Deleterious genetic changes in AGTPBP1 result in teratozoospermia with sperm head and flagella defects.

Approximately 10%-15% of couples worldwide are infertile, and male factors account for approximately half of these cases. Teratozoospermia is a major cause of male infertility. Although various mutations have been identified in teratozoospermia, these can vary among ethnic groups. In this study, we performed whole-exome sequencing to identify genetic changes potentially causative of teratozoospermia. Out of seven genes identified, one, ATP/GTP Binding Protein 1 (AGTPBP1), was characterized, and three missense changes were identified in two patients (Affected A: p.Glu423Asp and p.Pro631Leu; Affected B: p.Arg811His). In those two cases, severe sperm head and tail defects were observed. Moreover, AGTPBP1 localization showed a fragmented pattern compared to control participants, with specific localization in the neck and annulus regions. Using murine models, we found that AGTPBP1 is localized in the manchette structure, which is essential for sperm structure formation. Additionally, in Agtpbp1-null mice, we observed sperm head and tail defects similar to those in sperm from AGTPBP1-mutated cases, along with abnormal polyglutamylation tubulin and decreasing △-2 tubulin levels. In this study, we established a link between genetic changes in AGTPBP1 and human teratozoospermia for the first time and identified the role of AGTPBP1 in deglutamination, which is crucial for sperm formation.

Synthesis of Two-Dimensional (Cu-S)n Metal-Organic Framework Nanosheets Applied as Peroxidase Mimics for Detection of Glutathione.

Facilely synthesized peroxidase-like nanozymes with high catalytic activity and stability may serve as effective biocatalysts. The present study synthesizes peroxidase-like nanozymes with multinuclear active sites using two-dimensional (2D) metal-organic framework (MOF) nanosheets and evaluates them for their practical applications. A simple method involving a one-pot bottom-up reflux reaction is developed for the mass synthesis of (Cu-S)n MOF 2D nanosheets, significantly increasing production quantity and reducing reaction time compared to traditional autoclave methods. The (Cu-S)n MOF 2D nanosheets with the unique coordination of Cu(I) stabilized in Cu-based MOFs demonstrate impressive activity in mimicking natural peroxidase. The active sites of the peroxidase-like activity of (Cu-S)n MOF 2D nanosheets were predominantly verified as Cu(I) rather than Cu(II) of other Cu-based MOFs. The cost-effective and long-term stability of (Cu-S)n MOF 2D nanosheets make them suitable for practical applications. Furthermore, the inhibition of the peroxidase-like activity of (Cu-S)n MOF nanosheets by glutathione (GSH) could provide a simple strategy for colorimetric detection of GSH against other amino acids. This work remarkably extends the utilization of (Cu-S)n MOF 2D nanosheets in biosensing, revealing the potential for 2D (Cu-S)n MOFs.

Determination of potential sources of heavy metals in patients with urothelial carcinoma in central Taiwan: a biomonitoring case-control study.

The clarification of possible exposure sources of multiple metals to identify associations between metal doses and urothelial carcinoma (UC) risk is currently limited in the literature. We sought to identify the exposure sources of 10 metals (Vanadium, chromium, manganese, cobalt, nickel, copper, zinc, arsenic, cadmium, and lead) using principal component analysis (PCA) and then linked various principal component (PC) scores with environmental characteristics, including smoking-related indices, PM2.5, and distance to the nearest bus station. In addition, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and DNA hypomethylation markers (5-methyl-2'-deoxycytidine levels; %5-MedC) were investigated in combination with UC risks. We conducted this hospital-based case control study in 359 UC patients with histologically confirmed disease and 718 controls. All data were collected from face-to-face interviews and medical records. Approximately 6 mL blood was collected from participants for analysis of multiple heavy metal and DNA methylation in leukocyte DNA. Further, a 20 mL urine sample was collected to measure urinary cotinine and 8-OHdG levels. In addition, average values for PM2.5 for individual resident were calculated using the hybrid kriging/land-use regression model. In UC patients, significantly higher cobalt, nickel, copper, arsenic, and cadmium (µg/L) levels were observed in blood when compared with controls. Three PCs with eigenvalues > 1 accounted for 24.3, 15.8, and 10.7% of UC patients, and 26.9, 16.7, and 11.1% of controls, respectively. Environmental metal sources in major clusters were potentially associated with industrial activities and traffic emissions (PC1), smoking (PC2), and food consumption, including vitamin supplements (PC3). Multiple metal doses were linked with incremental urinary 8-OHdG and DNA hypomethylation biomarkers. For individuals with high PC1 and PC2 scores, both displayed an approximate 1.2-fold risk for UC with DNA hypomethylation.In conclusion, we provide a foundation for health education and risk communication strategies to limit metal exposure in environment, so that UC risks can be improved potentially.

