The Relationship Between Night Shift Work and the Risk of Abnormal Thyroid-Stimulating Hormone: A Hospital-Based Nine-Year Follow-up Retrospective Cohort Study in Taiwan.

BACKGROUND: Health-care providers typically undergo shift work and are subjected to increased stress. Night shift work may induce disturbed sleep cycles and circadian rhythm. The objective of this study was to explore if night shift workers (NSWs) show an increased risk of abnormal thyroid-stimulating hormone (TSH). METHODS: We conducted a retrospective cohort study of 574 employees without thyroid disease and abnormal TSH at baseline who underwent annual check-ups between 2007 and 2016 in a medical center. NSWs were defined as those with working time schedules other than daytime hours. We calculated the incidence rate and estimated the adjusted hazard ratio (HR) for incident abnormal TSH and subclinical hypothyroidism compared with non-NSWs using a Cox regression model. RESULTS: A total of 56 incident abnormal TSH cases and 39 subclinical hypothyroidism cases in NSWs were identified during 3000 person-years of follow-up. In models adjusted for age, sex, obesity, and working departments, we found no increased relative risk for incident abnormal TSH (HR: 0.72, 95% confidence interval: 0.33-1.60) or subclinical hypothyroidism (HR: 0.52, 95% confidence interval: 0.19-1.45) when comparing NSWs to non-NSWs; nor were incidence rates significantly different among exclusively medical employees after excluding administrative staff. CONCLUSION: In this hospital-based nine-year follow-up retrospective cohort study, NSWs were not associated with increased relative risk of incident abnormal TSH and subclinical hypothyroidism, in contrast to previous cross-sectional studies.

Association of metabolically healthy obesity and elevated risk of coronary artery calcification: a systematic review and meta-analysis.

BACKGROUND: Metabolically healthy obesity (MHO) is defined as obesity with less than two parameters of metabolic abnormalities. Some studies report that MHO individuals show similar risk of cardiovascular disease (CVD) compared with metabolically healthy non-obese (MHNO) individuals, but the results are conflicting. Coronary artery calcium (CAC) reflects the extent of coronary atherosclerosis and is a useful tool to predict future risk of CVD. The objective of this meta-analysis was to investigate whether MHO is associated with elevated risk of CAC. METHOD: We searched Cochrane, PubMed, and Embase up to April 19, 2019. Prospective cohort and cross-sectional studies examining the association between MHO subjects and CAC were included with MHNO as the reference. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random-effect models. Subgroup analysis and meta-regression were applied to define possible sources of heterogeneity. We conducted this research following a pre-established protocol registered on PROSPERO (CRD 42019135006). RESULTS: A total of nine studies were included in this review and six studies with 23,543 participants were eligible for the meta-analysis. Compared with MHNO subjects, MHO had a higher odds of CAC (OR 1.36, 95% CI [1.11 to 1.66]; I 2 = 39%). In the subgroup analysis, the risk associated with MHO participants was significant in cohort studies (OR = 1.47, 95% CI [1.15,1.87], I 2 = 0%), and borderline significant in cross-sectional studies. The risk of CAC was also significant in MHO participants defined by Adult Treatment Panel III (ATP III) (OR = 1.55, 95% CI [1.25,1.93], I 2 = 0%). The univariate meta-regression model showed that age and smoking status were possible effect modifiers for MHO and CAC risk. CONCLUSION: Our meta-analysis showed that MHO phenotypes were associated with elevated risk of CAC compared with MHNO, which reflects the extent of coronary atherosclerosis. People with obesity should strive to achieve normal weight even when only one metabolic abnormality is present.

Clinical efficacy of concurrent bevacizumab for malignant ascites in nonsquamous cell carcinoma of the lung.

