Rehydration during exercise prevents the increase of homocysteine concentrations.

This study aimed to assess the effect of rehydration during and after acute aerobic submaximal exercise on total homocysteine (tHcy) concentrations and related parameters in physically active adult males. Twenty trained males (29.4 ± 7.9 years old) completed four exercise tests: two without rehydration during exercise (NH1 and NH2), one with rehydration during exercise using water (H1) and one with rehydration during exercise using an isotonic sports drink (H2). After finishing the exercise tests, subjects followed a rehydration protocol for 2 h. Serum tHcy, vitamin B12, folate, creatine and creatinine were analysed before, after and at 2, 6 and 24 h after exercise. Data were analysed with and without correcting for haemoconcentration to assess the changes in tHcy related. The methylenetetrahydrofolate reductase (MTHFR) 677TT genotype was also analysed. THcy (uncorrected by haemoconcentration) increased significantly after exercise (P < 0.05) in the NH1 and NH2 tests [mean increase ± SD: 1.55 ± 0.33 (15.18%) and 1.76 ± 0.25 (17.69%) µmol/L, respectively], while no significant differences were found in the H1 and H2 tests [mean increase: 0.65 (6.29%) and 0.90 (8.69%) µmol/L, respectively]. The increase was partly due to haemoconcentration and partly due to the metabolism underlying acute exercise. THcy concentrations recovered to baseline after 24 h in all tests. In conclusion, adequate rehydration during acute aerobic exercise using either water or a sports drink maintains tHcy concentrations at baseline and for up to 2 h after exercise in physically active male adults and prevents further increases when compared to no rehydration.

What do we know about homocysteine and exercise? A review from the literature.

High total homocysteine (tHcy) concentrations contribute to an increased risk of cardiovascular diseases and neurodegenerative disorders. Several investigations have focused on the effect of exercise on tHcy concentrations, but results remain controversial. The differences among the methodologies in the investigations make difficult the interpretation of results. This review differentiates the effects of exercise on tHcy and establishes the relation with the implicated biomarkers on tHcy metabolism related to exercise. The electronic database MEDLINE (http://www.ncbi.nlm.nih.gov) was used for searching studies published between years 2002 and 2015. 'Homocysteine', 'Training ', 'Exercise', 'Physical Activity' as well as combinations out of these terms were entered in the database. Articles were grouped in: 1) Acute effect of exercise on tHcy, 2) chronic exercise and tHcy, 3) relationship of physical activity (PA) level and cardiorespiratory fitness with tHcy, and 4) biomarkers related to tHcy and exercise. From a total of 30 articles, most of the studies analyzing the acute effect of exercise showed an increase on tHcy concentrations. Studies analyzing the chronic effect on tHcy concentrations showed contradictory results and no consensus exists probably due to the differences in the methodology, exercise interventions and participants characteristics. Low cardiorespiratory fitness seems to be associated with high tHcy; in contrast, the relation of PA levels and tHcy needs further research. Regarding biomarkers related to tHcy and exercise, some studies showed an increase of folate, vitamin B12, and creatine after acute exercise that could to be due to requirement of protein turnover and an increased metabolic demand of vitamin-B.

A review of the cut-off points for the diagnosis of vitamin B12 deficiency in the general population.

Vitamin B12 deficit is one of the most common vitamin deficiencies. However, there is no consensus on the cut-off points for vitamin B12 and its co-markers, such as folate, holotranscobalamin, methylmalonic acid and homocysteine. In order to establish the state of the art about cut-off points used to determine vitamin B12 deficiency in the last decades, the database MEDLINE was used for searching studies published in adults between December 1992 and May 2014 (69 articles), using search terms like 'vitamin B12', 'cobalamin', 'cut-off', 'deficiency' alone or in combinations. Broad ranges of cut-off points for vitamin B12 and its biomarkers were identified: vitamin B12 ranged between 100 pmol/L and 350 pmol/L, holotranscobalamin 20-50 pmol/L, methylmalonic acid 0.210-0.470 µmol/L, homocysteine 10-21.6 µmol/L, serum folate 3.7-15.9 nmol/L and red blood cell 124-397 nmol/L. For the majority of studies, the potential influence of age, analytical methods, gender and fortified food consumption was not taken in account when choosing cut-off values. This could explain the discrepancies between studies on vitamin B12 and folate deficiency prevalences. We conclude that there is inconsistency in the literature regarding vitamin B12 cut-offs. It would be necessary to establish different reference cut-offs according to age, considering the analytical methods used.

