Dose-response effects of physical exercise standardized volume on peripheral biomarkers, clinical response, and brain connectivity in Parkinson's disease: a prospective, observational, cohort study.

Background: Exercise has been proposed as the "Universal Prescription for Parkinson's Disease"; however, the specificity of exercise dose in terms of frequency, intensity, duration, and type to be prescribed remains to be elucidated. The 2018 US updated guidelines and WHO Guidelines on Physical Activity and Sedentary Behavior recommend older adults (> 65+ years) to achieve weekly minimal activity levels, indicating the intensity of aerobic exercise as the metabolic equivalent of task and duration as minutes/week (150-300 min/week at a moderate intensity of 3-5.9 MET- or 75-150 min/week of a vigorous intensity of ≥6 MET). Translating these recommendations to PD patients, the study aimed to assess the dose-response effects of standardized volume of structured exercise, measured as METs-minutes/week (weekly energy expenditure) of two different rehabilitation settings to quantify the change in neurotrophic factors. The exercise-induced benefits between the two rehabilitation settings will be evaluated based on motor and non-motor symptoms, kinematic parameters of gait, cognitive function, quality of life, and cortical activity and brain connectivity. Methods: METEX-PD is a pilot, prospective, observational, cohort study. The study will enroll consecutively thirty (N = 30) participants with mild-to-moderate Parkinson's disease diagnosis to be assigned to a non-intensive or intensive rehabilitation group. The non-intensive rehabilitation group will achieve a range of 180-270 METs-min/week (90 min/week of low-intensity aerobic exercise, 2-3 METs), while the intensive rehabilitation group will exercise at 1350-1980 METs-min/week (225 min/week of high-intensity aerobic exercise, 6-8.8 METs). The METEX-PD trial will last 12 weeks, including 4 weeks of aerobic training program and two follow-ups. Assessments will be performed at baseline (T0), at the end of the exercise program (T1-end of the program), and 4- and 8 weeks after the end of the training program (FU-1 and FU-2). The primary outcome is the change from baseline in peripheral blood BDNF levels. Secondary outcomes are differences in peripheral biomarkers, functional-motor assessments, clinical-functional evaluations, and brain imaging. Conclusion: METEX-PD trial will enable us to estimate the change in BDNF levels and other peripheral biomarkers under precise exercise-induced energy expenditure. The primary results of the METEX-PD study will allow the development of a larger multicenter randomized controlled trial to investigate the molecular pathways inducing the change in selected neurotrophic factors, such as BDNF, IGF-1, or irisin, and the downstream mechanisms of neuroplasticity in PD patients.

Possible Role of Tauroursodeoxycholic Acid (TUDCA) and Antibiotic Administration in Modulating Human Gut Microbiota in Home Enteral Nutrition Therapy for the Elderly: A Case Report.

Tauroursodeoxycholic acid (TUDCA) increases the influx of primary bile acids into the gut. Results obtained on animal models suggested that Firmicutes and Proteobacteria phyla are more resistant to bile acids in rats. As part of a pilot study investigating the role of probiotics supplementation in elderly people with home enteral nutrition (HEN), a case of a 92-year-old woman with HEN is reported in the present study. She lives in a nursing home and suffers from Alzheimer's disease (AD); the patient had been prescribed TUDCA for lithiasis cholangitis. The aim of this case report is therefore to investigate whether long-term TUDCA administration may play a role in altering the patient's gut microbiota (GM) and the impact of an antibiotic therapy on the diversity of microbial species. Using next generation sequencing (NGS) analysis of the bacterial 16S ribosomal RNA (rRNA) gene a dominant shift toward Firmicutes and a remodeling in Proteobacteria abundance was observed in the woman's gut microbiota. Considering the patient's age, health status and type of diet, we would have expected to find a GM with a prevalence of Bacteroidetes phylum. This represents the first study investigating the possible TUDCA's effect on human GM.

Impaired myoblast differentiation and muscle IGF-1 receptor signaling pathway activation after N-glycosylation inhibition.

