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Insights into new mechanosensitive behaviors of G protein-coupled receptors.3 months agoG protein-coupled receptors (GPCRs) represent a diverse and vital family of membrane proteins that mediate intracellular signaling in response to extracellular stimuli, playing critical roles in physiology and disease. Traditionally recognized as chemical signal transducers, GPCRs have recently been implicated in mechanotransduction, the process of converting mechanical stimuli into cellular responses. This review explores the emerging role of GPCRs in sensing and responding to mechanical forces, with a particular focus on the cardiovascular system. Cardiovascular homeostasis is heavily influenced by mechanical forces such as shear stress, cyclic stretch, and pressure, which are central to both normal physiology and the pathogenesis of diseases like hypertension and atherosclerosis. GPCRs, including the angiotensin II type 1 receptor (AT1R) and the β2-adrenergic receptor (β2-AR), have demonstrated the ability to integrate mechanical and chemical signals, potentially through conformational changes and/or modulation of lipid interactions, leading to biased signaling. Recent studies highlight the dual activation mechanisms of GPCRs, with β2-AR now serving as a key example of how mechanical and ligand-dependent pathways contribute to cardiovascular regulation. This review synthesizes current knowledge of GPCR mechanosensitivity, emphasizing its implications for cardiovascular health and disease, and explores advancements in methodologies poised to further unravel the mechanistic intricacies of these receptors.Cardiovascular diseasesPolicy
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LINC00599 Promotes Pulmonary Hypertension via Liquid-Liquid Phase Separation With G3BP1 and MYH9.3 months agoPulmonary hypertension (PH) represents a significant cardiovascular disorder marked by both functional and structural alterations within the pulmonary vasculature. Long noncoding RNAs have been closely associated with PH pathogenesis and progression, particularly in vascular remodeling and cell proliferation. Nonetheless, how long noncoding RNAs interact with downstream targets to modulate PH remains unclear.
The expression levels of LINC00599 were quantified in the mouse lung tissues and pulmonary arterial smooth muscle cells (PASMCs) under hypoxic conditions. The involvement of LINC00599 in PH progression and vascular remodeling was evaluated through in vivo studies. To investigate its role in human PASMC proliferation, small interfering RNA and overexpression plasmids were used.
The expression of LINC00599 is upregulated in the medial layer of pulmonary arteries in experimental PH models and hypoxic PASMCs. Administration of lentivirus-mediated shRNA targeting LINC00599 reverses hypoxic PH in murine models. Mechanistically, LINC00599 promotes PASMC proliferation by modulating stress granule formation through m6A (N6-methyladenosine) modification and facilitating liquid-liquid phase separation with MYH9 (myosin heavy chain 9), a process previously implicated in cell-cycle regulation. Furthermore, its expression is driven by a super-enhancer mediated by the transcription factor ZNF263.
This study demonstrates that LINC00599 promotes PH progression by promoting PASMC proliferation via liquid-liquid phase separation-distinct from classical long noncoding RNA mechanisms. The identification of LINC00599 as a modulator of both m6A-dependent stress granule dynamics and MYH9-mediated phase separation expands our understanding of long noncoding RNA functionality in vascular diseases. As a target in a druggable pathway, LINC00599 holds promise for PH precision medicine.Cardiovascular diseasesPolicy -
Impacts of 21st‑Century Time Traps, Time Management, and Mental Well‑Being on Job Performance in Nurses.3 months agoThe rapid advancement of digital technologies in the 21st century has created new time traps that make time management difficult. Effective time management involves avoiding 21st-century time traps. Time management may enhance nurses' care quality, mental well-being and job performance. This study was conducted to examine the impact of the time traps of the 21st century, time management and mental well-being on nurses' individual job performance.
This cross-sectional study was conducted with 250 nurses working at a state hospital in Turkey. The data were collected using the 'Descriptive Characteristic Form', 'Modern Era Time Traps Scale', 'Time Management Scale', 'Warwick-Edinburgh Mental Well-Being Scale' and 'Individual Job Performance Scale' and analysed using descriptive statistics, pearson correlation and multiple linear regression. The STROBE checklist was utilised for reporting.
Nurses were moderately caught in the modern era time traps. Nurses' time management skills were found to be at a moderate level, while mental well-being and individual job performance were found to be above average. A significant association was found between time traps of the modern era, time management, mental well-being and individual job performance (p < 0.001). The time traps of the modern era, time management and mental well-being together explained 35.6% of the total variance in job performance (Adjusted R2 = 0.356).
