The early-life intestinal microenvironment plays a pivotal role in shaping immune cell development. Here, we identify a colonic Wnt4-expressing stromal cell, enriched during early-life, that promotes iNKT cell proliferation via BMP-MAPK signaling. These stromal cells are spatially associated with iNKT cells and macrophages and exhibit high Bmp2 expression during the neonatal period. Depletion of BMP2 in Wnt4+ stromal cells during, but not after, this time window leads to long-lasting reductions in iNKT cells. These stromal cells are shaped by microbial signals, as germ-free and early-life antibiotic-treated mice exhibit increased Wnt4+ stromal cell abundance and elevated Bmp2 expression, with excessive iNKT cell accumulation that lasts into adulthood. These persistent changes in iNKT cells due to early-life perturbations are associated with altered susceptibility to later-life mucosal disorders. Importantly, similar stromal cells are present in fetal and neonatal human colon, and human rBMP2 promotes iNKT cell growth. Together, our findings reveal a neonatal colonic stromal niche, orchestrated by microbial cues, that regulates colonic immune homeostasis in later-life.
Oral mucosal diseases (OMDs) are common and can severely affect quality of life through pain, functional limitations, and psychological distress. Their prevalence is influenced by lifestyle, socioeconomic factors, and healthcare access, making early diagnosis and effective management essential for improving patient outcomes. To assess OHRQoL in individuals affected by a variety of OMDs, examine the influence of demographic and clinical characteristics on quality-of-life outcomes, and provide insights into the factors most strongly associated with OHRQoL in this population. This cross-sectional study was conducted at an oral medicine clinic in Kuwait. Patients diagnosed with oral mucosal diseases who provided informed consent completed a paper-based, Arabic-translated version of the Oral Health Impact Profile-14 (OHIP-14) questionnaire. The survey collected demographic data and assessed the physical, psychological, and social impacts of oral disease on quality of life. Chi-square, Spearman correlation, Mann Whitney U, Kruskal Wallis, and regression tests were used to examine the associations between different variables at α = 0.05. A total of 103 patients with OMDs and 103 matched controls were included. Patients reported significantly higher psychological discomfort (P = .007) and psychological disability (P = .011) compared to controls. Females had worse Oral Health-Related Quality of Life (OHRQoL) scores than males (P < .05), while patients with premalignant and malignant lesions experienced the greatest impairments. Reactive lesions were associated with better OHRQoL outcomes than immune/infectious and malignant lesions (P < .05). OMDs significantly impair oral health-related quality of life, particularly in psychological domains, with gender and disease type emerging as key determinants. Incorporating psychosocial support into routine care is essential to enhance patient outcomes.
Physical inactivity constitutes a pressing societal problem. To realize physical activity's (PA) potential as a key health resource, mechanisms of PA engagement need to be understood. Laboratory and interventional studies documented that exercise relates to affective well-being (AWB) and suggested that AWB may shape PA behaviour. Digitalization enabled the investigation of how PA relates to AWB in everyday life, but findings from individual studies are ambiguous. Here we compiled 67 datasets (55.2% of eligible records) including 321,345 smartphone-based AWB ratings and nearly 1,000,000 h of accelerometer-measured PA (N = 8,223 participants) until December 2023 to clarify the nature and extent of PA-AWB associations. One- and two-stage individual participant data meta-analyses reveal that momentary AWB is associated with both prior (within, r = 0.05, 99.2% confidence intervals (CI) 0.03 to 0.06; between, r = 0.08, 99.2% CI 0.04 to 0.12) and subsequent (within, r = 0.04, 99.2% CI 0.03 to 0.05; between, r = 0.08, 99.2% CI 0.04 to 0.13) short-term PA in everyday life. Within persons, PA displays a positive association with energetic arousal, positive affective states and valence, yet a negative relation to calmness. The practical effect sizes are comparable to other daily life activities, with energetic arousal evincing the strongest relation to PA. Considerable heterogeneity in associations across individuals can be partially explained by sociodemographic moderators. Between participants, PA relates to positive affective states. The results document the critical relevance of PA-AWB relations in everyday life. They can contribute to the revision and development of health behaviour models and establish a starting point to approach behavioural, physiological and neuronal mechanisms underlying PA-AWB associations.
