Zasp52 strengthens whole embryo tissue integrity through supracellular actomyosin networks.

During morphogenesis, large-scale changes of tissue primordia are coordinated across an embryo. In Drosophila, several tissue primordia and embryonic regions are bordered or encircled by supracellular actomyosin cables, junctional actomyosin enrichments networked between many neighbouring cells. We show that the single Drosophila Alp/Enigma-family protein Zasp52, which is most prominently found in Z-discs of muscles, is a component of many supracellular actomyosin structures during embryogenesis, including the ventral midline and the boundary of the salivary gland placode. We reveal that Zasp52 contains within its central coiled-coil region a type of actin-binding motif usually found in CapZbeta proteins, and this domain displays actin-binding activity. Using endogenously-tagged lines, we identify that Zasp52 interacts with junctional components, including APC2, Polychaetoid and Sidekick, and actomyosin regulators. Analysis of zasp52 mutant embryos reveals that the severity of the embryonic defects observed scales inversely with the amount of functional protein left. Large tissue deformations occur where actomyosin cables are found during embryogenesis, and in vivo and in silico analyses suggest a model whereby supracellular Zasp52-containing cables aid to insulate morphogenetic changes from one another.

Syphilis Prevalence Among People Living With and Without HIV in Sub-Saharan Africa: A Systematic Review and Meta-Analysis.

BACKGROUND: Syphilis is a curable sexually transmitted infection that, untreated, is associated with significant morbidity and mortality. In people living with HIV (PLWH), syphilis carries greater risks of disease progression. We estimated syphilis prevalence among PLWH in the general population in sub-Saharan Africa and compared the prevalence among PLWH and without HIV. METHODS: We searched for studies published January 1, 2011, to March 28, 2022, reporting syphilis prevalence among PLWH in sub-Saharan Africa (PROSPERO No. CRD42020167328). We excluded studies in high-risk subpopulations. We estimated pooled syphilis prevalence among PLWH using random-effects modeling and compared the prevalence with people without HIV when included in the same study. We examined influences of region, study setting, and test type in subgroup analyses. RESULTS: We identified 926 studies; 53 were included in the meta-analysis. Pooled syphilis prevalence among PLWH was 7.3% (95% confidence interval [CI], 6.3%-8.5%). Prevalence differed by region: 3.1% (95% CI, 2.2%-4.0%) in Southern, 5.5% (95% CI, 2.3%-9.3%) in West/Central, and 10.5% (95% CI, 8.0%-13.1%) in Eastern Africa. Prevalence also differed by study setting: 13.8% (95% CI, 5.7%-23.0%) in sexual and reproductive health/sexually transmitted infection care, 8.7% (95% CI, 5.0%-12.8%) in HIV care, 7.1% (95% CI, 5.8%-8.5%) in antenatal care, and 3.8% (95% CI, 2.0%-5.8%) in household/community-based settings. Syphilis prevalence was higher among PLWH than without HIV (relative risk, 3.5; 95% CI, 2.8-4.5). CONCLUSIONS: Syphilis is highly prevalent among PLWH in sub-Saharan Africa and is more common among PLWH than without HIV. Integration of syphilis screening and management into HIV care may reduce complications of HIV-syphilis coinfection among PLWH in sub-Saharan Africa.

Systematic Review and Meta-analysis of Linkage to HIV Care Interventions in the United States, Canada, and Ukraine (2010-2021).

We conducted a systematic review and meta-analysis of interventions targeting linkage to HIV care in the US, Canada, and Europe. We searched six databases (PubMed, Embase, Cochrane Library, Web of Science and CINAHL). Inclusion criteria were English language studies in adults in the US, Canada, or Europe, published January 1, 2010 to January 1, 2021. We synthesized interventions by type and linkage to care outcome. The outcome was cumulative incidence of 3-month linkage. We estimated cumulative incidence ratios of linkage with 95% confidence intervals (CIs). We screened 945 studies; 13 met selection criteria (n = 1 from Canada, n = 1 from Ukraine, n = 11 from the US) and were included after full text review (total 37,549 individuals). The cumulative incidence of 3-month linkage in the intervention group was 0.82 (95% CI 0.68-0.94) and control group 0.71 (95% CI 0.50-0.90); cIR of linkage for intervention versus control was 1.30 (95% CI 1.13, 1.49). Interventions to improve linkage to care after HIV diagnosis warrant further attention.

