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Porcine idiopathic vesicular disease (PIVD), one of several clinically indistinguishable vesicular diseases of pigs, is caused by the emerging pathogen Senecavirus A (SVA). Despite the widespread prevalence of porcine SVA infection, no effective commercial vaccines for PIVD prevention and control are available, due to high costs associated with vaccine testing in pigs, considerable SVA diversity, and SVA rapid evolution. In this study, SVA CH/JL/2022 (OP562896), a novel mutant SVA strain derived from an isolate obtained from a pig farm in Jilin Province, China, was inactivated then combined with four adjuvants, MONTANIDETM GEL02 PR (GEL 02), MONTANIDETM ISA 201 VG (ISA 201), MONTANIDETM IMG 1313 VG N (IMS1313), or Rehydragel LV (LV). The resulting inactivated SVA CH/JL/2022 vaccines were assessed for efficacy in mice and found to induce robust in vivo lymphocyte proliferation responses and strong IgG1, IgG2a, and neutralizing antibody responses with IgG2a/IgG1 ratios of <1. Furthermore, all vaccinated groups exhibited significantly higher levels of serum cytokines IL-2, IL-4, IL-6, and IFN as compared to unvaccinated mice. These results indicate that all vaccines elicited both Th1 and Th2 responses, with Th2 responses predominating. Moreover, vaccinated mice exhibited enhanced resistance to SVA infection, as evidenced by reduced viral RNA levels and SVA infection-induced histopathological changes. Collectively, our results demonstrate that the SVA-GEL vaccine induced more robust immunological responses in mice than did the other three vaccines, thus highlighting the potential of SVA-GEL to serve an effective tool for preventing and controlling SVA infection.
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IMPORTANCE: Betacoronaviruses, including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and mouse hepatitis virus (MHV), exploit the lysosomal exocytosis pathway for egress. However, whether all betacoronaviruses members use the same pathway to exit cells remains unknown. Here, we demonstrated that porcine hemagglutinating encephalomyelitis virus (PHEV) egress occurs by Arl8b-dependent lysosomal exocytosis, a cellular egress mechanism shared by SARS-CoV-2 and MHV. Notably, PHEV acidifies lysosomes and activates lysosomal degradative enzymes, while SARS-CoV-2 and MHV deacidify lysosomes and limit the activation of lysosomal degradative enzymes. In addition, PHEV release depends on V-ATPase-mediated lysosomal pH. Furthermore, this is the first study to evaluate ßCoV using lysosome for spreading through the body, and we have found that lysosome played a critical role in PHEV neural transmission and brain damage caused by virus infection in the central nervous system. Taken together, different betacoronaviruses could disrupt lysosomal function differently to exit cells.
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Betacoronavirus 1 , Infecciones por Coronavirus , Exocitosis , Lisosomas , Neuronas , Animales , Ratones , Betacoronavirus 1/metabolismo , Lisosomas/enzimología , Lisosomas/metabolismo , Lisosomas/virología , Virus de la Hepatitis Murina/metabolismo , Neuronas/enzimología , Neuronas/metabolismo , Neuronas/patología , Neuronas/virología , SARS-CoV-2/metabolismo , Porcinos/virología , Concentración de Iones de Hidrógeno , ATPasas de Translocación de Protón Vacuolares/metabolismo , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virologíaRESUMEN
Objective: Little is known about the effect of age at first childbirth on lung function. We aimed to investigate the association between age at first childbirth and lung function in Chinese women and further test whether this association is mediated by body mass index (BMI). Methods: This cross-sectional study is a partial survey of the China Kadoorie Biobank (CKB) which was conducted in Xinxiang City, Henan Province between 2004 and 2008. A total of 16,584 postmenopausal women aged 30-79 years were enrolled. Multiple linear and logistic regression were used to investigate the association between age at first childbirth and lung function and overweight/obesity. The mediation analysis was performed using the PROCESS procedure for SPSS. Results: The mean (SD) age at first childbirth was 23.1 (2.7) years. Women with first childbirth aged ≤19 years and 20-22 years had lower lung function than women who gave first childbirth aged 23-25 years. Per 1-year increase in the age at first childbirth was associated with a 3.31 mL increase in FEV1 (95% CI = 1.27-5.35), 3.91 mL increase in FVC (95% CI = 1.63-6.18), 0.15% increase in FEV1, % predicted (95% CI = 0.05-0.24) and 0.14% increase in FVC, % predicted (95% CI = 0.05-0.22). There was no clear association between age at first childbirth and FEV1/FVC ratio. BMI played a contribution to the association between age at first childbirth and FEV1 and the proportion was 16.4% (indirect effect: ß = 0.65, 95% CI = 0.46-0.89; total effect: ß = 3.96, 95% CI = 1.92-5.99). Similarly, the proportion to FVC, FEV1, % predicted, and FVC, % predicted was 25.0%, 16.6%, and 25.0%, respectively. Conclusion: Early age at first childbirth was associated with lower lung function and BMI mediated the association. It is important to test lung function and popularize the knowledge of weight control in women who gave first childbirth at an early age.