The study results demonstrate that as nurses improve their time management and mental well-being, their job performance is also enhanced. Nursing service managers need to recognise the importance of this relationship and develop practices that support time management and mental well-being to increase nurses' job performance.Mental HealthAccessAdvocacy -
Sex differences in the impact of social determinants of health on substance use disorder treatment outcomes.3 months agoSocial determinants of health (SDOH) and clinical severity factors are known to shape substance use disorder (SUD) treatment outcomes, yet limited research has explored how these influences differ by sex. Understanding these differences is important to improving treatment equity and outcomes in publicly funded treatment systems.
This study analyzed data from the 2018-2022 Treatment Episode Data Set-Discharges (TEDS-D), a national dataset of adults discharged from publicly funded SUD treatment programs. Sex-stratified binary logistic regressions were used to examine predictors of two outcomes: treatment non-completion and substance use at discharge. Predictors included SDOH (i.e., employment, education level, housing status, criminal justice involvement, prior treatment history, marital status, health insurance coverage and treatment duration) and indicators of SUD severity (e.g., age at first use, polysubstance use, and co-occurring psychiatric disorders).
Both SDOH and clinical severity indicators were significantly associated with poorer treatment outcomes, with distinct patterns by sex. Women showed more consistent risk for poor treatment outcomes across predictors, including unemployment, psychiatric comorbidities, and polysubstance use, while lack of prior treatment history was the strongest predictor of substance use at discharge and dropout for men. Other predictors, such as housing instability, criminal justice involvement, and later-onset substance use, were also associated with increased risk of non-abstinence and dropout, with notable sex differences. Health insurance coverage was associated with better outcomes for both sexes, with the protective effect more consistent in women.
These findings emphasize the need for sex-informed treatment approaches that address both social determinants of health and clinical complexity. Tailoring care to the unique risks and contexts of men and women may improve retention and reduce substance use at discharge, particularly in publicly funded systems. Highlights We examined social determinants of health (SDOH), and substance use disorder (SUD) severity-related predictors of substance use and treatment completion in a national sample of approximately 7 million adults. Women demonstrated more consistent vulnerability across predictors, including unemployment, co-occurring psychiatric disorders, and polysubstance use. For men, lack of prior treatment for SUD was the most consistent predictor for substance use at discharge and treatment dropout. Housing instability, access to healthcare, and financial barriers showed sex-specific effects, with women generally experiencing great risk of unsuccessful treatment. Findings highlight the importance of improving SUD care to address sex-specific risks and structural barriers, especially in publicly funded systems. Plain English Summary Substance use treatment is not a one-size-fits-all process. Recovery is shaped by both structural challenges, such as housing instability or limited access to care, and the clinical severity of substance use. These factors influence whether someone completes treatment and stays abstinent, and they often affect men and women in different ways. In this study, we analyzed data from approximately 7 million publicly funded substance use treatment episodes across the United States. We looked at how social determinants of health (e.g. employment status, education, housing, access to treatment) and clinical factors (e.g. age of substance use onset, psychiatric comorbidities and polysubstance use), were associated with two key outcomes: whether a person completed treatment and whether they reported use of their primary substance at the end of care. We found that women often faced greater challenges, especially regarding unemployment, co-occurring mental health conditions and using more than one type of substance. For men, being new to treatment was a strong predictor of poorer treatment success. These findings demonstrate the need for treatment programs to offer support that meets men and women where they are, considering the different barriers and challenges each group may face along the path to sustained recovery.Mental HealthAccessCare/ManagementAdvocacy -
Association between DHA and depression: results from the NHANES 2011-2014 and a bidirectional Mendelian randomization analysis.3 months agoA great deal of research demonstrates that the pathophysiology and etiology of depression have been associated with dietary deficiencies in omega-3 polyunsaturated fatty acids (n-3 PUFAs). However, little is known about this association's common genetics and causal relationships. Therefore, we used observational studies combined with bidirectional Mendelian randomization (MR) to investigate a potential association between depression and docosahexaenoic acid (DHA).
Using data from the National Health and Nutrition Examination Survey (NHANES) in the United States from 2011 to 2014, we first conducted a cross-sectional study and analyzed the association between DHA and depression using a statistical method to adjust for confounders in logistic regression. We subsequently utilized genome-wide association study (GWAS) data in the UK to determine the causal relationship between DHA and depression by a genetic approach to assess causality for MR analysis. We used inverse variance weighting (IVW) methods to obtain the majority of the bidirectional causal estimates of MR. We additionally performed sensitivity analyses to analyze the horizontal pleiotropy and heterogeneity of MR results.
