Systemic inflammation and suicide risk: cohort study of 419 527 Korean men and women

BACKGROUND: Data from only one study have been used to examine the relationship between systemic inflammation and later suicide risk, and a strong positive association was apparent. More research is needed, particularly looking at gender, not least because women are seemingly more vulnerable to inflammation-induced mood changes than men. METHODS: The Korean Cancer Prevention Study had a cohort of over 1 million individuals aged 30-95 years at baseline examination between 1992 and 1995, when white blood cell count, our marker of systemic inflammation, was assessed. RESULTS: A mean of 16.6 years of mortality surveillance gave rise to 1010 deaths from suicide in 106 643 men, and 1019 deaths from suicide in 312 884 women. There was little evidence of an association between our inflammation marker and suicide mortality in men after multiple adjustments. In women, however, those in the second inflammation quartile and higher experienced around 30% increase risk of death (HR 1.35; 95% CI: 1.11-1.64). CONCLUSIONS: Higher levels of systemic inflammation were moderately related to an elevated risk of suicide death in women but not in men

Oral health and later coronary heart disease: Cohort study of one million people

AIMS: Systematic reviews report an association between poorer oral health and an increased risk of coronary heart disease. This contentious relationship may not be causal but existing studies have been insufficiently well powered comprehensively to examine the role of confounding, particularly by cigarette smoking. Accordingly, we sought to examine the role of smoking in generating the relationship between oral health and coronary heart disease in life-long non-smokers. METHODS AND RESULTS: In the Korean Cancer Prevention Study, 975,685 individuals (349,579 women) aged 30–95 years had an oral examination when tooth loss, a widely used indicator of oral health, was ascertained. Linkage to national mortality and hospital registers over 21 years of follow-up gave rise to 64,784 coronary heart disease events (19,502 in women). In the whole cohort, after statistical adjustment for age, there was a moderate, positive association between tooth loss and coronary heart disease in both men (hazard ratio for seven or more missing teeth vs. none; 95% confidence interval 1.08; 1.02, 1.14; Ptrend across tooth loss groups <0.0001) and women (1.09; 1.01, 1.18; Ptrend 0.0016). Restricting analyses to a subgroup of 464,145 never smokers (25,765 coronary heart disease events), however, resulted in an elimination of this association in men (1.01; 0.85, 1.19); Ptrend 0.7506) but not women (1.08; 0.99, 1.18; Ptrend 0.0086). CONCLUSION: In men in the present study, the relationship between poor oral health and coronary heart disease risk appeared to be explained by confounding by cigarette smoking so raising questions about a causal link

Heterogeneity of emergency treatment practices in wheezing preschool children

Aim Our aim was to survey treatment practices used for preschool children with wheezing in emergency rooms (ER) focussing on inhalation device choice and handling, face mask use, salbutamol dosing and written instructions. We sought to assess whether current protocols are in line with published evidence and guidelines. Methods This is a cross-sectional survey done in paediatric ER units located in Finnish municipalities with more than 10 000 inhabitants. Results Of the 100 units contacted, 50% responded. More than 50% of the units used nebulisers. Only 13% of the units administered salbutamol in single puffs. More than 30% of the units lacked criteria on face mask use. Poor co-operation had no effect on the dose of salbutamol in 62% of the units. Ensuring tight mask-to-face seal was included in the training in 20% of the units. A written action plan was provided to the caregivers in 28% of the units. Conclusion ER treatment guidelines for preschool children with wheezing are poorly endorsed. Research is needed to identify approaches to guideline implementation that are specific for primary care. Clinical research should focus on strengthening recommendations that are currently not embraced. ER treatment protocols need to be updated and adherence to guidelines should be re-evaluated.Peer reviewe

Amyotrophic Lateral Sclerosis Is Associated with Hypolipidemia at the Presymptomatic Stage in Mice

OBJECTIVE: To demonstrate that hypolipidemia is a typical feature of the mouse model of amyotrophic lateral sclerosis (ALS) and to assess the association between hypolipidemia and disease stage, dietary intake, and sex. METHODS: We compared daily dietary intake, body weight, and serumlipid and glucose levels in ALS mice and wild-type controls at different stages of the disease. FINDINGS: Total cholesterol low-density lipoprotein (LDL) and LDL/high-density lipoprotein (HDL) ratio were significantly lower in ALS mice compared with controls. Subgroup analysis revealed that the incidence of hypolipidemia was significantly greater in male, but not female, ALS mice compared with control mice and that hypolipidemia was present at the presymptomatic stage of the disease. This hypolipidemia can be found without a decrease in the serum levels of other energy sources, such as glucose, in the presymptomatic stage. CONCLUSIONS: Hypolipidemia is present at the presymptomatic stage of the ALS mouse model in the absence of malnutrition, significant neuromuscular degeneration or regeneration, and respiratory difficulty. Our findings suggest that hypolipidemia might be associated with the pathomechanism of ALS and/or lipid-specific metabolism rather than simply an epiphenomenon of neuromuscular degeneration or energy imbalance

Body mass index and smoking-related lung cancer risk in the Singapore Chinese Health Study

10.1038/sj.bjc.6605496British Journal of Cancer1023610-61

Regulation of Adipose Tissue Stromal Cells Behaviors by Endogenic Oct4 Expression Control

