RESUMEN
Mutations in LMNA, the gene encoding A-type lamins, cause laminopathies-diseases of striated muscle and other tissues. The aetiology of laminopathies has been attributed to perturbation of chromatin organization or structural weakening of the nuclear envelope (NE) such that the nucleus becomes more prone to mechanical damage. The latter model requires a conduit for force transmission to the nucleus. NE-associated Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes are one such pathway. Using clustered regularly interspaced short palindromic repeats to disrupt the Nesprin-1 KASH (Klarsicht, ANC-1, Syne Homology) domain, we identified this LINC complex protein as the predominant NE anchor for microtubule cytoskeleton components, including nucleation activities and motor complexes, in mouse cardiomyocytes. Loss of Nesprin-1 LINC complexes resulted in loss of microtubule cytoskeleton proteins at the nucleus and changes in nuclear morphology and positioning in striated muscle cells, but with no overt physiological defects. Disrupting the KASH domain of Nesprin-1 suppresses Lmna-linked cardiac pathology, likely by reducing microtubule cytoskeleton activities at the nucleus. Nesprin-1 LINC complexes thus represent a potential therapeutic target for striated muscle laminopathies.
Asunto(s)
Laminopatías , Músculo Estriado , Animales , Ratones , Proteínas de Microtúbulos/metabolismo , Proteínas Nucleares/metabolismo , Proteínas de la Membrana/genética , Citoesqueleto/genética , Citoesqueleto/metabolismo , Matriz Nuclear/genética , Microtúbulos/metabolismo , Membrana Nuclear/genética , Membrana Nuclear/metabolismo , Proteínas de Filamentos Intermediarios/metabolismo , Músculo Estriado/metabolismo , Laminopatías/metabolismoRESUMEN
Long interspersed element type 1 (LINE-1, also L1 for short) is the only autonomously transposable element in the human genome. Its insertion into a new genomic site may disrupt the function of genes, potentially causing genetic diseases. Cells have thus evolved a battery of mechanisms to tightly control LINE-1 activity. Here, we report that a cellular antiviral protein, myxovirus resistance protein B (MxB), restricts the mobilization of LINE-1. This function of MxB requires the nuclear localization signal located at its N-terminus, its GTPase activity and its ability to form oligomers. We further found that MxB associates with LINE-1 protein ORF1p and promotes sequestration of ORF1p to G3BP1-containing cytoplasmic granules. Since knockdown of stress granule marker proteins G3BP1 or TIA1 abolishes MxB inhibition of LINE-1, we conclude that MxB engages stress granule components to effectively sequester LINE-1 proteins within the cytoplasmic granules, thus hindering LINE-1 from accessing the nucleus to complete retrotransposition. Thus, MxB protein provides one mechanism for cells to control the mobility of retroelements.
Asunto(s)
Desoxirribonucleasa I/genética , Proteínas de Resistencia a Mixovirus/metabolismo , Núcleo Celular/metabolismo , Gránulos Citoplasmáticos/metabolismo , ADN Helicasas/genética , Desoxirribonucleasa I/metabolismo , Células HEK293 , Células HeLa , Humanos , Elementos de Nucleótido Esparcido Largo/genética , Proteínas de Resistencia a Mixovirus/genética , Proteínas de Unión a Poli-ADP-Ribosa/genética , ARN Helicasas/genética , Proteínas con Motivos de Reconocimiento de ARN/genética , RetroelementosRESUMEN
Functional near infrared spectroscopy (fNIRS) and functional magnetic resonance imaging (fMRI) both measure the hemodynamic response, and so both imaging modalities are expected to have a strong correspondence in regions of cortex adjacent to the scalp. To assess whether fNIRS can be used clinically in a manner similar to fMRI, 22 healthy adult participants underwent same-day fMRI and whole-head fNIRS testing while they performed separate motor (finger tapping) and visual (flashing checkerboard) tasks. Analyses were conducted within and across subjects for each imaging approach, and regions of significant task-related activity were compared on the cortical surface. The spatial correspondence between fNIRS and fMRI detection of task-related activity was good in terms of true positive rate, with fNIRS overlap of up to 68 % of the fMRI for analyses across subjects (group analysis) and an average overlap of up to 47.25 % for individual analyses within subject. At the group level, the positive predictive value of fNIRS was 51 % relative to fMRI. The positive predictive value for within subject analyses was lower (41.5 %), reflecting the presence of significant fNIRS activity in regions without significant fMRI activity. This could reflect task-correlated sources of physiologic noise and/or differences in the sensitivity of fNIRS and fMRI measures to changes in separate (vs. combined) measures of oxy and de-oxyhemoglobin. The results suggest whole-head fNIRS as a noninvasive imaging modality with promising clinical utility for the functional assessment of brain activity in superficial regions of cortex physically adjacent to the skull.
