SARS-CoV-2 nucleocapsid protein, rather than spike protein, triggers a cytokine storm originating from lung epithelial cells in patients with COVID-19.

PURPOSE: The aim of this study was to elucidate the factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that may initiate cytokine cascades and correlate the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with their serum cytokine profiles. METHODS: Recombinant baculoviruses displaying SARS-CoV-2 spike or nucleocapsid protein were constructed and transfected into A549 cells and THP-1-derived macrophages, to determine which protein initiate cytokine release. SARS-CoV-2-specific antibody titers and cytokine profiles of patients with COVID-19 were determined, and the results were associated with their clinical characteristics, such as development of pneumonia or length of hospital stay. RESULTS: The SARS-CoV-2 nucleocapsid protein, rather than the spike protein, triggers lung epithelial A549 cells to express IP-10, RANTES, IL-16, MIP-1α, basic FGF, eotaxin, IL-15, PDGF-BB, TRAIL, VEGF-A, and IL-5. Additionally, serum CTACK, basic FGF, GRO-α, IL-1α, IL-1RA, IL-2Rα, IL-9, IL-15, IL-16, IL-18, IP-10, M-CSF, MIF, MIG, RANTES, SCGF-ß, SDF-1α, TNF-α, TNF-ß, VEGF, PDGF-BB, TRAIL, ß-NGF, eotaxin, GM-CSF, IFN-α2, INF-γ, and MCP-1 levels were considerably increased in patients with COVID-19. Among them, patients with pneumonia had higher serum IP-10 and M-CSF levels than patients without. Patients requiring less than 3 weeks to show negative COVID-19 tests after contracting COVID-19 had higher serum IP-10 levels than the remaining patients. CONCLUSION: Our study revealed that nucleocapsid protein, lung epithelial cells, and IP-10 may be potential targets for the development of new strategies to prevent, or control, severe COVID-19.

Aluminum exposure induces nephrotoxicity via fibrosis and apoptosis through the TGF-ß1/Smads pathway in vivo and in vitro.

Aluminum (Al), the most common element in nature, can enter the body through various routes. Unfortunately, excessive accumulation of Al in the body can cause chronic toxicity. In this study, rats were randomly allocated to 4 groups and intraperitoneally injected with AlCl3 solution at 0, 5, 10, and 20 mg/(kg·d), respectively, for 4 weeks. The kidney function of rats and Al contents in the kidney were measured, and the pathological structural changes and apoptosis of the kidney were observed. Meanwhile, the expression of fibrosis- and apoptosis-related proteins was detected with western blot. For the in vitro assay, HK-2 cells were used to construct a model to evaluate the effects of Al exposure on cell viability, cell apoptosis, and the expression of fibrosis- and apoptosis-related proteins. Additionally, the TGF-ß1/Smads pathway was also altered in HK-2 cells, followed by the measurement of changes in apoptosis and fibrosis-related proteins. The results revealed that Al could accumulate in kidney tissues, then leading to histopathological changes and kidney function impairment, promoting renal tubular cell apoptosis and renal collagen fiber deposition, and also elevating the expression of TGF-ß1/Smads pathway-related proteins. In vitro experiments also exhibited that Al exposure increased apoptosis and the expression of fibrosis-related factors in HK-2 cells, accompanied by activation of the TGF-ß1/Smads pathway. Further modulation of the TGF-ß1/Smads pathway manifested that activation of the TGF-ß1/Smads pathway facilitated Al-induced apoptosis and fibrosis-related factor expression, while inhibition of the pathway negated this effect of Al. In conclusion, the findings of the present study illustrate that Al exposure damages kidney function and facilitate apoptosis and kidney fibrosis, which may be achieved through the activation of the TGF-ß1/Smads pathway. This study provides a new theoretical basis for the study of nephrotoxicity induced by excessive Al exposure.

Clinical Characteristics of COVID-19 Patients and Application to an Artificial Intelligence System for Disease Surveillance.

