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BACKGROUND: Ischemic stroke, accounting for 85% of stroke cases, leads to severe disabilities and increased mortality. Its global incidence rose by 87.55% from 1990 to 2019, posing significant health and economic burdens. The BRICS-plus nations-Brazil, Russia, India, China, South Africa, and five others-represent a large global population, presenting unique public health challenges. This study aims to evaluate the epidemiological trends and variations in the burden of ischemic stroke across BRICS-plus nations in a timely manner. METHODS: Data on the number, all-age rate, age-standardized rate, and relative change in ischemic stroke disability-adjusted life years (DALYs) from 1992 to 2021 within BRICS-plus were obtained from the Global Burden of Disease Study (GBD) 2021. Relationships between the DALYs rate and the Socio-demographic Index (SDI) were evaluated using Pearson correlation analyses. Additionally, age-period-cohort modeling was employed to estimate net drift, local drift, age, period, and cohort effects over the past three decades. RESULTS: From 1992 to 2021, total DALYs due to ischemic stroke increased by 47.14%, while the age-standardized DALYs rate decreased by 33.79%. All BRICS-plus countries exhibited a declining trend in the age-standardized DALYs rate over the past three decades. Egypt reported the highest age-standardized DALYs rate (2,462.60 per 100,000 population) in 2021, whereas the most substantial reduction of 59.37% was observed in Brazil. The annual net drift in the ischemic stroke DALYs rate ranged from -3.04% for Brazil to -0.48% for Egypt among the ten countries. A significant positive correlation was observed between the DALYs rate of ischemic stroke and SDI values. Countries exhibited similar age effect patterns, with an increasing risk of DALYs rate with advancing age. Period and cohort effects highlighted declines in observed nations, indicating improved ischemic stroke management strategies. CONCLUSION: The burden of ischemic stroke showed an overall declining trend across the BRICS-plus from 1992 to 2021, but persistent health inequalities between these countries were driven by socioeconomic disparities. Furthermore, it emphasizes the necessity for targeted interventions across age, period, and cohort dimensions to address the distinct challenges posed by ischemic stroke in these rapidly developing countries.

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Female sex workers (FSW) living with HIV experience greater depression and worse HIV outcomes than people living with HIV (PLHIV) overall. Mindfulness is related to lower depression and higher ART adherence in PLHIV. Few studies have assessed these relationships among FSW, especially longitudinally. This study assessed the temporal relationship between mindfulness, mental health and HIV outcomes among FSW from the Dominican Republic (DR). We analyzed data collected between 2018 and 2021 among 240 FSW using mixed modeling to assess contemporaneous relationships and time-lagged relationships between mindfulness and mental health (i.e., depression,HIV stigma, drug and alcohol use ), and HIV outcomes (i.e., ART adherence, viral suppression) , accounting for clustering of repeated measures. Greater mindfulness showed contemporaneous and time-lagged associations with lower depression (contemporaneous: b = -0.57, SE = 0.03, p < 0.001; time-lagged: b = -0.16, SE = 0.05, p < 0.001), lower HIV stigma (contemporaneous: b = -0.11, SE = 0.02, p < 0.001; time-lagged: b = -0.08, SE = 0.03, p = 0.003) and higher ART adherence (contemporaneous: b = 0.03, SE = 0.01, p = 0.003; time-lagged: b = 0.04, SE = 0.01, p = 0.004), and contemporaneous associations with reduced at-risk alcohol use and higher viral suppression (aOR = 0.99, 95% CI = 0.99-1.00, p = 0.003; aOR = 1.01, 95% CI: 1.00-1.01, p = 0.036, separately). Mindfulness instruction is a promising intervention for reducing depression and HIV stigma, and promoting better HIV outcomes among FSW living with HIV, meriting future intervention research in this area.

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Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that block inhibitors of T cell activation and function. With the widespread use of ICIs in cancer therapy, immune-related adverse events (irAEs) have gradually emerged as urgent clinical issues. Tumors not only exhibit high heterogeneity, and their response to ICIs varies, with "hot" tumors showing better anti-tumor effects but also a higher susceptibility to irAEs. The manifestation of irAEs displays a tumor-heterogeneous pattern, correlating with the tumor type in terms of the affected organs, incidence, median onset time, and severity. Understanding the mechanisms underlying the pathogenic patterns of irAEs can provide novel insights into the prevention and management of irAEs, guide the development of biomarkers, and contribute to a deeper understanding of the toxicological characteristics of ICIs. In this review, we explore the impact of tumor type on the therapeutic efficacy of ICIs and further elucidate how these tumor types influence the occurrence of irAEs. Finally, we assess key candidate biomarkers and their relevance to proposed irAE mechanisms. This paper also outlines management strategies for patients with various types of tumors, based on their disease patterns.

