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In South Africa, alcohol use during pregnancy is prevalent and associated with increased HIV risk. Developing locally sensitive and contextually appropriate evidence-based interventions to address alcohol use among pregnant and breastfeeding women in South Africa requires comprehensive understanding of the context of perinatal alcohol use and how relationships and lived environments may serve as barriers or supports for alcohol reduction. We conducted twenty in-depth qualitative interviews with isiXhosa speaking women who reported alcohol use during their recent pregnancy and/or recent intimate partner violence in Cape Town, South Africa between September and November 2022. We describe patterns and drivers of ongoing alcohol use during pregnancy and map them onto levels of the socioecological model. Data were analyzed utilizing the interpretivist paradigm and interpretive thematic analysis. Eight women reported alcohol use during pregnancy, sixteen reported experiencing recent IPV, and four women reported both alcohol use during pregnancy and recent IPV. In interviews, commonly cited reasons for continued alcohol use in pregnancy included stress (e.g., due to financial concerns), peer pressure, the central role of alcohol use in socialization and the persistence of misconceptions regarding the safety of alcohol use in pregnancy. Still, despite women reporting social norms that supported continued alcohol use in pregnancy, many altered who they drank with due to fear of judgement from close friends and family, leaving them isolated from their social support system. Interventions aimed at increasing interpersonal support, such as the use of peer mentors, could prove beneficial. Although the clinic provides messaging around the harms of alcohol use in pregnancy, these messages conflict with messaging received from their peers, limiting their impact on behavior. Locally sensitive tailored, relevant programming that intervenes on barriers to reducing alcohol use in pregnancy at multiple levels of the socioeconomic model are vital to effectively addressing this public health issue.

Abstract Intimate partner violence (IPV) occurs at alarmingly high rates towards pregnant women in South Africa. Experiences of emotional, physical, and sexual IPV in pregnancy can adversely impact the health and safety of mother and fetus. Furthermore, IPV is associated with increased risk of HIV, exacerbating the public health impact of violence among pregnant women in this HIV endemic setting. In-depth understanding of cultural and contextual drivers of experiences of IPV is a critical precursor to development of interventions effectively addressing this issue among pregnant women in South Africa. The present study examines factors contributing to IPV among pregnant women to identify potential points of intervention. We conducted twenty in-depth interviews with postpartum women who used oral pre-exposure prophylaxis (PrEP) in pregnancy and reported recent experiences of IPV and/or ongoing alcohol use in a township near Cape Town, South Africa that experiences a heavy burden of both HIV and IPV. Interpretive thematic analysis was used. Several patterns of IPV during pregnancy were identified and violence was frequently described as co-occurring with male partner alcohol use. A majority of women referenced oral PrEP as their preferred method for HIV prevention, highlighting the agency and discretion it provided as beneficial attributes for women experiencing IPV. Fear of judgement from peers for remaining with an abusive partner and a lack of clear community messaging around IPV were identified as barriers to disclosure and support-seeking. Addressing the lack of social support received by women experiencing IPV during pregnancy in South Africa is essential to comprehensive IPV programming.

Background: In March 2020, Uganda enforced country-wide restrictions to control the spread of SARS-CoV-2, categorizing some health services, including family planning (FP), as non-essential. Globally, similar COVID-19 restrictions have been associated with increased vulnerability to reproductive coercion (RC) among women, due to changes in FP service availability and restricted access by partners. This study aims to investigate these dynamics in Uganda, specifically examining the impact of the COVID-19 lockdown on women's access to FP, their experiences of RC, and the relationship between RC and intimate partner violence (IPV). Methods: We conducted a cross-sectional analysis of data from 960 women participating in the AMBSO Population Health Surveillance Study (APHS) between August 2020 and March 2021 across Wakiso (N = 164) and Hoima (N = 796) districts in Uganda. Our analysis focused on women who were sexually active in the past month, using bivariate analyses to explore the associations between RC and recent experiences of sexual, physical, and verbal IPV. Findings: The most commonly reported FP methods were injectables (36.8 %) and implants (16 %). Despite the COVID-19 lockdown, less than one percent of participants reported an inability to access their preferred FP method. Notably, 3 % of the women experienced RC in the past 12 months. There was a significant association between RC and sexual IPV (p