Associations between daily steps and cognitive function among inpatients with schizophrenia.

BACKGROUND: Walking is the fundamental component of taking steps and is the main form of physical activity among individuals with schizophrenia; it also offers a range of health benefits. This study aimed to examine the associations between daily steps and cognitive function and further explored how many steps were related to better cognitive function among inpatients with schizophrenia. METHODS: Inpatients with schizophrenia were recruited from long-stay psychiatric wards across two hospitals (n=199 at site 1 and n=195 at site 2). Daily steps were collected with an accelerometer for 7 days. Four cognitive domains (attention, processing speed, reaction time, and motor speed) were tested at site 1, and two cognitive domains (attention and processing speed) were tested at site 2. The associations of daily steps and levels of steps/day with cognitive function were tested using multivariable linear regressions separated by site. Covariates included demographic variables, weight status, metabolic parameters, and clinical state. RESULTS: Participants took an average of 7445 (±3442) steps/day. More steps were related to better attention, processing speed, reaction time, and motor speed after multivariable adjustments. Compared with participants taking <5000 steps/day, those taking ≥5000 steps/day showed significantly better processing speed. Participants taking ≥7500 steps/day were associated with better attention, better reaction time, and better motor speed than those taking <5000 steps/day. CONCLUSION: Daily steps are associated with better cognitive function among inpatients with schizophrenia. The optimal benefit for cognitive function among this clinical population is achieving 7500 steps/day or more.

Relationships of multiple metals exposure, global DNA methylation, and urothelial carcinoma in central Taiwan.

The relationship between heavy metal exposure and human health has been investigated mostly for individual metals, failing to consider their potential interactions. In this study, we assessed the joint effects of multiple metals using generalized weighted quantile sum (WQS) regression on the risk of urothelial carcinoma (UC). Also, we performed mediation analysis to evaluate the mediator %5-MedC in DNA involved in the mechanism of urothelial carcinogenesis. We conducted a hospital-based case-control study of 355 UC patients and 710 controls, where diagnosis of UC was histologically confirmed. All data were collected from face-to-face interviews and medical records. Also, we measured six metals and 8-OHdG in urine samples along with %5-MedC in peripheral blood. Ni and Pb levels increased with UC risk in single-pollutant analysis using traditional logistic regression, and similar results were obtained in multi-pollutant analysis, where all metals analyzed were considered. In WQS analysis, the weights of Ni (27%), Pb (20%), Cr (18%), and Co (16%) predominated in the metal mixture index. WQS score and UC risk showed odds ratios of 1.65 (95%CI: 1.26, 2.15) and 1.43 (95%CI: 1.00, 2.05) for a linear and non-linear relationship, respectively. Finally, we did not observe a natural indirect effect of %5-MedC in DNA; however, a marginal effect of WQS score and natural direct effect were still found after considering a natural indirect effect. In conclusion, positive associations between WQS scores and increased risk of UC were observed. Interactions of multiple metals should be considered in assessing human health risk.

Global DNA methylation mediates the association between serum perfluorooctane sulfonate and carotid intima-media thickness in young and middle-aged Taiwanese populations.