Asunto(s)
Imagen por Resonancia Magnética , Espectroscopía Infrarroja Corta , Adulto , Humanos , Imagen por Resonancia Magnética/métodos , Espectroscopía Infrarroja Corta/métodos , Hemodinámica/fisiología , CráneoRESUMEN
SERINC5 is a multi-span transmembrane protein that is incorporated into HIV-1 particles in producing cells and inhibits HIV-1 entry. Multiple retroviruses like HIV-1, equine infectious anemia virus and murine leukemia virus are subject to SERINC5 inhibition, while HIV-1 pseudotyped with envelope glycoproteins of vesicular stomatitis virus and Ebola virus are resistant to SERINC5. The antiviral spectrum and the underlying mechanisms of SERINC5 restriction are not completely understood. Here we show that SERINC5 inhibits influenza A virus infection by targeting virus-cell membrane fusion at an early step of infection. Further results show that different influenza hemagglutinin (HA) subtypes exhibit diverse sensitivities to SERINC5 restriction. Analysis of the amino acid sequences of influenza HA1 strains indicates that HA glycosylation sites correlate with the sensitivity of influenza HA to SERINC5, and the inhibitory effect of SERINC5 was lost when certain HA glycosylation sites were mutated. Our study not only expands the antiviral spectrum of SERINC5, but also reveals the role of viral envelope glycosylation in resisting SERINC5 restriction.
Asunto(s)
VIH-1 , Gripe Humana , Orthomyxoviridae , Ratones , Animales , Humanos , Productos del Gen nef del Virus de la Inmunodeficiencia Humana/metabolismo , Hemaglutininas/metabolismo , VIH-1/fisiología , Orthomyxoviridae/metabolismo , Antivirales/metabolismo , Glicoproteínas/metabolismoRESUMEN
The mpox outbreak has subdued with fewer reported cases at the present in high-income countries. It is known that mpox virus (MPXV) infection has been epidemic for more than 50 years in African countries. The ancestral MPXV strain has changed into multiple clades, indicating the ongoing evolution of MPXV, which reflects the historical neglect of mpox in Africa, especially after smallpox eradication, and bestows the danger of more severe mpox epidemics in the future. It is thus imperative to continue the development of mpox diagnostics and treatments so we can be prepared in the event of a new mpox epidemic. In this study, we have developed an MPXV detection tool that leverages the recombinase-aid amplification assay by integrating lateral flow strips (RAA-LF) and one-step sample DNA preparation, with visible readout, no need of laboratory instrument, and ready for field deployment. The detection limit reaches 10 copies per reaction. The performance of our RAA-FL assay in diagnosing mpox clinical samples is on par with that of the quantitative polymerase chain reaction (PCR) assay. Taken together, we have developed a point-of-care RAA-LF method of high accuracy and sensitivity, readily deployable for field detection of MPXV. This diagnostic tool is expected to improve and accelerate field- and self-diagnosis, allow timely isolation and treatment, reduce the spread of MPXV, thus effectively mitigate MPXV outbreak in the future.
Asunto(s)
Monkeypox virus , Mpox , Humanos , África , Bioensayo , Brotes de EnfermedadesRESUMEN
BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased risk of lung cancer mortality. Nevertheless, little is known about the underlying molecular mechanisms. This research aimed to investigate differentially expressed genes (DEGs) and explore their function in Lewis lung carcinoma (LLC)-bearing mice exposed to chronic intermittent hypoxia (CIH) by transcriptome sequencing. METHODS: Lung cancer tissues in LLC-bearing mice exposed to CIH or normoxia were subjected for transcriptome sequencing to examine DEGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were employed to explore the function of DEGs. To evaluate the prognostic value of DEGs, the Kaplan-Meier survival analysis in combination with Cox proportional hazard model were applied based on The Cancer Genome Atlas. RESULTS: A total of 388 genes with 207 up-regulated and 181 down-regulated genes were differentially expressed between the CIH and normoxia control groups. Bioinformatics analysis revealed that the DEGs were related to various signaling pathways such as chemokine signaling pathway, IL-17 signaling pathway, TGF-ß signaling pathway, transcriptional misregulation in cancer, natural killer cell mediated cytotoxicity, PPAR signaling pathway. In addition, the DEGs including APOL1, ETFB, KLK8, PPP1R3G, PRL, SPTA1, PLA2G3, PCP4L1, NINJ2, MIR186, and KLRG1 were proven to be significantly correlated with poorer overall survival in lung adenocarcinoma. CONCLUSIONS: CIH caused a significant change of gene expression profiling in LLC-bearing mice. The DEGs were found to be involved in various physiological and pathological processes and correlated with poorer prognosis in lung cancer.
