Association between TCF7L2 gene polymorphisms and susceptibility to Type 2 Diabetes Mellitus: a large Human Genome Epidemiology (HuGE) review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Transcription factor 7-like 2 (<it>TCF7L2</it>) has been shown to be associated with type 2 diabetes mellitus (T2MD) in multiple ethnic groups in the past two years, but, contradictory results were reported for Chinese and Pima Indian populations. The authors then performed a large meta-analysis of 36 studies examining the association of type 2 diabetes mellitus (T2DM) with polymorphisms in the <it>TCF7L2 </it>gene in various ethnicities, containing rs7903146 C-to-T (IVS3C>T), rs7901695 T-to-C (IVS3T>C), a rs12255372 G-to-T (IVS4G>T), and rs11196205 G-to-C (IVS4G>C) polymorphisms and to evaluate the size of gene effect and the possible genetic mode of action.</p> <p>Methods</p> <p>Literature-based searching was conducted to collect data and three methods, that is, fixed-effects, random-effects and Bayesian multivariate mete-analysis, were performed to pool the odds ratio (<it>OR</it>). Publication bias and study-between heterogeneity were also examined.</p> <p>Results</p> <p>The studies included 35,843 cases of T2DM and 39,123 controls, using mainly primary data. For T2DM and IVS3C>T polymorphism, the Bayesian <it>OR </it>for TT homozygotes and TC heterozygotes versus CC homozygote was 1.968 (95% credible interval (<it>CrI</it>): 1.790, 2.157), 1.406 (95% <it>CrI</it>: 1.341, 1.476), respectively, and the population attributable risk (PAR) for the TT/TC genotypes of this variant is 16.9% for overall. For T2DM and IVS4G>T polymorphism, TT homozygotes and TG heterozygotes versus GG homozygote was 1.885 (95%<it>CrI</it>: 1.698, 2.088), 1.360 (95% <it>CrI</it>: 1.291, 1.433), respectively. Four <it>OR</it>s among these two polymorphisms all yielded significant between-study heterogeneity (P < 0.05) and the main source of heterogeneity was ethnic differences. Data also showed significant associations between T2DM and the other two polymorphisms, but with low heterogeneity (<it>P </it>> 0.10). Pooled <it>OR</it>s fit a codominant, multiplicative genetic model for all the four polymorphisms of <it>TCF7L2 </it>gene, and this model was also confirmed in different ethnic populations when stratification of IVS3C>T and IVS4G>T polymorphisms except for Africans, where a dominant, additive genetic mode is suggested for IVS3C>T polymorphism.</p> <p>Conclusion</p> <p>This meta-analysis demonstrates that four variants of <it>TCF7L2 </it>gene are all associated with T2DM, and indicates a multiplicative genetic model for all the four polymorphisms, as well as suggests the <it>TCF7L2 </it>gene involved in near 1/5 of all T2MD. Potential gene-gene and gene-environmental interactions by which common variants in the <it>TCF7L2 </it>gene influence the risk of T2MD need further exploration.</p

A model for homeopathic remedy effects: low dose nanoparticles, allostatic cross-adaptation, and time-dependent sensitization in a complex adaptive system

BACKGROUND: This paper proposes a novel model for homeopathic remedy action on living systems. Research indicates that homeopathic remedies (a) contain measurable source and silica nanoparticles heterogeneously dispersed in colloidal solution; (b) act by modulating biological function of the allostatic stress response network (c) evoke biphasic actions on living systems via organism-dependent adaptive and endogenously amplified effects; (d) improve systemic resilience. DISCUSSION: The proposed active components of homeopathic remedies are nanoparticles of source substance in water-based colloidal solution, not bulk-form drugs. Nanoparticles have unique biological and physico-chemical properties, including increased catalytic reactivity, protein and DNA adsorption, bioavailability, dose-sparing, electromagnetic, and quantum effects different from bulk-form materials. Trituration and/or liquid succussions during classical remedy preparation create “top-down” nanostructures. Plants can biosynthesize remedy-templated silica nanostructures. Nanoparticles stimulate hormesis, a beneficial low-dose adaptive response. Homeopathic remedies prescribed in low doses spaced intermittently over time act as biological signals that stimulate the organism’s allostatic biological stress response network, evoking nonlinear modulatory, self-organizing change. Potential mechanisms include time-dependent sensitization (TDS), a type of adaptive plasticity/metaplasticity involving progressive amplification of host responses, which reverse direction and oscillate at physiological limits. To mobilize hormesis and TDS, the remedy must be appraised as a salient, but low level, novel threat, stressor, or homeostatic disruption for the whole organism. Silica nanoparticles adsorb remedy source and amplify effects. Properly-timed remedy dosing elicits disease-primed compensatory reversal in direction of maladaptive dynamics of the allostatic network, thus promoting resilience and recovery from disease. SUMMARY: Homeopathic remedies are proposed as source nanoparticles that mobilize hormesis and time-dependent sensitization via non-pharmacological effects on specific biological adaptive and amplification mechanisms. The nanoparticle nature of remedies would distinguish them from conventional bulk drugs in structure, morphology, and functional properties. Outcomes would depend upon the ability of the organism to respond to the remedy as a novel stressor or heterotypic biological threat, initiating reversals of cumulative, cross-adapted biological maladaptations underlying disease in the allostatic stress response network. Systemic resilience would improve. This model provides a foundation for theory-driven research on the role of nanomaterials in living systems, mechanisms of homeopathic remedy actions and translational uses in nanomedicine