Abstract Background Intimate partner violence (IPV) and alcohol use are interrelated public health issues. Heavy and frequent alcohol use increase the risk of IPV, but the relationship between alcohol use and IPV (including recent and lifetime IPV victimization and perpetration) has not been well described among persons living with HIV (PWH) in sub-Saharan Africa. Methods We used baseline data from the Drinker’s Intervention to Prevent Tuberculosis study. All participants were PWH co-infected with tuberculosis and had an Alcohol Use Disorders Identification Test – Consumption (AUDIT-C) positive score (hazardous drinking) and positive urine ethyl glucuronide test, indicating recent drinking. High-risk drinking was defined as AUDIT-C > 6 and/or alcohol biomarker phosphatidylethanol (PEth) ≥ 200 ng/mL. We measured IPV using the Conflict Tactics Scale. We estimated the association between alcohol use level and recent (prior six months) IPV victimization (recent perpetration was too low to study) using multivariable logistic regression models adjusted for gender, age, assets, education, spouse HIV status, religiosity, depressive symptoms, and social desirability. We additionally estimated the interaction of alcohol use and gender on IPV victimization and the association between alcohol use and lifetime victimization and perpetration. Results One-third of the 408 participants were women. Recent IPV victimization was reported by 18.9% of women and 9.4% of men; perpetration was reported by 3.1% and 3.6% of women and men. One-fifth (21.6%) of those reporting recent IPV victimization also reported perpetration. In multivariable models, alcohol use level was not significantly associated with recent IPV victimization (p = 0.115), nor was the interaction between alcohol use and gender (p = 0.696). Women had 2.34 times greater odds of recent IPV victimization than men (p = 0.016). Increasing age was significantly associated with decreased odds of recent IPV victimization (p = 0.004). Conclusion Prevalence of IPV victimization was comparable to estimates from a recent national survey, while perpetration among men was lower than expected. Alcohol use level was not associated with IPV victimization. It is possible that alcohol use in this sample was too high to detect differences in IPV. Our results suggest that women and younger PWH are priority populations for IPV prevention.

Abstract Background Persons who experience homelessness remain at increased risk for three viral blood-borne infections: human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). We assessed the yield of testing and linkage to care programs targeting this population for these infections in the United States (US). Methods We searched PubMed, Embase, Web of Science, and Cochrane Central for peer-reviewed articles through August 27, 2020. Additionally, we searched the grey literature. Two individuals independently reviewed all relevant studies to check for eligibility and extracted data for each step in the care cascade. We used random-effects model to generate weighted pooled proportions to assess yield at each step. Cumulative proportions were calculated as products of adjacent-step pooled proportions. We quantitatively synthesized data from the studies that focused on non-drug injecting individuals. Results We identified 24 studies published between 1996–2019 conducted in 19 US states. Seventeen studies screened for HIV, 12 for HCV, and two screened for HBV. For HIV, 72% of approached were recruited, 64% had valid results, 4% tested positive, 2% were given results, and 1% were referred and attended follow-up. Of positives, 25% were referred to treatment and started care. For HCV, 69% of approached were recruited, 63% had valid results, 16% tested positive, 14% were given results, and 3% attended follow-up. Of positives, 30% were referred for treatment and 19% started care. The yield at each care cascade step differs widely by recruitment strategy (for example, for HIV: 71.6% recruited of reached under service-based with zero yield under healthcare facility-based and outreach). Conclusions A very large proportion of this population reached for HIV and HCV care were lost in the follow-up steps and never received treatment. Future programs should examine drop-out reasons and intervene to reduce health disparities in this population.

