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The increased expression of programmed death-ligands 1 and 2 (PD-L1 and PD-L2, respectively) on tumour cells contributes to immune evasion, suggesting that these proteins are attractive therapeutic targets. This study aimed to evaluate the validity of cerebrospinal fluid (CSF) soluble PD-L1 (sPD-L1) and soluble PD-L2 (sPD-L2) as biomarkers for primary central nervous system lymphoma (PCNSL). We determined the CSF concentrations of sPD-L1 and sPD-L2 in 46 patients with PCNSL using enzyme-linked immunosorbent assays (ELISAs). A control group comprised 153 patients with other brain tumours, inflammatory/infectious status, or neurodegenerative diseases. Only CSF sPD-L1 levels were significantly higher in patients with PCNSL relative to the controls. CSF sPD-L1 also exhibited superior overall discrimination performance compared to CSF sPD-L2 in diagnosing PCNSL. Compared with patients with PCNSL with low CSF sPD-L1 levels, more patients with high levels had high serum lactate dehydrogenase levels, leptomeningeal involvement, and deep-brain involvement. Furthermore, CSF sPD-L1 could predict poor survival in PCNSL but CSF sPD-L2 could not. Intriguingly, CSF sPD-L1 levels were correlated with disease status and their dynamic changes post treatment could predict time to relapse. In conclusion, this study identified CSF sPD-L1 as a promising prognostic biomarker, indicating a therapeutic potential of PD-L1 blockade in PCNSL.
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Antígeno B7-H1 , Linfoma , Humanos , Antígeno B7-H1/metabolismo , Prognóstico , Sistema Nervoso Central , Linfoma/diagnósticoRESUMO
BACKGROUND: Exercise electrocardiography (ECG) is a noninvasive test aiming at producing ischemic changes. However, resting ECG cannot be adopted in diagnosing myocardial ischemia till ST-segment depressions. Therefore, this study aimed to detect myocardial energy defects in resting ECG using the Hilbert-Huang transformation (HHT) in patients with angina pectoris. METHODS: Electrocardiographic recordings of positive exercise ECG by performing coronary imaging test (n = 26) and negative exercise ECG (n = 47) were collected. Based on the coronary stenoses severity, patients were divided into three categories: normal, < 50%, and ≥ 50%. During the resting phase of the exercise ECG, all 10-s ECG signals are decomposed by HHT. The RT intensity index, composed of the power spectral density of the P, QRS, and T components, is used to estimate the myocardial energy defect. RESULTS: After analyzing the resting ECG using HHT, the RT intensity index was significantly higher in patients with positive exercise ECG (27.96%) than in those with negative exercise ECG (22.30%) (p < 0.001). In patients with positive exercise ECG, the RT intensity index was gradually increasing with the severity of coronary stenoses: 25.25% (normal, n = 4), 27.14% (stenoses < 50%, n = 14), and 30.75% (stenoses ≥ 50%, n = 8). The RT intensity index of different coronary stenoses was significantly higher in patients with negative exercise ECG, except for the normal coronary imaging test. CONCLUSIONS: Patients with coronary stenoses had a higher RT index at the resting stage of exercise ECG. Resting ECG analyzed using HHT could be a method for the early detection of myocardial ischemia.
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Doença da Artéria Coronariana , Estenose Coronária , Isquemia Miocárdica , Humanos , Constrição Patológica , Isquemia Miocárdica/diagnóstico , Eletrocardiografia , Estenose Coronária/diagnóstico , Teste de EsforçoRESUMO
OBJECTIVES: The purpose of this study was to identify occupational injuries and diseases associated with agriculture in Asia, to provide a reference for prevention and hypotheses for future research. METHODS: We matched data on agricultural workers (n = 963,124) enrolled in Taiwan's national Farmers Health Insurance since its inception in 1989, to general population controls of the same age, gender, and township. The study population was linked to the National Health Insurance Research Database from 2001 to 2016 for inpatient cases. Logistic regression was used to assess odds ratios for outcomes. RESULTS: Farmers had 2.76 times the risk of mycotic corneal ulcer (95% CI: 1.96-3.87) and 1.65 times the risk of typhus fever infections (95% CI: 1.47-1.85) compared to the general population. The odds ratio for poisonous animal bites was 2.22 (95% CI: 2.07-2.38), for falling into a storm drain or manhole was 2.04 (95% CI: 1.30-3.20), and for toxic effects from pesticides was 2.01 (95% CI: 1.92-2.11). The toxic effects of organophosphate and carbamate insecticides were correlated with the cultivation of rice, fruit trees, and flowers. Q fever and motorcycle accidents were associated with fruit tree cultivation. CONCLUSIONS: The study identifies agricultural occupational injuries and diseases that may inform occupational health policy and the development of prevention priorities to prevent occupational hazards for farmers.
