Intestinal Parasites in an Ottoman Period Latrine from Acre (Israel) Dating to the Early 1800s CE.

The aim of this study is to determine the species of parasites that affected the inhabitants of the city of Acre on the coast of the eastern Mediterranean during the Ottoman Period. This is the first archaeological study of parasites in the Ottoman Empire. We analysed sediment from a latrine dating to the early 1800s for the presence of helminth eggs and protozoan parasites which caused dysentery. The samples were examined using light microscopy and enzyme-linked immunosorbent assay (ELISA) kits. We found evidence for roundworm (Ascaris lumbricoides), whipworm (Trichuris trichiura), fish tapeworm (Dibothriocephalus sp.), Taenia tapeworm (Taenia sp.), lancet liver fluke (Dicrocoelium dendriticum), and the protozoa Giardia duodenalis and Entamoeba histolytica. The parasite taxa recovered demonstrate the breadth of species present in this coastal city. We consider the effect of Ottoman Period diet, culture, trade and sanitation upon risk of parasitism in this community living 200 years ago

Inhibition of preprotein translocation and reversion of the membrane inserted state of SecA by a carboxyl terminus binding MAb

SecA is the peripheral subunit of the preprotein translocase of Escherichia coli. SecA consists of two independently folding domains, i.e., the N-domain bearing the high-affinity nucleotide binding site (NBS-I) and the C-domain that harbors the low-affinity NBS-II. ATP induces SecA insertion into the membrane during preprotein translocation. Domain-specific monoclonal antibodies (mAbs) were developed to analyze the functions of the SecA domains in preprotein translocation. The antigen binding sites of the obtained mAbs were confined to five epitopes. One of the mAbs, i.e., mAb 300-1K5, recognizes an epitope in the C-domain in a region that has been implicated in membrane insertion. This mAb, either as IgG or as Fab, completely inhibits in vitro proOmpA translocation and SecA translocation ATPase activity. It prevents SecA membrane insertion and, more strikingly, reverses membrane insertion and promotes the release of SecA from the membrane. Surface plasmon resonance measurements demonstrate that the mAb recognizes the ADP- and the AMP-PNP-bound state of SecA either free in solution or bound at the membrane at the SecYEG protein. It is concluded that the mAb actively reverses a conformation essential for membrane insertion of SecA. The other mAbs directed to various epitopes in the N-domain were found to be without effect, although all bind the native SecA. These results demonstrate that the C-domain plays an important role in the SecA membrane insertion, providing further evidence that this process is needed for preprotein translocation.</p

Inactivation of glycogen synthase kinase-3 beta (GSK-3 beta) enhances skeletal muscle oxidative metabolism

Background: Aberrant skeletal muscle mitochondrial oxidative metabolism is a debilitating feature of chronic diseases such as chronic obstructive pulmonary disease, type 2 diabetes and chronic heart failure. Evidence in non-muscle cells suggests that glycogen synthase kinase-3 beta (GSK-3 beta) represses mitochondrial biogenesis and inhibits PPAR-gamma co-activator 1 (PGC-1), a master regulator of cellular oxidative metabolism. The role of GSK-3 beta in the regulation of skeletal muscle oxidative metabolism is unknown. Aims: We hypothesized that inactivation of GSK-3 beta stimulates muscle oxidative metabolism by activating PGC-1 signaling and explored if GSK-3 beta inactivation could protect against physical inactivity-induced alterations in skeletal muscle oxidative metabolism. Methods: GSK-3 beta was modulated genetically and pharmacologically in C2C12 myotubes in vitro and in skeletal muscle in vivo. Wild-type and muscle-specific GSK-3 beta knock-out (KO) mice were subjected to hind limb suspension for 14 days. Key constituents of oxidative metabolism and PGC-1. signaling were investigated. Results: In vitro, knock-down of GSK-3 beta increased mitochondrial DNA copy number, protein and mRNA abundance of oxidative phosphorylation (OXPHOS) complexes and activity of oxidative metabolic enzymes but also enhanced protein and mRNA abundance of key PGC-1 signaling constituents. Similarly, pharmacological inhibition of GSK-3 beta increased transcript and protein abundance of key constituents and regulators of mitochondrial energy metabolism. Furthermore, GSK-3 beta KO animals were protected against unloading-induced decrements in expression levels of these constituents. Conclusion: Inactivation of GSK-3 beta up-regulates skeletal muscle mitochondrial metabolism and increases expression levels of PGC-1 signaling constituents. In vivo, GSK-3 beta KO protects against inactivity-induced reductions in muscle metabolic gene expression

