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BACKGROUND: Previous studies have reported associations between obstructive sleep apnea (OSA) and several mental disorders. However, further research is required to determine whether these associations are causal. Therefore, we evaluated the bidirectional causality between the genetic liability for OSA and nine mental disorders by using Mendelian randomization (MR). METHOD: We performed two-sample bidirectional MR of genetic variants for OSA and nine mental disorders. Summary statistics on OSA and the nine mental disorders were extracted from the FinnGen study and the Psychiatric Genomics Consortium. The primary analytical approach for estimating causal effects was the inverse-variance weighted (IVW), with the weighted median and MR Egger as complementary methods. The MR Egger intercept test, Cochran's Q test, Rucker's Q test, and the MR pleiotropy residual sum and outlier (MR-PRESSO) test were used for sensitivity analyses. RESULT: MR analyses showed that genetic liability for major depressive disorder (MDD) was associated with an increased risk of OSA (odds ratio [OR] per unit increase in the risk of MDD, 1.29; 95% CI, 1.11-1.49; P < 0.001). In addition, genetic liability for OSA may be associated with an increased risk of attention-deficit/hyperactivity disorder (ADHD) (OR = 1.26; 95% CI, 1.02-1.56; p = 0.032). There was no evidence that OSA is associated with other mental disorders. CONCLUSION: Our study indicated that genetic liability for MDD is associated with an increased risk of OSA without a bidirectional relationship. Additionally, there was suggestive evidence that genetic liability for OSA may have a causal effect on ADHD. These findings have implications for prevention and intervention strategies targeting OSA and ADHD. Further research is needed to investigate the biological mechanisms underlying our findings and the relationship between OSA and other mental disorders.
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Transtorno Depressivo Maior , Análise da Randomização Mendeliana , Apneia Obstrutiva do Sono , Humanos , Apneia Obstrutiva do Sono/genética , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtornos Mentais/genética , Transtornos Mentais/epidemiologia , Predisposição Genética para Doença/genéticaRESUMO
BACKGROUND: Endosonographers are highly dependent on the diagnosis of pancreatic ductal adenocarcinoma (PDAC). The objectives of this study were to develop a deep-learning radiomics (DLR) model based on endoscopic ultrasonography (EUS) images for identifying PDAC and to explore its true clinical benefit. METHODS: A retrospective data set of EUS images that included PDAC and benign lesions was used as a training cohort (N = 368 patients) to develop the DLR model, and a prospective data set was used as a test cohort (N = 123 patients) to validate the effectiveness of the DLR model. In addition, seven endosonographers performed two rounds of reader studies on the test cohort with or without DLR assistance to further assess the clinical applicability and true benefits of the DLR model. RESULTS: In the prospective test cohort, DLR exhibited an area under the receiver operating characteristic curves of 0.936 (95% confidence interval [CI], 0.889-0.976) with a sensitivity of 0.831 (95% CI, 0.746-0.913) and 0.904 (95% CI, 0.820-0.980), respectively. With DLR assistance, the overall diagnostic performance of the seven endosonographers improved: one endosonographer achieved a significant expansion of specificity (p = .035,) and another achieved a significant increase in sensitivity (p = .038). In the junior endosonographer group, the diagnostic performance with the help of the DLR was higher than or comparable to that of the senior endosonographer group without DLR assistance. CONCLUSIONS: A prospective test cohort validated that the DLR model based on EUS images effectively identified PDAC. With the assistance of this model, the gap between endosonographers at different levels of experience narrowed, and the accuracy of endosonographers expanded.
