Cytokine mRNA expression responses to resistance, aerobic, and concurrent exercise in sedentary middle-aged men

Concurrent resistance and aerobic exercise (CE) is recommended to ageing populations, though is postulated to induce diminished acute molecular responses. Given that contraction-induced cytokine mRNA expression reportedly mediates remunerative postexercise molecular responses, it is necessary to determine whether cytokine mRNA expression may be diminished after CE. Eight middle-aged men (age, 53.3 ±1.8 years; body mass index, 29.4 ± 1.4 kg·m-2) randomly completed (balanced for completion order) 8 × 8 leg extensions at 70% maximal strength (RE), 40 min of cycling at 55% of peak aerobic workload (AE), or (workload-matched) 50% RE and 50% AE (CE). Muscle (vastus lateralis) was obtained pre-exercise, and at 1 h and 4 h postexercise, and analyzed for changes of glycogen concentration, tumor necrosis factor (TNF)α, TNF receptor-1 and -2 (TNF-R1 and TNF-R2, respectively), interleukin (IL)-6, IL-6R, IL-1β, and IL-1 receptor-antagonist (IL-1ra). All exercise modes upregulated cytokine mRNA expression at 1hpostexercise comparably (TNFα, TNF-R1, TNF-R2, IL-1β, IL-6) (p 0.05). Moreover, AE and RE upregulated IL-1β and IL-1ra expression, whereas CE upregulated IL-1β expression only (p 0.05). In conclusion, in middle-aged men, all modes induced commensurate cytokine mRNA expression at 1 h postexercise; however, only CE resulted in ameliorated expression at 4 h postexercise. Whether the RE or AE components of CE are independently or cumulatively sufficient to upregulate cytokine responses, or whether they collectively inhibit cytokine mRNA expression, remains to be determined

Comparative effects of single-mode vs. duration-matched concurrent exercise training on body composition, low-grade inflammation, and glucose regulation in sedentary, overweight, middle-aged men

The effect of duration-matched concurrent exercise training (CET) (50% resistance (RET) and 50% endurance (EET) training) on physiological training outcomes in untrained middle-aged men remains to be elucidated. Forty-seven men (age, 48.1 ± 6.8 years; body mass index, 30.4 ± 4.1 kg·m-2) were randomized into 12-weeks of EET (40-60 min of cycling), RET (10 exercises; 3-4 sets × 8-10 repetitions), CET (50% serial completion of RET and EET), or control condition. The following were determined: intervention-based changes in fitness and strength; abdominal visceral adipose tissue (VAT), total body fat (TB-FM) and fat-free (TB-FFM) mass; plasma cytokines (C-reactive protein (CRP), tumor necrosis factor-α (TNFα) interleukin-6 (IL-6)); muscle protein content of p110α and glucose transporter 4 (GLUT4); mRNA expression of GLUT4, peroxisome proliferator-activated receptor-γ coactivator-1α-β, cytochrome c oxidase, hexokinase II, citrate synthase; oral glucose tolerance; and estimated insulin sensitivity. CET promoted commensurate improvements of aerobic capacity and muscular strength and reduced VAT and TB-FM equivalently to EET and RET (p 0.05). EET reduced area under the curve for glucose, insulin, and C-peptide, whilst CET and RET respectively reduced insulin and C-peptide, and C-peptide only (p 0.05). In middle-aged men, 12 weeks of durationmatched CET promoted commensurate changes in fitness and strength, abdominal VAT, plasma cytokines and insulin sensitivity, and an equidistant glucose tolerance response to EET and RET; despite no change of measured muscle mechanisms associative to insulin action, glucose transport, and mitochondrial function

A comparison of course-related stressors in undergraduate problem-based learning (PBL) versus non-PBL medical programmes

Background: Medical students report high levels of stress related to their medical training as well as to other personal and financial factors. The aim of this study is to investigate whether there are differences in course-related stressors reported by medical students on undergraduate problem-based learning (PBL) and non-PBL programmes in the UK. Method: A cross-sectional study of second-year medical students in two UK medical schools (one PBL and one non-PBL programme) was conducted. A 16-question self-report questionnaire, derived from the Perceived Medical Student Stress Scale and the Higher Education Stress Inventory, was used to measure course-related stressors. Following univariate analysis of each stressor between groups, multivariate logistic regression was used to determine which stressors were the best predictors of each course type, while controlling for socio-demographic differences between the groups. Results: A total of 280 students responded. Compared to the non-PBL students (N = 197), the PBL students (N = 83) were significantly more likely to agree that: they did not know what the faculty expected of them (Odds Ratio (OR) = 0.38, p = 0.03); there were too many small group sessions facilitated only by students resulting in an unclear curriculum (OR = 0.04, p < 0.0001); and that there was a lack of opportunity to explore academic subjects of interest (OR = 0.40, p = 0.02). They were significantly more likely to disagree that: there was a lack of encouragement from teachers (OR = 3.11, p = 0.02); and that the medical course fostered a sense of anonymity and feelings of isolation amongst students (OR = 3.42, p = 0.008). Conclusion: There are significant differences in the perceived course-related stressors affecting medical students on PBL and non-PBL programmes. Course designers and student support services should therefore tailor their work to minimise, or help students cope with, the specific stressors on each course type to ensure optimum learning and wellbeing among our future doctors

Pre-cooling for endurance exercise performance in the heat: a systematic review.

