Stratigraphy and paleoenvironments of the early to middle Holocene Chipalamawamba Beds (Malawi Basin, Africa)

We describe the Chipalamawamba Beds, early to middle Holocene deposits at the southern margin of long-lived Lake Malawi. The beds are exposed because of downcutting of the upper Shire River. The Chipalamawamba sediments are medium to coarse, yellow to brown sands deposited in lenses varying in horizontal extent from a few meters to several hundreds of meters. Four units are recognized; the first three mainly contain lacustrine sediments deposited during lake high stands about 10.6–9.7 cal ka BP (Unit 1), 7.6–6.5 cal ka BP (Unit 2) and 5.9–5.3 cal ka BP (Unit 3). Sediments of Unit 4 overlay Units 1 to 3, are coarser and display regular foresets and oblique-bedding, suggesting deposition in riverine environments after installation of the Shire River (~ 5.5–5.0 ka BP). Freshwater mollusk assemblages and bioturbation regularly occur in the lacustrine sediments, but are largely absent from Unit 4. Diverse and often contradicting hypotheses on the lake levels of Lake Malawi have been proposed for the early and middle Holocene. The Chipalamawamba Beds allow straightforward recognition of water levels and provide strong evidence for oscillating lake levels during this period, rather than continuous high or low levels. Sedimentation rates have been high and individual shell beds have typically been deposited during a few decades. Because the Chipalamawamba Beds contain a sequence of mollusk assemblages with intervals between subsequent shell beds ranging from a century to a few millennia, they enable paleontological analysis of the fauna with an unusually high temporal resolution. That some mollusk lineages inhabiting Lake Malawi are in the early stages of diversification and radiation increases the paleobiological relevance of these beds

Evolution of antimicrobial resistance of Salmonella isolates from pigs in Belgium

The aim of the present study was to investigate the antimicrobial sensitivity of Salmonella isolates from pigs between 2011 and 2015. In total, 275 Salmonella isolates from samples originating from pigs sent in for diagnostic examination at Animal Health Care Flanders were tested for their sensitivity against different antimicrobials. Except for colistin, where the disk prediffusion test was used, the disk diffusion test was used. E. coli ATCC 25922 was used as reference isolate and the interpretative breakpoints were based on the Clinical and Laboratory Standards Institute

How sensitive and specific are MRI features of sacroiliitis for diagnosis of spondyloarthritis

'Objective: 'To determine the sensitivity and specificity of MRI features of sacroiliitis in spondyloarthritis (SpA). 'Materials and methods': A retrospective study reviewed MRI of the sacroiliac (SI) joints in 517 patients with inflammatory back pain. Sensitivity, specificity, positive and negative likelihood ratios of active and structural lesions of sacroiliitis with final clinical diagnosis as golden standard was calculated. 'Results: 'MRI showed active inflammation in 42% of patients (bone marrow oedema (BMO) (41.5%), capsulitis (3.3%), enthesitis (2.5%)) and structural changes in 48.8% of patients (erosion (25%), fat infiltration (31.6%), sclerosis (32%) and ankylosis (7.6%)). BMO was the MRI feature with the highest sensitivity (65.1%) for diagnosis of SpA. Capsulitis (99%), enthesitis (98.4%), ankylosis (97.4%) and erosion (94.8%) had a high specificity for diagnosis of SpA, whereas BMO?(74.3%), sclerosis (75.8%) and fat infiltration (84.0%) were less specific. BMO concomitant with enthesitis, capsulitis or erosions increased the specificity. Concomitant presence of BMO and sclerosis or fat infiltration decreased the specificity. 'Conclusion: 'BMO is moderately sensitive and specific for diagnosis of SpA in patients with inflammatory back pain. BMO concomitant with enthesitis, capsulitis, ankylosis or erosion increases the specificity. Concomitant fat infiltration or sclerosis decreases the specificity for diagnosis of SpA. Of all lesions, erosion had by far the highest positive likelihood ratio for diagnosis of SpA

Performance related factors are the main determinants of the von Willebrand factor response to exhaustive physical exercise

