Airway Expression of Smad7, a TGF-β-inducible Inhibitory Molecule of TGF-β Signaling, Decreases after Repeated Airway Antigen Challenges

Transforming growth factor-β (TGF-β) is a profibrogenic cytokine that is involved in airway remodeling largely associated with chronic asthma. Accordingly, regulators of TGF-β activity could also play some role in airway remodeling in asthma. In this study, we investigated expression of Smad 7, a major intracellular inhibitor of TGF-β signaling, in the airways of mouse models of acute and chronic asthma. Sensitized, repeatedly (14 days) ovalbumin (OVA)-inhaled BALB/c mice exhibited evidence of airway remodeling including prominent subepithelial fibrosis associated with airway hyperresponsiveness (AHR) and airway inflammation (chronic asthma model) whereas sensitized, shortly OVA-inhaled BALB/c mice showed only AHR and airway inflammation (acute asthma model). Immunohistochemical analysis showed that Smad 7 immunoreactivity in the airways was increased after the development of acute and chronic asthma models and mainly detected in bronchial epithelial cells. Interestingly, Smad 7 immunoreactivity was significantly less in the airways of chronic asthma model than in those of acute asthma model, which was also confirmed by real-time PCR analysis of Smad 7. In consistent with decreased Smad 7 expression in the airways of chronic asthma model, phosphorylation of Smad 2, a marker of active TGF-β signaling, was increased in bronchial epithelial cells of chronic asthma model when compared with acute asthma model. These results suggest that decreased Smad 7 expression and Smad 2 upregulation in bronchial epithelial cells might result in increased TGF-β activity and contribute to the development of airway remodeling seen in chronic asthma

BISON Code Lists

Clinical codes lists used in the Bendroflumethiazide versus Indapamide Study for Hypertension (BISON): a propensity score matched incident new-user design retrospective cohort stud

Combined GWAS of metaformin glycaemic reponse in 1372 GoDARTS patients

This dataset includes the GWAS screening results that were used to the supplementary Figure 1 in the paper “Variation in the Glucose Transporter gene SLC2A2 is associated with glycaemic response to metformin” by Zhou et al. in Nature Genetics. Brief descriptions of the 12 columns in this file are in the following table. Column Descriptions SNP SNP identifier CHR Chromosome BP Base pair (NCBI build 36) EFFECT_ALLELE The effect allele NMISS Number of subjects in the analyses OR Odds ratio in the logistic regression, achieving treatment target as cases STAT_logistic Test statistics from logistic regression P_logistic P values from logistic regression BETA Beta from linear regression of HbA1c reduction STAT_linear Test statistics from linear regression P_linear P values from linear regression P_combined Combined p values from linear and logistic regression The P_combined is derived from a geometric mean of P_logistic and P_linear given that the effect allele’s impact on glycaemic response were consistent between the linear and logistic regression models (STAT_logistic and STAT_linear). Missing values of P_combined are due to the discrepant impact in the two models

MATCH

Abstract 2000 health care workers in NHS Tayside and from social care will have blood samples tested to detect antibodies to SARS-CoV-2, to identify undiagnosed asymptomatic healthcare worker infections with COVID-19. Documentation Up to 20% of cases of COVID-19 disease in some countries have been reported to be healthcare workers. The prevalence of HCW infections has not been properly documented due to lack of comprehensive studies. This information is crucial for infection control and to maintain the workforce during a pandemic. In addition, as HCWs are frequently exposed to infected patients they represent an ideal population in which to characterise immune responses to the infection. Discovering the frequency and impact of HCW infections will allow better workforce planning in the NHS as well as establishing whether a positive antibody test can allow staff to safely return to work with a low risk of infection. 2000 HCW in NHS Tayside and from social care will have blood samples tested with a validated laboratory assay to detect antibodies to SARS-CoV-2. The aims of the study are to identify undiagnosed asymptomatic healthcare worker infections with COVID-19, to understand the burden of undetected infections and to identify in patients with detectable antibodies can be reinfected with COVID-19. Contact [email protected] for more informatio

Supplement to: "A case series of a rare diagnostic entity: Broadspectrum Abnormal Localised Photosensitivity Syndrome"

