Body composition and body fat distribution are related to cardiac autonomic control in non-alcoholic fatty liver disease patients

BACKGROUND/OBJECTIVES: Heart rate recovery (HRR), a cardiac autonomic control marker, was shown to be related to body composition (BC), yet this was not tested in non-alcoholic fatty liver disease (NAFLD) patients. The aim of this study was to determine if, and to what extent, markers of BC and body fat (BF) distribution are related to cardiac autonomic control in NAFLD patients. SUBJECTS/METHODS: BC was assessed with dual-energy X-ray absorptiometry in 28 NAFLD patients (19 men, 51±13 years, and 9 women, 47±13 years). BF depots ratios were calculated to assess BF distribution. Subjects’ HRR was recorded 1 (HRR1) and 2 min (HRR2) immediately after a maximum graded exercise test. RESULTS: BC and BF distribution were related to HRR; particularly weight, trunk BF and trunk BF-to-appendicular BF ratio showed a negative relation with HRR1 (r 1⁄4 0.613, r 1⁄4 0.597 and r 1⁄4 0.547, respectively, Po0.01) and HRR2 (r 1⁄4 0.484, r 1⁄4 0.446, Po0.05, and r 1⁄4 0.590, Po0.01, respectively). Age seems to be related to both HRR1 and HRR2 except when controlled for BF distribution. The preferred model in multiple regression should include trunk BF-to-appendicular BF ratio and BF to predict HRR1 (r2 1⁄4 0.549; Po0.05), and trunk BF-to-appendicular BF ratio alone to predict HRR2 (r2 1⁄4 0.430; Po0.001). CONCLUSIONS: BC and BF distribution were related to HRR in NAFLD patients. Trunk BF-to-appendicular BF ratio was the best independent predictor of HRR and therefore may be best related to cardiovascular increased risk, and possibly act as a mediator in age-related cardiac autonomic control variation.info:eu-repo/semantics/publishedVersio

Challenges and recent progress in drug discovery for tropical diseases

Infectious tropical diseases have a huge effect in terms of mortality and morbidity, and impose a heavy economic burden on affected countries. These diseases predominantly affect the world’s poorest people. Currently available drugs are inadequate for the majority of these diseases, and there is an urgent need for new treatments. This Review discusses some of the challenges involved in developing new drugs to treat these diseases and highlights recent progress. While there have been notable successes, there is still a long way to go.</p

Structured models of cell migration incorporating molecular binding processes

The dynamic interplay between collective cell movement and the various molecules involved in the accompanying cell signalling mechanisms plays a crucial role in many biological processes including normal tissue development and pathological scenarios such as wound healing and cancer. Information about the various structures embedded within these processes allows a detailed exploration of the binding of molecular species to cell-surface receptors within the evolving cell population. In this paper we establish a general spatio-temporal-structural framework that enables the description of molecular binding to cell membranes coupled with the cell population dynamics. We first provide a general theoretical description for this approach and then illustrate it with two examples arising from cancer invasion

Markedly lower follow-up rate after liver biopsy in patients with non-alcoholic fatty liver diseases than those with viral hepatitis in Japan

<p>Abstract</p> <p>Background</p> <p>Patients with non-alcoholic fatty liver diseases (NAFLD) are recommended to have periodic follow-up exams because these patients are at increased risk of the presence of non-alcoholic steatohepatitis (NASH), which can lead to cirrhosis or hepatocellular carcinoma. We investigated the follow-up status of NAFLD patients after a liver biopsy examination.</p> <p>Methods</p> <p>We compared the follow-up rates of NAFLD patients who had received an ultrasonography-guided liver biopsy and patients who had received a liver biopsy for chronic viral hepatitis (hepatitis B or C).</p> <p>Results</p> <p>The 1- and 3-year follow-up rates after the liver biopsy were 92.7% and 88.3% for patients with chronic HBV infection, and 93.4% and 88.2% for patients with chronic HCV infection, respectively. In contrast, the follow-up rates for NAFLD patients were 77.6% and 49.9%, respectively, which were significantly lower than those of patients with chronic viral hepatitis (<it>p </it>< 0.0001). Among NAFLD patients, the respective 1- and 3-year follow-up rates were 73.0% and 44.6% for patients with simple steatosis and 80.0% and 52.4% for patients with NASH based on a pathologic diagnosis, without significant difference between these two subgroups (<it>p </it>= 0.5202).</p> <p>Conclusions</p> <p>The outpatient-based follow-up rate after a liver biopsy was significantly lower in NAFLD patients compared to patients with chronic viral hepatitis, regardless of the presence of NASH. It is important to determine how to maintain regular hospital visits for NAFLD patients, preventing patient attrition.</p

