Tenofovir Disoproxil Fumarate/Emtricitabine and Baricitinib for Patients at High Risk of Severe Coronavirus Disease 2019: The PANCOVID Randomized Clinical Trial.

BACKGROUND: This study was designed to evaluate if patients with high risk for severe coronavirus disease 2019 (COVID-19) would benefit from treatment with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) followed by baricitinib in case of hypoxemia and systemic inflammation. METHODS: PANCOVID is an open-label, double-randomized, phase 3 pragmatic clinical trial including adults with symptomatic COVID-19 with ≥2 comorbidities or aged ≥60 years and was conducted between 10 October 2020 and 23 September 2021. In the first randomization, patients received TDF/FTC or no TDF/FTC. In the second randomization, patients with room air oxygen saturation <95% and at least 1 increased inflammatory biomarker received baricitinib plus dexamethasone or dexamethasone alone. The primary endpoint was 28-day mortality. Main secondary endpoint was 28-day disease progression or critical care unit admission or mortality. The trial was stopped before reaching planned sample size due to the decrease in the number of cases and a mortality rate substantially lower than expected. RESULTS: Of the 355 included participants, 97% were hospitalized at baseline. Overall, 28-day mortality was 3.1%. The 28-day mortality relative risk (RR) for participants treated with TDF/FTC was 1.76 (95% confidence interval [CI], .52-5.91; P = .379); it was 0.42 (95% CI, .11-1.59; P = .201) for those treated with baricitinib. The 28-day RR for the main secondary combined endpoint for participants treated with TDF/FTC was 0.95 (95% CI, .66-1.40; P = .774); it was 0.90 (95% CI, .61-1.33; P = .687) for those treated with baricitinib. CONCLUSIONS: Our results do not suggest a beneficial effect of TDF/FTC; nevertheless, they are compatible with the beneficial effect of baricitinib already established by other clinical trials. CLINICAL TRIALS REGISTRATION: EudraCT: 2020-001156-18.

Switching to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) plus darunavir/cobicistat in heavily antiretroviral-experienced, virologically suppressed HIV-infected adults receiving complex regimens.

OBJECTIVES: To evaluate the efficacy and safety of the two-pill regimen bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) plus darunavir/cobicistat as a switching strategy in heavily treatment-experienced people living with HIV (PLWH). METHODS: Multicentre, prospective, single-arm pilot clinical trial. Participants were virologically suppressed adults receiving a stable antiretroviral regimen of at least three pills from at least three drug families due to previous virological failures and/or toxicities with no documented resistance to integrase strand transfer inhibitors or darunavir (≥15 points, Stanford). Clinical and laboratory assessments were performed at 0, 4, 12, 24, 36 and 48 weeks. HIV-1 proviral DNA was amplified and sequenced by Illumina at baseline. Plasma bictegravir concentrations were determined in 22 patients using UHPLC-MS/MS. The primary study endpoint was viral load (VL)< 50 copies/mL at Week 48 (ITT). RESULTS: We enrolled 63 participants (92% men) with median baseline CD4 count of 515 cells/mm3 (IQR: 334.5-734.5), 24 years on ART (IQR: 15.9-27.8). The median number of pills was 4 (range: 3-10). At baseline, proviral DNA was amplified in 39 participants: 33/39 had resistance mutations. Three participants discontinued owing to toxicity. At 48 weeks, 95% had VL < 50 copies/mL by ITT and 100% by PP analysis. A modest increase was observed in the bictegravir plasma concentration, and a significant decrease in estimated glomerular filtration rate was observed only at Week 4, probably related to interaction with renal transporters. CONCLUSIONS: Our data suggest that BIC/FTC/TAF + darunavir/cobicistat is an effective, well-tolerated regimen that may improve convenience and, potentially, long-term success in stable heavily pre-treated PLWH.

Clinical Significance of Delirium With Catatonic Signs in Patients With Neurological Disorders.