Asunto(s)
Adenocarcinoma del Pulmón , Carcinoma Pulmonar de Lewis , Neoplasias Pulmonares , Animales , Ratones , Neoplasias Pulmonares/genética , Transcriptoma , Procesos Neoplásicos , Hipoxia/genéticaRESUMEN
Yeast, which plays a pivotal role in the brewing, food, and medical industries, exhibits a close relationship with human beings. In this study, we isolated and purified 60 yeast strains from the natural fermentation broth of Sidamo coffee beans to screen for indigenous beneficial yeasts. Among them, 25 strains were obtained through morphological characterization on nutritional agar medium from Wallerstein Laboratory (WL), with molecular biology identifying Saccharomyces cerevisiae strain YBB-47 and the remaining 24 yeast strains identified as Pichia kudriavzevii. We investigated the fermentation performance, alcohol tolerance, SO2 tolerance, pH tolerance, sugar tolerance, temperature tolerance, ester production capacity, ethanol production capacity, H2S production capacity, and other brewing characteristics of YBB-33 and YBB-47. The results demonstrated that both strains could tolerate up to 3% alcohol by volume at a high sucrose mass concentration (400 g/L) under elevated temperature conditions (40 â), while also exhibiting a remarkable ability to withstand an SO2 mass concentration of 300 g/L at pH 3.2. Moreover, S. cerevisiae YBB-47 displayed a rapid gas production rate and strong ethanol productivity. whereas P. kudriavzevii YBB-33 exhibited excellent alcohol tolerance. Furthermore, this systematic classification and characterization of coffee bean yeast strains from the Sidamo region can potentially uncover additional yeasts that offer high-quality resources for industrial-scale coffee bean production.
Asunto(s)
Etanol , Fermentación , Pichia , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/aislamiento & purificación , Pichia/metabolismo , Pichia/aislamiento & purificación , Pichia/genética , Pichia/clasificación , Etanol/metabolismo , Concentración de Iones de Hidrógeno , Café/microbiología , Coffea/microbiología , Temperatura , Semillas/microbiología , Sulfuro de Hidrógeno/metabolismoRESUMEN
Liver fibrosis, one of the leading causes of morbidity and mortality worldwide, lacks effective therapy. The activation of hepatic stellate cells (HSCs) is the dominant event in hepatic fibrogenesis. Luteolin-7-diglucuronide (L7DG) is the major flavonoid extracted from Perilla frutescens and Verbena officinalis. Their beneficial effects in the treatment of liver diseases were well documented. In this study we investigated the anti-fibrotic activities of L7DG and the potential mechanisms. We established TGF-ß1-activated mouse primary hepatic stellate cells (pHSCs) and human HSC line LX-2 as in vitro liver fibrosis models. Co-treatment with L7DG (5, 20, 50 µM) dose-dependently decreased TGF-ß1-induced expression of fibrotic markers collagen 1, α-SMA and fibronectin. In liver fibrosis mouse models induced by CCl4 challenge alone or in combination with HFHC diet, administration of L7DG (40, 150 mg·kg-1·d-1, i.g., for 4 or 8 weeks) dose-dependently attenuated hepatic histopathological injury and collagen accumulation, decreased expression of fibrogenic genes. By conducting target prediction, molecular docking and enzyme activity detection, we identified L7DG as a potent inhibitor of protein tyrosine phosphatase 1B (PTP1B) with an IC50 value of 2.10 µM. Further studies revealed that L7DG inhibited PTP1B activity, up-regulated AMPK phosphorylation and subsequently inhibited HSC activation. This study demonstrates that the phytochemical L7DG may be a potential therapeutic candidate for the treatment of liver fibrosis.
