06. The Influence of MED12 Knockdown on Adipogenesis

The ubiquity of obesity has increased exponentially, and the health burden of obesity-related diseases including type 2 diabetes, metabolic disorders, heart diseases, and some types of cancers is growing. Obesity is characterized by the excess accumulation of fat and adipose tissue and driven by adipogenesis, which is the process in which stem cells differentiate into adipocytes. We utilize human adipose derived stem cells (hASCs) isolated from adult fat tissue to study adipogenesis (the formation of fat tissue). This physiological potential, combined with non-invasive collection methods, make hASCs favorable in the search for new clinical stem cell treatments and for the study of cellular processes and differentiation. We are interested in understanding the function of MED12 in adipogenesis and determining its role in initiating cell type specific gene expression in hopes that this research can be used in treatments for obesity and related metabolic disorders. MED12 is a subunit of the Mediator complex kinase module that is critical in regulating cell-type specific gene expression. We have determined a decrease in MED12 leads to a decrease in adipogenesis as shown by the decrease in staining of lipid vesicles and the decrease in expression of adipogenic factors, CEPBɑ2, SREBP1c, and PPARɣ. This supports that MED12 does indeed play an important role in adipogenesis. We will continue to examine at what point during adipogenesis MED12 is most critical so that MED12 may be used as a therapeutic target to control adipogenesis and treat obesity in the future

Why teach “Bioethics and Human Rights” to healthcare professions undergraduates?

This article highlights the importance of teaching “bioethics and human rights” to undergraduate students seeking health care degrees and illustrates how this topic fits well within these programs of studies. Historical, cultural, anthropological and practical reasons support teaching these topics as enrichment of medical training. The years after the Second World War showed how bioethics, human rights and medicine are closely intertwined. Moreover the relationship between human rights and bioethics has grown ever closer increasingly involving medicine and health care professionals. The authors observe that medical students have to face a cultural pluralism in bioethics and biolaw and we give students the opportunity to develop their critical thinking and logical argumentation abilities as well as their interest in academic research. Furthermore, the authors – who draw up briefly the experience of the Institute of Bioethics at the Faculty of Medicine and Surgery of the UCSC (Rome) - assert the necessity to help medical students to be respectful of patients in every clinical setting. It is therefore of utmost importance to train students to focus on the ethical dimension of care and to make good ethical decisions even in dilemmatic cases. To achieve this outcome, healthcare professionals should possess an integral vision of their work (technical and humanistic competence) and sharp skills to reflect in depth, avoiding superficiality and negligence. From this perspective, the teaching of “bioethics and human rights” could be very useful

Metacarpophalangeal Pattern Profile Analysis in Sotos Syndrome

The metacarpophalangeal pattern profile (MCPP) was analyzed on 16 Sotos syndrome patients. A mean Sotos syndrome profile was produced. Correlation studies confirm clinical homogeneity of Sotos syndrome individuals. Discriminant analysis of Sotos syndrome patients and normal individuals produces a function of two MCPP variables and age, which may provide a useful tool for diagnosis

Sex and Haplotype Associations with Adverse Effects of Calcineurin Inhibitors Post-Renal Transplant

BACKGROUND: P-glycoprotein (P-gp), an ABC transport protein contributes to the interpatient pharmacokinetic and pharmacodynamic variability of calcineurin inhibitors(CNI), tacrolimus(TAC) and cyclosporine (CYA). ABCB1 encodes P-gp and the single nucleotide polymorphisms (SNP) 1236C\u3eT, 2677G\u3eT/A, 3435C\u3eT may alter protein expression or function. Our objective was to examine the association of ABCB1 haplotypes, sex and race with chronic CNI adverse effects (AE) in renal transplant recipients (RTR). METHODS: A meta-analysis of 3 prospective observational studies was completed in 149 stable RTR [GFR= 51 ±17 ml/min/1.73m2] using identical inclusion and exclusion criteria in 62 African Americans (AA) and 81 Caucasians (C) treated with CYA (troughs: 50- 150 ng/ml) and mycophenolate mofetil or TAC (troughs: 5-10 ng/ml) and mycophenolate sodium. Each RTR had AE assessed using standardized objective scales by study physicians. A Cumulative AE ratio was determined using 14 AE. Separate gastrointestinal (GI), central nervous system (CNS), and aesthetic AE ratios were also assessed. DNA from peripheral blood mononuclear cells was collected to characterize ABCB1 SNPs completed on 11/15/12. Haplotype computation and association with AE was completed by THESIAS program on 12/3/12. RESULTS: All genotypes were in Hardy-Weinberg equilibria. AA had a greater frequency of the C-G-C haplotype (SNPs: 1236-2677-3435) compared to C (71.6% vs. 44.2%; p\u3c0.001). A gender difference was noted for Cumulative (p\u3c0.001); GI (p=0.046); aesthetic (p=0.0002) and CNS (p=0.051) AE ratios with greater AE ratios in females. The Aesthetic AE ratio was associated with haplotype T-T-C (p=0.008). Haplotype C-T-T was associated with increased GI AE ratio (p=0.02) though the effect was not significant when sex was included as a covariate (p=0.13). Race had no associations with AE. CONCLUSION: RTR receiving CNI based immunosuppression within the therapeutic range exhibited interpatient variability in AE with associations to sex and ABCB1 haplotypes.https://dune.une.edu/pharmsci_facpost/1001/thumbnail.jp