Resveratrol and metabolic health in COPD:A proof-of-concept randomized controlled trial

Background: Patients with COPD are often characterized by disturbed metabolic health which is reflected in altered body composition. Current studies in healthy subjects suggest that resveratrol improves metabolic health by enhancing muscle mitochondrial function and adipose tissue morphology. The primary objective was to investigate the effect of four weeks resveratrol supplementation on muscle mitochondrial function in patients with COPD. Secondary objectives were to investigate the effect of resveratrol on adipose tissue inflammatory and metabolic gene expression, systemic inflammation and body composition in patients with COPD. Methods: In a double-blind randomized placebo-controlled proof-of-concept study, 21 COPD patients (FEVi: 53 +/- 15% predicted; age: 67 +/- 9 years and BMI: 24.5 +/- 3.3 kg/m(2)) received resveratrol (150 mg/day) or placebo for four weeks. Before and after intervention, blood samples, quadriceps muscle and subcutaneous abdominal fat biopsies were obtained for metabolic and inflammatory profiling. Body composition was assessed by dual energy X-ray absorptiometry. Results: Muscle mitochondrial biogenesis regulators AMPK, SIRT1 and PGC-1 alpha as well as mitochondrial respiration, Oxphos complexes, oxidative enzyme activities and kynurenine aminotransferases were not improved by resveratrol. Plasma high-sensitive C-reactive protein and kynurenine did not change after resveratrol supplementation. Adipose tissue inflammatory markers were unaffected by resveratrol, while markers of glycolysis and lipolysis were significantly increased compared to placebo supplementation. Body weight decreased after resveratrol supplementation (resveratrol -0.95 +/- 1.01 kg vs placebo -0.16 +/- 0.66 kg, p = 0.049) due to a reduction in lean mass (resveratrol -1.79 +/- 1.67 kg vs 0.37 +/- 0.86 kg, p = 0.026). Conclusion: We do not confirm previously reported positive effects of resveratrol on skeletal muscle mitochondrial function in patients with COPD, but show an unexpected decline in lean mass. (C) 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved

The effect of moderate alcohol consumption on adiponectin oligomers and muscle oxidative capacity: a human intervention study

Aims/hypothesis The aim of this study was to investigate whether moderate alcohol consumption increases plasma high molecular weight (HMW) adiponectin and/or muscle oxidative capacity. Materials and methods Eleven lean (BMI 18 - 25 kg/m(2)) and eight overweight ( BMI >= 27 kg/m(2)) men consumed 100 ml whisky (similar to 32 g alcohol) or water daily for 4 weeks in a randomised, controlled, crossover trial. After each treatment period, muscle biopsies and fasting blood samples were collected. Results Adiponectin concentrations increased ( p <0.001) by 12.5% after 4 weeks of moderate alcohol consumption. Moderate alcohol consumption tended to increase HMW adiponectin by 57% ( p= 0.07) and medium molecular weight adiponectin by 12.5% ( p= 0.07), but not low molecular weight (LMW) adiponectin. Skeletal muscle citrate synthase, cytochrome c oxidase and beta-3-hydroxyacyl coenzyme A dehydrogenase (beta-HAD) activity were not changed after moderate alcohol consumption, but an interaction between alcohol consumption and BMI was observed for cytochrome c oxidase ( p= 0.072) and citrate synthase ( p= 0.102) activity. Among lean men, moderate alcohol consumption tended to increase cytochrome c oxidase ( p= 0.08) and citrate synthase activity ( p= 0.12) by 23 and 26%, respectively, but not among overweight men. In particular, plasma HMW adiponectin correlated positively with activities of skeletal muscle citrate synthase ( r= 0.64, p= 0.009), cytochrome c oxidase ( p= 0.59, p= 0.009) and beta-HAD ( r= 0.46, p= 0.056), while such correlation was not present for LMW adiponectin. Whole-body insulin sensitivity and intramyocellular triacylglycerol content were not affected by moderate alcohol consumption. Conclusions/interpretation Moderate alcohol consumption increases adiponectin concentrations, and in particular HMW adiponectin. Concentrations of HMW adiponectin in particular were positively associated with skeletal muscle oxidative capacity