During the coronavirus disease (COVID-19) pandemic, we admitted suspected or confirmed COVID-19 patients to our isolation wards between 2 March 2020 and 4 May 2020, following a well-designed and efficient assessment protocol. We included 217 patients suspected of COVID-19, of which 27 had confirmed COVID-19. The clinical characteristics of these patients were used to train artificial intelligence (AI) models such as support vector machine (SVM), decision tree, random forest, and artificial neural network for diagnosing COVID-19. When analyzing the performance of the models, SVM showed the highest sensitivity (SVM vs. decision tree vs. random forest vs. artificial neural network: 100% vs. 42.86% vs. 28.57% vs. 71.43%), while decision tree and random forest had the highest specificity (SVM vs. decision tree vs. random forest vs. artificial neural network: 88.37% vs. 100% vs. 100% vs. 94.74%) in the diagnosis of COVID-19. With the aid of AI models, physicians may identify COVID-19 patients earlier, even with few baseline data available, and segregate infected patients earlier to avoid hospital cluster infections and to ensure the safety of medical professionals and ordinary patients in the hospital.

Molecular Mechanism of Aluminum-Induced Oxidative Damage and Apoptosis in Rat Cardiomyocytes.

Aluminum exposure can mediate either acute toxicity or chronic toxicity. Aluminum exerts toxic effects on the cardiovascular system, but there are few studies on its related mechanisms. In this study, we investigated the molecular mechanism of aluminum-induced oxidative damage and apoptosis in rat cardiomyocytes. Thirty-two male Wistar rats were randomly divided into four groups, including the control group (GC), low-dose group of aluminum exposure (GL), medium-dose group (GM), and high-dose group (GH), with eight rats in each group. The GL, GM, and GH groups were given 5, 10, and 20 mg/(kg·d) of AlCl3 solution by intraperitoneal injection, and the GC group received intraperitoneal injection of the same volume of normal saline (2 ml/rat/day), 5 times a week for 28 days. At the end of the experiment, the levels of aluminum, malondialdehyde (MDA), plasma lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzyme (CKMB), and alpha-hydroxybutyrate dehydrogenase (HBDH) were measured. The pathological changes of myocardium were observed by H&E staining. The apoptosis of cardiomyocytes was detected by TUNEL staining, and the expression of apoptosis-related proteins was determined by western blot. The results showed that the levels of CKMB and HBDH in the GM and GH groups were significantly higher than those in the GC group (P < 0.05). The content of aluminum in the myocardium and serum of the aluminum exposure groups was significantly higher than that of the GC group (P < 0.05). The level of MDA in the GM and GH groups was significantly higher than that in the GC group (P < 0.05). The pathological results showed that vacuolated and hypertrophied cardiomyocytes were found in aluminum exposure groups, especially in the GM and GH groups. The TUNEL staining showed that the apoptosis rate of the aluminum exposure groups was considerably higher than that of the GC group (P < 0.05). Western blot showed that the expression of Bcl-2, an anti-apoptotic protein, in cardiomyocytes of aluminum exposure groups was lower than that of the GC group (P < 0.05), while the levels of Bax and caspase-3 in the cardiomyocytes of the GM and GH groups were higher than those of the GC group (P < 0.05). The experimental results showed that aluminum could accumulate in myocardial tissues and cause damage to cardiomyocytes. It could induce oxidative stress damage by increasing the content of MDA in cardiomyocytes and trigger cardiomyocyte apoptosis by activating the pro-apoptotic proteins caspase-3 and Bax and reducing the anti-apoptotic protein Bcl-2.

Identification of a High-Risk Group of New-Onset Cardiovascular Disease in Occupational Drivers by Analyzing Heart Rate Variability.