PURPOSE: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a group of synthetic chemicals used in the manufacture of many everyday products. Previous reports have shown PFAS exposure may contribute to cardiovascular diseases (CVD). Recent studies have also identified a critical role for DNA methylation, a model of epigenetic regulation, in the pathogenesis of CVD. Additionally, PFAS has been shown to affect DNA methylation. Our previous study reported the positive association between serum perfluorooctane sulfonate (PFOS) levels and mean carotid intima-media thickness (CIMT), a biomarker of arteriosclerosis, in a cohort composed of adolescent and young adult Taiwanese. However, the contribution of DNA methylation in the mechanism of PFOS-induced arteriosclerosis has never been explored in previous literature. APPROACH AND RESULTS: In this cross-sectional study, we included 1425 young and middle-aged Taiwanese individuals (12-63 years) to investigate the correlation between serum PFOS levels, 5mdC/dG (a global DNA methylation marker) and the mean CIMT. We showed that the positive association between serum PFOS levels, 5mdC/dG, and mean CIMT. The regression coefficients of mean CIMT with a one-unit increase in ln-PFOS concentration were higher when the levels of 5mdC/dG were above the 50th percentile in the multiple regression analysis. In the structural equation model (SEM), the results showed that serum PFOS levels were directly correlated with mean CIMT and indirectly correlated with CIMT through 5mdC/dG. CONCLUSIONS: Our results showed that PFOS exposure has direct associations on arteriosclerosis and indirect direct associations on arteriosclerosis through DNA methylation. The results suggest that DNA methylation might regulate the relationship between PFOS and arteriosclerosis in the study subjects. Additional works are required to understand the causal inference between PFOS, DNA methylation, and arteriosclerosis.

Appraising Psychiatric Care From a Different Angle: Occupational Therapy Activities and Cardiorespiratory Fitness for Inpatients With Chronic Mental Illness.

IMPORTANCE: People with chronic mental illness (CMI) are at high risk of poor cardiorespiratory fitness as a result of sedentary behavior and physical inactivity. Occupational therapy practitioners play a key role as advocates for positive lifestyle change for people with CMI. OBJECTIVE: To determine the relationships between occupational therapy activities and cardiorespiratory fitness among inpatients with CMI. DESIGN: This retrospective research included three phases: descriptive cohort, case-control, and cross-sectional studies. SETTING: Psychiatric inpatient facility. PARTICIPANTS: Inpatients with CMI, ages 18 to 65 yr (N = 325). OUTCOMES AND MEASURES: Data were collected over a 12-mo period. Each daily occupational therapy activity performed by participants was converted to energy expenditure (in kcal). Cardiorespiratory fitness was measured by means of the 3-Minute Step Test. RESULTS: After daily occupational therapy activities, significantly more participants increased cardiorespiratory fitness than declined (McNemar χ2 [1] = 29.18, p < .05). Prevocational activities and moderate- to high-intensity exercises met the optimal energy expenditure level (>352 kcal) necessary to achieve an increase in cardiorespiratory fitness. CONCLUSIONS AND RELEVANCE: Occupational therapists in psychiatric inpatient settings should prescribe individualized occupation-based or physical activities that meet the optimal daily energy expenditure for each client to improve their cardiorespiratory function. What This Article Adds: This study is one of the first attempts to explore cardiorespiratory fitness outcomes after daily occupational therapy activities for people with CMI. Physical benefits unfolded throughout psychiatric care, echoing the profession's stance on holistic practice.

Association between the total plasma isomers of per- and polyfluoroalkyl substances and erythrograms in young and middle-aged Taiwanese populations.

