Influence of leptin on arterial distensibility - A novel link between obesity and cardiovascular disease?

Background-The mechanisms by which obesity increases the risk of atherosclerotic cardiovascular disease (CVD) are poorly understood. In experimental models, leptin, a hormone produced by adipose tissue, has been shown adversely to affect vascular health. Therefore, we tested the hypothesis that high leptin concentrations are associated with lower arterial distensibility, an index of circulatory function relevant to the atherosclerotic process.Methods and Results-Noninvasive, high-resolution, vascular ultrasound was used to measure brachial artery distensibility in 294 healthy adolescents (aged 13 to 16 years) who had a broad range of body mass indexes. Fat mass was measured by bioelectric impedance analysis; fasting serum leptin concentration by radioimmunoassay; and lipid profile, fasting insulin, glucose, and C-reactive protein concentrations by standard laboratory techniques. Higher leptin concentrations were associated with impaired arterial distensibility (regression coefficient, -1.3% change in arterial distension per 10% increase in leptin; 95% CI, -1.9% to -0.8%; P<0.001). This association was independent of fat mass, blood pressure, and C-reactive protein, fasting insulin, or LDL cholesterol concentrations.Conclusions-Elevation in leptin was associated with impaired vascular function, independent of the metabolic and inflammatory disturbances associated with obesity. Our observations are consistent with data from experimental models and suggest that high leptin concentration is an important mechanism for the adverse influence of body fatness on CVD

Journey of Trail From Bench to Bedside and Its Potential Role in Immuno-Oncology

Induction of apoptosis in cancer cells has increasingly been the focus of many therapeutic approaches in oncology field. Since its identification as a TNF family member, TRAIL (TNF-related apoptosis-inducing ligand) paved a new path in apoptosis inducing cancer therapies. Its selective ability to activate extrinsic and intrinsic cell death pathways in cancer cells only, independently from p53 mutations responsible for conventional therapeutics resistance, spotted TRAIL as a potent cancer apoptotic agent. Many recombinant preparations of TRAIL and death receptor targeting monoclonal antibodies have been developed and being tested pre-clinically and clinically both as a single agent and in combinations. Of note, the monoclonal antibodies were not the only type of antibodies developed to target TRAIL receptors. Recent technology has brought forth several single chain variable domains (scFv) designs fused recombinantly to TRAIL as well. Also, it is becoming progressively more understandable that field of nanotechnology has revolutionized cancer diagnosis and therapy. The recent breakthroughs in materials science and protein engineering have helped considerably in strategically loading drugs into nanoparticles or conjugating drugs to their surface. In this review we aim to comprehensively highlight the molecular knowledge of TRAIL in the context of its pathway, receptors and resistance factors. We also aim to review the clinical trials that have been done using TRAIL based therapies and to review various scFv designs, the arsenal of nano-carriers and molecules available to selectively target tumor cells with TRAIL

Serum Lipid Profile and Retinol in Rats Fed Micronutrient Rich Edible Vegetable Oil Blend

Khan HN, Farooqi H, Ali S, Khan JS. 2010. Serum lipid profile and retinol in rats fed micronutrient rich edible vegetable oilblend. Nusantara Bioscience 2: 109-116. The animal rats were given 10% oil mixed in fat free diet for one month or six months. In theexperiment, the groups of rats were fed with the micronutrient (MN) rich blends mixed previously with 1% cholesterol, and their effectswere tested on serum lipid profile. Most significant changes in the High Dencity Lipoprotein (HDL) cholesterol were observed in onemonthstudy where HDL increased from 24 mg/dl in group to 64 mg/dl in the Mustard palm olein oil blend (MP); in mustard oil (MO)alone fed rats, the HDL was 36 mg/dl. Serum retinol was analyzed as one of the important MN in rats receiving the diet mixed with theblend for various duration of time. The results assume great significance as MO or palm olein oil (PO) alone could not bring themaximum beneficial effects, and the blends appear to have more merit as health oils in alleviating adverse health condition such ascoronary heart disease (CHD), diabetes, obesity and hypertension

Changing pattern of antimicrobial susceptibility of organisms causing community acquired urinary tract infections