Influence of sex, age, pubertal maturation and body mass index on circulating white blood cell counts in healthy European adolescents­the HELENA study.

UNLABELLED: Percentiles 10th, 25th, 50th, 75th and 90th are presented for circulating white blood cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils and basophils in healthy European adolescents (12.5-17.5 years, n = 405, 48.9% boys), considering age, sex, puberty and body mass index (BMI). CD3(+) (mature T cells), CD4(+) (T helper), CD8(+) (T cytotoxic), CD16(+)56(+) (natural killer), CD19(+) (B cells), CD3(+)CD45RA(+), CD4(+)CD45RA(+), CD8(+)CD45RA(+) (naïve), CD3(+)CD45RO(+), CD4(+)CD45RO(+) and CD8(+)CD45RO(+) (memory) lymphocytes were also analysed by immunophenotyping. Girls presented higher WBC, neutrophil, CD3(+)CD45RO(+) and CD4(+)CD45RO(+) cell counts and CD3(+)/CD19(+) ratio, and lower CD3(+)CD45RA(+) and CD4(+)CD45RA(+) counts than boys. Age was associated with higher neutrophil counts and CD3(+)/CD19(+), and lower CD19(+) counts; in boys, with lower CD3(+)CD45RA(+), CD4(+)CD45RA(+) and CD8(+)CD45RA(+) counts as well; in girls, with higher WBC, CD3(+)CD45RO(+) and CD4(+)CD45RO(+) counts. Pubertal maturation in boys was associated with lower WBC and lymphocyte counts; in girls, with higher basophil, CD3(+)CD45RO(+) and CD4(+)CD45RO(+) values. BMI was associated with higher WBC counts; in boys, also with higher lymphocyte counts; in girls, with higher neutrophil, CD4(+), CD3(+)CD45RO(+) and CD4(+)CD45RO(+) counts. CONCLUSION: Our study provides normative values for circulating immune cells in adolescents, highlighting the importance of considering sex, age, pubertal maturation and BMI when establishing reference ranges for WBC in paediatric populations.

Hormone replacement with 17ß-estradiol plus dihydrotestosterone restores male sexual behavior in rats treated neonatally with clomipramine.

Male sexual behavior (MSB) in rodents, in both its consummatory and motivational components, is regulated by hormones such as testosterone, 17ß-estradiol and 5-α-dihydrotestosterone. In experiments, neonatal treatment with clomipramine (CMI; a serotonin reuptake inhibitor) reproduces some of the signs of depression in adult age, including reduced sexual behavior manifested in a lower percentage of subjects that mount, intromit and ejaculate, although their testosterone levels were not altered. However, the effect of this treatment on estrogen levels and the consequences of hormone substitution using 17ß-estradiol and 5-α-dihydrotestosterone on the expression of male sexual behavior are still unknown. Therefore, the objective of the present study was to analyze the effect of neonatal treatment with CMI on plasma testosterone and 17ß-estradiol levels, and the role of testosterone, 17ß-estradiol and 5-α-dihydrotestosterone in altering the consummatory and motivational components of sexual behavior in male rats. To this end, it analyzed the copulatory parameters and sexual incentive motivation (SIM) of rats treated with CMI under two conditions: basal and post-hormone replacements. Neonatal treatment with CMI did not affect plasma testosterone or 17ß-estradiol concentrations, but did decrease both the consummatory component and sexual motivation according to the results of the SIM test. These aspects were recovered after administering 17ß-estradiol +5-α-dihydrotestosterone, but not testosterone.

Associations between macronutrient intake and serum lipid profile depend on body fat in European adolescents: the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study.