OBJECTIVE: According to DSM-5, catatonia and delirium are mutually exclusive clinical syndromes. The investigators explored the co-occurrence of delirium and catatonia (i.e., catatonic delirium) and the clinical significance of this syndrome with a sample of neurological patients. METHODS: This prospective study with consecutive sampling included patients diagnosed with delirium at the National Institute of Neurology and Neurosurgery of Mexico. DSM-5 criteria for delirium, the Confusion Assessment Method, and the Delirium Rating Scale-Revised-98 were used to select and characterize patients. Catatonia was assessed using the Bush-Francis Catatonia Rating Scale and DSM-5 diagnostic criteria. Logistic regression analysis was performed to identify etiological factors associated with catatonic delirium. RESULTS: A total of 264 patients with delirium were included, 61 (23%) of whom fulfilled the criteria for catatonia and delirium simultaneously. Brain tumors, subarachnoid hemorrhage, acute hydrocephalus, and ischemic stroke were associated with delirium without catatonic signs. Catatonic delirium was observed among patients with encephalitis, epilepsy, brain neoplasms, and brain tuberculosis. After multivariate analysis, the association between catatonic delirium and encephalitis (both viral and anti-N-methyl-d-aspartate receptor [NMDAR]) was confirmed. CONCLUSIONS: Delirium is a common complication of neurological diseases, and it can coexist with catatonia. The recognition of catatonic delirium has clinical significance in terms of etiology, as it was significantly associated with viral and anti-NMDAR encephalitis.

Effect of Atom Transfer Radical Polymerization Reaction Time on PCB Binding Capacities of Styrene-CMA/QMA Core-Shell Iron Oxide Nanoparticles.

Water pollution continues to be one of the greatest challenges humankind faces worldwide. Increasing population growth, fast industrialization and modernization risk the worsening of water accessibility and quality in the coming years. Nanoadsorbents have steadily gained attention as remediation technologies that can meet stringent water quality demands. In this work, core-shell magnetic nanoparticles (MNPs) comprised of an iron oxide magnetic core and a styrene based polymer shell were synthesized via surface initiated atom transfer radical polymerization (SI-ATRP), and characterized them for their binding of polychlorinated biphenyls (PCBs), as model organic contaminants. Acrylated plant derived polyphenols, curcumin multiacrylate (CMA) and quercetin multiacrylate (QMA), and divinylbenzene (DVB) were incorporated into the polymeric shell to create high affinity binding sites for PCBs. The affinity of these novel materials for PCB 126 was evaluated and fitted to the nonlinear Langmuir model to determine binding affinities (KD). The KD values obtained for all the MNP systems showed higher binding affinities for PCB 126 that carbonaceous materials, like activated carbon and graphene oxide, the most widely used adsorption materials for water remediation today. The effect of increasing ATRP reaction time on the binding affinity of MNPs demonstrated the ability to tune polymer shell thickness by modifying the reaction extent and initial crosslinker concentrations in order to maximize pollutant binding. The enhancement in binding affinity and capacity for PCB 126 was demonstrated by the use of hydrophobic, aromatic rich molecules like styrene, CMA, QMA and DVB, within the polymeric shell provides more sites for π-π interactions to occur between the MNP surface and the PCB molecules. Overall, the high affinities for PCBs, as model organic pollutants, and magnetic capabilities of the core-shell MNPs synthesized provide a strong rationale for their application as nanoadsorbents in the environmental remediation of specific harmful contaminants.

Laboring With the Heart: Promotoras' Transformations, Professional Challenges, and Relationships With Communities.

Little is known about promotoras' professional experiences engaging in Latinx health promotion. In this promotora-led community-based participatory study, we purposively recruited and interviewed 30 Spanish-speaking promotoras who worked in Los Angeles County and who had at least 5 years of experience as promotoras. Using a constructivist grounded theory approach, findings revealed promotoras self-identified as health professionals who offered unique, insider perspectives. Challenges arose as employers viewed promotoras as volunteer lay health workers, while promotoras desired opportunities for professional growth. Motivation to continue working as promotoras stemmed from their commitment to Latinx communities. We provide recommendations to strengthen community-based capacity for advancing Latinx health.

Development of novel SSR molecular markers using a Next-Generation Sequencing approach (ddRADseq) in Stetsonia coryne (Cactaceae).

