When a dielectric object is placed between two opposed, nonfocused laser beams, the total force acting on the object is zero but the surface forces are additive, thus leading to a stretching of the object along the axis of the beams. Using this principle, we have constructed a device, called an optical stretcher, that can be used to measure the viscoelastic properties of dielectric materials, including biologic materials such as cells, with the sensitivity necessary to distinguish even between different individual cytoskeletal phenotypes. We have successfully used the optical stretcher to deform human erythrocytes and mouse fibroblasts. In the optical stretcher, no focusing is required, thus radiation damage is minimized and the surface forces are not limited by the light power. The magnitude of the deforming forces in the optical stretcher thus bridges the gap between optical tweezers and atomic force microscopy for the study of biologic materials.

SummaryBackgroundRemote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months.MethodsWe did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed.FindingsBetween Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91–1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed.InterpretationRemote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI.FundingBritish Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden.

Adiponectin is an anti-inflammatory protein that reduced in obesity. Exercise training may reduce the adipose tissue (AT), although it is not well known whether exercise-induced change in AT, increases the adiponectin mRNA expression and plasma concentrations or not; therefore, the purpose of this study was to investigate the adiponectin mRNA and plasma concentrations in middle-aged men after 12 weeks high-intensity exercise training and after a week detraining. Sixteen sedentary overweight and obese middle-aged men (age 41.18 ± 6.1 years; ± SD) volunteered to participate in this study. The subjects were randomly assigned to training group (n = 8) or control group (n = 8). The training group performed endurance training 4 days a week for 12 weeks at an intensity corresponding to 75-80% individual maximum oxygen consumption for 45 min. After 12 weeks of training, subjects underwent a week of detraining. The results showed that the BMI as well as central and peripheral AT volume were decreased in the training group compared to the control group (P < 0.05). After 12 weeks, the training group resulted in a significant increase (P < 0.05) in the adiponectin gene expression in abdominal and gluteal subcutaneous AT when compared with the control group. The results showed that plasma adiponectin concentrations increased and insulin resistance decreased after training compared to the control group (P < 0.05). After a week of detraining, the variables were not changed significantly in the training group. In conclusion, high-intensity endurance training caused an increase adiponectin mRNA in obese middle-aged men.

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Mohebbi H, Azizi M. Maximal fat oxidation at the different exercise intensity in obese and normal weight men in the morning and evening. J. Hum. Sport Exerc. Vol. 6, No. 1, pp. 49-58, 2011. Introduction: Circadian rhythms regulate some metabolic and hormonal variables that affect fat oxidation rates. Thus, the purpose of this study was to investigate Maximal fat oxidation (MFO) at a different exercise intensity in obese and normal weight men in the morning and evening. Methods: MFO was measured in 12 normal weight (BMI 20-25 kg/m 2 ; VO 2 max 45.7±3.44 ml/min/kg) and 10 obese (BMI >30 kg/m 2 ; VO 2 max 37.2±3.6 ml/min/kg) men during incremental running exercise test with 3 min stages on the treadmill by indirect calorimetry method. Student's t-test and one-way ANOVA with repeated measures were used to analysis variables. Results: We found that fat oxidation rates and energy expenditure in both groups in the evening were higher than morning; there were no significant differences in MFO between obese and normal groups. Furthermore, the fat oxidation rate in low intensity exercise (<60% VO 2 max) was similar in obese and normal weight groups, but in high exercise intensities, in normal weight men were significantly higher than obese men. Conclusion: Our results suggest that independent of exercise intensity and body fat mass, exercising in the evening is more effective on fat oxidation and decrease body fat mass; therefore, it is better for weight loss purposes in obese and normal weight men.

This study compares the effect of two types of exercise training, i.e., moderate-intensity continuous training (MICT) or high-intensity interval training (HIIT) on the browning of subcutaneous white adipose tissue (scWAT) in obese male rats. Effects on fat composition, metabolites, and molecular markers of differentiation and energy expenditure were examined. Forty male Wistar rats were assigned to lean (n = 8) or obese (n = 32) groups and fed either a standard chow or high-fat obesogenic diet for 10 weeks. Eight lean and obese rats were then blood and tissue sampled, and the remaining obese animals were randomly allocated into sedentary, MICT, or HIIT (running on a treadmill 5 days/week) groups that were maintained for 12 weeks. Obesity increased plasma glucose and insulin and decreased irisin and FGF-21. In scWAT, this was accompanied with raised protein abundance of markers of adipocyte differentiation, i.e., C/EBP-α, C/EBP-β, and PPAR-γ, whereas brown fat-related genes, i.e., PRDM-16, AMPK/SIRT1/PGC-1α, were reduced as was UCP1 and markers of fatty acid transport, i.e., CD36 and CPT1. Exercise training increased protein expression of brown fat-related markers, i.e., PRDM-16, AMPK/SIRT1/PGC-1α, and UCP1, together with gene expression of fatty acid transport, i.e., CD36 and CPT1, but decreased markers of adipocyte differentiation, i.e., C/EBP-α, C/EBP-β, and plasma glucose. The majority of these adaptations were greater with HIIT compared to MICT. Our findings indicate that prolonged exercise training promotes the browning of white adipocytes, possibly through suppression of adipogenesis together with white to beige trans-differentiation and is dependent on the intensity of exercise.

Epidermolysis bullosa (EB), the paradigm of heritable skin fragility disorders, is associated with mutations in as many as 20 distinct genes. One of the clinical variants, recessive dystrophic EB (RDEB), demonstrates sub-lamina densa blistering accompanied by alterations in anchoring fibrils due to mutations in COL7A1. In this study, we characterized a patient with widespread connective tissue abnormalities, including skin blistering similar to that in RDEB. Whole exome sequencing, combined with genome-wide homozygosity mapping, identified a homozygous missense mutation in PLOD3 encoding lysyl hydroxylase 3 (LH3). No mutations in COL7A1, the gene previously associated with RDEB, were detected. The level of LH3 was dramatically reduced in the skin and fibroblast cultures from the patient. The blistering in the skin occurred below the lamina densa and was associated with variable density and morphology of anchoring fibrils. The level of type VII collagen expression in the skin was markedly reduced. Analysis of hydroxylysine and its glycosylated derivatives (galactosyl-hydroxylysine and glucosyl-galactosyl-hydroxylysine) revealed marked reduction in glycosylated hydroxylysine. Collectively, these findings indicate that PLOD3 mutations can result in a dystrophic EB-like phenotype in the spectrum of connective tissue disorders and add it to the list of candidate genes associated with skin fragility.

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