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The optimal protocol for minimal stimulationAll cycles designated as minimal stimulation from 2014 to 2016 from the Society for Assisted Reproductive Technology Clinic Online Reporting System were identified. Cycles in which GnRH antagonist was administered (A total of 6750 patients undergoing 13,050 cycles were included. GnRH antagonist use was associated with a significantly higher total gonadotropin dosage (median 975.0 [interquartile range, IQR, 600.0, 1575.0] vs. median 660.0 [IQR 375.0, 975.0],The use of GnRH antagonist suppression during minimal stimulation IVF is associated with an improved live birth rate, especially in older women and in women with diminished ovarian reserve. Although GnRH antagonist use may increase costs, it significantly decreases cancelation rate, increases number of embryos cryopreserved, and should be encouraged for minimal stimulation IVF.

PURPOSE Efforts have been made to standardize laboratory variant interpretation, but clinicians are ultimately tasked with clinical correlation and application of genetic test results in patient care. This study aimed to explore processes clinicians utilize when reviewing and returning genetic test results, and how they impact patient care. METHODS Medical geneticists, genetic counselors, and nongenetics clinicians from two Midwestern states completed surveys (n = 98) and in-depth interviews (n = 29) on practices of reviewing and returning genetic test results. Retrospective chart review (n = 130) examined discordant interpretations and the impact on care. RESULTS Participants reported variable behaviors in both reviewing and returning results based on factors such as confidence, view of role, practice setting, and relationship with the lab. Providers did not report requesting changes to variant classifications from laboratories, but indicated relaying conflicting classifications to patients in some cases. Chart reviews revealed medically impactful differences in interpretation between laboratories and clinicians in 18 (13.8%) records. CONCLUSION Clinician practices for reviewing and integrating genetic test results into patient care vary within and between specialties and impact patient care. Strategies to better incorporate both laboratory and clinician expertise into interpretation of genetic results could result in improved care across providers and settings.

Background Individuals with substance use disorders (SUD) have disproportionately high rates of unintended pregnancy. Reducing harm associated with this risk and its biopsychosocial consequences requires evidence-based, non-coercive interventions that ensure access to contraception for individuals who choose to prevent pregnancy. We aimed to examine feasibility and impact of SexHealth Mobile, a mobile unit-based intervention aiming to increase access to patient-centered contraceptive care for individuals in SUD recovery programs. Methods We conducted a quasi-experimental study (enhanced usual care [EUC] followed by intervention) at three recovery centers with participants (n = 98) at risk for unintended pregnancy. EUC participants were offered printed information on community locations where they could access contraception care. SexHealth Mobile participants were offered same-day, onsite clinical consultation on a medical mobile unit and contraception if desired. The primary outcome was use of hormonal contraception/IUD at one-month post-enrollment. Secondary outcomes were use at two-weeks and three-months. Confidence in preventing unintended pregnancy, reasons for non-use of contraception at follow-up, and intervention feasibility were also assessed. Results Participants (median age = 31, range 19–40) enrolled in the intervention were almost 10 times more likely to be using contraception at one-month (51.5%) versus the those enrolled in the EUC period (5.4%) (unadjusted relative risk [URR] = 9.3 [95%CI: 2.3–37.1]; adjusted relative risk [ARR] = 9.8 [95%CI: 2.4–39.2]). Intervention participants were also more likely to be using contraception at 2-weeks (38.7% vs. 2.6%; URR = 14.3 [95%CI: 2.0-104.1]) and three-months (40.9% vs. 13.9%; URR = 2.9 [95% CI: 1.1–7.4]). EUC participants reported more barriers (cost, time) and less confidence in preventing unintended pregnancies. Mixed-methods feasibility data indicated high acceptability and feasible integration into recovery settings. Conclusions Mobile contraceptive care based on principles of reproductive justice and harm reduction reduces access barriers, is feasible to implement in SUD recovery settings, and increases contraception use. Following the overturning of Roe v. Wade, expanding interventions like SexHealth Mobile may help reduce harm from unintended pregnancies among individuals in SUD recovery. Trial Registration: NCT04227145

Bacteriophages Clayda5, Gshelby23, Wrigley, and Santhid were isolated from soil samples collected in Iowa, with genomes typical of actinobacteriophages from clusters EB, EM, CY, and DY, respectively. Wrigley and Santhid were isolated on Gordonia terrae and are likely to be temperate. Clayda5 and Gshelby23 were isolated on Microbacterium foliorum.

N-methyl-D-aspartate receptors (NMDARs) assemble as functionally diverse heterotetramers. Incorporation of the GluN3A subunit into NMDARs alters conventional NMDAR properties by reducing both magnesium sensitivity and calcium permeability. GluN1 together with GluN3A can also form functional receptors that lack a glutamate binding site and instead serve as excitatory glycine receptors (eGlyRs). GluN3A expression is high in early development but naturally declines to low levels in most brain regions by adulthood. Interestingly, GluN3A expression remains elevated in the CA1 of the adult ventral hippocampus (VH), but not in the dorsal hippocampus (DH). The DH and VH are now well-understood to play very different functional roles, with the DH being primarily involved in cognitive functions and the VH in emotional processing. Why GluN3A persists in the adult VH, and the impact its presence has on glutamatergic neurotransmission in the VH is currently unknown. Here, we show that GluN3A remains elevated both at synaptic and extrasynaptic locations in the adult VH, assembling as GluN1/GluN2/GluN3A NMDARs with reduced magnesium sensitivity, as well as GluN1/GluN3A eGlyRs. By comparing various synaptic properties in the DH and VH of wild-type (WT) and GluN3A knockout (KO) mice, we demonstrate that GluN3A persistence in the VH attenuates glutamate release, limits postsynaptic calcium influx through NMDARs, and reduces the magnitude of NMDAR-dependent long-term potentiation. In comparison, GluN3A KO had relatively little effect on these same properties in the DH. In all, our data demonstrate that GluN3A persistence in the VH represents a key modulator of VH excitability and therefore may play a central role in emotional processing.

