Occupational noise exposure is associated with hypertension in China: Results from project ELEFANT

OBJECTIVES: We investigated the association between occupational noise exposure and the risk of elevated blood pressure and hypertension by stage in young adults. METHODS: We utilized 124,286 young adults (18-40 years) from the Project ELEFANT study. We categorized occupational noise exposure as high (75 dBA noise exposure for more than 4 hours per day) or low, and measured blood pressure (mmHg) and categorized participants by hypertension stage (normal, elevated, Stage 1, Stage 2). We applied adjusted logistic regression models to identify associations with hypertension risk, and we further examined the noise-BMI, noise-gender, and noise-residence interactions on hypertension risk in separate models. RESULTS: High occupational noise exposure was associated with increases in blood pressure among participants with elevated blood pressure (Estimate = 0.23, 95% CI: 1.09, 1.46, p = 0.0009), in Stage 1 hypertension (Estimate = 0.15, 95% CI: 1.06, 1.25, p = 0.0008), and in Stage 2 hypertension (Estimate = 0.41 95% CI: 1.31, 1.73, p<0.0001). Likewise, noise exposure-BMI interaction was consistently positively associated with increases in blood pressure in participants with elevated blood pressure (Estimate = 0.71, 95% CI: 1.55, 2.69, p<0.0001), in Stage 1 hypertension (Estimate = 0.78, 95% CI: 1.82, 2.61, p<0.0001), and in Stage 2 hypertension (Estimate = 2.06, 95% CI: 5.64, 10.81, p<0.0001). The noise exposure-male interaction showed higher risk for hypertension compared to the noise exposure-female interaction in participants with elevated blood pressure (Estimate = 1.24, 95% CI: 2.56, 4.71, p<0.0001), Stage 1 (Estimate = 1.67, 95% CI: 4.34, 6.42, p<0.0001) and Stage 2 hypertension (Estimate = 1.70, 95% CI: 3.86, 7.77, p<0.0001). Finally, we found that noise exposure-urban interaction was consistently associated with an increase in blood pressure in elevated blood pressure (Estimate = 0.32, 95% CI: 1.19, 1.62, p<0.0001) and in Stage 2 hypertension (Estimate = 0.44, 95% CI: 1.31, 1.80, p<0.0001)

Age at menarche and prevention of hypertension through lifestyle in young Chinese adult women: result from project ELEFANT.

Early and late age at menarche are associated with risk of hypertension, but little is known whether modifiable lifestyle can reduce this risk. METHODS: Our study leverages 60,135 healthy young Chinese women from the Environmental and LifEstyle FActors iN metabolic health throughout life-course Trajectories (ELEFANT) study. Menarche age and lifestyle factors were assessed by self-reported questionnaires and hypertension was diagnosed by physicians. We estimated the odds ratios (ORs) of hypertension associated with menarche age using multivariable logistic regression. We further investigated whether modifiable lifestyles (body mass index, BMI; psychological stress; passive smoking; and imbalanced diet) increased risk in joint analyses. RESULTS: The association between age at menarche and hypertension was U-shaped, with age ≤ 12 at menarche giving the highest OR (1.46, 95% confidence interval [CI], 1.27-1.69) and ≥ 16 the second highest (OR = 1.36, 95% CI = 1.15-1.62). Simultaneous analysis of lifestyle risk factors and age of menarche showed that having one or more modifiable risk factors increased the menarche age-hypertension association. The risk of hypertension among participants with menarche age ≤ 12 decreased from OR 13.21 (95% CI = 5.17-29.36) with four high-risk lifestyle factors to 12.36 (95% CI = 9.51-16.05) with three high-risk factors, 5.24 (95% CI = 4.11-6.69) with two, and 2.76 (95% CI = 2.09-3.60) with one, in comparison to individuals with no high-risk lifestyle factors and menarche age 14. CONCLUSIONS: Our results suggest that modification of lifestyle, including maintenance of normal weight and a balanced diet, are associated with substantially reduce the risk of hypertension in high-risk individuals. Early and late age at menarche are risk factors for the development of hypertension in Western populations, and there is limited evidence that this is also true of Chinese populations. Targeted prevention of hypertension in vulnerable populations would be highly beneficial in efforts to reduce the incidence of cardiovascular disease, but it is not currently known whether lifestyle intervention could reduce hypertension risk. In this study, we analysed the risk of hypertension by age at menarche and four modifiable lifestyle factors (BMI, diet, psychological stress, and smoking tobacco) in a cohort of 60,135 young adult Chinese women (mean age 29). We identified that early and late age at menarche are associated with increased risk of hypertension in young Chinese women. There was joint effects between age at menarche and lifestyles on hypertension only participants with age at menarche ≤12 and being overweight or obese. Modification of lifestyle, including maintenance of normal weight and a balanced diet, can substantially reduce the risk of hypertension in high-risk individuals. In conclusion, our study has revealed that early and late menarche age are associated with the development of hypertension in young Chinese women, and that this risk is modified by healthy lifestyle traits

