Ecotoxicity assessment of additives in commercial biodegradable plastic products: Implications for sustainability and environmental risk.

Biodegradable plastics have gained popularity as environmentally friendly alternatives to conventional petroleum-based plastics, which face recycling and degradation challenges. Although the biodegradability of these plastics has been established, research on their ecotoxicity remains limited. Biodegradable plastics may still contain conventional additives, including toxic and non-degradable substances, to maintain their functionality during production and processing. Despite degrading the polymer matrix, these additives can persist in the environment and potentially harm ecosystems and humans. Therefore, this study aimed to assess the potential ecotoxicity of biodegradable plastics by analyzing the phthalate esters (PAEs) leaching out from biodegradable plastics through soil leachate. Sixteen commercial biodegradable plastic products were qualitatively and quantitatively analyzed using gas chromatography-mass spectrometry to determine the types and amounts of PAE used in the products and evaluate their ecotoxicity. Among the various PAEs analyzed, non-regulated dioctyl isophthalate (DOIP) was the most frequently detected (ranging from 40 to 212 µg g-1). Although the DOIP is considered one of PAE alternatives, the detected amount of it revealed evident ecotoxicity, especially in the aquatic environment. Other additives, including antioxidants, lubricants, surfactants, slip agents, and adhesives, were also qualitatively detected in commercial products. This is the first study to quantify the amounts of PAEs leached from biodegradable plastics through water mimicking PAE leaching out from biodegradable plastics to soil leachate when landfilled and evaluate their potential ecotoxicity. Despite their potential toxicity, commercial biodegradable plastics are currently marketed and promoted as environmentally friendly materials, which could lead to indiscriminate public consumption. Therefore, in addition to improving biodegradable plastics, developing eco-friendly additives is significant. Future studies should investigate the leaching kinetics in soil leachate over time and toxicity of biodegradable plastics after landfill disposal.

Reference Standards for C-Peptide in Korean Population: A Korean Endocrine Hormone Reference Standard Data Center Study.

Background: The Korean Endocrine Hormone Reference Standard Data Center (KEHRS DC) has created reference standards (RSs) for endocrine hormones since 2020. This study is the first of its kind, wherein the KEHRS DC established RSs for serum Cpeptide levels in a healthy Korean population. Methods: Healthy Korean adults were recruited from May 2021 to September 2023. After excluding participants according to our criteria, serum samples were collected; each participant could then choose between fasting glucose only or fasting glucose plus an oral glucose tolerance test (OGTT). If their sample showed high glucose (≥100 mg/dL) or hemoglobin A1c (HbA1c) (≥5.70%), their C-peptide levels were excluded from analyzing the RSs. Results: A total of 1,532 participants were recruited; however, only the data of 1,050 participants were analyzed after excluding those whose samples showed hyperglycemia or high HbA1c. Post-30-minute OGTT data from 342 subjects and post-120-minute OGTT data from 351 subjects were used. The means±2 standard deviations and expanded uncertainties of fasting, post-30-minute and 120-minute OGTT C-peptide levels were 1.26±0.82 and 0.34-3.18, 4.74±3.57 and 1.14-8.33, and 4.85±3.58 and 1.25-8.34 ng/mL, respectively. Serum C-peptide levels correlated with obesity, serum glucose levels, and HbA1c levels. Conclusion: The RSs for serum C-peptide levels established in this study are expected to be useful in both clinical and related fields.

Impaired autophagy in myeloid cells aggravates psoriasis-like skin inflammation through the IL-1ß/CXCL2/neutrophil axis.