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CONTEXT: Evidence about the effect of age at menarche (AAM) on blood pressure (BP) has largely been drawn from studies in developed countries. Studies in developing countries are expanding recently but have not been summarised. OBJECTIVE: To systematically explore the association between AAM and BP and the potential modifiers in developing countries. METHODS: We searched PubMed, Embase, and Web of Science for publications until March 2022. A random-effects model was used to calculate the pooled relative risk (RR) with 95% confidence interval (CI). RESULTS: Twenty studies were eligible. In studies with participants' mean age at BP assessment <55 years, women in the oldest group as compared with the middle or the youngest group of AAM had a higher risk of hypertension in those studies without adjustment for confounders (RR 1.79, 95% CI 1.41-2.28, I2=97.0%), those with adjustment for confounders excluding adiposity (1.25,1.04-1.51, I2=84.8%), and those with adjustment for confounders including adiposity (1.38,1.03-1.86, I2=91.8%). In studies with participants' mean age at BP assessment ≥55 years, no significant differences were found for studies without adjustment for confounders (RR 1.07, 95% CI 0.78-1.47, I2=90.3%), studies with adjustment for confounders excluding adiposity (0.85, 0.78-0.92, I2=12.3%), or studies with adjustment for confounders including adiposity (0.95, 0.80-1.11, I2=45.5%). A similar association was observed between AAM and baseline systolic BP and diabolic BP. CONCLUSION: Late menarche was associated with a higher risk of BP and this association was modified by age and adiposity in developing countries.
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Hipertensión , Menarquia , Adulto , Humanos , Femenino , Persona de Mediana Edad , Menarquia/fisiología , Presión Sanguínea , Factores de Riesgo , Países en Desarrollo , Hipertensión/epidemiología , Hipertensión/etiología , ObesidadRESUMEN
A cross-sectional study was conducted to estimate the age-stratified normal levels and age-related changes in the risk predictors of benign prostatic hyperplasia (BPH) progression. A total of 4706 male participants aged 40 years or older in Zhengzhou (China) were enrolled. The values of the International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA), prostate volume (PV), and postvoid residual urine volume (PVR) significantly increased with age. Nonlinear relationships between age and IPSS scores ≥8 (P for nonlinearity = 0.046), PSA level ≥1.6 ng ml-1, PV ≥31 ml, or PVR ≥39 ml (all P for nonlinearity <0.001) were observed. After the age of 61 years, the risk indicators related to BPH progression were positively correlated with age (odds ratio [OR] >1), regardless of the predictors of the IPSS score, PSA level, PV, or PVR; and the OR values increased gradually. Therefore, after the age of 61 years, the risk predictors related to BPH progression were positively correlated with age.