This NHANES analysis has shown that DHA is associated with depression in American adults (OR = 0.996, 95% CI 0.993-0.999, P = 0.014). Bidirectional MR analysis demonstrated a significant causal relationship between DHA and depression in the European population (OR = 0.9, 95% CI 0.84-0.97, P = 0.006).
This research provides new insights into the association between DHA and depression. This discovery needs to be validated in further prospective studies that require large sample sizes and sufficient follow-up time.Mental HealthAccessAdvocacy -
Constructing and validating a scale for technostress and employee behavior: evidence from business schools in a developing country.3 months agoThis research aimed to adapt and validate the Techno-Stress Construct in Higher Education (TCHS) for business school faculty in Pakistan. The study involved 300 faculty members from Khyber Paktunkhawa (KP) and Islamabad, who helped translate and adapt the TCHS into a 16-item Pakistani version.Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA) using AMOS 23 were employed to validate the factor structure. EFA identified four factors: techno-overload, techno-invasion, techno-complexity, and techno-uncertainty. CFA confirmed the structural model with excellent fit metrics.Reliability analysis showed strong Cronbach's alpha coefficients for both total and subscale measurements. Construct validity tests indicated significant relationships between TCHS components and faculty emotional exhaustion, work-life balance, and commitment.The findings suggest that the adapted TCHS is a valid tool for identifying techno-stress among educators in Pakistan, which can aid in developing interventions to enhance faculty welfare and productivity. Future research should explore its applicability across different populations.Mental HealthAccessAdvocacy
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Association of mold exposure and solid household fuel use with depression and anxiety among older adults in China.3 months agoExposure to mold and solid cooking fuels represents a significant environmental health concern, contributing substantially to indoor air pollution among elderly populations. However, the association between mold exposure, household fuel use, and mental health remains poorly understood. Here we examine individual and joint associations of these exposures on depression, anxiety, and their co-occurrence in older adults.
We evaluated 9,243 elderly participants from the eighth survey wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) to explore the associations between mold exposure, solid fuel use, and depression, anxiety, and their co-occurrence. Multivariable logistic regression models were employed to quantify these relationships, with adjusted odds ratios (aOR) and 95% confidence intervals (CI) reported.
The study identified a depression prevalence of 13.61% and an anxiety prevalence of 11.79%. Participants exposed to mold demonstrated significantly higher odds of depression (OR = 2.26, 95% CI = 1.93-2.63), anxiety (OR = 2.11, 95% CI = 1.80-2.48), and their co-occurrence (OR = 2.58, 95% CI = 2.10-3.16), compared to participants without mold exposure. Moreover, the use of solid fuels for cooking, as opposed to clean fuels, was correlated with higher occurrence of depression (OR = 1.27, 95% CI = 1.10-1.47), anxiety (OR = 1.31, 95% CI = 1.12-1.52), and their co-occurrence (OR = 1.36, 95% CI = 1.10-1.67). Notably, solid fuel use appeared to attenuate the association between mold exposure and anxiety (Relative excess risk due to interaction [RERI] = -0.22, 95% CI = -0.44, -0.01).
The study found that exposure to mold and use of solid fuels may be associated with higher prevalence of depression, anxiety, and their co-occurrence. Further prospective studies are warranted to validate our findings.Mental HealthAccessAdvocacy -
Partial femoral head replacement: a new innovative surgical technique for precise minimally invasive treatment of association research circulation osseous stage III femoral head necrosis.3 months agoAssociation Research Circulation Osseous (ARCO) stage III is the last chance for joint preservation in patients with osteonecrosis of the femoral head (ONFH). As the femoral head has collapsed at this stage, existing hip-preserving surgical treatments show limited success. We aimed to introduce a new surgical technique called partial femoral head replacement for the treatment of ARCO III femoral head necrosis and to evaluate its safety and efficacy.
Between November 2022 and December 2022, 11 symptomatic hips from 11 patients were enrolled in this retrospective study. The surgeon precisely removed the necrotic area of the femoral head through a bone tunnel at the femoral neck and implanted a prosthesis that matched each patient's anatomy and femoral head contour. Details of the demographics, surgical information, imaging findings, and any complications were retrospectively collected. Clinical scores, including the visual analogue scale (VAS) score, Harris Hip Score (HHS), and 12-Item Short-Form Health Survey (SF-12) scores, were determined. Each patient was followed for at least one year.
