Project description:BackgroundMidlife women have a higher risk of cardiometabolic disease than younger women, but the lifelong biological/lifestyle factors responsible for this increase are unclear.ObjectivesWe investigated whether pregnancy history is a risk factor for midlife overweight/obesity and evaluated potential hormonal mechanisms.MethodsThe Baltimore Midlife Women's Health Study, a prospective cohort, recruited 772 women aged 45-54 y. Women reported pregnancy characteristics via questionnaires, trained staff measured weight/height to calculate midlife BMI, and serum hormones were assessed by ELISA. Logistic regression models assessed associations of pregnancy history with risk of midlife overweight/obesity and BMI gain since age 18. We additionally explored whether associations differed by menopausal status, and whether midlife hormones mediated relationships of pregnancy history and midlife BMI.ResultsThese premenopausal or perimenopausal women were 66% Caucasian/White and 30% African American/Black, with a median of 2 live births (range: 0-11) and median age at first birth of 27 y (range: 12-46 y). Women with 0 and ?2 live births had lower odds of overweight/obesity than those with 1 birth (OR = 0.47; 95% CI: 0.23, 0.96; P = 0.04, and OR = 0.58; 95% CI: 0.35, 0.95; P = 0.03, respectively). Women with ?2 live births also had lower odds of BMI gain than those with 1 birth (OR = 0.66; 95% CI: 0.41, 1.06; P = 0.08). Furthermore, women who were older at their first birth had lower odds of overweight/obesity (OR = 0.96; 95% CI: 0.92, 1.00; P = 0.03) and BMI gain (OR = 0.97; 95% CI: 0.93, 1.00; P = 0.06). Number of pregnancies and age at last pregnancy were not associated with midlife overweight/obesity or BMI gain. Associations did not differ by menopausal status and were not explained by midlife hormones.ConclusionsEarlier childbirth and having 1 child increased women's risk of midlife overweight/obesity and BMI gain since age 18. Additional studies should focus on women's childbearing years as a critical determinant of midlife metabolic health.
Project description:TRACERx (TRAcking Cancer Evolution through therapy (Rx)) is a prospective cohort study designed to investigate intratumor heterogeneity (ITH) in relation to clinical outcome, and to determine the clonal nature of driver events and evolutionary processes in early stage non-small cell lung cancer (NSCLC). This study looks at the multi-region RNAseq data from the TRACERx100 cohort with high enough quality RNA available. There is RNAseq data from 164 regions (64 patients).
Project description:Infections by the New World alphaviruses, Eastern Equine encephalitis virus (EEEV), Venezuelan Equine encephalitis virus (VEEV), and Western Equine encephalitis virus (WEEV), cause febrile illness that can progress to fatal disease in humans and equids. Currently there are no FDA-approved antivirals for prophylactic or therapeutic treatment of human infection by these viruses. To combat these infections, we have developed a novel small molecule, BDGR-164, which has subnanomolar potency against VEEV, EEEV, and WEEV. Using an intranasal route of virus infection in a lethal BALB/c model, prophylactic subcutaneous administration of BDGR-164 conferred 100% (VEEV), 88% (EEEV), and 63% (WEEV) survival. To evaluate the ability of BDGR-164 to reduce viral RNA/antigen, inflammation, and pathogenesis, we used RNASeq and histopathology of whole brain at 4 days post-infection (dpi). Viral RNA levels and antigen were reduced significantly in virus-infected and BDGR-164-treated versus virus-infected, sham-treated mice. Moreover, there was a significant reduction in host immune responses associated with inflammatory signaling, immune cell recruitment, and programmed cell death in virus-infected, BDGR-164 treated mice. Cytokine analyses of sera corroborated the reduction in upregulation of the immune response in virus-infected, BDGR-164 treated mice. Limited antiviral resistance to BDGR-164 was detected in one mouse on 4 dpi at NSP2:Y102C. In conclusion, our studies suggest that BDGR-164 has broad and potent prophylactic efficacy against the neurotropic alphaviruses.
Project description:BACKGROUND:A declining trend in mean cholesterol levels and smoking has been observed in high-income western countries during the last few decades, whereas obesity rates have increased. Simultaneously, mortality from coronary heart disease has decreased. The aim of the present study was to determine whether the trends in cardiovascular risk factors have continued in successive cohorts of middle-aged women over a period of 34?years. METHODS:Six population-based, cross-sectional samples of women (n?=?2294) mean age: 49.8?years (range: 45-54), living in Gothenburg, Sweden, were investigated between 1980 and 2014. RESULTS:Body mass index (BMI) increased over time, with a mean BMI of 24.7?kg/m2 in 1980 to 25.7?kg/m2 in 2013-2014, corresponding to a weight gain of 4.5?kg, together with an increase in the proportion of obese individuals (BMI???30?kg/m2) from 10.4 to 16.6% (p?=?0.0012). The proportion of smokers and women with hypertension decreased from 34.5 to 12.8% (p?=?0.0006) and from 37.7 to 24.5% (p?<?0.0001) respectively. Mean total serum cholesterol levels decreased from 6.23 (SD 1.09) mmol/L in 1980 to 5.43 (SD 0.98) mmol/L in 2013-2014 (p?<?0.0001). Self-reported leisure time regular exercise increased from 7.8% in 1980 to 35.6% in 2013-2014 (p?<?0.0001). For women born in 1963, the prevalence ratio of not having any of five major cardiovascular risk factors was 1.82 (95% confidence interval (CI) 1.38-2.41), compared with women born in 1925-1934. CONCLUSION:The trend towards increasing obesity, more leisure-time physical activity and less smoking remains, while the decrease in serum cholesterol appears to have abated.