PURPOSE: Per- and polyfluoroalkyl substances (PFAS) are human-made chemicals used in daily use products. Recent studies have shown that different perfluorooctanoic acid (PFOA) and/or perfluorooctane sulfonate (PFOS) isomers may have different biological effects. In vitro studies have also reported that PFAS exposure can alter the structure of hemoglobin (Hb). In epidemiology, however, few studies have investigated the relationship between PFAS exposure and erythrocytes. Additionally, the correlation between PFOA/PFOS isomers and full erythrograms has never been explored. APPROACH AND RESULTS: In cohorts comprising young and middle-aged Taiwanese populations, we enrolled 1483 participants (aged between 12 and 63 years) to analyze the correlations between the plasma levels of PFOA/PFOS isomers and whole-blood erythrograms. The study comprised 868 men and 615 women with a mean age of 31.2 years. When all PFOA/PFOS isomers were entered into the multiple linear regression model, the linear PFOA (L-PFOA) levels were positively correlated with the Hb, hematocrit (HCT), mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) levels while the branched PFOS (B-PFOS) levels were positively associated with the Hb, HCT, and mean corpuscular hemoglobin concentration (MCHC). The mean value of Hb was the highest (14.66 mg/dL (95% CI =14.52-14.80); P for trend <0.001) when both the L-PFOA and B-PFOS levels were above the 50th percentile. CONCLUSIONS: The results imply that PFOA/PFOS isomers may increase the weight and volume of Hb/RBC and that L-PFOA/B-PFOS may have an additive effect on the Hb levels. However, it is also possible PFAS detected at a higher concentration may due to its binding to higher levels of Hb. Further studies are needed to investigate the effects of PFOA/PFOS isomers on RBCs in humans.

P wave duration ≥150 ms predicts poor left atrial function and ablation outcomes in non-paroxysmal atrial fibrillation.

BACKGROUND: It remains unknown whether P wave duration (PWD) ≥ 150 ms measured after extensive radiofrequency catheter ablation (RFCA) can identify non-paroxysmal atrial fibrillation (non-PAF) patients at increased risk of atrial tachyarrhythmia recurrence. We investigated the predicting power of PWD and its association with left atrial (LA) reverse remodeling in patients with non-PAF undergoing pulmonary vein isolation with LA linear ablation. METHODS: We retrospectively evaluated 136 patients who underwent RFCA for drug-refractory non-PAF. Electroanatomic mapping was acquired during AF. Low-voltage area (LVA) was defined as an area with bipolar voltage ≤0.5 mV. Electrocardiography and echocardiography were performed during sinus rhythm 1 day and 3 months after RFCA. PWD was measured using amplified 12­lead electrocardiography. Prolonged PWD was defined as maximum PWD ≥ 150 ms. RESULTS: Over a mean follow-up duration of 48 ± 35 months, 28 patients experienced atrial tachyarrhythmia recurrence. PWD was positively correlated with LVA (r = 0.527, p < 0.001) and inversely correlated with LA emptying fraction (r = -0.399, p < 0.001). PWD was shortened and LA emptying fraction (LAEF) was increased in patients without atrial tachyarrhythmia recurrence during follow-up. Atrial tachyarrhythmia-free survival was significantly more likely in patients without a prolonged PWD (83.5% vs 60.7%, p = 0.002). Multivariate analysis showed that LAEF and PWD were independent predictors of atrial tachyarrhythmia recurrence. CONCLUSIONS: PWD ≥ 150 ms measured after RFCA can identify patients with non-PAF at increased risk of atrial tachyarrhythmia recurrence. PWD is correlated with LVA and LAEF and reflects LA reverse remodeling.

How Emergency Nurses Develop Resilience in the Context of Workplace Violence: A Grounded Theory Study.

PURPOSE: To understand how emergency nurses develop resilience in the context of workplace violence. DESIGN: This study employed grounded theory methodology. Thirty nurses from three hospital emergency departments in Taiwan were interviewed between August and December 2018. METHODS: Semistructured interviews were used to collect data. Interviews were audio-recorded and transcribed verbatim. FINDINGS: The process through which emergency nurses who had experienced workplace violence developed resilience took place in three stages: the release of emotions after the assault; the interpretation of conflicting thoughts and actions; and the establishment of strategies to cope with workplace violence in the future. The core theme was the motivating role of professional commitment to emergency patient care. CONCLUSIONS: The results of this study can inform the development of support systems to enhance the resilience of nurses experiencing workplace violence by alerting healthcare administrators and governing institutions to their needs. CLINICAL RELEVANCE: Emergency nurses viewed professional growth and professional commitment as an invisible motivator in the development of resilience following an encounter with workplace violence.