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Carcinoma Ductal Pancreático , Aprendizado Profundo , Neoplasias Pancreáticas , Humanos , Endossonografia/métodos , Estudos Retrospectivos , Estudos Prospectivos , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/patologia , Neoplasias PancreáticasRESUMO
OBJECTIVE: To compare an autoregressive integrated moving average (ARIMA) model with a model that combines ARIMA with the Elman recurrent neural network (ARIMA-ERNN) in predicting the incidence of pertussis in mainland China. BACKGROUND: The incidence of pertussis has increased rapidly in mainland China since 2016, making the disease an increasing public health threat. There is a pressing need for models capable of accurately predicting the incidence of pertussis in order to guide prevention and control measures. We developed and compared two models for predicting pertussis incidence in mainland China. METHODS: Data on the incidence of pertussis in mainland China from 2004 to 2019 were obtained from the official website of the Chinese Center for Disease Control and Prevention. An ARIMA model was established using SAS (ver. 9.4) software and an ARIMA-ERNN model was established using MATLAB (ver. R2019a) software. The performances of these models were compared. RESULTS: From 2004 to 2019, there were 104,837 reported cases of pertussis in mainland China, with an increasing incidence over time. The incidence of pertussis showed obvious seasonal characteristics, with the peak lasting from March to September every year. Compared with the mean squared error (MSE), mean absolute error (MAE), and mean absolute percentage error (MAPE) of the ARIMA model, those of the ARIMA-ERNN model were 81.43%, 95.97% and 80.86% lower, respectively, in fitting performance. In terms of prediction performance, the MAE, MSE and MAPE were 37.75%, 56.88% and 43.75% lower, respectively. CONCLUSION: The fitting and prediction performances of the ARIMA-ERNN model were better than those of the ARIMA model. This provides theoretical support for the prediction of infectious diseases and should be beneficial to public health decision making.
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Coqueluche , China/epidemiologia , Previsões , Humanos , Incidência , Modelos Estatísticos , Redes Neurais de Computação , Software , Coqueluche/epidemiologia , Coqueluche/prevenção & controleRESUMO
Levels and constituents of ambient air pollution have substantially changed in China over the last decade. Such changes may lead to the variations in health effects of air pollution. Very limited studies, however, have investigated the temporal variations in health effects of air pollution on a long-term scale, especially in China. We evaluated the temporal variations in short-term associations between PM10 and NO2 concentrations and emergency department (ED) visits during a 12-year period from 2008 to 2019 in Shanghai, China. A quasi-Poisson generalized linear regression was performed to assess the associations between PM10 and NO2 concentrations and ED visits during entire study period and three specific periods. We evaluated the temporal variations of period-specific associations with an interaction variable between pollutant concentrations and period indicators. We further investigated the concentration-response relationships for specific periods. The effects on specific subpopulations (males and females; 18-65 years old and >65 years old) were also examined. A 10 µg/m3 increase of PM10 and NO2 corresponded to 0.48% (95% CI: 0.36%, 0.59%) and 1.51% (95% CI: 1.25%, 1.78%) increase in ED visits at lag0-7 day for entire study period, respectively. The short-term associations between ED visits and NO2 remained unchanged over time (P-value > 0.05), while the effects from PM10 were significantly inconsistent (P-value < 0.05), with the highest effect observed during the intermediate period of 2012-2015 and the lowest effect observed during the initial period of 2008-2011. Similar temporal trends were found in subgroups, except for elderly group. Despite substantial reduction in ambient PM10 and NO2 concentrations, the short-term effects on ED visits for NO2 remained stable and even increased for PM10. More efforts were needed to reduce harmful components in air pollution mixture to reduce the health hazards of air pollution.
