To estimate the prevalence of social isolation (SI) and loneliness by sociodemographic, information and communication technologies use, health behavior, and health status among Mexican older adults (OA) living alone (LA) and those living with others (LWO) during the Covid-19 pandemic.

Data from the Encuesta Nacional de Salud y Nutrición Continua 2021 conducted in Mexico were analyzed. SI and loneliness were measured using internationally validated scales (LSNS-6 and TILS respectively). Analyses were conducted on adults aged 65 years and older, LA and LWO, considering the survey design.

Approximately 30% of OA in Mexico were LA in 2021. Among those LA, the percentage of widowhood, low well-being index and suicidal ideation were higher than in those LWO. SI prevalence was similarly high among individuals LA and those LWO (81.1 and 81.9% respectively), while loneliness prevalence was higher among individuals LA (51.5%) compared to those LWO (35.4%). Some differences in the characteristics of OA with higher prevalences of SI and loneliness were observed between those LA and those LWO.

Targeted interventions are needed to address SI and loneliness in OA, based on whether they are LA or LWO, while considering the vulnerabilities of each living arrangement.

Many factors can influence the occurrence of postoperative pulmonary complications (PPCs) in the perioperative period, but it is unclear whether chronic high-altitude exposure (CHAE) affects the occurrence of PPCs.

This retrospective study included 235,128 surgical patients aged 18 years and older from January 2013 to December 2022. The occurrence of PPCs, such as pneumonia, atelectasis, and respiratory failure, was determined based on the admission and discharge diagnoses. To reduce the confounding effects caused by imbalances in demographic and clinical characteristics at baseline, we employed a 1:1 propensity score matching (PSM) to match the CHAE and non chronically high-altitude exposed (NCHAE) patients. Statistical analyses were conducted from January 1, 2025, to March 1, 2025.

A total of 235,128 cases were included, with 11,075 (4.7%) patients experiencing PPCs. There were 8,565 patients with CHAE, of whom 484 (5.7%) developed PPCs. In contrast, there were 226,562 patients NCHAE, with 10,591 (4.7%) experiencing PPCs. After 1:1 PSM, 8,564 CHAE were matched with 8,564 NCHAE. In the CHAE group, 484 (5.7%) experienced PPCs, while 394 (4.6%) in the NCHAE group shoewd a statistically significant difference (p = 0.002). Adjusted multivariable conditional logistic regression analysis indicated that CHAE increased the incidence of PPCs (odds ratio [OR], 1.25; 95% CI, 1.02-1.53). Furthermore, the length of hospitalization and postoperative hospitalization duration of patients in the CHAE group were longer than those in the NCHAE group.

This retrospective study suggests an association between CHAE and PPCs within 30 days after surgery. However, the undefined exposure duration highlight the need for prospective studies to definitively establish causality.

The Covid-19 pandemic highlighted the urgent need for effective therapies against emerging pathogens. Drug repurposing, defined as the use of existing medications for new therapeutic purposes, was extensively pursued for SARS-CoV-2 but has not yielded successful treatments. This narrative review critically examines the pharmacological and methodological factors that contributed to these unsuccessful outcomes, paying particular attention to tests of azithromycin and hydroxychloroquine. There are many reasons the promise of repurposed drugs was not realized. Many repurposed compounds displayed promising in vitro antiviral activity that did not translate into clinical efficacy. Major pharmacokinetic (PK) limitations, for example, poor oral bioavailability, low concentrations in pulmonary tissue, and extensive plasma protein binding, prevented these drugs from reaching therapeutic levels in humans. Preclinical research often relied on non-human cell lines and animal models that inadequately reflected human physiology, leading to misleading experimental outcomes. Clinical trials were often undermined by methodological limitations, including endpoints with uncertain clinical significance, suboptimal comparators, and insufficient attention paid to key PK and pharmacodynamic (PD) parameters such as half maximal effective concentration (EC50) values. This narrative review emphasizes the importance of integrating comprehensive PK/PD assessments, relevant experimental models, and rigorous trial design to strengthen drug development during future health crises. The relative success of antivirals including molnupiravir, nirmatrelvir, and remdesivir, which were either novel or previously unapproved compounds, suggests the value of designing and developing targeted antivirals. We must coordinate global research, develop pharmacologically sound strategies, and use evidence-based decision-making to effectively prepare for future pandemics and quickly produce effective treatments.