Root hairs are tubular tip-growing extensions of root epidermal cells that enhance root surface area for water and nutrient acquisition. While the mechanisms governing root hair fate, polarity and tip growth are well understood, the regulation of root hair longevity remains largely unknown. Here we show that root hair cells employ high levels of autophagy to maximize their lifespan in Arabidopsis thaliana. Loss-of-function mutations in the genes encoding the autophagy regulators ATG2, ATG5 or ATG7 induce a premature, cell-autonomous cell death program. This cell death is activated via a gene regulatory network promoted by the NAC transcription factors ANAC046 and ANAC087. Our findings uncover an antagonistic relationship between autophagy and senescence-controlled programmed cell death in root hair lifespan regulation, with potential implications for optimizing plant nutrient and water uptake in crop breeding.
Cancer significantly affects multiple dimensions of patients' well-being, making health-related quality of life (HRQoL) a key outcome in oncology. However, evidence on the clinical and socioeconomic determinants of HRQoL among cancer patients in Iran, particularly in southwestern regions, remains limited. This study aimed to assess HRQoL and to identify its clinical and socioeconomic determinants among cancer patients in southwestern Iran. This cross-sectional descriptive-analytical study was conducted in 2024 among cancer patients attending Shahid Jalil Hospital, Yasuj. A total of 166 eligible patients were recruited through consecutive sampling. HRQoL was assessed using the validated Persian version of the EORTC QLQ-C30. Sociodemographic, clinical, and treatment-related variables were collected through structured interviews and medical records. Data analysis was performed using SPSS 27. Median (IQR) values were reported for HRQoL domains. The Gamma regression model with log link was applied to identify predictors of overall HRQoL. Associations were expressed as Mean Ratios (MRs) with 95% confidence intervals. Participants had a mean age of 58.09 ± 16.08 years; 54.2% were male, and 58.5% had stage IV cancer. The lowest HRQoL scores were observed in cognitive functioning (median: 32.33), physical functioning (38), and role functioning (49), while social functioning showed higher scores (65.67). In multivariable analysis, stage IV cancer (MR = 0.33; 95% CI: 0.14-0.80) and metastatic disease (MR = 0.36; 95% CI: 0.17-0.77) were strongly associated with reduced HRQoL. Conversely, basic health insurance significantly improved HRQoL (MR = 2.15; 95% CI: 1.06-4.36). Other demographic variables were not significant predictors. Disease severity and insurance coverage are major determinants of HRQoL among cancer patients in southwestern Iran. Enhancing early detection, strengthening financial protection, and integrating supportive and palliative care services may improve patient outcomes. Longitudinal studies are recommended to better elucidate HRQoL trajectories.
Understanding patients as persons is foundational to person-centred care, yet this is particularly challenging in intensive care units (ICUs), where patients are often unable to communicate. The Patient Dignity Question (PDQ)-"What do we need to know about you as a person in order to give you the best care possible?"-offers a brief means of eliciting personhood. This study qualitatively examined PDQ responses provided by family members of critically ill ICU patients to understand what families want clinicians to know about their loved ones. Family members of critically ill adults admitted to four ICUs across three hospitals in Winnipeg, Canada, were recruited between July 2021 and August 2022. Following informed consent, participants completed brief PDQ-guided interviews conducted by trained researchers. Response summaries were verified with participants and analyzed using an interpretive description approach. Multiple coders iteratively identified themes describing patient personhood from the family perspective. PDQ responses from 33 family members revealed a central theme of Shared Narratives of Personal Identity, encompassing four interrelated themes: Patients at Their Core, Key Elements of the Person's Story, Illness Experience, and Messages from Family to Staff. Families highlighted personal qualities, relationships, values, roles, spirituality, life experiences, and the impact of illness. PDQs also conveyed practical care recommendations, gratitude, and hopes for comfort, dignity, and compassion. Family members provide rich insights into ICU patients' personhood. The PDQ is a feasible, low-resource tool for integrating personhood into ICU care and may support dignity-conserving, person-centred, and family-centred practice in high-acuity settings.