PURPOSE: This cohort study evaluated the effectiveness of noninvasive heart rate variability (HRV) analysis to assess the risk of cardiovascular disease over a period of 8 years. METHODS: Personal and working characteristics were collected before biochemistry examinations and 5 min HRV tests from the Taiwan Bus Driver Cohort Study (TBDCS) in 2005. This study eventually identified 161 drivers with cardiovascular disease (CVD) and 627 without between 2005 and 2012. Estimation of the hazard ratio was analyzed by using the Cox proportional-hazards model. RESULTS: Subjects with CVD had an overall lower standard deviation of NN intervals (SDNN) than their counterparts did. The SDNN index had a strong association with CVD, even after adjusting for risk factors. Using a median split for SDNN, the hazard ratio of CVD was 1.83 (95% CI = 1.10-3.04) in Model 1 and 1.87 (95% CI = 1.11-3.13) in Model 2. Furthermore, the low-frequency (LF) index was associated with a risk of CVD in the continuous approach. For hypertensive disease, the SDNN index was associated with increased risks in both the continuous and dichotomized approaches. When the root-mean-square of the successive differences (RMSSDs), high frequency (HF), and LF were continuous variables, significant associations with hypertensive disease were observed. CONCLUSIONS: This cohort study suggests that SDNN and LF levels are useful for predicting 8 year CVD risk, especially for hypertensive disease. Further research is required to determine preventive measures for modifying HRV dysfunction, as well as to investigate whether these interventions could decrease CVD risk among professional drivers.

Association between Dietary Patterns and Frailty Prevalence in Shanghai Suburban Elders: A Cross-Sectional Study.

OBJECTIVE: To investigate the association between dietary patterns with frailty phenotypes in an elderly Chinese population. METHODS: A cross-sectional study was performed in 780 Shanghai suburban elders aged 65-74 in 2019. Dietary data were collected using a food frequency questionnaire. Adherence to a priori dietary patterns, including the Chinese Healthy Eating Index (CHEI), Dietary Approaches to Stop Hypertension (DASH) diet and Mediterranean Diet (MD) were calculated. Three a posteriori dietary patterns were identified by factor analysis, namely, "protein-rich"; "vegetables"; and "sugar, oil, and condiments". Frailty was defined using the Fried frailty phenotype scale. Ordinal multiple logistic regression was applied to examine the associations between dietary patterns and frailty prevalence. RESULTS: The prevalences of pre-frailty and frailty were 47.69% and 3.85%, respectively. Participants with a higher DASH score had a lower frailty prevalence in the sex- and age-adjusted models of the 780 subjects (OR = 0.97 (95% CI: 0.94-0.99), p < 0.05). The association slightly strengthened in the multivariate adjusted model of the 555 subjects after excluding the participants with chronic diseases may influence frailty (OR = 0.96 (95% CI: 0.92-1.00), p < 0.05). High "protein-rich" dietary pattern scores were negatively associated with frailty prevalence in the multivariate adjusted model of the 780 subjects (OR = 0.82 (95% CI: 0.69-0.98), p < 0.05). The association attenuated in the sex- and age-adjusted model of the 555 subjects (OR = 0.84 (95% CI: 0.69-1.00, p = 0.056). CONCLUSION: A better diet quality as characterized by DASH and "protein-rich" was associated with a reduced prevalence of frailty in Shanghai suburban elders. The correlation of CHEI, MD or a posteriori dietary patterns with the development of frailty in Chinese older people remains to be explored.

Occupation and subcategories of asthma: a population-based incident case-control study.

BACKGROUND: We hypothesised that occupational exposures differently affect subtypes of adult-onset asthma. OBJECTIVE: We investigated potential relations between occupation and three subtypes of adult asthma, namely atopic asthma, non-atopic asthma and asthma-COPD overlap syndrome (ACOS). METHODS: This is a population-based case-control study of incident asthma among working-age adults living in Pirkanmaa Hospital District in Southern Finland. The determinant of interest was occupation at the time of diagnosis of asthma or the job that the subject had quit due to respiratory symptoms. Asthma was divided into three mutually exclusive subtypes on the basis of any positive IgE antibody (atopic and non-atopic asthma) and presence of persistent airways obstruction in spirometry (ACOS). We applied unconditional logistic regression analysis to estimate adjusted OR (aOR), taking into account gender, age and smoking. RESULTS: The following occupational groups showed significantly increased risk of atopic asthma: chemical industry workers (aOR 15.76, 95% CI 2.64 to 94.12), bakers and food processors (aOR 4.69, 95% CI 1.18 to 18.69), waiters (aOR 4.67, 95% CI 1.40 to 15.56) and those unemployed (aOR 3.06, 95% CI 1.52 to 6.17). The following occupations showed clearly increased risk of non-atopic asthma: metal workers (aOR 8.37, 95% CI 3.77 to 18.59) and farmers and other agricultural workers (aOR 2.36, 95% CI 1.10 to 5.06). Some occupational groups showed statistically significantly increased OR of ACOS: electrical and electronic production workers (aOR 30.6, 95% CI 6.10 to 153.35), fur and leather workers (aOR 16.41, 95% CI 1.25 to 215.85) and those retired (aOR 5.55, 95% CI 1.63 to 18.97). CONCLUSIONS: Our results show that different occupations are associated with different subtypes of adult-onset asthma.