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Doenças Profissionais , Exposição Ocupacional , Saúde Ocupacional , Traumatismos Ocupacionais , Praguicidas , Animais , Humanos , Traumatismos Ocupacionais/epidemiologia , Fazendeiros , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Agricultura , Exposição Ocupacional/efeitos adversosRESUMO
OBJECTIVES: We sought to investigate whether preoperative dual-phase 2-[18F]FDG PET-CT identify predictors for poor survival in patients with ampullary carcinoma receiving pancreaticoduodenectomy. METHODS: The preoperative PET-CT images of patients with resected ampullary carcinoma from June 2007 to July 2017 were analyzed. Survival curves were analyzed using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazard model was used to identify potential prognostic factors associated with disease-free survival (DFS) and overall survival (OS). RESULTS: Fifty-four subjects (26 men, 28 women) were enrolled with a median tumor size of 20 mm. All patients were followed for a median period of 36.9 months with 3- and 5-year DFS of 50.3% and 44.2%, and OS of 77.0% and 68.2%, respectively. Parameters associated with DFS in multivariate analysis were lymphovascular invasion (hazard ratio [HR]: 9.45, p < 0.001), involved margin in pathology (HR: 7.67, p < 0.001), and tumor retention index (RI) from the dual-phase PET (HR: 2.41, p = 0.03), whereas involved margin (HR: 13.14, p < 0.001), post-recurrence chemotherapy (HR: 0.10, p < 0.001), and metabolic tumor volume (MTV) (HR: 4.62, p = 0.009) emerged as independent prognostic factors for OS. CONCLUSIONS: Preoperative 2-[18F]FDG PET-CT offered independent prognostic biomarkers in patients with ampullary carcinoma receiving standard surgical resection. KEY POINTS: ⢠2-[18F]FDG PET-CT offers good survival prediction before operation in primary malignant neoplasms at ampulla of Vater. ⢠Dual-phase PET scan with bowel distention can better delineate Ampulla of Vater and characterize tumor physiology. ⢠Preoperative risk stratification might aid in better treatment planning.
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Ampola Hepatopancreática , Neoplasias Pulmonares , Ampola Hepatopancreática/diagnóstico por imagem , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Recidiva Local de Neoplasia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Carga TumoralRESUMO
Aqueous palladium-catalyzed direct arylation polymerization (DArP) of 2-bromothiophene derivatives 6-(2-(2-bromothiophen-3-yl)ethoxy)hexyl trimethylammonium bromide (T1) and 4-(2-(2-bromothien-3-yl)ethoxy)butylsulfonate (T2) is achieved. The supporting ligand, triphenylphosphine-3,3',3''-trisulfonic acid trisodium salt (m-TPPTs), facilitates DArP of both derivatives; however, its separation from the polymers by dialysis is difficult due to its strong aggregation in water and N,N-dimethylacetamide (DMAc). This is supported by dynamic light scattering, gel permeation chromatography (GPC), and single-crystal X-ray crystallography. Pyrimidine-Pd(OAc)2 is utilized in the DArP of T1 to afford PT1 without ligand contamination. Density functional theory calculations to determine the coordinating capability of the carboxylate/pivalic acid/water to palladium indicate the viability of implementing DArP in water. Finally, polyelectrolyte molecular-weight overestimation by GPC in water is attributed to the polyelectrolyte effect. Aggregation of the conjugated polyelectrolytes leads to a contracted hydrodynamic volume, and the molecular weight and dispersity assessed by GPC in DMAc significantly deviate from the actual values. An objective approach to evaluate the molecular weight for conjugated polyelectrolytes requires further development.