Abstract Background Depression is a prevalent and serious mood disorder and a major source of disability adjusted life years (DALY) in Uganda. Furthermore, evidence from Uganda and other countries throughout sub-Saharan Africa suggests that nearly a third of persons living with human immunodeficiency virus (HIV) suffer from depression and it adversely affects healthcare seeking behavior. The high burden of disease attributable to depression makes data on the prevalence of depression in Uganda, a country with a generalized HIV epidemic, a public health priority. This paper describes the psychometric properties of the Center for Epidemiologic Studies-Depression (CES-D) measure when administered to men and women residing in three fishing communities along the shore of Lake Victoria. Methods We applied methods based on item response theory and classical test theory approaches to assess individual item characteristics, conducted exploratory factor analysis and assessed internal reliability, and construct and content validity of the measure. All analyses were performed in R Studio. Results The study sample consisted of 300 residents of fishing communities in Wakiso District, Uganda. Fifty-six percent of the sample was female and 19.7% reported being HIV positive. Seven items of the measure that did not perform well, either because they could not differentiate between levels of the latent trait or because they did not map onto the primary factor, were removed from the scale. A single factor structure best fit our final set of 13-items and we found an overall coefficient alpha of 0.89, indicating high internal consistency in this population. Conclusions Based on our findings, we recommend that future use of the CES-D in this population utilize our revised scale with the final set of 13-items. The addition of other measures that can improve the rigor of CES-D validation efforts, such as inclusion of a clinical depression measure and administration in both a clinical and a general population sample in this setting are needed.

In Uganda, depression is a major public health issue. Psychometric assessment of translated depression measures is critical to public health planning to ensure proper screening, surveillance, and treatment of depression and related outcomes. We examined aspects of the validity and reliability of the Patient Health Questionnaire-9 (PHQ-9) translated into Luganda and Runyoro among Ugandan adolescents and adults. Data from the ongoing AMBSO Population Health Surveillance study were analyzed from the Wakiso and Hoima districts in Uganda. Descriptive statistics were calculated for the overall sample and stratified by translated language. Construct validity was assessed for each translated scale using confirmatory factor analysis for ordinal data. The internal consistency of each translated scale was assessed using Cronbach's alpha, McDonald's omega total and omega hierarchical. Both the Luganda- and Runyoro-translated PHQ-9 had similar sample means (3.46 [SD ​= ​3.26] and 3.58 [SD ​= ​3.00], respectively), supported a single-factor structure, and demonstrated satisfactory internal consistency (Cronbach's alpha of 0.73 and 0.72, respectively). Our preliminary findings indicate that the Luganda and Runyoro translations of the PHQ-9 had satisfactory construct validity and internal consistency in our sample. Future studies should expand on this promising work by assessing additional psychometric characteristics of these translated measures in other communities in Uganda.

Abstract Background Homelessness increases the risk of tuberculosis (TB) disease and latent TB infection (LTBI), but persons experiencing homelessness often lack access to testing and treatment. We assessed the yield of TB testing and linkage to care for programs targeting homeless populations in the United States. Methods We conducted a comprehensive search of peer-reviewed and grey literature, adapting Cochrane systematic review methods. Two reviewers independently assessed study eligibility and abstracted key data on the testing to care cascade: number of persons reached, recruited for testing, tested for LTBI, with valid test results, referred to follow-up care, and initiating care. We used random effects to calculate pooled proportions and 95% confidence intervals (CI) of persons retained in each step via inverse-variance weighted meta-analysis, and cumulative proportions as products of adjacent step proportions. Results We identified 23 studies published between 1986 and 2014, conducted in 12 states and 15 cities. Among studies using tuberculin skin tests (TST) we found that 93.7% (CI 72.4-100%) of persons reached were recruited, 97.9% (89.3-100%) of those recruited had tests placed, 85.5% (78.6-91.3%) of those with tests placed returned for reading, 99.9% (99.6-100%) of those with tests read had valid results, and 24.7% (21.0-28.5%) with valid results tested positive. All persons testing positive were referred to follow-up care, and 99.8% attended at least one session of follow-up care. Heterogeneity was high for most pooled proportions. For a hypothetical cohort of 1000 persons experiencing homelessness reached by a targeted testing program using TST, an estimated 917 were tested, 194 were positive, and all of these initiated follow-up care. Conclusions Targeted TB testing of persons experiencing homelessness appears effective in detecting LTBI and connecting persons to care and potential treatment. Future evaluations should assess diagnostic use of interferon gamma release assays and completion of treatment, and costs of testing and treatment.