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BACKGROUND: To investigate the efficiency of a new method for the prevention of argentinian flag sign during the process of continuous, circular, and centered anterior capsulotomy (CCC) on the anterior capsule in cortically liquefied intumescent cataracts. This study was registered in an appropriate registry and the registration number of registration was xyy11[2022]-XJSFX-087; The date of of registration was 2022-04-29. METHODS: Preoperative examinations including slit-lamp examination, ocular A-scan ultrasonography, and Ultrasound Biomicroscopy (UBM) UBM were conducted on 61 patients with intumescent cataracts. Cases with cortically liquefied intumescent cataracts were selected and after staining with indocyanine green, the anterior chamber air bubble technique was used to compress the anterior capsule, and liquefied cortex was aspirated using a puncture needle. Corrected Distance Visual Acuity (CDVA) and intraocular pressure were recorded on postoperative days 1, 1 week, 1 month, and 6 months. Intraoperative and postoperative complications were documented and analyzed. RESULTS: Fifty eyes were identified as having cortically liquefied intumescent cataracts. No cases of the Argentinian flag sign occurred, and standard capsulorrhexis was achieved, facilitating smooth phacoemulsification. All patients achieved satisfactory outcomes at follow-ups of 1 day, 1 week, 1 month, and 6 months postoperatively. Mild corneal edema was observed in three cases on the first postoperative day, with no other complications noted. CONCLUSIONS: The anterior chamber air bubble technique combined with cortical fluid release technique can prevent the occurrence of the Argentinian flag sign in cortically liquefied intumescent cataracts, this method is simple, convenient and economic for the clinical promotion.

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Long-term exposure to ambient air pollution raises the risk of deaths and morbidity worldwide. From 1990 to 2019, we observed the epidemiological trends and age-period-cohort effects on the cardiovascular diseases (CVD) burden attributable to ambient air pollution across Brazil, Russia, India, China, and South Africa (BRICS). The number of CVD deaths related to ambient particulate matter (PM) pollution increased nearly fivefold in China [5.0% (95% CI 4.7, 5.2)] and India [5.7% (95% CI 5.1, 6.3)] during the study period. The age-standardized CVD deaths and disability-adjusted life years (DALYs) due to ambient PM pollution significantly increased in India and China but decreased in Brazil and Russia. Due to air pollution, the relative risk (RR) of premature CVD mortality (< 70 years) was higher in Russia [RR 12.6 (95% CI 8.7, 17.30)] and India [RR 9.2 (95% CI 7.6, 11.20)]. A higher period risk (2015-2019) for CVD deaths was found in India [RR 1.4 (95% CI 1.4, 1.4)] followed by South Africa [RR 1.3 (95% CI 1.3, 1.3)]. Across the BRICS countries, the RR of CVD mortality markedly decreased from the old birth cohort to young birth cohorts. In conclusion, China and India showed an increasing trend of CVD mortality and morbidity due to ambient PM pollution and higher risk of premature CVD deaths were observed in Russia and India.

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OBJECTIVES: To describe the scope of left ventricular (LV) dysfunction and left heart hypoplasia (LHH) in infants with congenital diaphragmatic hernia (CDH), to determine associations with CDH severity, and to evaluate the odds of extracorporeal membrane oxygenation (ECMO) and death with categories of left heart disease. STUDY DESIGN: Demographic and clinical variables were collected from a single-center, retrospective cohort of patients with CDH from January 2017 through May 2022. Quantitative measures of LV function and LHH were prospectively performed on initial echocardiograms. LHH was defined as ≥2 of the following: z score ≤ -2 of any left heart structure or LV end-diastolic volume <3 mL. LV dysfunction was defined as shortening fraction <28%, ejection fraction <60%, or global longitudinal strain <20%. The exposure was operationalized as a 4-group categorical variable (LV dysfunction +/-, LHH +/-). Logistic regression models evaluated associations with ECMO and death, adjusting for CDH severity. RESULTS: One hundred eight-two patients (80.8% left CDH, 63.2% liver herniation, 23.6% ECMO, 12.1% mortality) were included. Twenty percent demonstrated normal LV function and no LHH (LV dysfunction-/LHH-), 37% normal LV function with LHH (LV dysfunction-/LHH+), 14% LV dysfunction without LHH (LV dysfunction+/LHH-), and 28% both LV dysfunction and LHH (LV dysfunction+/LHH+). There was a dose-response effect between increasing severity of left heart disease, ECMO use, and mortality. LV dysfunction+/LHH + infants had the highest odds of ECMO use and death, after adjustment for CDH severity [OR (95% CI); 1.76 (1.20, 2.62) for ECMO, 2.76 (1.63, 5.17) for death]. CONCLUSIONS: In our large single-center cohort, patients with CDH with LV dysfunction+/LHH + had the highest risk of ECMO use and death.