Level of daily physical activity in individuals with COPD compared with healthy controls

<p>Abstract</p> <p>Background</p> <p>Persons with Chronic Obstructive Pulmonary Disease (COPD), performing some level of regular physical activity, have a lower risk of both COPD-related hospital admissions and mortality. COPD patients of all stages seem to benefit from exercise training programs, thereby improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue. Physical inactivity, which becomes more severe with increasing age, is a point of concern in healthy older adults. COPD might worsen this scenario, but it is unclear to what degree. This literature review aims to present the extent of the impact of COPD on objectively-measured daily physical activity (DPA). The focus is on the extent of the impact that COPD has on duration, intensity, and counts of DPA, as well as whether the severity of the disease has an additional influence on DPA.</p> <p>Results</p> <p>A literature review was performed in the databases PubMed [MEDLINE], Picarta, PEDRO, ISI Web of Knowledge and Google scholar. After screening, 11 studies were identified as being relevant for comparison between COPD patients and healthy controls with respect to duration, intensity, and counts of DPA. Four more studies were found to be relevant to address the subject of the influence the severity of the disease may have on DPA. The average percentage of DPA of COPD patients vs. healthy control subjects for duration was 57%, for intensity 75%, and for activity counts 56%. Correlations of DPA and severity of the disease were low and/or not significant.</p> <p>Conclusions</p> <p>From the results of this review, it appears that patients with COPD have a significantly reduced duration, intensity, and counts of DPA when compared to healthy control subjects. The intensity of DPA seems to be less affected by COPD than duration and counts. Judging from the results, it seems that severity of COPD is not strongly correlated with level of DPA. Future research should focus in more detail on the relation between COPD and duration, intensity, and counts of DPA, as well as the effect of disease severity on DPA, so that these relations become more understandable.</p

Task-related oxygen uptake and symptoms during activities of daily life in CHF patients and healthy subjects

Patients with chronic heart failure (CHF) have a significantly lower peak aerobic capacity compared to healthy subjects, and, may therefore experience more inconvenience during the performance of domestic activities of daily life (ADLs). To date, the extent to which task-related oxygen uptake, heart rate, ventilation and symptoms during the performance of ADLs in CHF patients is different than in healthy subjects remains uncertain. General demographics, pulmonary function, body composition and peak aerobic capacity were assessed in 23 CHF outpatients and 20 healthy peers. In addition, the metabolic requirement of five simple self-paced domestic ADLs was assessed using a mobile oxycon. Task-related oxygen uptake (ml/min) was similar or lower in CHF patients compared to healthy subjects. In contrast, patients with CHF performing ADLs consumed oxygen at a higher proportion of their peak aerobic capacity than healthy subjects (p < 0.05). For example, getting dressed resulted in a mean task-related oxygen uptake of 49% of peak aerobic capacity, while sweeping the floor resulted in a mean task-related oxygen uptake of 52% of peak aerobic capacity, accompanied by significantly higher Borg symptom scores for dyspnea and fatigue (p < 0.05). Patients with CHF experience use a higher proportion of their peak aerobic capacity, peak ventilation and peak heart rate during the performance of simple self-paced domestic ADL than their healthy peers. These findings represent a necessary step in improving our understanding of improving what troubles patients the most—not being able to do the things that they could when they were healthy

