows the determination of the genotype of the larvae prior to eliciting an injury. Having determined the genotype, the muscle is injured using a needle stab, following which polarizing light microscopy is used to determine the extent of muscle regeneration. We therefore provide a high throughput pipeline which allows the examination of muscle regeneration in zebrafish models of muscle disease.

CDC, the Food and Drug Administration (FDA), state and local health departments, and public health and clinical stakeholders are investigating a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) (1). CDC has published recommendations for health care providers regarding EVALI (2-4). Recently, researchers from Utah and New York published proposed diagnosis and treatment algorithms for EVALI (5,6). EVALI remains a diagnosis of exclusion because, at present, no specific test or marker exists for its diagnosis, and evaluation should be guided by clinical judgment. Because patients with EVALI can experience symptoms similar to those associated with influenza or other respiratory infections (e.g., fever, cough, headache, myalgias, or fatigue), it might be difficult to differentiate EVALI from influenza or community-acquired pneumonia on initial assessment; EVALI might also co-occur with respiratory infections. This report summarizes recommendations for health care providers managing patients with suspected or known EVALI when respiratory infections such as influenza are more prevalent in the community than they have been in recent months (7). Recommendations include 1) asking patients with respiratory, gastrointestinal, or constitutional symptoms about the use of e-cigarette, or vaping, products; 2) evaluating those suspected to have EVALI with pulse oximetry and obtaining chest imaging, as clinically indicated; 3) considering outpatient management for clinically stable EVALI patients who meet certain criteria; 4) testing patients for influenza, particularly during influenza season, and administering antimicrobials, including antivirals, in accordance with established guidelines; 5) using caution when considering prescribing corticosteroids for outpatients, because this treatment modality has not been well studied among outpatients, and corticosteroids could worsen respiratory infections; 6) recommending evidence-based treatment strategies, including behavioral counseling, to help patients discontinue using e-cigarette, or vaping, products; and 7) emphasizing the importance of annual influenza vaccination for all persons aged ≥6 months, including patients who use e-cigarette, or vaping products., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Despite dramatic global progress with implementing prevention of mother-to-child HIV transmission (PMTCT) programs, there were 160,000 new pediatric HIV infections in 2016. More than 50% of infant HIV infections now occur in the postpartum period, reflecting the relatively high coverage of interventions in the antenatal period and the need for greater attention to the breastfeeding mother and her HIV-exposed infant (HEI). Early diagnosis and treatment are critical to prevent morbidity and mortality in HIV-infected children; however, early infant HIV testing rates remain low in most high HIV-burden countries. Furthermore, systematic retention and follow-up of HEI in the postpartum period and ascertainment of final HIV status remain major program gaps. Despite multiple calls to action to improve infant HIV testing rates, progress has been marginal due to a lack of focus on the critical health care needs of HEI coupled with health system barriers that result in fragmented services for HIV-infected mothers and their families. In this paper, we describe the available evidence on the health outcomes of HEI, define a comprehensive care package for HEI that extends beyond early HIV testing, and describe successful examples of integrated services for HEI.

Background and Purpose: The presence of apolipoprotein E4 ( APOE * E4 ) is the strongest currently known genetic risk factor for Alzheimer disease and is associated with brain gray matter loss, notably in areas involved in Alzheimer disease pathology. Our objective was to assess the effect of APOE * E4 on brain structures in healthy elderly controls who subsequently developed subtle cognitive decline., Materials and Methods: This prospective study included 382 community-dwelling elderly controls. At baseline, participants underwent MR imaging at 3T, extensive neuropsychological testing, and genotyping. After neuropsychological follow-up at 18 months, participants were classified into cognitively stable controls and cognitively deteriorating controls. Data analysis included whole-brain voxel-based morphometry and ROI analysis of GM., Results: APOE * E4 -related GM loss at baseline was found only in the cognitively deteriorating controls in the posterior cingulate cortex. There was no APOE * E4- related effect in the hippocampus, mesial temporal lobe, or brain areas not involved in Alzheimer disease pathology. Controls in the cognitively deteriorating group had slightly lower GM concentration in the hippocampus at baseline. Higher GM densities in the hippocampus, middle temporal lobe, and amygdala were associated with a decreased risk for cognitively deteriorating group status at follow-up., Conclusions: APOE * E4 -related GM loss in the posterior cingulate cortex (an area involved in Alzheimer disease pathology) was found only in those elderly controls who subsequently developed subtle cognitive decline but not in cognitively stable controls. This finding might explain the partially conflicting results of previous studies that typically did not include detailed neuropsychological assessment and follow-up. Most important, APOE * E4 status had no impact on GM density in areas affected early by neurofibrillary tangle formation such as the hippocampus and mesial temporal lobe., (© 2017 by American Journal of Neuroradiology.)