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Paládio/química , Ácidos Sulfônicos/química , Compostos de Trimetil Amônio/química , Catálise , Estrutura Molecular , Polimerização , Água/químicaRESUMO
BACKGROUND: Two main job stress models-the Demand-Control-Support (DC) model and the Effort-Reward Imbalance (ERI) model have been used to assess the impact of psychosocial work-related factors for cardiovascular disease (CVD). Limited evidence elaborates the independent and combined effects on CVD events, especially for professional drivers. This study assesses the independent and combined effects of DC and ERI models on an 8-year risk of CVD among professional drivers. METHODS: The Taiwan Bus Driver Cohort Study recruited 1650 professional drivers from a large bus company in 2005. The subjects were interviewed in person and completed the two job stress questionnaires. Researchers found 94 new cases of CVD (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]: 390-459) from 2006 to 2012. A Cox proportional hazards model was performed to estimate the hazard ratio (HR) for CVD events. RESULTS: Occupational drivers with high overcommitment scores (thresholds of 15) had an elevated risk for CVD (HR = 1.71; 95% CI = 1.04, 2.82). Regarding target disease, overcommitment had an increased risk for CVD (not including hypertensive disease) (HR = 1.27; 95% CI = 1.05, 1.54) and ischemic heart disease (HR = 1.32; 95% CI = 1.05-1.65). CONCLUSION: Overcommitment, which is associated with job stress, appears to be associated with CVD risk in professional drivers.
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Condução de Veículo/psicologia , Doenças Cardiovasculares/etiologia , Veículos Automotores , Estresse Ocupacional/complicações , Adulto , Condução de Veículo/estatística & dados numéricos , Doenças Cardiovasculares/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Ocupacional/epidemiologia , Modelos de Riscos Proporcionais , Fatores de Risco , Inquéritos e Questionários , Taiwan/epidemiologiaRESUMO
Influenza A viruses (IAV) are widespread in birds and domestic poultry, occasionally causing severe epidemics in humans and posing health threats. Hence, the need to develop a strategy for prophylaxis or therapy, such as a broadly neutralizing antibody against IAV, is urgent. In this study, single-chain variable fragment (scFv) phage display technology was used to select scFv fragments recognizing influenza envelope proteins. The Tomlinson I and J scFv phage display libraries were screened against the recombinant HA2 protein (rHA2) for three rounds. Only the third-round elution sample of the Tomlinson J library showed high binding affinity to rHA2, from which three clones (3JA18, 3JA62, and 3JA78) were chosen for preparative-scale production as soluble antibody by E. coli. The clone 3JA18 was selected for further tests due to its broad affinity for influenza H1N1, H3N2 and H5N1. Simulations of the scFv 3JA18-HA trimer complex revealed that the complementarity-determining region of the variable heavy chain (VH-CDR2) bound the stem region of HA. Neutralization assays using a peptide derived from VH-CDR2 also supported the simulation model. Both the selected antibody and its derived peptide were shown to suppress infection with H5N1 and H1N1 viruses, but not H3N2 viruses. The results also suggested that the scFvs selected from rHA2 could have neutralizing activity by interfering with the function of the HA stem region during virus entry into target cells.
