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    Design, adaptation, and diffusion of an innovative tool to support contraceptive decision-making: Balanced Counseling Strategy Plus

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    Contraceptive decision-making is highly complex, and family planning (FP) clients choose methods according to a host of personal, interpersonal, and context-specific considerations. These include concerns about side effects, confidence in their ability to adhere to daily or monthly use, efficacy of methods, partner support, and HIV vulnerability. FP decision support tools can support FP clients and providers to engage in a joint decision-making process to ensure clients make informed choices about contraception. For more than two decades, the Balanced Counseling Strategy (BCS) and Balanced Counseling Strategy Plus (BCS+) decision support tools have been used in lower- and middle-income countries, informed by implementation science research and iterative updates and refinements to reflect new developments in contraceptive technology and HIV prevention strategies. To inform the development and scale-up of future FP decision support tools, this article describes the development, evaluation, and proliferation of BCS and BCS+

    High throughput scRNA-Seq provides insights into leydig cell senescence induced by experimental autoimmune orchitis: A prominent role of interstitial fibrosis and complement activation

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    Leydig cells (Lc), located in the interstitial space of the testis between seminiferous tubules, produce 95% of testosterone in male individuals, which is pivotal for male sexual differentiation, spermatogenesis, and maintenance of the male secondary sex characteristics. Lc are prone to senescence in aging testes, resulting in compromised androgen synthesis capability upon aging. However, little is known about whether Lc undergo senescence in a chronic inflammatory environment. To investigate this question, mouse models of experimental autoimmune orchitis (EAO) were used, and Lc were analyzed by high throughput scRNA-Seq. Data were screened and analyzed by correlating signaling pathways with senescence, apoptosis, androgen synthesis, and cytokine/chemokine signaling pathways. EAO did induce Lc senescence, and Lc senescence in turn antagonized androgen synthesis. Based on the correlation screening of pathways inducing Lc senescence, a plethora of pathways were found to play potential roles in triggering Lc senescence during EAO, among which the Arf6 and angiopoietin receptor pathways were highly correlated with senescence signature. Notably, complement and interstitial fibrosis activated by EAO worsened Lc senescence and strongly antagonized androgen synthesis. Furthermore, most proinflammatory cytokines enhanced both senescence and apoptosis in Lc and spermatogonia (Sg) during EAO, and proinflammatory cytokine antagonism of the glutathione metabolism pathway may be key in inducing cellular senescence during EAO

    Contraceptive drug, Nestorone, enhances stem cell-mediated remodeling of the stroke brain by dampening inflammation and rescuing mitochondria

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    Ischemic stroke remains a significant unmet need causing massive mortality and morbidity due to few treatment options with limited therapeutic window. The progestin Nestorone® (segesterone acetate) displays high affinity for the progesterone receptor in exerting its potent birth control and hormone replacement therapy. Accumulating evidence implicates a new utility of Nestorone in affording neuroprotection in a variety of central nervous system diseases, including stroke. However, the mechanism of action mediating Nestorone\u27s neuroprotection in stroke remains unknown. Here, we showed that stand-alone treatments of Nestorone or human amniotic fluid-derived stem cells (hAFSc), but more pronounced with their combined treatment, led to significant improvements in behavioral function and reductions in infarction and peri-infarct cell loss in adult rats with ischemic stroke. We detected significantly lower levels of pro-inflammatory signals (OX6 and IBA1) coupled with enhanced levels of stem cell proliferation (Ki67) and differentiation (DCX and MAP2) in both brain and spleen of stroke rats that received stand-alone or combined treatments of Nestorone and hAFSc. In concert, the in vitro oxygen-glucose deprivation stroke model revealed that neural stem cells treated with Nestorone exhibited increased stem cell proliferation and differentiation that was accompanied by rescue of the mitochondrial respiratory activity characterized by reduced mitochondrial reactive oxygen species, increased ATP, elevated mitochondrial deacetylase Sirtuin 3 (SIRT3), and a normalized ratio of acetyl-superoxide dismutase 2 (Ac-SOD2)/SOD2, suggesting the key role of mitochondrial metabolism and oxidative protection in Nestorone\u27s therapeutic effects in stroke

    Key drivers of fertility levels and differentials in India, at the national, state and population subgroup levels, 2015–2016: An application of Bongaarts\u27 proximate determinants model