RESUMEN
OBJECTIVE: In China, bladder tumors rank first for morbidity and mortality among urological and reproductive system tumors. Total radical cystectomy plus urinary flow conversion is the gold standard for the treatment of muscle-layer invasive bladder cancer. With an increasing number of radical cystectomies each year, the number of patients living with urostomy is growing. After discharge, primary care of urostomy patients is given at home, and high demands are placed on home caregivers due to issues of privacy and the complexity of replacing the urostomy device. This research explored the challenges faced by the family caregivers of urostomy patients. METHODS: We used descriptive qualitative research methods to conduct interviews with twenty-five family caregivers of patients with urostomy. Survey subjects were from five general hospitals. All interviews were recorded, transcribed, and analyzed using thematic analysis. RESULTS: Three critical challenges were identified-confusion, family crisis, and struggle psychology. Within these three themes, six sub-themes were constructed by coders. They were knowledge and skill deficiency, strong insecurities and uncertainties, role conflict, economic burden, emotional overwhelmed and calm acceptance. CONCLUSION: Family caregivers play a critical role in patient care, and especially in urostomy care. Caregiving is associated with significant challenges that hinder the family caregiver's ability to effectively care for the patient, further diminishing the caregiver's quality of life. Therefore, healthcare professionals should consider the challenges faced by family caregivers and take measures to obviate them through education, preparation, and support.
Asunto(s)
Cuidadores , Neoplasias de la Vejiga Urinaria , Humanos , Cuidadores/psicología , Calidad de Vida , Emociones , Familia/psicología , Investigación CualitativaRESUMEN
BACKGROUND: This study compared the cost-effectiveness of open (ODP), laparoscopic (LDP), and robotic (RDP) distal pancreatectomy (DP). METHODS: Studies reporting the costs of DP were included in a literature search until August 2023. Bayesian network meta-analysis was conducted, and surface under cumulative ranking area (SUCRA) values, mean difference (MD), odds ratio (OR), and 95% credible intervals (CrIs) were calculated for outcomes of interest. Cluster analysis was performed to examine the similarity and classification of DP approaches into homogeneous clusters. A decision model-based cost-utility analysis was conducted for the cost-effectiveness analysis of DP strategies. RESULTS: Twenty-six studies with 29,164 patients were included in the analysis. Among the three groups, LDP had the lowest overall costs, while ODP had the highest overall costs (LDP vs. ODP: MD - 3521.36, 95% CrI - 6172.91 to - 1228.59). RDP had the highest procedural costs (ODP vs. RDP: MD - 4311.15, 95% CrI - 6005.40 to - 2599.16; LDP vs. RDP: MD - 3772.25, 95% CrI - 4989.50 to - 2535.16), but incurred the lowest hospitalization costs. Both LDP (MD - 3663.82, 95% CrI - 6906.52 to - 747.69) and RDP (MD - 6678.42, 95% CrI - 11,434.30 to - 2972.89) had significantly reduced hospitalization costs compared to ODP. LDP and RDP demonstrated a superior profile regarding costs-morbidity, costs-mortality, costs-efficacy, and costs-utility compared to ODP. Compared to ODP, LDP and RDP cost $3110 and $817 less per patient, resulting in 0.03 and 0.05 additional quality-adjusted life years (QALYs), respectively, with positive incremental net monetary benefit (NMB). RDP costs $2293 more than LDP with a negative incremental NMB but generates 0.02 additional QALYs with improved postoperative morbidity and spleen preservation. Probabilistic sensitivity analysis suggests that LDP and RDP are more cost-effective options compared to ODP at various willingness-to-pay thresholds. CONCLUSION: LDP and RDP are more cost-effective than ODP, with LDP exhibiting better cost savings and RDP demonstrating superior surgical outcomes and improved QALYs.
Asunto(s)
Análisis Costo-Beneficio , Laparoscopía , Metaanálisis en Red , Pancreatectomía , Procedimientos Quirúrgicos Robotizados , Pancreatectomía/economía , Pancreatectomía/métodos , Humanos , Procedimientos Quirúrgicos Robotizados/economía , Procedimientos Quirúrgicos Robotizados/métodos , Laparoscopía/economía , Laparoscopía/métodos , Tiempo de Internación/economía , Tiempo de Internación/estadística & datos numéricosRESUMEN
OBJECTIVES: To retrospectively assess the periodontal conditions of teeth adjacent to and contralateral to implants presenting with or without peri-implantitis, following non-surgical periodontal and peri-implant mechanical therapy. MATERIALS AND METHODS: One hundred and one patients with existing dental implants and chronic periodontitis, who underwent non-surgical periodontal and peri-implant mechanical therapy, were included. The periodontal clinical probing depth (PPD), gingival recession (GR), and bleeding on probing (BOP) were recorded at six sites around the adjacent (Adj-) teeth and the contralateral (CL-) teeth relative to the implant. The potential factors influencing the periodontal conditions of 316 teeth were analyzed by multivariate linear regression models with generalized estimating equation methods and α = .05. RESULTS: The PPD of Adj-teeth was significantly different from that of CL-teeth before and after non-surgical therapy when the implant was diagnosed with peri-implantitis (PI) (p < .05). The PPD of teeth was shown to be affected by neighboring implants diagnosed with peri-implantitis (ß = .825 mm, p < .001), teeth adjacent to implants (ß = .245 mm, p = .004), a molar tooth type (ß = .435 mm, p = .019), and non-surgical therapy (ß = -.522 mm, p < .001). CONCLUSIONS: Relatively compromised periodontal conditions at Adj-teeth after non-surgical PI therapy were detected. Therefore, clinicians should be aware that non-surgical therapy may be less successful at teeth adjacent to implants with PI.
