Chronic kidney disease in type 2 diabetic patients followed-up by primary care physicians in Switzerland: prevalence and prescription of antidiabetic drugs.

QUESTION UNDER STUDY: The aim of this study was to assess the prevalence of chronic kidney disease (CKD) among type 2 diabetic patients in primary care settings in Switzerland, and to analyse the prescription of antidiabetic drugs in CKD according to the prevailing recommendations. METHODS: In this cross-sectional study, each participating physician was asked to introduce anonymously in a web database the data from up to 15 consecutive diabetic patients attending her/his office between December 2013 and June 2014. Demographic, clinical and biochemical data were analysed. CKD was classified with the KDIGO nomenclature based on estimated glomerular filtration rate (eGFR) and urinary albumin/creatinine ratio. RESULTS: A total of 1 359 patients (mean age 66.5 ± 12.4 years) were included by 109 primary care physicians. CKD stages 3a, 3b and 4 were present in 13.9%, 6.1%, and 2.4% of patients, respectively. Only 30.6% of patients had an entry for urinary albumin/creatinine ratio. Among them, 35.6% were in CKD stage A2, and 4.1% in stage A3. Despite prevailing limitations, metformin and sulfonylureas were prescribed in 53.9% and 16.5%, respectively, of patients with advanced CKD (eGFR <30 ml/min). More than a third of patients were on a dipeptidyl-peptidase-4 inhibitor across all CKD stages. Insulin use increased progressively from 26.8% in CKD stage 1-2 to 50% in stage 4. CONCLUSIONS: CKD is frequent in patients with type 2 diabetes attending Swiss primary care practices, with CKD stage 3 and 4 affecting 22.4% of cases. This emphasizes the importance of routine screening of diabetic nephropathy based on both eGFR and urinary albumin/creatinine ratio, the latter being largely underused by primary care physicians. A careful individual drug risk/benefit balance assessment is mandatory to avoid the frequently observed inappropriate prescription of antidiabetic drugs in CKD patients.

The "Abdominal Circulatory Pump": An Auxiliary Heart during Exercise?

Apart from its role as a flow generator for ventilation the diaphragm has a circulatory role. The cyclical abdominal pressure variations from its contractions cause swings in venous return from the splanchnic venous circulation. During exercise the action of the abdominal muscles may enhance this circulatory function of the diaphragm. Eleven healthy subjects (25 ± 7 year, 70 ± 11 kg, 1.78 ± 0.1 m, 3 F) performed plantar flexion exercise at ~4 METs. Changes in body volume (ΔVb) and trunk volume (ΔVtr) were measured simultaneously by double body plethysmography. Volume of blood shifts between trunk and extremities (Vbs) was determined non-invasively as ΔVtr-ΔVb. Three types of breathing were studied: spontaneous (SE), rib cage (RCE, voluntary emphasized inspiratory rib cage breathing), and abdominal (ABE, voluntary active abdominal expiration breathing). During SE and RCE blood was displaced from the extremities into the trunk (on average 0.16 ± 0.33 L and 0.48 ± 0.55 L, p < 0.05 SE vs. RCE), while during ABE it was displaced from the trunk to the extremities (0.22 ± 0.20 L p < 0.001, p < 0.05 RCE and SE vs. ABE respectively). At baseline, Vbs swings (maximum to minimum amplitude) were bimodal and averaged 0.13 ± 0.08 L. During exercise, Vbs swings consistently increased (0.42 ± 0.34 L, 0.40 ± 0.26 L, 0.46 ± 0.21 L, for SE, RCE and ABE respectively, all p < 0.01 vs. baseline). It follows that during leg exercise significant bi-directional blood shifting occurs between the trunk and the extremities. The dynamics and partitioning of these blood shifts strongly depend on the relative predominance of the action of the diaphragm, the rib cage and the abdominal muscles. Depending on the partitioning between respiratory muscles for the act of breathing, the distribution of blood between trunk and extremities can vary by up to 1 L. We conclude that during exercise the abdominal muscles and the diaphragm might play a role of an "auxiliary heart."