BACKGROUND: Psoriasis is an inflammatory skin disease characterized by the hyperproliferative epidermal keratinocytes and significant immune cells infiltration, leading to cytokines production such as IL-1ß, TNF-α, IL-23, and IL-17. Recent study highlights the critical role of IL-1ß in the induction and activation of pathogenic Th17 and IL-17-producing γδ T cells, contributing to psoriasis. However, the mechanism underlying IL-1ß dysregulation in psoriasis pathogenesis is unclear. Autophagy regulates IL-1ß production and has a pleiotropic effect on inflammatory disorders. Previous studies showed controversial role of autophagy in psoriasis pathogenesis, either pro-inflammatory in autophagy-deficient keratinocyte or anti-inflammatory in pharmacologically autophagy-promoting macrophages. Thus, the direct role of autophagy and its therapeutic potential in psoriasis remains unclear. METHODS: We used myeloid cell-specific autophagy-related gene 7 (Atg7)-deficient mice and determined the effect of autophagy deficiency in myeloid cells on neutrophilia and disease pathogenesis in an imiquimod-induced psoriasis mouse model. We then assessed the pathogenic mechanism focusing on immune cells producing IL-1ß and IL-17 along with gene expression profiles associated with psoriasis in mouse model and public database on patients. Moreover, therapeutic potential of IL-1ß blocking in such context was assessed. RESULTS: We found that autophagy deficiency in myeloid cells exacerbated neutrophilic inflammation and disease pathogenesis in mice with psoriasis. This autophagy-dependent effect was associated with a significant increase in IL-1ß production from myeloid cells, particularly macrophages, Cxcl2 expression, and IL-17 A producing T cells including γδ T cells. Supporting this, treatment with systemic IL-1 receptor blocking antibody or topical saccharin, a disaccharide suppressing pro-IL-1ß expression, led to the alleviation of neutrophilia and psoriatic skin inflammation linked to autophagy deficiency. The pathophysiological relevance of this finding was supported by dysregulation of autophagy-related genes and their correlation with Th17 cytokines in psoriatic skin lesion from patients with psoriasis. CONCLUSIONS: Our results suggest that autophagy dysfunction in myeloid cells, especially macrophages, along with IL-1ß dysregulation has a causal role in neutrophilic inflammation and psoriasis pathogenesis.

Typology and implications of verified attacks on health care in Ukraine in the first 18 months of war.

Attacks on health care are part of the spectrum of threats that health care endures during conflict. Protecting health care services against attacks depends on understanding the nature and types of attacks that occur during conflict. The World Health Organisation has implemented the Surveillance System for Attacks on Health Care (SSA) in Ukraine since 2020, and the system has continued to monitor and report on attacks on health care during the war in Ukraine. This study aims to analyse the data reported through the SSA for the first 18 months of the war. This paper involves a retrospective, descriptive study based on the analysis of publicly available SSA data of all incidents of attacks on health care in Ukraine reported through the SSA between February 24th 2022 and August 24th 2023. Out of the 1503 verified attacks, 37% occurred in the initial six weeks of the war. Attacks involving violence with heavy weapons were among the most common incidents reported (83%). The reported attacks were associated with a total of 113 deaths and 211 injuries among health care workers and patients: 32 (2%) attacks were associated with a death of a health care worker or patient, and 63 (4%) were associated with an injury. Health transports facing attacks had a higher probability of experiencing casualties than other health resources (p<0.0001, RR 3.1, 95%CI 1.9-4.9). In conclusion, the burden of attacks on health care in Ukraine was high and sustained over the course of the first 18 months of the war. Reported casualties were not homogenously distributed among attack incidents, but occurred in a set of high-casualty incidents. Health transports were found to be particularly vulnerable. In addition to continued calls for a cessation of hostilities, prevention, protection, mitigation, and reconstruction strategies are urgently required.

Primary Intracranial Ewing Sarcoma With an Unusual Presentation: A Case Report.

Primary extraosseous intracranial Ewing sarcoma (ES) is an extremely rare disease, limited to the pediatric population, that primarily originates in the skull. Here, we present an unusual case of adult Ewing's sarcoma originating from the brain parenchyma. The 50-year-old male patient visited our hospital with severe headache lasting 3 weeks. MRI presented 6.1×6.2×5.2 cm sized heterogeneously enhanced mass containing peritumoral edema in the right frontal lobe. The patient underwent right frontal craniotomy, at which time the gray and red masses adhered to the surrounding brain parenchyma. The mass was completely resected using neuronavigation and electrophysiological monitoring. Histopathological examination revealed ES-compatible findings of small round cell tumor and CD-99 positive membranous immunostaining. Next generation sequencing revealed translocation and fusion of EWSR1 and FLI1, consistent with a confirmed diagnosis of ES. Consequently, the patient underwent postoperative radiotherapy. The present case revealed adult primary intracranial ES arising from the frontal lobe. Although its etiology remains poorly understood, intraparenchymal ES should be included in the differential diagnosis of parenchymal brain tumors.

