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.     

Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons

Mutations in superoxide dismutase-1 (SOD1) cause a form of the fatal paralytic disorder amyotrophic lateral sclerosis (ALS), presumably by a combination of cell-autonomous and non-cell-autonomous processes. Here, we show that expression of mutated human SOD1 in primary mouse spinal motor neurons does not provoke motor neuron degeneration. Conversely, rodent astrocytes expressing mutated SOD1 kill spinal primary and embryonic mouse stem cell-derived motor neurons. This is triggered by soluble toxic factor(s) through a Bax-dependent mechanism. However, mutant astrocytes do not cause the death of spinal GABAergic or dorsal root ganglion neurons or of embryonic stem cell-derived interneurons. In contrast to astrocytes, fibroblasts, microglia, cortical neurons and myocytes expressing mutated SOD1 do not cause overt neurotoxicity. These findings indicate that astrocytes may play a role in the specific degeneration of spinal motor neurons in ALS. Identification of the astrocyte-derived soluble factor(s) may have far-reaching implications for ALS from both a pathogenic and therapeutic standpoint.     

Polycyclotrimers of 1,4‐Diethynylbenzene, 2,6‐Diethynylnaphthalene,and 2,6‐Diethynylanthracene: Preparation and Gas Adsorption Properties

Hyperbranched partly cross‐linked polycyclotrimers of 1,4‐diethynylbenzene, 2,6‐diethynyl­naphthalene, and 2,6‐diethynylanthracene, Pc(1,4‐DEB), Pc(2,6‐DEN), and Pc(2,6‐DEA), respectively, are prepared using TaCl₅/Ph₄Sn catalyst. Brunauer–Emmett–Teller (BET) surface area, microporosity, and maximum sorption capacity for H₂ and CO₂ decrease in the order of decreasing relative content of branching points in polycyclotrimers Pc(1,4‐DEB) > Pc(2,6‐DEN) > Pc(2,6‐DEA), the highest values for Pc(1,4‐DEB) being S_BET = 1299 m² g^?1, a_H2 = 1.26 wt% (100 kPa, 77 K), and a_CO2 = 10.8 wt% (100 kPa, 273 K). N₂ isotherms show that adsorption/desorption hysteresis occurs already at low equilibrium pressures. CO₂ isotherms show that the time allotted to the measurement influences both the maximum adsorption capacity and the hysteresis upon desorption.

     

High‐Resolution Breakpoint Analysis Provides Evidence for the Sequence‐Directed Nature of Genome Rearrangements in Hereditary Disorders

Although most of the pertinent data on the sequence‐directed processes leading to genome rearrangements (GRs) have come from studies on somatic tissues, little is known about GRs in the germ line of patients with hereditary disorders. This study aims at identifying DNA motifs and higher order structures of genome architecture, which can result in losses and gains of genetic material in the germ line. We first identified candidate motifs by studying 112 pathogenic germ‐line GRs in hereditary colorectal cancer patients, and subsequently created an algorithm, termed recombination type ratio, which correctly predicts the propensity of rearrangements with respect to homologous versus nonhomologous recombination events.     

Long‐term follow‐up after endovascular treatment of hepatic venous outflow obstruction following liver transplantation

Hepatic venous outflow obstruction (HVOO) is a rare complication after liver transplantation (LT) associated with significant morbidity and reduced graft survival. Endovascular intervention has become the first‐line treatment for HVOO, but data on long‐term outcomes are lacking. We have analysed outcomes after endovascular intervention for HVOO in 905 consecutive patients who received 965 full‐size LT at our unit from January 2007 to June 2014. There were 27 (3%) patients who underwent hepatic venogram for suspected HVOO, with persistent ascites being the most common symptom triggering the investigation (n = 19, 70%). Of those, only 10 patients demonstrated either stricture or pressure gradient over 10 mmHg on venogram, which represents a 1% incidence of HVOO. The endovascular interventions were balloon dilatation (n = 3), hepatic vein stenting (n = 4) and stenting with dilatation (n = 3). Two patients required restenting due to stent migration. The symptoms of HVOO completely resolved in all but one patient, with a median follow‐up period of 74 (interquartile range 39–89) months. There were no procedure‐related complications or mortality. In conclusion, the incidence of HVOO in patients receiving full‐size LT is currently very low. Endovascular intervention is an effective and safe procedure providing symptom relief with long‐lasting primary patency.     

Effect of metformin therapy on cardiac function and survival in a volume-overload model of heart failure in rats

Advanced HF (heart failure) is associated with altered substrate metabolism. Whether modification of substrate use improves the course of HF remains unknown. The antihyperglycaemic drug MET (metformin) affects substrate metabolism, and its use might be associated with improved outcome in diabetic HF. The aim of the present study was to examine whether MET would improve cardiac function and survival also in non-diabetic HF. Volume-overload HF was induced in male Wistar rats by creating ACF (aortocaval fistula). Animals were randomized to placebo/MET (300 mg·kg(-1) of body weight·day(-1), 0.5% in food) groups and underwent assessment of metabolism, cardiovascular and mitochondrial functions (n=6-12/group) in advanced HF stage (week 21). A separate cohort served for survival analysis (n=10-90/group). The ACF group had marked cardiac hypertrophy, increased LVEDP (left ventricular end-diastolic pressure) and lung weight confirming decompensated HF, increased circulating NEFAs (non-esterified 'free' fatty acids), intra-abdominal fat depletion, lower glycogen synthesis in the skeletal muscle (diaphragm), lower myocardial triacylglycerol (triglyceride) content and attenuated myocardial (14)C-glucose and (14)C-palmitate oxidation, but preserved mitochondrial respiratory function, glucose tolerance and insulin sensitivity. MET therapy normalized serum NEFAs, decreased myocardial glucose oxidation, increased myocardial palmitate oxidation, but it had no effect on myocardial gene expression, AMPK (AMP-activated protein kinase) signalling, ATP level, mitochondrial respiration, cardiac morphology, function and long-term survival, despite reaching therapeutic serum levels (2.2±0.7 μg/ml). In conclusion, MET-induced enhancement of myocardial fatty acid oxidation had a neutral effect on cardiac function and survival. Recently reported cardioprotective effects of MET may not be universal to all forms of HF and may require AMPK activation or ATP depletion. No increase in mortality on MET supports its safe use in diabetic HF.