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Hiperplasia Prostática , Humanos , Masculino , Hiperplasia Prostática/epidemiología , Hiperplasia Prostática/diagnóstico , Antígeno Prostático Específico , Estudios Transversales , Pueblos del Este de Asia , Factores de RiesgoRESUMEN
BACKGROUND: Porcine hemagglutinating encephalomyelitis virus (PHEV), a member of the genus Betacoronavirus, is the causative agent of neurological disease in pigs. No effective therapeutics are currently available for PHEV infection. Resveratrol has been shown to exert neuroprotective and antiviral effects. Here resveratrol was investigated for its ability to inhibit PHEV replication in nerve cells and central nervous system tissues. METHODS: Anti-PHEV effect of resveratrol was evaluated using an in vitro cell-based PHEV infection model and employing a mouse PHEV infection model. The collected cells or tissues were used for quantitative PCR analysis, western blot analysis, or indirect immunofluorescence assay. The supernatants were collected to quantify viral loads by TCID50 assay in vitro. EC50 and CC50 were determined by dose-response experiments, and the ratio (EC50/CC50) was used as a selectivity index (SI) to measure the antiviral versus cytotoxic activity. RESULTS: Our results showed that resveratrol treatment reduced PHEV titer in a dose-dependent manner, with a 50% inhibition concentration of 6.24 µM. A reduction of > 70% of viral protein expression and mRNA copy number and a 19-fold reduction of virus titer were achieved when infected cells were treated with 10 µM resveratrol in a pre-treatment assay. Quantitative PCR analysis and TCID50 assay results revealed that the addition of 10 µM resveratrol to cells after adsorption of PHEV significantly reduced 56% PHEV mRNA copy number and eightfold virus titer. 10 µM resveratrol treatment reduced 46% PHEV mRNA copy number and fourfold virus titer in virus inactivation assay. Moreover, the in vivo data obtained in this work also demonstrated that resveratrol inhibited PHEV replication, and anti-PHEV activities of resveratrol treatment via intranasal installation displayed better than oral gavage. CONCLUSION: These results indicated that resveratrol exerted antiviral effects under various drug treatment and virus infection conditions in vitro and holds promise as a treatment for PHEV infection in vivo.
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Betacoronavirus 1 , Ratones , Porcinos , Animales , Resveratrol/farmacología , Resveratrol/metabolismo , Betacoronavirus 1/genética , Betacoronavirus 1/metabolismo , Neuronas , Antivirales/farmacología , Antivirales/metabolismo , Replicación ViralRESUMEN
Many members of the genus Betacoronavirus are neurotropic viruses that frequently cause serious harm to humans or animals, including highly neurotropic porcine hemagglutinating encephalomyelitis virus (PHEV). Nevertheless, very few approved treatments exist to combat these viruses. Lysosomotropic trehalose, a widely used, nontoxic, natural disaccharide that can traverse the blood-brain barrier, has been proposed as a potential antiviral agent for use in prevention or treatment of betacoronavirus-associated infections. The purpose of this study was to determine if trehalose could inhibit PHEV infection of cells of a mouse central nervous system-derived neuroblastoma cell line in vitro or brain cells in vivo. Our results demonstrated that treatment of PHEV-infected mouse neuroblastoma cells and mice with trehalose reduced viral replication and that these trehalose antiviral effects were dependent on expression of lysosomal protein progranulin. Collectively, these results indicated that trehalose holds promise as a new antiviral agent for use in controlling neurotropic betacoronavirus infections.