BACKGROUND: To clarify the role of the POU domain transcription factor Oct4 in Adipose Tissue Stromal Cells (ATSCs), we investigated the regulation of Oct4 expression and other embryonic genes in fully differentiated cells, in addition to identifying expression at the gene and protein levels. The ATSCs and several immature cells were routinely expressing Oct4 protein before and after differentiating into specific lineages. METHODOLOGY/PRINCIPAL FINDINGS AND CONCLUSIONS: Here, we demonstrated the role of Oct4 in ATSCs on cell proliferation and differentiation. Exogenous Oct4 improves adult ATSCs cell proliferation and differentiation potencies through epigenetic reprogramming of stemness genes such as Oct4, Nanog, Sox2, and Rex1. Oct4 directly or indirectly induces ATSCs reprogramming along with the activation of JAK/STAT3 and ERK1/2. Exogenic Oct4 introduced a transdifferentiation priority into the neural lineage than mesodermal lineage. Global gene expression analysis results showed that Oct4 regulated target genes which could be characterized as differentially regulated genes such as pluripotency markers NANOG, SOX2, and KLF4 and markers of undifferentiated stem cells FOXD1, CDC2, and EPHB1. The negatively regulated genes included FAS, TNFR, COL6A1, JAM2, FOXQ1, FOXO1, NESTIN, SMAD3, SLIT3, DKK1, WNT5A, BMP1, and GLIS3 which are implicated in differentiation processes as well as a number of novel genes. Finally we have demonstrated the therapeutic utility of Oct4/ATSCs were introduced into the mouse traumatic brain, engrafted cells was more effectively induces regeneration activity with high therapeutic modality than that of control ATSCs. Engrafted Oct4/ATSCs efficiently migrated and transdifferentiated into action potential carrying, functionally neurons in the hippocampus and promoting the amelioration of lesion cavities

Expression of CD82 in Human Trophoblast and Its Role in Trophoblast Invasion

BACKGROUND: Well-controlled trophoblast invasion at maternal-fetal interface is a critical event for the normal development of placenta. CD82 is a member of transmembrane 4 superfamily, which showed important role in inhibiting tumor cell invasion and migration. We surmised that CD82 are participates in trophoblast differentiation during placenta development. METHODOLOGY/PRINCIPAL FINDINGS: CD82 was found to be strongly expressed in human first trimester placental villous and extravillous trophoblast cells as well as in trophoblast cell lines. To investigate whether CD82 plays a role in trophoblast invasion and migration, we further utilized human villous explants culture model on matrigel and invasion/migration assay of trophoblast cell line HTR8/SVneo. CD82 siRNA significantly promoted outgrowth of villous explants in vitro (P<0.01), as well as invasion and migration of HTR8/SVneo cells (P<0.05), whereas the trophoblast proliferation was not affected. The enhanced effect of CD82 siRNA on invasion and migration of trophoblast cells was found associated with increased gelatinolytic activities of matrix metalloproteinase MMP9 while over-expression of CD82 markedly decreased trphoblast cell invasion and migration as well as MMP9 activities. CONCLUSIONS/SIGNIFICANCE: These findings suggest that CD82 is an important negative regulator at maternal-fetal interface during early pregnancy, inhibiting human trophoblast invasion and migration

HbA1C and Cancer Risk in Patients with Type 2 Diabetes – A Nationwide Population-Based Prospective Cohort Study in Sweden

Background: Diabetes is associated with increased cancer risk. The underlying mechanisms remain unclear. Hyperglycemia might be one risk factor. HbA1c is an indicator of the blood glucose level over the latest 1 to 3 months. This study aimed to investigate association between HbA1c level and cancer risks in patients with type 2 diabetes based on real life situations. Methods: This is a cohort study on 25,476 patients with type 2 diabetes registered in the Swedish National Diabetes Register from 1997-1999 and followed until 2009. Follow-up for cancer was accomplished through register linkage. We calculated incidences of and hazard ratios (HR) for cancer in groups categorized by HbA1c &lt;= 58 mmol/mol (7.5%) versus &gt;58 mmol/mol, by quartiles of HbA1c, and by HbA1c continuously at Cox regression, with covariance adjustment for age, sex, diabetes duration, smoking and insulin treatment, or adjusting with a propensity score. Results: Comparing HbA1c &gt;58 mmol/mol with &lt;= 58 mmol/mol, adjusted HR for all cancer was 1.02 [95% CI 0.95-1.10] using baseline HbA1c, and 1.04 [95% CI 0.97-1.12] using updated mean HbA1c, and HRs were all non-significant for specific cancers of gastrointestinal, kidney and urinary organs, respiratory organs, female genital organs, breast or prostate. Similarly, no increased risks of all cancer or the specific types of cancer were found with higher quartiles of baseline or updated mean HbA1c, compared to the lowest quartile. HR for all cancer was 1.01 [0.98-1.04] per 1%-unit increase in HbA1c used as a continuous variable, with non-significant HRs also for the specific types of cancer per unit increase in HbA1c. Conclusions: In this study there were no associations between HbA1c and risks for all cancers or specific types of cancer in patients with type 2 diabetes