Feasibility, acceptability, and efficacy of a positive emotion regulation intervention to promote resilience for healthcare workers during the COVID-19 pandemic: A randomized controlled trial.

INTRODUCTION: Burnout poses a substantial, ongoing threat to healthcare worker (HCW) wellbeing and to the delivery of safe, quality healthcare. While systemic and organization-level changes in healthcare are critically important, HCWs also need individual-level skills to promote resilience. The objective of this trial is to test feasibility, acceptability, and efficacy of PARK, an online self-guided positive affect regulation intervention, in a sample of healthcare workers during the COVID-19 pandemic. DESIGN AND METHODS: In the context of the unprecedented rise in burnout during the COVID-19 pandemic, we conducted a randomized waitlist-controlled trial of the Positive Affect Regulation sKills (PARK) program-a five-week, online, self-guided coping skills intervention nested within an ongoing cohort of HCWs. N = 554 healthcare workers were randomly assigned to receive the intervention immediately or to receive the intervention after approximately 12 weeks. Outcomes included change in burnout, emotional wellbeing (positive affect, meaning and purpose, depression, anxiety) and sleep over approximately 12 weeks. Analyses included mixed-effects linear regression models comparing change over time in outcomes between intervention and control conditions. RESULTS: One third (n = 554) of the participants in the cohort of HCWs consented to participate and enrolled in PARK in April 2022. Compared to those who did not enroll, participants in the trial reported higher burnout, poorer emotional wellbeing, and poorer sleep at baseline (April, 2022; all ps < .05). Intent-to-treat analyses showed that participants randomly assigned to the intervention immediately (PARK-Now) improved significantly on anxiety (within-group change on PROMIS T-score = -0.63; p = .003) whereas those in the waitlist (PARK-Later) did not (within group T-score change 0.04, p = 0.90). The between-group difference in change, however, was not statistically significant (B = -0.67 p = 0.10). None of the other wellbeing outcomes changed significantly in the intervention group compared to the waitlist. Additional as-treated analyses indicated that those participants who completed all 5 of the weekly online lessons (N = 52; 9.4%) improved significantly more on the primary outcome of positive affect compared to those who enrolled in PARK but completed zero lessons (n = 237; 42.8%; B = 2.85; p = .0001). CONCLUSIONS: Online self-guided coping skills interventions like PARK can be effective in targeted samples and future work will focus on adaptations to increase engagement and tailor PARK for HCWs who could most benefit.

In Vitro and in Silico Study of New Biscoumarin Glycosides from Paramignya trimera against Angiotensin-Converting Enzyme 2 (ACE-2) for Preventing SARS-CoV-2 Infection.

In Vietnam, the stems and roots of the Rutaceous plant Paramignya trimera (Oliv.) Burkill (known locally as "Xáo tam phân") are widely used to treat liver diseases such as viral hepatitis and acute and chronic cirrhosis. In an effort to search for Vietnamese natural compounds capable of inhibiting coronavirus based on molecular docking screening, two new dimeric coumarin glycosides, namely cis-paratrimerin B (1) and cis-paratrimerin A (2), and two previously identified coumarins, the trans-isomers paratrimerin B (3) and paratrimerin A (4), were isolated from the roots of P. trimera and tested for their anti-angiotensin-converting enzyme 2 (ACE-2) inhibitory properties in vitro. It was discovered that ACE-2 enzyme was inhibited by cis-paratrimerin B (1), cis-paratrimerin A (2), and trans-paratrimerin B (3), with IC50 values of 28.9, 68, and 77 µM, respectively. Docking simulations revealed that four biscoumarin glycosides had good binding energies (∆G values ranging from -10.6 to -14.7 kcal/mol) and mostly bound to the S1' subsite of the ACE-2 protein. The key interactions of these natural ligands include metal chelation with zinc ions and multiple H-bonds with Ser128, Glu145, His345, Lys363, Thr371, Glu406, and Tyr803. Our findings demonstrated that biscoumarin glycosides from P. trimera roots occur naturally in both cis- and trans-diastereomeric forms. The biscoumarin glycosides Lys363, Thr371, Glu406, and Tyr803. Our findings demonstrated that biscoumarin glycosides from P. trimera roots hold potential for further studies as natural ACE-2 inhibitors for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Utilization of at-home tests for coronavirus disease 2019 (COVID-19) among healthcare workers in Chicago.