Testis differentiation is initiated when Sry in pre-Sertoli cells directs the gonad toward a male-specific fate. Sertoli cells are essential for testis development, but cell types within the interstitial compartment, such as immune and endothelial cells, are also critical for organ formation. Our previous work implicated macrophages in fetal testis morphogenesis, but little is known about genes underlying immune cell development during organogenesis. Here we examine the role of the immune-associated genes Mafb and Maf in mouse fetal gonad development, and we demonstrate that deletion of these genes leads to aberrant hematopoiesis manifested by supernumerary gonadal monocytes. Mafb;Maf double knockout embryos underwent initial gonadal sex determination normally, but exhibited testicular hypervascularization, testis cord formation defects, Leydig cell deficit, and a reduced number of germ cells. In general, Mafb and Maf alone were dispensable for gonad development; however, when both genes were deleted, we observed significant defects in testicular morphogenesis, indicating that Mafb and Maf work redundantly during testis differentiation. These results demonstrate previously unappreciated roles for Mafb and Maf in immune and vascular development and highlight the importance of interstitial cells in gonadal differentiation.Summary statementDeletion of Mafb and Maf genes leads to supernumerary monocytes in fetal mouse gonads, resulting in vascular, morphogenetic, and differentiation defects during testicular organogenesis.

Objective Sequestosome 1 (p62/SQSTM1) is a multifunctional scaffold/adaptor protein encoded by the p62/SQSTM1 gene with function in cellular homeostasis. Mutations in the p62/SQSTM1 gene have been known to be associated with patients with amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Parkinson disease (PD). The aim of the present study was to create a novel model of human neurogenerative disease in Drosophila melanogaster by altering the expression of Ref(2)P, the Drosophila orthologue of the human p62/SQSTM1 gene. Ref(2)P expression was altered in all neurons, the dopaminergic neurons and in the motor neurons, with longevity and locomotor function assessed over time. Results Inhibition of Ref(2)P resulted in a significantly increased median lifespan in the motor neurons, followed by a severe decline in motor skills. Inhibition of Ref(2)P in the dopaminergic neurons resulted in a significant, but minimal increase in median lifespan, accompanied by a drastic decline in locomotor function. Inhibition of Ref(2)P in the ddc-Gal4-expressing neurons resulted in a significant increase in median lifespan, while dramatically reducing motor function.

OBJECTIVE To evaluate the willingness of young adult males to use male hormonal contraception and to determine the most desirable formulation. METHODS An institutional review board-approved survey measuring the willingness to use MHC was dispersed to two distinct populations: University of Cincinnati postgraduate programs and Cincinnati Health Department clinics. Questions on the survey allowed for the collection of demographic characteristics, as well as the preferred method of MHC, and concerns regarding potential adverse effects. This survey was directed at young adult males; therefore, only male participants who were 18 to 35 years old were included for analysis. Results were reported as frequencies in each group and χ2 analyses were performed to compare groups, with a P < 0.05 considered significant. RESULTS Of 162 total survey participants, 45% would use MHC, whereas 30.9% were unsure and 23.5% would not use MHC. Overall, the University of Cincinnati survey population was more likely to be interested in using MHC than the Cincinnati Health Department population (P < 0.05). In both populations, most were interested in using the injectable form. Cited concerns deterring participants from using MHC were different between these two populations, with University of Cincinnati participants more frequently expressing concerns about possible failure of the contraceptive method, whereas Cincinnati Health Department participants had concerns about potential adverse effects (P < 0.001). CONCLUSIONS There is significant interest among young adult males in using various forms of MHC, especially in injectable form. Differences in views of MHC were seen in two distinct male populations. Specifically, males who achieved a higher level of education, were employed, or in a relationship were found to more frequently be willing to use MHC. With further research and funding, MHC may serve as a significant way to decrease unintended pregnancies in the future.

Most research on glutamate spillover focuses on the deleterious consequences of postsynaptic glutamate receptor overactivation. However, two decades ago, it was noted that the glial coverage of hippocampal synapses is asymmetric: astrocytic coverage of postsynaptic sites exceeds coverage of presynaptic sites by a factor of four. The fundamental relevance of this glial asymmetry remains poorly understood. Here, we used the glutamate biosensor iGluSnFR, and restricted its expression to either CA3 or CA1 neurons to visualize glutamate dynamics at pre- and postsynaptic microenvironments, respectively. We demonstrate that inhibition of the primarily astrocytic glutamate transporter-1 (GLT-1) slows glutamate clearance to a greater extent at presynaptic compared to postsynaptic membranes. GLT-1 expression was reduced early in a mouse model of AD, resulting in slower glutamate clearance rates at presynaptic but not postsynaptic membranes that opposed presynaptic short-term plasticity. Overall, our data demonstrate that the presynapse is particularly vulnerable to GLT-1 dysfunction and may have implications for presynaptic impairments in a variety of brain diseases.

Uptake of pre-exposure prophylaxis (PrEP) fell short of targets for Sub-Saharan Africa's initial rollout, revealing the need for more effective promotion strategies. In Uganda, we explored potential benefits and challenges of integrating safer conception messaging to promote PrEP among serodiscordant couples. In-depth interviews were conducted with clients and personnel at three clinics and analyzed thematically. Participants (n = 58) valued PrEP as a safer conception method (SCM) but described lack of integration of safer conception and PrEP services as well as inconsistent practices in prescribing PrEP to couples pursuing conception. Participants reported that the wider population remains largely unaware of PrEP and SCM or harbors misconceptions that PrEP is primarily for highly stigmatized groups like sex workers. Participants further described how heterosexual couples can still be reluctant to test for HIV, unaware of tools like PrEP and SCM that would allow them to continue their relationship and/or pursuit of childbearing. Overall, findings suggest that integrating PrEP and SCM in messaging and services targeting serodiscordant couples holds untapped benefits throughout the HIV prevention cascade.