Adiponectin-to-leptin ratio and incident chronic kidney disease: Sex and body composition-dependent association.

BACKGROUND: The association between the adiponectin-to-leptin ratio (A/L ratio) and the risk of incident chronic kidney disease (CKD) is poorly understood. This study aimed to investigate the association between A/L ratio and the risk of incident CKD and to examine whether such a relationship varied according to sex and body composition. METHODS: In this prospective community-based cohort, participants with normal kidney function were analysed (N = 5192). The association between the A/L ratio at baseline and the risk of incident CKD, defined as two or more occasions with an estimated glomerular filtration rate of <60 mL/min/m2 or proteinuria of ≥1+ on a dipstick test during the follow-up period, was evaluated using multivariable Cox proportional hazards analyses. Subgroup analyses were conducted based on sex, body mass index (BMI) and the presence of sarcopenia. RESULTS: The participants' mean age was 57.2 ± 8.3 years, and 53.2% were women. The A/L ratio was higher in men compared with women (1.5 [0.8-3.2] and 0.5 [0.3-0.9] µg/ng, P < 0.001). During a median follow-up of 9.8 [9.5-10.0] years, 417 incident CKD events occurred (8.7 per 1000 person-years). Men in the highest quartile of A/L ratio had a lower risk of incident CKD (adjusted hazard ratio [aHR], 0.57; 95% confidence interval [CI], 0.33-0.99) than those in the lowest quartile. Additionally, a 1.0 increase in A/L ratio was associated with a 12% decreased risk of incident CKD in men (aHR, 0.88; 95% CI, 0.80-0.97). However, no significant association was observed in women. In subgroup analysis stratified by BMI and the presence of sarcopenia, the association between a high A/L ratio and a reduced risk of incident CKD was consistent in men with a BMI < 23.0 kg/m2 and those with sarcopenia. However, no significant association was observed between men with a BMI ≥ 23.0 kg/m2 and those without sarcopenia. CONCLUSIONS: A high A/L ratio is an independent marker of a reduced risk of incident CKD in men, especially in those with a BMI < 23.0 kg/m2 and sarcopenia.

Mer tyrosine kinase regulates bone metabolism, and its deficiency partially ameliorates periodontitis- and ovariectomy-induced bone loss in mice.

Bone homeostasis is maintained by tightly coordinated activities of bone-forming osteoblasts and bone-resorbing osteoclasts. In the present report, the role of Mer tyrosine kinase (MerTK) in bone metabolism was investigated. The expression of MerTK decreased upon BMP2 stimulation of osteoblast precursors. The femurs of Mertk-deficient mice showed significantly increased bone volume with concomitant increase of bone formation and reduction in bone resorption. These bone phenotypes were attributed to the increased osteoblast differentiation and mineralization accounted by the enhanced ß-catenin and Smad signaling in the absence of MerTK in osteoblast precursors. Although the Mertk-deficient bone marrow macrophages were predisposed to enhanced osteoclast differentiation via augmented Ca2+-NFATc1 signaling, the dramatic increase of Tnfsf11b/Tnfsf11 (Opg/Rankl) ratio in Mertk knockout bones and osteoblast precursors corroborated the reduction of osteoclastogenesis in Mertk deficiency. In ligature-induced periodontitis and ovariectomy models, the bone resorption was significantly attenuated in Mertk-deficient mice compared with wild-type control. Taken together, these data indicate novel role of MerTK in bone metabolism and suggest a potential strategy targeting MerTK in treating bone-lytic diseases including periodontitis and osteoporosis.

Higher potassium intake is associated with a lower risk of chronic kidney disease: population-based prospective study.