Objective: To describe utilization of at-home coronavirus disease 2019 (COVID-19) testing among healthcare workers (HCW). Design: Serial cross-sectional study. Setting and participants: HCWs in the Chicago area. Methods: Serial surveys were conducted from the Northwestern Medicine (NM HCW SARS-CoV-2) Serology Cohort Study. In April 2022, participants reflected on the past 30 days to complete an online survey regarding COVID-19 home testing. Surveys were repeated in June and November 2022. The percentage of completed home tests and ever-positive tests were reported. Multivariable Poisson regression was used to calculate prevalence rate ratios (PRR) and univariate analysis was used for association between participant characteristics with home testing and positivity. Results: Overall, 2,226 (62.4%) of 3,569 responded to the survey in April. Home testing was reported by 26.6% of respondents and 5.9% reported having at least one positive home test. Testing was highest among those 30-39 years old (35.9%) and nurses (28.3%). A positive test was associated (P < .001) with exposure to people, other than patients with known or suspected COVID-19. Home testing increased in June to 36.4% (positivity 19.9%) and decreased to 25% (positivity 13.5%) by November. Conclusion: Our cohort findings show the overall increase in both home testing and ever positivity from April to November - a period where changes in variants of concern of SARS-CoV-2 were reported nationwide. Having an exposure to people, other than patients with known or suspected COVID-19 was significantly associated with both, higher home testing frequency and ever-test positivity.

Enhanced plant-derived vesicles for nucleotide delivery for cancer therapy.

Small RNAs (microRNAs [miRNAs] or small interfering RNAs [siRNAs]) are effective tools for cancer therapy, but many of the existing carriers for their delivery are limited by low bioavailability, insufficient loading, impaired transport across biological barriers, and low delivery into the tumor microenvironment. Extracellular vesicle (EV)-based communication in mammalian and plant systems is important for many physiological and pathological processes, and EVs show promise as carriers for RNA interference molecules. However, some fundamental issues limit their use, such as insufficient cargo loading and low potential for scaling production. Plant-derived vesicles (PDVs) are membrane-coated vesicles released in the apoplastic fluid of plants that contain biomolecules that play a role in several biological mechanisms. Here, we developed an alternative approach to deliver miRNA for cancer therapy using PDVs. We isolated vesicles from watermelon and formulated a hybrid, exosomal, polymeric system in which PDVs were combined with a dendrimer bound to miRNA146 mimic. Third generation PAMAM was chosen due to its high branching structure and versatility for loading molecules of interest. We performed several in vivo experiments to demonstrate the therapeutic efficacy of our compound and explored in vitro biological mechanisms underlying the anti-tumor effects of miRNA146, which are mostly related to its anti-angiogenic activity.

Outcome of Mechanical Thrombectomy for Acute Basilar Artery Occlusion in Patients with Intracranial Atherosclerotic Disease.

INTRODUCTION: Intracranial atherosclerotic disease (ICAD) has been identified as a major cause of acute basilar artery occlusion (BAO).This study compared the characteristics and treatment outcomes in acute BAO patients with and without ICAD. METHODS: A prospective cohort study was conducted at 115 People's Hospital, Ho Chi Minh city, Vietnam from August 2021 to June 2023. Patients with acute BAO who underwent endovascular treatment within 24 h from symptom onset were included (thrombectomy alone or bridging with intravenous alteplase). The baseline characteristics and outcomes were analyzed and compared between patients with and without ICAD. Good functional outcome was defined as mRS ≤3 at 90 days. RESULTS: Among the 208 patients enrolled, 112 (53.8%) patients were categorized in the ICAD group, and 96 (46.2%) in the non-ICAD group. Occlusion in the proximal segment of the basilar artery was more common in patients with ICAD (55.4% vs. 21.9%, p < 0.001), whereas the distal segment was the most common location in the non-ICAD group (58.3% vs. 10.7%, p < 0.001). Patients in the ICAD group were more likely to undergo treatment in the late window, with a higher mean onset-to-treatment time compared to the non-ICAD group (11.6 vs. 9.5 h, p = 0.01). In multivariable logistic regression analysis, distal segment BAO was negatively associated with ICAD (aOR 0.13, 95% CI: 0.05-0.32, p < 0.001), while dyslipidemia showed a positive association (aOR 2.44, 95% CI: 1.15-5.17, p = 0.02). There was a higher rate for rescue stenting in the ICAD compared to non-ICAD group (15.2% vs. 0%, p < 0.001). However, no significant differences were found between the two groups in terms of good outcome (45.5% vs. 44.8%, p = 0.91), symptomatic hemorrhage rates (4.5% vs. 8.3%, p = 0.25), and mortality (42% vs. 50%, p = 0.25). CONCLUSION: ICAD was a common etiology in patients with BAO. The location segment of BAO and dyslipidemia were associated with ICAD in patients with BAO. There was no difference in 90-day outcomes between BAO patients with and without ICAD undergoing endovascular therapy.