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Poluentes Atmosféricos , Poluição do Ar , Adolescente , Adulto , Idoso , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , China , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dióxido de Nitrogênio/análise , Material Particulado/análise , Material Particulado/toxicidade , Adulto JovemRESUMO
BACKGROUND: From 2 January to 14 February 2021, a local outbreak of COVID-19 occurred in Shijiazhuang, the capital city of Hebei Province, with a population of 10 million. We analyzed the characteristics of the local outbreak of COVID-19 in Shijiazhuang and evaluated the effects of serial interventions. METHODS: Publicly available data, which included age, sex, date of diagnosis, and other patient information, were used to analyze the epidemiological characteristics of the COVID-19 outbreak in Shijiazhuang. The maximum likelihood method and Hamiltonian Monte Carlo method were used to estimate the serial interval and incubation period, respectively. The impact of incubation period and different interventions were simulated using a well-fitted SEIR+q model. RESULTS: From 2 January to 14 February 2021, there were 869 patients with symptomatic COVID-19 in Shijiazhuang, and most cases (89.6%) were confirmed before 20 January. Overall, 40.2% of the cases were male, 16.3% were aged 0 to 19 years, and 21.9% were initially diagnosed as asymptomatic but then became symptomatic. The estimated incubation period was 11.6 days (95% CI 10.6, 12.7 days) and the estimated serial interval was 6.6 days (0.025th, 0.975th: 0.6, 20.0 days). The results of the SEIR+q model indicated that a longer incubation period led to a longer epidemic period. If the comprehensive quarantine measures were reduced by 10%, then the nucleic acid testing would need to increase by 20% or more to minimize the cumulative number of cases. CONCLUSIONS: Incubation period was longer than serial interval suggested that more secondary transmission may occur before symptoms onset. The long incubation period made it necessary to extend the isolation period to control the outbreak. Timely contact tracing and implementation of a centralized quarantine quickly contained this epidemic in Shijiazhuang. Large-scale nucleic acid testing also helped to identify cases and reduce virus transmission.
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COVID-19 , Período de Incubação de Doenças Infecciosas , Quarentena , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , Criança , Pré-Escolar , China/epidemiologia , Surtos de Doenças , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , SARS-CoV-2 , Adulto JovemRESUMO
BACKGROUND: This article aims to understand the prevalence of hyperlipidemia and its related factors in Shanxi Province. On the basis of multivariate Logistic regression analysis to find out the influencing factors closely related to hyperlipidemia, the complex network connection between various variables was presented through Bayesian networks(BNs). METHODS: Logistic regression was used to screen for hyperlipidemia-related variables, and then the complex network connection between various variables was presented through BNs. Since some drawbacks stand out in the Max-Min Hill-Climbing (MMHC) hybrid algorithm, extra hybrid algorithms are proposed to construct the BN structure: MMPC-Tabu, Fast.iamb-Tabu and Inter.iamb-Tabu. To assess their performance, we made a comparison between these three hybrid algorithms with the widely used MMHC hybrid algorithm on randomly generated datasets. Afterwards, the optimized BN was determined to explore to study related factors for hyperlipidemia. We also make a comparison between the BN model with logistic regression model. RESULTS: The BN constructed by Inter.iamb-Tabu hybrid algorithm had the best fitting degree to the benchmark networks, and was used to construct the BN model of hyperlipidemia. Multivariate logistic regression analysis suggested that gender, smoking, central obesity, daily average salt intake, daily average oil intake, diabetes mellitus, hypertension and physical activity were associated with hyperlipidemia. BNs model of hyperlipidemia further showed that gender, BMI, and physical activity were directly related to the occurrence of hyperlipidemia, hyperlipidemia was directly related to the occurrence of diabetes mellitus and hypertension; the average daily salt intake, daily average oil consumption, smoking, and central obesity were indirectly related to hyperlipidemia. CONCLUSIONS: The BN of hyperlipidemia constructed by the Inter.iamb-Tabu hybrid algorithm is more reasonable, and allows for the overall linking effect between factors and diseases, revealing the direct and indirect factors associated with hyperlipidemia and correlation between related variables, which can provide a new approach to the study of chronic diseases and their associated factors.
