Informing patients of familial diabetes mellitus risk: How do they respond? A cross-sectional survey

<p>Abstract</p> <p>Background</p> <p>A strong family history of type 2 diabetes mellitus (DM) confers increased DM risk. This survey analysis determined whether patients who were informed by their doctors of familial DM risk acknowledged that risk and took steps to reduce it.</p> <p>Methods</p> <p>We conducted an analysis of the National <it>Health Styles 2004 </it>mail survey. All non-diabetic participants who responded to the question of whether their doctor had or had not informed them of their familial DM risk (<it>n </it>= 3,323) were compared for their risk-reducing behaviour and attitude to DM risk.</p> <p>Results</p> <p>Forty-one percent (<it>n </it>= 616) of the question responders that had DM family histories were informed by their doctors of their familial risk; the chance of being informed increased with the number of relatives that had the disease. Members of the informed group were more likely than those in the non-informed group to report lifestyle changes to prevent DM (odds ratio [OR] 4.3, 95% confidence interval [CI] 3.5–5.2) and being tested for DM (OR 2.9, 95% CI 2.4–3.6), although no significant improvement occurred in their U.S.-recommended exercise activity (OR 0.9, 95% CI 0.7–1.1). Overall, informed responders recognised both their familial and personal DM risk; most discussed diabetes with their family (69%), though less so with friends (42%); however, 44% of them still did not consider themselves to be at risk.</p> <p>Conclusion</p> <p>Responders who were informed by their doctors of being at familial DM risk reported greater incidences of lifestyle changes, DM screening, and awareness of risk than non-informed responders. Doctors were more likely to inform patients with stronger DM family histories. Identifying this higher risk group, either in isolation or in combination with other recognised risk factors, offers doctors the opportunity to target limited health promotion resources efficiently for primary DM prevention.</p

Femoroacetabular impingement: normal values of the quantitative morphometric parameters in asymptomatic hips.

OBJECTIVE: To determine the means and the reference intervals of the quantitative morphometric parameters of femoroacetabular impingement (FAI) in normal hips with high-resolution computed tomography (CT). METHODS: We prospectively included 94 adult individuals who underwent CT for thoracic, abdominal or urologic pathologies. Patients with a clinical history of hip pathology and/or with osteoarthritis on CT were excluded. We calculated means and 95 % reference intervals for imaging signs of cam-type (alpha angle at 90° and 45° and femoral head-neck offset) and pincer-type impingement (acetabular version angle, lateral centre-edge angle and acetabular index). RESULTS: The 95 % reference interval limits were all far beyond the abnormal thresholds found in the literature for cam-type and to a lesser extent for pincer-type FAI. The upper limits of the reference intervals for the alpha angles (at 90°/45°) were 68°/83° (men) and 69°/84° (women), compared to thresholds from the literature (50°, 55° or 60°). Reference intervals were similar between genders for cam-type parameters, and slightly differed for pincer-type. CONCLUSION: The 95 % reference intervals of morphometric measurements of FAI in asymptomatic hips were beyond the abnormal thresholds, which was especially true for cam-type FAI. Our results suggest the need for redefining the current morphometric parameters used in the diagnosis of FAI. KEY POINTS: ? 95 % reference intervals limits of FAI morphotype were beyond currently defined thresholds. ? Reference intervals of pincer-type morphotype measurements were close to current definitions. ? Reference intervals of cam-type morphotype measurements were far beyond the current definitions. ? Current morphometric definitions of cam-type morphotype should be used with care

Uncertainty analysis using Bayesian Model Averaging: a case study of input variables to energy models and inference to associated uncertainties of energy scenarios

Background Energy models are used to illustrate, calculate and evaluate energy futures under given assumptions. The results of energy models are energy scenarios representing uncertain energy futures. Methods The discussed approach for uncertainty quantification and evaluation is based on Bayesian Model Averaging for input variables to quantitative energy models. If the premise is accepted that the energy model results cannot be less uncertain than the input to energy models, the proposed approach provides a lower bound of associated uncertainty. The evaluation of model-based energy scenario uncertainty in terms of input variable uncertainty departing from a probabilistic assessment is discussed. Results The result is an explicit uncertainty quantification for input variables of energy models based on well-established measure and probability theory. The quantification of uncertainty helps assessing the predictive potential of energy scenarios used and allows an evaluation of possible consequences as promoted by energy scenarios in a highly uncertain economic, environmental, political and social target system. Conclusions If societal decisions are vested in computed model results, it is meaningful to accompany these with an uncertainty assessment. Bayesian Model Averaging (BMA) for input variables of energy models could add to the currently limited tools for uncertainty assessment of model-based energy scenarios

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Two randomised phase II trials of subcutaneous interleukin-2 and histamine dihydrochloride in patients with metastatic renal cell carcinoma