BackgroundChildren with acute respiratory tract infections (ARTIs) receive ≈11.4 million unnecessary antibiotic prescriptions annually. A noted contributor is inadequate parent–clinician communication, however, efforts to reduce overprescribing have only indirectly targeted communication or been impractical.ObjectivesCompare two feasible (higher vs lower intensity) interventions for enhancing parent–clinician communication on the rate of inappropriate antibiotic prescribing.DesignMultisite, parallel group, cluster randomised comparative effectiveness trial. Data collected between March 2017 and March 2019.SettingAcademic and private practice outpatient clinics.ParticipantsClinicians (n=41, 85% of eligible approached) and 1599 parent–child dyads (ages 1–5 years with ARTI symptoms, 71% of eligible approached).InterventionsAll clinicians received 20 min ARTI diagnosis and treatment education. Higher intensity clinicians received an additional 50 min communication skills training. All parents viewed a 90 second antibiotic education video.Main outcome(s) and measure(s)Inappropriate antibiotic treatment was assessed via blinded medical record review by study clinicians and a priori defined as prescriptions for the wrong diagnosis or use of the wrong agent. Secondary outcomes were revisits, adverse drug reactions (both assessed 2 weeks after the visit) and parent ratings of provider communication, shared decision-making and visit satisfaction (assessed at end of the visit on Likert-type scales).ResultsMost clinicians completed the study (n=38, 93%), were doctors (n=25, 66%), female (n=30, 78%) and averaged 8 years in practice. All parent–child dyad provided data for the main outcome (n=855 (54%) male, n=1043 (53%)<2 years). Inappropriate antibiotic prescribing was similar among patients who consulted with a higher intensity (54/696, 7.8%) versus a lower intensity (85/904, 9.4%) clinician. A generalised linear mixed effect regression model (adjusted for the two-stage nested design, clinician type, clinic setting and clinician experience) revealed that the odds of receiving inappropriate antibiotic treatment did not significantly vary by group (AOR 0.99, 95% CI: 0.52 to 1.89, p=0.98). Secondary outcomes of revisits and adverse reactions did not vary between arms, and parent ratings of satisfaction with quality of parent–provider communication (5/5), shared decision making (9/10) and visit satisfaction (5/5) were similarly high in both arms.Conclusions and relevanceRate of inappropriate prescribing was low in both arms. Clinician education coupled with parent education may be sufficient to yield low inappropriate antibiotic prescribing rates. The absence of a significant difference between groups indicates that communication principles previously thought to drive inappropriate prescribing may need to be re-examined or may not have as much of an impact in practices where prescribing has improved in recent years.Trial registration numberNCT03037112.

Huntington disease (HD) is a monogenic disease that results in a combination of motor, psychiatric and cognitive symptoms. HD is caused by a CAG trinucleotide repeat expansion in the huntingtin (HTT) gene, which results in the production of a pathogenic mutant HTT protein (mHTT). Although there is no cure at present for HD, a number of RNA-targeting therapies have recently entered clinical trials which aim to lower mHTT production through the use of antisense oligonucleotides (ASOs) and RNAi. However, many of these treatment strategies are non-selective in that they cannot differentiate between non-pathogenic wild type HTT (wtHTT) and the mHTT variant. As HD patients are already born with decreased levels of wtHTT, these genetic therapies may result in critically low levels of wtHTT. The consequence of wtHTT reduction in the adult brain is currently under debate, and here we argue that wtHTT loss is not well-tolerated at the synaptic level. Synaptic dysfunction is an extremely sensitive measure of subsequent cell death, and is known to precede neurodegeneration in numerous brain diseases including HD. The present review focuses on the prominent role of wtHTT at the synapse and considers the consequences of wtHTT loss on both pre- and postsynaptic function. We discuss how wtHTT is implicated in virtually all major facets of synaptic neurotransmission including anterograde and retrograde transport of proteins to/from terminal buttons and dendrites, neurotransmitter release, endocytic vesicle recycling, and postsynaptic receptor localization and recycling. We conclude that wtHTT presence is essential for proper synaptic function.

New international guidelines for antenatal care (ANC) will likely result in an increase in nutritional supplements and preventative medications for pregnant women in low and middle-income countries. Our objective was to understand how pregnant women in Mali perceive and experience multi-drug regimens in ANC in order to reveal factors that may influence uptake and adherence. We conducted 29 semi-structured interviews and three focus groups with 21 pregnant women in two urban ANC sites in Bamako, Mali. Interviews focused on perception of purpose of ANC pharmaceuticals (particularly iron supplements, sulfadoxine-pyrimethamine as intermittent prevention of malaria and antiretroviral therapy for HIV), beliefs regarding efficacy and risk, and understanding of dosage and regimen. Transcripts were inductively coded and analyzed using the ‘Framework’ method. Participant descriptions of medication purpose, understanding of dosing, and beliefs about risks and efficacy varied widely, revealing that many pregnant women lack complete information about their medications. While some were burdened by side effects or complex regimens, women generally held favorable attitudes toward ANC medications. Responses suggest major barriers to adherence lie in the health system, namely insufficient patient-provider communication and inconsistent prescribing practices. National health programs looking to improve maternal and child health with ANC pharmaceuticals need to place greater attention on patient counseling and consistent implementation of administration guidelines. Communication that positions pharmaceuticals as beneficial to mother and child, while presenting understandable information about purpose, dosing and potential side effects can promote uptake of multi-drug regimens and ANC services in general.

Early infant diagnosis (EID) involves age-specific tracking and testing of HIV-exposed infants during the first 18 months of life and rapid initiation of life-saving treatment for those infected. In Kenya, pre-2013 data estimate EID lost to follow-up (LTFU) at 39–65%, yet no study has documented LTFU rates and predictors throughout the EID cascade since Option B+ fundamentally changed services by placing all HIV-positive expectant mothers on lifelong treatment. Using an explanatory mixed-method design, we assessed LTFU rates and predictors among 870 mother–infant dyads enrolled in EID in six urban/peri-urban Kenyan government hospitals. Mothers completed baseline surveys, and dyads were tracked through EID. We selected 12 baseline variables and modeled odds of LTFU at 9 and 18 months using mixed logistic regression. Qualitative interviews were conducted with 61 mothers to assess barriers and facilitators to completing EID. Thematically coded transcripts were used to interpret quantitative predictors of LTFU. By the 18-month test, 145 dyads (22%) were LTFU, with three-quarters of LTFU occurring between 9- and 18-month tests. Odds of LTFU at 18 months decreased by 10% for each additional year of maternal age and by 66% with HIV status disclosure. Qualitative data revealed how disclosure facilitated essential social support for EID completion and how older mothers attributed maturity and life experience to successful engagement in care. Findings suggest LTFU rates in Kenya have declined, but gaps remain in ensuring universal coverage. Efforts to improve retention should focus on increasing support for younger mothers and those who have not disclosed their HIV status.