The development of a Chinese Healthy Eating Index for School-age Children and its Application in children from China Health and Nutrition Survey.

This study aimed to develop a Chinese Healthy Eating Index for School-age Children (CHEI-SC), apply it in the 2011 China Health and Nutrition Survey (CHNS) to assess dietary quality, and compared it with our former developed index named CHEI. Data of 3-day 24-hour diet recalls and household food inventory survey from 1600 school-age children in CHNS-2011 were used to develop the CHEI-SC, using the methods of standard portion size, energy-density-based approach, and least restrictive approach. The CHEI-SC included 19 components with a total score (T-score) ranging from 0 to 100. The investigated children had a median score of 49.6. Children with a higher T-score were more likely to have higher social economic status (SES), higher level of urbanisation, fewer family size, and regularly attending school. The CHEI-SC was able to assess dietary quality of Chinese school-age children, was sensitive to demographics, and more comprehensive and accurate than the CHEI.

Risk of Dementia in Patients with Leptospirosis: A Nationwide Cohort Analysis.

BACKGROUND: Studies have linked some bacterial infections with an increased likelihood for development of dementia. However, there is a paucity of data on the relationship between dementia and leptospirosis. In view of this, we conducted a retrospective cohort study to determine whether leptospirosis is a risk factor for dementia. METHODS: Data were collected from the Taiwan National Health Insurance Research Databases (2000-2010) to investigate the incidence of and risk factors for dementia in patients with leptospirosis. Patients with leptospirosis who did not have a history of dementia were enrolled in the study. For each leptospirosis patient, four controls were randomly selected after frequency matching of age, sex, and index date. Cox proportional hazard regression models were used for the analyses of dementia risk. RESULTS: A greater risk of dementia was observed in the leptospirosis cohort than in the non-leptospirosis cohort both in patients without any comorbidity (adjusted HR (aHR) = 1.23, 95% CI = 1.06-1.43) and with a comorbidity (aHR = 2.06, 95% CI = 1.7-2.5). Compared with the non-leptospirosis cohort without these comorbidities, the leptospirosis cohort with ≥2 comorbidities exhibited a significantly increased risk of dementia (aHR = 6.11, 95% CI = 3.15-11.9), followed by those with any one comorbidity (adjusted HR = 3.62, 95% CI = 1.76-7.46). CONCLUSIONS: Patients with leptospirosis were at a 1.89-fold greater risk of subsequent dementia, but potential genetic susceptibility bias in the study group is a major confound.

Fat-to-muscle ratio is a useful index for cardiometabolic risks: A population-based observational study.

Metabolic disorders are prevalent worldwide and have recently become public health problems recently. Previous studies have proposed different body composition indices for predicting future cardiovascular risks. We hypothesized an association among fat-to-muscle ratio (FMR), metabolic syndrome (MetS), hypertension (HTN), prediabetes, type 2 diabetes mellitus (DM), and cardiovascular risk in an adult population. A total of 66829 eligible subjects composed of 34182 males and 32647 females aged 20 years or older were obtained from health examinations in the Tri-Service General Hospital from 2011 to 2017. The body composition indices included fat and muscle mass measured by bioelectrical impedance analysis. A multivariable regression model was performed in a large population-based cross-sectional study. FMR was significantly associated with MetS, prediabetes, DM and HTN in all models of both genders. Based on quartile analysis, higher FMR had higher predictive ability for adverse health outcomes. The association between different definitions of MetS and the Framingham risk score was analyzed, and FMR-incorporated MetS was more useful for predicting higher Framingham risk scores than traditional definitions. FMR was a useful indicator for the presence of adverse cardiometabolic risks. Compared to traditional definition of MetS, FMR-incorporated MetS had a greater ability to predict incident cardiovascular risks. FMR seemed to be a simple and effective index for the early prevention and management of cardiometabolic events.