Background and Purpose: The presence of cerebral microbleeds has been associated with dementia and cognitive decline, although studies report conflicting results. Our aim was to determine the potential role of the presence and location of cerebral microbleeds in early stages of cognitive decline., Materials and Methods: Baseline 3T MR imaging examinations including SWI sequences of 328 cognitively intact community-dwelling controls and 72 subjects with mild cognitive impairment were analyzed with respect to the presence and distribution of cerebral microbleeds. A neuropsychological follow-up of controls was performed at 18 months post inclusion and identified cases with subtle cognitive deficits were referred to as controls with a deteriorating condition. Group differences in radiologic parameters were studied by using nonparametric tests, 1-way analysis of variance, and Spearman correlation coefficients., Results: Cerebral microbleed prevalence was similar in subjects with mild cognitive impairment and controls with stable and cognitively deteriorating conditions (25%-31.9%). In all diagnostic groups, lobar cerebral microbleeds were more common. They occurred in 20.1% of all cases compared with 6.5% of cases with deep cerebral microbleeds. None of the investigated variables (age, sex, microbleed number, location and depth, baseline Mini-Mental State Examination score, and the Fazekas score) were significantly associated with cognitive deterioration with the exception of education of >12 years showing a slight but significant protective effect (OR, 0.44; 95% CI, 0.22-0.92; P = .028). The Mini-Mental State Examination and the Buschke total score were correlated with neither the total number nor lobar-versus-deep location of cerebral microbleeds., Conclusions: Cerebral microbleed presence, location, and severity are not related to the early stages of cognitive decline in advanced age., (© 2017 by American Journal of Neuroradiology.)

Background and Purpose: Arterial spin-labeling is a noninvasive method to map cerebral blood flow, which might be useful for early diagnosis of neurodegenerative diseases. We directly compared 2 arterial spin-labeling techniques in healthy elderly controls and individuals with mild cognitive impairment., Materials and Methods: This prospective study was approved by the local ethics committee and included 198 consecutive healthy controls (mean age, 73.65 ± 4.02 years) and 43 subjects with mild cognitive impairment (mean age, 73.38 ± 5.85 years). Two pulsed arterial spin-labeling sequences were performed at 3T: proximal inversion with a control for off-resonance effects (PICORE) and flow-sensitive alternating inversion recovery technique (FAIR). Relative cerebral blood flow maps were calculated by using commercial software and standard parameters. Data analysis included spatial normalization of gray matter-corrected relative CBF maps, whole-brain average, and voxelwise comparison of both arterial spin-labeling sequences., Results: Overall, FAIR yielded higher relative CBF values compared with PICORE (controls, 32.7 ± 7.1 versus 30.0 ± 13.1 mL/min/100 g, P = .05; mild cognitive impairment, 29.8 ± 5.4 versus 26.2 ± 8.6 mL/min/100 g, P < .05; all, 32.2 ± 6.8 versus 29.3 ± 12.3 mL/min/100 g, P < .05). FAIR had lower variability (controls, 36.2% versus 68.8%, P < .00001; mild cognitive impairment, 18.9% versus 22.9%, P < .0001; all, 34.4% versus 64.9% P < .00001). The detailed voxelwise analysis revealed a higher signal for FAIR, notably in both convexities, while PICORE had higher signal predominantly in deep cerebral regions., Conclusions: Overall, FAIR had higher estimated relative CBF and lower interindividual variability than PICORE. In more detail, there were regional differences between both arterial spin-labeling sequences. In summary, these results highlight the need to calibrate arterial spin-labeling sequences., (© 2015 by American Journal of Neuroradiology.)