The NICU tracheostomy team: multidisciplinary collaboration for improvement in survival of complex patients.

OBJECTIVE: Evaluate feasibility and impact of "Tracheostomy Team" on survival and length of stay (LOS) at a level IV NICU. METHODS: Plan-do-study-act cycles targeted five Global Tracheostomy Collaborative "key drivers". From January 2017 to December 2022 multidisciplinary, bimonthly bedside rounds were conducted. RESULTS: After 3 cycles, in-hospital survival among 39 patients with tracheostomy improved and sustained from 67% to 100% (baseline 18/27; 66.7%; QI 35/39, 89.7%; p = 0.03). Median LOS (days [IQR]) did not significantly differ between baseline and QI (237 [57-308] vs. 217 [130-311]; p = 0.9). Among patients with BPD, median LOS was higher after QI interventions (baseline 248 [222-308] vs. QI 332.5 [283.5-392]; p = .02). Special cause variation resulted from peak increase in LOS during the COVID19 pandemic (2021). Tracheitis/pneumonia was treated significantly more frequently in QI BPD patients. CONCLUSION: Multidisciplinary approach is feasible, resulting in improved survival without a sustained increase in LOS. Future QI efforts should address post-operative infectious complications.

Evaluation of Hepatitis C Treatment Outcomes Among Patients Enrolled in Outpatient Parenteral Antibiotic Therapy-Boston, Massachusetts, 2016-2021.

In our Boston-based outpatient parenteral antibiotic therapy (OPAT) program between 2016 and 2021, we found that a low proportion of patients with active hepatitis C virus (HCV) were prescribed HCV treatment by their OPAT provider and few achieved sustained virologic response. Clinicians should consider concurrent HCV treatment during OPAT.

Factors Associated With Coronavirus Disease 2019 Vaccine Uptake Among Pregnant Women and Nonpregnant Women of Reproductive Age in Jamaica.

Background: Despite high rates of coronavirus disease 2019 (COVID-19)-related maternal mortality, Jamaica currently has little data on COVID-19 vaccine uptake among pregnant women. Methods: We conducted a cross-sectional, web-based survey of 192 reproductive-aged women in Jamaica from February 1 to 8, 2022. Participants were recruited from a convenience sample of patients, providers, and staff at a teaching hospital. We assessed self-reported COVID-19 vaccination status and COVID-19-related medical mistrust (operationalized as vaccine confidence, government mistrust, and race-based mistrust). We used multivariable modified Poisson regression to test the association between vaccine uptake and pregnancy. Results: Of 192 respondents, 72 (38%) were pregnant. Most (93%) were Black. Vaccine uptake was 35% in pregnant women versus 75% in nonpregnant women. Pregnant women were more likely to cite healthcare providers versus the government as trustworthy sources of COVID-19 vaccine information (65% vs 28%). Pregnancy, low vaccine confidence, and government mistrust were associated with a lower likelihood of COVID-19 vaccination (adjusted prevalence ratio [aPR] = 0.68 [95% confidence interval {CI}, .49-.95], aPR = 0.61 [95% CI, .40-.95], and aPR = 0.68 [95% CI, .52-.89], respectively). Race-based mistrust was not associated with COVID-19 vaccination in the final model. Conclusions: Pregnancy, low vaccine confidence, and government mistrust were associated with a lower likelihood of COVID-19 vaccination among reproductive-aged women in Jamaica. Future studies should evaluate the efficacy of strategies proven to improve maternal vaccination coverage, including standing "opt-out" vaccination orders and collaborative provider and patient-led educational videos tailored for pregnant individuals. Strategies that decouple vaccine messaging from government agencies also warrant evaluation.

Overweight and obese youth with type 1 or type 2 diabetes share similar elevation in triglycerides during middle and late adolescence.