Type I Interferon Signaling Regulates Ly6Chi Monocytes and Neutrophils during Acute Viral Pneumonia in Mice

Type I interferon (IFN-I) plays a critical role in the homeostasis of hematopoietic stem cells and influences neutrophil influx to the site of inflammation. IFN-I receptor knockout (Ifnar1−/−) mice develop significant defects in the infiltration of Ly6Chi monocytes in the lung after influenza infection (A/PR/8/34, H1N1). Ly6Chi monocytes of wild-type (WT) mice are the main producers of MCP-1 while the alternatively generated Ly6Cint monocytes of Ifnar1−/− mice mainly produce KC for neutrophil influx. As a consequence, Ifnar1−/− mice recruit more neutrophils after influenza infection than do WT mice. Treatment of IFNAR1 blocking antibody on the WT bone marrow (BM) cells in vitro failed to differentiate into Ly6Chi monocytes. By using BM chimeric mice (WT BM into Ifnar1−/− and vice versa), we confirmed that IFN-I signaling in hematopoietic cells is required for the generation of Ly6Chi monocytes. Of note, WT BM reconstituted Ifnar1−/− chimeric mice with increased numbers of Ly6Chi monocytes survived longer than influenza-infected Ifnar1−/− mice. In contrast, WT mice that received Ifnar1−/− BM cells with alternative Ly6Cint monocytes and increased numbers of neutrophils exhibited higher mortality rates than WT mice given WT BM cells. Collectively, these data suggest that IFN-I contributes to resistance of influenza infection by control of monocytes and neutrophils in the lung

Evaluation of Allelic Expression of Imprinted Genes in Adult Human Blood

Imprinted genes are expressed from only one allele in a parent-of-origin dependent manner. Loss of imprinted (LOI) expression can result in a variety of human disorders and is frequently reported in cancer. Biallelic expression of imprinted genes in adult blood has been suggested as a useful biomarker and is currently being investigated in colorectal cancer. In general, the expression profiles of imprinted genes are well characterised during human and mouse fetal development, but not in human adults

Sublingual Immunization with a Live Attenuated Influenza A Virus Lacking the Nonstructural Protein 1 Induces Broad Protective Immunity in Mice

The nonstructural protein 1 (NS1) of influenza A virus (IAV) enables the virus to disarm the host cell type 1 IFN defense system. Mutation or deletion of the NS1 gene leads to attenuation of the virus and enhances host antiviral response making such live-attenuated influenza viruses attractive vaccine candidates. Sublingual (SL) immunization with live influenza virus has been found to be safe and effective for inducing protective immune responses in mucosal and systemic compartments. Here we demonstrate that SL immunization with NS1 deleted IAV (DeltaNS1 H1N1 or DeltaNS1 H5N1) induced protection against challenge with homologous as well as heterosubtypic influenza viruses. Protection was comparable with that induced by intranasal (IN) immunization and was associated with high levels of virus-specific antibodies (Abs). SL immunization with DeltaNS1 virus induced broad Ab responses in mucosal and systemic compartments and stimulated immune cells in mucosa-associated and systemic lymphoid organs. Thus, SL immunization with DeltaNS1 offers a novel potential vaccination strategy for the control of influenza outbreaks including pandemics

Cohesin is required for higher-order chromatin conformation at the imprinted IGF2-H19 locus

Cohesin is a chromatin-associated protein complex that mediates sister chromatid cohesion by connecting replicated DNA molecules. Cohesin also has important roles in gene regulation, but the mechanistic basis of this function is poorly understood. In mammalian genomes, cohesin co-localizes with CCCTC binding factor (CTCF), a zinc finger protein implicated in multiple gene regulatory events. At the imprinted IGF2-H19 locus, CTCF plays an important role in organizing allele-specific higher-order chromatin conformation and functions as an enhancer blocking transcriptional insulator. Here we have used chromosome conformation capture (3C) assays and RNAi-mediated depletion of cohesin to address whether cohesin affects higher order chromatin conformation at the IGF2-H19 locus in human cells. Our data show that cohesin has a critical role in maintaining CTCF-mediated chromatin conformation at the locus and that disruption of this conformation coincides with changes in IGF2 expression. We show that the cohesin-dependent, higher-order chromatin conformation of the locus exists in both G1 and G2 phases of the cell cycle and is therefore independent of cohesin's function in sister chromatid cohesion. We propose that cohesin can mediate interactions between DNA molecules in cis to insulate genes through the formation of chromatin loops, analogous to the cohesin mediated interaction with sister chromatids in trans to establish cohesion