A graphene oxide based composite granule for methylene blue separation from aqueous solution: Adsorption, kinetics and thermodynamic studies.

Graphene oxide and chitosan composite material using as a high-efficiency and low-cost granular adsorbent for methylene blue removal was fabricated via self-assembling method. The effects of pH value, contact time, initial concentration, adsorbent dose, temperature, and recyclic stability on the adsorption performance of methylene blue in aqueous solution were investigated in detail. Desorption process with the effects of solvents, contact time, and temperature were also conducted carefully in this study. The adsorption kinetics and adsorption isotherm of dye adsorption process showed that dye adsorption process was fitted to the pseudo-second-order kinetic model and the Freundlich adsorption isotherm, indicating a physical adsorption process with multilayer adsorption. The intra-particle diffusion model indicated that the dye adsorption by the granular adsorbent was strongly happened during the first 4 h. The thermodynamic study showed that the adsorption was a spontaneous and exothermic process and dye ions were condensed onto the surface of adsorbent. The maximum adsorption capacity of dye on the granular adsorbent was calculated as 951.35 mg/g and the adsorbent could maintain its adsorption performance after six cycles. In general, this study provided an efficient, cost-effective, and recyclable the granular adsorbent for dye separation from aqueous solution.

Chemical constituents from the leaves of Sindora siamensis var. maritima and their antimicrobial and α-glucosidase inhibitory activities.

Two new glycosides, sindosides A-B (1-2), along with 11 previously identified metabolites (3-13), were isolated from an ethanolic extract of the leaves of Sindora siamensis var. maritima. The structures of the purified phytochemicals were elucidated by interpreting their spectroscopic data (IR, NMR, and HRMS). The absolute configuration of compound 1 was established by experimental and calculated ECD spectra. The antimicrobial results revealed that compound 8 selectively inhibited C. albicans fungal with a MIC value of 64 µg/mL, whereas 11 presented a weak inhibition toward E. faecalis, S. aureus, and B. cereus bacterial strains with the same MIC value of 128 µg/mL. Interestingly, compounds 1, 2, 8, 9, and 11 showed α-glucosidase inhibitory activity with IC50 values ranging from 14.42 ± 0.21 to 30.62 ± 0.18 µM, which were more active than the positive control (acarbose, with an IC50 value of 46.78 ± 1.37 µM). Enzyme kinetic analysis revealed that compounds 1, 2, and 11 behaved as uncompetitive inhibitors with Ki values of 8.60 ± 1.04, 5.16 ± 0.73, and 7.17 ± 0.98 µM, respectively.

Exploring the Phytochemical Diversity and Antioxidant Potential of the Vietnamese Smilax glabra Roxb: Insights from UPLC-QTOF-MS/MS and Zebrafish Model Studies.

