The distribution of different intensity demanding scenarios in elite rink hockey players using an electronic performance tracking system.

Despite the traditional use of average values for determining physical demands, the intermittent and fluctuating nature of team sports may lead to underestimation of the most demanding scenarios. All the most demanding scenario-related investigations to date only report one maximal scenario per game, the greatest. However, the latest research on this subject has shown additional scenarios of equal or similar magnitude that most researchers have not considered. This repetition concept started a new way of describing competition and training loads; then the study aims were: first, to quantify and assess differences between playing positions in terms of the most demanding scenarios in official matches; and second, to quantify and assess the differences between playing positions in the repetition of different intensity scenarios relative to the most demanding individual scenario. We monitored nine professional rink hockey players (7 exterior and 2 interior players) in 18 competitive matches using an electronic performance tracking system. The interior players are closest to the opponent's goal, while the exterior players are farthest from it. Peak physical demands variables included total distance (m), distance covered at >18 km·h-1 (m), the number of accelerations (≥2 m∙s-2, count) and decelerations (≤-2 m∙s-2, count) in 30 s. An average from the top three individual most demanding scenarios was used to define a reference value to quantify the distribution scenario repetition during matches. The results showed that peak demands in rink hockey are position-dependent, with more distance covered by exterior players and more accelerations performed by interior players. In addition, rink hockey matches include multiple scenario exposures that are close to the peak physical demands of a match. Using the results of this study, coaches can prepare tailored training plans for each position, focusing on distances covered or accelerations for exterior players.

Supervised physical activity in patients with symptomatic peripheral arterial disease: protocol for a randomized clinical trial (ARTPERfit Study).

INTRODUCTION: Peripheral arterial disease (PAD) is a marker of cardiovascular morbidity, causing disability, loss of mobility and poor quality of life, manifesting clinically in the form of intermittent claudication (IC). Physical exercise increases the distance walked and improves quality of life. The aim of our study will be increased walking distance prolonging the time of onset of pain in patients with symptomatic PAD (IC). METHODS AND ANALYSIS: This study will be performed in Mataró Hospital's vascular surgery service and School of Health Sciences, TecnoCampus. This population comes from 15 primary healthcare centres ofNorth Barcelona, Spain (450 000 inhabitants).This study will be a four-group parallel, longitudinal, randomised controlled trial, blind to analysis.The main primary outcome of this study will be the improvement in pain-free walking distance. Others primary objectives are and improvement in functional status, quality of life and Ankle-Brachial Index (ABI). Secondary outcomes will be the analysis of cardiorespiratory fitness, evaluation of muscle fitness, determine the maintenance of primary objectives at 6 and 12 months.We will be included 124 patients (31 per group). The changes of the outcome (Barthel, SF-12, VascQOL-6, ABI) of the three intervention groups vs the control group at 3, 6 and 12 months will be compared, both continuously (linear regression) and categorically (logistic regression). A person who has not performed at least 75% of the training will be considered to have not completed the intervention. ETHICS AND DISSEMINATION: The study will be conducted according to the Declaration of Helsinki . It was approved by the Ethics Committee of the Research Institute Primary Health IDIAP Jordi Gol (20/035 P),Barcelona 6 October 2020. Informed consent will be obtained from all patients before the start of the study. We will disseminate results through academic papers and conference presentations. TRIAL REGISTRATION NUMBER: NCT04578990.

Long-Term Effects of Ionizing Radiation on the Hippocampus: Linking Effects of the Sonic Hedgehog Pathway Activation with Radiation Response.

Radiation therapy represents one of the primary treatment modalities for primary and metastatic brain tumors. Although recent advances in radiation techniques, that allow the delivery of higher radiation doses to the target volume, reduce the toxicity to normal tissues, long-term neurocognitive decline is still a detrimental factor significantly affecting quality of life, particularly in pediatric patients. This imposes the need for the development of prevention strategies. Based on recent evidence, showing that manipulation of the Shh pathway carries therapeutic potential for brain repair and functional recovery after injury, here we evaluate how radiation-induced hippocampal alterations are modulated by the constitutive activation of the Shh signaling pathway in Patched 1 heterozygous mice (Ptch1+/-). Our results show, for the first time, an overall protective effect of constitutive Shh pathway activation on hippocampal radiation injury. This activation, through modulation of the proneural gene network, leads to a long-term reduction of hippocampal deficits in the stem cell and new neuron compartments and to the mitigation of radio-induced astrogliosis, despite some behavioral alterations still being detected in Ptch1+/- mice. A better understanding of the pathogenic mechanisms responsible for the neural decline following irradiation is essential for identifying prevention measures to contain the harmful consequences of irradiation. Our data have important translational implications as they suggest a role for Shh pathway manipulation to provide the therapeutic possibility of improving brain repair and functional recovery after radio-induced injury.