The present study aimed to investigate the relationships between macronutrient intake and serum lipid profile in adolescents from eight European cities participating in the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) cross-sectional study (2006-7), and to assess the role of body fat-related variables in these associations. Weight, height, waist circumference, skinfold thicknesses, total cholesterol, HDL-cholesterol (HDL-C), LDL-cholesterol, TAG, apoB and apoA1 were measured in 454 adolescents (44% boys) aged 12.5-17.5 years. Macronutrient intake (g/4180 kJ per d (1000 kcal per d)) was assessed using two non-consecutive 24 h dietary recalls. Associations were evaluated by multi-level analysis and adjusted for sex, age, maternal education, centre, sum of four skinfolds, moderate-to-vigorous physical activity, sedentary behaviours and diet quality index for adolescents. Carbohydrate intake was inversely associated with HDL-C (ß = - 0.189, P< 0.001). An inverse association was found between fat intake and TAG (ß = - 0.319, P< 0.001). Associations between macronutrient intake and serum lipids varied according to adiposity levels, i.e. an inverse association between carbohydrate intake and HDL-C was only observed in those adolescents with a higher waist:height ratio. As serum lipids and excess body fat are the major markers of CVD, these findings should be considered when developing strategies to prevent the risk of CVD among adolescents.

Impact of the COVID-19 pandemic on implantation of cardiac implantable electronic devices and remote monitoring activations.

INTRODUCTION AND OBJECTIVES: Remote monitoring (RM) of cardiac implantable electronic devices (CIEDs) is considered more reliable, efficient, and safer than conventional in-person follow-up. However, the implementation of RM is still suboptimal. This study aimed to analyze the impact of the COVID-19 pandemic on the rates of CIED implants and RM activations in Spain. METHODS: The COVID-19 RM Spain Registry was used to analyze the monthly number of all CIED implantations and RM activations from January 2018 to December 2021. A descriptive analysis was performed using aggregated data from the five major CIED manufacturers. RESULTS: A total of 205 345 CIEDs were recorded. The number of implants decreased sharply (48.2%) during the pandemic lockdown (March-June 2020) but gradually increased thereafter, compensating for the previous reduction. However, pacemakers and implantable cardiac defibrillators (ICD) showed an aggregate loss of 7% and 3%, respectively, from the annual average during 2020-2021. In contrast, cardiac resynchronization therapy defibrillators (CRT-D) increased by 17%, and pacemakers (CRT-P) by 4.5% over the 2-year period. The percentage of RM activations increased from 24.5% in 2018 to 49.0% in 2021, with a sharp increase during the lockdown. The RM activation rates consistently increased during the lockdown for all devices: pacemakers (14.4% vs 37.2%; P <.001); ICD (75.6% vs 94.2%; P <.001); CRT-D/CRT-P (68.6-44.2% vs 81.6-61%; P <.001), and implantable loop recorders (50.2% vs 68.7%; P <.001). CONCLUSIONS: The significant decline in implants during the lockdown gradually recovered, except for pacemakers and ICD. However, the COVID-19 pandemic boosted RM for all CIEDs in Spain.

Dietary and lifestyle quality indices with/without physical activity and markers of insulin resistance in European adolescents: the HELENA study.

Emerging data indicate that higher levels of insulin resistance (IR) are common among children and adolescents and are related to cardiometabolic risk; therefore, IR requires consideration early in life. In addition, there is a lack of conclusive evidence regarding the role of dietary nutrients on IR. The Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study (HELENA-CSS) was conducted in European adolescents aged 12·5­17·5 years. A total of 637 participants with valid homeostasis model assessment (HOMA) index data and who completed at least a 2 d 24 h dietary recall were included in the study (60% of the total HELENA-CSS sample). There were two dietary indices calculated, with the only difference between them being the inclusion or not of physical activity (PA). Markers of IR such as HOMA and the quantitative insulin sensitivity check index (QUICKI) were calculated. Pubertal status, BMI and cardiorespiratory fitness (CRF) were measured as potential confounders. The dietary index including PA was inversely associated with HOMA and directly with the QUICKI in females, but not in males, after adjusting for pubertal status, centre, BMI and CRF. In conclusion, the present study indicates that considering PA as part of the dietary index is of relevance as the resulted index is inversely related to IR independently of potential confounders including CRF. Overall, these findings suggest that intervention studies aimed at preventing IR in young people should focus on increasing the quality of the diet and also on including an optimal PA level in healthy adolescents.