Scrub typhus and depression: a nationwide cohort analysis.

BACKGROUND: Studies on the relationship between depression and scrub typhus are limited. We conducted a retrospective cohort study to investigate whether scrub typhus is a risk factor for depression. METHODS: Using Taiwan's National Health Insurance Research Database, this study investigated the incidence of depression, and its risk factors, in patients diagnosed with scrub typhus between 2000 and 2010. Scrub typhus patients who did not have a history of depression before the index date were enrolled. For each patient with scrub typhus, four controls without a history of scrub typhus and depression were randomly selected and frequency matched by sex, age, year of the index date, and comorbidities. The follow-up period was from the time of initial scrub typhus diagnosis to the date of diagnosis of depression, censoring, or December 31, 2010. Cox proportional hazards regression models were used to analyze the risk of depression according to sex, age, and comorbidities. RESULTS: The study comprised a 5238-patient scrub typhus group and a 20,952-patient non-scrub typhus group with similar sex and age distributions. During the follow-up period, the cumulative incidence of depression was higher in the scrub typhus than the non-scrub typhus group (log-rank test P < 0.001). In the scrub typhus group, 45 patients developed depression, yielding an incidence rate of 1.67 per 1000 person-years, and in the non-scrub typhus group, 117 patients developed depression, yielding an incidence rate of 1.08 per 1000 person-years. This yielded a crude hazard ratio (HR) of 1.55 (95% confidence interval [CI] 1.41-1.70) and adjusted HR (aHR) of 1.56 (95% CI 1.42-1.71). Compared with the non-scrub typhus group, the risk of depression in the scrub typhus group was higher in patients of both sexes (men: aHR = 1.46, 95% CI 1.29-1.64; women: aHR = 1.68, 95% CI 1.45-1.96), in patients aged younger than 65 (≤ 49 years: aHR = 1.95, 50-64 years: aHR = 1.73), and in patients without comorbidities (aHR = 2.06, 95% CI 1.85-2.29). CONCLUSIONS: The risk of depression was 1.56-fold higher in patients with scrub typhus than in the general population.

The impact of occupational psychological hazards and metabolic syndrome on the 8-year risk of cardiovascular diseases-A longitudinal study.

There was little information concerning the combined effect of occupational psychosocial hazards such as long working hours, high job stress, and high fatigue on the risk of cardiovascular and cerebrovascular diseases (CVD). The aim of this study was to investigate the interaction among occupational psychosocial hazards and the impact of metabolic syndrome (MetS) on the risk of CVD among bus drivers. The Taiwan Bus Driver Cohort Study involving 1014 professional drivers was established in 2005 and comprehensively studied. The interactions among occupational psychosocial hazards and the impact of MetS on the risk of CVD were measured. A working pattern questionnaire, job stress questionnaires, the Swedish occupational fatigue inventory, the stress satisfaction offset score, biochemical measurements, and physical examinations were used to assess psychosocial hazards and the presence of metabolic syndrome. There were 707 eligible bus drivers with a mean age of 43.5years old. During the 8-years of follow-up, 77 drivers were diagnosed with CVD. Long working hours, high job stress, and high fatigue were associated with an increased risk of cardiovascular disease incidence in the multivariate analysis. There were synergistic effects among long working hours, high job stress, and high fatigue only in drivers with MetS. A combination of long working hours, high job stress, and high fatigue increased the risk of developing CVD in bus drivers with MetS.

Evaluation of the Validity and Reliability of the Chinese Healthy Eating Index.