BACKGROUND: High-potassium intake is associated with a lower risk of cardiovascular disease. However, the association between potassium intake and the development of chronic kidney disease (CKD) remains unclear. OBJECTIVE: The objective of this study was to investigate whether potassium intake is associated with outcomes of incident CKD. METHODS: This is a population-based prospective observational cohort study from the UK Biobank cohort between 2006 and 2010. We included 317,162 participants without CKD from the UK Biobank cohort. The main predictor was spot urine potassium-to-creatinine ratio (KCR). The primary outcome was incident CKD, which was defined by the International Classification of Disease 10 codes or Operating Procedure Codes Supplement 4 codes. RESULTS: At baseline, individuals with higher KCR had lower blood pressure, body mass index, and inflammation, and were less likely to have diabetes and hypertension. During a median follow-up of 11.9 y, primary outcome events occurred in 15,246 (4.8%) participants. In the cause-specific model, the adjusted hazard ratio (aHR) per 1-standard deviation increase in KCR for incident CKD was 0.90 [95% confidence interval (CI): 0.89, 0.92]. Compared with quartile 1 of KCR, the aHRs (95% CIs) for quartiles 2-4 were 0.98 (0.94, 1.02), 0.90 (0.86, 0.95), and 0.80 (0.76, 0.84), respectively. In sensitivity analysis with different definitions of CKD, the results were similar. In addition, further analysis with dietary potassium intake also showed a negatively graded association with the primary outcome. CONCLUSIONS: Higher urinary potassium excretion and intake were associated with a lower risk of incident CKD.

Plasma Levels of Polyunsaturated Fatty Acids and Adverse Kidney Outcomes.

RATIONALE & OBJECTIVE: Many studies have reported polyunsaturated fatty acids (PUFA) as significant predictors of cardiovascular disease, but little is known about the relationship between PUFA levels and chronic kidney disease (CKD). This study explored this relationship among individuals with and without CKD. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 73,419 participants without CKD (cohort 1) and 6,735 participants with CKD (cohort 2) in the UK Biobank Study, with PUFA levels measured between 2007 and 2010. EXPOSURE: Percentage of plasma PUFA, omega-3 fatty acid (FA), omega-6 FA, docosahexaenoic acid (DHA), and linoleic acid relative to total FA. OUTCOME: Incident CKD for cohort 1 and incident kidney failure requiring replacement therapy (KFRT) for cohort 2. ANALYTICAL APPROACH: Cox proportional hazards regression analyses, including a cause-specific competing risk model. RESULTS: In cohort 1, individuals with higher quartiles of plasma PUFA levels had healthier lifestyles and fewer comorbidities. During 841,007 person-years of follow-up (median 11.9 years), incident CKD occurred in 4.5% of participants (incidence rate, 39.1 per 10,000 person-years). For incident CKD in cohort 1, the adjusted cause-specific hazard ratios for quartiles 2, 3, and 4 were 0.83 (95% CI, 0.75-0.92), 0.85 (95% CI, 0.76-0.96), 0.71 (95% CI, 0.62-0.82), respectively, compared with quartile 1. This inverse relationship was consistently observed for all PUFA types. In cohort 2, although total PUFA levels were not associated with KFRT, higher PUFA subtype levels of DHA were associated with a lower risk of KFRT. LIMITATIONS: Observational design and limited generalizability to individuals with higher disease severity; no data on eicosapentaenoic acid. CONCLUSIONS: Among individuals without CKD, higher plasma PUFA levels and all 4 PUFA components were associated with a lower risk of incident CKD. In individuals with CKD, only the omega-3 component of PUFA, DHA, was associated with a lower risk of KFRT. PLAIN-LANGUAGE SUMMARY: Low amounts of polyunsaturated fatty acids (PUFA) in the blood are suspected of increasing the chances of heart disease, but it is not known whether the PUFA relates to kidney disease occurrence. In a large group without kidney disease in the United Kingdom, people with higher levels of PUFA in their blood tended to have a lower risk of developing kidney disease compared to those with lower PUFA levels. This relationship was consistently observed for all PUFA types. However, in the group with kidney disease, only higher levels of docosahexaenoic acid, a subtype of PUFAs, were associated with a lower risk of developing severe kidney problems that required kidney replacement therapy. These findings suggest that higher levels of PUFA, found in certain healthy fats, might protect against the development of kidney disease in the general population. As kidney function declines, only the docosahexaenoic acid, a subtype of PUFA, appears to be associated with preserved kidney function.