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Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Fragmentos Fc das Imunoglobulinas/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Virus da Influenza A Subtipo H5N1/imunologia , Influenza Humana/virologia , Anticorpos de Cadeia Única/imunologia , Anticorpos Neutralizantes/genética , Anticorpos Neutralizantes/imunologia , Especificidade de Anticorpos , Humanos , Fragmentos Fc das Imunoglobulinas/genética , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H3N2/genética , Virus da Influenza A Subtipo H5N1/genética , Influenza Humana/imunologia , Anticorpos de Cadeia Única/genéticaRESUMO
BACKGROUND: Shipbreaking remains one of the most dangerous jobs worldwide. Shipbreaking workers are exposed to many hazardous chemicals, especially asbestos. Unfortunately, long-term follow-up studies of cancer incidence patterns in shipbreaking workers are lacking. This study examines whether there is an increased risk of cancer among male shipbreaking workers over a 24-year follow-up period. METHODS: 4155 male shipbreaking worker's information was retrospectively collected from Kaohsiung's Shipbreaking Workers Union database from 1985. The study cohort was linked to the Taiwan Cancer Registry from 1985 to 2008 for new cancer cases. The expected number of cancers for shipbreaking workers was calculated by using the age (5-year intervals) and calendar time-specific annual rates of cancer incidence with reference to the general population of Taiwan from 1985 to 2008. Standardized incidence ratios (SIRs) were calculated as relative risk estimates. The hazard ratio (HR) for cancer was calculated for the shipbreaking workers with Total Exposure Potential Scores for asbestos. RESULTS: After consideration of a 5-year latency period, an elevated incidence of overall cancer (N=368; SIR=1.13 (1.01-1.25)), oral cavity cancer (N=83; SIR=1.99 (1.58-2.46)), and trachea, bronchus, and lung cancers (N=53; SIR=1.36 (1.02-1.78)) was found among male shipbreaking employees. Moreover, mesothelioma cases were found in those who had the occupation of flame cutter. The high asbestos exposure group was associated with an increased SIR of developing overall cancer and oral cancer, whether we considered a 5-year or 10-year latency period. CONCLUSION: Asbestos-related diseases, including lung cancer and mesothelioma, were seen in excess in these shipbreaking workers and some cases appeared to have a dose-dependent relationship. Preventative measures among male shipbreaking workers should be researched further.
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Amianto/efeitos adversos , Neoplasias/epidemiologia , Exposição Ocupacional/efeitos adversos , Sistema de Registros , Adulto , Seguimentos , Humanos , Incidência , Masculino , Neoplasias/etiologia , Estudos Retrospectivos , Taiwan/epidemiologiaRESUMO
Background: Variant interpretation is essential for identifying patients' disease-causing genetic variants amongst the millions detected in their genomes. Hundreds of Variant Impact Predictors (VIPs), also known as Variant Effect Predictors (VEPs), have been developed for this purpose, with a variety of methodologies and goals. To facilitate the exploration of available VIP options, we have created the Variant Impact Predictor database (VIPdb). Results: The Variant Impact Predictor database (VIPdb) version 2 presents a collection of VIPs developed over the past 25 years, summarizing their characteristics, ClinGen calibrated scores, CAGI assessment results, publication details, access information, and citation patterns. We previously summarized 217 VIPs and their features in VIPdb in 2019. Building upon this foundation, we identified and categorized an additional 186 VIPs, resulting in a total of 403 VIPs in VIPdb version 2. The majority of the VIPs have the capacity to predict the impacts of single nucleotide variants and nonsynonymous variants. More VIPs tailored to predict the impacts of insertions and deletions have been developed since the 2010s. In contrast, relatively few VIPs are dedicated to the prediction of splicing, structural, synonymous, and regulatory variants. The increasing rate of citations to VIPs reflects the ongoing growth in their use, and the evolving trends in citations reveal development in the field and individual methods. Conclusions: VIPdb version 2 summarizes 403 VIPs and their features, potentially facilitating VIP exploration for various variant interpretation applications. Availability: VIPdb version 2 is available at https://genomeinterpretation.org/vipdb.
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BACKGROUND: Shipbreaking workers are typically exposed to a wide range of hazardous chemicals. However, long-term follow-up studies of their mortality patterns are lacking. This study examined mortality among shipbreaking workers over a 24-year follow-up period. METHODS: A total of 4,962 shipbreaking workers were recruited from the database of the Kaohsiung Shipbreaking Workers Union. The data were then linked to the Taiwan National Death Registry from 1985 to 2008. The mortality ratios-standardized for age and calendar years-(SMRs) for various causes of deaths were calculated with reference to the general population of Taiwan. RESULTS: Among men workers, a statistically significant increased SMR was observed for all causes (SMR = 1.28), all cancers (SMR = 1.26; particularly noteworthy for lesions of oral and nasopharyngeal: SMR 2.03, liver: SMR 4.63, and lung: SMR 1.36), cirrhosis of the liver (SMR = 1.32), and accidents (SMR = 1.91). A statistically significant increase in mortality was observed for respiratory system cancer (SMR = 1.87) and lung cancer (SMR = 1.91) among workers with a longer duration of employment (≥7 years). The result also showed that among shipbreaking workers who were still alive, two people had mesothelioma and 10 people have asbestosis. CONCLUSIONS: Those employed in shipbreaking industries experienced an increase in mortality from all causes. The increased SMR for lung cancer was probably related to asbestos, metals, and welding fume exposure.