Research on natural products is growing due to their potential health benefits and medicinal properties. Despite regional variations in phytochemical composition and bioactivity, Smilax glabra Roxb (SGB) has attracted the interest of researchers. Scientists are particularly interested in the Vietnamese SGB variant, which is influenced by biological and environmental factors. Despite geographical differences in phytochemical makeup and bioactivities, SGB remains a fascinating subject in traditional herbal medicine. Using ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS), the phytochemicals in Vietnamese SGB extracts were investigated. This study revealed a wide range of phytochemical compounds, including flavonoids, terpenoids, glycosides, alkaloids, organic acids, phenolics, and steroids. Furthermore, utilizing zebrafish as a model organism, we discovered that these extracts have the surprising ability to greatly improve the survival rate of zebrafish larvae exposed to oxidative stress caused by arsenite (NaAsO2) and hydrogen peroxide (H2O2). Notably, our discoveries suggest the occurrence of new antioxidative pathways in addition to the kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, expanding the understanding of the antioxidant properties and potential therapeutic uses of these plants. To summarize, our research findings shed light on the phytochemical composition of Vietnamese SGB, revealing its potential as a natural antioxidant and encouraging further exploration of its underlying mechanisms for future innovative antioxidant therapies.

Extracting lignin from sugarcane bagasse for methylene blue and hexavalent chromium adsorption in textile wastewater: a facile, green, and sustainable approach.

This study presents the process of extracting lignin from sugarcane bagasse collected in the Mekong Delta, Vietnam by the alkali method. NaOH has been used as an effective, environmentally friendly chemical to enhance the extraction process. The obtained lignin was applied for methylene blue (MB) and hexavalent chromium (Cr(vi)) removal. Factors influencing lignin extraction and adsorption processes of MB and Cr(vi) were investigated, showcasing the sustainable reusability of lignin extracted from sugarcane bagasse. Lignin characterization was also carried out by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA) techniques. The results showed that the extracted lignin content reached 38.61% under optimal conditions (NaOH concentration of 10%, reaction temperature of 90 °C and reaction time of 90 min). The adsorption efficiency and capacity of lignin reached 90.90% and 9.09 mg g-1 for MB and 80.10% and 28.04 mg g-1 for Cr(vi), respectively, under optimum adsorption conditions (pH, adsorption time, initial methylene blue concentration, and used lignin content). The adsorption process obeyed Langmuir adsorption and was principally physical adsorption. These findings prove sugarcane bagasse based lignin as a cheap and efficient adsorbent for MB and Cr(vi) removal, which contributes to the utilization of the abundant agricultural by-product for wastewater treatment.

Androgenicity in Young Women and Development of Metabolic Syndrome Before Menopause: The CARDIA and CARDIA Women's Studies.

Context: There are no reported data from prospective long-term studies on the relation of androgen levels in young women with development of metabolic syndrome (MetS) before menopause. Objective: We investigated associations of androgens and SHBG with incident MetS during 23 years of follow-up. Methods: We included 366 White and 375 Black women ages 20 to 32 years participating in the CARDIA study and CARDIA Women's study, free of MetS at baseline examination (1987-1988), and premenopausal 23 years later. Androgens and SHBG were categorized into quartiles. MetS was defined according to the American Heart Association/National Heart, Lung, and Blood Institute 2009 Joint Scientific Statement. Cox proportional hazards models were used. Results: By year 23, 30% of women developed MetS. Adjusting for baseline age, race, and education, hazard ratios (95% CI) of developing MetS were 1.46 (1.02-2.10) and 2.22 (1.53-3.21) for women in the highest vs lowest total testosterone (T) and free T quartile, respectively. The hazards of developing MetS were 47%, 59%, and 53% lower for women with SHBG in the second, third, and fourth quartiles (vs lowest quartile), respectively. Associations were attenuated for total T with further adjustments for smoking, physical activity, menstrual status, oral contraceptive/hormone (OCHM) use, insulin level, oligomenorrhea, and age at menarche, but remained statistically significant for free T and SHBG. Associations were similar for both Blacks and Whites, and OCHM nonusers, but not for OCHM users. Conclusion: High androgenicity in young premenopausal women is associated with higher risk of future MetS, suggesting that early assessment of androgens may contribute to prevention.

Prospective early adulthood risk factors for vasomotor symptoms in the Coronary Artery Risk Development in Young Adults study.