Supplementary material to: "A case series of a rare diagnostic entity: Broadspectrum Abnormal Localised Photosensitivity Syndrome" This data is made available under a CC-BY creative commons license https://creativecommons.org/licenses/by/4.0

Type 2 Diabetes, Metabolic Traits, and Risk of Heart Failure: A Mendelian Randomization Study

Objective: The aim of this study was to use Mendelian randomization (MR) techniques to estimate the causal relationships between genetic liability to type 2 diabetes, glycaemic traits and risk of HF. Research Design and Methods: Summary-level data were obtained from genome-wide association studies (GWAS) of type 2 diabetes, insulin resistance (IR), glycated haemoglobin, fasting insulin and glucose and HF. MR was conducted using the inverse variance weighted (IVW) method. Sensitivity analyses included MR-Egger, weighted median and mode methods, and multivariable MR conditioning on potential mediators. Results: Genetic liability to type 2 diabetes was causally related to higher risk of HF (OR: 1.13 per 1 log-unit higher risk of type 2 diabetes; 95% CI 1.11-1.14, p<0.001), however sensitivity analysis revealed evidence of directional pleiotropy. The relationship between type 2 diabetes and HF was attenuated when adjusted for coronary disease, body mass index, LDL-cholesterol and blood pressure. Genetically-instrumented higher IR was associated with higher risk of HF (OR 1.19 per 1 log-unit higher risk of IR; 95% CI 1.00-1.41, p=0.041). There were no notable associations identified between fasting insulin, glucose or glycated haemoglobin and risk of HF. Genetic liability to HF was causally linked to higher risk of type 2 diabetes (OR 1.49; 95% CI 1.01-2.19, p=0.042) though again with evidence of pleiotropy. Conclusions: These findings suggest a causal role of type 2 diabetes and IR in HF aetiology, though both the presence of bidirectional effects and directional pleiotropy highlight potential sources of bias that need to be considered

Haem-iron plays a key role in the regulation of the Ess/type VII secretion system of Staphylococcus aureus RN6390

RNA-seq data deposited at the European Nucleotide Archive with accession number ERP00927

Haem-iron plays a key role in the regulation of the Ess/type VII secretion system of Staphylococcus aureus RN6390

RNA-seq data deposited at the European Nucleotide Archive with accession number ERP00927

Data from: Higher insulin resistance &amp; adiposity in post-menopausal women with breast cancer treated with aromatase inhibitors

Context: Aromatase deficiency causes obesity and insulin resistance in aromatase knockout mice and humans with rare mutations of the aromatase gene (CYP19). Aromatase inhibitors are a commonly prescribed therapy in post-menopausal breast cancer. Objective: We hypothesized that aromatase inhibitors induce obesity and insulin resistance when used in treatment of breast cancer. Design: Case-control study Setting: University teaching hospital Participants: 20 post-menopausal breast cancer patients, treated with aromatase inhibitor and 20 age-matched controls. Main outcome measures: Primary outcome measure was insulin sensitivity index – Matsuda, derived from a 75g oral glucose tolerance test. Body composition was assessed by DEXA and subcutaneous adipose tissue biopsies obtained for assessment of mRNA transcript levels. Data are mean ± SEM (inhibitor vs controls). Results: Aromatase inhibitor therapy was associated with significantly lower insulin sensitivity (5.15 ± 0.45 vs. 6.80 ± 0.64, P = 0.041), higher peak insulin concentration following OGTT (693.4 ± 78.6 vs. 527.6 ± 85.5 pmol/L, P = 0.035), greater percentage body fat (38.4 ± 1.0 vs. 34.6 ± 1.3 %, P = 0.026), and higher plasma leptin concentration (23.5 ± 2.8 vs. 15.5 ± 2.3 ng/mL, P = 0.035). Conclusions: Women who received aromatase inhibitors for post-menopausal breast cancer have greater percentage body fat and insulin resistance compared to controls with no history of breast cancer.Gibb, F.W. et al. (2019), Data from: Higher insulin resistance &amp; adiposity in post-menopausal women with breast cancer treated with aromatase inhibitors, Dryad, Dataset, 10.5061/dryad.2n054k