Trace Elements in Blood of the Population Living near a Hazardous Waste Incinerator in Catalonia, Spain.

In 2012, the concentrations of trace elements (As, Be, Cd, Cr, Hg, Mn, Ni, Pb, Sn, Tl, and V) were measured in blood samples of the population living in the vicinity of a hazardous waste incinerator (HWI) located in Tarragona County (Catalonia, Spain). This study is part of a wide surveillance program aimed at assessing the impact of the facility on the public health conducted since 1998, before the HWI started operating. Lead was the metal occurring with the highest concentration (21.7 µg kg-1), followed by Mn (19.7 µg kg-1) and Hg (4.62 µg kg-1). Arsenic (6.99 µg kg-1) showed a low detection rate (49%), while the rest of the analyzed trace elements were not detected. In 2017, a new sampling campaign was conducted, and three new trace elements (Co, Cu, and Sb) were added. In the most recent survey, Cu reached a mean concentration of 931 µg kg-1, up to 60-fold higher than that corresponding to the remaining trace elements. Relatively high levels were also found for Sb (16.0 µg kg-1), Mn (13.9 µg kg-1), and Pb (13.0 µg kg-1). In comparison with the baseline study (1998), Hg, Mn, and Pb significantly decreased over time. Some trace elements showed significant differences according to sex, age, and area of residence. In general, the concentrations of trace elements in blood were similar to, or even lower than, those reported in the scientific literature. Hence, the exposure to trace elements does not mean any additional health risk for the population living near the HWI. This conclusion is in agreement with other studies carried out in the framework of this surveillance program, in which trace elements have been measured in different biological matrices, such as hair and autopsy tissues (brain, bone, kidney, liver, and lungs).

Effect of radiotherapy on the expression of cardiovascular disease-related miRNA-146a, -155, -221 and -222 in blood of women with breast cancer.

Breast cancer (BC) is one of the most important neoplasias among women. Many patients receive radiotherapy (RT), which involves radiation exposure of the thoracic zone, including the heart and blood vessels, leading to the development of cardiovascular disease (CVD) as a long-term side effect. The severity of CVD-related pathologies leads research on assessing novel CVD biomarkers as diagnostic, prognostic or therapeutic agents. Currently, the possible candidates include blood microRNAs (miRNAs). Previous studies have supported a role for miRNA-146a, -155, -221, and -222 in the progression of CVD. Our purpose was to evaluate the RT-induced modulation of the expression of these miRNAs in the blood of women with BC. Pre-RT control and post-RT blood samples were collected, and after miRNA isolation and reverse transcription, the levels of the selected miRNAs were measured by real-time PCR. Our results showed that miRNA-155 exhibited the lowest expression, while miRNA-222 exhibited the highest expression, followed by miRNA-221. The expression of each individual miRNA was positively correlated with that of the others both pre-RT control and post-RT and inversely correlated with age before RT. Furthermore, RT promoted the overexpression of the selected miRNAs. Their levels were also affected by CVD-linked clinical parameters, treatment and BC side. Modulation of the expression of the selected miRNAs together with other risk factors might be associated with the development of future cardiovascular pathologies. Further confirmatory studies are needed to assess their potential as possible biomarkers in the progression of or as therapeutic targets for RT-induced CVD in BC patients.

Effect of Radiation on the Expression of CVD-related miRNAs, Inflammation and Endothelial Dysfunction of HUVECs.