PURPOSE: Lung cancer with malignant peritoneal carcinomatosis and malignant ascites is rare, often indicates the terminal stage, and is refractory to treatment. The median survival time of lung cancer patients with malignant ascites has been reported to be as short as 15 days to 2 months in retrospective studies. METHODS: We reviewed all lung cancer patients who had cytologically or pathologically proven malignant ascites and received aggressive therapy including chemotherapy, anti-angiogenesis agents and target therapy at a Taiwan hospital from January 2015 to December 2017. In addition, we searched PubMed using the terms "lung cancer," "peritoneal carcinomatosis" and "malignant ascites" to find other studies reporting experience of such treatment. RESULTS: Three consecutive lung cancer patients with malignant ascites (3/265, 1.13%) were included in this case series study, all of whom received bevacizumab with three other drugs (erlotinib, afatinib and gemcitabine). All of the patients showed a good response to treatment with a marked decrease in ascites. Two of the patients had a long progression-free survival time of more than 5 months. In the literature review, several cases reports and case series documented the treatment efficacy, however no prospective or retrospective studies reported treatment strategies. CONCLUSIONS: Aggressive treatment for lung cancer with malignant ascites is encouraged when possible. Bevacizumab-based treatment may serve as one effective treatment strategy for non-squamous cell lung carcinoma with malignant ascites. Further prospective trials are urgently needed.

Alpha-tubulin acetyltransferase/MEC-17 regulates cancer cell migration and invasion through epithelial-mesenchymal transition suppression and cell polarity disruption.

MEC-17, a newly identified alpha-tubulin-N-acetyltransferase 1, serves as the major α-tubulin acetyltransferase to promote α-tubulin acetylation in vitro and in vivo. Alteration of α-tubulin acetylation may be involved in morphology regulation, cell migration, and tumour metastasis. However, MEC-17's role in cell physiology and its effect on epithelial-mesenchymal transition (EMT) and cell polarity remain elusive. In the present study, we characterized the overexpressed or downregulated cell models through gene targeting as MEC-17 gain- or loss-of-function. Overexpression of MEC-17 enhanced the cell spreading area, suppressed pseudopods formation in a three-dimensional (3D) culture system, and inhibited cancer cell migratory and invasive ability and tumour metastasis by orthotopic lung cancer animal model. Furthermore, morphological change and migration inhibition of cancer cells were accompanied by EMT repression, Golgi reorientation, and polarity disruption caused by alteration of cdc42 activity via a decrease in Rho-GAP, ARHGAP21. By contrast, a reduction in endogenous MEC-17 accelerated the pseudopods formation and EMT, and facilitated cell migration and invasion. These results demonstrated the crucial role of MEC-17 in the modulation of intrinsic cell morphogenesis, migration, and invasive function through regulation of EMT and cell polarity.

Effects of pre-irradiation and SDF-1 suppression on the progression of murine astrocytoma cells grown in different stromal beds.

PURPOSE: To examine whether brain tumors grown in pre-irradiated (PreIR) thigh have a similar tumor bed effect (TBE) as in PreIR brain tissue. MATERIAL AND METHODS: Tumor growth delay and immunohistochemical (IHC) staining for CD31, an endothelial surface marker, and PIMO, a hypoxia marker, were used to study the TBE of a murine astrocytoma, ALTS1C1, or a stromal-derived factor-1 (SDF-1) gene-silenced astrocytoma, ALTS1C1-SDFkd, growing in different PreIR stroma beds. RESULTS: ALTS1C1 tumors growing in both PreIR brain and PreIR thigh had reduced microvascular density (MVD) and more chronic hypoxia, but tumor growth delay was only seen in PreIR brain tissue. In contrast, ALTS1C1-SDFkd tumors showed tumor growth delay in PreIR thigh, with little effect in PreIR brain tissue. CONCLUSIONS: This study cautions that both the tumor and the nature of the PreIR stromal bed are important when using pre-irradiation as a model of recurrent brain tumors after radiation therapy.

Irradiation promotes an m2 macrophage phenotype in tumor hypoxia.