Obesity is a complex health condition marked by an excessive accumulation of adipose tissue. Bariatric surgery continues to be the most efficacious intervention for attaining significant and enduring weight loss. This study aimed to assess a 6-month probiotics supplementation effect on quality of life (QoL), bowel habits, excess weight loss (EWL) and changes in stool composition and fecal Calprotectin in severely obese patients undergoing different types of bariatric surgeries. This prospective randomized controlled trial involved 200 cases underwent standardized bariatric procedures. Cases were randomized into two equal groups: Probiotic group received either Enterogermina® 6 billion sachets or Lacteol forte® sachets, one sachet twice daily for 6 months postoperatively and control group: Patients received standard postoperative care without probiotics. At 1 month postoperatively, the probiotics group showed a significantly higher QOL and EWL% (p < 0.001) compared to controls. At 3 months, the probiotics group had a significantly higher QOL and EWL% (p < 0.001). At 6 months, the probiotics group showed a statistically significant improvements across all measured outcomes, including QOL, BHQ, and EWL% compared to the control group(p < 0.001). Probiotic group had a significantly lower fecal calprotectin compared to control group (p < 0.001). The probiotic use post-bariatric surgery offers measurable benefits in QOL, weight loss, and gastrointestinal inflammation, regardless of the surgical type. Although procedures like RYGB and OAGB yield superior weight loss, they may induce higher gut inflammation. Meanwhile, sleeve gastrectomy appears to be the most gut-friendly in terms of inflammatory markers and bowel consistency.
To evaluate the accuracy of expert-performed ultrasonography (US) for preoperative localization in minimally invasive parathyroidectomy (MIP) compared with community US and other imaging modalities. Retrospective cohort study. Tertiary referral center for endocrine surgery. A retrospective, single-center diagnostic accuracy study of 227 patients with primary hyperparathyroidism who underwent surgery and pre-operative imaging by a dedicated neck radiologist (expert US). Sensitivity, specificity, and positive predictive value (PPV) were calculated, and were compared to other imaging modalities including community US, 99mTc-MIBI, SPECT-CT and 4DCT. Expert US showed high sensitivity (89%), specificity (98%), and PPV (95%), correctly localizing adenomas in 89% of cases. It outperformed the sensitivity and specificity of community US (50%/95%), MIBI (75%/95%), SPECT-CT (82%/96%) and 4D-CT (52%/94%), respectively, particularly in atypical cases like ectopic adenomas (25% prevalence) and multiglandular disease (6% prevalence). Expert-performed US should be considered the primary imaging modality for guiding MIP. Surgeons should consider referring patients to an expert ultrasonographer in cases of suspected ectopic adenoma, presence of multiglandular disease, before referring to 4D-CT scans or when considering bilateral neck explorations.
Lowering LDL cholesterol (LDL-C) decreases cardiovascular risk substantially in type 2 diabetes. Despite stricter LDL-cholesterol targets in the 2019 ESC/EAS dyslipidemia guidelines, target achievement in clinical practice remains insufficient. TEMD-2 is designed to evaluate LDL-cholesterol target attainment in Turkish patients with type 2 diabetes in the context of the updated 2019 ESC/EAS guidelines. This multicenter cross-sectional study included adults with type 2 diabetes followed in 70 tertiary endocrine clinics across 36 cities between October 2022 and January 2023. Sociodemographic characteristics, comorbidities, lifestyle factors, complications, laboratory measurements, and lipid-lowering therapies were assessed using standardized questionnaires and clinical evaluations. LDL-C target was assigned according to cardiovascular risk categories. Independent predictors of goal attainment were identified using multivariable logistic regression. Among 4956 adults with type 2 diabetes, 99.5% required statin therapy, whereas 37.1% were on treatment. Overall, 8.3% of the cohort achieved LDL-cholesterol targets, with attainment lowest in those at very high risk (5.8%). Target achievement among statin users was 57.7% in moderate-risk, 18.1% in high-risk, and 9.4% in very-high-risk patients. Individuals on target had lower body mass index, haemoglobin A1c (HbA1c), triglycerides, and a lower prevalence of microvascular complications. Statin therapy was the strongest positive predictor of success (odds ratio 2.39), while smoking, presence of neuropathy, nephropathy, female sex, older age, and higher HbA1c were associated with lower likelihood of achieving LDL-cholesterol goals. Therapeutic inertia was present in 87.2% of patients, defined as no intensification of lipid-lowering therapy despite LDL-cholesterol levels above target. Three years after the implementation of the 2019 dyslipidemia guidelines, patients with type 2 diabetes remain far from achieving LDL-C targets, with fewer than one in ten reaching target levels. This shortfall is expected to translate into a growing burden of cardiovascular disease, morbidity, and premature mortality throughout the life course of individuals with diabetes.