BACKGROUND/AIM: Radiotherapy (RT) can lead to cardiovascular disease (CVD). Evidence suggests that radiation modulates miRNA levels. Our purpose was to assess the acute response to radiation-induced modulation of the expression of miRNA-146a, miRNA-155, miRNA-221, and miRNA-222, inflammatory response and endothelial dysfunction on endothelial cells. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were exposed to 2 Gy RT, and intracellular levels of selected miRNAs were measured by real-time polymerase chain reaction at 2 and 24 h. Cytokine and adhesion molecule release were also assessed. RESULTS: Results showed that 2 Gy significantly increased the expression of miRNA-221 and miRNA-222, and reduced the level of miRNA-155 after 2 h; whereas miRNA-146a and miRNA-155 were significantly overexpressed and miRNA-222 was significantly down-regulated at 24 h. Interleukin-8 and soluble vascular cell adhesion molecule 1 levels were not affected by the studied RT. CONCLUSION: RT at 2 Gy modulated expression of selected miRNAs by endothelial cells after 2 and 24 h, which might be related to CVD development in patients who receive RT.

How whole-body vibration can help our COPD patients. Physiological changes at different vibration frequencies.

OBJECTIVE: Evaluate cardiac, metabolic, and ventilatory changes during a training session with whole-body vibration training (WBVT) with 3 different frequencies in patients with chronic obstructive pulmonary disease (COPD). METHODS: This was a prospective, interventional trial in outpatients with severe COPD. Participants performed 3 vertical WBVT sessions once a week using frequencies of 35, 25 Hz and no vibration in squatting position (isometric). Cardiac, metabolic, and ventilator parameters were monitored during the sessions using an ergospirometer. Changes in oxygen pulse response (VO2/HR) at the different frequencies were the primary outcome of the study. RESULTS: Thirty-two male patients with a mean forced expiratory volume in 1 second of 39.7% completed the study. Compared to the reference of 35 Hz, VO2/HR at no vibration was 10.7% lower (P=0.005); however, no statistically significant differences were observed on comparing the frequencies of 35 and 25 Hz. The median oxygen uptake (VO2) at 25 Hz and no vibration was 9.43% and 13.9% lower, respectively, compared to that obtained at 35 Hz (both comparisons P<0.0001). The median expiratory volume without vibration was 9.43% lower than the VO2 at the end of the assessment at 35 Hz vibration (P=0.002). CONCLUSION: Vertical WBVT training sessions show greater cardiac, metabolic, and respiratory responses compared with the squat position. On comparing the 2 frequencies used, we observed that the frequency of 35 Hz provides higher cardiorespiratory adaptation.

Alterations in Morphology and Adult Neurogenesis in the Dentate Gyrus of Patched1 Heterozygous Mice.

Many genes controlling neuronal development also regulate adult neurogenesis. We investigated in vivo the effect of Sonic hedgehog (Shh) signaling activation on patterning and neurogenesis of the hippocampus and behavior of Patched1 (Ptch1) heterozygous mice (Ptch1+/- ). We demonstrated for the first time, that Ptch1+/- mice exhibit morphological, cellular and molecular alterations in the dentate gyrus (DG), including elongation and reduced width of the DG as well as deregulations at multiple steps during lineage progression from neural stem cells to neurons. By using stage-specific cellular markers, we detected reduction of quiescent stem cells, newborn neurons and astrocytes and accumulation of proliferating intermediate progenitors, indicative of defects in the dynamic transition among neural stages. Phenotypic alterations in Ptch1+/- mice were accompanied by expression changes in Notch pathway downstream components and TLX nuclear receptor, as well as perturbations in inflammatory and synaptic networks and mouse behavior, pointing to complex biological interactions and highlighting cooperation between Shh and Notch signaling in the regulation of neurogenesis.

In-vitro metabolomics to evaluate toxicity of particulate matter under environmentally realistic conditions.

In this pilot study three fractions of particulate matter (PM0.25, PM2.5-0.25, and PM10-2.5) were collected in three environments (classroom, home, and outdoors) in a village located nearby an industrial complex. Time-activity pattern of 20 students attending the classroom was obtained, and the dose of particles reaching the children's lungs under actual environmental conditions (i.e. real dose) was calculated via dosimetry model. The highest PM concentrations were reached in the classroom. Simulations showed that heavy intensity outdoor activities played a major role in PM deposition, especially in the upper part of the respiratory tract. The mass of PM10-2.5 reaching the alveoli was minor, while PM2.5-0.25 and PM0.25 apportion for most of the PM mass retained in the lungs. Consequently, PM2.5-0.25 and PM0.25 were the only fractions used in two subsequent toxicity assays onto alveolar cells (A549). First, a cytotoxicity dose-response assay was performed, and doses corresponding to 5% mortality (LC5) were estimated. Afterwards, two LC-MS metabolomic assays were conducted: one applying LC5, and another applying real dose. A lower estimated LC5 value was obtained for PM0.25 than PM2.5-0.25 (8.08 and 73.7 ng/mL respectively). The number of altered features after LC5 exposure was similar for both fractions (39 and 38 for PM0.25 and PM2.5-0.25 respectively), while after real dose exposure these numbers differed (10 and 5 for PM0.25 and PM2.5-0.25 respectively). The most metabolic changes were related to membrane and lung surfactant lipids. This study highlights the capacity of PM to alter metabolic profile of lung cells at conventional environmental levels.