The Cactaceae family is native to the American continent with several centers of diversity. In South America, one of these centers is the Central Andes and many species are considered to be threatened or vulnerable according to the International Union for Conservation of Nature (IUCN). Stetsonia coryne is an emblematic giant columnar cacti of the Chaco phytogeographic province. It has an extensive geographical distribution in many countries of the continent. However, to date there are no specific molecular markers for this species, neither reports of population genetic variability studies, such as for many cactus species. The lack of information is fundamentally due to the lack of molecular markers that allow these studies. In this work, by applying a Genotyping by Sequencing (GBS) technique, we developed polymorphic SSR markers for the Stetsonia coryne and evaluated their transferability to phylogenetically close species, in order to account for a robust panel of molecular markers for multispecies-studies within Cactaceae.

In silico and in vitro analysis of cation-activated potassium channels in human corneal endothelial cells.

The corneal endothelium is the inner cell monolayer involved in the maintenance of corneal transparence by the generation of homeostatic dehydration. The glycosaminoglycans of the corneal stroma develop a continuous swelling pressure that should be counteracted by the corneal endothelial cells through active transport mechanisms to move the water to the anterior chamber. Protein transporters for sodium (Na+), potassium (K+), chloride (Cl-) and bicarbonate (HCO3-) are involved in this endothelial "pump function", however despite its physiological importance, the efflux mechanism is not completely understood. There is experimental evidence describing transendothelial diffusion of water in the absence of osmotic gradients. Therefore, it is important to get a deeper understanding of alternative models that drive the fluid transport across the endothelium such as the electrochemical gradients. Three transcriptomic datasets of the corneal endothelium were used in this study to analyze the expression of genes that encode proteins that participate in the transport and the reestablishment of the membrane potential across the semipermeable endothelium. Subsequently, the expression of the identified channels was validated in vitro both at mRNA and protein levels. The results of this study provide the first evidence of the expression of KCNN2, KCNN3 and KCNT2 genes in the corneal endothelium. Differences among the level of expression of KCNN2, KCNT2 and KCNN4 genes were found in a differentially expressed gene analysis of the dataset. Taken together these results underscore the potential importance of the ionic channels in the pathophysiology of corneal diseases. Moreover, we elucidate novel mechanisms that might be involved in the pivotal dehydrating function of the endothelium and in others physiologic functions of these cells using in silico pathways analysis.

Association of Social Adversity with Comorbid Diabetes and Depression Symptoms in the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study: A Syndemic Framework.

BACKGROUND: U.S. Hispanics/Latinos experience high lifetime risk for Type 2 diabetes and concurrent psychological depression. This comorbidity is associated with poorer self-management, worse disease outcomes, and higher mortality. Syndemic theory is a novel social epidemiological framework that emphasizes the role of economic and social adversity in promoting disease comorbidity and health disparities. PURPOSE: Informed by the syndemic framework, this study explored associations of socioeconomic and psychosocial adversity (low income/education, trauma history, adverse childhood experiences, ethnic discrimination, neighborhood problems [e.g., violence]) with comorbidity of diabetes and depression symptoms in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and Sociocultural Ancillary Study. METHODS: Participants were 5,247 Latino adults, aged 18-74, enrolled in four U.S. cities from 2008 to 2011. Participants completed a baseline physical exam and measures of depression symptoms and psychosocial adversity. Multinomial logistic regression analyses were conducted to examine associations of adversity variables with comorbid diabetes and high depression symptoms. RESULTS: Household income below $30,000/year was associated with higher odds of diabetes/depression comorbidity (odds ratio [OR] = 4.61; 95% confidence interval [CI]: 2.89, 7.33) compared to having neither condition, as was each standard deviation increase in adverse childhood experiences (OR = 1.41; 95% CI: 1.16, 1.71), ethnic discrimination (OR = 1.23; 95% CI: 1.01, 1.50), and neighborhood problems (OR = 1.53; 95% CI: 1.30, 1.80). CONCLUSION: Low household income, adverse childhood experiences, ethnic discrimination, and neighborhood problems are related to comorbid diabetes and depression in U.S. Latinos. Future studies should explore these relationships longitudinally.

T2 formula in a highly myopic population, comparison with other methods and description of an improved approach for estimating corneal height.

