Impact of healthy lifestyle on the incidence and progression trajectory of mental disorders: A prospective study in the UK Biobank.

BACKGROUND: Healthier lifestyle decreased the risk of mental disorders (MDs) such as depression and anxiety. However, research on the effects of a comprehensive healthy lifestyle on their progression is lacking. METHODS: 385,704 individuals without baseline MDs from the UK Biobank cohort were included. A composite healthy lifestyle score was computed by assessing alcohol intake, smoking status, television viewing time, physical activity, sleep duration, fruit and vegetable intake, oily fish intake, red meat intake, and processed meat intake. Follow-up utilized hospital and death register records. Multistate model was used to examine the role of healthy lifestyle on the progression of specific MDs, while a piecewise Cox regression model was utilized to assess the influence of healthy lifestyle across various phases of disease progression. RESULTS: Higher lifestyle score reduced risks of transitions from baseline to anxiety and depression, as well as from anxiety and depression to comorbidity, with corresponding hazard ratios (HR) and 95 % confidence intervals (CI) of 0.94 (0.93, 0.95), 0.90 (0.89, 0.91), 0.94 (0.91, 0.98), and 0.95 (0.92, 0.98), respectively. Healthier lifestyle decreased the risk of transitioning from anxiety to comorbidity within 2 years post-diagnosis, with HR 0.93 (0.88, 0.98). Higher lifestyle scores at 2-4 years and 4-6 years post-depression onset were associated with reduced risk of comorbidity, with HR 0.93 (0.87, 0.99) and 0.92 (0.86, 0.99), respectively. LIMITATION: The generalizability to other ethnic groups is limited. CONCLUSION: This study observed a protective role of holistic healthy lifestyle in the trajectory of MDs and contributed to identifying critical progression windows.

Associations of blood biomarkers with arterial stiffness in patients with diabetes mellitus: A population-based study.

BACKGROUND: Arterial stiffness contributes to additional cardiovascular risks in diabetic patients by triggering the loss of vascular and myocardial compliance and promoting endothelial dysfunction. Thus, prevention of arterial stiffness is a public health priority, and the identification of potential biomarkers may provide benefits for early prevention. This study investigates the relationships between serum laboratory tests and pulse wave velocity (PWV) tests. We also investigated the associations between PWV and all-cause mortality. METHODS: We examined a panel of 33 blood biomarkers among diabetic populations in the Atherosclerosis Risk in Communities Study. The carotid-femoral (cfPWV) and femoral-ankle PWV (faPWV) were measured using an automated cardiovascular screening device. The aortic-femoral arterial stiffness gradient (afSG) was calculated as faPWV divided by cfPWV. Biomarker levels were log-transformed and correlated with PWV. Cox proportional hazard models were employed for survival analysis. RESULTS: Among 1079 diabetic patients, biomarkers including high-density lipoprotein cholesterol, glycated hemoglobin, high-sensitivity troponin T, cystatin C, creatinine, and albuminuria were significantly correlated with afSG (R = 0.078, -0.193, -0.155, -0.153, -0.116, and -0.137, respectively) and cfPWV (R = -0.068, 0.175, 0.128, 0.066, 0.202, and 0.062, respectively). Compared with the lowest tertile of afSG, the risk of all-cause mortality was lower in the highest tertile (hazard ratio 0.543; 95% confidence interval 0.328-0.900). CONCLUSION: Certain biomarkers related to blood glucose monitoring, myocardial injury, and renal function significantly correlated with PWV, suggesting that these putative risk factors are likely to be important atherosclerosis mechanisms in diabetic patients. AfSG may be an independent predictor of mortality among diabetic populations.

Epidural Steroid Injections and the Risk of Osteoporosis in Lumbar Spondylosis Patients: A Nationwide Population-Based Cohort Study.