Macrophages display different phenotypes with distinct functions and can rapidly respond to environmental changes. Previous studies on TRAMP-C1 tumor model have shown that irradiation has a strong impact on tumor microenvironments. The major changes include the decrease of microvascular density, the increase of avascular hypoxia, and the aggregation of tumor-associated macrophages in avascular hypoxic regions. Similar changes were observed no matter the irradiation was given to tissue bed before tumor implantation (pre-IR tumors), or to established tumors (IR tumors). Recent results on three murine tumors, TRAMP-C1 prostate adenocarcinoma, ALTS1C1 astrocytoma, and GL261 glioma, further demonstrate that different phenotypes of inflammatory cells are spatially distributed into different microenvironments in both IR and pre-IR tumors. Regions with avascular hypoxia and central necrosis have CD11b(high)/Gr-1+ neutrophils in the center of the necrotic area. Next to them are CD11b(low)/F4/80+ macrophages that sit at the junctions between central necrotic and surrounding hypoxic regions. The majority of cells in the hypoxic regions are CD11b(low)/CD68+ macrophages. These inflammatory cell populations express different levels of Arg I. This distribution pattern, except for neutrophils, is not observed in tumors receiving chemotherapy or an anti-angiogenesis agent which also lead to avascular hypoxia. This unique distribution pattern of inflammatory cells in IR tumor sites is interfered with by targeting the expression of a chemokine protein, SDF-1α, by tumor cells, and this also increases radiation-induced tumor growth delay. This indicates that irradiated-hypoxia tissues have distinct tumor microenvironments that favor the development of M2 macrophages and that is affected by the levels of tumor-secreted SDF-1α.

Begin with the real-world patients of non-goal-achieved hypercholesterolemia in taiwan through the ezetimibe/simvastatin tablet - The BRAVO Study.

OBJECTIVE: To assess the efficacy, safety, and tolerability of a combination of 10 mg ezetimibe and 20 mg simvastatin in Taiwanese patients with hypercholesterolemia. RESEARCH DESIGN AND METHODS: A prospective, open-label, multi-center, hospital-based cohort study was conducted to evaluate the efficacy, safety, and tolerability of a single tablet combination of ezetimibe/simvastatin for the treatment of hypercholesterolemia. Taiwanese adults without low-density lipoprotein cholesterol (LDL-C) goal achievement, based on the National Cholesterol Education Program Adult Treatment Panel III guidelines, were treated with ezetimibe/simvastatin once daily for 6 weeks. The primary endpoint was the percentage of patients achieving LDL-C treatment goals after 6 weeks of treatment. Secondary endpoints included percentage change from baseline of LDL-C, total cholesterol, high-density lipoprotein cholesterol, and triglyceride. Safety and tolerability were assessed via clinical and laboratory examinations. The clinicaltrial.gov identifier of this study was NCT00654628. RESULTS: In total, 173 patients with a mean age of 57.9 ± 10.4 years were included. Of these, 57.8% were female and the average body mass index was 25.5 ± 3.4 kg/m(2). After 6 weeks of treatment, the great majority of the patients had reached their treatment goals (90.4% for LDL-C; 87% for TC; and 59% for TG). LDL-C levels were significantly reduced from 156.8 ± 30.8 mg/dL at baseline to 75.9 ± 25.4 mg/dL (51.4%, P < 0.0001) after only 6 weeks of therapy. Forty-nine adverse events (AEs), including one non-drug related serious AE, were reported. For non-serious AEs, the most common reported AEs during the entire study period were myalgia and upper respiratory infection (both n = 7). Nine patients dropped out of the study, reportedly due to AEs. CONCLUSIONS: A single tablet combination of 10 mg ezetimibe and 20 mg simvastatin in Taiwanese patients with hypercholesterolemia provided high LDL-C goal attainment rates and resulted in significant reductions in LDL-C.