BACKGROUND: To determine the accuracy of the T2 formula as applied to highly myopic eyes, to compare the T2 formula to the SRK/T and Holladay 1 formulas, and to describe possible ways to improve the estimation of corneal height and prediction error in two settings, the Hadassah Hospital, Ophthalmology Department, Jerusalem, Israel and Clínica Barraquer, Bogotá, Colombia. METHODS: In this retrospective case series, optical biometer measurements were taken for 63 highly myopic patients (> 25 mm) undergoing uneventful crystalline lens phacoemulsification and insertion of an acrylic intraocular lens. Prediction errors were obtained, with estimations of ±0.50 D, ± 1.00 D, and greater than ±2.00 D. A method to improve the corneal height calculation is described. RESULTS: The SRK/T formula (mean absolute error [MAE] = 0.418; median absolute error [MedAE] = 0.352) was the most accurate, followed by the T2 (MAE = 0.435; MedAE = 0.381) and Holladay 1 (MAE = 0.455; MedAE = 0.389) formulas. Both the SRK/T and T2 formulas overestimated corneal height, but values were higher with the T2 formula. Corneal height was more precisely estimated using an alternative method that, when combined with axial length optimization, resulted in lower MAE (0.425) and MedAE (0.365) values than when applying the T2 formula alone. CONCLUSIONS: The T2 formula seems to be less accurate than the SRK/T formula in highly myopic eyes. An improved corneal height estimation method is described for the the T2 formula.

Extra-familial social factors and obesity in the Hispanic Community Children's Health Study/Study of Latino Youth.

Hispanic/Latino youth are disproportionately affected by obesity. However, how social factors outside of the family relate to Hispanic/Latino youth obesity is not well understood. We examined associations of extra-familial social factors with overweight/obesity prevalence, and their variation by sex and age, in 1444 Study of Latino Youth participants [48.6% female; 43.4% children (8-11 years); 56.6% adolescents (12-16 years)], who were offspring of the Hispanic Community Health Study/Study of Latinos participants. Youth self-reported general social support from friends, dietary-, and physical activity (PA)-specific support from peers, and awareness/internalization of thinness ideals. Overweight/obesity was defined as body mass index ≥ 85th percentile. Logistic regression models assessed effects of social factors and their interactions with age-group and sex, adjusting for potential confounders. Social support from friends interacted with both age and sex in relation to overweight/obesity. Female children who reported lesser (OR 0.60; 95% CI [0.39, 0.91]) and female adolescents who reported greater (OR 1.35; 95% CI [1.06, 1.74]) social support from friends had higher odds of overweight/obesity. Among males, greater awareness/internalization of thinness ideals related to higher odds of overweight/obesity (OR 2.30; 95% CI [1.59, 3.31]). Awareness/internalization of thinness ideals was not associated with overweight/obesity among females. Dietary and PA-specific peer support did not relate to overweight/obesity. Social support from friends and awareness/internalization of thinness ideals were significantly related to odds of overweight/obesity in Hispanic/Latino youth; associations varied by age and sex, and persisted after control for intra-familial factors (overall family support/function; diet and activity specific support).

Novel magnetic core-shell nanoparticles for the removal of polychlorinated biphenyls from contaminated water sources.

In this work, we developed novel core-shell nanoparticle systems with magnetic core and polymer shell via atom transfer radical polymerization for use as high affinity nanoadsorbents for organic contaminants in water and wastewater treatment. Polyphenolic-based moieties, curcumin multiacrylate (CMA) and quercetin multiacrylate (QMA), were incorporated into poly(ethylene glycol) (PEG) based polymeric shells to create high affinity binding sites for the capture of polychlorinated biphenyls (PCBs) as a model pollutant. The resulting magnetic nanoparticles (MNPs) were characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), transmission electron microscopy (TEM), X-ray diffraction (XRD), dynamic light scattering (DLS), and UV-visible spectroscopy. The affinity of these novel materials for PCB 126 was evaluated and fitted to the nonlinear Langmuir model to determine binding affinities (KD). The KD values obtained were: PEG MNPs (8.42 nM) < IO MNPs (8.23nM) < QMA MNPs (5.88 nM) < CMA MNPs (2.72 nM), demonstrating that the presence of polyphenolic-based moieties enhanced PCB 126 binding affinity, which is hypothesized to be a result of π - π stacking interactions. These values are lower that KD values for activated carbon, providing strong evidence that these novel core-shell nanoparticles have a promising application as nanoadsorbents for specific organic contaminants offering a cost effective alternative to current remediation approaches.