Autoimmune gastrointestinal complications in patients with Systemic Lupus Erythematosus: case series and literature review

The association of systemic lupus erythematosus (SLE) with gastrointestinal autoimmune diseases is rare, but has been described in the literature, mostly as case reports. However, some of these diseases may be very severe, thus a correct and early diagnosis with appropriate management are fundamental. We have analysed our data from the SLE patient cohort at University College Hospital London, established in 1978, identifying those patients with an associated autoimmune gastrointestinal disease. We have also undertaken a review of the literature describing the major autoimmune gastrointestinal pathologies which may be coincident with SLE, focusing on the incidence, clinical and laboratory (particularly antibody) findings, common aetiopathogenesis and complications

Withaferin A Alters Intermediate Filament Organization, Cell Shape and Behavior

Withaferin A (WFA) is a steroidal lactone present in Withania somnifera which has been shown in vitro to bind to the intermediate filament protein, vimentin. Based upon its affinity for vimentin, it has been proposed that WFA can be used as an anti-tumor agent to target metastatic cells which up-regulate vimentin expression. We show that WFA treatment of human fibroblasts rapidly reorganizes vimentin intermediate filaments (VIF) into a perinuclear aggregate. This reorganization is dose dependent and is accompanied by a change in cell shape, decreased motility and an increase in vimentin phosphorylation at serine-38. Furthermore, vimentin lacking cysteine-328, the proposed WFA binding site, remains sensitive to WFA demonstrating that this site is not required for its cellular effects. Using analytical ultracentrifugation, viscometry, electron microscopy and sedimentation assays we show that WFA has no effect on VIF assembly in vitro. Furthermore, WFA is not specific for vimentin as it disrupts the cellular organization and induces perinuclear aggregates of several other IF networks comprised of peripherin, neurofilament-triplet protein, and keratin. In cells co-expressing keratin IF and VIF, the former are significantly less sensitive to WFA with respect to inducing perinuclear aggregates. The organization of microtubules and actin/microfilaments is also affected by WFA. Microtubules become wavier and sparser and the number of stress fibers appears to increase. Following 24 hrs of exposure to doses of WFA that alter VIF organization and motility, cells undergo apoptosis. Lower doses of the drug do not kill cells but cause them to senesce. In light of our findings that WFA affects multiple IF systems, which are expressed in many tissues of the body, caution is warranted in its use as an anti-cancer agent, since it may have debilitating organism-wide effects

Sublingual Immunization with M2-Based Vaccine Induces Broad Protective Immunity against Influenza

The ectodomain of matrix protein 2 (M2e) of influenza A virus is a rationale target antigen candidate for the development of a universal vaccine against influenza as M2e undergoes little sequence variation amongst human influenza A strains. Vaccine-induced M2e-specific antibodies (Abs) have been shown to display significant cross-protective activity in animal models. M2e-based vaccine constructs have been shown to be more protective when administered by the intranasal (i.n.) route than after parenteral injection. However, i.n. administration of vaccines poses rare but serious safety issues associated with retrograde passage of inhaled antigens and adjuvants through the olfactory epithelium. In this study, we examined whether the sublingual (s.l.) route could serve as a safe and effective alternative mucosal delivery route for administering a prototype M2e-based vaccine. The mechanism whereby s.l. immunization with M2e vaccine candidate induces broad protection against infection with different influenza virus subtypes was explored.A recombinant M2 protein with three tandem copies of the M2e (3M2eC) was expressed in Escherichia coli. Parenteral immunizations of mice with 3M2eC induced high levels of M2e-specific serum Abs but failed to provide complete protection against lethal challenge with influenza virus. In contrast, s.l. immunization with 3M2eC was superior for inducing protection in mice. In the latter animals, protection was associated with specific Ab responses in the lungs.The results demonstrate that s.l. immunization with 3M2eC vaccine induced airway mucosal immune responses along with broad cross-protective immunity to influenza. These findings may contribute to the understanding of the M2-based vaccine approach to control epidemic and pandemic influenza infections