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Knowing vaccine effectiveness (VE) against variants of concern (VOCs) in the real-world setting is essential for public health decision-making. A systematic landscape of the VE against a series of clinical outcomes caused by the VOCs in the real-world setting is needed. We systematically searched for studies that evaluated VE against VOCs in the real-world setting and collected individual data. We identified 113 studies meeting the eligibility criteria. We found full vaccination provided strong protection against each clinical outcome with summary VE ranging from 86.8% to 96.0% Alpha, moderate protection against infection caused by Beta, Gamma and Delta with summary VE ranging from 70.9% to 72.8%, strong protection against severe disease caused by Delta with summary VE ranging from 84.9% to 90.3%, limited protection with summary VE of 23.5% (95% CI, 17.0-29.5) against infection and moderate protection with summary VE ranging from 56.5% to 82.4% against severe diseases caused by Omicron. Booster vaccination can provide a substantial improvement in protection against Delta and Omicron, but not as much as the Delta. The meta-regression analysis showed that the VE against the Omicron wanned over time, and the VE against hospitalization declined relatively slowly, compared to against infection. Those findings supported the need for public health measures, increasing booster vaccination coverage in response to current and new infectious waves driven by variants and developing broadly protective vaccines to confront virus evolution.
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Vacunas contra la COVID-19 , COVID-19 , COVID-19/prevención & control , Humanos , SARS-CoV-2/genética , VacunaciónRESUMEN
OBJECTIVES: To estimate the coverage and willingness of pneumococcal vaccination and further explore the influencing factors of vaccination willingness among people in mainland China. METHODS: Literature searches were conducted independently by two researchers in English- and Chinese-language databases from database inception to 6 October 2021. A random-effects meta-analysis model was used to derive summary vaccination coverage and willingness. Predefined subgroup analysis and meta-regression were performed to explore the sources of heterogeneity. RESULTS: A total of 97 studies were included in this meta-analysis. The summary vaccination coverage in 76 included studies was 21.7% (95% confidence interval [CI]: 17.2%-26.5%). Subgroup analysis shows that the summary coverage was 29.0% (95% CI, 20.4%-39.1%) among the permanent residents and 20.7% (95% CI, 12.4%-35.9%) among the floating residents. The eastern and central regions presented higher coverage than the western region. Notable differences were observed between the various study populations. A total of 27 studies provided an estimation of vaccination willingness, with a summary willingness of 51.2% (95% CI, 40.4%-61.9%). In subgroup analysis, the summary willingness was 57.9% (95% CI, 48.3%-67.2%) in urban areas and 52.3% (95% CI, 40.8%-63.8%) in rural areas. Parents with children and people with a history of pneumonia were more willing to be vaccinated than the elderly. Recommendations by family members and physicians, previous pneumococcal and influenza vaccination, perceived vaccination effectiveness and severity of disease and a history of pneumonia contributed to vaccination willingness. CONCLUSIONS: Compared to global estimates and other countries, pneumococcal vaccination coverage and willingness are at a lower level in mainland China. Recommendations for vaccination by family members and doctors, a history of vaccination and the perception of pneumonia and vaccination are associated with greater willingness to be vaccinated.
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Neumonía , Cobertura de Vacunación , Anciano , Niño , China , Humanos , Streptococcus pneumoniae , VacunaciónRESUMEN
Evidence from previous epidemiological studies on the effect of physical activity on the risk of Alzheimer's disease (AD) is conflicting. We performed a two-sample Mendelian randomization analysis to verify whether physical activity is causally associated with AD. This study used two-sample Mendelian randomization (MR) analysis to estimate the association between physical activity (including overall activity, sedentary behavior, walking, and moderate-intensity activity) and AD. Genetic instruments for physical activity were obtained from published genome-wide association studies (GWAS) including 91,105 individuals from UK Biobank. Summary-level GWAS data were extracted from the International Genomics of Alzheimer's Project IGAP (21,982 patients with AD and 41,944 controls). Inverse Variance Weighted (IVW) was used to estimate the effect of physical activity on AD. Sensitivity analyses including weighted median, MR-Egger, MR-PRESSO, and leave-one-out analysis were used to estimate pleiotropy and heterogeneity. Mendelian randomization evidences suggested a protective relationship between walking and AD (odds ratio (OR) = 0.30, 95% confidence interval (CI), 0.13-0.68, P = 0.0039). Genetically predicted overall activity, sedentary behavior, and moderate-intensity activity were not associated with AD. In summary, this study provided evidence that genetically predicted walking might associate with a reduced risk of AD. Further research into the causal association between physical activity and AD could help to explore the real relationship and provide more measures to reduce AD risk.