Stillbirth: Perceptions among hospital staff in the Middle East and the UK

Objectives Stillbirth is an important and yet relatively unacknowledged public health concern in many parts of the world. Public awareness of stillbirth and its potentially modifiable risk factors is a prerequisite to planning prevention measures. Cultural and regional differences may play an important role in awareness and attitudes to stillbirth prevention. The objective of this study was to evaluate and compare the awareness of stillbirth among hospital staff in Qatar and the UK, representing two culturally different regions. Study design An online population survey for anonymous completion was sent to the hospital email accounts of all grades of staff (clinical and non-clinical) at two hospitals in Qatar and one tertiary hospital Trust in the UK. The survey was used to gather information on the participants’ demographic background, the experience of stillbirth, knowledge of stillbirth, awareness of information and support sources, as well as attitude towards investigation and litigation. Data were analysed using descriptive and comparative statistics (Chi-Square test and Fisher’s exact test). Results 1002 respondents completed the survey, including 349 in the Qatar group and 653 in the UK group. There were significant differences in group demographics in terms of language, religion, gender, nationality and experience of stillbirth. The groups also differed significantly in the knowledge of stillbirth, its incidence and risk factors. The two groups took different views on apportioning blame on healthcare services in cases of stillbirth. The Qatar group showed significantly less awareness of available support organisations and relied significantly more on online sources of information for stillbirths (p < 0.001). Conclusions This comparative study demonstrated significant differences between the two culturally distinct regions in the awareness, knowledge and attitudes towards stillbirths. The complex cultural and other factors that may be contributory should be further studied. The results highlight the need for increasing public awareness around stillbirth as part of effective prevention strategies

Declining fitness and physical education lessons in UK adolescents

Objectives. The objective was to determine recent cross-sectional trends in health-related fitness (HRF) in secondary school students by studying the 13–14 years old age group repeatedly over 6 years, considering parallel national trends in physical education (PE). Methods. Height, weight, broad jump, grip strength, 20 m shuttle run and throwing and catching skills were measured by the same research team using standardised techniques from 2014 to 2019. Trends in these HRF measures were assessed by linear regression, adjusting for school, sex and height. Interactions with fitness and body mass index (BMI) were tested. The number of PE lessons reported in the UK Annual School Workforce Census between 2010 and 2019 for all state-funded secondary schools was analysed. Results. Grip strength (B=−0.60, 95% CI −0.78 to –0.41), broad jump (B=−1.16, 95% CI −1.99 to –0.34), 20 m shuttle run (B=−1.85, 95% CI −2.58 to –1.12) and throwing and catching skills (B=−0.12, 95% CI −0.15 to –0.08) declined significantly over the study period. There was a greater reduction in broad jump and grip strength in adolescents with low fitness and a greater reduction in fitness and motor competence in adolescents with normal BMI. These declines coincided with a 16% reduction nationally in secondary school PE between 2010 (333 800 hours) and 2019 (280 725 hours). Conclusion. Adolescent HRF has declined in recent years, in parallel with PE lessons. Declines were observed across all young people and particularly those of low fitness and normal BMI. To reach the majority of young people, policy makers could increase PE in schools to increase activity and prevent worsening fitness and health in future generations

Potential risk factors associated with human encephalitis: application of canonical correlation analysis

<p>Abstract</p> <p>Background</p> <p>Infection of the CNS is considered to be the major cause of encephalitis and more than 100 different pathogens have been recognized as causative agents. Despite being identified worldwide as an important public health concern, studies on encephalitis are very few and often focus on particular types (with respect to causative agents) of encephalitis (e.g. West Nile, Japanese, etc.). Moreover, a number of other infectious and non-infectious conditions present with similar symptoms, and distinguishing encephalitis from other disguising conditions continues to a challenging task.</p> <p>Methods</p> <p>We used canonical correlation analysis (CCA) to assess associations between set of exposure variable and set of symptom and diagnostic variables in human encephalitis. Data consists of 208 confirmed cases of encephalitis from a prospective multicenter study conducted in the United Kingdom. We used a covariance matrix based on Gini's measure of similarity and used permutation based approaches to test significance of canonical variates.</p> <p>Results</p> <p>Results show that weak pair-wise correlation exists between the risk factor (exposure and demographic) and symptom/laboratory variables. However, the first canonical variate from CCA revealed strong multivariate correlation (ρ = 0.71, se = 0.03, p = 0.013) between the two sets. We found a moderate correlation (ρ = 0.54, se = 0.02) between the variables in the second canonical variate, however, the value is not statistically significant (p = 0.68). Our results also show that a very small amount of the variation in the symptom sets is explained by the exposure variables. This indicates that host factors, rather than environmental factors might be important towards understanding the etiology of encephalitis and facilitate early diagnosis and treatment of encephalitis patients.</p> <p>Conclusions</p> <p>There is no standard laboratory diagnostic strategy for investigation of encephalitis and even experienced physicians are often uncertain about the cause, appropriate therapy and prognosis of encephalitis. Exploration of human encephalitis data using advanced multivariate statistical modelling approaches that can capture the inherent complexity in the data is, therefore, crucial in understanding the causes of human encephalitis. Moreover, application of multivariate exploratory techniques will generate clinically important hypotheses and offer useful insight into the number and nature of variables worthy of further consideration in a confirmatory statistical analysis.</p

Strange reading: Keith Windschuttle on race, Asia and White Australia

In his recently published book, The White Australia Policy, Keith Windschuttle accuses academic historians of errors of fact and judgement in their accounts of white Australia. This article examines these claims of exaggeration and distortion with particular reference to the nature and meaning of race, racism and representations of Asia in Australian history. The article rejects Winschuttle\u27s sweeping claim that academic historians have sought to make Australia appear a much more racist society than the historical record would suggest.<br /