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Causas de Morte , Indústrias , Neoplasias Pulmonares/mortalidade , Doenças Profissionais/mortalidade , Exposição Ocupacional/efeitos adversos , Adulto , Distribuição por Idade , Amianto/efeitos adversos , Estudos de Coortes , Intervalos de Confiança , Feminino , Humanos , Incidência , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/etiologia , Doenças Profissionais/fisiopatologia , Estudos Retrospectivos , Medição de Risco , Distribuição por Sexo , Análise de Sobrevida , Taiwan , Adulto JovemRESUMO
The yellow crazy ant (Anoplolepis gracilipes (Smith, 1857)) is a prominent invasive species exhibiting variable population dynamics. Through collecting long-term climate data and validating field surveys with MaxEnt SDM projections, our results indicated that winter temperature and precipitation accumulation strongly influence the population dynamics. An aggression analysis showed that A. gracilipes nests with higher aggression levels (over 2.5 scores) experienced a higher mean maximum temperature (31.84 ± 0.43 °C) and lower prevalence of wAgra (84.8 ± 4.70%) in A. gracilipes from June to October. The nest manipulation and aggression experiments confirmed that temperature increases aggression (1.3 to 2.8 scores) among A. gracilipes workers due to the reduced prevalence of wAgra. To the best of our knowledge, this is the first case of a notable reduction in the prevalence of Wolbachia (100 to 66%) within a colony of A. gracilipes while maintaining stable nests for further experiments.
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OBJECTIVE: Mental disorders are a global problem with growing importance. However, the contribution of work factors to the development of mental disorders is inconclusive. This study aimed to assess the impact of fatigue and job stress on mental disorders in a prospective cohort of bus drivers. METHODS: The Taiwan Bus Driver Cohort Study (TBDCS) recruited 1652 bus drivers from a bus company in 2005. Participants self-completed a structured questionnaire in 2007, which included the Demand-Control-Support (DCS) model questions and the Swedish Occupational Fatigue Inventory-Chinese (SOFI-C). Psychiatric care visits and admissions were obtained from the National Health Insurance Research Dataset (NHIRD) from 2003 to 2016 for as a proxy for psychiatric diagnoses. Drivers with a history of psychiatric disorders before the questionnaire survey time were excluded (N=69). During the follow-up period, a new diagnosis with a psychiatric disorder was defined as an event. Cox proportional hazards model was used to estimate the hazard ratio (HR) for new one-set psychiatric disorders, adjusting for age, body mass index, marital status, education, alcohol consumption, smoking, exercise, bus driving experience, shift work, and chronic diseases. RESULTS: Among the 896 bus drivers retained for analysis, 85 were newly diagnosed with a psychiatric disorders. DCS score was not associated with the risk of developing a psychiatric disorders, but bus drivers with high SOFI-C scores (≥5) had an elevated risk for anxiety or mood disorders (HR 3.35, 95% confidence interval 1.23-9.09). CONCLUSIONS: Among bus drivers, occupational fatigue, as indicated by high a SOFI-C score, might result in an elevated risk of anxiety or mood disorders. Health service organizations should provide recommendations and guidance for drivers with high fatigue levels to avoid anxiety or mood disorders.