Sexual violence is a well-recognized global health problem, albeit with limited population-based data available from sub-Saharan Africa. We sought to measure the prevalence of forced sex in Kisumu, Kenya, and identify its associated factors. The data were drawn from a population-based cross-sectional survey. A two-stage sampling design was used: 40 clusters within Kisumu municipality were enumerated and households within each cluster selected by systematic random sampling. Demographic and sexual histories, including questions on forced sex, were collected privately using a structured questionnaire. The prevalence of forced sex was 13% (women) and 4.5% (men). After adjusting for age and cluster, forced sex among women was associated with transactional sex (OR 2.33; 95%CI 1.38-3.95), having more than two lifetime partners (OR 1.9; 95%CI 1.20-3.30), having postprimary education (OR 1.49; 95%CI 1.04-2.14) and a high economic status (OR 1.87; 95%CI 1.2-2.9). No factors were significantly associated with forced sex among the male respondents. Intimate partners were the most common perpetrators of forced sex among both women (50%) and men (62.1%). Forced sex prevention programs need to target the identified associated factors, and educate the public on the high rate of forced sex perpetrated by intimate partners.

Attitudes and beliefs about antiretroviral therapy (ART) may affect sexual risk behaviors among the general population in sub-Saharan Africa. We performed a cross-sectional population-based study in Kisumu, Kenya to test this hypothesis in October 2006. A total of 1655 participants were interviewed regarding attitudes and beliefs about ART and their sexual risk behaviors. The majority of participants, (71%) men and (70%) women, had heard of ART. Of these, 20% of men and 29% of women believed ART cures HIV. Among women, an attitude that "HIV is more controllable now that ART is available" was associated with sex with a non-spousal partner, increased lifetime number of sexual partners as well as a younger age at sexual debut. No significant associations with this factor were found among men. The belief that "ART cures HIV" was associated with younger age of sexual debut among women. The same belief was associated with an increased likelihood of exchanging sex for money/gifts and decreased likelihood of condom use at last sex among men. These findings were most significant for people aged 15-29 years. In high HIV seroprevalence populations with expanding access to ART, prevention programs must ensure their content counteracts misconceptions of ART in order to reduce high risk sexual behaviors, especially among youth.

HIV testing has been promoted as a key HIV prevention strategy in low-resource settings, despite studies showing variable impact on risk behavior. We sought to examine rates of HIV testing and the association between testing and sexual risk behaviors in Kisumu, Kenya. Participants were interviewed about HIV testing and sexual risk behaviors. They then underwent HIV serologic testing. We found that 47% of women and 36% of men reported prior testing. Two-thirds of participants who tested HIV-positive in this study reported no prior HIV test. Women who had undergone recent testing were less likely to report high-risk behaviors than women who had never been tested; this was not seen among men. Although rates of HIV testing were higher than seen in previous studies, the majority of HIV-infected people were unaware of their status. Efforts should be made to increase HIV testing among this population.

Using a population-based survey we examined the behaviors, beliefs, and HIV/HSV-2 serostatus of men and women in the traditionally non-circumcising community of Kisumu, Kenya prior to establishment of voluntary medical male circumcision services. A total of 749 men and 906 women participated. Circumcision status was not associated with HIV/HSV-2 infection nor increased high risk sexual behaviors. In males, preference for being or becoming circumcised was associated with inconsistent condom use and increased lifetime number of sexual partners. Preference for circumcision was increased with understanding that circumcised men are less likely to become infected with HIV.

Background: Since antiretroviral therapy (ART) became available in the developed world, the prevalence of unprotected sex and the incidence of sexually transmitted infections (STIs) and HIV have increased. We hypothesized that a similar phenomenon may be occurring in sub-Saharan Africa concomitant with the scale-up of HIV treatment., Methods: We conducted a general population-based survey in Kisumu, Kenya. Participants completed an interview that included demographics as well as ART-related attitudes and beliefs (AB) and then underwent HIV serological testing. Exploratory and confirmatory factor analyses of AB about ART indicated two factors: 1) ART-related risk compensation (increased sexual risk taking now that ART is available); and 2) a perception that HIV is more controllable now that ART is available. Logistic regression was used to determine associations of these factors with HIV-seroprevalence after controlling for age., Findings: 1,655 (90%) of 1,844 people aged 15-49 contacted, including 749 men and 906 women, consented to participate in the study. Most participants (n = 1164; 71%) had heard of ART. Of those who had heard of ART, 23% believed ART was a cure for HIV. ART-related risk compensation (Adjusted (A)OR = 1.45, 95% CI 1.16-1.81), and a belief that ART cures HIV (AOR = 2.14, 95% CI 1.22-3.76) were associated with an increased HIV seroprevalence in men but not women after controlling for age. In particular, ART-related risk compensation was associated with an increased HIV-seroprevalence in young (aged 15-24 years) men (OR = 1.56; 95% CI 1.12-2.19)., Conclusions: ART-related risk compensation and a belief that ART cures HIV were associated with an increased HIV seroprevalence among men but not women. HIV prevention programs in sub-Saharan Africa that target the general population should include educational messages about ART and address the changing beliefs about HIV in the era of greater ART availability.

