Investigation of MC4 receptor polymorphisms and the effect of bariatric surgery on a selected group of South African obese patients

A) Bariatric surgery for the treatment of obesity has shown much promise. The Roux-en-Y gastric bypass is a procedure that combines both restrictive and malabsorptive elements. Post-operative weight loss and co-morbidity improvements previously achieved are over and above those which are seen during life style modification and drug therapy. 330 patients (2005-2007) with a mean BMI of 45.87 ± 0.63 were characterised pre-operatively with regard to clinical, anthropometric and DEXA scan measurements. 130 were matched for the same parameters post-operatively over a 9-12 month observation period. The data was analysed statistically using paired t-tests and regression analyses. Significant post-operative improvements were observed with regard to patients’ weight loss and co-morbidity improvement. Positive and significant correlations of anthropometric measures to biochemical parameters ensued. Risk factor scoring methodology produced an average total score of 17 points / 36. Average post-op weight loss at 9-12 months follow-up was 20% of initial pre-op weight. Co-morbid diseases and anthropometric measurements illustrated significant changes following surgery. Risk factor scoring is a valuable pre-op tool for assessing eligibility for medical aid re-imbursement for surgery. B) Obesity is a global epidemic and is increasing the worlds’ mortality rate. Genetic predisposition to obesity is recognized as being significant. Polymorphisms within the Melanocortin 4 Receptor (MC4R) gene, which encodes a G-protein coupled receptor responsible for post-prandial satiety signalling, have been associated with monogenic obesity. Obesity prevalence in South Africa is drastically increasing, however there has been no causative investigation done. Thus we sought to perform an initial assessment of the prevalence of MC4R polymorphisms within a South African representative group. Blood was drawn from a mixed Body Mass Index (BMI) cohort of 259 adult individuals and their DNA was extracted. The MC4R gene was PCR amplified from the DNA, the amplicon sequenced and the sequence data was analyzed for polymorphisms. A polymorphism prevalence of 13.51% was found within the patients across a BMI range that spanned from underweight (19.6) to super-obese (126.0). In addition to MC4R polymorphisms that had been identified previously, two new polymorphisms namely R7H and S36T were observed. Four haplotypes were also identified. MC4R mutation frequency was observed to be ethnically dependant; however the hypothesis of differing ethnic backgrounds illustrating varying mutational penetrance was not confirmed. The expected trend regarding MC4R polymorphism functional effect and associated pathogenicity was not followed in light of our results. The question of whether or not MC4R polymorphisms contribute to the development of obesity is indisputable; however the current accepted trend regarding their precise role may be incorrect and must be challenged.Dissertation (MSc)--University of Pretoria, 2009.Immunologyunrestricte

NONLINEAR ESTIMATION OF GROWTH CURVE MODELS FOR GERMINATION DATA ANALYSIS

Logistic, Gompertz, Richards and Weibull growth curves were evaluated for their suitability as mathematical and empirical models to represent cumulative germination. By avoiding the limitations associated with the method of moments and single-value germination indices, the fitted models provided superior description of the time course of germination. The four-parameter Weibull model gave the best fit across a relatively wide range of seed species and germination conditions, and the resulting parameter estimates reflected identifiable aspects of the germination process. The nonlinear estimation of the germination response included a parameter summary, together with their asymptotic standard errors and correlation matrix, along with an approximate band for the expectation function, pairwise plots of the parameter inference region, and profile t plots. Evaluation of the fitted models also included information on lack of fit and residual structure. Empirical results and hypothesis testing were demonstrated with reference to a replicated experiment designed to determine the effects of reduced water potential on germination of onion seeds

Uniform rotating field network structure to efficiently package a magnetic bubble domain memory

A unique and compact open coil rotating magnetic field network structure to efficiently package an array of bubble domain devices is disclosed. The field network has a configuration which effectively enables selected bubble domain devices from the array to be driven in a vertical magnetic field and in an independent and uniform horizontal rotating magnetic field. The field network is suitably adapted to minimize undesirable inductance effects, improve capabilities of heat dissipation, and facilitate repair or replacement of a bubble device

Nine years of comparative effectiveness research education and training: initiative supported by the PhRMA Foundation

The term comparative effectiveness research (CER) took center stage with passage of the American Recovery and Reinvestment Act (2009). The companion US$1.1 billion in funding prompted the launch of initiatives to train the scientific workforce capable of conducting and using CER. Passage of the Patient Protection and Affordable Care Act (2010) focused these initiatives on patients, coining the term ‘patient-centered outcomes research’ (PCOR). Educational and training initiatives were soon launched. This report describes the initiative of the Pharmaceutical Research and Manufacturers Association of America (PhRMA) Foundation. Through provision of grant funding to six academic Centers of Excellence, to spearheading and sponsoring three national conferences, the PhRMA Foundation has made significant contributions to creation of the scientific workforce that conducts and uses CER/PCOR

Lanthanoid Biphenolates as a Rich Source of Lanthanoid-Main Group Heterobimetallic Complexes