Chronic kidney disease is an increasing global public health concern, and the Developmental Origins of Health and Disease (DOHaD) concept proposes that adverse conditions during critical developmental windows predispose offspring to chronic disorders later in life. Maternal protein restriction (MPR), a well-established experimental model reflecting food insecurity, has been shown to impair nephrogenesis and promote long-term renal dysfunction. In this study, we investigated renal metabolic-epigenetic programming induced by gestational and lactational MPR in post-weaning male rats using a global kidney proteomic approach. MPR altered renal structure and profoundly dysregulated protein networks, characterized by downregulation of energy metabolism, ion transport, cytoskeletal organization, membrane integrity, and mitochondrial function, alongside upregulation of innate immune pathways, glutathione metabolism, vesicular trafficking, and cytoskeletal dynamics. Integrated pathway and disease enrichment analyses revealed the potential risk to hypertension, acid-base imbalance, renal tubular transport disorders, nephrosis, and renal failure. Key differentially expressed proteins (e.g., GPX1, CYCS, ATP1A2/ATP1B1, TUBB/TUBA isoforms, ANPEP, and metabolic enzymes) emerged as potential biomarkers of renal metabolic-epigenetic programming. Collectively, these findings identify molecular signatures that link early-life protein restriction to long-term risk of kidney disease and provide mechanistic insight into the nephron- and cell-specific consequences of MPR.
Body image significantly impacts the psychological and physical well-being of breast cancer survivors, with cultural factors shaping its expression and effects. This study aimed to examine the cultural differences in positive and negative body image of female breast cancer survivors in Australia (N = 338) and China (N = 116) and their associations with well-being. We assessed a path model examining how self-objectification, mindful self-care, and body acceptance by others influences body appreciation, functionality appreciation, and body dissatisfaction-and, in turn, their impact on well-being outcomes (quality of life and psychological distress). No significant between-group differences in body image were observed after controlling for demographic and medical factors. Across both countries, mindful self-care and body acceptance by others were associated with higher positive body image. However, the role of body acceptance by others differed culturally: in the Chinese sample it was associated with both positive and negative body image pathways, whereas in the Australian sample it was more directly related to well-being outcomes. Body dissatisfaction consistently predicted poorer well-being across both groups. Positive body image showed a more differentiated pattern: functionality appreciation predicted quality of life in Australian but not in Chinese participants, while body appreciation was associated with lower psychological distress only in the Chinese sample. These findings suggest that positive and negative body image contribute differently to well-being across cultures and that the psychological mechanisms underlying positive body image may vary across cultural contexts. Understanding these culturally embedded pathways may inform more tailored psychosocial interventions for breast cancer survivors.