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    Objectives: The transition to small family size is at an advanced phase in India, with a national TFR of 2.2 in 2015–16. This paper examines the roles of four key determinants of fertility—marriage, contraception, abortion and postpartum infecundability—for India, all 29 states and population subgroups. Methods: Data from the most recent available national survey, the National Family Health Survey, conducted in 2015–16, were used. The Bongaarts proximate determinants model was used to quantify the roles of the four key factors that largely determine fertility. Methodological contributions of this analysis are: adaptations of the model to the Indian context; measurement of the role of abortion; and provision of estimates for sub-groups nationally and by state: age, education, residence, wealth status and caste. Results: Nationally, marriage is the most important determinant of the reduction in fertility from the biological maximum, contributing 36%, followed by contraception and abortion, contributing 24% and 23% respectively, and post-partum infecundability contributed 16%. This national pattern of contributions characterizes most states and subgroups. Abortion makes a larger contribution than contraception among young women and better educated women. Findings suggest that sterility and infertility play a greater than average role in Southern states; marriage practices in some Northeastern states; and male migration for less-educated women. The absence of stronger relationships between the key proximate fertility determinants and geography or socio-economic status suggests that as family size declined, the role of these determinants is increasingly homogenous. Conclusions: Findings argue for improvements across all states and subgroups, in provision of contraceptive care and safe abortion services, given the importance of these mechanisms for implementing fertility preferences. In-depth studies are needed to identify policy and program needs that depend on the barriers and vulnerabilities that exist in specific areas and population groups

    Exposed and sequestered antigens in testes and their protection by regulatory T cell-dependent systemic tolerance

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    Continuous exposure of tissue antigen (Ag) to the autoantigen-specific regulatory T cells (Treg) is required to maintain Treg-dependent systemic tolerance. Thus, testis autoantigens, previously considered as sequestered, may not be protected by systemic tolerance. We now document that the complete testis antigen sequestration is not valid. The haploid sperm Ag lactate dehydrogenase 3 (LDH3) is continuously exposed and not sequestered. It enters the residual body (RB) to egress from the seminiferous tubules and interact with circulating antibody (Ab). Some LDH3 also remains inside the sperm cytoplasmic droplets (CD). Treg-depletion in the DEREG mice that express diphtheria toxin receptor on the Foxp3 promoter results in spontaneous experimental autoimmune orchitis (EAO) and Ab to LDH3. Unlike the wild-type male mice, mice deficient in LDH3 (wild-type female or LDH3 NULL males) respond vigorously to LDH3 immunization. However, partial Treg depletion elevated the wild-type male LDH3 responses to the level of normal females. In contrast to LDH3, zonadhesin (ZAN) in the sperm acrosome displays properties of a sequestered Ag. However, when ZAN and other sperm Ag are exposed by vasectomy, they rapidly induce testis Ag-specific tolerance, which is terminated by partial Treg-depletion, leading to bilateral EAO and ZAN Ab response. We conclude that some testis/sperm Ag are normally exposed because of the unique testicular anatomy and physiology. The exposed Ag: 1) maintain normal Treg-dependent systemic tolerance, and 2) are pathogenic and serve as target Ag to initiate EAO. Unexpectedly, the sequestered Ags, normally non-tolerogenic, can orchestrate de novo Treg-dependent, systemic tolerance when exposed in vasectomy

    Sexually transmitted infections in pregnant people with human immunodeficiency virus: Temporal trends, demographic correlates, and association with preterm birth

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    Background: We describe trends in prevalence and identify factors associated with Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), syphilis, and Trichomonas vaginalis (TV) diagnosed in pregnancy among US people with human immunodeficiency virus (PWH) and evaluate associations of sexually transmitted infections (STIs) with preterm birth (PTB). Methods: We included pregnant PWH enrolled in the Surveillance Monitoring for ART Toxicities dynamic cohort of the Pediatric HIV/AIDS Cohort Study network who delivered between 2010 and 2019. Multivariable log-binomial or Poisson generalized estimating equation models were used to estimate the association of calendar year with each STI, controlling for confounders; the association of demographic and clinical factors with each STI; and the association of each STI with PTB. Results: The sample included 2241 pregnancies among 1821 PWH. Median age at delivery was 29.2 years; 71% of participants identified as Black or African American. STI prevalence was: CT 7.7%, NG 2.3%, syphilis 2.4%, and TV 14.5%; 30% had unknown TV status. There were no temporal changes in STI prevalence. Younger age and initial HIV viral load ≥400 copies/mL were associated with increased risk of CT, NG, and TV. Recreational substance use was a risk factor for NG, syphilis, and TV. No STI was associated with PTB. Conclusions: Unlike nationwide trends, no changes in STI prevalence during the study period were observed. The large proportion with unknown TV status underscores the need for increased adherence to screening guidelines. STIs diagnosed during pregnancy in PWH were not associated with risk of PTB