OBJECTIVE: Previous studies have assessed potential risk factors for vasomotor symptoms (VMS) beginning in midlife. We examined whether early adulthood risk factors predict VMS trajectories over time. METHODS: We performed a secondary data analysis of the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based cohort. We included women who answered questions about VMS at three or more examinations (n = 1,966). We examined whether risk factors at baseline (when participants were aged 18-30 y; average age, 25 y) and the year 15 (Y15) exam (at ages 33-45 y; average age, 40 y) were associated with VMS trajectories from Y15 through Y35. Logistic regression models were used to evaluate the associations with VMS trajectories. RESULTS: We identified three trajectories of VMS presence: minimal (40%), increasing over time (27%), and persistent (33%). Baseline factors associated with persistent VMS over time included Black race, less than a high school education, depressive symptoms, migraines, cigarette use, and at Y15 hysterectomy. Baseline factors associated with increasing VMS over time included Black race and lower body mass index. Risk factors for bothersome VMS were similar and also included thyroid disease, although thyroid disease was not associated with persistence of VMS over time. Associations were similar among women who had not undergone hysterectomy and in Black and White women. CONCLUSIONS: Risk factors for VMS may be identified in early adulthood. Further examination of risk factors such as migraines and depressive symptoms in early adulthood may be helpful in identifying therapies for VMS.

Ultrasensitive Upconversion Nanoparticle Immunoassay for Human Serum Cardiac Troponin I Detection Achieved with Resonant Waveguide Grating.

Selective detection of biomarkers at low concentrations in blood is crucial for the clinical diagnosis of many diseases but remains challenging. In this work, we aimed to develop an ultrasensitive immunoassay that can detect biomarkers in serum with an attomolar limit of detection (LOD). We proposed a sandwich-type heterogeneous immunosensor in a 3 × 3 well array format by integrating a resonant waveguide grating (RWG) substrate with upconversion nanoparticles (UCNPs). UCNPs were used to label a target biomarker captured by capture antibody molecules immobilized on the surface of the RWG substrate, and the RWG substrate was used to enhance the upconversion luminescence (UCL) of UCNPs through excitation resonance. The LOD of the immunosensor was greatly reduced due to the increased UCL of UCNPs and the reduction of nonspecific adsorption of detection antibody-conjugated UCNPs on the RWG substrate surface by coating the RWG substrate surface with a carboxymethyl dextran layer. The immunosensor exhibited an extremely low LOD [0.24 fg/mL (9.1 aM)] and wide detection range (1 fg/mL to 100 pg/mL) in the detection of cardiac troponin I (cTnI). The cTnI concentrations in human serum samples collected at different times during cyclophosphamide, epirubicin, and 5-fluorouracil (CEF) chemotherapy in a breast cancer patient were measured by an immunosensor, and the results showed that the CEF chemotherapy did cause cardiotoxicity in the patient. Having a higher number of wells in such an array-based biosensor, the sensor can be developed as a high-throughput diagnostic tool for clinically important biomarkers.

EphA2- and HDAC-Targeted Combination Therapy in Endometrial Cancer.

Endometrial cancer is the most frequent malignant tumor of the female reproductive tract but lacks effective therapy. EphA2, a receptor tyrosine kinase, is overexpressed by various cancers including endometrial cancer and is associated with poor clinical outcomes. In preclinical models, EphA2-targeted drugs had modest efficacy. To discover potential synergistic partners for EphA2-targeted drugs, we performed a high-throughput drug screen and identified panobinostat, a histone deacetylase inhibitor, as a candidate. We hypothesized that combination therapy with an EphA2 inhibitor and panobinostat leads to synergistic cell death. Indeed, we found that the combination enhanced DNA damage, increased apoptosis, and decreased clonogenic survival in Ishikawa and Hec1A endometrial cancer cells and significantly reduced tumor burden in mouse models of endometrial carcinoma. Upon RNA sequencing, the combination was associated with downregulation of cell survival pathways, including senescence, cyclins, and cell cycle regulators. The Axl-PI3K-Akt-mTOR pathway was also decreased by combination therapy. Together, our results highlight EphA2 and histone deacetylase as promising therapeutic targets for endometrial cancer.

Relationship of calcium and magnesium intakes with the dietary approaches to stop hypertension score and blood pressure: the International Study of Macro/micronutrients and Blood Pressure.