The Chinese Healthy Eating Index (CHEI) is a measuring instrument of diet quality in accordance with the Dietary Guidelines for Chinese (DGC)-2016. The objective of the study was to evaluate the validity and reliability of the CHEI. Data from 12,473 adults from the China Health and Nutrition Survey (CHNS)-2011, including 3-day-24-h dietary recalls were used in this study. The CHEI was assessed by four exemplary menus developed by the DGC-2016, the general linear models, the independent t-test and the Mann-Whitney U-test, the Spearman's correlation analysis, the principal components analysis (PCA), the Cronbach's coefficient, and the Pearson correlation with nutrient intakes. A higher CHEI score was linked with lower exposure to known risk factors of Chinese diets. The CHEI scored nearly perfect for exemplary menus for adult men (99.8), adult women (99.7), and the healthy elderly (99.1), but not for young children (91.2). The CHEI was able to distinguish the difference in diet quality between smokers and non-smokers (P < 0.0001), people with higher and lower education levels (P < 0.0001), and people living in urban and rural areas (P < 0.0001). Low correlations with energy intake for the CHEI total and component scores (|r| < 0.34, P < 0.01) supported the index assessed diet quality independently of diet quantity. The PCA indicated that underlying multiple dimensions compose the CHEI, and Cronbach's coefficient α was 0.22. Components of dairy, fruits and cooking oils had the greatest impact on the total score. People with a higher CHEI score had not only a higher absolute intake of nutrients (P < 0.001), but also a more nutrient-dense diet (P < 0.001). Our findings support the validity and reliability of the CHEI when using the 3-day-24-h recalls.

Influence of ethanol concentration in the phagocytic function of neutrophils against Klebsiella pneumoniae isolates in an experimental model.

BACKGROUND/PURPOSE: Although the prevalence of pneumonia or other extrapulmonary infections is higher in people with alcoholism or acute alcohol intoxication, the possible relationship of acute alcohol intoxication to phagocytic function has not been investigated. Our aim was to determine whether acute alcohol intoxication suppresses phagocytic function in human neutrophils. METHODS: Twenty healthy individuals were enrolled for isolating neutrophils to evaluate the neutrophil phagocytic function at different alcohol concentrations. Klebsiella pneumoniae was isolated from clinical specimens of liver abscesses. The rate of K. pneumonia phagocytosis (K2 and non-K1/K2 isolates) by neutrophils was determined using flow cytometry and compared among the nine groups with different alcohol concentrations. RESULTS: The rate of phagocytic uptake decreased significantly with increasing alcohol concentration in both the K2 and non-K1/K2 K. pneumonia groups (r = -0.866, p = 0.03 vs. r = -0.975, p < 0.001). Moreover, the percentage of K. pneumoniae ingested by neutrophils decreased with age. CONCLUSION: The ability of neutrophils to phagocytose virulent K2 K. pneumoniae was suppressed by ethanol at high concentrations. This finding may account for the higher prevalence of pneumonia or other extrapulmonary infection in people with acute alcohol intoxication.

Exposure to fine particulate matter causes oxidative and methylated DNA damage in young adults: A longitudinal study.

An increased understanding is needed of the physiological effects and plausible biological mechanisms that link PM2.5 (particulate matter with an aerodynamic diameter below 2.5µm) exposure to mortality and morbidities such as atherosclerosis and respiratory disease. PM2.5 causes carcinogenic health effects. Biomonitoring in humans has suggested that 8-oxo-7, 8-dihydro-2-deoxyguanosine (8-oxodG) and N7-methylguanine (N7-MeG) are correlated with oxidative and methylated DNA damage. Thus, it is meaningful to explore the mechanisms of mutagenesis and carcinogenesis associated with oxidative and methylated DNA damage by simultaneously measuring these two markers. We recruited 72 participants from 2 areas (residential and commercial as well as residential and industrial) in the greater Taipei metropolitan area at baseline. Personal samplers were used to collect 24-hour PM2.5-integrated samples. All participants completed an interview, and blood and urine samples were collected the next morning. All collection procedures were repeated twice after a two-month follow-up period. Urinary 8-oxodG and N7-MeG were assayed as biomarkers of oxidative and methylated DNA damage, respectively. Plasma superoxide dismutase (SOD) and glutathione peroxidase-1 (GPX-1) were measured as biomarkers of antioxidants. Urinary 1-hydroxypyrene (1-OHP) was used as a biomarker of exposure to polycyclic aromatic hydrocarbons (PAHs). The mean PM2.5 level was 37.3µg/m3 at baseline. PM2.5 concentrations were higher during winter than during spring and summer. After adjusting for confounds through a generalized estimating equation (GEE) analysis, N7-MeG was significantly increased by 8.1% (ß=0.034, 95% CIs=0.001-0.068) per 10µg/m3 increment in PM2.5. 8-oxodG levels were positively correlated with N7-MeG according to both cross-sectional and longitudinal analyses, and 1-OHP was significantly associated with increasing 8-oxodG and N7-MeG concentrations. Exposure to PM2.5 increases methylated DNA damage. The mean level of urinary N7-MeG was 1000-fold higher than that of 8-oxodG.