The HIV Infant Tracking System (HITSystem) is an eHealth intervention to improve early infant diagnosis (EID) through alerts to providers and text messages to mothers. This study explored mothers' experiences receiving standard and HITSystem-enhanced EID services to assess perceived intervention benefits, acceptability, and opportunities for improvement. This qualitative study was embedded within a cluster-randomized control trial to evaluate the HITSystem at six Kenyan government hospitals (3 intervention, 3 control). We conducted semi-structured interviews with 137 mothers attending EID follow-up visits. Compared to control sites, participants at HITSystem sites described enhanced EID quality; HITSystem-generated texts informed them of result availability and retesting needs, provided cues-to-action for clinic attendance, and engendered opportunities for patient support. They described improved EID efficiency through shorter waiting periods for results and fewer hospital visits. Participants reported high satisfaction with EID and acceptability of text messages; however, modifications to ensure text delivery, increase repeat testing reminders, include low literacy content options, and provide encouraging messages were suggested. These user experience data suggest improvements in EID at HITSystem sites when compared with control sites.

Objective Shared decision-making (SDM) measures have never been assessed for validity and feasibility in pediatric outpatient settings. We compared psychometric performance of parent adaptations of a well-established measure (SDM-Q-9) to a newer measure focusing on provider effort in facilitating SDM (CollaboRATE) in two clinics. Methods English (n = 955) and Spanish (n = 58) speaking parents of children ages 1–5 years with symptoms of acute respiratory tract infections (ARTI) completed post-visit SDM-Q-9, CollaboRATE, satisfaction items (visit, provider communication, and study participation), and qualitative feedback. Results Parents felt CollaboRATE was more comprehensible and relevant than SDM-Q-9, which refers to decision-making actions difficult to define in ARTI visits. Among English-speakers, both measures showed high internal consistency (α = 0.91, α = 0.97). SDM-Q-9 reliability was strong (split-half, r = 0.83) and CollaboRATE weak-to-moderate (two-week test-retest, ρ = 0.41-0.66). Convergent validity with communication and visit satisfaction was poor for SDM-Q-9 (r=0.38, r=0.34) but higher for CollaboRATE (r=0.59, r = 0.52). Both showed divergent validity with study participation satisfaction (r=0.08, r=0.13). Spanish versions demonstrated similar results. Conclusions Parent preference and correlations with satisfaction support CollaboRATE over SDM-Q-9, however psychometrics were borderline acceptable. Practice Implications Tools like CollaboRATE that focus on provider effort appear more appropriate for routine pediatric visits where SDM outcomes may be difficult to identify, yet additional validation research is needed.

Background Safer conception counseling (SCC) to promote the use of safer conception methods (SCM) is not yet part of routine family planning or HIV care. Guidelines for the use of SCM have been published, but to date there are no published controlled evaluations of SCC. Furthermore, it is unknown whether standard methods commonly used in resource constrained settings to integrate new services would be sufficient, or if enhanced training and supervision would result in a more efficacious approach to implementing SCC. Methods In a hybrid, cluster randomized controlled trial, six HIV clinics were randomly assigned to implement the SCC intervention Our Choice using either a high (SCC1) or low intensity (SCC2) approach (differentiated by amount of training and supervision), or existing family planning services (usual care). Three hundred eighty-nine HIV clients considering childbearing with an HIV-negative partner enrolled. The primary outcome was self-reported use of appropriate reproductive method (SCM if trying to conceive; modern contraceptives if not) over 12 months or until pregnancy. Results The combined intervention groups used appropriate reproductive methods more than usual care [20.8% vs. 6.9%; adjusted OR (95% CI)=10.63 (2.79, 40.49)], and SCC1 reported a higher rate than SCC2 [27.1% vs. 14.6%; OR (95% CI)=4.50 (1.44, 14.01)]. Among those trying to conceive, the intervention arms reported greater accurate use of SCM compared to usual care [24.1% vs. 0%; OR (95% CI)=91.84 (4.94, 1709.0)], and SCC1 performed better than SCC2 [34.6% vs. 11.5%; OR (95% CI)=6.43 (1.90, 21.73)]. The arms did not vary on modern contraception use among those not trying to conceive. A cost of $631 per person was estimated to obtain accurate use of SCM in SCC1, compared to $1014 in SCC2. Conclusions More intensive provider training and more frequent supervision leads to greater adoption of complex SCM behaviors and is more cost-effective than the standard low intensity implementation approach. Trial registration Clinicaltrials.gov, NCT03167879; date registered May 23, 2017.

Background The sharp rise in opioid use disorder (OUD) among women coupled with disproportionally high rates of unintended pregnancy have led to a four-fold increase in the number of pregnant women with OUD in the United States over the past decade. Supporting intentional family planning can have multiple health benefits and reduce harms related to OUD but requires a comprehensive understanding of women’s perspectives of preventing unintended pregnancies. The purpose of this study was to comprehensively evaluate the knowledge, attitudes and experiences as they relate to seeking contraception, particularly LARCs, among women with active or recovered opioid misuse. Methods In-depth interviews and focus group discussions with 36 women with current or past opioid misuse were recorded and transcribed. Transcripts were coded by ≥ 2 investigators. Themes related to contraceptive care seeking were identified and contextualized within the Health Belief Model. Results Our analysis revealed seven interwoven themes that describe individual level factors associated with contraceptive care seeking in women with current or past opioid misuse: relationship with drugs, reproductive experiences and self-perceptions, sexual partner dynamics, access, awareness of options, healthcare attitudes/experiences, and perceptions of contraception efficacy/ side effects. Overall, perceived susceptibility and severity to unintended pregnancy varied, but most women perceived high benefits of contraception, particularly LARC. However, perceived barriers were too high for most to obtain desired contraception to support family planning intentions. Conclusions The individual-level factors identified should inform the design of integrated services to promote patient-centered contraceptive counseling as a form of harm reduction. Interventions should reduce barriers to contraceptive access, particularly LARCs, and establish counseling strategies that use open, non-judgmental communication, acknowledge the continuum of reproductive needs, explore perceived susceptibility to pregnancy, and utilize peer educators.