The role of N-glycosylation in the myogenic process remains poorly understood. Here, we evaluated the impact of N-glycosylation inhibition by Tunicamycin (TUN) or by phosphomannomutase 2 (PMM2) gene knockdown, which encodes an enzyme essential for catalyzing an early step of the N-glycosylation pathway, on C2C12 myoblast differentiation. The effect of chronic treatment with TUN on tibialis anterior (TA) and extensor digitorum longus (EDL) muscles of WT and MLC/mIgf-1 transgenic mice, which overexpress muscle Igf-1Ea mRNA isoform, was also investigated. TUN-treated and PMM2 knockdown C2C12 cells showed reduced ConA, PHA-L, and AAL lectin binding and increased ER-stress-related gene expression (Chop and Hspa5 mRNAs and s/uXbp1 ratio) compared to controls. Myogenic markers (MyoD, myogenin, and Mrf4 mRNAs and MF20 protein) and myotube formation were reduced in both TUN-treated and PMM2 knockdown C2C12 cells. Body and TA weight of WT and MLC/mIgf-1 mice were not modified by TUN treatment, while lectin binding slightly decreased in the TA muscle of WT (ConA and AAL) and MLC/mIgf-1 (ConA) mice. The ER-stress-related gene expression did not change in the TA muscle of WT and MLC/mIgf-1 mice after TUN treatment. TUN treatment decreased myogenin mRNA and increased atrogen-1 mRNA, particularly in the TA muscle of WT mice. Finally, the IGF-1 production and IGF1R signaling pathways activation were reduced due to N-glycosylation inhibition in TA and EDL muscles. Decreased IGF1R expression was found in TUN-treated C2C12 myoblasts which was associated with lower IGF-1-induced IGF1R, AKT, and ERK1/2 phosphorylation compared to CTR cells. Chronic TUN-challenge models can help to elucidate the molecular mechanisms through which diseases associated with aberrant N-glycosylation, such as Congenital Disorders of Glycosylation (CDG), affect muscle and other tissue functions.

Effect of a lifestyle intervention program's on breast cancer survivors' cardiometabolic health: Two-year follow-up.

The purpose of this study is to assess the cardiometabolic responses of a lifestyle intervention (LI) conducted at home among breast cancer (BC) survivors during the two years of COVID-19 pandemic. A 3-month LI focused on diet and exercise was performed on thirty BC survivors (women; stages 0-II; non-metastatic; aged 53.6 ± 7.6 years; non-physically active) with a risk factor related to metabolic/endocrine diseases. Anthropometrics, cardiorespiratory fitness (V˙O2max), physical activity level (PAL), adherence to the Mediterranean diet (MeDiet modified questionnaire), and several biomarkers (i.e., glycemia, insulin, insulin resistance [HOMA-IR] index, triglycerides, high- [HDL] and low- [LDL] density lipoproteins, total cholesterol, progesterone, testosterone, and hs-troponin) were evaluated before and 3-, 6-, 12-, and 24-month after the LI. Beneficial effects of the LI were observed on several variables (i.e., body mass index, waist circumference, MeDiet, PAL, V˙ O2max, glycemia, insulin, HOMA-IR index, LDL, total cholesterol, triglycerides, testosterone) after 3-month. The significant effect on Mediterranean diet adherence and V˙ O2max persisted up to the 24-month follow-up. Decreases in HOMA-IR index and triglycerides were observed up to 12-month, however did not persist afterward. This study provides evidence on the positive association between LI and cardiometabolic health in BC survivors.

Physical activity and neurotrophic factors as potential drivers of neuroplasticity in Parkinson's Disease: A systematic review and meta-analysis.