BACKGROUND: Epidural steroid injections (ESIs) involve the administration of steroids and local anesthetics into the spinal epidural space, and they are performed by inserting a needle between the ligamentum flavum and dura. This procedure is suitable for patients with lumbosacral radiculopathy secondary to disc herniation or postsurgical radicular pain. The relief period of the analgesic medications may be prolonged by > 6 weeks, resulting in nonsurgical management becoming a suitable option. However, the negative effect of ESIs on bone mineral density has been reported. OBJECTIVES: We aimed to clarify the association between ESIs and osteoporosis risk by analyzing a nationwide population database. STUDY DESIGN: This study is a nationwide retrospective cohort study. SETTING: Data on 1 million cases randomly selected from the 2000 Registry for Beneficiaries of the National Health Insurance Research Database (NHIRD) were collected. METHODS: In total, 4,957 patients who were diagnosed with lumbar spondylosis and received ESIs between 2000 and 2013 were identified from the NHIRD. Subsequently, another 4,957 patients with lumbar spondylosis were randomly selected from the same database and frequency matched by age, gender, and index year with the patients who received ESIs. RESULTS: The mean age of the patients were 50.3 ± 17.1 years. The incident rates of osteoporosis in the ESI and non-ESI groups were 7.95 and 7.01 per 1,000 person-years, respectively. Osteoporosis risk was significantly higher in the ESI cohort than in the non-ESI cohort (absolute standardized hazard ratio = 1.23, 95% confidence interval = 1.05-1.45, P = 0.01). The risk factors for osteoporosis were old age, being female, and undergoing ESIs. Osteoporosis risk was significantly higher in the ESI cohort than in the non-ESI cohort in the male, lowest-urbanization-level (fourth level), other-occupations, and comorbidity-free subgroups. LIMITATIONS: The NHIRD did not provide information on osteoporosis-related scales, renal function, blood pressure, smoking habit, pulmonary function, daily activities, and dosage of injected steroids. CONCLUSIONS: For patients diagnosed with lumbar spondylosis, ESIs are associated with a high osteoporosis risk. Thus, this therapy should be recommended with caution, especially for patients with correlated risk factors (e.g., high risk of osteoporotic fracture, low socioeconomic status, and retired or unemployed status).

The independent and joint association of accelerometer-measured physical activity and sedentary time with dementia: a cohort study in the UK Biobank.

BACKGROUND: Research on the association of physical activity and sedentary time with dementia is accumulating, though elusive, and the interaction effects of the two remain unclear. We analysed the joint associations of accelerometer-measured physical activity and sedentary time with risk of incident dementia (all-cause dementia, Alzheimer's disease and vascular dementia). METHODS: A total of 90,320 individuals from the UK Biobank were included. Accelerometer-measured total volume of physical activity (TPA) and sedentary time were measured at baseline and dichotomised by median (low TPA [< 27 milli-gravity (milli-g)], high TPA [≥ 27 milli-g]; low sedentary time [< 10.7 h/day], high sedentary time [≥ 10.7 h/day]). Cox proportional hazards models were used to evaluate the joint associations with incident dementia on both additive and multiplicative scales. RESULTS: During a median follow-up of 6.9 years, 501 cases of all-cause dementia were identified. Higher TPA was associated with a lower risk of all-cause dementia, Alzheimer's disease and vascular dementia; the multivariate adjusted hazard ratios (HRs) (95% CI) per 10 milli-g increase were 0.63 (0.55-0.71), 0.74 (0.60-0.90) and 0.69 (0.51-0.93), respectively. Sedentary time was only found to be linked to all-cause dementia, and the HR for high sedentary time was 1.03 (1.01-1.06) compared with that for low sedentary time. No additive and multiplicative relationship of TPA and sedentary time to incident dementia was found (all P values > 0.05). CONCLUSION: Higher TPA level was related to a lower risk of incident dementia irrespective of sedentary time, which highlighted the implication of promoting physical activity participation to counteract the potential detrimental effect of sedentary time on dementia.

The Risk of Venous Thromboembolism after Thoracolumbar Spine Surgery: A Population-Based Cohort Study.

Background: Although venous thromboembolism (VTE) is rare, including deep vein thrombosis (DVT) and pulmonary embolism (PE), it is a catastrophic complication after spinal surgery. This study was aimed to investigate the risk factors and incidence of VTE after thoracolumbar spine surgery (TLSS). Methods: We retrieved the data of 8697 patients >20 years old who underwent TLSS between 2000 and 2013 from Taiwan's Longitudinal Health Insurance Database 2000. Each patient was randomly frequency-matched with four individuals who did not undergo TLSS by age, sex, and index year (the control group). Results: The incidence rates of VTE in the TLSS and control groups were 1.84 and 0.69 per 1000 person-years, respectively. The TLSS group had a higher VTE risk (adjusted HR (aHR): 2.13, 95% confidence interval [95%CI]: 1.41−3.21), DVT (aHR: 2.20, 95%CI: 1.40−3.46), and PE (aHR: 1.60, 95%CI: 0.68−3.78) than the control group. The correlated risk factors of VTE included older age (50−64 years: aHR: 2.16, 95%CI: 1.14−4.09; ≥65 years: aHR: 3.18, 95%CI: 1.65−6.13), a history of cancer (aHR: 2.96, 95%CI: 1.58−5.54), heart failure (aHR: 2.19, 95%CI: 1.27−3.78), and chronic kidney disease (aHR: 1.83, 95%CI: 1.18−2.83). Conclusions: The overall VTE risk following TLSS was less than 2% but correlated with certain risk factors. This information could help the spine surgeon help the patient prevent this fatal complication.

The incidence of mental disorder increases after hip fracture in older people: a nationwide cohort study.

BACKGROUND: People living with dementia seem to be more likely to experience delirium following hip fracture. The association between mental disorders (MD) and hip fracture remains controversial. We conducted a nationwide study to examine the prevalence of MD in geriatric patients with hip fractures undergoing surgery and conducted a related risk factor analysis. MATERIAL AND METHODS: This retrospective cohort study used data from Taiwan's National Health Insurance Research Database between 2000 and 2012 and focused on people who were older than 60 years. Patients with hip fracture undergoing surgical intervention and without hip fracture were matched at a ratio of 1:1 for age, sex, comorbidities, and index year. The incidence and hazard ratios of age, sex, and multiple comorbidities related to MD and its subgroups were calculated using Cox proportional hazards regression models. RESULTS: A total of 1408 patients in the hip fracture group and a total of 1408 patients in the control group (no fracture) were included. The overall incidence of MD for the hip fracture and control groups per 100 person-years were 0.8 and 0.5, respectively. Among MD, the incidences of transient MD, depression, and dementia were significantly higher in the hip fracture group than in the control group. CONCLUSIONS: The prevalence of newly developed MD, especially transient MD, depression, and dementia, was higher in the geriatric patients with hip fracture undergoing surgery than that in the control group. Prompt and aggressive prevention protocols and persistent follow-up of MD development is highly necessary in this aged society.

Hyperpolyploidization of hepatocyte initiates preneoplastic lesion formation in the liver.

Hepatocellular carcinoma (HCC) is the most predominant primary malignancy in the liver. Genotoxic and genetic models have revealed that HCC cells are derived from hepatocytes, but where the critical region for tumor foci emergence is and how this transformation occurs are still unclear. Here, hyperpolyploidization of hepatocytes around the centrilobular (CL) region is demonstrated to be closely linked with the development of HCC cells after diethylnitrosamine treatment. We identify the CL region as a dominant lobule for accumulation of hyperpolyploid hepatocytes and preneoplastic tumor foci formation. We also demonstrate that upregulation of Aurkb plays a critical role in promoting hyperpolyploidization. Increase of AURKB phosphorylation is detected on the midbody during cytokinesis, causing abscission failure and hyperpolyploidization. Pharmacological inhibition of AURKB dramatically reduces nucleus size and tumor foci number surrounding the CL region in diethylnitrosamine-treated liver. Our work reveals an intimate molecular link between pathological hyperpolyploidy of CL hepatocytes and transformation into HCC cells.

Risk factors for carpal tunnel syndrome or trigger finger following distal radius fracture: a nationwide study.

New-onset carpal tunnel syndrome (CTS) and trigger finger after distal radius fractures (DRFs) with or without open reduction and internal fixation (ORIF) have been reported inconsistently across different studies. This study assessed the incidence of CTS and trigger finger after DRFs using Taiwan National Health Insurance Research Database. In total, 1454 patients in the case (ORIF) cohort and 1454 patients in the control (non-ORIF) cohort were included in this retrospective study. The mean age was approximately 55 years old, and the female to male ratio was approximately 3/2. Nine patients underwent carpal tunnel release (CTR) surgery after diagnosis of CTS in the case group, and no patients did in the control group; whereas 19 cases of CTS were diagnosed without CTR in the case group, and 4 such cases were observed in the control group. Five cases of trigger finger were diagnosed in the case group, and 3 cases were diagnosed in the control group. CTS were significantly associated with ORIF for DRFs within 9 months after the fracture, whereas trigger finger was not significantly different between groups. Diabetes mellitus was a significant risk factor for CTS and trigger finger within 9 months after the incidence of DRFs.