Leptospirosis and Depression: A Nationwide Cohort Analysis.

OBJECTIVE: We conducted a retrospective cohort study to investigate whether leptospirosis is a risk factor for depression. METHOD: From the Taiwan National Health Insurance Research Database between 2000 and 2010, patients with leptospirosis (ICD-9 code 100) who did not have a history of depression (ICD-9-CM codes 296.2, 296.3, 300.4, and 311) before the index date were enrolled (leptospirosis cohort). For each patient with leptospirosis, 1 control without a history of leptospirosis and depression was randomly selected (nonleptospirosis cohort). Cox proportional hazards regression models were used to analyze the risk of depression according to sex, age, and comorbidities. RESULTS: In the leptospirosis and nonleptospirosis cohorts, we observed 34 patients with depression, with the incidence rate of 2.87 per 1,000 person-years, and 25 patients with depression, with the incidence rate of 1.93 per 1,000 person-years, respectively, yielding a crude hazard ratio (HR) of 1.49 (95% confidence interval [CI], 1.25-1.77) and an adjusted HR (aHR) of 1.58 (95% CI, 1.34-1.88). Compared with the nonleptospirosis cohort, the leptospirosis cohort had a risk of depression stratified by sex, age, and comorbidity that was higher in female patients (aHR = 2.08; 95% CI, 1.54-2.80), patients younger than 49 years old (aHR = 3.19; 95% CI, 2.39-4.27), and patients without comorbidity (aHR = 2.14; 95% CI, 1.68-2.71). The risk of depression was higher in women than in men (aHR = 1.90; 95% CI, 1.61-2.25) and in patients with comorbidities, namely hyperlipidemia (aHR = 1.80; 95% CI, 1.40-2.31), coronary artery disease (aHR = 2.47; 95% CI, 1.96-3.12), stroke (aHR = 1.77; 95% CI, 1.39-2.24), and septicemia (aHR = 2.06; 95% CI, 1.64-2.58). CONCLUSIONS: Patients with leptospirosis have a 1.58-fold higher risk of depression than that in the general population. Physicians should be alert to the emotional condition and depression symptoms of people who had been suffering from leptospirosis.

Effect of CYP3A4 genetic polymorphisms on the genotoxicity of 4,4'-methylene-bis(2-chloroaniline)-exposed workers.

OBJECTIVES: We investigated the relationship between 4,4'-methylene-bis(2-chloroaniline) (MBOCA) exposure and micronucleus (MN) frequency, and how this association was affected by genetic polymorphism of the cytochrome P450 enzyme (CYP3A4). METHODS: We divided the study population into an exposed group (n=44 with total urine MBOCA ≥20 µg/g creatinine) and a control group (n=47 with total urine MBOCA <20 µg/g creatinine). Lymphocyte MN frequency (MNF) and micronucleated cell (MNC) frequency were measured by the cytokinesis-block MN assay method. MNF reported as the number of micronuclei in binucleated cells per 1000 cells, and MNC reported as the number of binucleated cells with the presence of MN per 1000 cells. CYP3A4 alleles were measured by PCR-based restriction fragment length polymorphism (PCR-RFLP). RESULTS: The mean MNF (6.11 vs 4.46 MN/1000 cells, p<0.001) and MNC (5.75 vs 4.15 MN/1000 cells, p<0.001) in the exposed workers was significantly higher than that in the controls. The CYP3A4 polymorphism A/A+A/G influenced the difference in the mean MNF (5.97 vs 4.38 MN/1000 cells, p<0.001) and MNC (5.60 vs 4.15 MN/1000 cells, p<0.001) between the MBOCA-exposed and control groups. After adjusting risk factors, the MNF level in the MBOCA-exposed workers was 0.520 MN cells/1000 cells (p<0.001) higher than the control group among the CYP3A4 A/A+A/G genotype. Similarly, the MNC level in the MBOCA-exposed workers was 0.593 MN/1000 cells (p<0.001) higher than the control group among the CYP3A4 A/A+A/G genotype. However, the difference in adjusted MNF and MNC between the exposed and control groups was not significant for the CYP3A4 polymorphism with the G/G genotype. CONCLUSIONS: We recommend that lymphocytes MNF and MNC are good indicators to evaluate MBOCA genotoxicity. Individuals with the CYP3A4 polymorphism A/A and A/G genotypes appear to be more susceptible to MBOCA genotoxicity.