Histamine inhibits formation and release of phagocyte-derived reactive oxygen species, and thereby protects natural killer and T cells against oxidative damage. Thus, the addition of histamine may potentially improve the efficacy of interleukin-2 (IL-2). Two randomised phase II trials of IL-2 with or without histamine dihydrochloride (HDC) in patients with metastatic renal cell carcinoma (mRCC) were run in parallel. A total of 41 patients were included in Manchester, UK and 63 in Aarhus, Denmark. The self-administered, outpatient regimen included IL-2 as a fixed dose, 18 MIU s.c. once daily, 5 days per week for 3 weeks followed by 2 weeks rest. Histamine dihydrochloride was added twice daily, 1.0 mg s.c., concomitantly with IL-2. A maximum of four cycles were given. The Danish study showed a statistically significant 1-year survival benefit (76 vs 47%, P=0.03), a trend towards benefit in both median survival (18.3 vs 11.4 months, P=0.07), time to PD (4.5 vs 2.2 months, P=0.13) and clinical benefit (CR+PR+SD) (58 vs 37%, P=0.10) in favour of IL-2/HDC, whereas the UK study was negative for all end points. Only three patients had grade 4 toxicity; however, two were fatal. A randomised phase III trial is warranted to clarify the potential role of adding histamine to IL-2 in mRCC

Measuring subjective well-being from a multidimensional and temporal perspective: Italian adaptation of the I COPPE scale

Background: The objective of this study is to present the psychometric and cultural adaptation of the I COPPE scale to the Italian context. The original 21-item I COPPE was developed by Isaac Prilleltensky and colleagues to integrate a multidimensional and temporal perspective into the quantitative assessment of people’s subjective well-being. The scale comprises seven domains (Overall, Interpersonal, Community, Occupation, Psychological, Physical, and Economic well-being), which tap into past, present, and future self-appraisals of well-being. Methods: The Italian adapted version of the I COPPE scale underwent translation and backtranslation procedure. After a pilot study was conducted on a local sample of 683 university students, a national sample of 2432 Italian citizens responded to the final translated version of the I COPPE scale, 772 of whom re-completed the same survey after a period of four months. Respondents from both waves of the national sample were recruited partly through on-line social networks (i.e. Facebook, Twitter, and SurveyMonkey) and partly by university students who had been trained in Computer-Assisted Survey Information Collection. Results: Data were first screened for non-valid cases and tested for multivariate normality and missing data. The correlation matrix revealed highly significant correlation values, ranging from medium to high for nearly all congeneric variables of the I COPPE scale. Results from a series of nested and non-nested model comparisons supported the 7-factor correlated-traits model originally hypothesised, with factor loadings and inter-item reliability ranging from medium to high. In addition, they revealed that the I COPPE scale has strong internal reliability, with composite reliability always higher than .7, satisfactory construct validity, with average variance extracted nearly always higher than .5, and and full strict invariance across time. Conclusions: The Italian adaptation of the I COPPE scale presents appropriate psychometric properties in terms of both validity and reliability, and therefore can be applied to the Italian context. Some limitation and recommendations for future studies are discussed

Influence of ischemic core muscle fibers on surface depolarization potentials in superfused cardiac tissue preparations: a simulation study

Thin-walled cardiac tissue samples superfused with oxygenated solutions are widely used in experimental studies. However, due to decreased oxygen supply and insufficient wash out of waste products in the inner layers of such preparations, electrophysiological functions could be compromised. Although the cascade of events triggered by cutting off perfusion is well known, it remains unclear as to which degree electrophysiological function in viable surface layers is affected by pathological processes occurring in adjacent tissue. Using a 3D numerical bidomain model, we aim to quantify the impact of superfusion-induced heterogeneities occurring in the depth of the tissue on impulse propagation in superficial layers. Simulations demonstrated that both the pattern of activation as well as the distribution of extracellular potentials close to the surface remain essentially unchanged. This was true also for the electrophysiological properties of cells in the surface layer, where most relevant depolarization parameters varied by less than 5.5 %. The main observed effect on the surface was related to action potential duration that shortened noticeably by 53 % as hypoxia deteriorated. Despite the known limitations of such experimental methods, we conclude that superfusion is adequate for studying impulse propagation and depolarization whereas repolarization studies should consider the influence of pathological processes taking place at the core of tissue sample

Lactic Acidosis Triggers Starvation Response with Paradoxical Induction of TXNIP through MondoA

Although lactic acidosis is a prominent feature of solid tumors, we still have limited understanding of the mechanisms by which lactic acidosis influences metabolic phenotypes of cancer cells. We compared global transcriptional responses of breast cancer cells in response to three distinct tumor microenvironmental stresses: lactic acidosis, glucose deprivation, and hypoxia. We found that lactic acidosis and glucose deprivation trigger highly similar transcriptional responses, each inducing features of starvation response. In contrast to their comparable effects on gene expression, lactic acidosis and glucose deprivation have opposing effects on glucose uptake. This divergence of metabolic responses in the context of highly similar transcriptional responses allows the identification of a small subset of genes that are regulated in opposite directions by these two conditions. Among these selected genes, TXNIP and its paralogue ARRDC4 are both induced under lactic acidosis and repressed with glucose deprivation. This induction of TXNIP under lactic acidosis is caused by the activation of the glucose-sensing helix-loop-helix transcriptional complex MondoA:Mlx, which is usually triggered upon glucose exposure. Therefore, the upregulation of TXNIP significantly contributes to inhibition of tumor glycolytic phenotypes under lactic acidosis. Expression levels of TXNIP and ARRDC4 in human cancers are also highly correlated with predicted lactic acidosis pathway activities and associated with favorable clinical outcomes. Lactic acidosis triggers features of starvation response while activating the glucose-sensing MondoA-TXNIP pathways and contributing to the “anti-Warburg” metabolic effects and anti-tumor properties of cancer cells. These results stem from integrative analysis of transcriptome and metabolic response data under various tumor microenvironmental stresses and open new paths to explore how these stresses influence phenotypic and metabolic adaptations in human cancers