Teacher education in the United States operates within the same politically polarized and tense contexts as schools. Research predominantly relies on the voices and experiences of scholars and professionals, despite the importance of community-engaged pedagogies and learning approaches. Collective work that bridges the roles of scholars and community activists requires a shift in how teacher education is conceptualized for a new generation of intersectionality-focused anti-racist and anti-ableist teachers and teacher educators. Centering the knowledge of disabled activists, poverty scholars, and community scholars in partnership with educational professionals, we introduce Disability Centered Culturally Sustaining Pedagogies (DCCSPs), a conceptual framework and pedagogical application integrating Disability Critical Race Theory and culturally sustaining pedagogies in teacher education. We outline the critical need for this theory in teacher education in the United States and globally, opportunities for practical integration, and conclude with future directions.

The experiences of disabled girls of color have historically been ignored within and/or excluded from US educational research and thus, are often unheard and under-recognized. Few scholars use an intersectional lens to examine how inequities impact disabled girls of color. In this call to action to the research community, existing scholarship focused on their lived experiences is reviewed first. Next, the affordances of intersectionality as an axiological, methodological, and theoretical approach to educational research are discussed. As such, scholars, educators, and policymakers can use intersectionality to learn about the types of experiences disabled girls of color are having in school, including what is working and what is not working for them, from their perspectives. Therefore, intersectionality supports a deeper and more complex understanding of how schooling inequities impact students. Moreover, intersectionality supports engagement and transformation wherein scholars, educators, and policymakers act on the suggestions and solutions disabled girls of color bring forth for dismantling unjust educational systems to (re)imagine, (re)design, and (re)construct them. Finally, implications for research, practice, and policy are discussed. In sum, honoring the experiences and perspectives of disabled girls of color has the power to transform schooling.

Abstract Background Angiotensin-(1-7) is a beneficial hormone of the renin-angiotensin system known to play a positive role in regulation of blood pressure and glucose homeostasis. Previous studies have shown that in high-fat diet (HFD)-induced obese male mice, circulating angiotensin-(1-7) levels are reduced and chronic restoration of this hormone reverses diet-induced insulin resistance; however, this has yet to be examined in female mice. We hypothesized angiotensin-(1-7) would improve insulin sensitivity and glucose tolerance in obese female mice, to a similar extent as previously observed in male mice. Methods Five-week-old male and female C57BL/6J mice (8–12/group) were placed on control diet or HFD (16% or 59% kcal from fat, respectively) for 11 weeks. After 8 weeks of diet, mice were implanted with an osmotic pump for 3-week subcutaneous delivery of angiotensin-(1-7) (400 ng/kg/min) or saline vehicle. During the last week of treatment, body mass and composition were measured and intraperitoneal insulin and glucose tolerance tests were performed to assess insulin sensitivity and glucose tolerance, respectively. Mice were euthanized at the end of the study for blood and tissue collection. Results HFD increased body mass and adiposity in both sexes. Chronic angiotensin-(1-7) infusion significantly decreased body mass and adiposity and increased lean mass in obese mice of both sexes. While both sexes tended to develop mild hyperglycemia in response to HFD, female mice developed less marked hyperinsulinemia. There was no effect of angiotensin-(1-7) on fasting glucose or insulin levels among diet and sex groups. Male and female mice similarly developed insulin resistance and glucose intolerance in response to HFD feeding. Angiotensin-(1-7) improved insulin sensitivity in both sexes but corrected glucose intolerance only in obese female mice. There were no effects of sex or angiotensin-(1-7) treatment on any of the study outcomes in control diet-fed mice. Conclusions This study provides new evidence for sex differences in the impact of chronic angiotensin-(1-7) in obese mice, with females having greater changes in glucose tolerance with treatment. These findings improve understanding of sex differences in renin-angiotensin mechanisms in obesity and illustrate the potential for targeting angiotensin-(1-7) for treatment of this condition.

Objective: Patients diagnosed with peripheral artery disease are difficult to recruit into clinical trials. However, there is currently no high-quality, patient-centered information explaining why peripheral artery disease patients choose to participate or not participate in clinical research studies. Methods: The current study was a prospective community engagement initiative that specifically asked patients with and without peripheral artery disease: (1) what motivates them to participate in clinical research studies, (2) their willingness to participate in different research procedures, (3) the barriers to participation, (4) preferences about study design, and (5) demographic and disease-related factors influencing participation. Data were gathered through focus groups ( n = 19, participants aged 55–79 years) and mailed questionnaires ( n = 438, respondents aged 18–85 years). Results: More than half of the respondents stated that they would be willing to participate in a study during evening or weekend time slots. Peripheral artery disease patients ( n = 45) were more willing than those without peripheral artery disease ( n = 360) to participate in drug infusion studies (48% versus 18%, p

