Debate: The potential role of estrogen in the prevention of heart disease in women after menopause

Large numbers of observational studies have described a decrease in the incidence of cardiovascular disease in women taking hormone replacement therapy (HRT). The potential mechanisms for this effect are numerous, including direct effects on lipid levels and lipid metabolism, cardiovascular dynamics, and endothelial reactivity. The beneficial effects of HRT are probably affected by various factors, including the age of onset of therapy, the presence of coronary artery disease, the type of estrogen and whether it is used in combination with progesterone, concurrent modification of other cardiac risk factors, and duration of therapy. Until further prospective clinical trials are done, HRT should be considered in those women for whom the potential benefits exceed the potential risks, on the basis of an individualized patient evaluation

Alumnae Association Bulletin of the School of Nursing, 1972

Alumnae Calendar The President\u27s Message Officers and Chairmen of Committees Financial Report Address by President Herbut School of Nursing Report School of Practical Nursing Report Report by Dr. Mary Louise Soentgen, M.D., F.A.A.P. Report of Patient Services Department Report of Staff Nurses\u27 Association Progress Report of Hospital Activities Scholarship Committee Report - Clerk-Typist Annual Luncheon - Head Table Social Events for 1971-1972 Missing Alumnae Members Jefferson Today Ways and Means Committee Report Constitution and By-Laws Report Sick and Welfare Committee Women\u27s Board Report Baccalaureate Degree Program Luncheon Pictures Resume of Minutes of Alumnae Association Meeting Class News Poem by Rosa Diseroad - 1923 Marriages Births - Hello World In Memoriam Notice

The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study

Objective To determine whether there is a link between hypoglycaemia and mortality among participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial

Investigation of the Strontium-90 Contaminant Plume along the Shoreline of the Columbia River at the 100-N Area of the Hanford Site

Efforts are underway to remediate strontium-laden groundwater to the Columbia River at the 100-N Area of the Hanford Site. Past practices of the 100-N reactor liquid waste disposal sites has left strontium-90 sorbed onto sediments which is a continuing source of contaminant discharge to the river. The Remediation Task of the Science and Technology Project assessed the interaction of groundwater and river water at the hyporheic zone. Limited data have been obtained at this interface of contaminant concentrations, geology, groundwater chemistry, affects of river stage and other variables that may affect strontium-90 release. Efforts were also undertaken to determine the extent, both laterally and horizontally, of the strontium-90 plume along the shoreline and to potentially find an alternative constituent to monitor strontium-90 that would be more cost effective and could possibly be done under real time conditions. A baseline of strontium-90 concentrations along the shoreline was developed to help assess remediation technologies

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

Advancing specificity in delirium: The delirium subtyping initiative

BACKGROUND: Delirium, a common syndrome with heterogeneous etiologies and clinical presentations, is associated with poor long-term outcomes. Recording and analyzing all delirium equally could be hindering the field's understanding of pathophysiology and identification of targeted treatments. Current delirium subtyping methods reflect clinically evident features but likely do not account for underlying biology. METHODS: The Delirium Subtyping Initiative (DSI) held three sessions with an international panel of 25 experts. RESULTS: Meeting participants suggest further characterization of delirium features to complement the existing Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revision diagnostic criteria. These should span the range of delirium-spectrum syndromes and be measured consistently across studies. Clinical features should be recorded in conjunction with biospecimen collection, where feasible, in a standardized way, to determine temporal associations of biology coincident with clinical fluctuations. DISCUSSION: The DSI made recommendations spanning the breadth of delirium research including clinical features, study planning, data collection, and data analysis for characterization of candidate delirium subtypes. HIGHLIGHTS: Delirium features must be clearly defined, standardized, and operationalized. Large datasets incorporating both clinical and biomarker variables should be analyzed together. Delirium screening should incorporate communication and reasoning

Implementation of an Outpatient HD-MTX Initiative

Introduction: Methotrexate (MTX) a folate antagonist is often given in high doses (≥500 mg/m2) to treat a variety of disease processes. While inpatient administration has been the norm, outpatient administration, has been shown to be safe, effective, and patient centered. Here in we describe development of an outpatient HDMTX protocol and our initial experience. Methods: All patients were to receive their first cycle of HDMTX in the hospital to ensure they tolerate it well and also to use this time to assist in training for home administration. The outpatient protocol involved continuous IV sodium bicarbonate, along with oral leucovorin and acetazolamide. Patients were required to visit the infusion center daily for labs and methotrexate levels. Clear criteria for admission were developed in the case of delayed clearance or methotrexate toxicity. Results: Two patients completed the safety run-in phase. Both patients tolerated treatment well. There were no associated toxicity. Methotrexate cleared within 3 days for all cycles. Both patients were able to follow the preadmission instructions for sodium bicarbonate and acetazolamide. The patients reported adequate teaching on the protocol and were able to maintain frequency of urine dipstick checks. Conclusion: We developed and implemented an outpatient protocol for high dose methotrexate. This study largely details the development of this protocol and its initial safety evaluation. More work needs to be done to assess its feasibility on a larger number of patients who receive more cycles in the outpatient setting

Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial

BACKGROUND: STAMPEDE has previously reported that radiotherapy (RT) to the prostate improved overall survival (OS) for patients with newly diagnosed prostate cancer with low metastatic burden, but not those with high-burden disease. In this final analysis, we report long-term findings on the primary outcome measure of OS and on the secondary outcome measures of symptomatic local events, RT toxicity events, and quality of life (QoL). METHODS AND FINDINGS: Patients were randomised at secondary care sites in the United Kingdom and Switzerland between January 2013 and September 2016, with 1:1 stratified allocation: 1,029 to standard of care (SOC) and 1,032 to SOC+RT. No masking of the treatment allocation was employed. A total of 1,939 had metastatic burden classifiable, with 42% low burden and 58% high burden, balanced by treatment allocation. Intention-to-treat (ITT) analyses used Cox regression and flexible parametric models (FPMs), adjusted for stratification factors age, nodal involvement, the World Health Organization (WHO) performance status, regular aspirin or nonsteroidal anti-inflammatory drug (NSAID) use, and planned docetaxel use. QoL in the first 2 years on trial was assessed using prospectively collected patient responses to QLQ-30 questionnaire. Patients were followed for a median of 61.3 months. Prostate RT improved OS in patients with low, but not high, metastatic burden (respectively: 202 deaths in SOC versus 156 in SOC+RT, hazard ratio (HR) = 0·64, 95% CI 0.52, 0.79, p < 0.001; 375 SOC versus 386 SOC+RT, HR = 1.11, 95% CI 0.96, 1.28, p = 0·164; interaction p < 0.001). No evidence of difference in time to symptomatic local events was found. There was no evidence of difference in Global QoL or QLQ-30 Summary Score. Long-term urinary toxicity of grade 3 or worse was reported for 10 SOC and 10 SOC+RT; long-term bowel toxicity of grade 3 or worse was reported for 15 and 11, respectively. CONCLUSIONS: Prostate RT improves OS, without detriment in QoL, in men with low-burden, newly diagnosed, metastatic prostate cancer, indicating that it should be recommended as a SOC. TRIAL REGISTRATION: ClinicalTrials.gov NCT00268476, ISRCTN.com ISRCTN78818544

RNAcentral : a hub of information for non-coding RNA sequences

RNAcentral is a comprehensive database of non-coding RNA (ncRNA) sequences, collating information on ncRNA sequences of all types from a broad range of organisms. We have recently added a new genome mapping pipeline that identifies genomic locations for ncRNA sequences in 296 species. We have also added several new types of functional annotations, such as tRNA secondary structures, Gene Ontology annotations, and miRNA-target interactions. A new quality control mechanism based on Rfam family assignments identifies potential contamination, incomplete sequences, and more. The RNAcentral database has become a vital component of many workflows in the RNA community, serving as both the primary source of sequence data for academic and commercial groups, as well as a source of stable accessions for the annotation of genomic and functional features. These examples are facilitated by an improved RNAcentral web interface, which features an updated genome browser, a new sequence feature viewer, and improved text search functionality. RNAcentral is freely available at https://rnacentral.org

The Identification of Zebrafish Mutants Showing Alterations in Senescence-Associated Biomarkers

There is an interesting overlap of function in a wide range of organisms between genes that modulate the stress responses and those that regulate aging phenotypes and, in some cases, lifespan. We have therefore screened mutagenized zebrafish embryos for the altered expression of a stress biomarker, senescence-associated β-galactosidase (SA-β-gal) in our current study. We validated the use of embryonic SA-β-gal production as a screening tool by analyzing a collection of retrovirus-insertional mutants. From a pool of 306 such mutants, we identified 11 candidates that showed higher embryonic SA-β-gal activity, two of which were selected for further study. One of these mutants is null for a homologue of Drosophila spinster, a gene known to regulate lifespan in flies, whereas the other harbors a mutation in a homologue of the human telomeric repeat binding factor 2 (terf2) gene, which plays roles in telomere protection and telomere-length regulation. Although the homozygous spinster and terf2 mutants are embryonic lethal, heterozygous adult fish are viable and show an accelerated appearance of aging symptoms including lipofuscin accumulation, which is another biomarker, and shorter lifespan. We next used the same SA-β-gal assay to screen chemically mutagenized zebrafish, each of which was heterozygous for lesions in multiple genes, under the sensitizing conditions of oxidative stress. We obtained eight additional mutants from this screen that, when bred to homozygosity, showed enhanced SA-β-gal activity even in the absence of stress, and further displayed embryonic neural and muscular degenerative phenotypes. Adult fish that are heterozygous for these mutations also showed the premature expression of aging biomarkers and the accelerated onset of aging phenotypes. Our current strategy of mutant screening for a senescence-associated biomarker in zebrafish embryos may thus prove to be a useful new tool for the genetic dissection of vertebrate stress response and senescence mechanisms