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INTRODUCTION: Immune-mediated inflammatory diseases including rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), non-radiographic axial spondylarthritis (nr-axSpA), atopic dermatitis (AD), ulcerative colitis (UC), and Crohn's disease (CD) pose a substantial burden on patients and their quality of life. Upadacitinib is an orally administered, selective, and reversible Janus kinase inhibitor indicated for seven conditions, but data on its safety versus other active treatments are limited. A systematic literature review of indirect and direct treatment comparisons of randomized controlled trials (RCTs) was conducted to assess the safety profile of upadacitinib. METHODS: MEDLINE, Embase, and Cochrane Library databases were searched for indirect and direct treatment comparisons of RCTs that (1) included licensed upadacitinib dosages; (2) studied any of the seven conditions; (3) reported any adverse events (AEs), serious AEs (SAEs), AEs leading to discontinuation, major adverse cardiovascular event, venous thromboembolism, malignancies, infections or serious infections, and death; and (4) were published between January 2018 and August 2022. RESULTS: A total of 25 studies were eligible for inclusion. SAEs, AEs leading to discontinuation, and any AEs were commonly studied. RA was the most studied condition, followed by AD and UC. Most studies (16/25, 64%) reported no statistically significant difference in the studied safety outcomes between upadacitinib and other active treatments (e.g., tumor necrosis factor blockers, interleukin receptor antagonists, integrin receptor antagonists, T cell co-stimulation modulator), or placebo (placebo ± methotrexate or topical corticosteroids). Other studies (9/25, 36%) reported mixed results of no statistically significant difference and either statistically higher (8/25, 32%) or lower rates (1/25, 4%) on upadacitinib. CONCLUSION: Most studies suggested that upadacitinib has no statistically significant difference in the studied safety outcomes compared to active treatments or placebo in patients with RA, PsA, AS, AD, UC, and CD. A few studies reported higher rates, but findings were inconsistent with limited interpretation.

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PURPOSE: A substantial amount of evidence demonstrates suggests that long non-coding RNAs (lncRNAs) play a key role in the progression of various malignancies, cervical squamous cell carcinoma (CSCC) included. In our study, we deeply investigated the role and molecular mechanism of lncRNA NPHS2-6 in CSCC. METHODS: The expression level of gene and protein expression were measured by qRT-PCR and western blot. To test the cell proliferation and cell metastasis ability, we carried out the CCK-8 experiment, clone formation assay, transwell assay and wound healing, respectively. The interactivity among NPHS2-6, miR-1323 and SMC1B were co demonstrated using the bioinformatics tool, dual-luciferase reporter system, and RNA pulldown assay. The subcutaneous tumor model of nude mice was established to verify the results of previous studies at the in vivo. NPHS2-6 was upregulated in CSCC tissues and cells. RESULTS: NPHS2-6 deficiency significantly inhibited CSCC cell growth and EMT in vitro. In addition, NPHS2-6 deficiency also inhibited the growth of CSCC xenograft tumors in mice in vivo. Importantly, NPHS2-6 was a competing endogenous RNA (ceRNA) to increases SMC1B levels by binding to miR-1323, leading to activate the PI3K/Akt pathway, thereby exacerbating tumorigenesis of CSCC. CONCLUSIONS: In conclusion, NPHS2-6/miR-1323/SMC1B/PI3K/Akt signaling accelerates the progression of CSCC, providing a new direction for the treatment strategy of CSCC.

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Violence against women research largely excludes transgender women's experiences and violence from perpetrators other than intimate partners. This study compares patterns of violence exposure among cisgender and transgender female sex workers (FSWs) and the associations with syndemic health outcomes. We used cross-sectional surveys from samples of cisgender and transgender FSWs living with HIV in the Dominican Republic (N = 211 and 100, respectively). We used latent class analysis to identify patterns of emotional, physical, and sexual violence and harassment by partners, clients, and police. We assessed sociodemographic and occupational predictors in relation to class membership, and class membership in relation to health (HIV continuum of care outcomes, mental health, substance use), using logistic regression. Two classes were identified in cisgender sample: Low Reported Violence Exposure (Class 1) and Sex Work-related Police Harassment (Class 2). Class 2 participants had greater odds of scoring abnormal or borderline abnormal anxiety on the Hospital Anxiety and Depression Scale (HADS-A) (adjusted OR = 3.97, p<0.01), moderate-to-severe depression per the Patient Health Questionnaire-9 (PHQ-9) (aOR = 5.74, p<0.01), and any illicit drug use in the past six months (aOR = 3.06, p<0.05), compared to Class 1. The transgender sample produced three classes: Low Reported Violence Exposure (Class 1); Sex Work-related Police Harassment (Class 2); and Sex Work-related Violence and Harassment (Class 3). Class 3 participants had greater odds of having anxiety (aOR = 6.65, p<0.01) and depression (aOR = 4.45, p<0.05), while Class 2 participants had greater odds of perfect ART adherence during the previous four days (aOR = 2.78, p<0.05), compared to Class 1. The more diverse and extreme violence patterns uncovered for the transgender sample show this group's heightened risk, while similar patterns across groups regarding police abuse highlight a need for police-focused violence prevention interventions. Each sample's highest violence class was associated with poor mental health, underscoring the need for mental health interventions for all FSWs.