Abstract Early life adversity (ELA) is associated with earlier initiation and maintenance of tobacco smoking and with a greater risk of subsequent relapse. There is growing evidence that appetite hormones, including peptide YY (PYY), which modulates craving and satiety responses, play a role in stress and addiction processes. This study employed a quasi‐experimental design to examine the association between ELA and circulating PYY stress responses in smokers and nonsmokers (N = 152, ages 19–73 years) to examine the effects of nicotine addiction. Smokers initiated a quit attempt as part of the study and were classified as either abstinent smokers or relapsed smokers based on their nicotine use during the follow‐up period. PYY levels were measured at five timepoints during three lab sessions and compared between nonsmokers and the two smoking groups (abstainers, relapsers): while smokers were using nicotine ad libitum, 24 h after smokers initiated a quit attempt, and 4 weeks after smokers initiated a quit attempt. Multivariate analyses showed the main effects of time on PYY, which decreased over time within each session. The main effects of ELA during the first (ad libitum smoking) and second (24‐h post‐cessation for smokers) sessions indicated that experiencing ELA was associated with lower PYY. No systematic effect of nicotine addiction or relapse was observed in this study. These findings suggest that adults with higher ELA may experience lower PYY. Additional research is needed to further explore the role of PYY in stress and addiction processes.

Streptococcus thermophilus strain B59671 naturally produces thermophilin 110, a broad-spectrum bacteriocin encoded within the bacteriocin-like peptide (blp) gene cluster, and thermophilin 13 from a separate chromosomal locus. Analysis of the blp gene cluster revealed two genes, blpU and blpK, as potentially encoding bacteriocins. Deletion of blpK from the B59671 chromosome did not result in a loss of antimicrobial activity against either S. thermophilus ST113 or Pediococcus acidilactici F. A deletion mutant of blpU could not be generated in B59671, but the mature BlpU peptide obtained through overexpression in E. coli BL21 or chemical synthesis inhibited the growth of S. thermophilus strains, Streptococcus mutans UA159, P. acidilactici F, and Listeria innocua GV9 L-S, evidencing as a broad-spectrum bacteriocin that does not require modification for activity. This study also showed that the transcription of blpU was approximately 16-fold higher in B59671 than in an induced culture of S. thermophilus LMD-9, which produces a blp-encoded bacteriocin. The increased expression of BlpU in B59671 may explain the unique antimicrobial spectrum associated with this strain. Additionally, it was shown that a blpC deletion mutant of B59671, which prevents expression of BlpU and BlpK, inhibited the growth of other S. thermophilus strains and Bacillus cereus, suggesting that thermophilin 13 produced by B59671 possessed both intra- and interspecies antimicrobial activity. While this study confirmed that BlpU can function as an independent antimicrobial peptide, further studies are required to determine if BlpK can function independently as a broad-spectrum antimicrobial.