Objective: Sequestosome 1 (p62/SQSTM1) is a multifunctional scaffold/adaptor protein encoded by the p62/SQSTM1 gene with function in cellular homeostasis. Mutations in the p62/SQSTM1 gene have been known to be associated with patients with Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Dementia (FTD), and Parkinson Disease (PD). The aim of the present study was to create a novel model of human neurogenerative disease in Drosophila melanogaster by altering the expression of Ref(2)P, the Drosophila orthologue of the human p62/SQSTM1 gene. Ref(2)P expression was altered in all neurons, the dopaminergic neurons and in the motor neurons, with longevity and locomotor function assessed over time.Results: Inhibition of Ref(2)P resulted in a significantly increased median lifespan in the motor neurons, followed by a severe decline in motor skills. Inhibition of Ref(2)P in the dopaminergic neurons resulted in a significant, but minimal increase in median lifespan, accompanied by a drastic decline in locomotor function. Inhibition of Ref(2)P in the ddc-Gal4-expressing neurons resulted in a significant increase in median lifespan, while dramatically reducing motor function.

Background: Low- and middle-income countries (LMIC) are experiencing major increases in diabetes and cardiovascular conditions linked to overweight and obesity. We evaluated an adapted version of the Diabetes Prevention Program (DPP) named Lifestyle Africa, tailored for an under-resourced community in South Africa. Methods: Participants with BMI ≥ 25 kg/m2 who were members of existing social support groups or “clubs” based in low-income townships were enrolled in a cluster-randomized controlled trial that compared the adapted intervention to usual care. The Lifestyle Africa intervention consisted of 17 video-based group sessions delivered by trained community health workers (CHWs). CHWs, participants, and research team members could not be blinded to condition. Percentage weight loss (primary outcome), HbA1c, blood pressure, triglycerides, and LDL cholesterol were assessed 7–9 months after enrollment. An individual-level intention-to-treat analysis was conducted adjusting for clustering within clubs and baseline values. Findings: Between February 2018 and May 2019, 782 individuals were screened and 494 (89% female) were enrolled. Participants from 28 clusters were allocated to Lifestyle Africa (15, n=240) or usual care (13, n=254). Fidelity assessments indicated the intervention was generally delivered as intended. The modal number of sessions held across all clubs was 17 and the mean attendance of participants across all sessions was 61%. Outcome assessment was completed by 215 (90%) intervention and 223 (88%) control participants. Average weight change was -0·67% (95% CI = -1·28 – -0·06) in Lifestyle Africa and 0·47% (95% CI = -1·08 – 0·14) in control with no significant difference (group difference = -0·20%, 95% CI -1·06 – 0·67; p = 0·65). However, HbA1c was significantly lower at follow-up in Lifestyle Africa compared to the usual care group (mean difference = -0·26, 95% CI -0·41 – -0·11, p = 0·0009). There were no significant differences between groups in the other outcomes. Interpretation: Lifestyle Africa was feasible for CHWs to deliver and although it had no effect on weight loss it had a significant effect on HbA1c. The intervention holds promise for addressing cardiovascular disease and diabetes at scale in LMIC. Clinical Trial Registration Details: ClinicalTrials.gov (NCT03342274). Funding Information: Supported by the National Heart Lung and Blood Institute of the National Institutes of Health (R01HL126099). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The study was approved by the ethics committees at the University of Cape Town (primary) and Children’s Mercy Kansas City. Participants completed written informed consent.

Background Low- and middle-income countries (LMICs) are experiencing major increases in diabetes and cardiovascular conditions linked to overweight and obesity. Lifestyle interventions such as the United States National Diabetes Prevention Program (DPP) developed in high-income countries require adaptation and cultural tailoring for LMICs. The objective of this study was to evaluate the efficacy of “Lifestyle Africa,” an adapted version of the DPP tailored for an underresourced community in South Africa compared to usual care. Methods and findings Participants were residents of a predominantly Xhosa-speaking urban township of Cape Town, South Africa characterized by high rates of poverty. Participants with body mass index (BMI) ≥ 25 kg/m2 who were members of existing social support groups or “clubs” receiving health services from local nongovernmental organizations (NGOs) were enrolled in a cluster randomized controlled trial that compared Lifestyle Africa (the intervention condition) to usual care (the control condition). The Lifestyle Africa intervention consisted of 17 video-based group sessions delivered by trained community health workers (CHWs). Clusters were randomized using a numbered list of the CHWs and their assigned clubs based on a computer-based random allocation scheme. CHWs, participants, and research team members could not be blinded to condition. Percentage weight loss (primary outcome), hemoglobin A1c (HbA1c), blood pressure, triglycerides, and low-density lipoprotein (LDL) cholesterol were assessed 7 to 9 months after enrollment. An individual-level intention-to-treat analysis was conducted adjusting for clustering within clubs and baseline values. Trial registration is at ClinicalTrials.gov (NCT03342274). Between February 2018 and May 2019, 782 individuals were screened, and 494 were enrolled. Participants were predominantly retired (57% were receiving a pension) and female (89%) with a mean age of 68 years. Participants from 28 clusters were allocated to Lifestyle Africa (15, n = 240) or usual care (13, n = 254). Fidelity assessments indicated that the intervention was generally delivered as intended. The modal number of sessions held across all clubs was 17, and the mean attendance of participants across all sessions was 61%. Outcome assessment was completed by 215 (90%) intervention and 223 (88%) control participants. Intent-to-treat analyses utilizing multilevel modeling included all randomized participants. Mean weight change (primary outcome) was −0.61% (95% confidence interval (CI) = −1.22, −0.01) in Lifestyle Africa and −0.44% (95% CI = −1.06, 0.18) in control with no significant difference (group difference = −0.17%; 95% CI = −1.04, 0.71; p = 0.71). However, HbA1c was significantly lower at follow-up in Lifestyle Africa compared to the usual care group (mean difference = −0.24, 95% CI = −0.39, −0.09, p = 0.001). None of the other secondary outcomes differed at follow-up: systolic blood pressure (group difference = −1.36; 95% CI = −6.92, 4.21; p = 0.63), diastolic blood pressure (group difference = −0.39; 95% CI = −3.25, 2.30; p = 0.78), LDL (group difference = −0.07; 95% CI = −0.19, 0.05; p = 0.26), triglycerides (group difference = −0.02; 95% CI = −0.20, 0.16; p = 0.80). There were no unanticipated problems and serious adverse events were rare, unrelated to the intervention, and similar across groups (11 in Lifestyle Africa versus 13 in usual care). Limitations of the study include the lack of a rigorous dietary intake measure and the high representation of older women. Conclusions In this study, we found that Lifestyle Africa was feasible for CHWs to deliver and, although it had no effect on the primary outcome of weight loss or secondary outcomes of blood pressure or triglycerides, it had an apparent small significant effect on HbA1c. The study demonstrates the potential feasibility of CHWs to deliver a program without expert involvement by utilizing video-based sessions. The intervention may hold promise for addressing cardiovascular disease (CVD) and diabetes at scale in LMICs. Trial registration ClinicalTrials.gov NCT03342274.