High HIV incidence in men who have sex with men following an early syphilis diagnosis: is there room for pre-exposure prophylaxis as a prevention strategy?

OBJECTIVES: HIV pre-exposure prophylaxis (PrEP) is becoming a pivotal strategy for HIV prevention. Understanding the impact of risk factors for HIV transmission to identify those at highest risk would favour the implementation of PrEP, currently limited by costs. In this service evaluation, we estimated the incidence of bacterial STIs in men who have sex with men (MSM) diagnosed with early syphilis attending a London sexual health clinic according to their HIV status. In addition, we estimated the incidence of HIV infection in HIV-negative MSM, following a diagnosis of early syphilis. METHODS: We undertook a retrospective case note review of all MSM patients diagnosed with early syphilis between January and June 2014. A number of sexual health screens and diagnoses of chlamydia, gonorrhoea and HIV were prospectively analysed following the syphilis diagnosis. RESULTS: 206 MSM were diagnosed with early syphilis. 110 (53%) were HIV-negative at baseline, 96 (47%) were HIV-positive. Only age (37 vs 32 years, p=0.0005) was significantly different according to HIV status of MSM at baseline. In HIV-negative versus HIV-positive MSM, incidence of rectal chlamydia infection at follow-up was 27 cases vs 50/100 person-years of follow-up (PYFU) (p=0.0039), 33 vs 66/100 PYFU (p=0.0044) for rectal gonorrhoea and 10 vs 26/100 PYFU (p=0.0044) for syphilis reinfection, respectively. Total follow-up for 110 HIV-negative MSM was 144 person-years. HIV incidence was 8.3/100 PYFU (CI 4.2 to 14). CONCLUSIONS: A diagnosis of early syphilis carries a high risk of consequent HIV seroconversion and should warrant prioritised access to prevention measures such as PrEP and regular STI screening to prevent HIV transmission.

Curcumin Acrylation for Biological and Environmental Applications.

Curcumin has recently gained interest for use in drug delivery, chemical sensing, and environmental applications. As a result, the development of synthesis strategies for the incorporation of curcumin into novel materials has become a priority. One such strategy, curcumin acrylation, involves the introduction of acrylate functional groups to the curcumin scaffold, with the potential generation of mono-, di-, and triacrylate curcumin species. The relative populations of these species in the resulting multiacrylate mixture can be controlled by the ratio of curcumin to acryloyl chloride in the initial reaction formulation. Characterization of the acrylation reaction and the resulting curcumin multiacrylate product is essential for the effective preparation of new curcumin-containing materials. In this work, a synthesis method for curcumin acrylation is presented and the resulting curcumin multiacrylate product is characterized via various techniques, i.e., HPLC, LCMS, and NMR, as a basis to establish the relationship between synthesis conditions and the extent of acrylation that is achieved.

"One Scar Too Many:" The Associations Between Traumatic Events and Psychological Distress Among Undocumented Mexican Immigrants.

Undocumented immigration often presents with multiple stressors and contextual challenges, which may diminish mental health. This study is the first to provide population-based estimates for the prevalence of traumatic events and its association to clinically significant psychological distress among undocumented Mexican immigrants in the United States. This cross-sectional study used respondent-driven sampling to obtain and analyze data from clinical interviews with 248 undocumented Mexican immigrants residing in high-risk neighborhoods near the California-Mexico border. Overall, 82.7% of participants reported a history of traumatic events, with 47.0% of these meeting the criteria for clinically significant psychological distress. After controlling for relevant covariates, having experienced material deprivation, odds ratio (OR) = 2.26, 95% CI [1.18, 4.31], p = .013, and bodily injury, OR = 2.96, 95% CI [1.50, 5.83], p = .002, and not having a history of deportation, OR = 0.36, 95% CI [0.17, 0.79], p = .011, were associated with clinically significant psychological distress. These results support the need to revisit health and immigration policies and to devise solutions grounded in empirical evidence aimed at preventing the negative effects of trauma and psychological distress in this population.