Prescription in the proposal for a common european sales law

The rules on prescription in Part VIII, Chapter 18, of the Proposal for a Common European Sales Law (CESL) follow the provisions of the Principles of European Contract Law (PECL) and the Draft Common Frame of Reference (DCFR), which, in general, have deserved favourable comments. Yet, a number of rules contained in those texts have been omitted. It is necessary to ascertain whether the CESL rules only apply to provisions on rights and claims resulting from sales or related services contracts, or whether they are also applicable to any other contractual right or claim and also to rights or claims of non-contractual origin. One of the most problematic issues concerns general prescription periods: firstly, because there are two general periods, a short one and a long one, without any specification about the claims or rights covered by each one of them; secondly, because neither period is suitable in case of non-conformity. There are also some interpretation problems due to missing, ambiguous or defective definitions. The systematic approach demands clarification too.

Circulating progenitor cells during exercise, muscle electro-stimulation and intermittent hypobaric hypoxia in patients with traumatic brain injury. A pilot study

BACKGROUND: Circulating progenitor cells (CPC) treatments may have great potential for the recovery of neurons and brain function. OBJECTIVE: To increase and maintain CPC with a program of exercise, muscle electro-stimulation (ME) and/or intermittent-hypobaric-hypoxia (IHH), and also to study the possible improvement in physical or psychological functioning of participants with Traumatic Brain Injury (TBI). METHODS: Twenty-one participants. Four groups: exercise and ME group (EEG), cycling group (CyG), IHH and ME group (HEG) and control group (CG). Psychological and physical stress tests were carried out. CPC were measured in blood several times during the protocol. RESULTS: Psychological tests did not change. In the physical stress tests the VO2 uptake increased in the EEG and the CyG, and the maximal tolerated workload increased in the HEG. CPC levels increased in the last three weeks in EEG, but not in CyG, CG and HEG. CONCLUSIONS: CPC levels increased in the last three weeks of the EEG program, but not in the other groups and we did not detect performed psychological test changes in any group. The detected aerobic capacity or workload improvement must be beneficial for the patients who have suffered TBI, but exercise type and the mechanisms involved are not clear.

Epigenetic alterations in hippocampus of SAMP8 senescent mice and modulation by voluntary physical exercise.

The senescence-accelerated SAMP8 mouse model displays features of cognitive decline and Alzheimer's disease. With the purpose of identifying potential epigenetic markers involved in aging and neurodegeneration, here we analyzed the expression of 84 mature miRNAs, the expression of histone-acetylation regulatory genes and the global histone acetylation in the hippocampus of 8-month-old SAMP8 mice, using SAMR1 mice as control. We also examined the modulation of these parameters by 8 weeks of voluntary exercise. Twenty-one miRNAs were differentially expressed between sedentary SAMP8 and SAMR1 mice and seven miRNAs were responsive to exercise in both strains. SAMP8 mice showed alterations in genes involved in protein acetylation homeostasis such as Sirt1 and Hdac6 and modulation of Hdac3 and Hdac5 gene expression by exercise. Global histone H3 acetylation levels were reduced in SAMP8 compared with SAMR1 mice and reached control levels in response to exercise. In sum, data presented here provide new candidate epigenetic markers for aging and neurodegeneration and suggest that exercise training may prevent or delay some epigenetic alterations associated with accelerated aging.

Macroautophagic process was differentially modulated by long-term moderate exercise in rat brain and peripheral tissues

The autophagic process is a lysosomal degradation pathway, which is activated during stress conditions, such as starvation or exercise. Regular exercise has beneficial effects on human health, including neuroprotection. However, the cellular mechanisms underlying these effects are incompletely understood. Endurance and a single bout of exercise induce autophagy not only in brain but also in peripheral tissues. However, little is known whether autophagy could be modulated in brain and peripheral tissues by long-term moderate exercise. Here, we examined the effects on macroautophagy process of long-term moderate treadmill training (36 weeks) in adult rats both in brain (hippocampus and cerebral cortex) and peripheral tissues (skeletal muscle, liver and heart). We assessed mTOR activation and the autophagic proteins Beclin 1, p62, LC3B (LC3B-II/LC3B-I ratio) and the lysosomal protein LAMP1, as well as the ubiquitinated proteins. Our results showed in the cortex of exercised rats an inactivation of mTOR, greater autophagy flux (increased LC3-II/LC3-I ratio and reduced p62) besides increased LAMP1. Related with these effects a reduction in the ubiquitinated proteins was observed. No significant changes in the autophagic pathway were found either in hippocampus or in skeletal and cardiac muscle by exercise. Only in the liver of exercised rats mTOR phosphorylation and p62 levels increased, which could be related with beneficial metabolic effects in this organ induced by exercise. Thus, our findings suggest that long-term moderate exercise induces autophagy specifically in the cortex

Epigenetic alterations in hippocampus of SAMP8 senescent mice and modulation by voluntary physical exercise.