Background: Physical stress triggers the endothelium to release von Willebrand Factor (VWF) from the Weibel Palade bodies. Since VWF is a risk factor for arterial thrombosis, it is of great interest to discover determinants of VWF response to physical stress. We aimed to determine the main mediators of the VWF increase by exhaustive physical exercise. Methods: 105 healthy individuals (18-35 years) were included in this study. Each participant performed an incremental exhaustive exercise test on a cycle ergometer. Respiratory gas exchange measurements were obtained while cardiac function was continuously monitored. Blood was collected at baseline and directly after exhaustion. VWF antigen (VWF:Ag) levels, VWF collagen binding (VWF:CB) levels, ADAMTS13 activity and common variations in Syntaxin Binding Protein-5 (STXBP5, rs1039084 and rs9399599), Syntaxin-2 (STX2, rs7978987) and VWF (promoter, rs7965413) were determined. Results: The median VWF:Ag level at baseline was 0.94 IU/mL [IQR 0.8-1.1] and increased with 47% [IQR 25-73] after exhaustive exercise to a median maximum VWF:Ag of 1.38 IU/mL [IQR 1.1-1.8] (p<0.0001). VWF:CB levels and ADAMTS13 activity both also increased after exhaustive exercise (median increase 43% and 12%, both p<0.0001). The strongest determinants of the VWF:Ag level increase are performance related (p<0.0001). We observed a gender difference in VWF:Ag response to exercise (females 1.2 IU/mL; males 1.7 IU/mL, p = 0.001), which was associated by a difference in performance. Genetic variations in STXBP5, STX2 and the VWF promoter were not associated with VWF:Ag levels at baseline nor with the VWF:Ag increase. Conclusions: VWF:Ag levels strongly increase upon exhaustive exercise and this increase is strongly determined by physical fitness level and the intensity of the exercise, while there is no clear effect of genetic variation in STXBP5, STX2 and the VWF promoter

No evidence for involvement of SDHD in neuroblastoma pathogenesis

BACKGROUND: Deletions in the long arm of chromosome 11 are observed in a subgroup of advanced stage neuroblastomas with poor outcome. The deleted region harbours the tumour suppressor gene SDHD that is frequently mutated in paraganglioma and pheochromocytoma, which are, like neuroblastoma, tumours originating from the neural crest. In this study, we sought for evidence for involvement of SDHD in neuroblastoma. METHODS: SDHD was investigated on the genome, transcriptome and proteome level using mutation screening, methylation specific PCR, real-time quantitative PCR based homozygous deletion screening and mRNA expression profiling, immunoblotting, functional protein analysis and ultrastructural imaging of the mitochondria. RESULTS: Analysis at the genomic level of 67 tumour samples and 37 cell lines revealed at least 2 bona-fide mutations in cell lines without allelic loss at 11q23: a 4bp-deletion causing skip of exon 3 resulting in a premature stop codon in cell line N206, and a Y93C mutation in cell line NMB located in a region affected by germline SDHD mutations causing hereditary paraganglioma. No evidence for hypermethylation of the SDHD promotor region was observed, nor could we detect homozygous deletions. Interestingly, SDHD mRNA expression was significantly reduced in SDHD mutated cell lines and cell lines with 11q allelic loss as compared to both cell lines without 11q allelic loss and normal foetal neuroblast cells. However, protein analyses and assessment of mitochondrial morphology presently do not provide clues as to the possible effect of reduced SDHD expression on the neuroblastoma tumour phenotype. CONCLUSIONS: Our study provides no indications for 2-hit involvement of SDHD in the pathogenesis of neuroblastoma. Also, although a haplo-insufficient mechanism for SDHD involvement in advanced stage neuroblastoma could be considered, the present data do not provide consistent evidence for this hypothesis

Prediction of Muscle Energy States at Low Metabolic Rates Requires Feedback Control of Mitochondrial Respiratory Chain Activity by Inorganic Phosphate

