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1.
Ann Occup Environ Med ; 36: e13, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38872634

RESUMO

Background: After the coronavirus disease 2019 pandemic, the widespread adoption of working from home, or teleworking, has prompted extensive research regarding its effects on work productivity and the physical and mental health of employees. In this context, our study aimed to investigate the association between working from home and health-related productivity loss (HRPL). Methods: An online survey was conducted with a sample of 1,078 workers. HRPL was estimated by the Work Productivity and Activity Impairment Questionnaire: General Health version. Workers that have been working from home in the last 6 months were categorized into the "work from home" group. Generalized linear models were used to compare the mean difference of HRPL between "work from home" and "commuters" group. Stratified analyses were conducted based on various factors including gender, age, income level, occupation, education level, previous diagnosis of chronic disease, presence of preschool children, living in studio apartment, living alone, commuting time, working hours and regular exercise. Results: The overall HRPL was higher in the "work from home" group than in the "commuters" group with a mean difference of 4.05 (95% confidence interval [CI]: 0.09-8.01). In the stratified analyses, significant differences were observed in workers with chronic diseases (mean difference: 8.23, 95% CI: 0.38-16.09), who do not live alone (mean difference: 4.84, 95% CI: 0.35-9.33), and workers that do not exercise regularly (mean difference: 4.96, 95% CI: 0.12-9.80). Conclusions: Working from home is associated with an increased HRPL in the Korean working population, especially among those with chronic diseases, those who do not live alone, and those who do not exercise regularly.

2.
Circ Cardiovasc Qual Outcomes ; : e010595, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38873761

RESUMO

BACKGROUND: Atrial fibrillation (AF) can lead to stroke, heart failure, and mortality and has a greater prevalence in dialysis patients than in the general population. Several studies have suggested that uremic toxins may contribute to the development of AF. However, the association between dialysis adequacy and incident AF has not been well established. METHODS: In this retrospective nationwide cohort study, we analyzed data from the Korean National Periodic Hemodialysis Quality Assessment from 2013 to 2015 of patients who received outpatient maintenance hemodialysis 3× a week. The main exposure was single pooled Kt/V (spKt/V), which is the dialysis adequacy index, and the primary outcome was the development of AF. For the primary analysis, patients were categorized into quartiles according to baseline spKt/V. The lowest quartile, representing the lowest adequacy, was used as the reference group. Fine-Gray subdistribution hazard models were used, treating all-cause mortality as a competing risk. RESULTS: Of 25 173 patients, the mean age was 60 (51-69) years, and 14 772 (58.7%) were men. During a median follow-up of 5.7 years, incident AF occurred in a total of 3883 (15.4%) patients. Participants with a higher spKt/V tended to have lower AF incidence. In survival analysis, a graded association was observed between the risk of incident AF and spKt/V quartiles: subdistribution hazard ratios and 95% CIs for the second, third, and the highest quartile compared with the lowest quartile were 0.90 (95% CI, 0.82-0.98), 0.84 (95% CI, 0.77-0.93), and 0.79 (95% CI, 0.72-0.88), respectively. CONCLUSIONS: This nationwide cohort study showed that a higher spKt/V is associated with a reduced risk of incident AF. These findings suggests that reducing uremic toxin burden through enhanced dialysis clearance may be associated with a lower risk of AF development in patients undergoing maintenance hemodialysis.

3.
Cell Biosci ; 14(1): 57, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704587

RESUMO

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.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38721635

RESUMO

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.

5.
Sci Total Environ ; 931: 172903, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38697526

RESUMO

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.


Assuntos
Plásticos Biodegradáveis , Ácidos Ftálicos , Ácidos Ftálicos/análise , Medição de Risco , Monitoramento Ambiental/métodos , Poluentes do Solo/análise , Poluentes do Solo/toxicidade
6.
Anticancer Res ; 44(6): 2577-2585, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38821598

