Dysglycemia and Abnormal Adiposity Drivers of Cardiometabolic-Based Chronic Disease in the Czech Population: Biological, Behavioral, and Cultural/Social Determinants of Health

In contrast to the decreasing burden related to cardiovascular disease (CVD), the burden related to dysglycemia and adiposity complications is increasing in Czechia, and local drivers must be identified. A comprehensive literature review was performed to evaluate biological, behavioral, and environmental drivers of dysglycemia and abnormal adiposity in Czechia. Additionally, the structure of the Czech healthcare system was described. The prevalence of obesity in men and diabetes in both sexes has been increasing over the past 30 years. Possible reasons include the Eastern European eating pattern, high prevalence of physical inactivity and health illiteracy, education, and income-related health inequalities. Despite the advanced healthcare system based on the compulsory insurance model with free-for-service healthcare and a wide range of health-promoting initiatives, more effective strategies to tackle the adiposity/dysglycemia are needed. In conclusion, the disease burden related to dysglycemia and adiposity in Czechia remains high but is not translated into greater CVD. This discordant relationship likely depends more on other factors, such as improvements in dyslipidemia and hypertension control. A reconceptualization of abnormal adiposity and dysglycemia into a more actionable cardiometabolic-based chronic disease model is needed to improve the approach to these conditions. This review can serve as a platform to investigate causal mechanisms and secure effective management of cardiometabolic-based chronic disease

The insect-focused classification of fruit syndromes in tropical rainforests: an inter-continental comparison

We propose a new classification of rainforest plants into eight fruit syndromes, based on fruit morphology and other traits relevant to fruit-feeding insects. This classification is compared with other systems based on plant morphology or traits relevant to vertebrate fruit dispersers. Our syndromes are based on fruits sampled from 1,192 plant species at three Forest Global Earth Observatory plots: Barro Colorado Island (Panama), Khao Chong (Thailand) and Wanang (Papua New Guinea). The three plots differed widely in fruit syndrome composition. Plant species with fleshy, indehiscent fruits containing multiple seeds were important at all three sites. However, in Panama a high proportion of species had dry fruits, while in New Guinea and Thailand, species with fleshy drupes and thin mesocarps were dominant. Species with dry, winged seeds that do not develop as capsules were important in Thailand, reflecting the local importance of Dipterocarpaceae. These differences can also determine differences among frugivorous insect communities. Fruit syndromes and colours were phylogenetically flexible traits at the scale studied, as only three of the eight seed syndromes, and one of the 10 colours, showed significant phylogenetic clustering at either genus or family levels. Plant phylogeny was, however, the most important factor explaining differences in overall fruit syndrome composition among individual plant families or genera across the three study sites

Recruitment of rare 3-grams at functional sites: Is this a mechanism for increasing enzyme specificity?

<p>Abstract</p> <p>Background</p> <p>A wealth of unannotated and functionally unknown protein sequences has accumulated in recent years with rapid progresses in sequence genomics, giving rise to ever increasing demands for developing methods to efficiently assess functional sites. Sequence and structure conservations have traditionally been the major criteria adopted in various algorithms to identify functional sites. Here, we focus on the distributions of the 20³different types of <it>3</it>-grams (or triplets of sequentially contiguous amino acid) in the entire space of sequences accumulated to date in the UniProt database, and focus in particular on the rare <it>3</it>-grams distinguished by their high entropy-based information content.</p> <p>Results</p> <p>Comparison of the UniProt distributions with those observed near/at the active sites on a non-redundant dataset of 59 enzyme/ligand complexes shows that the active sites preferentially recruit <it>3</it>-grams distinguished by their low frequency in the UniProt. Three cases, Src kinase, hemoglobin, and tyrosyl-tRNA synthetase, are discussed in details to illustrate the biological significance of the results.</p> <p>Conclusion</p> <p>The results suggest that recruitment of rare <it>3</it>-grams may be an efficient mechanism for increasing specificity at functional sites. Rareness/scarcity emerges as a feature that may assist in identifying key sites for proteins function, providing information complementary to that derived from sequence alignments. In addition it provides us (for the first time) with a means of identifying potentially functional sites from sequence information alone, when sequence conservation properties are not available.</p

The oral HDAC inhibitor pracinostat (SB939) is efficacious and synergistic with the JAK2 inhibitor pacritinib (SB1518) in preclinical models of AML

Acute myeloid leukemia (AML) is currently treated with aggressive chemotherapy that is not well tolerated in many elderly patients, hence the unmet medical need for effective therapies with less toxicity and better tolerability. Inhibitors of FMS-like tyrosine kinase 3 (FLT3), JAK2 and histone deacetylase inhibitors (HDACi) have been tested in clinical studies, but showed only moderate single-agent activity. High efficacy of the HDACi pracinostat treating AML and synergy with the JAK2/FLT3 inhibitor pacritinib is demonstrated. Both compounds inhibit JAK-signal transducer and activator of transcription (STAT) signaling in AML cells with JAK2V617F mutations, but also diminish FLT3 signaling, particularly in FLT3-ITD (internal tandem duplication) cell lines. In vitro, this combination led to decreased cell proliferation and increased apoptosis. The synergy translated in vivo in two different AML models, the SET-2 megakaryoblastic AML mouse model carrying a JAK2V617F mutation, and the MOLM-13 model of FLT3-ITD-driven AML. Pracinostat and pacritinib in combination showed synergy on tumor growth, reduction of metastases and synergistically decreased JAK2 or FLT signaling, depending on the cellular context. In addition, several plasma cytokines/growth factors/chemokines triggered by the tumor growth were normalized, providing a rationale for combination therapy with an HDACi and a JAK2/FLT3 inhibitor for the treatment of AML patients, particularly those with FLT3 or JAK2 mutations

Compromise or Capitulation? US Food and Drug Administration Jurisdiction Over Tobacco Products

Stanton Glantz and colleagues critique the recent policy decision in the United States to grant the FDA regulatory authority over tobacco products, a decision that has broad but not unanimous support among health care professionals

Assessing risk of breast cancer in an ethnically South-East Asia population (results of a multiple ethnic groups study)

10.1186/1471-2407-12-529BMC Cancer12-BCMA

Racial differences in smoking abstinence rates in a multicenter, randomized, open-label trial in the United States

Background: This study evaluates differences in smoking abstinence between white and minority smokers using pharmaceutical aids. Methods: This is an analysis of data from a multi-center, randomized, clinical trial conducted in the United States. Of the 1,684 subjects randomized to one of three medications (nicotine inhaler, bupropion, or a combination of both), 60% were women and 10% were minority races. Results: Factors associated with a decreased likelihood of smoking at 12 weeks were older age (OR = 0.971, p\u3c 0.0001), being married (OR = 0.678, p= 0.0029), using bupropion SR (OR = 0.480, p∈\u3c∈0.0001), and using combination therapy (OR = 0.328, p∈\u3c∈0.0001). Factors associated with an increased likelihood of smoking were higher tobacco dependence scores (OR = 1.244, p \u3c 0.0001), prior quit attempts (OR = 1.812, p=0.004), and being a minority (OR = 1.849, p=0.0083). Compared to white smokers, minority smokers were significantly older at time of study entry (46 vs. 42 years, p\u3c 0.0001), less likely to be married (35% vs. 59%, p\u3c 0.0001), older at smoking initiation (21 vs. 19 years of age, p\u3c 0.0001), and had a lower abstinence rate (16% vs. 26%, p=0.0065). Conclusion: Regardless of the treatment used, minority smokers in the US have lower smoking abstinence after treatment for tobacco dependence. Future research should focus on the improvement in treatment strategies for minority smokers