Experiments on the synthesis of coumaryl styrenes

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Nuclear oxidation in flavones and related compounds. Part XLV. A synthesis of carajuridin chloride and carajurin

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Phosphoprotein Associated with Glycosphingolipid-Enriched Microdomains Differentially Modulates Src Kinase Activity in Brain Maturation

Src family kinases (SFK) control multiple processes during brain development and function. We show here that the phosphoprotein associated with glycosphigolipid-enriched microdomains (PAG)/Csk binding protein (Cbp) modulates SFK activity in the brain. The timing and localization of PAG expression overlap with Fyn and Src, both of which we find associated to PAG. We demonstrate in newborn (P1) mice that PAG negatively regulates Src family kinases (SFK). P1 Pag1-/- mouse brains show decreased recruitment of Csk into lipid rafts, reduced phosphorylation of the inhibitory tyrosines within SFKs, and an increase in SFK activity of >/ = 50%. While in brain of P1 mice, PAG and Csk are highly and ubiquitously expressed, little Csk is found in adult brain suggesting altered modes of SFK regulation. In adult brain Pag1-deficiency has no effect upon Csk-distribution or inhibitory tyrosine phosphorylation, but kinase activity is now reduced (−20–30%), pointing to the development of a compensatory mechanism that may involve PSD93. The distribution of the Csk-homologous kinase CHK is not altered. Importantly, since the activities of Fyn and Src are decreased in adult Pag1-/- mice, thus presenting the reversed phenotype of P1, this provides the first in vivo evidence for a Csk-independent positive regulatory function for PAG in the brain

Risk factors for myocardial infarction among low socioeconomic status South Indian population

<p>Abstract</p> <p>Background</p> <p>As longevity increases, cases of myocardial infarction (MI) are likely to be more. Cardiovascular disease (CVD) is a major global health problem reaching epidemic proportions in the Indian subcontinent, also among low socio-economic status (SES) and thin individuals.</p> <p>Objectives</p> <p>The present study was undertaken to elicit risk factors for MI among low SES Southern Indians and to find out its association with body mass index (BMI).</p> <p>Materials and methods</p> <p>A case-control study of patients with MI matched against healthy control subjects was carried out in a tertiary care teaching hospital. Standard methods were followed to elicit risk factors and BMI. Chi-square and Fishers exact test for categorical versus categorical, to show relationship with risk factors were analyzed.</p> <p>Results</p> <p>A total of 949 patients (male (M) = 692 and post menopausal female (F) = 257) and 611 age and sex matched healthy controls were included. In our study, BMI was below 23 in 48.2% of patients and below 21 in 22.5%. The risk of developing MI was significantly more in males (odds ratio (OR) = 3.3, 95% confidence interval (C.I.) = 2.69-4.13), among females with post-menopausal duration (PMD) of more than or equal to 3 years (OR = 9.27, 95% C.I. = 6.36-13.50) and in those with BMI less than 23 with one or other risk factors (P = 0.002, OR = 1.38, 95% C.I. = 1.13-1.70).</p> <p>Conclusion</p> <p>BMI cannot be considered as a lone independent risk factor, as the study population had low BMI but had one or more modifiable risk factors. It would be advisable to keep BMI at least 21 kg/m²for screening program. Health education on life style modification and programs to diagnose and control diabetes and hypertension have to be initiated at community level in order to reduce the occurrence.</p