Insufficient Acidification of Autophagosomes Facilitates Group A Streptococcus Survival and Growth in Endothelial Cells.

UNLABELLED: Group A streptococcus (GAS) is an important human pathogen, and its invasion via blood vessels is critically important in serious events such as bacteremia or multiorgan failure. Although GAS was identified as an extracellular bacterium, the internalization of GAS into nonphagocytic cells may provide a strategy to escape from immune surveillance and antibiotic killing. However, GAS has also been reported to induce autophagy and is efficiently killed within lysosome-fused autophagosomes in epithelial cells. In this study, we show that GAS can replicate in endothelial cells and that streptolysin O is required for GAS growth. Bacterial replication can be suppressed by altering GAS gene expression in an acidic medium before internalization into endothelial cells. The inhibitory effect on GAS replication can be reversed by treatment with bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPase. Compared with epithelial cells in which acidification causes autophagy-mediated clearance of GAS, there was a defect in acidification of GAS-containing vesicles in endothelial cells. Consequently, endothelial cells fail to maintain low pH in GAS-containing autophagosomes, thereby permitting GAS replication inside LAMP-1- and LC3-positive vesicles. Furthermore, treatment of epithelial cells with bafilomycin A1 resulted in defective GAS clearance by autophagy, with subsequent bacterial growth intracellularly. Therefore, low pH is a key factor for autophagy-mediated suppression of GAS growth inside epithelial cells, while defective acidification of GAS-containing vesicles results in bacterial growth in endothelial cells. IMPORTANCE: Previous reports showed that GAS can induce autophagy and is efficiently killed within lysosome-fused autophagosomes in epithelial cells. In endothelial cells, in contrast, induction of autophagy is not sufficient for GAS killing. In this study, we provide the first evidence that low pH is required to prevent intracellular growth of GAS in epithelial cells and that this mechanism is defective in endothelial cells. Treatment of GAS with low pH altered GAS growth rate and gene expression of virulence factors and resulted in enhanced susceptibility of GAS to intracellular lysosomal killing. Our findings reveal the existence of different mechanisms of host defense against GAS invasion between epithelial and endothelial cells.

[Relationship between apolipoprotein e4 allele and emergence agitation in patients undergoing general anesthesia].

OBJECTIVE: To investigate the relationship between apolipoprotein e4 allele and emergence agitation (EA) in patients undergoing general anesthesia. METHODS: A nested cohort study was conducted in elderly patients (over 60 years old) scheduled for major abdominal surgery requiring general anesthesia. A structured interview was conducted in PACU to determine EA, defined using the Sedation-Agitation Scale (SAS). Blood samples were obtained for measurement of the apolipoprotein genotypes. RESULTS: Of the 196 patients studied, 22.4% developed EA. Thirty-eight patients (19.4%) had the apolipoprotein e4 allele. The presence of the e4 allele and low level of education were both associated with an increased risk of EA (36.9% vs15.8%, P=0.005; 30% vs 14.3%, P=0.01). After adjustment for covariates, the patients with the copy of e4 allele were shown to have a greater likeliness of an increased risk of EA (odds ratio: 4.32; 95% CI: 1.75-10.05) than those without the e4 allele. CONCLUSION: Apolipoprotein e4 carrier status is associated with an increased risk for EA.

Nitrosylated iron-thiolate-sulfinate complexes with {Fe(NO)}6/7 electronic cores: relevance to the transformation between the active and inactive NO-bound forms of iron-containing nitrile hydratases.