Project description:Triplicate samples of RAW 264.7 murine macrophages either untreated, stimulated with 100 ng/ml LPS for 18 hours, or constituitively over-expressing CstF-64 were analyzed by microarray using Affymetrix murine gene chip 430A. Keywords = RAW 264.7 macrophages Keywords = LPS Keywords = CstF-64 Keywords: repeat sample
2005-01-01 | GSE2002 | GEO
Project description:TCR sequencing in NSCLC (TRACERx)
Project description:BackgroundThe frequency of surgical site infection (SSI) following orthopaedic implant placement in horses has been reported but not compared with respect to specific antibiotic protocols administered.ObjectivesTo determine factors associated with SSI in horses undergoing proximal interphalangeal joint (PIPJ) arthrodesis including perioperative antibiotic protocols.MethodsRecords were evaluated (2010-2019), and horses undergoing PIPJ arthrodesis were identified. Patient signalment, supervising surgeon, reason for surgery, limb, implants placed, anaesthetic time, duration casting/coaptation postoperatively, antibiotic regimen and incidence/onset SSI were recorded. Bayesian and frequentist logistic regressions were used to estimate the contribution of covariates to infection occurrence.ResultsFifty-four PIPJ arthrodeses were performed. SSI occurred in 2/54 (3.7%) on day 15,30. Arthrodesis was performed most commonly for osteoarthritis (33/54, 61.1%), fracture (11/54, 20.4%), and subluxation (5/54, 9.3%). Perioperative systemic antibiotics were administered 1-3 days (15/54, 27.8%) or > 3 days (39/54, 72.2%). Antibiotic protocols included cefazolin/gentamicin (20/54, 37%), cefazolin/gentamicin/doxycycline (14/54, 25.9%) and potassium penicillin/gentamicin (10/54, 18.5%). Regional limb perfusion was performed preoperatively 31/54 (57.4%) and postoperatively 7/54 (13%). Survival to dismissal was 98.1% (53/54 horses) with one horse euthanized due to support limb laminitis. No association was identified between antibiotic selection or duration (1-3 vs. > 3 days), pre-operative regional antibiotic perfusion, intraoperative antibiotic lavage or anaesthetic time (< or > 3 h) and SSI; however, modelling was complicated by quasi-complete or complete separation of the data. Bayesian analysis (but not frequentist analysis) indicated an association between post-operative regional antibiotic perfusion and SSI. Limitations include the retrospective nature of data collection and the low rate of infection overall.ConclusionsThe prevalence of SSI in this population was lower than that in previous reports of equine orthopaedic internal fixation. There was no difference in SSI rate in cases administered systemic antibiotics for 1-3 days or >3 days, or for those horses that did or did not receive preoperative regional antibiotic perfusion.
Project description:PurposeElective pelvic lymph node radiotherapy (PLNRT) in prostate cancer is often omitted from definitive (n = 267) and post prostatectomy (n = 160) radiotherapy (RT) due to concerns regarding toxicity and efficacy. Data comparing patient-reported outcome measures (PROMs) with or without PLNRT is limited. Our long-term supposition is that PLNRT, particularly to higher doses afforded by IMRT, will decrease pelvic failure rate in select patients. We aim to establish the impact of two different PLNRT doses on long term quality of life (QOL).Methods and materialsProstate cancer patients (n = 428) recorded baseline scores using the Expanded Prostate Cancer Index Composite (EPIC), prior to definitive or post-prostatectomy RT. PLNRT, if given, was prescribed to 45 or 54 Gy at 1.8 Gy per fraction. New EPIC scores were recorded 20-36 months after radiotherapy. Absolute change in each domain subscale and summary score was recorded, along with if these changes met minimally important difference (MID) criteria. A separate multivariate analysis (MVA) was performed for each measure. Subsequent dosimetric analysis was performed.ResultsFrequency of a MID decline was significantly greater with PLNRT to 54 Gy for urinary function, incontinence, and overall. No urinary decline was correlated with PLNRT to 45 Gy. PLNRT to 54 Gy was significant for decline in urinary function, bother, irritative, incontinence, and overall score in one or both MVA models while 45 Gy was not. Postoperative status was significant for decline in urinary function, incontinence, and overall. Amongst postoperative patients, there was significantly greater decline in urinary function score in the salvage setting. Neither 54 nor 45 Gy significantly affected bowel subscale or overall score decline.ConclusionsUsing conventional fractionation, adding PLNRT to 54 Gy, but not 45 Gy, correlates with worse urinary QOL, with postoperative patients experiencing a steeper decline. PLNRT had no significant impact on bowel QOL with either dose.