Dimerization of Receptor Protein-Tyrosine Phosphatase alpha in living cells

BACKGROUND: Dimerization is an important regulatory mechanism of single membrane-spanning receptors. For instance, activation of receptor protein-tyrosine kinases (RPTKs) involves dimerization. Structural, functional and biochemical studies suggested that the enzymatic counterparts of RPTKs, the receptor protein-tyrosine phosphatases (RPTPs), are inhibited by dimerization, but whether RPTPs actually dimerize in living cells remained to be determined. RESULTS: In order to assess RPTP dimerization, we have assayed Fluorescence Resonance Energy Transfer (FRET) between chimeric proteins of cyan- and yellow-emitting derivatives of green fluorescent protein, fused to RPTPα, using three different techniques: dual wavelength excitation, spectral imaging and fluorescence lifetime imaging. All three techniques suggested that FRET occurred between RPTPα -CFP and -YFP fusion proteins, and thus that RPTPα dimerized in living cells. RPTPα dimerization was constitutive, extensive and specific. RPTPα dimerization was consistent with cross-linking experiments, using a non-cell-permeable chemical cross-linker. Using a panel of deletion mutants, we found that the transmembrane domain was required and sufficient for dimerization. CONCLUSIONS: We demonstrate here that RPTPα dimerized constitutively in living cells, which may be mediated by the transmembrane domain, providing strong support for the model that dimerization is involved in regulation of RPTPs

Globalisation from Above? Corporate Social Responsibility, the Workers' Party and the Origins of the World Social Forum

In its assessment of the origins and early development of the World Social Forum this article challenges traditional understandings of the Forum as representing ‘globalisation from below’. By tracing the intricate relations among elements of business, civil society, and the Workers’ Party in the first years of the Forum, this article reveals the major role played by a corporate movement stemming from the Brazilian democratisation process in the 1980s, and how this combined with the transformed agenda of the Workers’ Party as it gained higher political offices to constrain the Forum’s activities from the outset. In so doing, this article challenges not only widespread conceptions of the Forum as a counter‐hegemonic alternative but also current critiques concerning its subsequent limitations. Furthermore, it reveals how traditional understandings of the World Social Forum and of global civil society are underpinned by flawed assumptions which typecast political activities in the global ‘South’

A role for pharmacists in community-based post-discharge warfarin management: protocol for the 'the role of community pharmacy in post hospital management of patients initiated on warfarin' study

<p>Abstract</p> <p>Background</p> <p>Shorter periods of hospitalisation and increasing warfarin use have placed stress on community-based healthcare services to care for patients taking warfarin after hospital discharge, a high-risk period for these patients. A previous randomised controlled trial demonstrated that a post-discharge service of 4 home visits and point-of-care (POC) International Normalised Ratio (INR) testing by a trained pharmacist improved patients' outcomes. The current study aims to modify this previously trialled service model to implement and then evaluate a sustainable program to enable the smooth transition of patients taking warfarin from the hospital to community setting.</p> <p>Methods/Design</p> <p>The service will be trialled in 8 sites across 3 Australian states using a prospective, controlled cohort study design. Patients discharged from hospital taking warfarin will receive 2 or 3 home visits by a trained 'home medicines review (HMR)-accredited' pharmacist in their 8 to 10 days after hospital discharge. Visits will involve a HMR, comprehensive warfarin education, and POC INR monitoring in collaboration with patients' general practitioners (GPs) and community pharmacists. Patient outcomes will be compared to those in a control, or 'usual care', group. The primary outcome measure will be the proportion of patients experiencing a major bleeding event in the 90 days after discharge. Secondary outcome measures will include combined major bleeding and thromboembolic events, death, cessation of warfarin therapy, INR control at 8 days post-discharge and unplanned hospital readmissions from any cause. Stakeholder satisfaction will be assessed using structured postal questionnaire mailed to patients, GPs, community pharmacists and accredited pharmacists at the completion of their study involvement.</p> <p>Discussion</p> <p>This study design incorporates several aspects of prior interventions that have been demonstrated to improve warfarin management, including POC INR testing, warfarin education and home visits by trained pharmacists. It faces several potential challenges, including the tight timeframe for patient follow-up in the post-discharge period. Its strengths lie in a strong multidisciplinary team and the utilisation of existing healthcare frameworks. It is hoped that this study will provide the evidence to support the national roll-out of the program as a new Australian professional community pharmacy service.</p> <p>Trial Registration</p> <p>Australian New Zealand Clinical Trials Registry Number <a href="http://www.anzctr.org.au/trial_view.aspx?ID=82959">12608000334303</a>.</p

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P &lt; 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P &lt; 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk