creased by 0.47 SDs under active learning (n = 158 studies), and that the odds ratio for failing was 1.95 under traditional lecturing (n = 67 studies). These results indicate that average examination scores improved by about 6% in active learning sections, and that students in classes with traditional lecturing were 1.5 times more likely to fail than were students in classes with active learning. Heterogeneity analyses indicated that both results hold across the STEM disciplines, that active learning increases scores on concept inventories more than on course examinations, and that active learning appears effective across all class sizes—although the greatest effects are in small (n ≤ 50) classes. Trim and fill analyses and fail-safe n calculations suggest that the results are not due to publication bias. The results also appear robust to variation in the methodological rigor of the included studies, based on the quality of controls over student quality and instructor identity. This is the largest and most comprehensive metaanalysis of undergraduate STEM education published to date. The results raise questions about the continued use of traditional lecturing as a control in research studies, and support active learning as the preferred, empirically validated teaching practice in regular classrooms.

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Active learning increases student performance in science, engineering, and mathematics

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(12)62167-9.pdf

Frailty in elderly people

The emergence of publications on extracellular RNA (exRNA) and extracellular vesicles (EV) has highlighted the potential of these molecules and vehicles as biomarkers of disease and therapeutic targets. These findings have created a paradigm shift, most prominently in the field of oncology, prompting expanded interest in the field and dedication of funds for EV research. At the same time, understanding of EV subtypes, biogenesis, cargo and mechanisms of shuttling remains incomplete. The techniques that can be harnessed to address the many gaps in our current knowledge were the subject of a special workshop of the International Society for Extracellular Vesicles (ISEV) in New York City in October 2012. As part of the “ISEV Research Seminar: Analysis and Function of RNA in Extracellular Vesicles (evRNA)”, 6 round-table discussions were held to provide an evidence-based framework for isolation and analysis of EV, purification and analysis of associated RNA molecules, and molecular engineering of EV for therapeutic intervention. This article arises from the discussion of EV isolation and analysis at that meeting. The conclusions of the round table are supplemented with a review of published materials and our experience. Controversies and outstanding questions are identified that may inform future research and funding priorities. While we emphasize the need for standardization of specimen handling, appropriate normative controls, and isolation and analysis techniques to facilitate comparison of results, we also recognize that continual development and evaluation of techniques will be necessary as new knowledge is amassed. On many points, consensus has not yet been achieved and must be built through the reporting of well-controlled experiments. Keywords: extracellular vesicle; exosome; microvesicle; standardization; isolation (Published: 27 May 2013) Citation: Journal of Extracellular Vesicles 2013, 2 : 20360 - http://dx.doi.org/10.3402/jev.v2i0.20360

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Standardization of sample collection, isolation and analysis methods in extracellular vesicle research

Skeletal muscle has recently been identified as an endocrine organ. It has, therefore, been suggested that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert paracrine, autocrine, or endocrine effects should be classified as "myokines." Recent research demonstrates that skeletal muscles can produce and express cytokines belonging to distinctly different families. However, the first identified and most studied myokine is the gp130 receptor cytokine interleukin-6 (IL-6). IL-6 was discovered as a myokine because of the observation that it increases up to 100-fold in the circulation during physical exercise. Identification of IL-6 production by skeletal muscle during physical activity generated renewed interest in the metabolic role of IL-6 because it created a paradox. On one hand, IL-6 is markedly produced and released in the postexercise period when insulin action is enhanced but, on the other hand, IL-6 has been associated with obesity and reduced insulin action. This review focuses on the myokine IL-6, its regulation by exercise, its signaling pathways in skeletal muscle, and its role in metabolism in both health and disease.

/pdf/muscle-as-an-endocrine-organ-focus-on-muscle-derived-3c7h8gsq1u.pdf

Muscle as an endocrine organ: focus on muscle-derived interleukin-6.

Childhood obesity affects both the physical and psychosocial health of children and may put them at risk of ill health as adults. More information is needed about the best way to treat obesity in children and adolescents. In this review, 64 studies were examined including 54 studies on lifestyle treatments (with a focus on diet, physical activity or behaviour change) and 10 studies on drug treatment to help overweight and obese children and their families with weight control. No surgical treatment studies were suitable to include in this review. This review showed that lifestyle programs can reduce the level of overweight in child and adolescent obesity 6 and 12 months after the beginning of the program. In moderate to severely obese adolescents, a reduction in overweight was found when either the drug orlistat, or the drug sibutramine were given in addition to a lifestyle program, although a range of adverse effects was also noted. Information on the long-term outcome of obesity treatment in children and adolescents was limited and needs to be examined in some high quality studies.