Fatalism and hypertension prevalence, awareness, treatment and control in US Hispanics/Latinos: results from HCHS/SOL Sociocultural Ancillary Study.

Compared with non-Hispanic whites, US Hispanics/Latinos display similar hypertension prevalence, but lower awareness, treatment, and control. Sociocultural factors may affect these patterns. Fatalism, the belief that health is predetermined by fate, relates to poorer adoption of risk reducing health behaviors. We examined the association of fatalism with hypertension prevalence, awareness, treatment, and control among 5313 Hispanics/Latinos, ages 18-74, who were enrolled from four US communities in the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study. After accounting for socioeconomic status and acculturation in logistic regression analyses, higher fatalism was associated with increased odds of hypertension (OR 1.14, 95 % CI 1.02, 1.28). This association was non-significant when diabetes and other health-related covariates were statistically adjusted. Fatalism was not associated with hypertension awareness, treatment, or control. Findings suggest that the association of fatalism with hypertension may be due largely to its association with SES, acculturation, or related health conditions.

A comparison of women with fibromyalgia syndrome to criterion fitness standards: a pilot study.

PURPOSE: To compare fitness of women with fibromyalgia syndrome (FMS) aged 50+ with performance standards associated with functional independence in late life. METHODS: Data came from a longitudinal study tracking physical and cognitive function of 93 women with FMS and included the most recent symptoms, activity levels, and fitness assessments. RESULTS: Most women performed below criterion-referenced fitness standards for all measures. Nearly 90% percent of those < 70 years scored below the standard for lower body strength. Only ~20% of respondents < 70 years old met the criteria for aerobic endurance. A third of those aged over 70 met the standard in agility and dynamic balance. Physical activity was positively associated with fitness performance, while pain and depression symptoms were negatively associated. DISCUSSION: High proportions of women with FMS do not meet fitness standards recommended for maintaining physical independence in late life, indicating a risk for disability. Regular fitness assessments and targeted exercise interventions are warranted.

Underlining neighbourhood perception: a possible risk factor for dementia that deserves more attention.

This essay highlights the interplay between the neighbourhood structural environment and neighbourhood perceptions on dementia by articulating how an individual's perception of neighbourhood, with respect to their individual differences, may provide key insights to understand the link between the neighbourhood and dementia.

Adverse childhood experiences and adult disease: Examining mediating pathways in the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study.

OBJECTIVES: Adverse childhood experiences (ACEs) have been linked to adulthood chronic diseases, but there is little research examining the mechanisms underlying this association. We tested pathways from ACEs to adult disease mediated via risk factors of depression, smoking, and body mass index. METHOD: Prospective data from adults 18 to 74 years old from the Hispanic Community Health Study/Study of Latinos and Sociocultural Ancillary Study were used. Retrospectively reported ACEs and hypothesized mediators were measured at Visit 1 (2008-2011). Outcomes of disease prevalence were assessed at Visit 2, approximately 6 years later. The analytic sample includes 5,230 Hispanic/Latino participants with ACE data. Statistical mediation was examined using structural equation modeling on cardiometabolic and pulmonary disease prevalence and reported probit regression coefficients with 95% confidence intervals (CIs). RESULTS: We found a significant association between ACEs and the prevalence of asthma/chronic obstructive pulmonary disorder (standardized ß = .07, 95% CI [0.02, 0.12]). In the mediational model, the direct association was nonsignificant (ß = .02, 95% CI [-0.04, 0.07]) but was mediated by depressive symptoms (ß = .03, 95% CI [0.02, 0.04]). There were no associations between ACEs and the prevalence of diabetes and self-reported coronary heart disease or cerebrovascular disease. However, a small indirect effect was identified via depressive symptoms and coronary heart disease (ß = .02, 95% CI [0.01, 0.03]). CONCLUSION: In this diverse Hispanic/Latino sample, depressive symptoms were found to be a pathway linking ACEs to self-reported cardiopulmonary diseases, although the effects were of small magnitude. Future work should replicate pathways, confirm the magnitude of effects, and examine cultural moderators that may dampen expected associations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).