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Condução de Veículo , Transtornos Mentais , Humanos , Estudos de Coortes , Estudos Prospectivos , Condução de Veículo/psicologia , Transtornos Mentais/epidemiologia , Fadiga/epidemiologia , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: The purpose of this study was to assess cancer risk among agricultural workers compared to the general population. METHODS: The study utilized data from Farmers' Health Insurance (FHI) in Taiwan, which enrolled agricultural workers (N=1 175 149). The enrolled workers were matched to a general population (N=1 175 149) of the same age, gender, township, and enrollment year. The study population was linked to the National Cancer Registry to identify new cancer cases between 2000 and 2018. The Cox proportional hazards model was used to estimate the hazard ratio and 95% confidence interval for outcomes. RESULTS: During the study period, 136 913 new cancers among agricultural workers were identified. The study found that male farmers had an increased cancer risk, including lymphocytic leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma (NHL), oral cancer, lip cancer, esophagus cancer, rectum and rectosigmoid junction cancer, liver and intrahepatic bile duct cancer, lung cancer, trachea and bronchi cancer, and other non-melanoma skin cancer, even when considering the latency period. Female farmers had an elevated risk of multiple myeloma and other non-melanoma skin cancer. Moreover, only lymphoma, NHL, other lymphoid, and multiple myeloma, were both found to occur at different insurance periods. CONCLUSIONS: This study provides farmer cancer patterns and risk, adding to the evidence that farmers are at increased risk of certain types of cancer, especially for hematological cancers. As exposure varies by farm operation type, individual farmer exposure may vary widely. Further understanding of the complex relationship between occupational exposure, environmental factors, and lifestyle factors is needed.
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Doenças dos Trabalhadores Agrícolas , Linfoma não Hodgkin , Mieloma Múltiplo , Exposição Ocupacional , Neoplasias Cutâneas , Humanos , Masculino , Feminino , Fazendeiros , Estudos de Coortes , Taiwan/epidemiologia , Linfoma não Hodgkin/epidemiologia , Neoplasias Cutâneas/complicações , Exposição Ocupacional/efeitos adversos , Fatores de Risco , Doenças dos Trabalhadores Agrícolas/epidemiologia , Doenças dos Trabalhadores Agrícolas/etiologiaRESUMO
INTRODUCTION: Trabecular bone score (TBS) is a novel way for clinicians to evaluate bone quality. It is directly associated with the mechanical strength of bones and helps predict fractures. Vitamin D, a secosteroid that enhances calcium absorption, is commonly used to strengthen the skeletal system. OBJECTIVES: The present analysis aimed to determine the relationship between vitamin D levels and TBS by analyzing data from the National Health and Nutrition Examination Survey. PATIENTS AND METHODS: A total of 4464 persons (2148 men and 2316 women) were included in our study. The participants were analyzed according to sex, obesity status, and Tscore using regression models. RESULTS: We noted a remarkably positive relationship between serum levels of 25hydroxyvitamin D (25[OH]D) and TBS after the results were fully adjusted (ß = 0.319; 95% CI, 0.145-0.494; P <0.001). Tscore analysis showed that serum 25(OH)D levels were related to TBS in the group of participants with normal bone mineral density (Tscore >-1) (ß = 0.311; 95% CI, 0.097-0.525; P = 0.005). However, in the osteopenia (Tscore between -1 and -2.5) and osteoporosis (Tscore <-2.5) group there was no such association (P >0.05). CONCLUSIONS: Our study shows that low serum levels of 25(OH)D may decrease the TBS, which represents the skeletal microarchitecture and is a fracture risk factor in individuals with normal Tscores.
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Cálcio , Osso Esponjoso , Adulto , Masculino , Feminino , Humanos , Osso Esponjoso/diagnóstico por imagem , Inquéritos Nutricionais , Vitamina D , Densidade ÓsseaRESUMO
Poloxamer-188 (P188) is a nonionic triblock linear copolymer that can be used as a pharmaceutical excipient because of its amphiphilic nature. This study investigated whether P188 can act as an adjuvant to improve the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domain (RBD) subunit vaccine. BALB/c mice were vaccinated twice with the RBD antigen alone or in combination with P188 or MF59 (a commercial adjuvant for comparison purposes). The resulting humoral and cellular immunity were assessed. Results showed that P188 helped elicit higher neutralizing activity than MF59 after vaccination. P188 induced significant humoral immune response, along with type 1 T helper (Th1) and type 2 T helper (Th2) cellular immune response when compared with MF59 due to repressing p38MAPK phosphorylation. Furthermore, P188 did not result in adverse effects such as fibrosis of liver or kidney after vaccination. In conclusion, P188 is a novel adjuvant that may be used for safe and effective immune enhancement of the SARS-CoV-2 RBD antigen.