Objective: Sequestosome 1 (p62/SQSTM1) is a multifunctional scaffold/adaptor protein encoded by the p62/SQSTM1 gene with function in cellular homeostasis. Mutations in the p62/SQSTM1 gene have been known to be associated with patients with Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Dementia (FTD), and Parkinson Disease (PD). The aim of the present study was to create a novel model of human neurogenerative disease in Drosophila melanogaster by altering the expression of Ref(2)P, the Drosophila orthologue of the human p62/SQSTM1 gene. Ref(2)P expression was altered in all neurons, the dopaminergic neurons and in the motor neurons, with longevity and locomotor function assessed over time.Results: Inhibition of Ref(2)P resulted in a significantly increased median lifespan in the motor neurons, followed by a severe decline in motor skills. Inhibition of Ref(2)P in the dopaminergic neurons resulted in a significant, but minimal increase in median lifespan, accompanied by a drastic decline in locomotor function. Inhibition of Ref(2)P in the ddc-Gal4-expressing neurons resulted in a significant increase in median lifespan, while dramatically reducing motor function.

Background: Valosin-Containing Protein (VCP) is an essential AAA+ ATPase with diverse functions within the cell. Mutations in the VCP gene have been detected in patients with familial amyotrophic lateral sclerosis (ALS). The aim of this study is to create a novel model of human neurodegenerative disease in Drosophila melanogaster by altering the expression of TER94, the Drosophila orthologue of the human VCP gene. TER94 expression was altered in all neurons, the dopaminergic neurons and in the motor neurons, with longevity and locomotor function assessed over time. Altered TER94 expression in combination with the altered expression of known Parkinson Disease (PD) genes was examined to investigate potential interactions.Results: Inhibition of TER94 altered median lifespan in a manner dependent upon the transgene selected for use and the tissue-specific expression directed by the Gal4 transgene selected. Locomotor ability was significantly reduced in all cases of TER94 inhibition tested. The inhibition of TER94 by two TER94-RNAi inhibitory transgenes, in the motor neurons via D42-Gal4 lead to increases in median lifespan, with one inhibitory transgene generating a slightly reduced lifespan. Inhibition of TER94 in the dopaminergic neurons resulted in a severe reduction in lifespan. The co-inhibition of TER94 and parkin in the neurons resulted in a major decline in lifespan by approximately 30%. While the inhibition of TER94 and the co-expression of alpha-synuclein in the neurons resulted in an increase in lifespan by approximately 28%. Conclusions: The inhibition of TER94 in the motor neurons is an interesting model of ALS, due to the small, but reduced lifespan coupled with a strong decline in locomotor function. The inhibition of TER94 in the dopaminergic neurons is a potential model of ALS, due to the reduction of both lifespan and locomotor function over time. The co-inhibition of TER94 and parkin in the neurons provides a promising novel model of neurodegenerative disease, displaying a great reduction in lifespan and in locomotor ability over time.

Background Maternal retention in HIV care is lower for women in the postpartum period than during pregnancy, but the reasons are poorly understood. We examined key differences in barriers to retention in HIV care during and after pregnancy. Methods We conducted semi-structured, in-depth interviews with 30 postpartum women living with HIV. Participants were recruited from two tertiary facilities implementing Option B+ for prevention of mother-to-child HIV transmission in Accra, Ghana. We collected data from mothers who had disengaged from HIV care and those who were still engaged in care. The interviews were analyzed using principles adapted from grounded theory. Results Participants’ experiences and narratives showed that retention in HIV care was more challenging during the postpartum period than during pregnancy. Poor maternal physical health (from birth complications and cesarean section), socio-cultural factors (norms about newborn health and pregnancy), and economic difficulties linked to childbirth (such as unemployment, under-employment, and debt) made the costs of retention in HIV care more economically and socially expensive in the postpartum period than during pregnancy. Some participants also shared that transportation costs and resulting dependence on a partner to pay increased during the postpartum period because of a strong shift in maternal preference for private modes of transportation due to HIV stigma and the desire to protect the newborn. These factors played a larger role in the postpartum period than during pregnancy and created a significant barrier to retention. A conceptual model of how these factors interrelate, the synergy between them, and how they affect retention in the postpartum period is presented. Conclusions In Ghana, lower retention in HIV care in the postpartum period compared to in pregnancy may be primarily driven by social, economic, and newborn health factors. Multifaceted economic-based and stigma-reduction interventions are needed to increase retention in maternal HIV care after childbirth.

Context Among people living with HIV in Uganda, desires to have a child and unplanned pregnancies are both common, while utilization of safer conception methods (SCM) and modern contraceptives are low. Methods Three hundred eighty-nine HIV clients who reported considering childbearing with their uninfected partner enrolled in a safer conception counseling intervention trial in Uganda. Multiple regression analysis and baseline data were used to examine correlates of reproductive intentions and behaviors, including use of safer conception methods and contraception. Results Most (n = 313; 80.5%) reported that both they and their partner wanted to have a child now, which was associated with being married, in a longer relationship, not having a child with partner, greater SCM knowledge, lower internalized childbearing stigma, and higher perceived community stigma of childbearing. However, just 117 reported trying to conceive in the prior 6 months, which was associated with being female, not having a child with their partner, less decision-making control within the relationship, and greater perceived cultural acceptability of SCM. Among those who had tried to conceive in the past 6 months, 14 (11.9%) used SCM, which was associated with greater control in decision making. Of the 268 who were not trying to conceive, 69 (25.7%) were using a modern contraceptive, which was associated with being in a shorter relationship, less control over decision-making, more positive attitudes towards contraception and lower depression. Conclusion Methods to promote reproductive goals are underused by HIV serodiscordant couples, and relationships characteristics and childbearing-related stigma appear to be most influential and thus targets for intervention. Trial registration Clinicaltrials.gov, NCT03167879; date registered May 23, 2017.