Leptospirosis and Peripheral Artery Occlusive Disease: A Nationwide Cohort Analysis.

Data on the association between peripheral artery occlusive disease (PAOD) and leptospirosis are limited. We conducted a retrospective cohort study for determining whether leptospirosis is one of the possible risk factors for PAOD. Patients diagnosed with leptospirosis by using 2000 to 2010 data from the Taiwan National Health Insurance Research Database. Patients with leptospirosis without a history of PAOD were selected. For each leptospirosis patient, 4 controls without a history of leptospirosis and PAOD were randomly selected and frequency-matched for sex, age, the year of the index date, and comorbidity diseases. The follow-up period was from the time of the initial diagnosis of leptospirosis to the diagnosis date of PAOD, or December 31, 2011. The Cox proportional hazard regression models were used for analyzing the risk of PAOD. During the follow-up period, the cumulative incidence of PAOD was higher among the patients from the leptospirosis cohort than among the nonleptospirosis cohort (log-rank test, P < 0.001). In total, 29 patients with PAOD from the leptospirosis cohort and 81 from the nonleptospirosis cohort were observed with the incidence rates of 2.1 and 1.3 per 1000 person-years, respectively, yielding a crude hazards ratio (HR) of 1.62 (95% confidence interval [CI] = 1.44-1.81) and adjusted HR (aHR) of 1.75 (95% CI = 1.58-1.95).The risk of PAOD was 1.75-fold higher in the patients with leptospirosis than in the general population.

Coping Card Usage can Further Reduce Suicide Reattempt in Suicide Attempter Case Management Within 3-Month Intervention.

This randomized controlled trial was designed to evaluate the effectiveness of using crisis coping cards (n = 32) in the case management of suicide prevention compared with case management without the use of coping cards (n = 32) over a 3-month intervention period. The generalized estimating equation was used to examine the interaction effect between treatments and time on suicide risk, depression, anxiety, and hopelessness. Results indicated that subsequent suicidal behaviors, severity of suicide risk, depression, anxiety, and hopelessness were reduced more in the coping card intervention group compared to the case management only group. Moreover, for the survival curves of time to suicide reattempt, the coping card group showed a significantly longer time to reattempt than the case management only group at 2-month and 3-month intervention periods.

An Elevated Glycemic Gap is Associated With Adverse Outcomes in Diabetic Patients With Community-Acquired Pneumonia.

Several studies argue against the association between admission hyperglycemia and adverse outcomes in infected diabetic patients. When investigating the association, it is necessary to consider preexisting hyperglycemia. The objective of this study was to assess whether stress-induced hyperglycemia, determined by the glycemic gap between admission glucose levels and A1c-derived average glucose levels adversely affects outcomes in diabetic patients admitted to hospital with community-acquired pneumonia (CAP).We retrospectively analyzed the glycemic gap and adverse outcomes of diabetic patients hospitalized because of CAP from June 1, 2007 to August 31, 2012 in single medical center in Taiwan.A total of 203 patients admitted with principal diagnosis of CAP and available data of glycemic gap.Patients with glycemic gaps ≥40 mg/dL had greater AUROC values for the development of adverse outcomes compared with acute hyperglycemia and long-term glycemic controls. Patients with an elevated glycemic gap had an odds ratio of 3.84 for the incidence of combined adverse outcomes. Incorporation of the glycemic gap into pneumonia severity index, CURB-65 or SMART-COP scores, increased the discriminative performance of predicting the development of adverse outcomes.Glycemic gaps were associated with adverse outcomes of diabetic CAP patients. The discriminative performance of the calculated glycemic gaps was comparable with those of current clinical scoring systems and may further increase the AUROC of each system.