RESUMEN
PURPOSE: This study evaluated the accuracy of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) calculator in predicting outcomes after hepatectomy for colorectal cancer (CRC) liver metastasis in a Southeast Asian population. METHODS: Predicted and actual outcomes were compared for 166 patients undergoing hepatectomy for CRC liver metastasis identified between 2017 and 2022, using receiver operating characteristic curves with area under the curve (AUC) and Brier score. RESULTS: The ACS-NSQIP calculator accurately predicted most postoperative complications (AUC > 0.70), except for surgical site infection (AUC = 0.678, Brier score = 0.045). It also exhibited satisfactory performance for readmission (AUC = 0.818, Brier score = 0.011), reoperation (AUC = 0.945, Brier score = 0.002), and length of stay (LOS, AUC = 0.909). The predicted LOS was close to the actual LOS (5.9 vs. 5.0 days, P = 0.985). CONCLUSION: The ACS-NSQIP calculator demonstrated generally accurate predictions for 30-day postoperative outcomes after hepatectomy for CRC liver metastasis in our patient population.
Asunto(s)
Neoplasias Colorrectales , Hepatectomía , Neoplasias Hepáticas , Complicaciones Posoperatorias , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Asia Sudoriental , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Tiempo de Internación , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/secundario , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Medición de Riesgo , Pueblos del Sudeste AsiáticoRESUMEN
BACKGROUND: Focal cortical dysplasia (FCD) is the most common epileptogenic developmental malformation. The diagnosis of FCD is challenging. We generated a radiomics nomogram based on multiparametric magnetic resonance imaging (MRI) to diagnose FCD and identify laterality early. METHODS: Forty-three patients treated between July 2017 and May 2022 with histopathologically confirmed FCD were retrospectively enrolled. The contralateral unaffected hemispheres were included as the control group. Therefore, 86 ROIs were finally included. Using January 2021 as the time cutoff, those admitted after January 2021 were included in the hold-out set (n = 20). The remaining patients were separated randomly (8:2 ratio) into training (n = 55) and validation (n = 11) sets. All preoperative and postoperative MR images, including T1-weighted (T1w), T2-weighted (T2w), fluid-attenuated inversion recovery (FLAIR), and combined (T1w + T2w + FLAIR) images, were included. The least absolute shrinkage and selection operator (LASSO) was used to select features. Multivariable logistic regression analysis was used to develop the diagnosis model. The performance of the radiomic nomogram was evaluated with an area under the curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration and clinical utility. RESULTS: The model-based radiomics features that were selected from combined sequences (T1w + T2w + FLAIR) had the highest performances in all models and showed better diagnostic performance than inexperienced radiologists in the training (AUCs: 0.847 VS. 0.664, p = 0.008), validation (AUC: 0.857 VS. 0.521, p = 0.155), and hold-out sets (AUCs: 0.828 VS. 0.571, p = 0.080). The positive values of NRI (0.402, 0.607, 0.424) and IDI (0.158, 0.264, 0.264) in the three sets indicated that the diagnostic performance of Model-Combined improved significantly. The radiomics nomogram fit well in calibration curves (p > 0.05), and decision curve analysis further confirmed the clinical usefulness of the nomogram. Additionally, the contrast (the radiomics feature) of the FCD lesions not only played a crucial role in the classifier but also had a significant correlation (r = -0.319, p < 0.05) with the duration of FCD. CONCLUSION: The radiomics nomogram generated by logistic regression model-based multiparametric MRI represents an important advancement in FCD diagnosis and treatment.