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Hiperlipidemias , Algoritmos , Teorema de Bayes , Estudos Transversais , Humanos , Hiperlipidemias/epidemiologia , Modelos LogísticosRESUMO
This study aims to explore the relationship between ambient NO2 levels and the transmission ability (basic reproductive number, R0) of COVID-19 in 63 Chinese cities. After adjustment for temperature and relative humidity, R0 was positively associated with NO2 concentration at city level. The temporal analysis within Hubei province indicated that all the 11 Hubei cities (except Xianning City) had significant positive correlations between NO2 concentration (with 12-day time lag) and R0 (r > 0.51, p < 0.005). Since the association between ambient NO2 and R0 indicated NO2 may increase underlying risk of infection in the transmission process of COVID-19. In addition, NO2 is also an indicator of traffic-related air pollution, the association between NO2 and COVID-19's spreadability suggest that reduced population movement may have reduced the spread of the SARS-CoV-2.
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Poluentes Atmosféricos/análise , COVID-19/epidemiologia , COVID-19/transmissão , Dióxido de Nitrogênio/análise , Material Particulado/análise , China/epidemiologia , Cidades , Exposição Ambiental/análise , Exposição Ambiental/prevenção & controle , Humanos , SARS-CoV-2 , TemperaturaRESUMO
The coronavirus (COVID-19) epidemic reported for the first time in Wuhan, China at the end of 2019, which has caused 4648 deaths in China as of July 10, 2020. This study explored the temporal correlation between the case fatality rate (CFR) of COVID-19 and particulate matter (PM) in Wuhan. We conducted a time series analysis to examine the temporal day-by-day associations. We observed a higher CFR of COVID-19 with increasing concentrations of inhalable particulate matter (PM) with an aerodynamic diameter of 10 µm or less (PM10) and fine PM with an aerodynamic diameter of 2.5 µm or less (PM2.5) in the temporal scale. This association may affect patients with mild to severe disease progression and affect their prognosis.
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Poluição do Ar , Infecções por Coronavirus/mortalidade , Material Particulado/análise , Pneumonia Viral/mortalidade , Poluentes Atmosféricos/análise , Betacoronavirus , COVID-19 , China/epidemiologia , Humanos , Pandemias , SARS-CoV-2 , TempoAssuntos
Infecções por Coronavirus/transmissão , Coronavirus , Pneumonia Viral/transmissão , Temperatura , Raios Ultravioleta , Betacoronavirus , COVID-19 , China/epidemiologia , Cidades , Infecções por Coronavirus/epidemiologia , Humanos , Pandemias , Pneumonia Viral/epidemiologia , SARS-CoV-2 , População UrbanaRESUMO
Bacillus thuringiensis produces chitinases, which are involved in its antifungal activity and facilitate its insecticidal activity. In our recent work, we found that a 16-bp sequence, drechiB (AGACTTCGTGATGTCT), downstream of the minimal promoter region of the chitinase B gene (chiB) was a critical site for the inducible expression of chiB in B. thuringiensis Bti75. In this work, we show that a GntR family transcriptional regulator (named YvoABt), which is homologous to YvoA of Bacillus subtilis, can specifically bind to the drechiB oligonucleotide sequences in vitro by using electrophoretic mobility shift assays (EMSAs) and isothermal titration calorimetry (ITC) assays. The results of quantitative real-time reverse transcription-PCR (qRT-PCR) and Western blotting indicated that deletion of yvoA caused an â¼7.5-fold increase in the expression level of chiB. Furthermore, binding of purified YvoABt to its target DNA could be abolished by glucosamine-6-phosphate (GlcN-6-P). We also confirmed, in the presence of the phosphoprotein Hpr-Ser45-P, that purified CcpABt bound specifically to the promoter of chiB, which contains the "crechiB" sequence (ATAAAGCGTTTACA). According to the results of qRT-PCR and Western blotting, deletion of ccpA resulted in a 39-fold increase in the chiB expression level, and glucose no longer influenced the expression of chiB. We confirm that chiB is negatively controlled by both CcpABt and YvoABt in Bti75.