The Effect of Roux-en-Y vs. Omega-Loop Gastric Bypass on Liver, Metabolic Parameters, and Weight Loss

BACKGROUND: Omega-loop gastric bypass (OLGB) results in weight loss (WL) but data on its impact on liver and glucose metabolism compared to Roux-en-Y gastric bypass (RYGB) is lacking. Therefore, the aim of this study was to compare the development of hepatic and metabolic markers as well as WL between the above-mentioned surgical groups during the first postoperative year. METHODS: We retrospectively evaluated the respective parameters in non-diabetic morbidly obese patients who underwent either RYGB (n = 25) or OLGB (n = 25). RESULTS: Compared to RYGB, OLGB showed a greater WL percentage. Liver transaminases dropped in RYGB, while rose in OLGB. No correlation between aspartate transaminase, alanine transaminase, and WL could be detected. Gamma-glutamyltransferase decreased significantly in RYGB over the first 3 months, while it increased in OLGB. We found higher levels of triglycerides, insulin, homeostasis model assessment of insulin resistance (HOMA2-IR), and liver fat percentage in RYGB at baseline, despite matching the groups for age, sex, and BMI. Those differences disappeared, except for triglycerides, within 1 year. All metabolic parameters correlated with WL. CONCLUSION: OLGB results in greater WL but transiently deteriorated several liver parameters in the first postoperative year. This was not associated with WL. The impact of these results on hepatic outcomes such as non-alcoholic steatohepatitis and fibrosis progression requires further studies. In both groups, improved insulin resistance and sensitivity were correlated with higher WL and lower liver fat percentage, respectively

Long-term outcome in relationship to neonatal transfusion volume in extremely premature infants: a comparative cohort study

<p>Abstract</p> <p>Background</p> <p>In premature born infants red blood cell (RBC) transfusions have been associated with both beneficial and detrimental sequels. Upon RBC transfusion, improvement in cerebral blood flow and oxygenation have been observed, while a more liberal transfusion policy may be associated with a better developmental outcome. The effect of the transfusion volume on long-term outcome is not known.</p> <p>Methods</p> <p>Observational follow-up study of a cohort of extremely premature born infants, treated in 2 neonatal intensive care units using a different transfusion volume (15 ml/kg in Unit A and 20 ml/kg in Unit B). The primary outcome was a composite of post discharge mortality, neuromotor developmental delay, blindness or deafness, evaluated at a mean corrected age (CA) of 24 months related to the transfusion volume/kg bodyweight administered during the postnatal hospital stay.</p> <p>Results</p> <p>Despite the difference in transfusion volume in clinically comparable groups of infants, they received a similar number of transfusions (5.5 ± 3.2 versus 5.5 ± 2.3 respectively in Unit A and B). The total transfused volume in unit A was 79 ± 47 ml/kg and 108 ± 47 ml/kg in unit B (p = 0.02). Total transfused RBC volume per kg bodyweight was not an independent predictor of the composite outcome (p = 0.96, OR 1.0 (CI 0.9-1.1).</p> <p>Conclusion</p> <p>There was no relationship between the composite outcome at 24 months CA and transfusion volume received during the post natal hospital stay. As there was no clinical advantage of the higher transfusion volume, a more restrictive volume will reduce total transfusion volume and donor exposure. Future research on the optimal transfusion volume per event to extreme preterm infants should include larger, prospective studies with a longer follow-up period through to childhood or even adolescence.</p