* Abbreviations: COVID-19 — : coronavirus disease SNAP — : Supplemental Nutrition Assistance Program Nationwide closures of elementary and secondary schools due to the novel coronavirus disease (COVID-19) have severed nearly 60 million students from critical educational and health resources. As the impact of COVID-19 unfolds, pandemic-related trauma and economic instability will disproportionately impact children in poverty, who most heavily rely on school-based services for nutritional, physical, and mental health needs. Yet amid months of public health and political discourse and the passage of 4 federal relief bills, including the historically unmatched $2 trillion Coronavirus Aid, Relief, and Economic Security Act, measures to mitigate risk for educational and health disparities among children have been woefully lacking. Beyond provision of clinical and infection control guidance, the pediatric community must advocate for stronger action to ensure the educational, nutritional, physical, and mental health needs of children are met during periods of school closures and addressed during plans for reopening (Table 1). View this table: TABLE 1 Pediatric advocacy suggestions, tools, and resources. Action is needed to offset the risk for educational losses among all children as well as exacerbated educational disparities among children in poverty. Unforeseen extended school closures can lead to lower test scores, lower educational attainment, and decreased earning potential.1 During closures, students need reliable access to technology, a stable learning environment, and parents with the necessary time and skills to support for remote learning. Although remote learning presents a challenge for all families, those in poverty are at greater … Address correspondence to Abbey R. Masonbrink, MD, MPH, Department of Pediatrics, Children’s Mercy Kansas City, 2401 Gilham Rd, Kansas City, MO 64108. E-mail: armasonbrink{at}cmh.edu

Background Children in food-insecure families face increased barriers to meeting recommendations for fruit and vegetable consumption. Hospitals and pediatric healthcare institutions have attempted to alleviate food-insecurity through various internal programs like food prescriptions, yet little evidence for these programs exist. Consistent with a patient-centered perspective, we sought to develop a comprehensive understanding of barriers to fruit and vegetable consumption and a parent-driven agenda for healthcare system action. Methods We conducted six qualitative focus group discussions (four in English, two in Spanish) with 29 parents and caregivers of patients who had screened positive for food-insecurity during visits to a large pediatric healthcare system in a midwestern U.S. city. Out iterative analysis process consisted of audio-recording, transcribing and coding discussions, aiming to produce a) a conceptual framework of barriers to fruit and vegetable consumption and b) a synthesis of participant programmatic suggestions for their healthcare system. Results Participants were 90% female, 41% Black/African American and 41% Hispanic/Latino. Barriers to fruit and vegetable consumption in their families fell into three intersecting themes: affordability, accessibility and desirability. Participant-generated intervention recommendations were multilevel, suggesting healthcare systems focus not only on clinic and community-based action, but also advocacy for broader policies that alleviate barriers to acquiring healthy foods. Conclusion Parents envision an expanded role for healthcare systems in ensuring their children benefit from a healthy diet. Finding offers critical insight on why clinic-driven programs aimed to address healthy eating may have failed and healthcare organizations may more effectively intervene by adopting a multilevel strategy.

To assess the impact of a 90-second animated video on parents' interest in receiving an antibiotic for their child.This pre-post test study enrolled English and Spanish speaking parents (n = 1051) of children ages 1-5 years presenting with acute respiratory tract infection symptoms. Before meeting with their provider, parents rated their interest in receiving an antibiotic for their child, answered 6 true/false antibiotic knowledge questions, viewed the video, and then rated their antibiotic interest again. Parents rated their interest in receiving an antibiotic using a visual analogue scale ranging from 0 to 100, with 0 being "I definitely do not want an antibiotic," 50 "Neutral," and 100 "I absolutely want an antibiotic."Parents were 84% female, with a mean age of 32 ± 6.0, 26.0% had a high school education or less, 15% were black, and 19% were Hispanic. After watching the video, parents' average antibiotic interest ratings decreased by 10 points (mean, 57.0 ± 20 to M ± 21; P .0001). Among parents with the highest initial antibiotic interest ratings (≥60), even greater decreases were observed (83.0 ± 12.0 to 63.4 ± 22; P .0001) with more than one-half (52%) rating their interest in the low or neutral ranges after watching the video.A 90-second video can decrease parents' interest in receiving antibiotics, especially among those with higher baseline interest. This scalable intervention could be used in a variety of settings to reduce parents' interest in receiving antibiotics.ClinicalTrials.gov: NCT03037112.

Rates of cardiovascular disease and diabetes are rising in low- and middle-income countries (LMIC), but there is a dearth of research devoted to developing and evaluating chronic disease interventions in these settings, particularly in Africa. Lifestyle Africa is a novel, culturally adapted version of the Diabetes Prevention Program (DPP) being evaluated in an ongoing community-based cluster-randomized trial in an underresourced urban community in South Africa. The purpose of this study is to describe the adaptations and adaptation process used to develop the program and to report preliminary implementation findings from the first wave of groups (n = 11; 200 individuals) who participated in the intervention. The RE-AIM model and community advisory boards guided the adaptation process. The program was designed to be delivered by community health workers (CHWs) through video-assisted sessions and supplemented with text messages. Participants in the trial were overweight and obese members of existing chronic disease “support groups” served via CHWs. Implementation outcomes included completion of sessions, session attendance, fidelity of session delivery, and participant satisfaction. Results indicated that 10/11 intervention groups completed all 17 core sessions. Average attendance across all sessions and groups was 54% and the percentage who attended at least 75% of sessions across all groups was 35%. Fidelity monitoring indicated a mean of 84% of all required procedures were completed while overall communication skills were rated as “good" to “excellent”. These preliminary results support the feasibility of culturally adapting the DPP for delivery by CHWs in underresourced settings in LMIC.