Sacubitril/Valsartan Therapy Ameliorates Ventricular Tachyarrhythmia Inducibility in a Rabbit Myocardial Infarction Model.

BACKGROUND: Coronary artery disease is the most common cause of heart failure (HF) in developed countries. The aim of this study was to elucidate the mechanisms of reduction of arrhythmias after sacubitril/valsartan (LCZ696) therapy in a myocardial infarction (MI)-HF rabbit model. METHODS AND RESULTS: Chronic MI in rabbits with HF were divided into 3 groups: placebo control, valsartan 30 mg/day and LCZ696 60 mg/day. After 4 weeks of therapy, an electrophysiologic study and a dual voltage-calcium optical mapping study were performed. The LCZ696 group had significantly better left ventricular ejection fraction and lower ventricular tachyarrhythmia inducibility than the valsartan and placebo groups. The most common ventricular tachyarrhythmia pattern was 1 or 2 ectopic beats originating from the peri-infarct areas, followed by re-entrant beats surrounding phase singularity points. Compared to the valsartan and placebo groups, the LCZ696 group had significantly shorter action-potential duration, shorter intracellular calcium tau constant, faster conduction velocity, and shorter pacing cycle length to induce arrhythmogenic alternans. LCZ696 therapy reduced the phosphorylated calmodulin-dependent protein kinase II (CaMKII-p) expression. CONCLUSIONS: In a rabbit model with chronic MI and HF, LCZ696 therapy ameliorated postinfarct heart function impairment and electrophysiologic remodeling and altered CaMKII-p expression, leading to reduced ventricular tachyarrhythmia inducibility.

Single Bolus Rosuvastatin Accelerates Calcium Uptake and Attenuates Conduction Inhomogeneity in Failing Rabbit Hearts With Regional Ischemia-Reperfusion Injury.

Acute statin therapy reduces myocardial ischemia/reperfusion (IR) injury-induced ventricular fibrillation (VF), but the underlying electrophysiological mechanisms remain unclear. This study sought to investigate the antiarrhythmic effects of a single bolus rosuvastatin injection in failing rabbit hearts with IR injury and to unveil the underlying molecular mechanisms. Rabbits were divided into rosuvastatin, rosuvastatin + L-NAME, control, and L-NAME groups. Intravenous bolus rosuvastatin (0.5 mg/kg) and/or L-NAME (10 mg/kg) injections were administered 1 hour and 15 minutes before surgery, respectively. Heart failure was induced using rapid ventricular pacing. Under general anesthesia with isoflurane, an IR model was created by coronary artery ligation for 30 minutes, followed by reperfusion for 15 minutes. Plasma NO end product levels were measured during IR. Then, hearts were excised and Langendorff-perfused for optical mapping studies. Cardiac tissues were sampled for Western blot analysis. Rosuvastatin increased plasma NO levels during IR, which was abrogated by L-NAME. Spontaneous VF during IR was suppressed by rosuvastatin (P < 0.001). Intracellular calcium (Cai) decay and conduction velocity were significantly slower in the IR zone. Rosuvastatin accelerated Cai decay, ameliorated conduction inhomogeneity, and reduced the inducibility of spatially discordant alternans and VF significantly. Western blots revealed significantly higher expression of enhancing endothelial NO-synthase and phosphorylated enhancing endothelial NO-synthase proteins in the Rosuvastatin group. Furthermore, SERCA2a, phosphorylated connexin43, and phosphorylated phospholamban were downregulated in the IR zone, which was attenuated or reversed by rosuvastatin. Acute rosuvastatin therapy before ischemia reduced IR-induced VF by improving SERCA2a function and ameliorating conduction disturbance in the IR zone.

The association between total serum isomers of per- and polyfluoroalkyl substances, lipid profiles, and the DNA oxidative/nitrative stress biomarkers in middle-aged Taiwanese adults.