This study investigated whether soluble fms-like tyrosine kinase-1 (sFlt-1) and angiotensin II type 1 receptor autoantibodies (AT1-AA) - key mediators of preeclampsia (PE) pathophysiology - remain elevated ten years postpartum, thereby contributing to the long-term cardiovascular disease (CVD) risk in women with a history of PE. In a retrospective cohort nested within the PERLA-Brazil project, 205 women were enrolled: 103 with a documented history of PE (PH group) and 102 with normotensive pregnancies (NH group). Participants completed standardized interviews, underwent physical evaluations, and provided blood samples for sFlt-1 and AT1-AA quantification by enzyme-linked immunosorbent assay (ELISA), alongside comprehensive clinical and demographic data collection. No significant differences were observed in circulating sFlt-1 (90.25 ± 6.11 pg/mL in PH vs. 93.30 ± 5.54 pg/mL in NH, p = 0.886) or AT1-AA levels (6.80 ± 0.16 ng/mL in PH vs. 6.34 ± 0.18 ng/mL in NH, p = 0.060) between groups a decade after the index pregnancy. Clinical and biochemical data were collected and compared between groups, with multivariable models adjusted for age, body mass index, and educational attainment. As results, it was observed that women with severe PE history had higher systolic and diastolic blood pressure, higher low-density lipoprotein cholesterol, and a greater prevalence of hypertension. These findings suggest that the long-term cardiovascular burden after PE is not explained by increased plasma levels of sFlt-1 or AT1-AA, but may instead reflect durable downstream vascular and metabolic remodeling. The study underscores PE as a marker of future cardiovascular vulnerability and highlights the need to identify additional mechanisms and biomarkers underlying this risk.This highlights PE as an early-life stressor with persistent effects and underscores the need of lifelong CVD prevention strategies for affected women, as well as the importance of identifying additional biological or physiological markers associated with their sustained risk.
Biochar is a carbon-rich byproduct of biomass pyrolysis. It has emerged as a promising tool in environmental biomanufacturing specifically for the remediation of polycyclic aromatic hydrocarbons (PAHs). PAHs are persistent organic pollutants with significant ecotoxicological and human health risks. This review provides a comprehensive analysis of PAH formation during biochar production, advanced analytical techniques for PAH quantification, and the role of biochar in mitigating PAH contamination in soil and water systems. The effectiveness of biochar in PAH remediation is governed by several mechanisms including π-π interactions, pore-filling, electrostatic forces, and hydrogen bonding. These processes influence sorption efficiency and bioavailability. Moreover, biochar-based bioremediation strategies, including microbial-assisted degradation and engineered biochar composites, offer innovative solutions for contaminated environments. Yet there are several challenges that persists such as PAH desorption, biochar stability, and large-scale deployment persist. To bridge lab performance and field reliability, this study outlines an AI-enabled pipeline for data standards, predictive modelling, and inverse design of biochar tailored to site chemistry. Followed by embedding sustainability through cradle-to-grave life-cycle assessment and decision frameworks that weigh trade-offs among sorption efficacy, by-product risks, and deployment logistics. Future research should prioritize optimizing biochar functionalization, enhancing microbial synergistic interactions, and integrating life cycle assessments to advance scalable and sustainable biomanufacturing approaches for restoring polluted environment.
Water is essential component of life; thus access to clean and safe water is crucial for human consumption, agriculture and other life-sustaining activities. However, water contamination remains a major global concern. Among various pollutants, heavy metals pose significant threat to environment and health due to their high toxicity and carcinogenic nature which has attracted considerable attention of researchers. In this study, CeO2/coconut shell nanocomposites were synthesized and characterized using X-ray Diffraction, Scanning electron microscopy, Energy Dispersive X-ray Spectroscopy, Fourier Transform Infrared Spectroscopy, TGA, and UV-Visible spectroscopy to investigate their structural, morphological, and chemical properties. The objective of this study is to investigate efficiency of the synthesized nanocomposites as an economical and environmental friendly adsorbent to eliminate Cr(VI) from water. Adsorption experiments in batch mode were conducted to determine the effect of key parameters including initial Cr(VI) concentration, pH, adsorbent dosage, and contact time. The analysis of Cr(VI) was performed using UV-Visible Double Beam Spectrophotometer. The synthesized nanocomposites exhibited significant Cr(VI) elimination efficiency. Equilibrium adsorption data were best described by the Langmuir isotherm model, indicating monolayer adsorption on a relatively homogeneous surface, while the Freundlich model suggested the presence of limited surface heterogeneity. To understand the adsorption behavior, five kinetic models (pseudo first order, pseudo second order, intraparticle diffusion, fractional power, and Elovich) were used to analyze the experimental results. Among these, pseudo second order showed the best correlation with the experimental data (R2 = 0.96088) indicating that chemisorption was the dominant mechanism governing Cr(VI) uptake. The Elovich model also demonstrated a reasonably high correlation (R2 = 0.88706), further supporting the presence of heterogeneous surface interactions and activation energy barriers. The findings suggest that CeO2/coconut shell nanocomposites offer an efficient, eco-friendly and cost-effective solution for Cr(VI) removal from water.