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Enfermedad de Alzheimer , Análisis de la Aleatorización Mendeliana , Enfermedad de Alzheimer/genética , Ejercicio Físico , Estudio de Asociación del Genoma Completo , Humanos , Polimorfismo de Nucleótido SimpleRESUMEN
The recent novel coronavirus (SARS-CoV-2) disease (COVID-19) outbreak created a severe public health burden worldwide. Unfortunately, the SARS-CoV-2 variant is still spreading at an unprecedented speed in many countries and regions. There is still a lack of effective treatment for moderate and severe COVID-19 patients, due to a lack of understanding of the SARS-CoV-2 life cycle. Lysosomes, which act as "garbage disposals" for nearly all types of eukaryotic cells, were shown in numerous studies to support SARS-CoV-2 replication. Lysosome-associated pathways are required for virus entry and exit during replication. In this review, we summarize experimental evidence demonstrating a correlation between lysosomal function and SARS-CoV-2 replication, and the development of lysosomal perturbation drugs as anti-SARS-CoV-2 agents.
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Tratamiento Farmacológico de COVID-19 , SARS-CoV-2 , Antivirales/uso terapéutico , Humanos , Lisosomas/metabolismo , Replicación ViralRESUMEN
Canine distemper (CD) caused by canine distemper virus (CDV) is one of the major infectious diseases in minks, bringing serious economic losses to the mink breeding industry. By an integrated analysis of microRNA (miRNA)-messenger RNA (mRNA), the present study analyzed the changes in the mink transcriptome upon CDV infection in mink lung epithelial cells (Mv. l. Lu cells) for the first time. A total of 4,734 differentially expressed mRNAs (2,691 upregulated and 2,043 downregulated) with |log2(FoldChange) |>1 and P-adj<0.05 and 181 differentially expressed miRNAs (152 upregulated and 29 downregulated) with |log2(FoldChange) |>2 and P-adj<0.05 were identified. Gene Ontology (GO) enrichment indicated that differentially expressed genes (DEGs) were associated with various biological processes and molecular function, such as response to stimulus, cell communication, signaling, cytokine activity, transmembrane signaling receptor activity and signaling receptor activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the combination of miRNA and mRNA was done for immune and inflammatory responses, such as Janus kinase (JAK)-signal transducer and activator (STAT) signaling pathway and nuclear factor (NF)-kappa B signaling pathway. The enrichment analysis of target mRNA of differentially expressed miRNA revealed that mir-140-5p and mir-378-12 targeted corresponding genes to regulate NF-kappa B signaling pathway. JAK-STAT signaling pathway could be modulated by mir-425-2, mir-139-4, mir-140-6, mir-145-3, mir-140-5p and mir-204-2. This study compared the influence of miRNA-mRNA expression in Mv. l. Lu cells before and after CDV infection by integrated analysis of miRNA-mRNA and analyzed the complex network interaction between virus and host cells. The results can help understand the molecular mechanism of the natural immune response induced by CDV infection in host cells.
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OBJECTIVE: To estimate the coronavirus disease 2019 (COVID-19) vaccine effectiveness (VE) against concerned outcomes in real-world settings. METHODS: Studies reporting COVID-19 VE from August 6, 2020 to October 6, 2021 were included. The summary VE (with 95% confidence intervals (95% CI)) against disease related to COVID-19 was estimated. The results were presented in forest plots. Predefined subgroup analyses and sensitivity analyses were also performed. RESULTS: A total of 51 records were included in this meta-analysis. In fully vaccinated populations, the VE against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, COVID-19-related hospitalization, admission to the intensive care unit, and death was 89.1% (95% CI 85.6-92.6%), 97.2% (95% CI 96.1-98.3%), 97.4% (95% CI 96.0-98.8%), and 99.0% (95% CI 98.5-99.6%), respectively. The VE against infection in the general population aged ≥16 years, the elderly, and healthcare workers was 86.1% (95% CI 77.8-94.4%), 83.8% (95% CI 77.1-90.6%), and 95.3% (95% CI 92.0-98.6%), respectively. For those fully vaccinated against infection, the observed effectiveness of the Pfizer-BioNTech vaccine was 91.2% and of the Moderna vaccine was 98.1%, while the effectiveness of the CoronaVac vaccine was found to be 65.7%. CONCLUSIONS: The COVID-19 vaccines are highly protective against SARS-CoV-2-related diseases in real-world settings.