PMCID: PMC3568721The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1741-7015/10/166. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Endurance exercise capacity diminishes under hot environmental conditions. Time to exhaustion can be increased by lowering body temperature prior to exercise (pre-cooling). This systematic literature review synthesizes the current findings of the effects of pre-cooling on endurance exercise performance, providing guidance for clinical practice and further research

Tissue Microenvironments Define and Get Reinforced by Macrophage Phenotypes in Homeostasis or during Inflammation, Repair and Fibrosis

Current macrophage phenotype classifications are based on distinct in vitro culture conditions that do not adequately mirror complex tissue environments. In vivo monocyte progenitors populate all tissues for immune surveillance which supports the maintenance of homeostasis as well as regaining homeostasis after injury. Here we propose to classify macrophage phenotypes according to prototypical tissue environments, e.g. as they occur during homeostasis as well as during the different phases of (dermal) wound healing. In tissue necrosis and/or infection, damage- and/or pathogen-associated molecular patterns induce proinflammatory macrophages by Toll-like receptors or inflammasomes. Such classically activated macrophages contribute to further tissue inflammation and damage. Apoptotic cells and antiinflammatory cytokines dominate in postinflammatory tissues which induce macrophages to produce more antiinflammatory mediators. Similarly, tumor-associated macrophages also confer immunosuppression in tumor stroma. Insufficient parenchymal healing despite abundant growth factors pushes macrophages to gain a profibrotic phenotype and promote fibrocyte recruitment which both enforce tissue scarring. Ischemic scars are largely devoid of cytokines and growth factors so that fibrolytic macrophages that predominantly secrete proteases digest the excess extracellular matrix. Together, macrophages stabilize their surrounding tissue microenvironments by adapting different phenotypes as feed-forward mechanisms to maintain tissue homeostasis or regain it following injury. Furthermore, macrophage heterogeneity in healthy or injured tissues mirrors spatial and temporal differences in microenvironments during the various stages of tissue injury and repair. Copyright (C) 2012 S. Karger AG, Base

Phytochemicals as antibiotic alternatives to promote growth and enhance host health

There are heightened concerns globally on emerging drug-resistant superbugs and the lack of new antibiotics for treating human and animal diseases. For the agricultural industry, there is an urgent need to develop strategies to replace antibiotics for food-producing animals, especially poultry and livestock. The 2nd International Symposium on Alternatives to Antibiotics was held at the World Organization for Animal Health in Paris, France, December 12-15, 2016 to discuss recent scientific developments on strategic antibiotic-free management plans, to evaluate regional differences in policies regarding the reduction of antibiotics in animal agriculture and to develop antibiotic alternatives to combat the global increase in antibiotic resistance. More than 270 participants from academia, government research institutions, regulatory agencies, and private animal industries from >25 different countries came together to discuss recent research and promising novel technologies that could provide alternatives to antibiotics for use in animal health and production; assess challenges associated with their commercialization; and devise actionable strategies to facilitate the development of alternatives to antibiotic growth promoters (AGPs) without hampering animal production. The 3-day meeting consisted of four scientific sessions including vaccines, microbial products, phytochemicals, immune-related products, and innovative drugs, chemicals and enzymes, followed by the last session on regulation and funding. Each session was followed by an expert panel discussion that included industry representatives and session speakers. The session on phytochemicals included talks describing recent research achievements, with examples of successful agricultural use of various phytochemicals as antibiotic alternatives and their mode of action in major agricultural animals (poultry, swine and ruminants). Scientists from industry and academia and government research institutes shared their experience in developing and applying potential antibiotic-alternative phytochemicals commercially to reduce AGPs and to develop a sustainable animal production system in the absence of antibiotics.Fil: Lillehoj, Hyun. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Liu, Yanhong. University of California; Estados UnidosFil: Calsamiglia, Sergio. Universitat Autònoma de Barcelona; EspañaFil: Fernandez Miyakawa, Mariano Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; ArgentinaFil: Chi, Fang. Amlan International; Estados UnidosFil: Cravens, Ron L.. Amlan International; Estados UnidosFil: Oh, Sungtaek. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Gay, Cyril G.. United States Department of Agriculture. Agricultural Research Service; Argentin