OBJECTIVE: Research investigating calcium and magnesium intakes from the Dietary Approaches to Stop Hypertension (DASH) pattern and other sources in association with blood pressure is limited. We aimed to characterize sources/intake levels of calcium and magnesium in relation to overall diet quality (DASH-score) and determine modification effects with DASH score and blood pressure. METHODS: Cross-sectional United States data (average dietary and supplement intake from four 24 h recalls and eight blood pressure measurements) from two separate visits, 2195 men and women (40-59 years) in the International Study of Macro/Micronutrients and Blood Pressure were analysed. Food-based adherence to the DASH diet was estimated. Linear models tested associations between each 1-point DASH score with blood pressure. Participants were stratified by adherence to sex-specific recommended allowance for magnesium and calcium intakes. Effect-modification was tested across DASH-score quintiles and median of urinary sodium. RESULTS: DASH-score was inversely associated with SBP in fully adjusted models (-0.27; 95%CI: -0.38 to -0.15 mmHg). SBP was inversely associated with dietary calcium intake from DASH food groups: -1.54 (95% CI: -2.65 to -0.43) mmHg; calcium intake from other non-DASH food groups: -1.62 (95% CI: -2.94 to -0.29) mmHg. Dietary magnesium intake from DASH food groups (-1.59; 95% CI: -2.79, -0.40 mmHg) and from other non-DASH foods (-1.92; 95% CI: -3.31, -0.53 mmHg) was inversely associated with SBP. CONCLUSION: A higher DASH score showed a consistent association with lower BP suggesting a relationship between intakes of calcium and Mg with BP regardless of whether the source is part of the DASH diet or not, even when adjusted for supplement intakes.The INTERMAP is registered as NCT00005271 at www.clinicaltrials.gov .

Endovascular treatment for acute ischemic stroke beyond the 24-h time window: Selection by target mismatch profile.

INTRODUCTION: Endovascular treatment for acute ischemic stroke patients with large vessel occlusion (LVO) has been established as a promising clinical intervention within a late time window of 6-24 h after symptom onset. Patients with slow progression, however, may still benefit from endovascular treatment beyond the 24-h time window (very late window). AIM: The aim of this study is to report insight into the potential clinical benefits of endovascular treatment for acute ischemic stroke beyond 24 h from symptom onset. METHODS: A retrospective analysis was performed on consecutive patients undergoing endovascular treatment for acute anterior circulation LVO ischemic stroke beyond 24 h. Participants were recruited between July 2019 and November 2020. Patients were selected based on the DAWN/DEFUSE 3 criteria (Perfusion-RAPID, iSchemaView) and patients receiving treatment beyond 24 h were compared to a group of patients receiving endovascular treatment between 6 and 24 h after symptom onset. The primary outcome was the proportion of patients with functional independence at 90 days (modified Rankin Scale score of 0-2). The secondary outcomes were shift modified Rankin Scale (mRS) analysis and successful reperfusion was defined by thrombolysis in cerebral infarction (TICI) 2b-3 on the final procedure. Safety outcomes were symptomatic intracranial hemorrhage and death at the 90-day follow-up. Propensity score (PS)-matched analyses were employed to rectify the imbalanced baseline characteristics between the two groups. RESULTS: A total of 166 patients were recruited with a median age of 63.0 (56.0-69.0) and 28.9% of all patients were females. Patients in the beyond 24-h group had a longer onset-to-groin time (median = 27.2 vs 14.3 h, p < 0.001) than those in the 6- to 24-h group. There were no statistically significant differences between the two groups in National Institutes of Health Stroke Scale (NIHSS) (median = 12.0 vs 15.0, p = 0.37), perfusion imaging characteristics (core: median = 11.0 vs 9.0 mL, p = 0.86; mismatch volume: median = 106.0 vs 96.0, p = 0.44; mismatch ratio = 6.46 vs 7.24, p = 0.91), and perfusion-to-groin time (median = 72.5 vs 76.0 min, p = 0.77). No significant differences were noted among patients between the two groups in the primary endpoint functional independence analysis (50.0% vs 46.6%, p = 0.77) and in the safety endpoint analysis: mortality (15.0% vs 11.0%, p = 0.71) or symptomatic hemorrhage (0% vs 3.42%, p > 0.999). In PS-matched analyses, there were no significant differences among patients between the two groups in functional independence (50.0% vs 54.8%, p = 0.74), mortality (16.7% vs 9.68%, p = 0.50), or symptomatic hemorrhage (0% vs 6.45%, p = 0.53). CONCLUSION: Endovascular treatment can be performed safely and effectively in LVO patients beyond 24 h from symptom onset when selected by target mismatch profile. The clinical outcome of these patients was comparable to those treated in the 6- to 24-h window. Larger studies are needed to confirm these findings.