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Individuals with metabolic syndrome (MetS) are known to have an increased risk of carcinogenesis. Human epididymis protein 4 (HE4) is a tumor marker and prognostic factor for epithelial ovarian carcinoma (EOC) patients. However, no studies have evaluated the association between MetS and HE4 levels. This study aimed to evaluate the relationship between HE4 levels and MetS in the National Health and Nutrition Examination Survey (NHANES 2001−2002). This cross-sectional analysis assessed all five components of MetS and HE4 levels in 2104 females (age ≥20 years) from the NHANES dataset. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII) criteria. The analysis indicated MetS in 593 individuals, and the ß coefficient of their HE4 levels was 0.097 (95% CIs, 0.028−0.166, p = 0.006). Specifically, the ß coefficients of the HE4 levels of participants with 1, 2, 3, and ≥4 features of MetS were 0.072 (95% confidence interval (CI): −0.015−0.159), 0.125 (95% CI: 0.030−0.220), 0.161 (95% CI: 0.053−0.270), and 0.242 (95% CI: 0.117−0.368), respectively, and all p values were <0.001. The p-value for the trend was <0.001. There was a significant association between the presence of MetS and HE4 levels. There were positive relationships between HE4 levels and an increased number of MetS components (with 1, 2, 3, and ≥4 features of MetS, all p values <0.001). Among the MetS components, low high-density lipoprotein levels and high triglyceride levels were independently associated with HE4 levels.
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PURPOSE: Studies have reported a positive association between hepatitis B surface antigen (HBsAg)-positive hepatitis B virus (HBV) infection and follicular lymphoma (FL). Nevertheless, clinical information concerning chronic HBV infection in FL is sparse. METHODS: This retrospective cohort study investigated the prognostic impact of HBsAg in immunocompetent patients with FL treated with frontline rituximab-containing chemoimmunotherapy in an HBV-endemic area between 2006 and 2016. RESULTS: Among the 149 analyzed patients, 32 (21.5%) were HBsAg-positive. HBsAg positivity was positively associated with symptomatic splenomegaly, significant serous effusions, and peritreatment hepatic dysfunction. HBsAg-positive patients had a trend of lower complete remission rate (59.4% vs. 76.9%, P = 0.07), significantly poorer overall survival (hazard ratio for death, 2.68; 95% confidence interval, 1.21-5.92), and shorter progression-free survival than had HBsAg-negative patients. Multivariate analysis revealed that HBsAg is an independent adverse prognostic factor for overall survival. Intriguingly, HBsAg-positive patients had a higher incidence of progression of disease within 24 months (POD24) than had HBsAg-negative patients (cumulative incidence rate, 25.8% vs. 12.4%, P = 0.045). CONCLUSION: This study revealed that patients with FL and chronic HBV infection represent a distinct subgroup with a markedly poor prognosis. HBsAg was positively associated with POD24 and might serve as a new prognostic predictor of the survival of FL patients in endemic regions for HBV infection.
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Hepatite B , Linfoma Folicular , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Humanos , Linfoma Folicular/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Rituximab/uso terapêuticoRESUMO
We have developed a rapid, reproducible, easy to execute, surface enhanced Raman scattering (SERS) method for detection of low volumes and total amounts of biological antigens using an analyte capture system derived from methods commonly used in Western blotting. Our method is a "half-sandwich" assay with an antigen detection scheme that employs a nitrocellulose (NC) membrane with 200 nm pore size to capture subnanograms of analyte and concentrate them in a small area from applied volumes as low as one microliter. The SERS probes used for detection consist of gold-silica nanoshells modified with a two-component mixed monolayer system. One component consists of a poly(ethylene glycol) (PEG)-modified Raman-active chromophore bound to the gold surface which allows for SERS detection and imparts particle stability. The second component uses (ortho-pyridyl) disulfide-PEG-succinimidyl ester to couple the recognition antibody to the particle surface. By controlling the reaction time and concentration of thiols, a mixed monolayer is prepared on the nanoshell surface with the ability to recognize low concentrations of analyte and generate reproducible SERS signals. Using this strategy, we have achieved SERS signals that are proportional to antigen present on the membrane allowing detection of total antigen amounts as low as 1.25 ng for some cases. The performance of this new SERS bioassay has been tested with a variety of potential antigens, demonstrating the potential for multiplexed detection of analytes.