    Impact of COVID-19 on adolescent HIV prevention and treatment services in the AHISA network

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    We investigated perceived impacts of COVID-19 on the delivery of adolescent HIV treatment and prevention services in sub-Saharan Africa (SSA) by administering a survey to members of the Adolescent HIV Prevention and Treatment Implementation Science Alliance (AHISA) from February to April 2021. We organized COVID-19 impacts, as perceived by AHISA teams, under three themes: service interruptions, service adjustments, and perceived individual-level health impacts. AHISA teams commonly reported interruptions to prevention programs, diagnostic testing, and access to antiretroviral therapy (ART). Common service adjustments included decentralization of ART refills, expanded multi-month ART distribution, and digital technology use. Perceived individual-level impacts included social isolation, loss to follow-up, food insecurity, poverty, and increases in adolescent pregnancies and sexually transmitted infections. The need for collaboration among stakeholders were commonly cited as lessons learned by AHISA teams. Survey findings highlight the need for implementation science research to evaluate the effects of pandemic-related HIV service adaptations in SSA

    Changes in clients\u27 perceptions of family planning quality of care in Kaduna and Lagos States, Nigeria: A mixed methods study

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    Community Pharmacists (CPs) and Patent and Proprietary Medicine Vendors (PPMVs) are crucial to improving access to family planning (FP) services in Nigeria. Although the private sector is preferred for convenience, availability of commodity, privacy, and timeliness, less well known is the quality of care received by clients who obtain FP services from CPs and PPMVs. This paper seeks to explore the use of validated quality of care measures for programming in Kaduna and Lagos States and to assess how these measures worked in capturing changes in quality of care using client exit interviews implemented at two time points. Using validated measures of quality of care, 598 and 236 exit interviews in rounds 1 and 2 were conducted with FP clients aged 18–49 years old. The quality of care domains were assessed using 22 questions. A weighted additive quality score was created, and scores were grouped into three: low, medium, and high quality. Changes in quality of care received were examined using χ2 test. A subset of 53 clients were selected for in-depth interviews. Deductive and inductive approaches were used for coding, and data analysis was thematic. In Lagos, we observed increases in 16 out of 22 items while in Kaduna increases were only observed in 8 items. For instance, increases were observed in the proportion of women who experienced visual privacy between rounds 1 and 2 in Lagos (74%–89%) and Kaduna (66%–82%). The quality of care received by clients changed over time. Women who reported high quality care in Lagos increased from 42% to 63%, whereas women who reported high quality care in Kaduna decreased from 35% to 21%. In both states, in-depth interviews revealed that women felt they were treated respectfully, that their sessions with providers were visually private, that they could ask questions, and that they were asked about their preferred method. This study demonstrates that clients received high quality of care services from providers (CPs and PPMVs) especially in Lagos, and such services can be improved over time. Continuous support may be required to maintain and prevent reduction in quality of FP counseling and services, particularly in Kaduna

    A content analysis of Reddit users’ posts about challenges to contraceptive care-seeking during COVID-19-related restrictions in the United States

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    The COVID-19 pandemic in the United States caused disruptions in care seeking and delivery during the spring of 2020, including for contraceptive care. We examined how some individuals experienced and responded to barriers to accessing contraceptive care by conducting a content analysis of relevant Reddit posts. We collected 2666 posts by scraping relevant subreddits from February 1, 2020, to April 15, 2020, and filtering by selected keywords. Among the 101 posts on contraception and the COVID-19 pandemic, we explored three main themes: barriers to accessing general healthcare during the early pandemic, problems and concerns specific to contraceptive use, and attempts to navigate the obstacles to contraceptive care or use-related concerns. The Reddit posts demonstrated the disruptive force the early pandemic had on contraceptive care and provided a unique window into the concerns posters expressed on Reddit during this time. Many posters asked questions related to accessing contraception and side effects and sought reassurance from these online forums. Our results suggest that there were barriers to accessing reliable, high-quality, and evidence-based information about contraception during this disruption in care. The findings also underscore that conversational and interactive means of seeking out information are important modes for learning about and discussing contraception for some and may be especially helpful during clinic closures and other restrictions on access

    Breakthrough RESEARCH\u27s evaluation of Breakthrough ACTION Nigeria’s community capacity strengthening approach

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    This docuslide presents an abridged synthesis of the Qualitative evaluation of Breakthrough ACTION/Nigeria\u27s community capacity strengthening approach to sustaining integrated social and behavior change programming: Phase I study report. Use this docuslide to explore key findings and takeaways and refer to the full study report for more details and information

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