The association of burnout with work absenteeism and the frequency of thoughts in leaving their job in a cohort of healthcare workers during the COVID-19 pandemic.

Introduction: During the coronavirus disease 2019 pandemic, high levels of burnout were reported among healthcare workers. This study examines the association of work absenteeism and frequency of thoughts in leaving current job with burnout among a cohort of healthcare workers during the COVID-19 pandemic. Methods: A cross-sectional survey of healthcare workers was conducted from April-May, 2022 on healthcare workers from 10 hospitals, 18 immediate care centers, and 325 outpatient practices in the Chicago area and surrounding Illinois suburbs. Logistic regression models were used to assess the association of burnout scores (Oldenburg Burnout Inventory-OLBI) and its sub-scores (exhaustion and disengagement scores) with work absenteeism and thoughts of leaving work. Results: One-fifth and 60% of respondents (n = 1,825) reported unplanned absenteeism and thoughts of leaving their job, respectively. After adjusting for covariates, higher burnout scores, especially exhaustion scores, were associated with increased odds of unplanned absenteeism (OR = 1.04, 95% CI: 1.01-1.08). Burnout scores and both sub-scores were also positively associated with the frequency of thoughts of leaving work, e.g., each unit increase in the OLBI burnout score was associated with 1.39 (95% CI: 1.34-1.43) times higher odds of thinking about leaving work "a lot/constantly" vs. "never". Discussion: Overall, this study cohort showed a positive association between burnout scores and unplanned work absenteeism (and frequency of thoughts in leaving job) during the COVID-19 pandemic. More research is needed to support healthcare worker well-being during times of stress and direct solutions to addressing unplanned absenteeism in the light of a pandemic.

Antimicrobial constituents from the leaves of Hibiscus tiliaceus L.

Repeated column chromatography resulted in the isolation of two new megastigmane derivatives, methyl-tiliaceates A and B (1 and 2), along with four known metabolites (3-6) from the leaves of Hibiscus tiliaceus L. The structures of the purified phytochemicals were elucidated by interpreting their NMR, HRESIMS, and CD spectroscopic data, as well as comparison with the previous literature. The compounds isolated were subjected to in vitro antimicrobial assays against a panel of pathogenic microorganisms (Enterococcus faecalis, Staphylococcus aureus, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica, and Candida albicans). Compound 1 showed obvious selective inhibition against the B. cereus strain, whereas 3 - 5 showed weak inhibitory activities against E. faecalis and S. aureus bacterial, and C. albicans fungal strains (with MIC values ranging from 128 to 256 µg/mL).

Computational assessment and in vitro test of phytochemicals of Usnea aciculifera as potential inhibitors of Escherichia coli efflux pump AcrB.