NLRP3 inflammasome activation and NETosis positively regulate each other and exacerbate proinflammatory responses: implications of NETosis inhibition for acne skin inflammation treatment.

Inflammasomes are multiprotein complexes involved in the host immune response to pathogen infections. Thus, inflammasomes participate in many conditions, such as acne. Recently, it was shown that NETosis, a type of neutrophil cell death, is induced by bacterial infection and is involved in inflammatory diseases such as delayed wound healing in patients with diabetes. However, the relationship between inflammasomes and NETosis in the pathogenesis of inflammatory diseases has not been well studied. In this study, we determined whether NETosis is induced in P. acnes-induced skin inflammation and whether activation of the nucleotide-binding domain, leucine-rich family, and pyrin domain-containing-3 (NLRP3) inflammasome is one of the key factors involved in NETosis induction in a mouse model of acne skin inflammation. We found that NETosis was induced in P. acnes-induced skin inflammation in mice and that inhibition of NETosis ameliorated P. acnes-induced skin inflammation. In addition, our results demonstrated that inhibiting inflammasome activation could suppress NETosis induction in mouse skin. These results indicate that inflammasomes and NETosis can interact with each other to induce P. acnes-induced skin inflammation and suggest that targeting NETosis could be a potential treatment for inflammasome-mediated diseases as well as NETosis-related diseases.

OsLRR-RLP2 Gene Regulates Immunity to Magnaporthe oryzae in Japonica Rice.

Rice is an important cereal crop worldwide, the growth of which is affected by rice blast disease, caused by the fungal pathogen Magnaporthe oryzae. As climate change increases the diversity of pathogens, the disease resistance genes (R genes) in plants must be identified. The major blast-resistance genes have been identified in indica rice varieties; therefore, japonica rice varieties with R genes now need to be identified. Because leucine-rich repeat (LRR) domain proteins possess R-gene properties, we used bioinformatics analysis to identify the rice candidate LRR domain receptor-like proteins (OsLRR-RLPs). OsLRR-RLP2, which contains six LRR domains, showed differences in the DNA sequence, containing 43 single-nucleotide polymorphisms (SNPs) in indica and japonica subpopulations. The results of the M. oryzae inoculation analysis indicated that indica varieties with partial deletion of OsLRR-RLP2 showed susceptibility, whereas japonica varieties with intact OsLRR-RLP2 showed resistance. The oslrr-rlp2 mutant, generated using clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), showed increased pathogen susceptibility, whereas plants overexpressing this gene showed pathogen resistance. These results indicate that OsLRR-RLP2 confers resistance to rice, and OsLRR-RLP2 may be useful for breeding resistant cultivars.

The Piezo channel is a mechano-sensitive complex component in the mammalian inner ear hair cell.

The inner ear is the hub where hair cells (HCs) transduce sound, gravity, and head acceleration stimuli to the brain. Hearing and balance rely on mechanosensation, the fastest sensory signals transmitted to the brain. The mechanoelectrical transducer (MET) channel is the entryway for the sound-balance-brain interface, but the channel-complex composition is not entirely known. Here, we report that the mouse utilizes Piezo1 (Pz1) and Piezo2 (Pz2) isoforms as MET-complex components. The Pz channels, expressed in HC stereocilia, and cell lines are co-localized and co-assembled with MET complex partners. Mice expressing non-functional Pz1 and Pz2 at the ROSA26 locus have impaired auditory and vestibular traits that can only be explained if the Pzs are integral to the MET complex. We suggest that Pz subunits constitute part of the MET complex and that interactions with other MET complex components yield functional MET units to generate HC MET currents.