BACKGROUND: Overweight and obesity have been observed in children with type 1 diabetes (T1D). This further increases their future risk of Cardiovascular Disease (CVD) as well as the development of other risk factors, such as dyslipidemia. AIMS: To compare lipid profiles in children and adolescents with Type 1 diabetes and lean mass (T1L), Type 1 diabetes and overweight or obese (T1OW/OB), and type 2 diabetes (T2D). METHODS: This was a cross-sectional study of 669 patients with T1D or T2D aged 2-19 years using retrospective data collected from 2003 to 2014. Included patients were categorized into lean (BMI < 85th ile and overweight or Obese (BMI ≥ 85th ile). Patients were subcategorized into three age groups: < 10 years, 10-14 years, and 15-19 years. RESULTS: 7.6% of patients had T2D. Of the patients with T1D, 58.9% were lean, 26.4% were overweight, and 14.7% were obese. Total Cholesterol (TC), Low-density lipoprotein cholesterol (LDL-C) and Non-HDL-C levels were similar across groups. In the 15-19 years group, Triglycerides (TG) levels were significantly higher in T1OW/OB and similar to T2D. High-density lipoprotein Cholesterol (HDL-C) was significantly lower in T2D. Weight status significantly correlated with TG and HDL-C levels in T1D and T2D groups. CONCLUSIONS: T1OW/OB constitutes a significant proportion of the T1D population. Patients with obesity and T1D, especially if in their late adolescence, have an adverse lipid profile pattern that is comparable to adolescents with T2D. Based on these findings, risk for future CVD in T1OW/OB and T2D may be equivalent.

Breast Cancer Awareness and Barriers to Early Presentation in the Gaza-Strip: A Cross-Sectional Study.

PURPOSE: Timely detection of breast cancer (BC) is important to reduce its related deaths. Hence, high awareness of its symptoms and risk factors is required. This study aimed to assess the awareness level of BC among females in Gaza. MATERIALS AND METHODS: A cross-sectional study was performed during September and October 2017 in Gaza, Palestine. Stratified sampling was used to recruit patients from four hospitals and seven high schools. The validated Breast Cancer Awareness Measure (BCAM) was used to assess confidence and behavior in relation to breast changes, awareness of BC symptoms and risk factors, barriers to seek medical help, and knowledge of BC screening. Women (age ≥ 18 years) visiting or admitted to any of the four hospitals, and female adolescents (age 15 to 17 years) in any of the seven schools, were recruited for face-to-face interviews to complete the BCAM. RESULTS: Of 3,055 women approached, 2,774 participants completed the BCAM questionnaire (response rate, 90.8%); 1,588 (57.2%) were adults, and 1,186 (42.8%) were adolescents. Of these, 1,781 (64.2%) rarely (or never) checked their breasts, and 909 (32.8%) were not confident to notice changes. In total, 1,675 (60.4%) were aware of the availability of BC screening programs. The overall mean ± standard deviation score for awareness of BC symptoms was 5.9 ± 2.9 of 11, and that of risk factors 7.5 ± 3.1 of 16. Feeling scared was the most reported barrier to seeking advice reported among women (n = 802; 50.2%), whereas feeling embarrassed was the most reported in adolescents (n = 745; 62.8%). CONCLUSION: Awareness of BC symptoms, risk factors, and screening programs is suboptimal in Gaza. Educational interventions are necessary to increase public awareness of BC and to train local female breast surgeons to address barriers to early detection.

The catalytic domain of inositol-1,4,5-trisphosphate 3-kinase-a contributes to ITPKA-induced modulation of F-actin.

Inositol-1,4,5-trisphosphate-3-kinase-A (ITPKA) has been considered as an actin bundling protein because its N-terminal actin binding domain (ABD) induces formation of linear actin bundles. Since in many cancer cell lines ITPKA is essential for formation of lamellipodia, which consist of cross-linked actin filaments, here we analyzed if full length-ITPKA may induce formation of more complex actin structures. Indeed, we found that incubation of F-actin with ITPKA resulted in formation of dense, branched actin networks. Based on our result that ITPKA does not exhibit an additional C-terminal ABD, we exclude that ITPKA cross-links actin filaments by simultaneous F-actin binding with two different ABDs. Instead, stimulated-emission-depletion-microscopy and measurement of InsP3 Kinase activity give evidence that that N-terminal ABD-homodimers of ITPKA bind to F-actin while the monomeric C-termini insert between adjacent actin filaments. Thereby, they prevent formation of thick actin bundles but induce formation of thin branched actin structures. Interestingly, when embedded in this dense actin network, InsP3 Kinase activity is doubled and the product of InsP3 Kinase activity, Ins(1,3,4,5)P4 , inhibits spontaneous actin polymerization which may reflect a local negative feedback regulation of InsP3 Kinase activity. In conclusion, we demonstrate that not only the ABD of ITPKA modulates actin dynamics but reveal that the InsP3 Kinase domain substantially contributes to this process.