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Vacunas contra la COVID-19 , COVID-19 , Anciano , Hospitalización , Humanos , SARS-CoV-2 , Eficacia de las VacunasRESUMEN
A cross-sectional study based on the community was conducted to explore the association between sleep status and LUTS among middle and old-aged men. Male residents in Zhengzhou aged 40 or older were recruited. Participants received the Pittsburgh Sleep Quality Index questionnaire and the International Prostate Symptom Score questionnaire to evaluate sleep status and the severity of lower urinary tract symptoms (LUTS), respectively. Logistic regression analyses and linear regression analyses were performed to evaluate the relationship between sleep quality and sleep duration and LUTS. A total of 5785 participants were enrolled. Multivariable analyses showed a positive relationship between sleep quality and LUTS (ß 0.716, 95% CI 0.647-0.784), and poor sleepers were significantly associated with moderate or severe LUTS (OR 2.486, 95% CI 2.095-2.950). U-shaped dose-response relationship revealed that sleeping less than 5.8 h/day and more than 7.9 h/day was related to moderate or severe LUTS and more than 7.9 h/day of sleep duration was associated with poor voiding and storage symptoms (P for nonlinearity < 0.001). Similar relationship was observed between sleep status and nocturia. It showed a significantly positive relationship between sleep quality and LUTS. U-shaped dose-response relationships between sleep duration and LUTS were observed.
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This study was conducted to evaluate the effects of Clostridium butyricum dietary supplementation on the growth, antioxidant, immune response, gut microbiota, and intestinal barrier function of broilers under high stocking density (HSD) stress. A total of 324 1-day-old Arbor Acres male broilers were randomly assigned to three treatments with six replicates, each replicate including 18 chickens (18 birds/m2). The experiment lasted 6 weeks. The three treatments were basal diet (control, CON), basal diet supplemented with 1 × 109 colony forming units (cfu)/kg C. butyricum (CB), and basal diet supplemented with 10 mg/kg virginiamycin (antibiotic, ANT). The results showed that the body weight (BW) and average daily gain (ADG) of broilers in the CB group were significantly higher than those in the CON group in three periods (p < 0.05). The total antioxidant capacity (T-AOC) and the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity in serum of the CB group were significantly increased compared with those in the CON and ANT groups at 42 days (p < 0.05). At 42 days, the serum immunoglobulin M (IgM) and immunoglobulin G (IgG) levels of the CB group were significantly higher than those of the CON group. Compared with the CON group, interleukin-1ß (IL-1ß) in the CB group was significantly decreased in the starter and grower stages (p < 0.05), but there was no significant difference between the two treatment groups (p > 0.05). C. butyricum significantly decreased the high stocking density-induced expression levels of IL-1ß and tumor necrosis factor-α (TNF-α) in the ileum of broilers at different stages. Additionally, C. butyricum could increase the expressions of claudin-1 and zonula occludens-1 (ZO-1) in intestinal tissue. Moreover, C. butyricum significantly increased the Sobs and Shannon indices in the CB group compared with the ANT group (p < 0.05), while the Ace index in the CB group was significantly higher than that of the CON group (p < 0.05). Furthermore, by using 16S rRNA gene sequencing, the proportion of Bacteroides in the CB group was increased compared to those in the CON and ANT groups at the genus level. In conclusion, C. butyricum supplemented into feed could improve the growth performance and feed utilization of broilers by promoting immune and intestinal barrier function and benefiting the cecal microflora.