Bacterial Effector Binding to Ribosomal Protein S3 Subverts NF-κB Function

Enteric bacterial pathogens cause food borne disease, which constitutes an enormous economic and health burden. Enterohemorrhagic Escherichia coli (EHEC) causes a severe bloody diarrhea following transmission to humans through various means, including contaminated beef and vegetable products, water, or through contact with animals. EHEC also causes a potentially fatal kidney disease (hemolytic uremic syndrome) for which there is no effective treatment or prophylaxis. EHEC and other enteric pathogens (e.g., enteropathogenic E. coli (EPEC), Salmonella, Shigella, Yersinia) utilize a type III secretion system (T3SS) to inject virulence proteins (effectors) into host cells. While it is known that T3SS effectors subvert host cell function to promote diarrheal disease and bacterial transmission, in many cases, the mechanisms by which these effectors bind to host proteins and disrupt the normal function of intestinal epithelial cells have not been completely characterized. In this study, we present evidence that the E. coli O157:H7 nleH1 and nleH2 genes encode T3SS effectors that bind to the human ribosomal protein S3 (RPS3), a subunit of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) transcriptional complexes. NleH1 and NleH2 co-localized with RPS3 in the cytoplasm, but not in cell nuclei. The N-terminal region of both NleH1 and NleH2 was required for binding to the N-terminus of RPS3. NleH1 and NleH2 are autophosphorylated Ser/Thr protein kinases, but their binding to RPS3 is independent of kinase activity. NleH1, but not NleH2, reduced the nuclear abundance of RPS3 without altering the p50 or p65 NF-κB subunits or affecting the phosphorylation state or abundance of the inhibitory NF-κB chaperone IκBα NleH1 repressed the transcription of a RPS3/NF-κB-dependent reporter plasmid, but did not inhibit the transcription of RPS3-independent reporters. In contrast, NleH2 stimulated RPS3-dependent transcription, as well as an AP-1-dependent reporter. We identified a region of NleH1 (N40-K45) that is at least partially responsible for the inhibitory activity of NleH1 toward RPS3. Deleting nleH1 from E. coli O157:H7 produced a hypervirulent phenotype in a gnotobiotic piglet model of Shiga toxin-producing E. coli infection. We suggest that NleH may disrupt host innate immune responses by binding to a cofactor of host transcriptional complexes

High-resolution haplotype block structure in the cattle genome

<p>Abstract</p> <p>Background</p> <p>The Bovine HapMap Consortium has generated assay panels to genotype ~30,000 single nucleotide polymorphisms (SNPs) from 501 animals sampled from 19 worldwide taurine and indicine breeds, plus two outgroup species (Anoa and Water Buffalo). Within the larger set of SNPs we targeted 101 high density regions spanning up to 7.6 Mb with an average density of approximately one SNP per 4 kb, and characterized the linkage disequilibrium (LD) and haplotype block structure within individual breeds and groups of breeds in relation to their geographic origin and use.</p> <p>Results</p> <p>From the 101 targeted high-density regions on bovine chromosomes 6, 14, and 25, between 57 and 95% of the SNPs were informative in the individual breeds. The regions of high LD extend up to ~100 kb and the size of haplotype blocks ranges between 30 bases and 75 kb (10.3 kb average). On the scale from 1–100 kb the extent of LD and haplotype block structure in cattle has high similarity to humans. The estimation of effective population sizes over the previous 10,000 generations conforms to two main events in cattle history: the initiation of cattle domestication (~12,000 years ago), and the intensification of population isolation and current population bottleneck that breeds have experienced worldwide within the last ~700 years. Haplotype block density correlation, block boundary discordances, and haplotype sharing analyses were consistent in revealing unexpected similarities between some beef and dairy breeds, making them non-differentiable. Clustering techniques permitted grouping of breeds into different clades given their similarities and dissimilarities in genetic structure.</p> <p>Conclusion</p> <p>This work presents the first high-resolution analysis of haplotype block structure in worldwide cattle samples. Several novel results were obtained. First, cattle and human share a high similarity in LD and haplotype block structure on the scale of 1–100 kb. Second, unexpected similarities in haplotype block structure between dairy and beef breeds make them non-differentiable. Finally, our findings suggest that ~30,000 uniformly distributed SNPs would be necessary to construct a complete genome LD map in <it>Bos taurus </it>breeds, and ~580,000 SNPs would be necessary to characterize the haplotype block structure across the complete cattle genome.</p

Citizen Science to Raise Antimicrobial Resistance Awareness in the Community: The MicroMundo Project in Spain and Portugal

Antimicrobial resistance (AMR) poses a global threat to human, animal and environmental health. Among the multidisciplinary tasks aimed at collectively tackling the AMR crisis, surveillance, research and education stand as major priorities. Based on a crowdsourcing research strategy, the MicroMundo project, a partner of the Tiny Earth initiative in Spain and Portugal, has been developed and consolidated with success in the academic environment. The objectives are focused on promoting research and, especially, on bringing knowledge of One Health and microbiology concepts, as well as AMR awareness to the community. Following a service-learning approach, MicroMundo integrates university and secondary/high school students in a citizen science-based research project to collectively isolate microorganisms with the potential to produce new antibiotics from soil environments. Over the last 7 years, 32 MicroMundo hubs operating across 31 different Portuguese and Spanish universities have recruited thousands of teenagers in this quest. Here we review the outcome of this unprecedented effort from a scientific and an educational perspective