Infants born to HIV-infected mothers are more likely to be low birthweight (LBW) than other infants, a condition that is stigmatized in many settings worldwide, including sub-Saharan Africa. Few studies have characterized the social-cultural context and response to LBW stigma among mothers in sub-Saharan Africa or explored the views of women living with HIV (WLHIV) on the causes of LBW. We purposively sampled thirty postpartum WLHIV, who had given birth to either LBW or normal birthweight infants, from two tertiary hospitals in Accra, Ghana. Using semi-structured interviews, we explored women's understanding of the etiology of LBW, and their experiences of caring for a LBW infant. Interviews were analyzed using interpretive phenomenology. Mothers assessed their babies' smallness based on the baby's size, not hospital-recorded birthweight. Several participants explained that severe depression and a loss of appetite, linked to stigma following an HIV diagnosis during pregnancy, contributed to infants being born LBW. Women with small babies also experienced stigma due to the newborns' "undesirable" physical features and other people's unfamiliarity with their size. Consequently, mothers experienced blame, reluctance showing the baby to others, and social gossip. As a result of this stigma, women reported self-isolation and depressive symptoms. These experiences were layered on the burden of healthcare and infant feeding costs for LBW infants. LBW stigma appeared to attenuate with increased infant weight gain. A few of the women also did not breastfeed because they thought their baby's small size indicated pediatric HIV infection. Among WLHIV in urban areas in Ghana, mother and LBW infants may experience LBW-related stigma. A multi-component intervention that includes reducing LBW incidence, treating antenatal depression, providing psychosocial support after a LBW birth, and increasing LBW infants' weight gain are critically needed.

Background With rates of childhood obesity continually increasing, effective physical activity and nutrition interventions are needed. Formative research is used to tailor interventions to different cultural and geographic contexts and can be vital in adapting intervention strategies in the face of significant disruptive circumstances (like COVID-19). Objective We conducted formative research via in-person and web-based focus groups among middle schoolers and parents to better understand the facilitators and barriers to physical activity and fruit and vegetable consumption and to inform the design of a large intervention for a low-income, urban setting in the US Midwest. Methods We conducted 2 phases of qualitative focus groups with parents (n=20) and 6th-9th grade middle schoolers (n=23). Phase 1 was conducted prior to the COVID-19 pandemic in late 2019, and phase 2 was conducted during the COVID-19 pandemic in the summer of 2020. Focus groups were transcribed and thematically coded using the Dedoose software. Results The main facilitators of physical activity prior to the pandemic included the opportunity to have fun, peer influence, competition (for some), and incentives, while the main barriers to physical activity were time constraints and social discomfort. The main facilitators of eating fruits and vegetables included parental influence, preparation technique, and convenience, while barriers included dislike of vegetables, time constraints, and preparation or freshness. During the pandemic, facilitators of physical activity remained the same, while additional barriers to physical activity such as lack of motivation and limited time spent outside of the home were reported. For fruit and vegetable consumption, both facilitators and barriers remained the same for both time periods. Additionally, for some participants, the pandemic offered an opportunity to offer more fruits and vegetables to middle schoolers throughout the day. Conclusions Some themes identified were common to those reported in previous studies, such as peer influence on physical activity and parental influence on fruit and vegetable consumption. Novel themes such as lack of motivation to be active and limited time outside the home helped improve intervention adaptation, specifically during the COVID-19 pandemic. The continuity of formative research after a major unexpected change in the intervention context can be essential in targeting areas of an intervention that can be retained and those that need to be adjusted.

About 40% of HIV-positive women in sub-Saharan Africa become pregnant post-diagnosis. Despite about half of their pregnancies being planned, safer conception methods (SCM) are underutilized among serodiscordant couples, partially due to the fact that safer conception counseling (SCC) has not been integrated into routine HIV family planning (FP) services. Our Choice is a comprehensive FP intervention that promotes unbiased childbearing consultations to ensure clients receive SCC or contraception services to achieve their desired reproductive goals. The intervention is theoretically grounded and has demonstrated preliminarily feasibility and acceptance through pilot testing. This three-arm cluster randomized controlled trial compares two implementation strategies for integrating Our Choice into routine FP services vs. usual care. Six sites in Uganda will be randomized to receive either (1) Our Choice intervention with enhanced training and supervision provided by study staff (SCC1), (2) Our Choice intervention implemented by the Ministry of Health’s standard approach to disseminating new services (SCC2), or (3) existing FP services (usual care). Our Choice and usual care FP services will be implemented simultaneously over a 30-month period. Sixty clients in serodiscordant relationships who express childbearing desires will be enrolled by a study coordinator at each site (n = 360) and followed for 12 months or post-pregnancy (once, if applicable). Analysis will compare intervention arms (SCC1 and SCC2) to usual care and then to each other (SCC1 vs. SCC2) on the primary outcome of correct use of either SCM (if trying to conceive) or dual contraception (if pregnancy is not desired). Secondary outcomes (i.e., pregnancy, use of prevention of mother-to-child transmission services, condom use, and partner seroconversion) and cost-effectiveness will also be examined. Findings will provide critical information about the success of implementation models of varying intensity for integrating SCC into FP, thereby informing policy and resource allocation within and beyond Uganda. NCT03167879 ClinicalTrials.gov, Registered 30 May, 2017.

High rates of fertility desires, childbearing and serodiscordant partnerships among people living with HIV (PLHIV) in Uganda underscore the need to promote use of safer conception methods (SCM). Effective SCM exist but few PLHIV benefit from provider-led safer conception counseling (SCC) and comprehensive national SCC guidelines are still lacking. Providers' self-efficacy, intentions and attitudes for SCC impact provision and should inform development of services, but there are no longitudinal studies that assess these important constructs. This study reports on changes in providers' knowledge, attitudes, motivation and confidence to provide SCC among a 24-month observational cohort of Ugandan HIV providers. Compared to baseline, providers evidenced increased awareness of SCM, perceived greater value in providing SCC, saw all SCM but sperm washing as likely to be acceptable to clients, reported consistently high interest in and peer support for providing SCC, and perceived fewer barriers at the 24-month follow-up. Providers' intentions for providing SCC stayed consistently high for all SCM except manual self-insemination which decreased at 24 months. Self-efficacy for providing SCC increased from baseline with the greatest improvement in providers' confidence in advising serodiscordant couples where the man is HIV-infected. Providers consistently cite the lack of established guidelines, training, and their own reluctance to broach the issue with clients as significant barriers to providing SCC. Despite providers being more interested and open to providing SCC than ever, integration of SCC into standard HIV services has not happened. Concerted efforts are needed to address remaining barriers by establishing national SCC guidelines and implementing quality provider training.