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Artificial neural network (ANN) is the main tool to dig data and was inspired by the human brain and nervous system. Several studies clarified its application in medicine. However, none has applied ANN to predict the efficacy of folic acid treatment to Hyperhomocysteinemia (HHcy). The efficacy has been proved to associate with both genetic and environmental factors while previous studies just focused on the latter one. The explained variance genetic risk score (EV-GRS) had better power and could represent the effect of genetic architectures. Our aim was to add EV-GRS into environmental factors to establish ANN to predict the efficacy of folic acid therapy to HHcy. We performed the prospective cohort research enrolling 638 HHcy patients. The multilayer perception algorithm was applied to construct ANN. To evaluate the effect of ANN, we also established logistic regression (LR) model to compare with ANN. According to our results, EV-GRS was statistically associated with the efficacy no matter analyzed as a continuous variable (OR = 3.301, 95%CI 1.954-5.576, P < 0.001) or category variable (OR = 3.870, 95%CI 2.092-7.159, P < 0.001). In our ANN model, the accuracy was 84.78%, the Youden's index was 0.7073 and the AUC was 0.938. These indexes above indicated higher power. When compared with LR, the AUC, accuracy, and Youden's index of the ANN model (84.78%, 0.938, 0.7073) were all slightly higher than the LR model (83.33% 0.910, 0.6687). Therefore, clinical application of the ANN model may be able to better predict the folic acid efficacy to HHcy than the traditional LR model. When testing two models in the validation set, we got the same conclusion. This study appears to be the first one to establish the ANN model which added EV-GRS into environmental factors to predict the efficacy of folic acid to HHcy. This model would be able to offer clinicians a new method to make decisions and individual therapeutic plans.
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Algoritmos , Ácido Fólico/uso terapéutico , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Hiperhomocisteinemia/tratamiento farmacológico , Redes Neurales de la Computación , Anciano , Femenino , Humanos , Hiperhomocisteinemia/genética , Hiperhomocisteinemia/patología , Masculino , Estudios Prospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
OBJECTIVES: This study aimed to explore the reporting of workplace violence against nurses and the reasons why they did not reported. METHODS: A self-designed questionnaire regarding workplace violence and reporting was used to conduct a cross-sectional survey on nurses who submitted a manuscript to a Chinese nursing journal from 2016 to 2017. A total of 324 nurses agreed to participate in this study and 266 participants from 165 hospitals in 72 cities returned questionnaires. RESULTS: A total of 172 nurses (64.7%) experienced violent incidents during the past year. Of these incidents, 45.5% were reported; and the reporting rate of physical assaults (69.0%) was higher than those of verbal abuse (36.9%), threatening behavior (51.7%), and sexual harassment (60.0%). Formal reporting accounted for 25.4% (15.4% in written form and 10.0% through a computer-assisted reporting system). Almost half of the nurses (49.6%) stated that the hospital had no reporting system or they were uncertain about the reporting system. For reasons of not reporting, 51.9% of the nurses were unware of how and what types of violence to report, and 50.6% of the nurses believed that the hospital paid greater attention to patients rather than staff. CONCLUSIONS: A clear definition of workplace violence and reporting procedures, establishment of a facile system for reporting, and supervisory support following a reporting are urgently required.
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Porcine hemagglutinating encephalomyelitis virus (PHEV) displays neurotropism and induces atypical autophagy. However, the exact mechanisms mediating autophagy induced by PHEV remains uncharacterized. Transcription factor EB (TFEB) is a master transcriptional regulator playing a key role in autophagy and its activity is regulated by MTORC1 kinase on the surface of lysosomes. We first found that PHEV infection decreases TFEB expression, while it activates TFEB by inhibiting MTORC1 activation, indicating that TFEB plays a complex role in the process of PHEV-induced autophagy through opposite regulation of its expression and activity. Furthermore, this study preliminarily demonstrated that PHEV replication is dependent on TFEB expression.