Asunto(s)
Displasia Cortical Focal , Imágenes de Resonancia Magnética Multiparamétrica , Nomogramas , Radiómica , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Adulto Joven , Displasia Cortical Focal/diagnóstico por imagen , Lateralidad Funcional , Imágenes de Resonancia Magnética Multiparamétrica/métodos , Estudios RetrospectivosRESUMEN
Using seven indicator traits, we investigated the genetic basis of bull fertility and predicted gene interactions from SNP associations. We used percent normal sperm as the key phenotype for the association weight matrix-partial correlation information theory (AWM-PCIT) approach. Beyond a simple list of candidate genes, AWM-PCIT predicts significant gene interactions and associations for the selected traits. These interactions formed a network of 537 genes: 38 genes were transcription cofactors, and 41 genes were transcription factors. The network displayed two distinct clusters, one with 294 genes and another with 243 genes. The network is enriched in fertility-associated pathways: steroid biosynthesis, p53 signalling, and the pentose phosphate pathway. Enrichment analysis also highlighted gene ontology terms associated with 'regulation of neurotransmitter secretion' and 'chromatin formation'. Our network recapitulates some genes previously implicated in another network built with lower-density genotypes. Sequence-level data also highlights additional candidate genes relevant to bull fertility, such as FOXO4, FOXP3, GATA1, CYP27B1, and EBP. A trio of regulatory genes-KDM5C, LRRK2, and PME-was deemed core to the network because of their overarching connections. This trio probably influences bull fertility through their interaction with genes, both known and unknown as to their role in male fertility. Future studies may target the trio and their target genes to enrich our understanding of male fertility further.
Asunto(s)
Fertilidad , Polimorfismo de Nucleótido Simple , Masculino , Fertilidad/genética , Animales , Bovinos/genética , Bovinos/fisiología , Fenotipo , Redes Reguladoras de GenesRESUMEN
BACKGROUND: Kawasaki disease (KD) is the most important acquired heart disease in children. This study investigated annual incidence, seasonality, secular trend and the correlation of KD incidence with viral activity in Taiwan. METHODS: Through the national health insurance database, we identified KD during 2001-2020. The viral activity was obtained from nationwide surveillance database. We analyzed KD age-specific annual incidence, secular trends, seasonality and the correlation between KD incidence and common enteric or respiratory viral activity. RESULTS: The KD incidence of subjects younger than 18 years significantly increased from 2001 to 2020 (11.78 and 22.40 per 100,000 person-years, respectively), and substantially decreased with age. Infants younger than 1 year presented the highest KD annual incidence at 105.82 to 164.34 per 100,000 person-years from 2001 to 2020. For all KD patients, the most frequently occurring season was summer followed by autumn. The KD incidence of infants younger than 1 year had significantly positive correlation with enteric (r = 0.14) and respiratory (r = 0.18) viral activity. CONCLUSIONS: This study demonstrates the increasing trend of KD annual incidence and seasonality (more in summer and autumn) in Taiwan. The activity of common respiratory and enteric viruses was significantly correlated with KD incidence in infants.
Asunto(s)
Síndrome Mucocutáneo Linfonodular , Estaciones del Año , Humanos , Síndrome Mucocutáneo Linfonodular/epidemiología , Taiwán/epidemiología , Lactante , Incidencia , Preescolar , Masculino , Femenino , Niño , Adolescente , Recién Nacido , Vigilancia de la PoblaciónRESUMEN
OBJECTIVE: This study investigates the associations of α1-antitrypsin, inter-α-trypsin inhibitor heavy chain (ITIH4), and 8-isoprostane with lung function in shipyard workers exposed to occupational metal fume fine particulate matter (PM2.5), which is known to be associated with adverse respiratory outcomes. METHODS: A 3-year follow-up study was conducted on 180 shipyard workers with 262 measurements. Personal exposure to welding fume PM2.5 was collected for an 8-h working day. Pre-exposure, post-exposure, and delta (∆) levels of α1-antitrypsin, ITIH4, and 8-isoprostane were determined in urine using enzyme-linked immunosorbent assays. Post-exposure urinary metals were sampled at the beginning of the next working day and analyzed by inductively coupled plasma-mass spectrometry. Lung function measurements were also conducted the next working day for post-exposure. RESULTS: An IQR increase in PM2.5 was associated with decreases of 2.157% in FEV1, 2.806% in PEF, 4.328% in FEF25%, 5.047% in FEF50%, and 7.205% in FEF75%. An IQR increase in PM2.5 led to increases of 42.155 µg/g in ∆α1-antitrypsin and 16.273 µg/g in ∆ITIH4. Notably, IQR increases in various urinary metals were associated with increases in specific biomarkers, such as post-urinary α1-antitrypsin and ITIH4. Moreover, increases in ∆ α1-antitrypsin and ∆ITIH4 were associated with decreases in FEV1/FVC by 0.008% and 0.020%, respectively, and an increase in ∆8-isoprostane resulted in a 1.538% decline in FVC. CONCLUSION: Our study suggests that urinary α1-antitrypsin and ITIH4 could indicate early lung function decline in shipyard workers exposed to metal fume PM2.5, underscoring the need for better safety and health monitoring to reduce respiratory risks.