BackgroundPeripheral arterial disease (PAD) is a prevalent vascular disorder characterized by atherosclerotic occlusion of peripheral arteries, resulting in reduced blood flow to the lower extremities and poor walking ability. Older patients with PAD are also at a markedly increased risk of cardiovascular events, including myocardial infarction. Recent evidence indicates that inorganic nitrate supplementation, which is abundant in certain vegetables, augments nitric oxide (NO) bioavailability and may have beneficial effects on walking, blood pressure, and vascular function in patients with PAD.ObjectiveWe sought to determine if short-term nitrate supplementation (via beetroot juice) improves peak treadmill time and coronary hyperemic responses to plantar flexion exercise relative to placebo (nitrate-depleted juice) in older patients with PAD. The primary endpoints were peak treadmill time and the peak coronary hyperemic response to plantar flexion exercise.MethodsEleven PAD patients (52–80 yr.; 9 men/2 women; Fontaine stage II) were randomized (double-blind) to either nitrate-rich (Beet-IT, 0.3 g inorganic nitrate twice/day; BRnitrate) or nitrate-depleted (Beet-IT, 0.04 g inorganic nitrate twice/day, BRplacebo) beetroot juice for 4 to 6 days, followed by a washout of 7 to 14 days before crossing over to the other treatment. Patients completed graded plantar flexion exercise with their most symptomatic leg to fatigue, followed by isometric handgrip until volitional fatigue at 40% of maximum on day 4 of supplementation, and a treadmill test to peak exertion 1–2 days later while continuing supplementation. Hemodynamics and exercise tolerance, and coronary blood flow velocity (CBV) responses were measured.ResultsAlthough peak walking time and claudication onset time during treadmill exercise did not differ significantly between BRplacebo and BRnitrate, the diastolic blood pressure response at the peak treadmill walking stage was significantly lower in the BRnitrate condition. Increases in CBV from baseline to peak plantar flexion exercise after BRplacebo and BRnitrate showed a trend for a greater increase in CBV at the peak workload of plantar flexion with BRnitrate (p = 0.06; Cohen’s d = 0.56).ConclusionOverall, these preliminary findings suggest that inorganic nitrate supplementation in PAD patients is safe, well-tolerated, and may improve the coronary hyperemic and blood pressure responses when their calf muscles are most predisposed to ischemia.Clinical trial registration:https://clinicaltrials.gov/, identifier NCT02553733.

ABSTRACT: Consumers' growing interest in fermented dairy foods necessitates research on a wide array of lactic acid bacterial strains to be explored and used. This study aimed to investigate the differences in the proteolytic capacity of Lactobacillus helveticus strains B1929 and ATCC 15009 on the fermentation of commercial ultra-pasteurized (UHT) skim milk and reconstituted nonfat dried milk powder (at a comparable protein concentration, 4%). The antihypertensive properties of the fermented milk, measured by angiotensin-I-converting enzyme inhibitory (ACE-I) activity, were compared. The B1929 strain lowered the pH of the milk to 4.13 ± 0.09 at 37°C after 24 h, whereas ATCC 15009 needed 48 h to drop the pH to 4.70 ± 0.18 at 37°C. Two soluble protein fractions, one (CFS1) obtained after fermentation (acidic conditions) and the other (CFS2) after the neutralization (pH 6.70) of the pellet from CFS1 separation, were analyzed for d-/l-lactic acid production, protein concentration, the degree of protein hydrolysis, and ACE-I activity. The CFS1 fractions, dominated by whey proteins, demonstrated a greater degree of protein hydrolysis (7.9%) than CFS2. On the other hand, CFS2, mainly casein proteins, showed a higher level of ACE-I activity (33.8%) than CFS1. Significant differences were also found in the d- and l-lactic acid produced by the UHT milk between the 2 strains. These results attest that milk casein proteins possessed more detectable ACE-I activity than whey fractions, even without a measurable degree of hydrolysis. Findings from this study suggest that careful consideration must be given when selecting the bacterial strain and milk substrate for fermentation.

BackgroundGlobally, the prevalence of chronic non-communicable diseases (C-NCDs) and occurrence of multi-morbidity specifically, has been increasing and will continue to rise as life expectancy increases. The burden of mental health disorders has also been rising globally. In sub-Saharan Africa (SSA), literature on these health issues, which are interrelated, is scarce. This study assesses the prevalence of C-NCDs, and depressive and anxiety symptomology and examines the relationship between these issues among a sample of older adults in Uganda.MethodsBetween 2021-2022, 604 consenting adults aged 35 years and older were surveyed on a broad range of health issues for the ongoing AMBSO Population Health Surveillance (APHS) cohort study in Wakiso district. Descriptive analyses were performed to characterize the burden of C-NCDs (e.g. diabetes, hypertension), depression (PHQ-9 using a cutoff of ResultsMajority of participants were females (63.6%), median age was 46 (IQR: 39-54). Any C-NCDs prevalence was 18.7%, while 18.9% and 11.4%, had screening scores indicative of depressive and anxiety symptomology, respectively. Three percent (3.2%) had PHQ-9 scores indicative of moderate to severe depressive symptomology. In models adjusted for sociodemographic characteristics, there was 12% increased odds of suffering from C-NCDs for every unit increase in PHQ-9 score (AOR = 1.12, 95% CI: 1.10-1.20). Participants with any anxiety symptoms had 2.1 greater odds of suffering from C-NCD compared to those who did not have anxiety symptoms (AOR = 2.10, 95% CI: 1.21-3.70).ConclusionC-NCDs were prevalent in older adults, particularly among those experiencing mental health symptoms. Screening for C-NCDs and mental health disorders should be integrated into routine health care for older adults in the country. Early screening and identification of these health issues through primary health care could significantly reduce the public health burden attributable to mental health disorders and the incidence of multi-morbidity in Uganda.