Health Risk, Functional Markers and Cognitive Status in Institutionalized Older Adults: A Longitudinal Study.

A Follow-up of vitamin B12 and lipids status is essential in older people, being closely related to non-communicable diseases. Their relationships with cognitive and physical status are not clear. The aim was to analyze the evolution of vitamin B12 and related parameters, lipid and hematological profiles, and their relationships with cognitive and physical status among institutionalized elderly. Sixty residents, ranged from 62 to 99, were evaluated. Biomarkers (vitamin B12 and related parameters, lipid and hematological profiles), functional capacity (handgrip, arm and leg strength), and cognitive status (Mini-Mental State Examination) were evaluated four times at 4-month intervals. At the beginning of the study, 63% and 70% of the sample showed abnormal homocysteine and folate values, respectively. At the end of the year, abnormal homocysteine increased to 68%, abnormal folate values decreased to 50%. Throughout the year, serum folate showed a significant increase (14.9 vs. 16.3 nmol/L), (p < 0.05). Serum cobalamin (299 vs. 273 pmol/L). HDL-cholesterol (49.9 vs. 47.0 mg/dL) and triglyceride levels (102.4 vs. 123.2 mg/dL) showed a significant decrease and increase respectively in mean values (all p < 0.05). Serum cobalamin and HDL-cholesterol were the most important biomarkers associated with cognitive function (both p < 0.05). The most relevant biomarkers associated with poor physical strength depending on the body part analyzed were low concentrations of HDL-cholesterol, LDL-cholesterol, apolipoprotein A1, and albumin (all p < 0.05). The evolution of lipid biomarkers, their significance with cognitive values, and association with handgrip, point to the importance of the handgrip measurement, a very simple test, as an important health marker. Both serum albumin and physical strength are important health markers in older people.

Association between blood marker analyses regarding physical fitness levels in Spanish older adults: A cross-sectional study from the PHYSMED project.

Biomarkers have been postulated as essential variables to measure the effects of exercise on the human body. To investigate the relationship between physical fitness (PF) and blood biomarkers that are associated with disease risk in Spanish older adults, four hundred and twenty-nine adults (57% females) aged older than 55 years from a cross-sectional study were included. A battery of PF test was performed, and participants were divided into 3 groups: low, medium and high fitness. Blood samples were collected, and subjects were also grouped based on a particular biomarker being within its reference range. Furthermore, drug intake and dietary intake were considered for each participant. Higher concentrations out of the reference range were observed for vitamin 25(OH)D (67.9%) and total cholesterol (TC) (58.6%). Participants from the low PF group presented lower significant concentrations out of the reference range for vitamin B12 and triglycerides; however, participants in the low PF group showed higher significant concentrations out of the reference range for total homocysteine, creatinine, TC, HDL-cholesterol and LDL-cholesterol (LDL-c) than those in the high PF group (all p<0.05). Considering drugs related to blood lipid modifications, subjects who regularly consumed lipid reducers presented higher significant concentrations out of the reference range for TC and LDL-c than participants who did not take these drugs (p<0.01). Participants from the high PF group presented better blood marker profiles, namely, lower blood markers related to disease risk out of the reference range. These blood markers could be used as a routine method for considering PF groups in older adults.

Cytokine and microRNA levels during different periods of paradoxical sleep deprivation and sleep recovery in rats.