Enveloped virus invasion relies on spike glycoprotein-mediated membrane fusion. Cholesterol that serves crucial roles in modulating protein conformations and membrane properties, plays an essential role in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry. However, the precise regulatory mechanism of cholesterol in SARS-CoV-2 fusion remains unknown. Here, using an in vitro vesicle-vesicle content mixing assay, we demonstrated that the addition of cholesterol enhanced SARS-CoV-2 spike-mediated vesicle-vesicle fusion, with this enhancement being dependent on the C-terminal cytoplasmic domain of spike. Further single-vesicle analyses demonstrate this enhancement primarily stems from increased docking probability, with cholesterol exerting mild effect on fusion probabilities. In the cell-based membrane fusion assay, cholesterol depletion from spike containing membrane significantly reduces syncytia formation and SARS-CoV-2 pseudovirus infection, indicating its modulatory role in this process. Using structured illumination microscopy (SIM) based super-resolution imaging and single-molecule photobleaching microscopy, we demonstrated that spike proteins tended to form into an oligomeric cluster in the presence of cholesterol, likely through the interaction between cholesterol and palmitoylated cysteine rich region (CRR) in the C-terminus of spike. Last, substitution of residues of CRR with alanine in the C-terminus of spike abolished both the cholesterol-induced spike clustering and the cholesterol-dependent enhancement of vesicle docking. Taken together, our results suggest that cholesterol may induce the oligomerization of spike through specific interactions with its CRR, with this structural clustering critically mediating viral docking to host cell membranes, thereby promoting the subsequent membrane fusion and viral entry processes.

Idiopathic pulmonary fibrosis (IPF) carries high mortality and short survival, presenting significant clinical challenges. Current treatments primarily target to mitigate IPF progression, with insufficient focus on prevention.

We established bleomycin (BLM)-induced IPF model in mice and alveolar epithelial cells. Quercetin (QUE) was administered under two mutually exclusive dosing windows: preventive (pre-BLM only) and therapeutic (post-BLM only).

Prophylactic QUE administration in mice prior to BLM challenge achieved fibrosis reduction comparable to post-injury treatment, while better mitigating peaks of epithelial damage, ferroptosis, and senescence. The preventive regimen also accelerated GSH and GPx4 recovery. Mechanistically, QUE triggers adaptive stress in healthy alveolar epithelial cells, evidenced by mild ROS elevation and oxidative stress response pathway activation. This adaptive stress minimally impacts cellular viability, proliferation, clonogenicity, apoptosis, or senescence in healthy cells. Instead, it primes 14-3-3γ-mediated phosphorylation to enhance NRF2 nuclear translocation, driving sustained elevation of GSH and GPx4 and conferring ferroptosis resistance, thereby limiting fibrogenesis. Crucially, co-administration of Mito-TEMPO or Z-VAD-FMK suppressed QUE-induced ROS but concurrently abolished prevention against BLM injury, confirming preconditioning via adaptive stress as the core mechanism.

Our findings unveil QUE as a promising preventive agent against IPF, mediated through alveolar epithelial preconditioning to enhance ferroptosis resistance.

Anaphylaxis is a life-threatening hypersensitivity reaction. Clinical observations suggest heightened susceptibility during viral infections, yet the mechanisms remain poorly defined. Here, we show that both active and passive IgG-mediated anaphylaxis were exacerbated in the setting of acute viral infection. In mice, this enhancement was driven predominantly by FcγRIV, the homolog of human FcγRIIIa. FcγRIV crosslinking induced anaphylactic symptoms selectively in infected animals, with no effect in naive conditions. Among leukocytes, inflammatory monocytes emerged as the principal drivers of this lethal reaction. Viral infection triggered a strong upregulation of FcγRIV on inflammatory monocytes, an effect absent in type I IFN receptor-deficient (Ifnar1-deficient) mice. Extending these findings, we observed increased frequencies of CD16-expressing classical monocytes in patients with acute COVID-19, and murine SARS-CoV-2 infection recapitulated this phenotype. Mechanistically, FcγRIV crosslinking during infection promoted the production of platelet-activating factor, the key mediator of mortality, in a type I IFN-dependent (IFN-I-dependent) manner. Together, these findings indicate that viral infection creates an immune milieu that heightens monocyte sensitivity to Fcγ receptor engagement, positioning these cells as major effectors of IgG-mediated hypersensitivity in the infected host. They further suggest that Fc receptor pathway modulation merits further investigation in contexts with heightened IFN-I responses, such as in systemic lupus erythematosus.

The objective of this research is to explore the combined effect of hemoglobin glycation index (HGI) and clonal hematopoiesis of indeterminate potential (CHIP) on all-cause mortality among patients diagnosed with acute myocardial infarction (AMI).

The presence of CHIP in peripheral blood cells was detected using deep targeted sequencing. AMI patients were divided into groups based on the median value of HGI and assessed for the effect of CHIP on all-cause mortality using multivariable Cox regression and Kaplan-Meier analysis.

Multivariable Cox regression indicated that among patients with HGI above the median value, CHIP carriers exhibited a significantly higher all-cause mortality (any CHIP, adjusted HR: 2.06 95% CI: 1.10-3.85; p = 0.023), with analysis of specific mutations identifying particularly high risks for TET2 (adjusted HR: 3.72, 95% CI: 1.37-10.09; p = 0.010) and TET2/ASXL1 co-mutations (adjusted HR: 2.61, 95% CI: 1.08-6.30; p = 0.033). Kaplan-Meier analysis in the high-HGI group confirmed that carriers of any CHIP (p < 0.001) and common CHIP (p = 0.019) had a higher risk of mortality than noncarriers.

Our study reveals that HGI significantly modifies CHIP-related all-cause mortality risk, which provides a way for refined risk stratification in patients with AMI.