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Bacillus thuringiensis/enzimologia , Quitinases/genética , Regulação para Baixo , Proteínas Repressoras/metabolismo , Bacillus thuringiensis/genética , Bacillus thuringiensis/metabolismo , Proteínas de Bactérias/genética , Quitinases/metabolismo , Regulação Bacteriana da Expressão Gênica , Regiões Promotoras Genéticas , Proteínas Repressoras/genéticaRESUMO
The immunotherapy for gastrointestinal tumors, as a significant research direction in the field of oncology treatment in recent years, has garnered extensive attention due to its potential therapeutic efficacy and promising clinical application prospects. Recent advances in immunotherapy notwithstanding, challenges persist, such as side effects, the complexity of the tumor immune microenvironment, variable patient responses, and drug resistance. Consequently, there is a pressing need to explore novel adjunctive therapeutic modalities. ß-glucan, an immunomodulatory agent, has exhibited promising anti-tumor efficacy in preclinical studies involving colorectal cancer, pancreatic cancer, and gastric cancer, while also mitigating the adverse reactions associated with chemotherapy and enhancing patients' quality of life. However, further clinical and fundamental research is warranted to comprehensively evaluate its therapeutic potential and underlying biological mechanisms. In the future, ß-glucan holds promise as an adjunctive treatment for gastrointestinal tumors, potentially bringing significant benefits to patients.
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Neoplasias Gastrointestinais , Imunoterapia , beta-Glucanas , Humanos , beta-Glucanas/uso terapêutico , beta-Glucanas/imunologia , Neoplasias Gastrointestinais/terapia , Neoplasias Gastrointestinais/imunologia , Neoplasias Gastrointestinais/tratamento farmacológico , Imunoterapia/métodos , Animais , Adjuvantes Imunológicos/uso terapêutico , Microambiente Tumoral/imunologia , Microambiente Tumoral/efeitos dos fármacosRESUMO
Background: Economic data on congenital heart disease are scarce in economically underdeveloped areas of China. Therefore, this study aimed to shed light on the level and changing trend of congenital heart disease inpatients' economic burden in underdeveloped areas. Method: This study used a multi-stage stratified cluster sampling method to select 11,055 inpatients with congenital heart disease from 197 medical and health institutions in Gansu Province. Their medical records and expenses were obtained from the Hospital Information System. Univariate analysis was conducted using the rank sum test and Spearman rank correlation. Quantile regression and random forest were used to analyze the influencing factors. Results: From 2015 to 2020, the average length of stay for congenital heart disease patients in Gansu Province was 10.09 days, with an average inpatient cost of USD 3,274.57. During this period, the average inpatient costs per time increased from USD 3,214.85 to USD 3,403.41, while the average daily inpatient costs increased from USD 330.05 to USD 376.56. The average out-of-pocket costs per time decreased from USD 2,305.96 to USD 754.77. The main factors that affected the inpatient costs included length of stay, cardiac procedure, proportion of medications, age, and hospital level. Conclusion: Congenital heart disease causes a significant economic burden on both families and society. Therefore, to further reduce the patient's financial burden, the length of stay should be reasonably reduced, and the rational distribution of medical resources should be continuously promoted to ensure equitable access to healthcare services.