Macrophage-colony stimulating factor (M-CSF) plays a crucial role in the proliferation and differentiation of the monocyte-macrophage lineage across vertebrates. In this study, we identified and characterized two CSF1 paralogues and their corresponding receptor genes in the intestine of the goldfish (Carassius auratus), showing sequence homology with known teleost species. Immunohistochemical analysis confirmed the presence of CSF, its receptor CSF-R1, and bone morphogenetic protein 2 (BMP2) in intestinal macrophages. These macrophages were localized within mucosal, submucosal, and muscularis layers, suggesting distinct functional subtypes. Quantitative PCR analysis revealed differential gene expression patterns, with csf1a, csf1b, and csf1ra highly expressed in the brain, while csf1rb transcripts were predominant in the intestine. Immunophenotypic characterization using CD14 and CD86 markers further demonstrated macrophage heterogeneity. Additionally, BMP2-expressing macrophages were observed in the muscularis externa, implying a potential role in neuromuscular regulation. These findings provide novel insights into the molecular and immunohistochemical profiles of goldfish intestinal macrophages, highlighting their potential role in immune responses and gut homeostasis.
The aging process exhibits tissue-specific characteristics, yet its underlying mechanisms remain poorly understood. While it is widely accepted that a reduction in blood vessels in hard tissues contributes to aging, such as in osteoporosis, the vascular changes driving soft tissue aging and degeneration remain unclear. Here, by integrating single-cell transcriptomics and light-sheet imaging, we uncover a striking infiltration of type H-like blood vessels and an aging-specific Coch+ cell subpopulation in aging soft tissues. In a tamoxifen-inducible type H-like blood vessel proliferation mouse model, type H-like blood vessel expansion correlates with impaired locomotor function and accelerated senescence in soft tissues. Following infiltration, type H-like blood vessels secrete CXCL12, driving aberrant differentiation of stem/progenitor cells. Furthermore, Coch+ cell subpopulation promotes type H-like blood vessel invasion via ANG2/VEGF-A signaling. Notably, reducing type H-like blood vessels or inhibiting ANG2/VEGF-A in aging mice, we observed delayed soft tissue aging and improved locomotor function. These findings reveal an underlying mechanism linking vascular infiltration and pathological cell fate transitions in soft tissue aging, highlighting the therapeutic potential of targeting the coupling of type H-like blood vessels and cell fate transition to delay soft tissue aging.
A prospective observational cohort study. To determine whether machine learning models using radiomic features derived from preoperative MRI, clinical variables, or their combination can predict achievement of the minimum clinically important difference (MCID) in function and quality of life after surgery for degenerative cervical myelopathy (DCM). Predicting surgical outcomes in DCM remains challenging, as conventional MRI and clinical scores incompletely reflect spinal cord pathology. Radiomics quantifies voxel-level intensity and texture patterns from routine MRI, providing quantitative measures of tissue heterogeneity that may serve as imaging biomarkers of recovery potential. Forty-six patients with DCM underwent preoperative 3D T2-weighted MRI and surgical decompression. Spinal cord radiomic features (Shape3D, First-Order, GLCM, and GLSZM) were extracted using PyRadiomics. Baseline clinical variables included age, sex, duration of symptoms, T2 hyperintensity, and functional scores assessed with the baseline mJOA and SF-36 PCS scores. Three-month MCID achievement was defined using established thresholds. Predictive models were developed using radiomic features, clinical variables, or their combination. For mJOA MCID, the combined radiomics-clinical model achieved the best performance (AUC = 0.88 ± 0.13). For SF-36 PCS MCID, the combined model achieved an AUC = 0.78 ± 0.17 and an AUCPR of 0.82 ± 0.14. SHapley Additive exPlanations identified texture-based radiomic features and age as dominant predictors for mJOA MCID, whereas first-order radiomic features and baseline SF-36 PCS were most influential for SF-36 PCS MCID. MRI-based spinal cord radiomics improves prediction of meaningful postoperative recovery beyond clinical data, supporting their potential as imaging biomarkers for individualized prognostication in DCM.
