Shortened Telomere Length in Sputum Cells of Bronchiectasis Patients is Associated with Dysfunctional Inflammatory Pathways

Telomere attrition is an established ageing biomarker and shorter peripheral blood leukocyte telomere length has been associated with increased risks of respiratory diseases. However, whether telomere length in disease-relevant sputum immune cells of chronic respiratory disease patients is shortened and which pathways are dysfunctional are not clear. Here we measured telomere length from sputum samples of bronchiectasis and asthmatic subjects and determined that telomere length in sputum of bronchiectasis subjects was significantly shorter (Beta?=????1.167, P_Adj?=?2.75?×?10^?4). We further performed global gene expression analysis and identified genes involved in processes such as NLRP3 inflammasome activation and regulation of adaptive immune cells when bronchiectasis sputum telomere length was shortened. Our study provides insights on dysfunctions related to shortened telomere length in sputum immune cells of bronchiectasis patients.

     

Effect of dose adjustments on the efficacy and safety of tofacitinib in patients with rheumatoid arthritis: a post hoc analysis of an open-label,long-term extension study (ORAL Sequel)

Clinical Rheumatology - We assess the impact of switching versus staying on the same tofacitinib dose on efficacy and safety in patients with rheumatoid arthritis (RA). ORAL Sequel was an...     

Depressive symptoms and smoking among Hong Kong Chinese adolescents

AIMS: To examine associations among depressive symptoms, smoking, smoking trajectories and quitting smoking in Hong Kong. DESIGN: Prospective longitudinal design, with wave 1 at baseline (T1) and wave 2 (T2) 12 months later. SETTING AND PARTICIPANTS: Form 1 (equivalent to 7th grade in the United States) students, mean age = 12.7 years, n = 1894. MEASUREMENTS: Self-reported smoking status, attempts to quit and depressive symptoms. FINDINGS: At both waves, current as well as ex-smokers had higher depressive symptoms than never smokers. T1 smoking predicted T2 depressive symptoms among those with low baseline depressive symptoms. Depressive symptoms at T1 predicted smoking at T2 among non-smokers at T1. Trajectories were defined by separating participants who were never smokers at both waves ('non-smokers'), those who smoked at both waves ('persistent smokers'), those who smoked at one time but were not smoking at either wave ('past smokers), and those who had never smoked at T1 but reported smoking a year later ('new smokers'). Persistent, past and new smokers had higher depressive symptoms at both waves than non-smokers. Smokers who reported not wanting or trying to quit and those who had been unsuccessful at quitting had higher depressive symptoms at T2 than those who successfully quit. CONCLUSION: Our results suggest that depressive symptoms promote tobacco use in Asian adolescents by making it more likely that an adolescent will begin smoking and less likely that she or he will quit. These findings elucidate risk factors in Hong Kong for two important public health concerns for adolescents: smoking and depression.     

Impact of hypotension after return of spontaneous circulation on survival in patients of out-of-hospital cardiac arrest

Objective

To investigate the relationship between hypotension in the first 3 h after return of spontaneous circulation (ROSC) in patients with out-of-hospital cardiac arrest.

Pulmonary Embolism Response Team activation during the COVID-19 pandemic in a New York City Academic Hospital: a retrospective cohort analysis

Journal of Thrombosis and Thrombolysis - Coronavirus disease 2019 (COVID-19) is associated with increased rates of deep vein thrombosis (DVT) and pulmonary embolism (PE). Pulmonary Embolism...     

Circulating anti-pericyte autoantibodies are present in Type 2 diabetic patients and are associated with non-proliferative retinopathy

AIMS/HYPOTHESIS: This study aims to determine the prevalence of anti-pericyte autoantibodies in Type 2 diabetes and to characterize these autoantibodies as new markers of disease activity in diabetic retinopathy. METHODS: A total of 299 patients with Type 2 diabetes participated in this study. Retinopathy was assessed by 7-field stereo fundus photography and was graded according to the ETDRS scale. Serum anti-pericyte autoantibodies were detected by immunofluorescence on tissue cultured bovine retinal pericytes. RESULTS: The prevalence of anti-pericyte autoantibodies in Type 2 diabetic patients was 54% and was approximately equal in men and women. The prevalence was approximately 55% with retinopathy at grades from 10 to 53. At grades above 53 the prevalence declined to 23% ( p<0.0001). The highest prevalence by duration of diabetes, 70%, was found at 0 to 5 years and the lowest, 25% at more than 25 years duration ( p<0.0001). CONCLUSION/INTERPRETATION: Anti-pericyte autoantibodies are present at high prevalence in Type 2 diabetes. Their presence during earlier stages of retinopathy could be due to a reaction with antigens expressed by "activated" pericytes. The decline in antibody prevalence in advanced retinopathy could mark pericyte loss and progression to an angiogenic retinal milieu.     