RESUMO

BACKGROUND/AIM: Nuclear factor erythroid-derived 2-related factor-2 (NRF2) is a transcription factor that regulates stress response genes. It negatively regulates the immune system by acting as a transcriptional repressor of inflammatory genes or suppressing type I interferon (IFN) production pathways. NRF2 is often over-expressed in some tumors, including non-small cell lung cancer, and modulates these tumors via an immune-cold microenvironment. Thus, strategies to convert cold tumors into hot tumors are effective for cancer treatment. MATERIALS AND METHODS: NRF2 was knocked-down or over-expressed in human cancer cells (A549, HeLa, H1299, H1650) and mouse mammary adenocarcinoma TS/A cells. Cells were irradiated or transfected with poly(I:C), and changes in type I IFN levels were examined using quantitative real-time polymerase chain reaction and western blotting. Cytosolic DNA was assayed via PicoGreen staining and immune and cancer cells were co-cultured. RESULTS: Regulation of NRF2 expression altered type I IFN levels in the human lung cancer cell line A549 and several solid tumors. Down-regulation of NRF2 resulted in increased levels of cytosolic DNA and activated the cGAS-STING pathway. We confirmed that type I IFN was induced in NRF2-down-regulated tumor cells using ionizing radiation (IR). Furthermore, when dendritic cells and macrophages were co-cultured with IR-exposed NRF2 knockdown tumor cells, the immune cells produced more IFNB1 and CXCL10. CONCLUSION: The immunosuppressive tumor cell environment is improved by NRF2 down-regulation, and IR treatment may promote immune cell signaling activation.


Assuntos
Interferon Tipo I , Fator 2 Relacionado a NF-E2 , Radiação Ionizante , Transdução de Sinais , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Humanos , Interferon Tipo I/metabolismo , Animais , Camundongos , Linhagem Celular Tumoral , Células A549 , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Microambiente Tumoral/imunologia , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo
7.
PLOS Glob Public Health ; 4(5): e0003064, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38781240

RESUMO

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.

8.
Brain Tumor Res Treat ; 12(2): 115-120, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38742260

RESUMO

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.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38632706

RESUMO

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.

10.
JBMR Plus ; 8(2): ziad014, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38505527

RESUMO

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.

11.
Am J Clin Nutr ; 119(4): 1044-1051, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38346560

RESUMO

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.


Assuntos
Insuficiência Renal Crônica , Humanos , Estudos Prospectivos , Taxa de Filtração Glomerular , Fatores de Risco , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/prevenção & controle , Potássio
12.
Am J Kidney Dis ; 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38423161

RESUMO

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.

13.
Cell Mol Immunol ; 21(5): 466-478, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38409251

RESUMO

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.


Assuntos
Acne Vulgar , Armadilhas Extracelulares , Inflamassomos , Inflamação , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Inflamassomos/metabolismo , Armadilhas Extracelulares/metabolismo , Armadilhas Extracelulares/imunologia , Acne Vulgar/imunologia , Camundongos , Inflamação/imunologia , Inflamação/patologia , Pele/patologia , Pele/imunologia , Neutrófilos/imunologia , Neutrófilos/metabolismo , Camundongos Endogâmicos C57BL , Humanos , Modelos Animais de Doenças
14.
Int J Mol Sci ; 25(4)2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38396893

RESUMO

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.


Assuntos
Ascomicetos , Magnaporthe , Oryza , Magnaporthe/fisiologia , Melhoramento Vegetal , Proteínas/metabolismo , Resistência à Doença/genética , Proteínas de Repetições Ricas em Leucina , Oryza/microbiologia , Doenças das Plantas/microbiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
15.
Nat Commun ; 15(1): 526, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38228630

RESUMO

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.


Assuntos
Orelha Interna , Células Ciliadas Auditivas Internas , Animais , Camundongos , Células Ciliadas Auditivas Internas/metabolismo , Células Ciliadas Auditivas/metabolismo , Estereocílios/metabolismo , Orelha Interna/metabolismo , Audição , Mecanotransdução Celular , Mamíferos/metabolismo , Canais Iônicos/genética , Canais Iônicos/metabolismo
16.
Korean J Intern Med ; 39(1): 148-159, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38145616

RESUMO

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.


Assuntos
Conservadores da Densidade Óssea , Osteoporose Pós-Menopausa , Osteoporose , Insuficiência Renal Crônica , Humanos , Feminino , Denosumab/efeitos adversos , Conservadores da Densidade Óssea/efeitos adversos , Cálcio , Osteoporose/tratamento farmacológico , Densidade Óssea , Vitamina D , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/tratamento farmacológico , Carbonato de Cálcio , República da Coreia , Osteoporose Pós-Menopausa/induzido quimicamente
17.
Ann Occup Environ Med ; 35: e47, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38148918

RESUMO

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.

18.
PLOS Glob Public Health ; 3(11): e0002422, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37917598

RESUMO

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.

19.
Nat Commun ; 14(1): 7777, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38012176

RESUMO

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.

20.
Artigo em Inglês | MEDLINE | ID: mdl-37935519

RESUMO

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.

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