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OBJECTIVE: To evaluate associations between cardiac catheterization (cath) hemodynamics, quantitative measures of right ventricular (RV) function by echocardiogram, and survival in patients with congenital diaphragmatic hernia (CDH). STUDY DESIGN: This single-center retrospective cohort study enrolled patients with CDH who underwent index cath from 2003 to 2022. Tricuspid annular plane systolic excursion z score, RV fractional area change, RV free wall and global longitudinal strain, left ventricular (LV) eccentricity index, RV/LV ratio, and pulmonary artery acceleration time were measured from preprocedure echocardiograms. Associations between hemodynamic values, echocardiographic measures, and survival were evaluated by Spearman correlation and Wilcoxon rank sum test, respectively. RESULTS: Fifty-three patients (68% left-sided, 74% liver herniation, 57% extracorporeal membrane oxygenation, 93% survival) underwent cath (39 during index hospitalization, 14 later) including device closure of a patent ductus arteriosus in 5. Most patients (n = 31, 58%) were on pulmonary hypertension treatment at cath, most commonly sildenafil (n = 24, 45%) and/or intravenous treprostinil (n = 16, 30%). Overall, hemodynamics were consistent with precapillary pulmonary hypertension. Pulmonary capillary wedge pressure was >15 mm Hg in 2 patients (4%). Lower fractional area change and worse ventricular strain were associated with higher pulmonary artery pressure while higher LV eccentricity index and higher RV/LV ratio were associated with both higher pulmonary artery pressure and higher pulmonary vascular resistance. Hemodynamics did not differ based on survival status. CONCLUSIONS: Worse RV dilation and dysfunction by echocardiogram correlate with higher pulmonary artery pressure and pulmonary vascular resistance on cath in this CDH cohort. These measures may represent novel, noninvasive clinical trial targets in this population.

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The tetra fish species Astyanax mexicanus comprises two morphotypes: cavefish that live in caves and surface fish that inhabit rivers and lakes. Because cavefish have adapted to the nutrient-poor conditions in their habitat whereas the surface fish populations can be used as a proxy for the ancestral condition, this species has become a powerful model system for understanding genetic variation underlying metabolic adaptation. The liver plays a critical role in glucose and fat metabolism in the body and hence is an important tissue for studying altered metabolism in health and disease. Cavefish morphs of A. mexicanus have been shown to develop fatty livers and exhibit massive differences in gene expression and chromatin architecture. Primary cell lines from various tissues have become invaluable tools for biochemical, toxicology, and cell biology experiments, as well as genetic and genomic analyses. To enhance the utility of the model system by enabling an expanded set of biochemical and in vitro experiments, we developed protocols for the isolation and maintenance of primary liver cells from A. mexicanus surface fish and cavefish. We also describe methods that can be used for primary cell characterization, including cloning, characterization of cell growth pattern, and lentivirus transduction. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Primary culture of liver cells Support Protocol 1: Maintenance of A. mexicanus primary liver cells Support Protocol 2: Banking of A. mexicanus primary liver cells Support Protocol 3: Recovery of A. mexicanus primary liver cells Support Protocol 4: Primary liver cell cloning Support Protocol 5: Characterization of A. mexicanus primary liver cell growth pattern Basic Protocol 2: Lentiviral transduction of A. mexicanus primary liver cells.

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BACKGROUND/AIMS: Diabetes mellitus (DM) is highly susceptible to diabetic hind limb ischemia (DHI). MicroRNA (MiR)-17-5p is downregulated in DM and plays a key role in vascular protection. Endothelial progenitor cell (EPC)-released exosomes (EPC-EXs) contribute to vascular protection and ischemic tissue repair by transferring their contained miRs to target cells. Here, we investigated whether miR-17-5p-enriched EPC-EXs (EPC-EXsmiR-17-5p) had conspicuous effects on protecting vascular and skeletal muscle in DHI in vitro and in vivo. METHODS: EPCs transfected with scrambled control or miR-17-5p mimics were used to generate EPC-EXs and EPC-EXsmiR-17-5p. Db/db mice were subjected to hind limb ischemia. After the surgery, EPC-EXs and EPC-EXsmiR-17-5p were injected into the gastrocnemius muscle of the hind limb once every 7 days for 3 weeks. Blood flow, microvessel density, capillary angiogenesis, gastrocnemius muscle weight, structure integrity, and apoptosis in the hind limb were assessed. Vascular endothelial cells (ECs) and myoblast cells (C2C12 cells) were subjected to hypoxia plus high glucose (HG) and cocultured with EPC-EXs and EPC-EXsmiR-17-5p. A bioinformatics assay was used to analyze the potential target gene of miR-17-5p, the levels of SPRED1, PI3K, phosphorylated Akt, cleaved caspase-9 and cleaved caspase-3 were measured, and a PI3K inhibitor (LY294002) was used for pathway analysis. RESULTS: In the DHI mouse model, miR-17-5p was markedly decreased in hind limb vessels and muscle tissues, and infusion of EPC-EXsmiR-17-5p was more effective than EPC-EXs in increasing miR-17-5p levels, blood flow, microvessel density, and capillary angiogenesis, as well as in promoting muscle weight, force production and structural integrity while reducing apoptosis in gastrocnemius muscle. In Hypoxia plus HG-injured ECs and C2C12 cells, we found that EPC-EXsmiR-17-5p could deliver their carried miR-17-5p into target ECs and C2C12 cells and subsequently downregulate the target protein SPRED1 while increasing the levels of PI3K and phosphorylated Akt. EPC-EXsmiR-17-5p were more effective than EPC-EXs in decreasing apoptosis and necrosis while increasing viability, migration, and tube formation in Hypoxia plus HG-injured ECs and in decreasing apoptosis while increasing viability and myotube formation in C2C12 cells. These effects of EPC-EXsmiR-17-5p could be abolished by a PI3K inhibitor (LY294002). CONCLUSION: Our results suggest that miR-17-5p promotes the beneficial effects of EPC-EXs on DHI by protecting vascular ECs and muscle cell functions.