Efficacy and safety of denosumab treatment for Korean patients with Stage 3b-4 chronic kidney disease and osteoporosis.

BACKGROUND/AIMS: We evaluated the efficacy and safety of denosumab treatment in severe chronic kidney disease (CKD) patients with osteoporosis. We also investigated whether the treatment affects the coronary artery calcifications. METHODS: Twenty-seven postmenopausal women with Stage 3b-4 CKD and osteoporosis were enrolled. Twenty patients received denosumab plus calcium carbonate and vitamin D, and seven controls received calcium carbonate and vitamin D for 1 year. Dual-energy X-ray absorptiometry and coronary artery calcium (CAC) scoring computed tomography were performed before and after treatment. Hypocalcemic symptoms and serum calcium levels were evaluated. RESULTS: After 1 year of treatment, the percent changes of femur neck (3.6 ± 3.2% vs. -0.7 ± 4.4%, p = 0.033) and total hip (3.4 ± 3.8% vs. -1.9 ± 2.1%, p = 0.001) bone mineral density (BMD) were significantly increased in the denosumab treated group compared to the control group. However, the percent change of lumbar spine BMD did not differ between two groups (5.6 ± 5.9% vs. 2.7 ± 3.9%, p = 0.273). The percent change of bone alkaline phosphatase was significantly different in the denosumab-treated group and control group (-31.1 ± 30.0% vs. 0.5 ± 32.0%, p = 0.027). CAC scores did not differ between groups. No hypocalcemic events occurred in both groups. CONCLUSION: If carefully monitored and supplemented with calcium and vitamin D, denosumab treatment for 1 year provides significant benefits in patients with Stage 3b-4 CKD and osteoporosis. However, denosumab treatment did not affect coronary artery calcifications in these patients.

Mediation analysis of chronotype, sleep-related factors, and depressive symptoms among workers: a cross-sectional study.

Background: This study aimed to examine the impact of chronotype on depressive symptoms and explore the mediating effects of sleep quality, pre-sleep cognitive arousal, and social jetlag in a sample of wage earners. Methods: A total of 3,917 waged workers were surveyed online in July 2022. Logistic regression and mediation analysis were used to assess the relationship between chronotype (morningness, intermediate, and eveningness) and depressive symptoms (Patient Health Questionnaire ≥ 5), and the mediating effects of Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), and Pre-Sleep Arousal Scale (PSAS). All analyses were adjusted for age, education level, income level, marital status, coffee consumption, alcohol consumption, physical activity, occupation, employment status, and working hours to calculate odds ratios (ORs). Results: The chronotypes of all the participants were divided into morningness (4.7%), intermediate (93.5%), and eveningness (1.8%). Multiple logistic regression analysis showed an increased risk of depression in the eveningness chronotype (OR: 2.96; 95% confidence interval [CI]: 1.51, 5.86). Regarding the mediation analysis, ISI mediated 28.44% (95% CI: 16.39-40.5), PSQI for 31.25% (95% CI: 19.36, 43.15), and PSAS-Cognitive Score (PSAS-C) for 23.58% (95% CI: 10.66, 36.50) of the association between chronotype and depressive symptoms. However, social jetlag did not significantly mediate this relationship. (percentage mediated = 0.75%, 95% CI: -3.88, 5.39). Conclusions: Evening chronotypes exhibit an increased risk of depressive symptoms, which ISI, PSQI, and PSAS-C partially mediated. This suggests that interventions to improve sleep quality and maintain adequate sleep habits may effectively prevent and treat depression in employees with an eveningness chronotype.

"It is because of the love for the job that we are still here": Mental health and psychosocial support among health care workers affected by attacks in the Northwest and Southwest regions of Cameroon.