The mean operative time per hip was 57.27 ± 15.23 min, the mean estimated blood loss was 110 ± 60.62 ml, and the mean incision length was 3.35 ± 0.38 cm. The VAS score at the one-year follow-up showed great pain relief (7.5 ± 0.9 vs. 1.6 ± 1.2, P < 0.01). The HHS improved significantly compared to the preoperative score (90.3 ± 3.7 vs. 42.9 ± 4.4, P < 0.01). The SF-12 scores also showed that all patients experienced varying degrees of physical (42.1 ± 5.1 vs. 27.7 ± 7.1, P<0.01) and mental (44.3 ± 4.7 vs. 36.4 ± 3.8, P<0.01) health improvement. Radiologically, there were no abnormalities on the latest imaging examination. Clinically, no serious postoperative complications occurred during the treatment.
Our preliminary clinical results showed that partial femoral head replacement was a safe and effective method for the treatment of ARCO III femoral head necrosis. With the trend of younger ONFH patients and increasing emphasis on hip preservation, partial femoral head replacement may provide a new minimally invasive hip-preserving option for these patients.Mental HealthAccessCare/ManagementAdvocacy -
Assessment of medical errors awareness among nursing students during their clinical internship: Palestinian perspectives.3 months agoMedical errors are a major concern for patient safety in healthcare institutions globally, making this a critical public health issue leading to significant problems, including increased hospital stays and higher mortality rates.
This study aims to assess nursing students' awareness of medical errors during their clinical internship.
A cross-sectional study was conducted with 280 intern nursing students from the Arab American University in Palestine. A self-administered questionnaire, comprising 43 items across six subscales based on a medical error scale was used to collect data. The analysis was performed using SPSS version 29, with data collected during the Fall of semester 2024.
The overall mean awareness score was 161 (SD = 75.34) out of a possible 215, with a mean item-level score of 3.74 (on a 5-point scale). Among the subscales, the highest mean score was observed in Care Practices (M = 4.06), while the lowest was in Patient Falls (M = 3.38). Approximately 39.6% of students reported medical errors, with 12.5% involving blood transfusion, 11.4% medication errors, and 20.1% categorized as other errors (e.g., needlestick injuries). The majority (65.7%) reported not committing any errors during their clinical practice.
The study suggests that intern nursing students have a low tendency to commit medical errors, which bodes well for the implementation of future patient safety protocols. These findings indicate that nursing students are becoming increasingly proficient in safe care practices, thereby reducing medical error rates, and enhancing patient safety in clinical settings.
Not applicable.Mental HealthAccessCare/ManagementAdvocacyEducation -
Validity of the Nepali Ask Suicide Screening Questions tool for medical inpatients.3 months agoNepal has one of the highest youth suicide rates in the world. Suicide screening is rarely performed during hospitalization, partly due to the lack of validated tools in the local language. We evaluated the validity of the Nepali version of the Ask Suicide-Screening Questions (ASQ) tool in youth population in medical inpatient settings.
We conducted a cross-sectional validation study at two urban hospitals in Nepal between January and July 2022. Patients aged 10 to 24 years admitted to medical wards were recruited through convenience sampling. Patients with significant cognitive impairment, non-fluent in Nepali, or planned early discharge limiting participation were excluded. Trained nurses administered the ASQ followed by the adolescent version of Patient Health Questionnaire (PHQ - 9) and completed a demographic survey. Thereafter a separate team of psychologists, blind to ASQ results, conducted a brief suicide safety assessment (BSSA) as the gold standard for suicide risk screening.
All study procedures were completed by 309 [54.0% male, mean age = 15.79(± 4.2) years] participants and were included in analysis. In our sample, 15.9% (49/309) screened positive with ASQ; 8.4% (26/309) had elevated suicide risk on the BSSA. The ASQ demonstrated good sensitivity (77%; 95% CI: 56-91), specificity (90%; 95% CI: 86-93), positive predictive value (41%; 95% CI: 27-56) and negative predictive value (98%; 95% CI: 95-99) against BSSA.
The Nepali version of ASQ is a good, brief screening tool for identifying suicidal risk. Further validation in wider populations including outpatient setting and routine implementation in clinical practice should be considered.Mental HealthAccessCare/ManagementAdvocacyEducation