Secondary prevention is critical for patients with established atherosclerotic cardiovascular diseases (ASCVD). The SMART2 model predicts recurrent ASCVD risk but does not account for psychiatric disorders, socioeconomic deprivation or ethnicity. We aimed to evaluate SMART2 model performance overall and in subgroups defined by these factors.

SMART2 was externally validated using electronic health records of patients aged 40-80 in the Leiden-The Hague region. Patients hospitalised for cardiovascular disease or coronary interventions between 1 January 2010 and 31 December 2021 were included. Model performance was assessed using discrimination (10-year area under ROC curve (AUC)) and calibration (observed/expected (OE) ratios and plots, adjusted for competing risks), both overall and in subgroups defined by three factors: psychiatric history, socioeconomic status (SES) and ethnicity.

Among 15 528 patients (66% male, mean age 65) with established ASCVD, median follow-up was 6.0 years. Recurrent cardiovascular events occurred in 2220 patients, and 1820 had competing events. Overall AUC was 0.63 (95% CI 0.61 to 0.65). OE ratio was 0.96 (95% CI 0.92 to 1.00). The model underestimated risk in patients with low SES (OE 1.09, 95% CI 1.02 to 1.17) and in non-Western patients (OE 1.16, 95% CI 1.02 to 1.31). Calibration was adequate in patients with psychiatric history, but the model was substantially underestimating for patients with multiple vulnerabilities-combinations of low SES, non-Western ethnicity and psychiatric history-with OE ranging from 1.19 to 1.29, depending on the combination.

The SMART2 model is well-calibrated in the general population but underestimates risk, especially in subgroups with multiple vulnerabilities. Patients in these vulnerable subgroups may require intensified monitoring. Clinicians should consider social, ethnic and psychiatric factors when interpreting risk estimates.

The limited literature provides minimal information on clinical outcomes among patients undergoing percutaneous coronary intervention (PCI) under different healthcare funding systems, especially in Thailand.

The study aimed to investigate the association between in-hospital clinical outcomes of patients treated with PCI and different types of healthcare funding in Thailand.

The Thai PCI registry is a multicentre, prospective national registry with 39 participating medical centres. Web-based data entry, collected between May 2018 and August 2020, was centrally managed and analysed, providing clinical characteristics, medical management and in-hospital outcomes.

A total of 22 741 patients were analysed and classified into four groups: the Universal Health Coverage Scheme (UC) (63.1%), Government Service Scheme (GS) (26.8%), Social Security Service Scheme (SS) (6.8%) and other payment fund (3.2%). The SS group was younger and predominantly male, whereas cardiovascular risk factors were higher in the GS group. After adjusting for baseline characteristics and management strategies, in-hospital MACE outcomes of ACS patients were significantly higher in patients in the SS (OR=1.81 (1.38, 2.37), p<0.001) and UC group (OR=1.22 (1.04, 1.44), p=0.017) compared with the GS group. Post-procedural myocardial infarction was also higher across all groups. Though differences in all-cause death and cerebrovascular accident/stroke were not statistically significant.

Healthcare funding policies in Thailand significantly associated with disparities in-hospital outcomes of patients undergoing PCI. Patients receiving treatment under the GS scheme demonstrated better clinical outcomes compared to other schemes. These findings highlight the need for policy adjustments aimed at reducing healthcare disparities to improve patient outcomes.

Anticoagulation non-adherence is attributed to myriad factors in patient populations across the world. While direct oral anticoagulants (DOACs) have demonstrated several clinical advantages over other anticoagulant classes, non-adherence persists and the underlying contributors vary by geography.

Outline patient and system level factors involved in DOAC non-adherence in the Bronx.

This retrospective review used all available electronic medical records on patients receiving active DOAC therapy from primary care centres in the Bronx between 2017-2024. Adherent and non-adherent groups were determined by prescription fill status and provider documentation. The two groups were compared by age, gender, race, ethnicity, insurance type, diagnostic indication for DOAC, pharmacy type, employment status, number of comorbidities, number of home medications and primary language. Univariable and multivariable logistic regressions were applied between the groups and categories. P values <0.05 were deemed significant.

The cohort had 938 patients with non-adherence reported in 227 (24.2%) patients. In multivariable logistic regression, non-adherence was more common in younger patients (OR 1.19, CI 1.03 to 1.37, p=0.020) and in males (OR 1.41, CI 1.02 to 1.95, p=0.039). It was also more frequent among patients prescribing from hospital pharmacies (OR 2.70, CI 1.96 to 3.85, p=0.001) and the employed versus retired (OR 1.92, CI 1.09 to 3.57, p=0.032). Non-adherence was borderline significant in Black Non-Hispanics versus White Non-Hispanics (OR 1.75, CI 0.98 to 3.24, p=0.065) and in White Hispanics versus White Non-Hispanics (OR 1.98, CI 0.89 to 4.43, p=0.095). It was also borderline significant in English primary speakers versus Spanish primary speakers (OR 1.64, CI 0.96 to 2.86, p=0.071).

DOAC non-adherence in the Bronx is significantly associated with patient age, gender, employment status and prescribing pharmacy type. Other factors investigated in this study had borderline significant or no significant association and warrant further investigation.