Asunto(s)
Exposición Profesional , Soldadura , Humanos , Estudios de Seguimiento , Estudios Prospectivos , Exposición Profesional/efectos adversos , Exposición Profesional/análisis , Metales , Material Particulado/análisis , Pulmón , Biomarcadores/orinaRESUMEN
Dengue is one of the world's most rapidly spreading mosquito-borne viral diseases. As it is found mostly in urban and semi-urban areas, urbanization and associated human activities that affect the environment and larval habitats could become risk factors (e.g., lane width, conditions of street ditches) for the spread of dengue. However, there are currently no systematic studies of micro-scale urbanization-based risk factors for the spread of dengue epidemics. We describe the study area, two micro-scale environmental risk factors associated with urbanization, and meteorological data. Since the observations involve spatial and temporal correlations, we also use some statistical methods for the analysis of spatial and spatial-temporal data for the relationship between urbanization and dengue. In this study, we analyzed data from Kaohsiung, a densely populated city in southern Taiwan, and found a positive correlation between environmental risk factors associated with urbanization (ditches positive for mosquito larvae and closely packed streets termed "dengue lanes") and clustering effects in dengue cases. The statistical analysis also revealed that the occurrence of positive ditches was significantly associated with that of dengue lanes in the study area. The relationship between climate variables and positive ditches was also analyzed in this paper, indicating a relationship between dengue and both rainfall and temperature, with temperature having a greater effect. Overall, this work is immediately relevant and applicable for policymakers in government, who will need to reduce these favorable habitats for vector-born disease spreaders and implement regulations for new urban constructions to thus reduce dengue spread in future outbreaks.
Asunto(s)
Dengue , Epidemias , Animales , Humanos , Urbanización , Dengue/epidemiología , Ciudades/epidemiología , Factores de Riesgo , LarvaRESUMEN
OBJECTIVE: To analyze the risk factors associated with postoperative stroke complications in cardiac surgery. METHODS: A retrospective analysis was conducted on the clinical data of 549 patients who underwent cardiac surgery. Among these patients, 501 did not experience a stroke postoperatively (non-stroke group), while 48 developed a postoperative stroke (stroke group). Patients who experienced a stroke postoperatively were divided into two groups based on the type of surgery: those who underwent surgery with cardiopulmonary bypass (18 patients) and those without cardiopulmonary bypass (30 patients). The clinical characteristics of the two groups of patients with postoperative strokes were compared, and the risk factors influencing the occurrence of postoperative stroke complications in cardiac surgery were analyzed. RESULTS: â Clinical findings: Cardiopulmonary bypass group had lower cortical infarction rates but higher large-area and bilateral infarction rates compared to the non-cardiopulmonary bypass group (p < 0.05). No significant gender, age, or infarction type differences were observed (p > 0.05). â¡ Univariate analysis: No significant differences were found in gender, smoking, alcohol, lipids, or glucose levels (p > 0.05). However, age, education, hypertension, diabetes, hypotension, and atrial fibrillation showed significant differences (p < 0.05). ⢠Multivariate Logistic regression: Age, education, hypertension, diabetes, hypotension, and atrial fibrillation were independent risk factors for postoperative stroke complications (p < 0.05). CONCLUSION: Cardiopulmonary bypass increases risk of large-area and bilateral strokes; non-bypass surgery associates with cortical strokes. Age, educational level, hypertension, diabetes, postoperative hypotension, and atrial fibrillation are all factors independently associated with the occurrence of postoperative cerebral infarctions in cardiac surgery. Early interventions may reduce postoperative strokes.