The senescence-accelerated SAMP8 mouse model displays features of cognitive decline and Alzheimer's disease. With the purpose of identifying potential epigenetic markers involved in aging and neurodegeneration, here we analyzed the expression of 84 mature miRNAs, the expression of histone-acetylation regulatory genes and the global histone acetylation in the hippocampus of 8-month-old SAMP8 mice, using SAMR1 mice as control. We also examined the modulation of these parameters by 8 weeks of voluntary exercise. Twenty-one miRNAs were differentially expressed between sedentary SAMP8 and SAMR1 mice and seven miRNAs were responsive to exercise in both strains. SAMP8 mice showed alterations in genes involved in protein acetylation homeostasis such as Sirt1 and Hdac6 and modulation of Hdac3 and Hdac5 gene expression by exercise. Global histone H3 acetylation levels were reduced in SAMP8 compared with SAMR1 mice and reached control levels in response to exercise. In sum, data presented here provide new candidate epigenetic markers for aging and neurodegeneration and suggest that exercise training may prevent or delay some epigenetic alterations associated with accelerated aging.

Macroautophagic process was differentially modulated by long-term moderate exercise in rat brain and peripheral tissues

The autophagic process is a lysosomal degradation pathway, which is activated during stress conditions, such as starvation or exercise. Regular exercise has beneficial effects on human health, including neuroprotection. However, the cellular mechanisms underlying these effects are incompletely understood. Endurance and a single bout of exercise induce autophagy not only in brain but also in peripheral tissues. However, little is known whether autophagy could be modulated in brain and peripheral tissues by long-term moderate exercise. Here, we examined the effects on macroautophagy process of long-term moderate treadmill training (36 weeks) in adult rats both in brain (hippocampus and cerebral cortex) and peripheral tissues (skeletal muscle, liver and heart). We assessed mTOR activation and the autophagic proteins Beclin 1, p62, LC3B (LC3B-II/LC3B-I ratio) and the lysosomal protein LAMP1, as well as the ubiquitinated proteins. Our results showed in the cortex of exercised rats an inactivation of mTOR, greater autophagy flux (increased LC3-II/LC3-I ratio and reduced p62) besides increased LAMP1. Related with these effects a reduction in the ubiquitinated proteins was observed. No significant changes in the autophagic pathway were found either in hippocampus or in skeletal and cardiac muscle by exercise. Only in the liver of exercised rats mTOR phosphorylation and p62 levels increased, which could be related with beneficial metabolic effects in this organ induced by exercise. Thus, our findings suggest that long-term moderate exercise induces autophagy specifically in the cortex

Asma y actividad física. Revisión

El asma es una enfermedad inflamatoria crónica de elevada prevalencia a nivel mundial, siendo el colectivo más afectado el formado por niños y adolescentes. Su sintomatología se caracteriza por la aparición de tos, disnea, sibilancias, sensación de opresión en el pecho y broncoconstricción. Tradicionalmente se había pensado que el deporte y el ejercicio físico estaban contraindicados en pacientes asmáticos. Por otro lado, el paciente asmático suele presentar niveles de condición física y práctica deportiva menores que los sujetos sanos. Actualmente se ha propuesto la actividad física regular como un camino válido para mejorar la percepción y el autoconocimiento personal sobre esta enfermedad. Se aconseja la prescripción de actividad física como forma de mejorar su sintomatología y evolución. La práctica de una actividad física regular en pacientes asmáticos debería ser considerada dentro de los actuales y futuros programas de salud como un objetivo fundamental.

Establishing Zebrafish as a Novel Exercise Model: Swimming Economy, Swimming-enhanced Growth and Muscle Growth Marker Gene Expression

Zebrafish has been largely accepted as a vertebrate multidisciplinary model but its usefulness as a model for exercise physiology has been hampered by the scarce knowledge on its swimming economy, optimal swimming speeds and cost of transport. Therefore, we have performed individual and group-wise swimming experiments to quantify swimming economy and to demonstrate the exercise effects on growth in adult zebrafish.