Despite advances in oral and injectable HIV prevention options and oral prophylaxis for sexually transmitted infections (STIs) of bacterial origin, there remains a critical need for effective on-demand topical (vaginal and rectal) products for pre- and post-exposure prophylaxis (PrEP and PEP). To fill this gap, we have developed single and first-in-kind multi-active topical inserts for bacterial STIs and HIV/STIs prevention. We have formulated two different inserts, one containing doxycycline (DOX) at 10, 50, and 100 mg doses for bacterial STI prevention, and a multipurpose prevention product (TED insert) that combines DOX (10 mg) with the antiretrovirals tenofovir alafenamide (TAF; 20 mg) and elvitegravir (EVG; 16 mg) to target both bacterial STIs and HIV. Inserts were manufactured using a simple and cost-effective process. Drug loading was within 95-105% of the labeled amount, confirming a robust manufacturing process. In vitro, the inserts disintegrated within 10 min with > 95% drug release within 60 min. The dissolution behavior of DOX inserts showed surface erosion but was affected by medium volume and drug amount. The inserts met key physicochemical targets: hardness (5-8 kg), friability (< 1%), moisture content (< 2%), and osmolality (< 550 mOsm/kg). Based on 6-month storage stability, DOX inserts maintained their physicochemical properties, indicating a shelf life of > 2 years. Preliminary 1-month stability of TED inserts under accelerated conditions showed preservation of their physicochemical properties. These data describe the formulation development and in vitro characterization of topical inserts containing DOX alone or in combination with antiretrovirals (TAF and EVG). Both inserts offer a novel, on-demand topical STI prevention option that supports flexible PrEP/PEP use by both women and men.
Direct exposure to fires and floods adversely impacts mental health, although less is known about youth wellbeing after compounding natural hazards in short time frames. A youth sample aged 16-25 years completed self-report measures of adjustment disorder, alcohol/substance misuse and dependence, depression, anxiety and stress symptoms, and climate change anxiety after drought, bushfire and flood events in New South Wales. From 877 respondents, direct exposure to compounding (i.e., ≥ 2) natural hazards occurred in 182 persons and single hazard in 267. Compounding hazards increased odds for alcohol/substance misuse and dependence (adjusted odds ratio [OR] 2.19, 95% confidence interval [CI] 1.39-3.45) and anxiety (adjusted OR 1.55, 95% CI 1.04-2.30) by comparison to single hazard exposure. There was no interaction between compound hazard and life stressors (quantified by the Adjustment Disorder New Module-8). The association between compounding hazard exposure with mental health was mediated by climate change anxiety; full mediation for adjustment disorder, depression, anxiety, and stress, and partial mediation for alcohol/substance misuse and dependence. Compounding natural hazard exposure may have specific rather than global mental health impacts and is mediated by climate change anxiety. Youth may require specific support to recover from compounding hazards to promote wellbeing and manage climate change anxiety.
As rare earth elements (REEs) are increasingly used in production and daily life, the threat that REEs in urban soil pose to human health has become increasingly prominent. This study focused on urban soils in Kaifeng City. A total of 70 surface soil samples were collected to determine the concentrations of 13 REEs and conduct a risk assessment. To reduce the impact of uncertainties, Monte Carlo simulation was incorporated into the US EPA model to perform uncertainty analysis for health risk assessment. The results showed that: (1) The average total concentration of REEs in the soil of Kaifeng City was 139.36 mg kg-1, and the ecological risk index ranged from 33.98 to 227.01. (2) The average daily doses for adults and children were 0.208 μg kg-1 d-1 and 1.39 μg kg-1 d-1, respectively, both of which were far below the reference threshold (70 μg kg-1 d-1). (3) Monte Carlo simulation revealed that the mean ecological risk index and average daily human exposure dose were similar to the corresponding values obtained from deterministic analysis. The sensitivity contribution rate of exposure parameters was around 80%, remarkably higher than that of REEs concentrations. Consequently, the influence of exposure parameters on the evaluation results should not be underestimated.