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BACKGROUND: In the treatment of oral squamous cell carcinoma (OSCC), radiation resistance remains an important obstacle to patient outcomes. Progress in understanding the molecular mechanisms of radioresistance has been limited by research models that do not fully recapitulate the biological features of solid tumors. In this study, we aimed to develop novel in vitro models to investigate the underlying basis of radioresistance in OSCC and to identify novel biomarkers. METHODS: Parental OSCC cells (SCC9 and CAL27) were repeatedly exposed to ionizing radiation to develop isogenic radioresistant cell lines. We characterized the phenotypic differences between the parental and radioresistant cell lines. RNA sequencing was used to identify differentially expressed genes (DEGs), and bioinformatics analysis identified candidate molecules that may be related to OSCC radiotherapy. RESULTS: Two isogenic radioresistant cell lines for OSCC were successfully established. The radioresistant cells displayed a radioresistant phenotype when compared to the parental cells. Two hundred and sixty DEGs were co-expressed in SCC9-RR and CAL27-RR, and thirty-eight DEGs were upregulated or downregulated in both cell lines. The associations between the overall survival (OS) of OSCC patients and the identified genes were analyzed using data from the Cancer Genome Atlas (TCGA) database. A total of six candidate genes (KCNJ2, CLEC18C, P3H3, PIK3R3, SERPINE1, and TMC8) were closely associated with prognosis. CONCLUSION: This study demonstrated the utility of constructing isogenic cell models to investigate the molecular changes associated with radioresistance. Six genes were identified based on the data from the radioresistant cells that may be potential targets in the treatment of OSCC.

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OBJECTIVE: To describe our experience with treprostinil, evaluate correlations with cardiac function, and assess for adverse effects in neonates with congenital diaphragmatic hernia-related pulmonary hypertension (CDH-PH). STUDY DESIGN: A retrospective review of a single-center prospective registry at a quaternary care children's hospital. Patients included in the study had CDH-PH treated with treprostinil between April 2013 and September 2021. Assessed outcomes were brain-type natriuretic peptide levels and quantitative echocardiographic parameters collected at baseline, 1 week, 2 weeks, and 1 month after treprostinil initiation. Right ventricular (RV) function was assessed by tricuspid annular plane systolic excursion Z-score and speckle tracking echocardiography (global longitudinal and free wall strain). Septal position and left ventricular (LV) compression were assessed by eccentricity index and M-mode Z-scores. RESULTS: Fifty-one patients were included, with an average expected/observed lung-to-head ratio of 28.4 ± 9.0%. Most patients required extra-corporeal membrane oxygenation (n = 45, 88%). Survival to hospital discharge was 31/49 (63%). Treprostinil was initiated at a median age of 19 days with a median effective dose of 34 ng/kg/minute. Median baseline brain-type natriuretic peptide level decreased from 416.9 pg/mL to 120.5 pg/mL after 1 month. Treprostinil was associated with improved tricuspid annular plane systolic excursion Z-score, RV global longitudinal strain, RV free wall strain, LV eccentricity index, and LV diastolic and systolic dimensions, reflecting less compression by the RV, regardless of ultimate patient survival. No serious adverse effects were recorded. CONCLUSIONS: In neonates with CDH-PH, treprostinil administration is well tolerated and is associated with improved RV size and function.

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Female sex workers (FSW) have worse HIV outcomes in part due to lower anti-retroviral therapy (ART) adherence. Substance use and depression are important barriers to ART adherence, yet few studies have assessed these relationships among FSW in longitudinal studies. Cross-Lagged Panel Models and autoregressive mediation analyses assessed substance use (illicit drug use and alcohol use disorders) in relation to ART non-adherence and the mediation role of depressive symptoms among 240 FSW living with HIV in the Dominican Republic. In annual visits (T1, T2, T3), the majority (70%, 66%, and 53%) reported at-risk drinking and 15%, 13% and 9% used illicit drug during the past 6 months. Most FSW (70%, 62% and 46%) had mild-to-severe depression. Illicit drug use predicted later ART non-adherence. This relationship was not mediated via depressive symptoms. Integrated substance use and HIV care interventions are needed to promote ART adherence and viral suppression among FSW.