Bacteriocin production in Streptococcus thermophilus is regulated by cell density-dependent signaling molecules, including BlpC, which regulates transcription from within the bacteriocin-like peptide (blp) gene cluster. In some strains, such as S. thermophilus ST106, this signaling system does not function properly, and BlpC must be supplied exogenously to induce bacteriocin production. In other strains, such as S. thermophilus B59671, bacteriocin (thermophilin 110 in strain B59671) production occurs naturally. Here, transcriptomic analyses were used to compare global gene expression within ST106 in the presence or absence of synthetic BlpC and within B59671 to determine if BlpC regulates the expression of genes outside the blp cluster. Real-time semi-quantitative PCR was used to find genes differentially expressed in the absence of chromosomal blpC in the B59671 background. Growth curve experiments and bacteriocin activity assays were performed with knockout mutants and BlpC supplementation to identify effects on growth and bacteriocin production. In addition to the genes involved in bacteriocin production, BlpC affected the expression of several transcription regulators outside the blp gene cluster, including a putative YtrA-subfamily transcriptional repressor. In strain B59671, BlpC not only regulated the expression of thermophilin 110 but also suppressed the production of another bacteriocin, thermophilin 13, and induced the same YtrA-subfamily transcriptional repressor identified in ST106. Additionally, it was shown that the broad-spectrum antimicrobial activity associated with strain B59671 was due to the production of thermophilin 110, while thermophilin 13 appears to be a redundant system for suppressing intraspecies growth. BlpC production or induction negatively affected the growth of strains B59671 and ST106, revealing selective pressure to not produce bacteriocins that may explain bacteriocin production phenotype differences between S. thermophilus strains. This study identifies additional genes regulated by BlpC and assists in defining conditions to optimize the production of bacteriocins for applications in agriculture or human and animal health.

This duoethnography weaves the experiences and perspectives of disabled activists, poverty scholars, community scholars of color, and university-based scholars partnering on a teacher preparation professional development project that (re)centers disability and its intersections by (a) reconsidering who creates knowledge, (b) positioning disabled activists, poverty scholars, and community scholars of color as experts with pedagogical authority, and (c) providing opportunities for teacher candidates (current and future teachers) to learn from activists and scholars in accessible, online spaces. The experiences and perspectives of multiply marginalized disabled youth and adults are often ignored and/or discounted in teacher preparation programs. However, one way to re-zone and re-people disability studies in teacher education is by teaching and learning at the intersections of critical race studies and disability studies through cross-coalitional community-university partnerships.

Abstract A cell-free DNA (cfDNA) assay would be a promising approach to early cancer diagnosis, especially for patients with dense tissues. Consistent cfDNA signatures have been observed for many carcinogens. Recently, investigations of cfDNA as a reliable early detection bioassay have presented a powerful opportunity for detecting dense tissue screening complications early. We performed a prospective study to evaluate the potential of characterizing cfDNA as a central element in the early detection of dense tissue breast cancer (BC). Plasma samples were collected from 32 consenting subjects with dense tissue and positive mammograms, 20 with positive biopsies and 12 with negative biopsies. After screening and before biopsy, cfDNA was extracted, and whole-genome next-generation sequencing (NGS) was performed on all samples. Copy number alteration (CNA) and single nucleotide polymorphism (SNP)/insertion/deletion (Indel) analyses were performed to characterize cfDNA. In the positive-positive subjects (cases), a total of 5 CNAs overlapped with 5 previously reported BC-related oncogenes (KSR2, MAP2K4, MSI2, CANT1 and MSI2). In addition, 1 SNP was detected in KMT2C, a BC oncogene, and 9 others were detected in or near 10 genes (SERAC1, DAGLB, MACF1, NVL, FBXW4, FANK1, KCTD4, CAVIN1; ATP6V0A1 and ZBTB20-AS1) previously associated with non-BC cancers. For the positive–negative subjects (screening), 3 CNAs were detected in BC genes (ACVR2A, CUL3 and PIK3R1), and 5 SNPs were identified in 6 non-BC cancer genes (SNIP1, TBC1D10B, PANK1, PRKCA and RUNX2; SUPT3H). This study presents evidence of the potential of using cfDNA somatic variants as dense tissue BC biomarkers from a noninvasive liquid bioassay for early cancer detection.