Lichens produce secondary metabolites that have many pharmaceutical activities such as antimicrobial, antioxidant, antiviral, anticancer, antigenotoxic, anti-inflammatory, analgesic and antipyretic activities. However, there is limited research on their efflux pump inhibitory activities. Twelve phytochemicals were isolated from Usnea aciculifera, and their activity of AcrAB-TolC efflux pump inhibition was evaluated. Four potential compounds, which are diffractaic acid (2), 8' -O- methylstictic acid (5), 3-hydroxy-4-(methoxycarbonyl)-2,5-dimethylphenyl 2,4-dimethoxy-3,6-dimethylbenzoate (8) and 3-hydroxy-4-(methoxycarbonyl)-2,5-dimethylphenyl 2-hydroxy-4-methoxy-3,6-dimethylbenzoate (9), were found by virtual screening using pharmacophore and 2D-QSAR model. Compound 8 exhibited AcrB inhibition activity in vitro with an accumulation H33342 percentage compared with untreated control of 202% at a concentration of 50 µM and increased the antibacterial activity of levofloxacin by four-fold at a concentration of 200 µM. By molecular docking and molecular dynamics (MD) simulation, the binding affinity of depside and depsidone derivatives to AcrB was also clarified. Despite the poor docking score to the AcrB binding site, compound 8 was the most stable among the four complexes at 20 ns of MD simulation. The analysis of long MD at 100 ns indicated that compound 8 interacts strongly with the residues in the distal pocket, creating a stable complex with ΔGbind of -31.51 kcal.mol-1. According to the ADMETlab 2.0 web server's predictions of pharmacokinetics and toxicities, compound 8 has the potential for drug development.Communicated by Ramaswamy H. Sarma.

Identification of efflux pump inhibitors for Pseudomonas aeruginosa MexAB-OprM via ligand-based pharmacophores, 2D-QSAR, molecular docking, and molecular dynamics approaches.

Efflux pumps have been reported as one of the significant mechanisms by which bacteria evade the effects of multiple antibiotics. The tripartite efflux pump MexAB-OprM in Pseudomonas aeruginosa is one of the most significant multidrug efflux systems due to its broad resistance to antibiotics such as chloramphenicol, fluoroquinolones, lipophilic ß-lactam antibiotics, nalidixic acid, novobiocin, rifampicin, and tetracycline. A promising strategy to overcome this resistance mechanism is to combine antibiotics with efflux pump inhibitors (EPIs), which can increase their intracellular concentration to enhance their biological activities. Based on 143 EPIs with chemically diverse skeletons, the 3D pharmacophore and 2D-QSAR modelings were developed and used for the virtual screening on 9.2 million compounds including ZINC15, DrugBank, and Traditional Chinese Medicine databases to identify new EPIs. The molecular docking was also performed to evaluate the binding affinity of potential EPIs to the distal-binding pocket of MexB and resulted in 611 potential EPIs. The structure-activity relationship analyses suggested that nitrogen heterocyclic compounds, piperazine and pyridine scaffolds, and amide derivatives are the most favorable chemically features for MexAB inhibitory activities. The results from molecular dynamics analysis in 100 ns indicated that ZINC009296881 and ZINC009200074 were the most potential MexB inhibitors with strong binding affinity to the distal pocket and MM/GBSA ∆Gbind values of - 38.97 and - 30.19 kcal mol-1, respectively. The predicted pharmacokinetic properties and toxicity of these compounds indicated their potential oral drugs. Multistep virtual screening of EPIs for MexAB-OprM, efflux pump multidrug resistant of P. aeruginosa.

Economic burden of Thalassemia treatment: An analysis from the Vietnam Social Security perspective.

OBJECTIVES: Thalassemia is a genetic disorder that significantly impacts the health and well-being of individuals in Vietnam. This study aimed to assess the economic burden of Thalassemia treatment in Lam-Dong Province from the perspective of the Vietnam Social Security and to develop a model to forecast these costs. METHODS: This study analyzed the medical records of all 288 health-insured Thalassemia patients who received treatment in Lam-Dong Province from 2019-2021. The annual economic burden was calculated as the total direct medical cost of treatment per patient over one year. Bayesian Model Averaging (BMA) was utilized to forecast economic burdens. The best fit model was selected based on evaluation criteria including the R2 value, the Bayesian information criterion (BIC), and posterior model probabilities. RESULTS: The study found that the average annual economic burden of Thalassemia treatment was VND 9,947,000 (±6,854,000), equivalent to approximately USD 426.7 (±294.0), with blood transfusions being the main contributor to costs (63%). Using BMA, the best fit model to forecast economic burdens included variables including patient age, sex, and length of hospitalization, with age being the key factor with the greatest impact on the increase in economic burden. CONCLUSION: These findings provided important information for policymakers in Vietnam, as they highlighted the significant economic burden of Thalassemia treatment in the country. By developing a model to forecast these costs, policymakers can make informed decisions on how to allocate resources and support individuals with Thalassemia and their families.