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Colódio/química , Ouro/química , Nanoconchas/química , Dióxido de Silício/química , Análise Espectral Raman/métodos , Imunoglobulina G/análise , Polietilenoglicóis/químicaRESUMO
An in vitro model was set up to investigate the effects of low frequency pulsed electromagnetic fields (PEMF) and its induced electric fields on osteoblast cells under inflammatory conditions. Osteoblasts (7F2) were seeded on top of chitosan scaffolds and co-cultured with macrophage cells (RAW 264.7) growing on the bottom of culture wells, stimulated by lipopolysaccharide to release reactive oxygen species including nitric oxide (NO). The co-culture was exposed to PEMF (magnitude of the magnetic field = 1.5 mT; induced electric voltage = 2.5 mV; frequency = 75 Hz; pulse duration = 1.3 ms) for 9 h. The osteoblasts were examined for their proliferation, viability, alkaline phosphatase (ALP) activity, and genetic expressions of type I collagen (COL I) and osteocalcin (OC), immediately and 7 days after PEMF exposure (days 0 and 7). Macrophage cell viability and NO concentration in the medium were monitored before and after PEMF exposure. The PEMF-exposed co-culture released a significantly higher amount of NO (65 µM) compared to control (17 µM) on day 7. Despite the high level of NO in the medium that was reported to be cytotoxic, PEMF-exposed osteoblasts had enhanced cell proliferation (23%), viability (36%), and COL I mRNA expression (3.4-fold) compared to the controls. The osteoblasts subjected to the PEMF had 41% less ALP activity than the control, which was associated with the active cell proliferation and COL I expression. The expression of OC mRNA was not seen in either the PEMF or control group, indicating cells had not entered the mineralization stage by day 7.
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Campos Eletromagnéticos , Inflamação/radioterapia , Macrófagos/patologia , Osteoblastos/patologia , Osteoblastos/efeitos da radiação , Fosfatase Alcalina/efeitos dos fármacos , Fosfatase Alcalina/metabolismo , Fosfatase Alcalina/efeitos da radiação , Animais , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Células Cultivadas , Técnicas de Cocultura , Colágeno Tipo I/efeitos dos fármacos , Colágeno Tipo I/metabolismo , Colágeno Tipo I/efeitos da radiação , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/administração & dosagem , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteocalcina/efeitos dos fármacos , Osteocalcina/metabolismo , Osteocalcina/efeitos da radiação , Radiação não Ionizante , Espécies Reativas de Oxigênio/administração & dosagemRESUMO
ABSTRACT: There are only a few studies that have shown an association of peripheral neuropathy with cognitive impairment in elderly individuals. Therefore, we investigated the relationship between cognitive performance and peripheral neuropathy.From the database of the National Health and Nutrition Examination Survey (NHANES, 1999-2002), each participant completed a household interview, physical performance test, questionnaire regarding personal health, and Digit Symbol Substitution Test (DSST) to evaluate cognitive performance. The severity of peripheral neuropathy was assessed based on the number of insensate areas in both feet during monofilament examination. We used the multivariate linear regression to analyze the association of the DSST findings with insensate areas of the worse foot.There were 828 participants in our study from NHANES 1999 to 2002; their mean age was 69.96â±â7.38 years, and 51.3% were male. The ß coefficients of the number of insensate areas associated with the DSST findings were all negative values, and the absolute value increased as the number of insensate areas increased. After adjustment for pertinent variables, the correlations remained significantly negative (all P for trend <.001). In addition, subgroup analysis showed no gender differences in the negative association, but this association was not significant in obese participants (Pâ>â.05).Our study provides evidence that the severity of peripheral neuropathy is significantly negatively correlated with cognitive performance.