Objective: To assess common organisms causing Urinary Treat Infection (UTI) in this community and to see antimicrobial susceptibility pattern of these isolates. Design: Prospective study on urine samples. Setting: Tertiary care hospital in Karachi.Methods: Over a period of 8 years (1990-97) 9,892 urine samples grew significant bacteriuria for various organisms. All Gram negative rods and entercocci was identified by using API 20E and API 32 strips respectively. Staphylococci were identified by catalase, coagulase and D\u27Nase tests. Antimicrobial sensitivity testing of all isolates was performed on Diagnostic Sensitivity Test plates by Kerby Bauer method. The discs used were ampicillin, trimethoprim-sulfamethoxazole, cefotaxime, ceftriaxone, aztreonam, ofloxacin, carbenicillin, amikacin, gentamicin, penicillin, clindamycin, methicillin, vancomycin, ceftazidime, cefuroxime, Nalidixic acid, pipemedic acid and Nitrofurantoin. Results: Our results indicate that E. coli and Klebsiella aerogenes are the most common organisms causing UTI in this community. Other organisms involved are Pseudomonas aeroginosa, Enterobacter species, Enterococcus, Proteus mirabillus, Staphylococcus aureus and Staphylococcus saprophyticus. Organisms resistant to various antimicrobial agents such as gentamicin, Amikacin, Ofloxacin, Cefotaxime and Ceftazidime are increasing. Conclusion: In conclusion, E. coli and Klebsiella aerogenes are the most common organisms causing UTI in this community. Pattern of antibiotic susceptibility to first line antibiotics is changing. Antimicrobial susceptibility testing of all isolates is crucial for the treatment of UTI

Real Activities Manipulation by Bidders Prior to Mergers and Acquisitions

This study examines the ability of investors to process signs of real activities manipulations at bidder firms in the quarters leading to the announcement of a merger. It further provides a supplementary explanation for the post-merger underperformance puzzle. Examining a sample of cash-only, stock-swap, and mixed mergers completed between 1980 and 2011, we find that bidder firms increase the use of real activities manipulation in the quarters leading up to the merger announcements. Using the average abnormal stock return method, we show that the short-term positive effect of real activities manipulation on share prices is stronger than accrual based earnings management. While bidders are able to escape investors’ scrutiny in the short run, it is not the case in the long run. We find that bidders’ long run stock performance―measured by matched buy-and-hold stock returns―is inversely related to their pre-announcement level of earnings management. We contribute to the literature on earnings management by considering how real activities manipulations affect stock prices in mergers and acquisitions

Management of chronic cardiometabolic conditions and mental health during COVID-19

A novel coronavirus disease (COVID-19) originated in Wuhan, China December 2019 and quickly became a global pandemic. The elderly and those with underlying health conditions may show more severe manifestations and poorer outcomes associated with COVID-19. The most prevalent underlying diseases in patients hospitalised with COVID-19 include hypertension, cardiovascular disease, diabetes mellitus, and chronic obstructive pulmonary disease [1]. Comorbidities are often also associated with depression, which can worsen outcomes [2]. Early detection is vital, and it is important that those with underlying health conditions have access to appropriate health care support at home, particularly in light of the concerns of the impact of social isolation relating to the COVID-19 pandemic on mental health and well-being

Impact of the 2016 American College of Surgeons Guideline Revision on Overlapping Lumbar Fusion Cases at a Large Academic Medical Center

OBJECTIVE: The American College of Surgeons (ACS) u pdated its guidelines on overlapping surgery in 2016. The objective was to examine differences in postoperative outcomes after overlapping surgery either pre-ACS guide-line revision or post-guideline revision, in a coarsened exact matching sample. -METHODS: A total of 3327 consecutive adult patients u ndergoing single-level posterior lumbar fusion from 2013 to 2019 were retrospectively analyzed. Patients were separated into a pre-ACS guideline revision cohort (surgery before April 2016) or a post-guideline revision cohort (surgery after October 2016) for comparison. The primary outcomes were proportion of cases performed with any degree of overlap, and adverse events including 30-day and 90-day rates of readmission, reoperation, emergency department visit, morbidity, and mortality. Subsequently, coarsened exact matching was used among overlapping surgery patients only to assess the impact of the ACS guideline revision on overlapping outcomes, and control-ling for attending surgeon and key patient characteristics known to affect surgical outcomes. -RESULTS: After the implementation of the ACS guide-lines, fewer cases were performed with overlap (22.0% vs. 53.7%; P \u3c 0.001). Patients in the post-ACS guideline revi-sion cohort experienced improved rates of readmission and reoperation within 30 and 90 days. However, when limited to overlapping cases only, no differences were observed in overlap outcomes pre-ACS versus post-ACS guideline revision. Similarly, when exact matched on risk-associated patient characteristics and attending surgeon, overlapping surgery patients pre-ACS and post-ACS guideline revision experienced similar rates of 30-day and 90-day outcomes. -CONCLUSIONS: After the ACS guideline revision, no discernable impact was observed on postoperative out-comes after lumbar fusion performed with overlap