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Cardiopatias Congênitas , Hospitalização , Humanos , Pacientes Internados , Gastos em Saúde , China/epidemiologia , Cardiopatias Congênitas/epidemiologiaRESUMO
Metals have been proved to be one of risk factors for chronic kidney disease (CKD) and diabetes, but the effect of mixed metal co-exposure and potential interaction between metals are still unclear. We assessed the urine and whole blood levels of cadmium (Cd), manganese (Mn), lead (Pb), mercury (Hg), and renal function in 3080 adults from National Health and Nutrition Survey (NHANES) (2011-2018) to explore the effect of mixed metal exposure on CKD especially in people with type 2 diabetes mellitus (T2DM). Weighted quantile sum regression model and Bayesian Kernel Machine Regression model were used to evaluate the overall exposure impact of metal mixture and potential interaction between metals. The results showed that the exposure to mixed metals was significantly associated with an increased risk of CKD in blood glucose stratification, with the risk of CKD being 1.58 (1.26,1.99) times in urine and 1.67 (1.19,2.34) times in whole blood higher in individuals exposed to high concentrations of the metal mixture compared to those exposed to low concentrations. The effect of urine metal mixture was elevated magnitude in stratified analysis. There were interactions between urine Pb and Cd, Pb and Mn, Pb and Hg, Cd and Mn, Cd and Hg, and blood Pb and Hg, Mn and Cd, Mn and Pb, Mn and Hg on the risk of CKD in patients with T2DM and no significant interaction between metals was observed in non-diabetics. In summary, mixed metal exposure increased the risk of CKD in patients with T2DM, and there were complex interactions between metals. More in-depth studies are needed to explore the mechanism and demonstrate the causal relationship.
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Exposição Ambiental , Inquéritos Nutricionais , Insuficiência Renal Crônica , Humanos , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/urina , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Exposição Ambiental/efeitos adversos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Cádmio/sangue , Cádmio/urina , Cádmio/efeitos adversos , Cádmio/toxicidade , Fatores de Risco , Chumbo/sangue , Chumbo/urina , Chumbo/toxicidade , Metais Pesados/sangue , Metais Pesados/urina , Metais Pesados/efeitos adversos , Metais Pesados/toxicidade , Idoso , Metais/urina , Metais/sangue , Metais/efeitos adversos , Manganês/urina , Manganês/sangue , Manganês/efeitos adversos , Teorema de BayesRESUMO
There is evidence to support the links between lead and cadmium exposure with hypertension and also with leukocyte telomere length (LTL). The objective of this study is to investigate the role that LTL may play in the relationship between lead and cadmium exposure and hypertension. This study consisted of 3718 participants from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. Logistic regression was used to analyze the relationship between blood metals with hypertension, and the mediating model was used to evaluate the mediating effect of LTL. In the fully adjusted model, both blood lead and cadmium ln-transformed concentrations were significantly positively associated with hypertension risk, as were all quartiles of blood lead. Additionally, we observed positive linear dose-response relationships with hypertension by restricted cubic spline analysis (both p overall < 0.001, p non-linear = 0.3008 for lead and p non-linear = 0.7611 for cadmium). The ln-transformed blood lead and cadmium concentrations were associated with shorter LTL. LTL was inversely related to hypertension and the OR was 0.65 (95% CI: 0.47 to 0.89). Furthermore, LTL had mediating effects on the associations of blood lead and cadmium with hypertension risk, and the mediation proportions were 2.25% and 4.20%, respectively. Our findings suggested that exposure to lead and cadmium raised the risk of hypertension, while LTL played as a mediating factor.
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Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are associated with adverse health effects. This study examined the trend of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) levels in individuals with and without pre-existing comorbidities. We analyzed the characteristics of 13,887 participants across nine U.S. NHANES cycles (1999-2000 to 2017-2018) and calculated the geometric mean (GM) of PFOA and PFOS levels, standardized by sex and age. A joinpoint regression model was used to analyze the temporal trends of serum PFOA and PFOS levels. We observed declining PFOA and PFOS serum levels among adults in NHANES from 1999-2000 to 2017-2018. Serum PFOA and PFOS concentrations were higher in men, smokers, and individuals with pre-existing CKD, hyperlipidemia, CVD, and cancer. We observed faster decline rates in PFOA levels among individuals with diabetes and CKD and faster decline rates in PFOS levels among individuals with diabetes and those without CKD. This study provided evidence of varying levels and changing trends of PFOA and PFOS between groups with and without established chronic disease, highlighting the role of environmental chemicals in the onset and development of chronic diseases.
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BACKGROUND: Frailty is highly prevalent in hospitalized older patients and may increase the risk of adverse health outcomes. Understanding the experiences of older patients and the management strategies they use to recover from frailty is crucial to developing appropriate interventions. PURPOSE: This study was designed to explore the frailty experiences of older adults and the management strategies they use to recover from frailty. METHODS: Using purposive sampling, semistructured, face-to-face interviews were conducted with 16 older patients with frailty. Data were analyzed using content analysis. RESULTS: The experiences of participants were classified into three phases, including the (a) individual sensing phase, (b) daily-living-threatening phase, and (c) acclimatization and acceptance phase. When experiencing frailty, the participants developed management strategies to facilitate recovery, which manifested in three phases: (a) making flexible adjustments to the daily routine, (b) using adequate support systems, and (c) adopting positive thinking. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The results indicate that familial support and positive thinking are important management strategies for successful recovery in frail individuals. Older patients require adequate support systems. Positive thinking was also found to be an effective management strategy for recovery. Healthcare professionals should not only focus on providing supportive resources but also provide support to older patients to facilitate their adoption of positive thinking to face life changes brought on by frailty.
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Fragilidade , Idoso , Humanos , Atitude do Pessoal de Saúde , Pessoal de Saúde , Pesquisa Qualitativa , Atividades CotidianasRESUMO
Preclinical studies have proven that nanosecond pulsed electric field (nsPEF) ablation can be a safe and effective treatment for humans with unresectable liver cancer that are ineligible for thermal ablation. The concomitant activation of antitumor immunity by nsPEF can also potentially prevent tumor recurrence. However, whether nsPEF exhibits similar efficacy in a clinical setting remains to be investigated. A prospective clinical trial (clinicaltrials.gov identifier: NCT04039747) was conducted to evaluate the safety and efficacy of ultrasound (US)-guided nsPEF ablation in 15 patients with unresectable liver cancer that were ineligible for thermal ablation. We found that nsPEF ablation was safe and produced a 12-month recurrence-free survival (RFS) and local RFS of 60% (9/15) and 86.7% (13/15), respectively, in the enrolled patients. Integrative proteomic and metabolomic analysis showed that sphingolipid metabolism was the most significantly enriched pathway in patient sera after nsPEF without recurrence within 8 months. A similar upregulation of sphingolipid metabolism was observed in the intratumoral mononuclear phagocytes (MNPs), rather than other immune and nonimmune cells, of an nsPEF-treated mouse model. We then demonstrated that lymphocyte antigen 6 complex, locus C2-positive (Ly6c2+ ) monocytes first differentiated into Ly6c2+ monocyte-derived macrophages with an increase in sphingolipid metabolic activity, and subsequently into Ly6c2+ dendritic cells (DCs). Ly6c2+ DCs communicated with CD8+ T cells and increased the proportions of IFN-γ+ CD8+ memory T cells after nsPEF, and this finding was subsequently confirmed by depletion of liver Ly6c2+ MNPs. In conclusion, nsPEF was a safe and effective treatment for liver cancer. The alteration of sphingolipid metabolism induced by nsPEF was associated with the differentiation of Ly6c2+ MNPs, and subsequently induced the formation of memory CD8+ T cells with potent antitumor effect.
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Linfócitos T CD8-Positivos , Neoplasias Hepáticas , Camundongos , Animais , Humanos , Linfócitos T CD8-Positivos/patologia , Estudos Prospectivos , Proteômica , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Macrófagos/patologia , Diferenciação CelularRESUMO
Epidemiological evidence for the relationship between cadmium exposure and mortality in specific chronic kidney disease (CKD) populations remains scarce. We aimed to explore the relationships between cadmium concentrations in urine and blood and all-cause mortality among CKD patients in the USA. This cohort study was composed of 1825 CKD participants from the National Health and Nutrition Examination Survey (NHANES) (1999-2014) who were followed up to December 31, 2015. All-cause mortality was ascertained by matching the National Death Index (NDI) records. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality in relation to urinary and blood cadmium concentrations by Cox regression models. During an average follow-up period of 82 months, 576 CKD participants died. Compared with the lowest quartiles, HRs (95% CIs) for all-cause mortality associated with the fourth weighted quartiles of urinary and blood cadmium concentrations were 1.75 (1.28 to 2.39) and 1.59 (1.17 to 2.15), respectively. Furthermore, the HRs (95% CIs) for all-cause mortality per ln-transformed IQR increment in cadmium concentrations in urine (1.15 µg/g UCr) and blood (0.95 µg/L) were 1.40 (1.21 to 1.63) and 1.22 (1.07 to 1.40), respectively. Linear concentration-response relationships between urinary and blood cadmium concentrations and all-cause mortality were also found. Our findings suggested that increased cadmium concentrations in both urine and blood significantly contributed to enhanced mortality risk in CKD patients, thus highlighting that efforts to reduce cadmium exposure may reduce mortality risk in high-risk populations with CKD.
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Cádmio , Insuficiência Renal Crônica , Humanos , Adulto , Cádmio/urina , Inquéritos Nutricionais , Estudos de Coortes , Estudos Prospectivos , Exposição Ambiental , Insuficiência Renal Crônica/epidemiologiaRESUMO
Background: The association between exposure to trace elements mixture and the prevalence of kidney stones and the interactions between elements are unclear. The aim of this study was to explore the association between exposure to trace elements mixture and the prevalence of kidney stones and the interactions between the elements. Methods: A total of 1,244 participants (139 kidney stone formers and 1,105 non-stone former participants) in NHANES 2017-2018 were included. The exposure to trace elements was evaluated by measuring their concentration in urine samples. Three methods, Logistic regression, quantile-based g computation (qgcomp), and Bayesian kernel machine regression (BKMR), were used for analysis. Results: According to the results from qgcomp and BKMR, a negative association was found between exposure to the 13 trace elements and the prevalence of kidney stones [OR = 0.50 (0.32, 0.78)]. Subgroup analysis revealed that Co, As, and iodine in the whole population, Co, As, and Ni in males, and Cs, iodine, and Sb in females, were most strongly associated with kidney stones. Kidney stone was found to be positively correlated with Co and negatively correlated with the other elements. Besides, there were significant interactions between Ni and Pb in the whole population, Co and iodine in males, and Pb and iodine in females. Conclusion: There was a negative association between exposure to the mixture of 13 trace elements and the prevalence of kidney stones.
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Iodo , Cálculos Renais , Oligoelementos , Feminino , Masculino , Humanos , Prevalência , Teorema de Bayes , Chumbo , Inquéritos Nutricionais , Cálculos Renais/epidemiologia , Cálculos Renais/etiologiaRESUMO
As the COVID-19 pandemic disturbed people's daily life for more than 2 years, many COVID-19 vaccines have been carried forward systematically to curb the transmission of the virus. However, high vaccination tasks bring great challenges to personnel allocation. We observed nine vaccination clinics in Huzhou and Shanghai and built a discrete-event simulation model to simulate the optimal staffing of vaccination clinics under 10 different scenarios. Based on the result of the simulations, we optimized the allocation of vaccination staff in different stages of epidemic development by province in China. The results showed that optimizing staffing could both boost service utilization and shorten the queuing time for vaccination recipients. Taking Jilin Province as an example, to increase the booster vaccination rate within 3 months, the number of vaccination staff members needed was 2028, with a continuous small-scale breakout and 2,416 under a stable epidemic situation. When there was a shortage of vaccination staff, the total number of vaccination clinic staff members needed could be significantly reduced by combining the preview and registration steps. This study provides theoretical support for the personnel arrangement of COVID-19 vaccinations of a booster dose by province and the assessment of current vaccination staff reserves.