Attacks on health care have important consequences for the mental health (MH) and work availability of health care workers (HCW). In the conflict-affected Northwest and Southwest (NWSW) regions of Cameroon, health care attacks are common; however, little is known on the MH burden and/or (mental) health-seeking behavior among affected HCW. We therefore conducted a survey on mental conditions (relying on SRQ-20 and WASSS assessments) and access to MH services among 470 HCW from 12 districts in NWSW Cameroon in January-February 2022. In-depth interviews on personal experiences with attacks and on accessing MH services were conducted with a subset of 96 HCW. Among surveyed HCW, 153 (33%) had experienced an attack in the past 6 months, and a further 121 (26%) had experienced attacks more than 6 months ago. HCW facing attacks <6 months ago had significantly higher odds of exhibiting mental disorders (aOR 5.8, 95%CI 3.0-11.3, p<0.001) and of being unable to function (aOR 3.3, 95%CI 1.9-5.7, p<0.001). HCW who experienced an attack >6 months also had higher odds of being unable to function (aOR 2.9, 95%CI 1.7-5.2, p<0.001), and of missing time off work in the week preceding the survey (aOR 3.1, 95%CI 1.8-5.5, p<0.001). Previous access to MH services was also higher among HCW facing attacks. HCW showed a good understanding of the added values of accessing MH services, but faced multiple access barriers (including poor availability of services and their own prioritization of the care of others) and indicated a preference for self-care, peer-support and/or religious support. In conclusion, health care attacks in NWSW Cameroon contributed significantly to severe mental conditions and absenteeism rates among HCW. Strengthening access to MH support among attack-affected HCW is indicated; this should include strengthening of formal MH services and building the capacity of HCW and religious leaders to provide peer-support.

Ocean fronts as decadal thermostats modulating continental warming hiatus.

Over the past decade, an unexpected cooling trend has been observed in East Asia and North America during winter. Climate model simulations suggest that this pattern of stalled warming, besides accelerated warming, will repeat throughout the course of global warming, influenced by the natural decade-long variations in the climate system. However, understanding the exact factors affecting the pace of warming remains a challenge. Here we show that a pause in warming over continental areas-namely, local warming hiatus-can be accompanied by excessive heat accumulation north of the ocean fronts. This oceanic condition, often manifesting in the form of marine heatwaves, constrains the subseasonal growth of atmospheric planetary waves, significantly increasing the likelihood of cold extremes in downstream continents. Our results underscore the importance of closely monitoring changing ocean fronts in response to human-induced warming, which can potentially reshape the inherent decade-long fluctuations within regional climates over the long term.

Insomnia in patients on incident maintenance dialysis and the risk of major acute cardio-cerebrovascular events and all-cause mortality.

BACKGROUND AND HYPOTHESIS: Insomnia is a known risk factor for cardio-cerebrovascular disease in the general population; however, its effect on cardio-cerebrovascular outcomes in end-stage kidney disease patients is unclear. Therefore, this study aimed to investigate the association between cardio-cerebrovascular outcomes and insomnia in patients who initiated maintenance dialysis. METHODS: This study used nationwide Korean health insurance claims data to analyze 79 420 patients who initiated maintenance dialysis from January 2009 to December 2017. Insomnia was defined using claim codes and sleep medication prescription data. Patients were categorized according to the presence of insomnia before and after dialysis initiation: a) no insomnia, b) insomnia before dialysis only (improved insomnia), c) insomnia after dialysis only (developed insomnia), and d) insomnia in both periods (persistent insomnia). The primary and secondary outcomes were major adverse cardiac and cerebrovascular events (MACCE) and all-cause mortality, respectively. The outcome risks were estimated by Cox regression models with inverse probability of treatment weighting. RESULTS: The mean age was 61.4 ± 13.4 years, and 39.7% were women. During the transition period from pre-dialysis to maintenance dialysis, 13.2% experienced insomnia. The insomnia groups showed significantly higher risks for MACCE (weighted hazard ratios [95% confidence intervals]: developed insomnia, 1.26 [1.25-1.28]; improved insomnia, 1.31 [1.29-1.33]; persistent insomnia, 1.39 [1.37-1.41]) and higher all-cause mortality risks than the no insomnia group. The insomnia related cardio-cerebrovascular disease risk elevation was more prominent in younger and male patients. CONCLUSIONS: Insomnia may increase cardio-cerebrovascular disease and all-cause mortality risk among end-stage kidney disease patients who initiate maintenance dialysis.