RESUMEN
This study investigated the protective effect of ginsenoside Rg_1(GRg_1) on oxygen and glucose deprivation/reoxygenation(OGD/R)-injured rat adrenal pheochromocytoma(PC12) cells and whether the underlying mechanism was related to the regulation of inositol-requiring enzyme 1(IRE1)-c-Jun N-terminal kinase(JNK)-C/EBP homologous protein(CHOP) signaling pathway. An OGD/R model was established in PC12 cells, and PC12 cells were randomly classified into control, model, OGD/R+GRg_1(0.1, 1, 10 µmol·L~(-1)), OGD/R+GRg_1+rapamycin(autophagy agonist), OGD/R+GRg_1+3-methyladenine(3-MA,autophagy inhibitor), OGD/R+GRg_1+tunicamycin(endoplasmic reticulum stress agonist), OGD/R+GRg_1+4-phenylbutyric acid(4-PBA, endoplasmic reticulum stress inhibitor), and OGD/R+GRg_1+3,5-dibromosalicylaldehyde(DBSA, IRE1 inhibitor) groups. Except the control group, the other groups were subjected to OGD/R treatment, i.e., oxygen and glucose deprivation for 6 h followed by reoxygenation for 6 h. Cell viability was detected by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide(MTT) assay. Apoptosis was detected by Hoechst 33342 staining, and the fluorescence intensity of autophagosomes by the monodansylcadaverine(MDC) assay. Western blot was employed to determine the expression of autophagy-related proteins(Beclin1, LC3-â ¡, and p62) and the pathway-related proteins [IRE1, p-IRE1, JNK, p-JNK, glucose-regulated protein 78(GRP78), and CHOP]. The results showed that GRg_1 dose-dependently increased the viability of PC12 cells and down-regulated the expression of Beclin1, LC3-â ¡, p-IRE1, p-JNK, GRP78, and CHOP, compared with the model group. Furthermore, GRg_1 decreased the apoptosis rate and MDC fluorescence intensity and up-regulated the expression of p62 protein. Compared with the OGD/R+GRg_1(10 µmol·L~(-1)) group, OGD/R+GRg_1+rapamycin and OGD/R+GRg_1+tunicamycin groups showed increased apoptosis rate and MDC fluorescence intensity, up-regulated protein levels of Beclin1, LC3-â ¡, p-IRE1, p-JNK, GRP78, and CHOP, decreased relative cell survival rate, and down-regulated protein level of p62. The 3-MA, 4-PBA, and DBSA groups exerted the opposite effects. Taken together, GRg_1 may ameliorate OGD/R-induced PC12 cell injury by inhibiting autophagy via the IRE1-JNK-CHOP pathway.
Asunto(s)
Apoptosis , Ginsenósidos , Glucosa , Proteínas Serina-Treonina Quinasas , Factor de Transcripción CHOP , Animales , Ratas , Células PC12 , Factor de Transcripción CHOP/metabolismo , Factor de Transcripción CHOP/genética , Glucosa/metabolismo , Ginsenósidos/farmacología , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Apoptosis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Autofagia/efectos de los fármacos , Endorribonucleasas/metabolismo , Endorribonucleasas/genética , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/genética , Oxígeno/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Complejos MultienzimáticosRESUMEN
BACKGROUND: The genetics of male fertility is complex and not fully understood. Male subfertility can adversely affect the economics of livestock production. For example, inadvertently mating bulls with poor fertility can result in reduced annual liveweight production and suboptimal husbandry management. Fertility traits, such as scrotal circumference and semen quality are commonly used to select bulls before mating and can be targeted in genomic studies. In this study, we conducted genome-wide association analyses using sequence-level data targeting seven bull production and fertility traits measured in a multi-breed population of 6,422 tropically adapted bulls. The beef bull production and fertility traits included body weight (Weight), body condition score (CS), scrotal circumference (SC), sheath score (Sheath), percentage of normal spermatozoa (PNS), percentage of spermatozoa with mid-piece abnormalities (MP) and percentage of spermatozoa with proximal droplets (PD). RESULTS: After quality control, 13,398,171 polymorphisms were tested for their associations with each trait in a mixed-model approach, fitting a multi-breed genomic relationship matrix. A Bonferroni genome-wide significance threshold of 5 × 10- 8 was imposed. This effort led to identifying genetic variants and candidate genes underpinning bull fertility and production traits. Genetic variants in Bos taurus autosome (BTA) 5 were associated with SC, Sheath, PNS, PD and MP. Whereas chromosome X was significant for SC, PNS, and PD. The traits we studied are highly polygenic and had significant results across the genome (BTA 1, 2, 4, 6, 7, 8, 11, 12, 14, 16, 18, 19, 23, 28, and 29). We also highlighted potential high-impact variants and candidate genes associated with Scrotal Circumference (SC) and Sheath Score (Sheath), which warrants further investigation in future studies. CONCLUSION: The work presented here is a step closer to identifying molecular mechanisms that underpin bull fertility and production. Our work also emphasises the importance of including the X chromosome in genomic analyses. Future research aims to investigate potential causative variants and genes in downstream analyses.