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Interventions for treating obesity in children

Purpose: Excessive, chronic whole-body vibration (WBV) has a number of negative side effects on the human body, including disorders of the skeletal, digestive, reproductive, visual, and vestibular systems. Whole-body vibration training (WBVT) is intentional exposure to WBV to increase leg muscle strength, bone mineral density, health-related quality of life, and decrease back pain. The purpose of this study was to quantitatively evaluate vibration exposure and biodynamic responses during typical WBVT regimens.

Methods: Healthy men and women (N = 16) were recruited to perform slow, unloaded squats during WBVT (30 Hz; 4 mm p-p), during which knee flexion angle (KA), mechanical impedance, head acceleration (Harms), and estimated vibration dose value (eVDV) were measured. WBVT was repeated using two forms of vibration: 1) vertical forces to both feet simultaneously (VV), and 2) upward forces to only one foot at a time (RV).

Results: Mechanical impedance varied inversely with KA during RV (effect size, ?p2: 0.668, P < 0.01) and VV (?p2: 0.533, P < 0.05). Harms varied with KA (?p2: 0.686, P < 0.01) and is greater during VV than during RV at all KA (P < 0.01). The effect of KA on Harms is different for RV and VV (?p2: 0.567, P < 0.05). The eVDV associated with typical RV and VV training regimens (30 Hz, 4 mm p-p, 10 min·d-1) exceeds the recommended daily vibration exposure as defined by ISO 2631-1 (P < 0.01).

Conclusions: ISO standards indicate that 10 min·d-1 WBVT is potentially harmful to the human body; the risk of adverse health effects may be lower during RV than VV and at half-squats rather than full-squats or upright stance. More research is needed toexplore the long-term health hazards of WBVT.

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Vibration exposure and biodynamic responses during whole-body vibration training.

Purpose: Leg muscle strength and power are increased after whole-body vibration (WBV) exercise. These effects may result from increased neuromuscular activation during WBV; however, previous studies of neuromuscular responses during WBV have not accounted for motion artifact.

Methods: Sixteen healthy adults performed a series of static and dynamic unloaded squats with and without two different directions of WBV (rotational vibration, RV; and vertical vibration, VV; 30 Hz; 4 mmp-p). Activation of unilateral vastus lateralis, biceps femoris, gastrocnemius, and tibialis anterior was recorded using EMG. During RV and VV, increases in EMG relative to baseline were compared over a range of knee angles, contraction types (concentric, eccentric, isometric), and squatting types (static, dynamic).

Results: After removing large, vibration-induced artifacts from EMG data using digital band-stop filters, neuromuscular activation of all four muscles increased significantly (P = 0.05) during RV and VV. Average responses of the extensors were significantly greater during RV than VV, whereas responses of the tibialis anterior were significantly greater during VV than RV. For all four muscles, responses during static squatting were greater than or equal to responses during dynamic squatting, whereas responses during eccentric contractions were equal to or smaller than responses during concentric and isometric contractions. Neuromuscular responses of vastus lateralis, gastrocnemius, and tibialis anterior were affected by knee angle, with greatest responses at small knee angles.

Conclusions: Motion artifacts should be removed from EMG data collected during WBV. We propose that neuromuscular responses during WBV may be modulated by leg muscle cocontraction as a postural control strategy and/or muscle tuning by the CNS intended to minimize soft-tissue vibration.

/pdf/variation-in-neuromuscular-responses-during-acute-whole-body-33oixj9w6h.pdf

Variation in neuromuscular responses during acute whole-body vibration exercise.

Purpose: The purpose of this study was to examine the influence of a 12-wk exercise training program on inflammatory cytokine and C-reactive protein (CRP) concentrations. A secondary purpose was to determine whether training-induced changes in cytokines and CRP were influenced by age.