RESUMEN: Las trabajadoras sexuales (TRSX) tienen peores resultados de VIH debido en parte a la menor adherencia a la terapia antirretroviral (TAR). El uso de sustancias y la depresión son barreras importantes para la adherencia; sin embargo, pocos estudios longitudinales han evaluado estas relaciones entre las TRSX. Utilizamos modelos de panel y análisis de mediación para evaluar el uso de sustancias en relación a la falta de adherencia al TAR y el papel de mediación de los síntomas depresivos entre 240 TRSX con VIH en la República Dominicana. En visitas anuales (T1, T2, T3), la mayoría (70%, 66%, and 53%) reportó consumo riesgoso de alcohol y 15%, 13% y 9% consumieron alguna droga ilícita durante los últimos 6 meses. La mayoría (70%, 62% y 46%) tenían depresión leve a grave. El uso de drogas ilícitas predijo la falta de adherencia al TAR. Esta relación no fue mediada por síntomas depresivos. Se necesitan intervenciones integradas de atención del VIH y el uso de sustancias para promover la adherencia al TAR y la supresión viral entre TRSX.

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Resumo Objetivo Avaliar os efeitos da intervenção terapêutica de enfermagem baseada no modelo de trajetória da doença crônica na ansiedade e na qualidade de vida de pacientes com doença cardíaca coronária (DCC). Métodos Um total de 118 pacientes com DCC admitidos entre fevereiro de 2019 e fevereiro de 2021 foram distribuídos aleatoriamente em grupos controle e observação (n = 59). O grupo controle recebeu intervenção de enfermagem de rotina, enquanto o grupo observação recebeu intervenção com base no modelo de trajetória da doença crônica. Os sintomas clínicos, a escala de autoavaliação de ansiedade (SAS), a qualidade de vida (QV) e as pontuações de autoeficácia foram comparados. As taxas de incidência de complicações foram comparadas. A análise de regressão linear multivariada foi realizada para o efeito mediador da autoeficácia na relação entre ansiedade e QV. Um modelo de equação estrutural foi construído e validado. Resultados Após a intervenção, os sintomas clínicos e a pontuação da SAS diminuíram significativamente em ambos os grupos, especialmente no grupo observação (P<0,05). As pontuações de QV e autoeficácia aumentaram significativamente em ambos os grupos, particularmente no grupo de observação (P<0,05). A pontuação de autoeficácia correlacionou-se negativamente com a pontuação SAS e positivamente com a pontuação QV. Houve correlação negativa entre a pontuação SAS e a pontuação QV (P<0,05). O modelo de autoeficácia, ansiedade e QV apresentou boa adequação, e o efeito mediador da autoeficácia na relação entre ansiedade e QV foi de 0,896. A taxa de incidência de complicações foi significativamente menor no grupo observação do que no grupo controle (P <0,05). Conclusão A intervenção de enfermagem baseada no modelo de trajetória da doença crônica alivia significativamente a ansiedade, melhora a QV e aumenta a pontuação de autoeficácia de pacientes com DCC. A autoeficácia é um mediador da relação entre ansiedade e QV.

Resumen Objetivo Evaluar los efectos de la intervención terapéutica de enfermería con base en el modelo de trayectoria de la enfermedad crónica en la ansiedad y en la calidad de vida de pacientes con enfermedad arterial coronaria (EAC). Métodos Un total de 118 pacientes con EAC admitidos entre febrero de 2019 y febrero de 2021 fueron distribuidos aleatoriamente en grupos control y observación (n = 59). El grupo control recibió intervención de enfermería de rutina, mientras el grupo observación recibió intervención con base en el modelo de trayectoria de la enfermedad crónica. Se compararon los síntomas clínicos, la escala de autoevaluación de ansiedad (EAA), la calidad de vida (CV) y el puntaje de autoeficacia. Se compararon las tasas de incidencia de complicaciones. El análisis de regresión lineal multivariado se realizó para el efecto mediador de la autoeficacia en la relación entre ansiedad y CV. Se elaboró y validó un modelo de ecuación estructural. Resultados Después de la intervención, los síntomas clínicos y el puntuaje de la EAA disminuyeron de forma considerable en ambos grupos, especialmente en el grupo observación (P<0,05). Los puntajes de CV y de autoeficacia aumentaron considerablemente en ambos grupos, particularmente en el grupo de observación (P<0,05). El puntaje de autoeficacia se correlacionó negativamente con el puntaje EAA y positivamente con el puntaje CV. Hubo una correlación negativa entre el puntaje EAA y el puntaje CV (P<0,05). El modelo de autoeficacia, ansiedad y CV presentó una buena adecuación y el efecto mediador de la autoeficacia en la relación entre ansiedad y CV fue de 0,896. La tasa de incidencia de complicaciones fue considerablemente inferior en el grupo observación que en el grupo control (P <0,05). Conclusión La intervención de enfermería con base en el modelo de trayectoria de la enfermedad crónica alivia de forma considerable la ansiedad, mejora la CV y aumenta el puntaje de autoeficacia de pacientes con EAC. La autoeficacia es un mediador de la relación entre ansiedad y CV.