BACKGROUND: Sleep has a fundamental role in the regulation of homeostasis. The aim of this study was to assess the effect of different periods of paradoxical sleep deprivation (PSD) and recovery on serum levels of cytokines and miRNAs related to inflammatory responses. METHODS: Male Wistar rats were submitted to a PSD of 24, 96, or 192 h, or of 192 h followed by 20 days of recovery (192 h PSD+R). The concentrations of corticosterone, cytokines (IL-6, TNF, IL-10, Adiponectin) and miRNAs (miR-146a, miR-155, miR-223, miR-16, miR-126, miR-21) in serum were evaluated. RESULTS: At PSD 24 h a significant increase of IL-6 and decrease of IL-10 were observed. At PSD 96h adiponectin increased. At 192 h of PSD IL-6 increased significantly again, accompanied by a threefold increase of IL-10 and an increase of serum corticosterone. After 20 days of recovery (192 h PSD+R) corticosterone, IL-6 and TNF levels increased significantly, while IL-10 decreased also significantly. Regarding the miRNAs at 24 h of PSD serum miR-146a, miR-155, miR-223, and miR-16 levels all increased. At 96 h of PSD miR-223 decreased. At 192 h of PSD decreases in miR-16 and miR-126 were observed. After recovery serum miR-21 increased and miR-16 decreased. CONCLUSION: PSD induces a dynamic response likely reflecting the induced cellular stress and manifested as variating hormonal and inflammatory responses. Sleep deprivation disturbed corticosterone, cytokine and miRNA levels in serum related to the duration of sleep deprivation, as short-term PSD produced effects similar to those of an acute inflammatory response and long-term PSD induced long-lasting disturbances of biological mediators.

A Novel Physical Activity and Sedentary Behavior Classification and Its Relationship With Physical Fitness in Spanish Older Adults: The PHYSMED Study.

BACKGROUND: As there is no gold-standard methodology to classify older people in relation to physical activity (PA) and sedentary behavior (SB), this paper aimed to propose a classification combining PA and SB. METHODS: Within a broader study, 433 subjects, aged 55 years and older (57% females) from Madrid and Majorca, were evaluated for PA and SB by means of validated questionnaires. Physical fitness was analyzed objectively using the EXERNET test battery. Cluster analyses were used to establish behavioral patterns, combining PA and SB. RESULTS: Males spent more time doing regular PA but less time walking and working at home than females (P < .001). Comparing the groups (inactive and high sedentary, inactive and low sedentary, active and high sedentary, and active and low sedentary), the worst aerobic endurance (P < .001) and lower body strength (P < .05) were obtained in males from both inactive groups. Agility was highest in the active and low sedentary group (P < .05). No significant differences were observed in females. CONCLUSIONS: The proposed classification is valid, as it classifies subjects according to their PA and SB, and outcomes are related to objectively measured fitness. It could facilitate the work of public health authorities, researchers, and physicians.

Western and Mediterranean Dietary Patterns and Physical Activity and Fitness among Spanish Older Adults.

Objectives: To assess prevailing food patterns, and its association with physical activity and fitness among Spanish older adults. Methods: Cross-sectional study in Spain, collecting data from a sample (n = 380; 54% female) aged 55-80 years (men) and 60-80 years (women) with no previously documented cardiovascular disease. Body weight, body fat and waist circumference were assessed. Physical activity performed was measured using the Minnesota Leisure-time Physical Activity Questionnaire (LTPA). Physical fitness was assessed using a validated physical fitness test battery. Food consumption was assessed by a validated semi-quantitative food-frequency questionnaire. Factor analysis identified two major dietary food patterns: "Western" (WDP) and "Mediterranean" (MDP) dietary patterns. Results: Participants in MDP's fourth quartile were classified in the second (men) and third (men and women) tertile of LTPA. After adjusting for age, body fat, waist-to-height ratio, and METs, in both sexes, a negative significant association was found between 30-s Chair stand and 6-min walking test, a positive significant association was found between 30-m Gait speed and 8-foot Time Up-and-Go (except in men) tests with WDP. The 30-m Gait speed test was negatively associated with MDP in men. Conclusions: MDP is associated with more time spent on LTPA, and this association was independent of body composition and a fast gait speed in men. WDP is associated with slower gait speed and lower body strength, agility and aerobic endurance. MDP has protective effect on healthy physical fitness, and WDP may be a contributor to frailty.

Chronic unpredictable mild stress generates oxidative stress and systemic inflammation in rats.