Reversibility of liver fibrosis

Liver fibrosis, and its end stage cirrhosis are a major cause of morbidity and mortality and therapeutic options are limited. However, the traditional view of liver disease as an irreversible process is obsolete and it is now evident that the development of liver fibrosis is a dynamic and potentially bidirectional process. Spontaneous resolution of scarring is seen in animal models of liver fibrosis and in human trials in which the stimuli responsible for chronic or repeated hepatic inflammation is successfully removed. Key players in the process are hepatic stellate cells, macrophages, MMPs and their inhibitors Timps. It is also evident that in advanced fibrotic liver disease, specific histological features define what is currently described as "irreversible" fibrosis. This includes the development of paucicellular scars enriched in extensively cross-linked matrix components, such as fibrillar collagen and elastin. Our recent work has focused on the role of macrophage metalloelastase (MMP-12) in the turnover of elastin in reversible and irreversible models of fibrosis. We have shown that elastin turnover in liver injury and fibrosis is regulated by macrophages via Mmp-12 expression, activity and ratio to its inhibitor Timp-1. Failure of elastin degradation, together with increased deposition leads to accumulation of elastin in the fibrotic scars

Mini-open anterior spine surgery for anterior lumbar diseases

Minimally invasive surgeries including endoscopic surgery and mini-open surgery are current trend of spine surgery, and its main advantages are shorter recovery time and cosmetic benefits, etc. However, mini-open surgery is easier and less technique demanding than endoscopic surgery. Besides, anterior spinal fusion is better than posterior spinal fusion while considering the physiological loading, back muscle function, etc. Therefore, we aimed to introduce the modified “mini-open anterior spine surgery” (MOASS) and to evaluate the feasibility, effectiveness and safety in the treatment of various anterior lumbar diseases with this technique. A total of 61 consecutive patients (46 female, 15 male; mean age 58.2 years) from 1997 to 2004 were included in this study, with an average follow-up of 24–52 (mean 43) months. The disease entities included vertebral fracture (20), failed back surgery (13), segmental instability or spondylolisthesis (10), infection (8), herniated disc (5), undetermined lesion for biopsy (4), and hemivertebra (1). Lesions involved 13 cases at T12–L1, 18 at L1–L2, 18 at L2–L3, 22 at L3–L4 and 11 at L4–L5 levels. All patients received a single stage anterior-only procedure for their anterior lumbar disease. We used the subjective clinical results, Oswestry disability index, fusion rate, and complications to evaluate our clinical outcome. Most patients (91.8%) were subjectively satisfied with the surgery and had good-to-excellent outcomes. Mean operation time was 85 (62–124) minutes, and mean blood loss was 136 (minimal-250) ml in the past 6 years. Hospital stay ranged from 4–26 (mean 10.6) days. Nearly all cases had improved back pain (87%), physical function (90%) and life quality (85%). Most cases (95%) achieved solid or probable solid bony fusion. There were no major complications. Therefore, MOASS is feasible, effective and safe for patients with various anterior lumbar diseases

Selective depletion of mouse kidney proximal straight tubule cells causes acute kidney injury

The proximal straight tubule (S3 segment) of the kidney is highly susceptible to ischemia and toxic insults but has a remarkable capacity to repair its structure and function. In response to such injuries, complex processes take place to regenerate the epithelial cells of the S3 segment; however, the precise molecular mechanisms of this regeneration are still being investigated. By applying the “toxin receptor mediated cell knockout” method under the control of the S3 segment-specific promoter/enhancer, Gsl5, which drives core 2 β-1,6-N-acetylglucosaminyltransferase gene expression, we established a transgenic mouse line expressing the human diphtheria toxin (DT) receptor only in the S3 segment. The administration of DT to these transgenic mice caused the selective ablation of S3 segment cells in a dose-dependent manner, and transgenic mice exhibited polyuria containing serum albumin and subsequently developed oliguria. An increase in the concentration of blood urea nitrogen was also observed, and the peak BUN levels occurred 3–7 days after DT administration. Histological analysis revealed that the most severe injury occurred in the S3 segments of the proximal tubule, in which tubular cells were exfoliated into the tubular lumen. In addition, aquaporin 7, which is localized exclusively to the S3 segment, was diminished. These results indicate that this transgenic mouse can suffer acute kidney injury (AKI) caused by S3 segment-specific damage after DT administration. This transgenic line offers an excellent model to uncover the mechanisms of AKI and its rapid recovery

A Distinct Macrophage Population Mediates Metastatic Breast Cancer Cell Extravasation, Establishment and Growth

Background: The stromal microenvironment and particularly the macrophage component of primary tumors influence their malignant potential. However, at the metastatic site the role of these cells and their mechanism of actions for establishment and growth of metastases remain largely unknown. Methodology/Principal Findings: Using animal models of breast cancer metastasis, we show that a population of host macrophages displaying a distinct phenotype is recruited to extravasating pulmonary metastatic cells regardless of species of origin. Ablation of this macrophage population through three independent means (genetic and chemical) showed that these macrophages are required for efficient metastatic seeding and growth. Importantly, even after metastatic growth is established, ablation of this macrophage population inhibited subsequent growth. Furthermore, imaging of intact lungs revealed that macrophages are required for efficient tumor cell extravasation. Conclusion/Significance: These data indicate a direct enhancement of metastatic growth by macrophages through their effects on tumor cell extravasation, survival and subsequent growth and identifies these cells as a new therapeutic target fo