Development and use of a chromogenic macroarray system for the detection of Staphylococcus aureus with enterotoxin A, B, C, D, E, and G genes in food and milk samples.

Abstract Staphylococcus aureus is one of the major pathogens that can cause staphylococcal infection and food poisoning. There are five major classical types of staphylococcal enterotoxins (SEs): SEA, SEB, SEC, SED, and SEE, as well as new SEs or SE-like superantigens (SAgs), such as SEG to SEU. Since many S. aureus strains harbor more than one SE gene and identification of SEs involved in food poisoning cases is time consuming, we developed a chromogenic macroarray method that allows convenient and simultaneous detection of classical SE genes and a new SE gene (seg), which is phylogenetically highly related to seb and sec. Two sets of degenerated primers labeled with biotin were used to co-amplify all SE genes in S. aureus strains through the polymerase chain reaction (PCR). Afterwards, these biotin-labeled PCR products were hybridized with SE gene-specific probes spotted on the nitrocellulose membrane. When this macroarray was used to detect enterotoxingenic S. aureus in milk or beef homogenate containing 10(0)-10(4) target cells per milliliter or gram of the sample, all six enterotoxin genes could be identified after a 12-hour enrichment step. This macroarray offers clinical and food inspection laboratories a rapid and economical visual method to detect common enterotoxigenic S. aureus strains.

Characterization and bond strength of electrolytic HA/TiO2 double layers for orthopaedic applications.

Insufficient bonding of juxtaposed bone to an orthopaedic/dental implant could be caused by material surface properties that do not support new bone growth. For this reason, fabrication of biomaterials surface properties, which support osteointegration, should be one of the key objectives in the design of the next generation of orthopaedic/dental implants. Titanium and titanium alloy have been widely used in several bioimplant applications, but when implanted into the human body, these still contain some disadvantages, such as poor osteointegration (forming a fibrous capsule), wear debris and metal ion release, which often lead to clinical failure. Electrolytic hydroxyapatite/titanium dioxide (HA/TiO2) double layers were successfully deposited on titanium substrates in TiCl4 solution and subsequently in the mixed solution of Ca(NO3)2 and NH4H2PO4, respectively. After annealing at 300 degrees C for 1 h in the air, the coated specimens were evaluated by dynamic cyclic polarization tests, immersion tests, tensile tests, surface morphology observations, XRD analyses and cells culture. The adhesion strength of the HA coating were improved by the intermediate coating of TiO2 from 11.3 to 46.7 MPa. From cell culture and immersion test results, the HA/TiO2 coated specimens promoted not only cells differentiation, but also appeared more bioactive while maintaining non-toxicity.

Characterization and bond strength of electrolytic HA/TiO2 double layers for orthopedic applications.

Insufficient bonding of juxtaposed bone to an orthopedic/dental implant could be caused by material surface properties that do not support new bone growth. For this reason, fabrication of biomaterials surface properties, which support osteointegration, should be one of the key objectives in the design of the next generation of orthopedic/dental implants. Titanium and titanium alloy have been widely used in several bioimplant applications, but when implanted into the human body, these still contain some disadvantages, such as poor osteointegration (forming a fibrous capsule), wear debris and metal ion release, which often lead to clinical failure. Electrolytic hydroxyapatite/titanium dioxide (HA/TiO2) double layers were successfully deposited on titanium substrates in TiCl4 solution and subsequently in the mixed solution of Ca(NO3)2 and NH4H2PO4, respectively. After annealing at 300 degrees C for 1 h in the air, the coated specimens were evaluated by dynamic cyclic polarization tests, immersion tests, tensile tests, surface morphology observations, XRD analyses and cells culture. The adhesion strength of the HA coating were improved by the intermediate coating of TiO2 from 11.3 to 46.7 MPa. From cell culture and immersion test results, the HA/TiO2 coated specimens promoted not only cells differentiation, but also appeared more bioactive while maintaining non-toxicity.