Outcome and prognostic indicators of diffuse proliferative lupus glomerulonephritis treated with sequential oral cyclophosphamide and azathioprine

OBJECTIVE: To study the outcome and prognostic indicators of diffuse proliferative glomerulonephritis (DPGN) in patients with systemic lupus erythematosus (SLE) treated with sequential oral cyclophosphamide (CYC) and azathioprine (AZA). METHODS: SLE patients with biopsy-proven DPGN treated with sequential oral CYC and AZA were studied. Those who achieved renal remission at 12 months were identified, and the clinical predictors of complete remission were evaluated by regression analysis. All patients were followed up until a relapse of the nephritis or a doubling of the serum creatinine level occurred. The timing and risk factors for flares and creatinine doubling were evaluated by Kaplan-Meier analysis and with the Cox proportional hazards model. RESULTS: We studied 55 patients (47 women, 8 men; mean +/- SD age at renal biopsy 31.1 +/- 10.4 years); 25 (46%) had a serum creatinine level >106 micromoles/liter, and 29 (53%) had nephrotic syndrome. At 12 months posttreatment, 37 (67%) had complete remission and 12 (22%) had partial remission. The initial serum creatinine level was an independent predictor of complete remission. Excluding the 4 patients who were treatment- resistant or died, 21 patients (41%) had renal flares during a median followup of 4 years. The cumulative risk of renal flare was 6% at 1 year, 21% at 3 years, and 32% at 5 years. The median time to relapse was 43 months. The histologic activity score and the mean daily dose of CYC were multivariate predictors of renal flare, by Cox regression. At the last followup visit, 9 of 54 patients (17%) had a doubling of the creatinine level, 6 of whom (11%) underwent dialysis. The cumulative risk of creatinine doubling was 8.4% at 5 years and 18.2% at 10 years. An increasing chronicity index at the time of initial renal biopsy was an independent predictor of deterioration in renal function. CONCLUSION: Sequential therapy with oral CYC followed by AZA appears to be an effective treatment regimen for DPGN in patients with SLE, with 89% of patients achieving complete or partial remission at 12 months, 62.8% remaining in remission after 5 years, and 81.8% having stable renal function after 10 years. Predictors of treatment resistance and relapse include increasing serum creatinine level, higher histologic activity scores, and a lower dose of CYC. Increasing chronicity indices predict a deterioration of renal function.     

Evidence that endothelin-1 (ET-1) inhibits insulin-stimulated glucose uptake in rat adipocytes mainly through ETa receptors

The specificity of endothelin (ET) receptors involved in the inhibition of insulin-stimulated glucose uptake (ISGU) in rat adipocytes was investigated. Adipocytes were isolated from the epididymal fat pads of Sprague-Dawley rats. To determine receptor subtypes, we used three ET isopeptides, ET-1 and ET-2, both of which are nonselective agonists, and ET-3, a selective agonist for ETc receptors, to displace [¹²⁵I]ET-1 binding from the fat cells. The efficiency of displacement was ET-1 > ET-2 ? ET-3, indicating that the primary receptors involved belonged to the ETa subtype. At an equal concentration of 1 μmol/L, BQ-610, a selective ETa antagonist, displaced [¹²⁵I]ET-1 from binding to fat cells, whereas IRL-1038, a selective ETb antagonist, did not. Using [³H]2-deoxy-d-1-glucose ([³H]2-DG) as a tracer in studies of glucose uptake, we found that equimolar BQ-610 completely reversed the inhibitory effect of ET-1 on ISGU, whereas IRL-1038 was ineffective. Northern blot analysis of adipocyte receptors showed abundant mRNA for ETa, but no ETb subtype. These results clearly demonstrate that ETa is the predominant receptor in rat adipocytes.     

Detection of bioactive peptides including gonadotrophin‐releasing factors (GnRHs) in horse urine using ultra‐high performance liquid chromatography–high resolution mass spectrometry (UHPLC/HRMS)

The use of bioactive peptides as a doping agent in both human and animal sports has become increasingly popular in recent years. As such, methods to control the misuse of bioactive peptides in equine sports have received attention. This paper describes a sensitive accurate mass method for the detection of 40 bioactive peptides and two non‐peptide growth hormone secretagogues (< 2 kDa) at low pg/mL levels in horse urine using ultra‐high performance liquid chromatography‐high resolution mass spectrometry (UHPLC/HRMS). A simple mixed‐mode cation exchange solid‐phase extraction (SPE) cartridge was employed for the extraction of 42 targets and/or their in vitro metabolites from horse urine. The final extract was analyzed using UHPLC/HRMS in positive electrospray ionization (ESI) mode under both full scan and data independent acquisition (DIA, for MS²). The estimated limits of detection (LoD) for most of the targets could reach down to 10 pg/mL in horse urine. This method was validated for qualitative detection purposes. The validation data, including method specificity, method sensitivity, extraction recovery, method precision, and matrix effect were reported. A thorough in vitro study was also performed on four gonadotrophin‐releasing factors (GnRHs), namely leuprorelin, buserelin, goserelin, and nafarelin, using the S9 fraction isolated from horse liver. The identified in vitro metabolites have been incorporated into the method for controlling the misuse of GnRHs. The applicability of this method was demonstrated by the identification of leuprorelin and one of its metabolites, Leu M4, in urine obtained after intramuscular administration of leuprorelin to a thoroughbred gelding (castrated horse).