Abstract Objective We aimed to assess the effects of nursing intervention therapy based on chronic disease trajectory model on anxiety and quality of life (QOL) of patients with coronary heart disease (CHD). Methods A total of 118 CHD patients admitted from February 2019 to February 2021 were randomly assigned into control and observation groups (n=59). Control group was given routine nursing intervention, while observation group was given intervention based on chronic disease trajectory model. Clinical symptom, self-rating anxiety scale (SAS), QOL and self-efficacy scores were compared. Incidence rates of complications were compared. Multivariate linear regression analysis was performed for the mediating effect of self-efficacy on relationship between anxiety and QOL. A structural equation model was constructed and verified. Results After intervention, clinical symptom and SAS scores significantly declined in both groups, especially in observation group (P<0.05). QOL and self-efficacy scores rose significantly in both groups, particularly in observation group (P<0.05). Self-efficacy score was negatively correlated with SAS score and positively correlated with QOL score, and there was a negative correlation between SAS score and QOL score (P<0.05). The model of self-efficacy, anxiety and QOL had good fitness, and the mediating effect of self-efficacy on relationship between anxiety and QOL was 0.896. The incidence rate of complications was significantly lower in observation group than in control group (P<0.05). Conclusion Nursing intervention based on chronic disease trajectory model significantly relieves the anxiety, improves QOL, and increases the self-efficacy score of CHD patients. Self-efficacy is a mediator for the relationship between anxiety and QOL.

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BACKGROUND/AIMS: Diabetes mellitus (DM) is highly susceptible to diabetic hind limb ischemia (DHI). MicroRNA (MiR)-17-5p is downregulated in DM and plays a key role in vascular protection. Endothelial progenitor cell (EPC)-released exosomes (EPC-EXs) contribute to vascular protection and ischemic tissue repair by transferring their contained miRs to target cells. Here, we investigated whether miR-17-5p-enriched EPC-EXs (EPC-EXsmiR-17-5p) had conspicuous effects on protecting vascular and skeletal muscle in DHI in vitro and in vivo. METHODS: EPCs transfected with scrambled control or miR-17-5p mimics were used to generate EPC-EXs and EPC-EXsmiR-17-5p. Db/db mice were subjected to hind limb ischemia. After the surgery, EPC-EXs and EPC-EXsmiR-17-5p were injected into the gastrocnemius muscle of the hind limb once every 7 days for 3 weeks. Blood flow, microvessel density, capillary angiogenesis, gastrocnemius muscle weight, structure integrity, and apoptosis in the hind limb were assessed. Vascular endothelial cells (ECs) and myoblast cells (C2C12 cells) were subjected to hypoxia plus high glucose (HG) and cocultured with EPC-EXs and EPC-EXsmiR-17-5p. A bioinformatics assay was used to analyze the potential target gene of miR-17-5p, the levels of SPRED1, PI3K, phosphorylated Akt, cleaved caspase-9 and cleaved caspase-3 were measured, and a PI3K inhibitor (LY294002) was used for pathway analysis. RESULTS: In the DHI mouse model, miR-17-5p was markedly decreased in hind limb vessels and muscle tissues, and infusion of EPC-EXsmiR-17-5p was more effective than EPC-EXs in increasing miR-17-5p levels, blood flow, microvessel density, and capillary angiogenesis, as well as in promoting muscle weight, force production and structural integrity while reducing apoptosis in gastrocnemius muscle. In Hypoxia plus HG-injured ECs and C2C12 cells, we found that EPC-EXsmiR-17-5p could deliver their carried miR-17-5p into target ECs and C2C12 cells and subsequently downregulate the target protein SPRED1 while increasing the levels of PI3K and phosphorylated Akt. EPC-EXsmiR-17-5p were more effective than EPC-EXs in decreasing apoptosis and necrosis while increasing viability, migration, and tube formation in Hypoxia plus HG-injured ECs and in decreasing apoptosis while increasing viability and myotube formation in C2C12 cells. These effects of EPC-EXsmiR-17-5p could be abolished by a PI3K inhibitor (LY294002). CONCLUSION: Our results suggest that miR-17-5p promotes the beneficial effects of EPC-EXs on DHI by protecting vascular ECs and muscle cell functions.