The regulation of the 100-fold dynamic range of mitochondrial ATP synthesis flux in skeletal muscle was investigated. Hypotheses of key control mechanisms were included in a biophysical model of oxidative phosphorylation and tested against metabolite dynamics recorded by 31P nuclear magnetic resonance spectroscopy (31P MRS). Simulations of the initial model featuring only ADP and Pi feedback control of flux failed in reproducing the experimentally sampled relation between myoplasmic free energy of ATP hydrolysis (ΔGp = ΔGpo′+RT ln ([ADP][Pi]/[ATP]) and the rate of mitochondrial ATP synthesis at low fluxes (<0.2 mM/s). Model analyses including Monte Carlo simulation approaches and metabolic control analysis (MCA) showed that this problem could not be amended by model re-parameterization, but instead required reformulation of ADP and Pi feedback control or introduction of additional control mechanisms (feed forward activation), specifically at respiratory Complex III. Both hypotheses were implemented and tested against time course data of phosphocreatine (PCr), Pi and ATP dynamics during post-exercise recovery and validation data obtained by 31P MRS of sedentary subjects and track athletes. The results rejected the hypothesis of regulation by feed forward activation. Instead, it was concluded that feedback control of respiratory chain complexes by inorganic phosphate is essential to explain the regulation of mitochondrial ATP synthesis flux in skeletal muscle throughout its full dynamic range

Exercise therapy in Type 2 diabetes

Structured exercise is considered an important cornerstone to achieve good glycemic control and improve cardiovascular risk profile in Type 2 diabetes. Current clinical guidelines acknowledge the therapeutic strength of exercise intervention. This paper reviews the wide pathophysiological problems associated with Type 2 diabetes and discusses the benefits of exercise therapy on phenotype characteristics, glycemic control and cardiovascular risk profile in Type 2 diabetes patients. Based on the currently available literature, it is concluded that Type 2 diabetes patients should be stimulated to participate in specifically designed exercise intervention programs. More attention should be paid to cardiovascular and musculoskeletal deconditioning as well as motivational factors to improve long-term treatment adherence and clinical efficacy. More clinical research is warranted to establish the efficacy of exercise intervention in a more differentiated approach for Type 2 diabetes subpopulations within different stages of the disease and various levels of co-morbidity

The T7-Related Pseudomonas putida Phage ϕ15 Displays Virion-Associated Biofilm Degradation Properties

Formation of a protected biofilm environment is recognized as one of the major causes of the increasing antibiotic resistance development and emphasizes the need to develop alternative antibacterial strategies, like phage therapy. This study investigates the in vitro degradation of single-species Pseudomonas putida biofilms, PpG1 and RD5PR2, by the novel phage ϕ15, a ‘T7-like virus’ with a virion-associated exopolysaccharide (EPS) depolymerase. Phage ϕ15 forms plaques surrounded by growing opaque halo zones, indicative for EPS degradation, on seven out of 53 P. putida strains. The absence of haloes on infection resistant strains suggests that the EPS probably act as a primary bacterial receptor for phage infection. Independent of bacterial strain or biofilm age, a time and dose dependent response of ϕ15-mediated biofilm degradation was observed with generally a maximum biofilm degradation 8 h after addition of the higher phage doses (104 and 106 pfu) and resistance development after 24 h. Biofilm age, an in vivo very variable parameter, reduced markedly phage-mediated degradation of PpG1 biofilms, while degradation of RD5PR2 biofilms and ϕ15 amplification were unaffected. Killing of the planktonic culture occurred in parallel with but was always more pronounced than biofilm degradation, accentuating the need for evaluating phages for therapeutic purposes in biofilm conditions. EPS degrading activity of recombinantly expressed viral tail spike was confirmed by capsule staining. These data suggests that the addition of high initial titers of specifically selected phages with a proper EPS depolymerase are crucial criteria in the development of phage therapy

A Research Agenda for Helminth Diseases of Humans: Social Ecology, Environmental Determinants, and Health Systems

In this paper, the Disease Reference Group on Helminth Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR), with the mandate to review helminthiases research and identify research priorities and gaps, focuses on the environmental, social, behavioural, and political determinants of human helminth infections and outlines a research and development agenda for the socioeconomic and health systems research required for the development of sustainable control programmes. Using Stockols' social-ecological approach, we describe the role of various social (poverty, policy, stigma, culture, and migration) and environmental determinants (the home environment, water resources development, and climate change) in the perpetuation of helminthic diseases, as well as their impact as contextual factors on health promotion interventions through both the regular and community-based health systems. We examine these interactions in regard to community participation, intersectoral collaboration, gender, and possibilities for upscaling helminthic disease control and elimination programmes within the context of integrated and interdisciplinary approaches. The research agenda summarises major gaps that need to be addressed