Renal and hepatic effects following neonatal exposure to low doses of Bisphenol-A and 137Cs.

137-Cesium (137Cs) is one of the most important distributed radionuclides after a nuclear accident. Humans are usually co-exposed to various environmental toxicants, being Bisphenol-A (BPA) one of them. Exposure to IR and BPA in early life is of major concern, due to the higher vulnerability of developing organs. We evaluate the renal and hepatic effects of low doses of ionizing radiation (IR) and BPA. Sixty male mice (C57BL/6J) were randomly assigned to six experimental groups (n=10) and received a single subcutaneous dose of 0.9% saline solution, 137Cs and/or BPA on postnatal day 10: control, BPA (25 µg/kgbw), Cs4000 (4000 Bq 137Cs/kgbw), Cs8000 (8000 Bq 137Cs/kgbw), BPA/Cs4000 and BPA/Cs8000. At the age of two months, urines (24h) and blood samples were collected from animals of each group to determine biochemical parameters. Finally, kidneys and liver were removed to quantify DNA damage (8-OHdG), as well as to determine CYP1A2 mRNA expression. Data suggest that both BPA and 137Cs induced renal and liver damage evidenced by oxidative stress. However, when there is a co-exposure, it seems that there are compensatory mechanisms that may reverse the damage induced by each toxic itself. Notwithstanding, more studies are necessary to better understand the synergistic mechanisms behind.

Environmental exposure to low-doses of ionizing radiation. Effects on early nephrotoxicity in mice.

Nuclear accidents of tremendous magnitude, such as those of Chernobyl (1986) and Fukushima (2011), mean that individuals living in the contaminated areas are potentially exposed to ionizing radiation (IR). However, the dose-response relationship for effects of low doses of radiation is not still established. The present study was aimed at investigating in mice the early effects of low-dose internal radiation exposure on the kidney. Adult male (C57BL/6J) mice were divided into three groups. Two groups received a single subcutaneous (s.c.) doses of cesium (137Cs) with activities of 4000 and 8000Bq/kg bw. A third group (control group) received a single s.c. injection of 0.9% saline. To evaluate acute and subacute effects, mice (one-half of each group) were euthanized at 72h and 10 days post-exposure to 137Cs, respectively. Urine samples were collected for biochemical analysis, including the measurement of F2-isoprostane (F2-IsoP) and kidney injury molecule-1 (KIM-1) levels. Moreover, the concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a sensitive marker of oxidative DNA damage, were measured in renal tissue. Urinary excretion of total protein significantly increased at 72h in mice exposed to Cs4000. Uric acid and lactate dehydrogenase (LDH) decreased significantly at both times post-exposure in animals exposed to Cs8000. After 72h and 10d of exposure to Cs4000, a significant increase in the γ-glutamil transferase (GGT) and N-acetyl-ß-D-glucosaminidase (NAG) activities was observed. In turn, F2-IsoP levels increased -mainly in the Cs4000 group- at 72h post-exposure. Following irradiation (137Cs), the highest level of KIM-1 was corresponded to the Cs4000 group at 72h. Likewise, the main DNA damage was detected in mice exposed to Cs4000, mainly at 10d after irradiation. The alterations observed in several biomarkers suggest an immediate renal damage following exposure to low doses of IR (given as 137Cs). Further investigations are required to clarify the mechanisms involved in the internal IR-induced nephrotoxicity.

Exposure to low doses of 137cesium and nicotine during postnatal development modifies anxiety levels, learning, and spatial memory performance in mice.

