Silica-Supported Oligomeric Benzyl Phosphate (Si-OBP) and Triazole Phosphate (Si-OTP) Alkylating Reagents

The syntheses of silica-supported oligomeric benzyl phosphates (Si-OBPn) and triazole phosphates (Si-OTPn) using ring-opening metathesis polymerization (ROMP) for use as efficient alkylating reagents is reported. Ease of synthesis and grafting onto the surface of norbornenyl-tagged (Nb-tagged) silica particles has been demonstrated for benzyl phosphate and triazole phosphate monomers. It is shown that these silica polymer hybrid reagents, Si-OBPn and Si-OTPn, can be used to carry out alkylation reactions with an array of different nucleophiles to afford the corresponding benzylated and (triazolyl)methylated products in good yield and high purity

Genome-wide copy number alterations in subtypes of invasive breast cancers in young white and African American women.

Genomic copy number alterations (CNA) are common in breast cancer. Identifying characteristic CNAs associated with specific breast cancer subtypes is a critical step in defining potential mechanisms of disease initiation and progression. We used genome-wide array comparative genomic hybridization to identify distinctive CNAs in breast cancer subtypes from 259 young (diagnosed with breast cancer at 40%) for TN breast tumors at 10q, 11p, 11q, 16q, 20p, and 20q. In addition, we report CNAs that differ in frequency between TN breast tumors of AA and CA women. This is of particular relevance because TN breast cancer is associated with higher mortality and young AA women have higher rates of TN breast tumors compared to CA women. These data support the possibility that higher overall frequency of genomic alteration events as well as specific focal CNAs in TN breast tumors might contribute in part to the poor breast cancer prognosis for young AA women

Sexual Satisfaction and the Importance of Sexual Health to Quality of Life Throughout the Life Course of U.S. Adults

Discussions about sexual health are uncommon in clinical encounters, despite the sexual dysfunction associated with many common health conditions. Understanding of the importance of sexual health and sexual satisfaction among US adults is limited

The microaerophilic microbiota of de-novo paediatric inflammatory bowel disease: the BISCUIT study

<p>Introduction: Children presenting for the first time with inflammatory bowel disease (IBD) offer a unique opportunity to study aetiological agents before the confounders of treatment. Microaerophilic bacteria can exploit the ecological niche of the intestinal epithelium; Helicobacter and Campylobacter are previously implicated in IBD pathogenesis. We set out to study these and other microaerophilic bacteria in de-novo paediatric IBD.</p> <p>Patients and Methods: 100 children undergoing colonoscopy were recruited including 44 treatment naïve de-novo IBD patients and 42 with normal colons. Colonic biopsies were subjected to microaerophilic culture with Gram-negative isolates then identified by sequencing. Biopsies were also PCR screened for the specific microaerophilic bacterial groups: Helicobacteraceae, Campylobacteraceae and Sutterella wadsworthensis.</p> <p>Results: 129 Gram-negative microaerophilic bacterial isolates were identified from 10 genera. The most frequently cultured was S. wadsworthensis (32 distinct isolates). Unusual Campylobacter were isolated from 8 subjects (including 3 C. concisus, 1 C. curvus, 1 C. lari, 1 C. rectus, 3 C. showae). No Helicobacter were cultured. When comparing IBD vs. normal colon control by PCR the prevalence figures were not significantly different (Helicobacter 11% vs. 12%, p = 1.00; Campylobacter 75% vs. 76%, p = 1.00; S. wadsworthensis 82% vs. 71%, p = 0.312).</p> <p>Conclusions: This study offers a comprehensive overview of the microaerophilic microbiota of the paediatric colon including at IBD onset. Campylobacter appear to be surprisingly common, are not more strongly associated with IBD and can be isolated from around 8% of paediatric colonic biopsies. S. wadsworthensis appears to be a common commensal. Helicobacter species are relatively rare in the paediatric colon.</p&gt

Corticosterone pattern-dependent glucocorticoid receptor binding and transcriptional regulation within the liver

Ultradian glucocorticoid rhythms are highly conserved across mammalian species, however, their functional significance is not yet fully understood. Here we demonstrate that pulsatile corticosterone replacement in adrenalectomised rats induces a dynamic pattern of glucocorticoid receptor (GR) binding at ~3,000 genomic sites in liver at the pulse peak, subsequently not found during the pulse nadir. In contrast, constant corticosterone replacement induced prolonged binding at the majority of these sites. Additionally, each pattern further induced markedly different transcriptional responses. During pulsatile treatment, intragenic occupancy by active RNA polymerase II exhibited pulsatile dynamics with transient changes in enrichment, either decreased or increased depending on the gene, which mostly returned to baseline during the inter-pulse interval. In contrast, constant corticosterone exposure induced prolonged effects on RNA polymerase II occupancy at the majority of gene targets, thus acting as a sustained regulatory signal for both transactivation and repression of glucocorticoid target genes. The nett effect of these differences were consequently seen in the liver transcriptome as RNA-seq analysis indicated that despite the same overall amount of corticosterone infused, twice the number of transcripts were regulated by constant corticosterone infusion, when compared to pulsatile. Target genes that were found to be differentially regulated in a pattern-dependent manner were enriched in functional pathways including carbohydrate, cholesterol, glucose and fat metabolism as well as inflammation, suggesting a functional role for dysregulated glucocorticoid rhythms in the development of metabolic dysfunction

Assessment of human resources management practices in Lebanese hospitals

© 2009 El-Jardali et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

A Model for Rigorously Applying the Exploration, Preparation, Implementation, Sustainment (EPIS) Framework in the Design and Measurement of a Large Scale Collaborative Multi-Site Study

Background This paper describes the means by which a United States National Institute on Drug Abuse (NIDA)-funded cooperative, Juvenile Justice-Translational Research on Interventions for Adolescents in the Legal System (JJ-TRIALS), utilized an established implementation science framework in conducting a multi-site, multi-research center implementation intervention initiative. The initiative aimed to bolster the ability of juvenile justice agencies to address unmet client needs related to substance use while enhancing inter-organizational relationships between juvenile justice and local behavioral health partners. Methods The EPIS (Exploration, Preparation, Implementation, Sustainment) framework was selected and utilized as the guiding model from inception through project completion; including the mapping of implementation strategies to EPIS stages, articulation of research questions, and selection, content, and timing of measurement protocols. Among other key developments, the project led to a reconceptualization of its governing implementation science framework into cyclical form as the EPIS Wheel. The EPIS Wheel is more consistent with rapid-cycle testing principles and permits researchers to track both progressive and recursive movement through EPIS. Moreover, because this randomized controlled trial was predicated on a bundled strategy method, JJ-TRIALS was designed to rigorously test progress through the EPIS stages as promoted by facilitation of data-driven decision making principles. The project extended EPIS by (1) elucidating the role and nature of recursive activity in promoting change (yielding the circular EPIS Wheel), (2) by expanding the applicability of the EPIS framework beyond a single evidence-based practice (EBP) to address varying process improvement efforts (representing varying EBPs), and (3) by disentangling outcome measures of progression through EPIS stages from the a priori established study timeline. Discussion The utilization of EPIS in JJ-TRIALS provides a model for practical and applied use of implementation frameworks in real-world settings that span outer service system and inner organizational contexts in improving care for vulnerable populations. Trial registration NCT02672150. Retrospectively registered on 22 January 2016

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

Improving Patients' Understanding of Terms and Phrases Commonly Used in Self‐Reported Measures of Sexual Function

There is a significant gap in research regarding the readability and comprehension of existing sexual function measures. Patient-reported outcome measures may use terms not well understood by respondents with low literacy