The five-coordinated iron-thiolate nitrosyl complexes [(NO)Fe(S,S-C6H3R)2]- (R = H (1), m-CH3 (2)), [(NO)Fe(S,S-C6H2-3,6-Cl2)2]- (3), [(NO)Fe(S,S-C6H3R)2]2- (R = H (10), m-CH3 (11)), and [(NO)Fe(S,S-C6H2-3,6-Cl2)2]2- (12) have been isolated and structurally characterized. Sulfur oxygenation of iron-thiolate nitrosyl complexes 1-3 containing the {Fe(NO)}6 core was triggered by O2 to yield the S-bonded monosulfinate iron species [(NO)Fe(S,SO2-C6H3R)(S,S-C6H3R)]- (R = H (4), m-CH3 (5)) and [(NO)Fe(S,SO2-C6H2-3,6-Cl2)(S,S-C6H2-3,6-Cl2)]2(2-) (6), respectively. In contrast, attack of O2 on the {Fe(NO)}7 complex 10 led to the formation of complex 1 accompanied by the minor products, [Fe(S,S-C6H4)2]2(2-) and [NO3]- (yield 9%). Reduction of complexes 4-6 by [EtS]- in CH3CN-THF yielded [(NO)Fe(S,SO2-C6H3R)(S,S-C6H3R)]2- (R = H (7), m-CH3 (8)) and [(NO)Fe(S,SO2-C6H2-3,6-Cl2)(S,S-C6H2-3,6-Cl2)]2- (9) along with (EtS)2 identified by 1H NMR. Compared to complex 10, complexes 7-9 with the less electron-donating sulfinate ligand coordinated to the {Fe(NO)}7 core were oxidized by O2 to yield complexes 4-6. Obviously, the electronic perturbation of the {Fe(NO)}7 core caused by the coordinated sulfinate in complexes 7-9 may serve to regulate the reactivity of complexes 7-9 toward O2. The iron-sulfinate nitrosyl species with the {Fe(NO)}6/7 core exhibit the photolabilization of sulfur-bound [O] moiety. Complexes 1-4-7-10 (or 2-5-8-11 and 3-6-9-12) are interconvertible under sulfur oxygenation, redox processes, and photolysis, respectively.

Homodinuclear iron thiolate nitrosyl compounds [(ON)Fe(S,S-C6H4)2 Fe(NO)2]- and [(ON)Fe(SO2,S-C6H4)(S,S-C6H4)Fe(NO)2]- with {Fe(NO)}7-{Fe(NO)2}9 electronic coupling: new members of a class of dinitrosyl iron complexes.

Reaction of Fe(CO)2(NO)2 and [(ON)Fe(S,S-C6H3R)2]- (R = H (1), CH3 (1-Me))/[(ON)Fe(SO2,S-C6H4)(S,S-C6H4)]- (4) in THF afforded the diiron thiolate/sulfinate nitrosyl complexes [(ON)Fe(S,S-C6H3R)2 Fe(NO)2]- (R = H (2), CH3 (2-Me)) and [(ON)Fe(S,SO2-C6H4)(S,S-C6H4)Fe(NO)2]- (3), respectively. The average N-O bond lengths ([Fe(NO)2] unit) of 1.167(3) and 1.162(4) A in complexes 2 and 3 are consistent with the average N-O bond length of 1.165 A observed in the other structurally characterized dinitrosyl iron complexes with an {Fe(NO)2}9 core. The lower nu(15NO) value (1682 cm(-1) (KBr)) of the [(15NO)FeS4] fragment of [(15NO)Fe(S,S-C6H3CH3)2 Fe(NO)2]- (2-Me-15N), compared to that of [(15NO)Fe(S,S-C6H3CH3)2]- (1-Me-15N) (1727 cm(-1) (KBr)), implicates the electron transfer from {Fe(NO)2}10 Fe(CO)2(NO)2 to complex 1-Me/1 may occur in the process of formation of complex 2-Me/2. Then, the electronic structures of the [(NO)FeS4] and [S2Fe(NO)2] cores of complexes 2, 2-Me, and 3 were best assigned according to the Feltham-Enemark notation as the {Fe(NO)}7-{Fe(NO)2}9 coupling (antiferromagnetic interaction with a J value of -182 cm(-1) for complex 2) to account for the absence of paramagnetism (SQUID) and the EPR signal. On the basis of Fe-N(O) and N-O bond distances, the dinitrosyliron {L2Fe(NO)2} derivatives having an Fe-N(O) distance of approximately 1.670 A and a N-O distance of approximately 1.165 A are best assigned as {Fe(NO)2}9 electronic structures, whereas the Fe-N(O) distance of approximately 1.650 A and N-O distance of approximately 1.190 A probably imply an {Fe(NO)2}10 electronic structure.