Per- and polyfluoroalkyl substances (PFAS) have been widely used in consumer products. In vitro and animal studies have demonstrated that exposure to perfluorooctanoic acid (PFOA) and/or perfluorooctane sulfonate (PFOS) increases oxidative/nitrative stress. Recent studies have also found that isomers of PFOA/PFOS may have unique biological effects on clinical parameters. However, the correlation between PFOA/PFOS isomers and markers of oxidative/nitrative stress has never been investigated in the general population. In the current study, 597 adult subjects (ages between 22 and 63 years old) were enrolled from a control group of a case-control study entitled "Work-related risk factors and coronary heart disease". We investigated the correlation between the serum isomers of PFOA/PFOS, lipid profiles, and the urine compounds 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8-nitroguanine (8-NO2Gua) in these participants. There were 519 men and 78 women with a mean age of 45.8 years. Linear PFOA levels were positively correlated with serum low density lipoprotein cholesterol (LDL-C), small dense LDL, and triglyceride, and linear PFOS levels were positively correlated with LDL-C and HDL-C in multiple linear regression analyses. After controlling for potential confounders, the mean levels of 8-OHdG and 8-NO2Gua significantly increased across the quartiles of linear PFOS in multiple linear regression analyses. When both the 8-OHdG and 8-NO2Gua levels were above the 50th percentile, the odds ratio (OR) of higher levels of LDL-C (>75th percentile) with one unit increase in ln linear PFOS level was the highest (OR 3.15 (95% CI = 1.45-6.64), P = 0.003) in logistic regression models. In conclusion, serum linear PFOA/PFOS were correlated with lipid profiles, and linear PFOS was associated with urine oxidative/nitrative stress biomarkers. The positive correlation between linear PFOS and LDL-C was more marked when concentrations of urine oxidative/nitrative stress biomarkers were elevated. Further studies are needed to elucidate the causal relationships among PFAS isomers, lipid profiles, and oxidative/nitrative stress.

Urinary heavy metals, DNA methylation, and subclinical atherosclerosis.

PURPOSE: Lead (Pb) or cadmium (Cd) exposure has been linked to atherosclerosis. Co-exposure of these two heavy metals often occurs in humans. Recent evidence has indicated a crucial role of DNA methylation in atherosclerosis, while Pb or Cd exposure has also been shown to alter DNA methylation. However, it is still unknown whether DNA methylation plays a role in the pathological mechanism of these two heavy metals in atherosclerosis. APPROACH AND RESULTS: We enrolled 738 participants (12-30 years) to investigate the association among concentrations of urine Pb or Cd, the 5mdC/dG value (a global DNA methylation marker) and the carotid intima-media thickness (CIMT). When each heavy metal was modeled separately, the results showed urine Pb and Cd concentrations were positively associated with the 5mdC/dG value and CIMT, respectively. When the two heavy metals were analyzed in the same model, urinary Pb concentrations were positively associated with the 5mdC/dG value and CIMT, while urinary Cd concentrations were only positively associated with the CIMT. When Pb and Cd are simultaneously considered in the same logistic regression model, the odds ratios (OR) of thicker CIMT (greater than 75th percentile) with one unit increase in ln-Pb level was 1.67 (95% C.I. = 1.17-2.46, P = 0.005) when levels of 5mdC/dG were above 50th percentile, which is higher than 5mdC/dG bellow the 50th percentile (OR = 1.50 (95% C.I. = 0.96-2.35), P = 0.076). In structural equation model (SEM), Pb or Cd levels are directly associated with CIMT. Moreover, Pb or Cd had an indirect association with CIMT through the 5mdC/dG. When we considered Pb and Cd together, Pb levels had a direct association with CIMT and an indirect association with CIMT through the 5mdC/dG value, while Cd only had a direct association with CIMT. CONCLUSIONS: Our findings imply that Pb and Cd exposure might be associated with subclinical atherosclerosis, and global DNA methylation might mediate Pb-associated subclinical atherosclerosis in this young population. Future effort is necessary to elucidate the causal relationship.

Workplace Violence Against Emergency Nurses in Taiwan: A Cross-Sectional Study.

INTRODUCTION: Workplace violence against emergency nurses is common worldwide. This study aimed to gain a more thorough overview of the point prevalence of workplace violence against emergency nurses and the preventive measures used in emergency departments in Taiwan. METHODS: In this multicenter, descriptive, cross-sectional study, the questionnaire, Violence Against Nurses Working in Emergency Departments, was used to collect data from 407 nurses working at 5 emergency departments in Taiwan from May to October 2015. RESULTS: The results revealed that 378 emergency nurses (92.9%) experienced workplace violence over the last 2 years. The average visual analog scale score (1-10) of security effectiveness in preventing workplace violence was 5.0 (SD = 1.97). The average visual analog scale score of perceived safety level in terms of workplace violence was 4.38 (SD = 2.06). The average visual analog scale score of meeting nurses' needs was 5.72 (SD = 2.23). DISCUSSION: This questionnaire survey revealed that the current preventive measures for workplace violence against emergency nurses in Taiwan were not effective. The relevant measures should be improved, thereby reducing the prevalence and severity of workplace violence against emergency nurses.

Assessing vocational outcome expectancy in individuals with serious mental illness: a factor-analytic approach.

Background: Self-determination theory (SDT) and self-efficacy theory (SET) can be used to conceptualize self-determined motivation to engage in mental health and vocational rehabilitation (VR) services and to predict recovery. To incorporate SDT and SET as a framework for vocational recovery, developing and validating SDT/SET measures in vocational rehabilitation is warranted. Outcome expectancy is an important SDT/SET variable affecting rehabilitation engagement and recovery.Aims: The purpose of this study was to validate the Vocational Outcome Expectancy Scale (VOES) for use within the SDT/SET vocational recovery framework.Methods: One hundred and twenty-four individuals with serious mental illness (SMI) participated in this study. Measurement structure of the VOES was evaluated using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA).Results: Both EFA and CFA results supported a two-factor structure: (a) positive outcome expectancy, and (b) negative outcome expectancy. The internal consistency reliability coefficients for both factors were acceptable. In addition, positive outcome expectancy correlated stronger than negative outcome expectancy with other SDT/SET constructs in the expected directions.Conclusions: The VOES is a brief, reliable and valid instrument for assessing vocational outcome expectancy in individuals with SMI that can be integrated into SDT/SET as a vocational rehabilitation engagement and recovery model in psychiatric rehabilitation.

Longitudinal follow-up of health effects among workers handling engineered nanomaterials: a panel study.

BACKGROUND: Although no human illness to date is confirmed to be attributed to engineered nanoparticles, occupational epidemiological studies are needed to verify the health effects of nanoparticles. This study used a repeated measures design to explore the potential adverse health effects of workers handling nanomaterials. METHODS: Study population was 206 nanomaterial-handling workers and 108 unexposed controls, who were recruited from 14 nanotechnology plants. They were followed up no less than two times in four years. A questionnaire was used to collect potential confounders and detailed work conditions. Control banding was adopted to categorize risk level for each participant as a surrogate marker of exposure. Health hazard markers include cardiopulmonary dysfunction markers, inflammation and oxidative damage markers, antioxidant enzymes activity, and genotoxicity markers. The Generalized Estimating Equation model was applied to analyze repeated measurements. RESULTS: In comparison to the controls, a significant dose-dependent increase on risk levels for the change of superoxide dismutase (p<0.01) and a significant increase of glutathione peroxidase change in risk level 1 was found for nanomaterial-handling workers. However, the change of cardiovascular dysfunction, lung damages, inflammation, oxidative damages, neurobehavioral and genotoxic markers were not found to be significantly associated with nanomaterials handling in this panel study. CONCLUSIONS: This repeated measurement study suggests that there was no evidence of potential adverse health effects under the existing workplace exposure levels among nanomaterials handling workers, except for the increase of antioxidant enzymes.

Engineering microbes for targeted strikes against human pathogens.

Lack of pathogen specificity in antimicrobial therapy causes non-discriminant microbial cell killing that disrupts the microflora present. As a result, potentially helpful microbial cells are killed along with the pathogen, altering the biodiversity and dynamic interactions within the population. Moreover, the unwarranted exposure of antibiotics to microbes increases the likelihood of developing resistance and perpetuates the emergence of multidrug resistance. Synthetic biology offers an alternative solution where specificity can be conferred to reduce the non-specific, non-targeted activity of currently available antibiotics, and instead provides targeted therapy against specific pathogens and minimising collateral damage to the host's inherent microbiota. With a greater understanding of the microbiome and the available genetic engineering tools for microbial cells, it is possible to devise antimicrobial strategies for novel antimicrobial therapy that are able to precisely and selectively remove infectious pathogens. Herein, we review the strategies developed by unlocking some of the natural mechanisms used by the microbes and how these may be utilised in targeted antimicrobial therapy, with the promise of reducing the current global bane of multidrug antimicrobial resistance.

Measurement of urinary arsenic profiles and DNA hypomethylation in a case-control study of urothelial carcinoma.

Environmental exposure to arsenic may be involved in the disturbance of DNA hypomethylation. The aim of this study is the first to explore the effect of interactions of urinary total arsenic levels, arsenic methylation capacity, 8-hydroxy-2'-deoxyguanosine (8-OHdG), plasma folate, and global 5-methyl-2'-deoxycytidine (5-MedC) levels on the risk of urothelial carcinoma (UC). A hospital-based case-control study was constructed. The research involved the histological recruitment and pathological verification of 178 UC patients and 356 age-/sex-matched controls without prior history of cancer. Arsenic species were determined by high-performance liquid chromatography (HPLC)-hydride generation and atomic absorption. 5-MedC levels were detected by HPLC and triple-quadrupole mass spectrometry (MS). 8-OHdG was processed by an online solid-phase extraction LC-MS/MS. Plasma folate levels were measured using the chemiluminescent technology. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by multiple logistic regression analysis. Results indicate that the high levels of total urinary arsenic, inorganic arsenic percentage, and 8-OHdG and the low levels of DMA % and plasma folate were independent factors of UC. In addition, global 5-MedC levels in the first quartile versus fifth quartile significantly increased the twofold OR of UC after potential factors were adjusted (95% CI:1.10-4.03). The interaction of 5-MedC level and high total arsenic level, insufficient arsenic capacity, high 8-OHdG, and low folate levels was insignificant. Results of stepwise logistic regression analysis indicate that high total urinary arsenic levels (Q3 versus Q1), low plasma folate level, and low global 5-MedC (Q4 versus Q5) significantly increased the ORs of UC. The above results suggest that high total arsenic, low plasma folate, and 5-MedC levels affect the ORs of UC independently.

Paradoxical Effects of Sodium-Calcium Exchanger Inhibition on Torsade de Pointes and Early Afterdepolarization in a Heart Failure Rabbit Model.

Calcium homeostasis plays an important role in development of early afterdepolarizations (EADs) and torsade de pointes (TdP). The role of sodium-calcium exchanger (NCX) inhibition in genesis of secondary Ca rise and EAD-TdP is still debated. Dual voltage and intracellular Ca optical mapping were conducted in 6 control and 9 failing rabbit hearts. After baseline electrophysiological and optical mapping studies, E4031 was given to simulate long QT syndrome. ORM-10103 was then administrated to examine the electrophysiological effects on EAD-TdP development. E4031 enhanced secondary Ca rise, EADs development, and TdP inducibility in both control and failing hearts. The results showed that ORM-10103 reduced premature ventricular beats but was unable to suppress the inducibility of TdP or EADs. The electrophysiological effects of ORM-10103 included prolongation of action potential duration (APD) and increased APD heterogeneity in failing hearts. ORM-10103 had a neutral effect on the amplitude of secondary Cai rise in control and heart failure groups. In this model, most EADs generated from long-short APD junction area. In conclusion, highly selective NCX inhibition with ORM-10103 reduced premature ventricular beat burden but was unable to suppress secondary Ca rise, EADs development, or inducibility of TdP. The possible electrophysiological mechanisms include APD prolongation and increased APD heterogeneity.