Stress is considered to be a causal agent of chronic degenerative diseases, such as cardiovascular disease, diabetes mellitus, arthritis and Alzheimer's. Chronic glucocorticoid and catecholamine release into the circulation during the stress response has been suggested to activate damage mechanisms, which in the long term produce metabolic alterations associated with oxidative stress and inflammation. However, the consequences of stress in animal models for periods longer than 40days have not been explored. The goal of this work was to determine whether chronic unpredictable mild stress (CUMS) produced alterations in the redox state and the inflammatory profile of rats after 20, 40, and 60days. CUMS consisted of random exposure of the animals to different stressors. The following activities were measured in the liver and pancreas: reduced glutathione (GSH), lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC), and protein oxidation. Similarly, serum cytokine levels (IL-6, TNF-α, IL-1ß, and IL-10) were determined. CUMS activated the stress response from day 20 until day 60. In the liver and pancreas, GHS levels were decreased from day 40, whereas protein lipid peroxidation and protein oxidation were increased. This is the first work to report that the pancreas redox state is subject to chronic stress conditions. The TAC was constant in the liver and reduced in the pancreas. An increase in the TNF-α, IL-1ß, and IL-6 inflammatory markers and a decrease in the IL-10 level due to CUMS was shown, thereby resulting in the generation of a systemic inflammation state after 60days of treatment. Together, the CUMS consequences on day 60 suggest that both processes can contribute to the development of chronic degenerative diseases, such as cardiovascular disease and diabetes mellitus. CUMS is an animal model that in addition to avoiding habituation activates damage mechanisms such as oxidative stress and low-grade chronic inflammation, which allows the study of physio-pathological stress aspects over prolonged time periods of at least 60days.

Impact of physical activity and sedentarism on hydration status and liquid intake in Spanish older adults. The PHYSMED study.

INTRODUCTION: Data on hydration status in older adults are scarce and there are very few studies focusing on the impact of physical activity (PA) on drinking behavior. OBJECTIVE: To assess the impact of physical activity and sedentarism on fluid intake in Spanish elderly. METHODS: 433 non-institutionalized Spanish older adults (58% females), aged 55-88 years, volunteered for the PHYSMED study. PA data were obtained by means of the Minnesota and EXERNET questionnaires. Population was divided into four groups: ILS (inactive and low sedentary), IHS (inactive and high sedentary), ALS (active and low sedentary) and AHS (active and high sedentary). Serum from fasting blood samples was analysed for osmolarity. RESULTS: The mean of total liquid intake was 1,751 ± 628 mL/d. Significant differences were observed for total liquid intake between ILS/ALS and IHS/ALS (p < 0.001). ALS subjects consumed a higher amount of beverages such as water, juice, milk, coffee, sport drink, beer, wine and distilled drinks than the other PA groups. There was a significant difference for water intake between PA groups (p < 0.01). Serum osmolarity values were within references ranges in all subjects, and there was a signifi cant difference between PA groups (p < 0.01). CONCLUSIONS: Spanish older adults meet the DACH recommendations set by the German, Austrian and Swiss nutrition societies' liquid intake recommendations in the mean independently of PA and sedentary level. All participants are within reference ranges of serum osmolarity. Subjects in the active and low sedentary group consumed higher amounts of water and other beverages than in the other PA groups.

Effects of different periods of paradoxical sleep deprivation and sleep recovery on lipid and glucose metabolism and appetite hormones in rats.

Sleep has a fundamental role in the regulation of energy balance, and it is an essential and natural process whose precise impacts on health and disease have not yet been fully elucidated. The aim of this study was to assess the consequences of different periods of paradoxical sleep deprivation (PSD) and recovery from PSD on lipid profile, oral glucose tolerance test (OGTT) results, and changes in insulin, corticosterone, ghrelin, and leptin concentrations. Three-month-old male Wistar rats weighing 250-350 g were submitted to 24, 96, or 192 h of PSD or 192 h of PSD with 480 h of recovery. The PSD was induced by the multiple platforms method. Subsequently, the animals were submitted to an OGTT. One day later, the animals were killed and the levels of triglycerides, total cholesterol, lipoproteins (low-density lipoprotein, very-low-density lipoprotein, and high-density lipoprotein), insulin, ghrelin, leptin, and corticosterone in plasma were quantified. There was a progressive decrease in body weight with increasing duration of PSD. The PSD induced basal hypoglycemia over all time periods evaluated. Evaluation of areas under the curve revealed progressive hypoglycemia only after 96 and 192 h of PSD. There was an increase in corticosterone levels after 192 h of PSD. We conclude that PSD induces alterations in metabolism that are reversed after a recovery period of 20 days.