Several new trivalent dinuclear rare earth 2,2’-methylenebis(6-tert-butyl-4-methylphenolate) (mbmp²¯) complexes with the general form [Ln₂(mbmp)₃(thf)n] (Ln=Sm 1, Tb 2 (n=3), and Ho 3, Yb 4 (n=2), and a tetravalent cerium complex [Ce(mbmp)₂(thf)₂] (5) have been synthesised by RTP (redox transmetallation/protolysis) reactions from lanthanoid metals, Hg(C₆F₅)₂ and the biphenol mbmpH₂. These new complexes and some previously reported partially protonated rare earth biphenolate complexes [Ln(mbmp)(mbmpH)(thf)n] react with lithium, aluminium, potassium and zinc organometallic reagents to form lanthanoid-main group heterobimetallic species. When reaction mixtures containing the Ln biphenolate complexes were treated with n-butyllithium, both molecular ([Li(thf)₂Ln(mbmp)₂(thf)n] (Ln=La 6, Pr 7 (n=2) and Er 8, Yb 9, and Lu 10 (n=1)) and charge separated ([Li(thf)₄][Ln(mbmp)₂(thf)₂] (Ln=Y 11, Sm 12, Dy 13, and Ho 14) complexes were isolated. Treatment with trimethylaluminium also led to isolation of molecular ([AlMe₂Ln(mbmp)₂(thf)₂] (Ln=Pr 15, Sm 16, and Tb 17)) and ionic [La(mbmp)(thf)₅][AlMe₂(mbmp)] (18) complexes. One gadolinium-potassium ([K(thf)₃Gd(mbmp)₂(thf)₂] (19)), and one ytterbium-zinc species ([ZnEtYb(mbmp)₂(thf)] (20)) were isolated from treatment of reaction mixtures with potassium bis(trimethylsilyl)amide and diethylzinc respectively

Improved physical health in middle-older aged golf caddies following 24-weeks of high-volume physical activity

Background: The physical demands of golf caddying, including walking while carrying a golf bag, may potentially affect body composition, and markers of metabolic, cardiovascular, and musculoskeletal health. Therefore, this study examined the impact of 24 weeks of caddying on physical health in middle-older aged males. Methods: Eleven full-time experienced male caddies (age: 59 [8] y; caddying experience: 14 [12] y) were recruited from a local golf course. The following were assessed at preseason and after 24 weeks of caddying (March–September 2022): body composition, heart rate, blood pressure, blood lipids, and performance tests (static and dynamic balance, strength, and submaximal fitness). Physical activity (PA) levels were assessed at preseason and at the mid-point of the caddying season. Across the caddying season, participants completed a monthly average of 24.0 (3.8) rounds. Results: Following the caddying season, improvements in static balance (Δ = 13.5 s), dynamic balance (Δ = −1.8 s), and lower back absolute strength (Δ = 112.8 N), and muscle quality (Δ = 2.0 N·kg−1) were observed (all P < .05). Additionally, blood lipids, including total cholesterol (Δ = −0.6 mmol·L−1), high-density lipoprotein cholesterol (Δ = 0.1 mmol·L−1), low-density lipoprotein cholesterol (Δ = −0.6 mmol·L−1) (all P < .05), and body composition, including body mass (Δ = −2.7 kg), fat mass (Δ = −1.9 kg), fat percentage (Δ = −1.4%), fat-to-muscle ratio (Δ = −0.03), and body mass index (Δ = −0.9 kg·m−2) (all P < .05) improved. Caddying did not offer beneficial changes to cardiovascular variables or cardiorespiratory fitness (P > .05), while coronary heart disease risk score decreased (Δ = −3.3%) (P < .05). In relation to PA, light- (Δ = 145 min) and moderate-intensity (Δ = 71 min) PA, moderate to vigorous PA (Δ = 73 min), and total PA (Δ = 218 min) between preseason and the mid-point of the caddying season increased, while sedentary time (Δ = −172 min) decreased (all P < .05). Conclusion: Golf caddying can provide several physical health benefits such as improvements in various markers of cardiometabolic health, lower back absolute strength, and static and dynamic balance. The physical health improvements that caddying offers is likely contributed to by increased PA volume and intensity through walking on the golf course. Therefore, caddying may represent a feasible model for increasing PA volume and intensity and achieve physical health–related benefits

Cheminformatics Research at the Unilever Centre for Molecular Science Informatics Cambridge.

The Centre for Molecular Informatics, formerly Unilever Centre for Molecular Science Informatics (UCMSI), at the University of Cambridge is a world-leading driving force in the field of cheminformatics. Since its opening in 2000 more than 300 scientific articles have fundamentally changed the field of molecular informatics. The Centre has been a key player in promoting open chemical data and semantic access. Though mainly focussing on basic research, close collaborations with industrial partners ensured real world feedback and access to high quality molecular data. A variety of tools and standard protocols have been developed and are ubiquitous in the daily practice of cheminformatics. Here, we present a retrospective of cheminformatics research performed at the UCMSI, thereby highlighting historical and recent trends in the field as well as indicating future directions.J. E. F thanks the Medical Research Council for funding (Grant Number MR/K020919/1). Furthermore, the UCMSI acknowledges all funding sources for continuous support over the past 15 years.This is the final published version. It first appeared at http://onlinelibrary.wiley.com/doi/10.1002/minf.201400166/abstract