Abstract Background Awake prone positioning (APP) is widely used in the management of patients with coronavirus disease (COVID-19). The primary objective of this study was to compare the outcome of COVID-19 patients who received early versus late APP. Methods Post hoc analysis of data collected for a randomized controlled trial (ClinicalTrials.gov NCT04325906). Adult patients with acute hypoxemic respiratory failure secondary to COVID-19 who received APP for at least one hour were included. Early prone positioning was defined as APP initiated within 24 h of high-flow nasal cannula (HFNC) start. Primary outcomes were 28-day mortality and intubation rate. Results We included 125 patients (79 male) with a mean age of 62 years. Of them, 92 (73.6%) received early APP and 33 (26.4%) received late APP. Median time from HFNC initiation to APP was 2.25 (0.8–12.82) vs 36.35 (30.2–75.23) hours in the early and late APP group (p

Abstract Although the role of magnesium in blood pressure has been well studied among hypertensive patients, no study has explored the role of magnesium in hypertensive crises. The primary objective of this study is to evaluate the differences in serum magnesium levels between hypertensive crises patients and matched controls (age‐, sex‐, race‐, and diabetes‐matched) in a 1:1 random match. This study is a single‐center, retrospective, chart review, case‐control study of patients with hypertensive crises (case group) and patients without hypertensive crises (control group). Patients were included in the case group if they were 18 years of age or older with hypertensive crises and have a documented magnesium level. The control group patients were required to be 18 years of age or older, have no diagnosis of hypertensive crises, and have a documented magnesium level. The primary outcome of the study was to compare the mean serum magnesium in patients with hypertensive crises versus patients without hypertensive crises. Three hundred and fifty‐eight patients were included in the study: 179 patients in both the case group and control group. The primary outcome results showed that serum magnesium concentration was not significantly different between the case group (1.89 ± 0.29 mg/dl) and control group (1.90 ± 0.31 mg/dl) (p = .787). This study found no significant difference in serum magnesium levels in patients with hypertensive crises compared to a random matched control group. Larger observational or experimental studies may be useful to evaluate the effect of magnesium on blood pressure in hypertensive crises.

Deposition of human amyloids is associated with complex human diseases such as Alzheimer's and Parkinson's. Amyloid proteins are also produced by bacteria. The bacterial amyloid curli, found in the extracellular matrix of both commensal and pathogenic enteric bacterial biofilms, forms complexes with extracellular DNA, and recognition of these complexes by the host immune system may initiate an autoimmune response. Here, we isolated early intermediate, intermediate, and mature curli fibrils that form throughout the biofilm development and investigated the structural and pathogenic properties of each. Early intermediate aggregates were smaller than intermediate and mature curli fibrils, and circular dichroism, tryptophan, and thioflavin T analyses confirmed the establishment of a beta-sheet secondary structure as the curli conformations matured. Intermediate and mature curli fibrils were more immune stimulatory than early intermediate fibrils in vitro. The intermediate curli was cytotoxic to macrophages independent of Toll-like receptor 2. Mature curli fibrils had the highest DNA content and induced the highest levels of Isg15 expression and TNFα production in macrophages. In mice, mature curli fibrils induced the highest levels of anti-double-stranded DNA autoantibodies. The levels of autoantibodies were higher in autoimmune-prone NZBWxF/1 mice than wild-type C57BL/6 mice. Chronic exposure to all curli forms led to significant histopathological changes and synovial proliferation in the joints of autoimmune-prone mice; mature curli was the most detrimental. In conclusion, curli fibrils, generated during biofilm formation, cause pathogenic autoimmune responses that are stronger when curli complexes contain higher levels of DNA and in mice predisposed to autoimmunity.