Background: Current microbicide clinical trials primarily enroll adult participants; however, females under the age of 18, because of their high rates of HIV acquisition, represent an important population for future microbicide clinical research. We sought to understand the individual, family and community-level factors that may influence the acceptability of microbicide use and research involving adolescent girls., Methods: We conducted 30 interviews with adolescent girls aged 14-17 and nine focus group discussions with adolescent girls, parents and community leaders in Kisumu, Kenya. Participants discussed adolescent sexuality, HIV prevention methods, perceptions about microbicide use and views about microbicide research involving adolescent girls., Results: Adolescent sexual activity is stigmatised yet acknowledged to be a natural part of the 'adolescent stage.' Desperation to stop the spread of HIV among youth and support for female-initiated HIV prevention methods led to enthusiasm about microbicides and future microbicide research. Yet concerns about microbicides were numerous and included: difficulty using it in a timely manner due to the rushed, unplanned nature of adolescent sex; a fear of trying experimental products; concerns about microbicide efficacy; and parental worry that supporting microbicide use in youth would defy societal pressures that denounce adolescent sexual activity., Conclusions: Microbicide acceptability for youth in sub-Saharan Africa may be bolstered by desperation for new methods to stop the spread of HIV, yet hindered by misgivings about experimental HIV prevention methods for youth. Understanding and addressing the microbicide's perceived benefits and shortcomings, as well as the broader context of adolescent sexuality and HIV prevention, may facilitate future research and promotion of microbicides in this high-risk group.

Health care rationing, when defined as resource allocation that makes use of a power relationship, is inescapable in every health care system. Central to this paper is the question: Is visible (publicized and centralized) health care rationing a requirement of justice or an affront to public morality? Inasmuch as health care is a public good, it is argued that health care resources should be visibly rationed in order to satisfy prevailing notions of procedural justice.

Microscopic examination of blood films is essential in clinical medicine despite automatic cell counters. To acquire this skill takes time, an adequate technical infrastructure and experienced instructors. In many cases all these things are not readily available. A computer-based learning program such as "HemoSurf" helps to supply these needs. In its learning part, "HemoSurf" allows the user to develop pattern recognition by offering more than 2000 images of blood and bone marrow films. In a stepwise manner the learner is enabled to differentiate leukocytes and recognize qualitative alterations to blood cells. In the reference part the user can look up blood films and some of the corresponding bone marrow films of over 30 diseases. In the World Wide Web "HemoSurf" is accessible via the following URL: [http./(/)www.aum.iawf.unibe.ch/VLZ/ BWL/HemoSurf/Index.htm]. A publication on CD-ROM with different language versions is in preparation.

The specific gravity of urine (SG) indicates the number and weight of solute particles in urine; its measurement is helpful in interpreting proteinuria detected by dipstick tests and in monitoring adequate hydration in patients with nephrolithiasis. Four methods for measuring SG or osmolality of urine are currently available (depression of the freezing-point, urometry, refractometry, cation exchange on a reagent strip). Using a recently developed reagent strip, we have measured SG in morning urines of 340 non-selected outpatients and compared the results with SG measurements by refractometry of the same urines. In 86.2% of all urines, a good positive correlation between SG measured by reagent strip and refractometry was noted (r = 0.913, p = 0.0001). In 13.8% of the urines, however, the SG measured by reagent strip deviated by more than +/- 5 from the value obtained by refractometry; in 90% of these urines, glucosuria (reagent strip values too low or too high), proteinuria (values too high), or bacteriuria/leukocyturia (values too low or too high) could be found. In alkaline urine (pH > 7.0), SG values obtained by reagent strip have to be corrected by +5.