Circular waste management: Superworms as a sustainable solution for biodegradable plastic degradation and resource recovery.

Bioplastics offer a promising solution to plastic pollution, however, their production frequently relies on edible biomass, and their degradation rates remain inadequate. This study investigates the potential of superworms (Zophobas atratus larvae) for polybutylene succinate (PBS) waste management, aiming to achieve both resource recovery and biodegradation. Superworms exclusively fed on PBS for a month exhibited the same survival rate as those on a standard bran diet. PBS digestion yielded a 5.13% weight gain and a 23.23% increase in protein composition in superworms. Additionally, carbon isotope analyses substantiated the conversion of PBS into superworm components. Gut microbes capable of PBS biodegradation became progressively prominent, further augmenting the degradation rate of PBS under composting conditions (ISO 14855-1). Gut-free superworms fed with PBS exhibited antioxidant activities comparable to those of blueberries, renowned for their high antioxidant activity. Based on these findings, this study introduces a sustainable circular solution encompassing recycling PBS waste to generate insect biomass, employing insect gut and frass for PBS degradation and fertilizer, and harnessing insect residue as a food source. In essence, the significance of this research extends to socio-economic and environmental spheres, impacting waste management, resource efficiency, circular economy promotion, environmental preservation, industrial advancement, and global sustainability objectives. The study's outcomes possess the potential to reshape society's approach to plastic waste, facilitating a shift toward more sustainable paradigms.

Exosome-Based Drug Delivery: Translation from Bench to Clinic.

Exosome-based drug delivery is emerging as a promising field with the potential to revolutionize therapeutic interventions. Exosomes, which are small extracellular vesicles released by various cell types, have attracted significant attention due to their unique properties and natural ability to transport bioactive molecules. These nano-sized vesicles, ranging in size from 30 to 150 nm, can effectively transport a variety of cargoes, including proteins, nucleic acids, and lipids. Compared to traditional drug delivery systems, exosomes exhibit unique biocompatibility, low immunogenicity, and reduced toxicity. In addition, exosomes can be designed and tailored to improve targeting efficiency, cargo loading capacity, and stability, paving the way for personalized medicine and precision therapy. However, despite the promising potential of exosome-based drug delivery, its clinical application remains challenging due to limitations in exosome isolation and purification, low loading efficiency of therapeutic cargoes, insufficient targeted delivery, and rapid elimination in circulation. This comprehensive review focuses on the transition of exosome-based drug delivery from the bench to clinic, highlighting key aspects, such as exosome structure and biogenesis, cargo loading methods, surface engineering techniques, and clinical applications. It also discusses challenges and prospects in this emerging field.

The Piezo channel is central to the mechano-sensitive channel complex in the mammalian inner ear.

The inner ear is the hub where hair cells transduce sound, gravity, and head acceleration stimuli carried by neural codes to the brain. Of all the senses, hearing and balance, which rely on mechanosensation, are the fastest sensory signals transmitted to the central nervous system. The mechanoelectrical transducer (MET) channel in hair cells is the entryway for the sound-balance-brain interface, but the channel's composition has eluded biologists due to its complexity. Here, we report that the mouse utilizes Piezo1 (Pz1) and Piezo2 (Pz2) isoforms as central components of the MET complex. The Pz channel subunits are expressed in hair-cell stereocilia, are co-localized and co-assembled, and are essential components of the MET complex in vitro and in situ, including integration with the transmembrane channel (Tmc1/2) protein. Mice expressing non-functional Pz1 and Pz2, but not functional Pz1 at the ROSA26 locus under the control of hair-cell promoters, have impaired auditory and vestibular traits that can only be explained if Pz channel multimers are integral to the MET complex. We affirm that Pz protein subunits constitute MET channels and that functional interactions with components of the MET complex yield current properties resembling hair-cell MET currents. Our results demonstrate Pz is a MET channel component central to interacting with MET complex proteins. Results account for the MET channel pore and complex.