Community health : health realities and the responsibilities of a university

A short review is presented of the service and academic commitments and activities of the Department of Community Health in the three divisions of the discipline ie Epidemiology and Biostatistics Health Administration Environmental Health The problems being experienced by the Department at present and the implications thereof, due to the absence of responsibility and service to an own community, environment and health service are discussed. Training without service is sterile and the student cannot relate his knowledge to personal experiences, observations and actual situations and problems. A review of existing and future health and training realities is given. The most important realities are summarised herewith: (a) The population of the RSA will by the year 2 000 be 50 million and by 202080 million. The RSA can only carry a population of 80 million. To reduce the growthrate, it is essential to restrict the number of children per woman to 2,1 and to improve the quality of life. (b) The ratio of elderly to youth will be 1:5 by the year 2000 and 1:2 by 2040 compared to 1: 10 at present. (c) Road accidents claimed 8 3751ifes during 1985 and the RSA has 16 times more deaths per 100 km travelled than the USA although the accidents per 100 km travelled are the same. (d) The old world diseases of Malaria, Bilharzia, Leprosy, Tuberculosis etc still plague the world and are in fact increasing: During 1985 11 322 malaria cases and 53 910 cases of Tuberculosis were notified in the RSA and there were 1 229 deaths due to measles during 1985. There are 12 million known cases of leprosy in the world. (e) In certain areas of the RSA 4% of children suffer from severe malnutrition and 22 - 25% are underweight for age. (f) In National States up to 50% of Medical Posts are vacant and para- 30 Digitised by the University of Pretoria, Library Services medical personnel are a luxury. Although the RSA has sufficient doctors for its population, there is a maldistribution of doctors. The reasons for this are discussed and include: Academic isolation of workers in rural areas; curricula are not directed at problems and needs of Africa; insufficient health and school facilities and deficient infrastructure in rural areas. (g) General Medical education and practical training programmes are to a large extent irrelevant to the problems and needs of Africa for both developed and developing communities. After completion of his/her studies, many students are not familiar wit!;, rural conditions and do not identify with the problems of the communities. Too little emphasis is placed on primary health care, appropriate technology and self-help to prepare student to practice rural medicine with confidence. These statements may equally apply to other Faculties. (h) Black secondary science teaching is in a crisis due to acute shortage of trained teachers. The result is a continued lowering of the matriculation standard and pass rates, insufficient inflow of suitable candidates to universities and therefore insufficient flow of teachers to schools. The responsibilities of the university of student training, research and service rendering are discussed with regard to the challenges presented by the health and training realities in Southern Africa ie create opportunities outside the campus for full-fledged, appropriate, real life training, research, service and experience; relevant education directed towards the needs of the whole community; balanced training/exposure of students in high technology and primary health care/appropriate technology, self-help etc; involvement with all community activities by rendering of service as part of training. As a solution the following is proposed: A massive service and training outreach programme by the whole university towards all population groups of the community, as part of the students' compulsory training and in co-operation with other universities and the private sector. Universities must accept that: Training involves service and responsibility to the Community.http://explore.up.ac.za/record=b129176

Analytical investigation of aerosol jet printing

Aerosol jet printing is a technology for contactless printing of narrow line shaped features down to a width of about 20 \u7fm. Until now, process optimization was only done empirically because there was no manageable model to describe it. The process was only modeled numerically regarding Stokes and Saffman force on the aerosol particles. In this article, we introduce a simple analytical model to predict the printed line width. Experimentally, we show that the model is a valid approach for a wide range of parameters. A close look on the quality of the printed lines reveals that depending on the process parameters the droplets are distributed more or less inhomogeneously within the printed lines. We attribute this to the Saffman force, which should be taken into account for a more accurate description, especially when only little sheath gas is applied. However, the printed line width generally agrees with our model, making our model a valuable tool for process control

Ethambutol in the treatment of patients with chronic pulmonary tuberculosis

SAMJ 45(6): 171-17