Radiation therapy is a major cause of long-term complications observed in survivors of pediatric brain tumors. However, the effects of low-doses of ionizing radiation (IR) to the brain are less studied. On the other hand, tobacco is one of the most heavily abused drugs in the world. Tobacco is not only a health concern for adults. It has also shown to exert deleterious effects on fetuses, newborns, children and adolescents. Exposure to nicotine (Nic) from smoking may potentiate the toxic effects induced by IR on brain development. In this study, we evaluated in mice the cognitive effects of concomitant exposure to low doses of internal radiation (137Cs) and Nic during neonatal brain development. On postnatal day 10 (PND10), two groups of C57BL/6J mice were subcutaneously exposed to 137-Cesium (137Cs) (4000 and 8000 Bq/kg) and/or Nic (100 µg/ml). At the age of two months, neurobehavior of mice was assessed. Results showed that exposure to IR-alone or in combination with Nic-increased the anxiety-like of the animals without changing the activity levels. Moreover, exposure to IR impaired learning and spatial memory. However, Nic administration was able to reverse this effect, but only at the low dose of 137Cs.

Simvastatin Increases Fibulin-2 Expression in Human Coronary Artery Smooth Muscle Cells via RhoA/Rho-Kinase Signaling Pathway Inhibition.

The composition and structure of the extracellular matrix (ECM) in the vascular wall and in the atherosclerotic plaque are important factors that determine plaque stability. Statins can stabilize atherosclerotic plaques by modulating ECM protein expression. Fibulins are important components of the ECM. We evaluated the in vitro effect of simvastatin on the expression of fibulin-1, -2, -4 and -5 in human coronary artery smooth muscle cells (SMCs) and the mechanisms involved. Cells were incubated with simvastatin (0.05-1 µM), mevalonate (100 and 200 µM), geranylgeranyl pyrophosphate (GGPP) (15 µM), farnesyl pyrophosphate (FPP) (15 µM), the Rho kinase (ROCK) inhibitor Y-27632 (15 and 20 µM), the Rac-1 inhibitor (another member of Rho family) NSC23766 (100 µM), arachidonic acid (a RhoA/ROCK activator, 25-100 µM) and other fatty acids that are not activators of RhoA/ROCK (25-100 µM). Gene expression was analyzed by quantitative real-time PCR, and fibulin protein levels were analyzed by western blotting and ELISA. Simvastatin induced a significant increase in mRNA and protein levels of fibulin-2 at 24 hours of incubation (p<0.05), but it did not affect fibulin-1, -4, and -5 expression. Mevalonate and GGPP were able to reverse simvastatin's effect, while FPP did not. In addition, Y-27632, but not NSC23766, significantly increased fibulin-2 expression. Furthermore, activation of the RhoA/ROCK pathway with arachidonic acid decreased fibulin-2 mRNA. Simvastatin increased mRNA levels and protein expression of the ECM protein fibulin-2 through a RhoA and Rho-Kinase-mediated pathway. This increase could affect the composition and structure of the ECM.

Two variants in the fibulin2 gene are associated with lower systolic blood pressure and decreased risk of hypertension.

Arterial stiffness is an important factor in hypertension. Fibulin 2 is an extracellular matrix scaffold protein involved in arterial stiffness and, hence, the fibulin 2 (FBLN2) gene may be a candidate for hypertension susceptibility. 4 single nucleotide polymorphisms (SNPs) of FBLN2 were evaluated in an association case-control study containing 447 hypertensive patients and 344 normotensive control subjects. The minor allele frequencies of rs3732666 and rs1061376 were significantly lower in hypertensives. The odds ratios (OR) for having the protective G (rs3732666) and T (rs1061376) alleles were 0.75 (95%CI: 0.58 to 0.96) and 0.83 (95%CI: 0.66 to 1.02), respectively. For rs3732666, the OR for hypertension in AG+GG subjects, compared with AA, was 0.71 (95%CI: 0.52 to 0.95). The protective genotype AG+GG was associated with significantly lower systolic blood pressure (SBP) [-3.6 mmHg (P = 0.048)]. There was a significant age interaction with rs3732666; the effect decreasing with increasing age. For rs1061376, TT subjects had an OR for hypertension of 0.53 (95%CI: 0.32 to 0.87) compared with CC subjects, with reduced SBP (-7.91 mmHg; P = 0.008) and diastolic BP (DBP) (-3.69 mmHg; P = 0.015). The presence of a G allele was an independent predictor of intima-media thickness (IMT); G carrier's having lower mean IMT (-0.037 mm, P = 0.027) compared with AA. Our results provide the first evidence for FBLN2 as a new gene associated with hypertension.