The effect of acute and 7-days dietary nitrate on mechanical efficiency, exercise performance and cardiac biomarkers in patients with chronic obstructive pulmonary disease

Background & aims Many COPD patients have a reduced exercise capacity and mechanical efficiency and are at increased cardiometabolic risk. This study aimed to assess acute and 7-days effects of dietary nitrate on mechanical efficiency, exercise performance and cardiac biomarkers in patients with COPD. Methods This double-blind, randomized cross-over placebo controlled trial included 20 mild-to-moderate COPD patients (66.6 ± 7.5 years) with moderate exercise impairments and decreased mechanical efficiency, normal BMI (26 ± 3 kg/m2) but high prevalence of abdominal obesity (83.3%). Subjects were randomly allocated to the treatment order of 7 days sodium nitrate ingestion (∼8 mmol/day) and 7 days placebo (NaCl solution) or vice versa, separated by a washout period. Before (Day-1) and after (Day-7) both intervention periods resting metabolic rate and the metabolic response during submaximal cycle ergometry, cycling endurance time, plasma nitrate and nitrite levels, cardiac plasma biomarkers (e.g. cardiac troponin T, Nt-proBNP and creatinine kinase) and blood pressure were measured. Subsequently, gross, net and delta mechanical efficiency were calculated. Results Plasma nitrate and nitrite concentrations increased at Day-1 and Day-7 after sodium nitrate but not after placebo ingestion. Systolic and diastolic blood pressure did not change following nitrate ingestion. Furthermore, no differences were observed in gross, net, and delta mechanical efficiency during submaximal exercise, cycling endurance time and cardiac biomarkers between nitrate and placebo on Day-1 and Day-7. Meta-analysis of all available studies in COPD also showed no beneficial effect of beetroot juice on systolic and diastolic blood pressure. Conclusion Acute as well as 7-days sodium nitrate supplementation does not modulate mechanical efficiency, blood pressure or cardiac biomarkers in mild-to-moderate COPD patients

Muscle fatigue resistance during stimulated contractions is reduced in young male smokers.

Aim: To determine whether muscle function is compromised in healthy smokers in comparison with activity-matched non-smokers. Methods: Nine male smokers (aged 22.2 ± 2.5 years: mean ± SD) with a smoking history of 2.5 ± 3.1 pack years, and ten male control participants (25.4 ± 2.9 years) matched for physical activity level participated in this study. Knee extensor strength was measured using isometric maximal voluntary contractions. Voluntary activation of the quadriceps and co-activation of the biceps femoris were determined using interpolated twitches and surface electromyography respectively. The frequency-torque relationship and fatigue resistance were assessed with electrically evoked contractions. A fatigue index was determined as the ratio of final torque to initial torque during a series of isometric contractions (2 min; 30 Hz; 1 s contraction/1 s rest). Quadriceps anatomical cross sectional area was measured with MRI at 50% of femur length. Results: Maximal voluntary contraction torque, quadriceps anatomical cross sectional area, knee extensor torque/quadriceps cross sectional area, activation, co-activation and force-frequency relationship were similar, whereas the fatigue index was 17% lower in smokers than non-smokers. Conclusion: In young men smoking does not significantly affect quadriceps muscle mass and contractile properties, but does reduce fatigue resistance of the quadriceps muscle, which was not attributable to differences in physical activity. © 2007 The Authors

A Systems Biology Approach Identifies Molecular Networks Defining Skeletal Muscle Abnormalities in Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory process of the lung inducing persistent airflow limitation. Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy. Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate. In this study, we have applied a network biology approach to model the relationship between muscle molecular and physiological response to training and systemic inflammatory mediators. Our model shows that failure to co-ordinately activate expression of several tissue remodelling and bioenergetics pathways is a specific landmark of COPD diseased muscles. Our findings also suggest that this phenomenon may be linked to an abnormal expression of a number of histone modifiers, which we discovered correlate with oxygen utilization. These observations raised the interesting possibility that cell hypoxia may be a key factor driving skeletal muscle degeneration in COPD patients