Methods: Twenty-nine younger (18-35 yr) and 31 older (65-85 yr) subjects were assigned to young physically active (YPA, N = 15; 25 ± 5 yr), young physically inactive (YPI, N= 14; 25 ± 4.7 yr), old physically active (OPA, N = 14; 71 ± 4 yr), or old physically inactive (OPI, N = 17; 71 ± 4 yr) groups. The inactive groups completed 12 wk (3 d·wk-1) of aerobic and resistance exercises, and the physically active control groups continued their normal exercise programs. Blood samples were collected before and after the 12-wk period, and the concentrations of serum CRP, plasma interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-a), and interleukin-1 beta (IL-1s) were determined using separate ELISA.

Results: Control (YPA and OPA) estimated V?O2max was unchanged. Exercise training increased estimated V?O2max an average of 10.4% and increased strength by an average of 38.1% in both PI groups. Serum CRP decreased with training (YPI and OPI) groups and was not different from the YPA and OPA groups after training. Plasma IL-6 and IL-1s did not change, whereas TNF-a was higher than YPI and YPA at baseline and after the intervention period.

Conclusion: These results support the use of combined aerobic/resistance training as a modality to reduce the risk of cardiovascular disease development as defined by a decrease in serum CRP concentration in healthy humans.

The influence of exercise training on inflammatory cytokines and C-reactive protein.

Toll-like receptors (TLRs) are highly conserved trans-membrane proteins that play an important role in the detection and recognition of microbial pathogens The key product of TLR signalling in antigen presenting cells is the production of inflammatory cytokines and proteins The TLR pathway plays an important role in mediating whole body inflammation, which has been implicated in the development of chronic disease An accumulation of chronic, low-grade inflammation is common in individuals that live a sedentary lifestyle; however, the mechanism underlying this connection is not fully understood There is evidence to show that TLRs may be involved in the link between a sedentary lifestyle, inflammation, and disease Recent studies have shown that both acute aerobic and chronic resistance exercise resulted in decreased monocyte cell-surface expression of TLRs Furthermore, a period of chronic exercise training decreases both inflammatory cytokine production and the cell-surface expression of TLR4 on monocytes These effects may contribute to post-exercise immunodepression and the reported higher susceptibility to infection in athletes However over the long-term, a decrease in TLR expression may represent a beneficial effect because it decreases the inflammatory capacity of leukocytes, thus altering whole body chronic inflammation The precise physiological stimulus mediating an exercise-induced decrease in cell-surface TLR expression is not known; however a number of possible signals have been implicated including anti-inflammatory cytokines, stress hormones and heat shock proteins

Exercise and Toll-like receptors.

The influence of an exercise training program and age on inflammatory cytokine production and CD14+cell-surface expression of toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4) was examined in 60 younger and older subjects. Subjects were assigned to: young physically active (YPA, n = 15; 25.2 +/- 5.0 years), young physically inactive (YPI, n = 14; 24.9 +/- 4.7 years), older physically active (OPA, n = 14; 71.2 +/- 4.4 years) or older physically inactive (OPI, n = 17; 71.0 +/- 4.3 years) groups. YPI and OPI completed 12 weeks (3 days/week) of endurance (20 min) and resistance exercise (eight exercises, two sets). YPA and OPA groups were instructed to continue their normal activity for 12 weeks. Blood was collected at rest, before and after the 12-week training and control period. A whole blood method was used to determine lipopolysaccharide-(LPS) and peptidoglycan-(PGN) stimulated IL-6, IL-1beta, and TNF-alpha production with supernatants analyzed using ELISA. CD14+ cell-surface expression of TLR2 and TLR4 were measured using flow cytometry. Training increased estimated VO(2max) by 10.4% and increased strength by an average of 38.1%. YPI and OPI had a post-training reduction in LPS-stimulated IL-6 production (P < .01), but LPS-stimulated IL-1beta and TNF-alpha and PGN-stimulated cytokines were not changed. CD14+ cell TLR4 was significantly reduced (P < .05) in YPI and OPI groups after training, but TLR2 was not significantly changed. An exercise training program reduced LPS-stimulated IL-6, concomitant with lower TLR4. These results provide further support for a training- or physical activity-induced lowering of TLR4 and inflammation.

Brian K. McFarlin

Papers

Vibration exposure and biodynamic responses during whole-body vibration training.

Variation in neuromuscular responses during acute whole-body vibration exercise.

The influence of exercise training on inflammatory cytokines and C-reactive protein.

Exercise and Toll-like receptors.

Influence of exercise training and age on CD14+ cell-surface expression of toll-like receptor 2 and 4.