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Abstract Introduction: High mobility group box 1 protein participates in the pathogenesis of allergic rhinitis. Activation of the inflammasome can mediate the release of high mobility group box 1. The role of the absent in melanoma 2 inflammasome in allergic rhinitis remains unclear. Objective: This study aimed to investigate the function of absent in melanoma 2 inflammasome in murine allergic rhinitis and the interaction between high mobility group box 1 and the absent in melanoma 2 inflammasome. Methods: A murine allergic rhinitis model was established using twenty Balb/c mice. Expression of the components of the absent in melanoma 2 inflammasome: absent in melanoma 2, apoptosis-associated speck-like protein containing a CARD (Asc), caspase-1 p20, and additional nod-like receptor family pyrin domain containing 3 (Nlrp3) were detected by western blotting during allergic rhinitis. Alterations of absent in melanoma 2, caspase-1, and high mobility group box 1 after ovalbumin challenge were demonstrated by immunohistochemistry. TdT-mediated dUTP Nick end labeling, TUNEL assay, and cleavage of caspase-3 and PARP-1 were used for the observation of pyroptosis. Results: Eosinophilia and goblet cell infiltration were observed in the nasal mucosa of mice in the allergic rhinitis group. Absent in melanoma 2, Asc, and caspase-1 p20 increased after ovalbumin exposure while Nlrp3 did not. High mobility group box 1 was released in the nasal mucosa of allergic rhinitis mice. TUNEL-positive cells increased in the epithelium and laminae propria, whereas cleavage of caspase-3 and PARP-1 was not observed. Conclusions: The absent in melanoma 2 inflammasome was activated and pyroptosis may occur in the nasal mucosa after ovalbumin treatment. These may contribute to the translocation of high mobility group box 1 and the development of allergic rhinitis.

Resumo Introdução: A proteína do grupo Box-1 de alta mobilidade participa da patogênese da rinite alérgica. A ativação do inflamassoma pode mediar a liberação de proteína do grupo Box-1 de alta mobilidade. O papel do inflamassoma ausente no melanoma 2 na rinite alérgica permanece incerto. Objetivo: Investigar a função do inflamassoma ausente no melanoma 2 em um modelo murino de rinite alérgica e a interação entre a proteína do grupo Box-1 de alta mobilidade e o inflamassoma ausente no melanoma 2. Método: Um modelo murino de rinite alérgica foi estabelecido com 20 camundongos Balb/c. A expressão dos componentes do inflamassoma ausente no melanoma 2, da proteína speck-like associada à apoptose com CARD (Asc), da caspase-1 p20 e do domínio de pirina da família NLR adicional com 3 (Nlrp3) foi detectada por western blotting durante a rinite alérgica. Alterações de inflamassoma ausente no melanoma 2, na caspase-1 e na proteína do grupo Box-1 de alta mobilidade após o teste de provocação com ovalbumina foram demonstradas por imuno-histoquímica. O ensaio dUTP Nick-End Labeling mediado por TdT, TUNEL e clivagem de caspase-3 e PARP-1 foram usados para a observação de piroptose. Resultados: Eosinofilia e infiltração de células caliciformes foram observadas na mucosa nasal de camundongos do grupo rinite alérgica. Inflamassoma ausente no melanoma 2, Asc e caspase-1 p20 aumentou após a exposição à ovalbumina, enquanto Nlrp3 não aumentou. A proteína do grupo Box-1 de alta mobilidade foi liberada na mucosa nasal de camundongos com rinite alérgica. As células TUNEL-positivas aumentaram no epitélio e na lâmina própria, enquanto a clivagem da caspase-3 e a PARP-1 não foram observadas. Conclusão: O inflamassoma ausente no melanoma 2 foi ativado e pode ocorrer piroptose na mucosa nasal após o tratamento com ovalbumina. Esses fatores podem contribuir para a translocação de proteína do grupo Box-1 de alta mobilidade e o desenvolvimento de rinite alérgica.

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Co-occurrence of myelodysplastic syndrome (MDS) and plasma cell neoplasm in patients with no history of chemo and/or radiotherapy is rarely reported. Herein, we report a case of a female in her seventieth decade of life who was referred to the hospital for pancytopenia. The patient was asymptomatic and was doing well overall. Serum protein electrophoresis was remarkable for a lambda-restricted monoclonal protein (IgG) estimated at 1.8g/dL. Immunoglobulin G serum level was also elevated, and serum Kappa/Lambda free light chain ratio was decreased. At that time, a bone marrow biopsy showed myelodysplastic syndrome with excess blasts-2 (MDS-EB2) and a monoclonal plasma cell proliferation. Some studies have shown that patients with plasma cell neoplasm could be associated with an increased risk of developing MDS compared to the general population. Based on reviewing the literature, to our knowledge, the pathological mechanism of the co-occurrence of both diseases is not yet clear.

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Cell lines have become an integral resource and tool for conducting biological experiments ever since the Hela cell line was first developed (Scherer et al. in J Exp Med 97:695-710, 1953). They not only allow detailed investigation of molecular pathways but are faster and more cost-effective than most in vivo approaches. The last decade saw many emerging model systems strengthening basic science research. However, lack of genetic and molecular tools in these newer systems pose many obstacles. Astyanax mexicanus is proving to be an interesting new model system for understanding metabolic adaptation. To further enhance the utility of this system, we developed liver-derived cell lines from both surface-dwelling and cave-dwelling morphotypes. In this study, we provide detailed methodology of the derivation process along with comprehensive biochemical and molecular characterization of the cell lines, which reflect key metabolic traits of cavefish adaptation. We anticipate these cell lines to become a useful resource for the Astyanax community as well as researchers investigating fish biology, comparative physiology, and metabolism.