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Autofagia/fisiología , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Betacoronavirus 1 , Regulación de la Expresión Génica , Proteínas de Membrana de los Lisosomas/metabolismo , Replicación Viral/fisiología , Transporte Activo de Núcleo Celular , Animales , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Línea Celular , Proteínas de Membrana de los Lisosomas/genética , Diana Mecanicista del Complejo 1 de la Rapamicina/genética , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Ratones , PorcinosRESUMEN
The objective of present study was to investigate the effects of alpha-lipoic acid (ALA) dietary supplementation on the behavior, physiological and oxidant stress indicators, and bone quality in broilers under high stocking density (HSD) stress. A total of one thousand eight hundred 22-day-old Arbor Acres male broiler chicks were randomly allocated to 18 pens (2.97 × 2.03 m) in 3 groups: 14 birds/m2 (NSD, normal stocking density) or 18 birds/m2 (HSD) or 18 birds/m2 plus 300 mg/kg ALA dietary supplement (HSD + ALA, high stocking density + alpha-lipoic acid). Each treatment had 6 replicates, and the experiment lasted 3 wk. The HSD group was significantly lower than the NSD group (P < 0.05) in the frequency of eating, walking, and preening behavior. The alkaline phosphatase activity and serum calcium content were significantly higher, and the parathyroid hormone (PTH) level was significantly lower in the HSD group than in the NSD group (P < 0.05). When compared with the NSD group, the HSD group showed an increase (P < 0.05) in serum heterophil/lymphocyte ratio (H/L ratio), corticosterone (CORT), malondialdehyde (MDA) content, and catalase (CAT) activity, whereas a decrease (P < 0.05) in total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) concentrations. The HSD group was also significantly lower (P < 0.05) than the NSD group in the tibia and femur breaking strength, bone mineral density, and BMC. Importantly, the addition of ALA into the diets of the HSD group enabled the HSD + ALA group to recover to the levels of NSD group (P > 0.05) in the standing and preening behavior, alkaline phosphatase activity, PTH concentration, H/L ratio, CAT, T-AOC, MDA, SOD, and GSH-Px. These results indicate that the increase of stocking density lowered the bone quality, increased the physiological and oxidative stress indicators, and modified the behavior of broilers, whereas ALA dietary supplementation could counteract the reduction in the performance and physiological responses of broilers under high-density environmental stress.
Asunto(s)
Conducta Animal , Huesos , Pollos , Suplementos Dietéticos , Estrés Fisiológico , Ácido Tióctico , Alimentación Animal/análisis , Animales , Antioxidantes/farmacología , Conducta Animal/efectos de los fármacos , Huesos/efectos de los fármacos , Pollos/sangre , Masculino , Densidad de Población , Distribución Aleatoria , Estrés Fisiológico/efectos de los fármacos , Ácido Tióctico/sangre , Ácido Tióctico/farmacologíaRESUMEN
Lysosomes are involved in pathogenesis of a variety of neurodegenerative diseases and play a large role in neurodegenerative disorders caused by virus infection. However, whether virus-infected cells or animals can be used as experimental models of neurodegeneration in humans based on virus-related lysosomal dysfunction remain unclear. Porcine hemagglutinating encephalomyelitis virus displays neurotropism in mice, and neural cells are its targets for viral progression. PHEV infection was confirmed to be a risk factor for neurodegenerative diseases in the present. The findings demonstrated for the first time that PHEV infection can lead to lysosome disorders and showed that the specific mechanism of lysosome dysfunction is related to PGRN expression deficiency and indicated similar pathogenesis compared with human neurodegenerative diseases upon PHEV infection. Trehalose can also increase progranulin expression and rescue abnormalities in lysosomal structure in PHEV-infected cells. In conclusion, these results suggest that PHEV probably serve as a disease model for studying the pathogenic mechanisms and prevention of other degenerative diseases.