Parkinson's disease (PD) is a neurodegenerative disorder, characterized by motor and non-motor symptoms, that still lacks of a disease-modifying treatment. Consistent evidence proved the benefits of physical therapy on motor and non-motor symptoms in PD patients, leading the scientific community to propose physical activity as disease-modifying therapy for PD and suggesting the involvement of neurotrophic factors (NFs) as key mediators of neuroplasticity. However, the lack of standardized exercise training and methodological flaws of clinical trials have limited the evidence demonstrating the exercise-induced changes in serum and plasma neurotrophic factors concentration. A systematic search, covering 20 years of research in this field and including randomized and non-randomized controlled trials (RCTs and non-RCTs), which reported changes in serum and plasma NFs after a specific intervention, were reviewed. Pooled effect sizes (p-ESs) and 95% confidence intervals (95%CIs) were calculated using a random effects model with R software. A total of 18 articles, of which exercise programs of interventions were codified in terms of type, intensity and duration adopting a standardisation methodology, were included in the systematic review. Six papers, describing the effect of different training programs on BDNF and IGF-1 levels, were included and independently analysed in two meta-analyses. Quantitative analysis for BDNF indicated a statistically significant improvement in serum concentration of PD patients (MD: 5.99 ng/mL; 95%IC: 0.15 -11.83; I2 = 77%) performing physical activity compared with control conditions in RCTs. Preliminary evidence supported the hypothesis that a moderate intensity aerobic exercise (MIAE) would be necessary to induce the changes in NFs. However, sensitivity analysis of meta-analysis and the few studies included in subgroup analysis did not support these results. Alongside, meta-analysis followed by sensitivity analysis revealed a potential change in serum IGF-1 (MD: 33.47 ng/mL; 95%IC: 8.09-58.85) in PD patients performing physical activity with respect controls in RCT studies. Considering the limited evidence to support or refute the increase in NFs levels in PD patients performing physical activity, there is a need to develop a rigorous controlled randomized trial, with standardization for loading intensity of physical activity, greater sample size, and a correct stratification of PD patients to establish a well-defined correlation between physical activity and NFs levels.

Changes in gut microbiota composition after 12 weeks of a home-based lifestyle intervention in breast cancer survivors during the COVID-19 lockdown.

Background: Breast cancer (BC) is the second-leading cause of cancer-related death worldwide. This study aimed to investigate the effects of a 12-week home-based lifestyle intervention (based on nutrition and exercise) on gut microbial composition in twenty BC survivors of the MoviS clinical trial (protocol: NCT04818359). Methods: Gut microbiota analysis through 16S rRNA gene sequencing, anthropometrics, Mediterranean Diet (MD) adherence, and cardiometabolic parameters were evaluated before (Pre) and after (Post) the lifestyle intervention (LI). Results: Beneficial effects of the LI were observed on MD adherence, and cardiometabolic parameters (pre vs post). A robust reduction of Proteobacteria was observed after LI, which is able to reshape the gut microbiota by modulating microorganisms capable of decreasing inflammation and others involved in improving the lipid and glycemic assets of the host. A significant negative correlation between fasting glucose and Clostridia_vadinBB60 (r = -0.62), insulin and homeostatic model assessment (HOMA) index and Butyricicoccus genera (r = -0.72 and -0.66, respectively), and HDL cholesterol and Escherichia/Shigella (r = -0.59) have been reported. Moreover, positive correlations were found between MD adherence and Lachnospiraceae_ND3007 (r = 0.50), Faecalibacterium (r = 0.38) and Butyricimonas (r = 0.39). Conclusion: These data suggest that adopting a healthy lifestyle, may contribute to ameliorate several biological parameters that could be involved in the prevention of cancer relapses through the modulation of gut microbiota.

An Integrated Approach to Skeletal Muscle Health in Aging.

A decline in muscle mass and function represents one of the most problematic changes associated with aging, and has dramatic effects on autonomy and quality of life. Several factors contribute to the inexorable process of sarcopenia, such as mitochondrial and autophagy dysfunction, and the lack of regeneration capacity of satellite cells. The physiologic decline in muscle mass and in motoneuron functionality associated with aging is exacerbated by the sedentary lifestyle that accompanies elderly people. Regular physical activity is beneficial to most people, but the elderly need well-designed and carefully administered training programs that improve muscle mass and, consequently, both functional ability and quality of life. Aging also causes alteration in the gut microbiota composition associated with sarcopenia, and some advances in research have elucidated that interventions via the gut microbiota-muscle axis have the potential to ameliorate the sarcopenic phenotype. Several mechanisms are involved in vitamin D muscle atrophy protection, as demonstrated by the decreased muscular function related to vitamin D deficiency. Malnutrition, chronic inflammation, vitamin deficiencies, and an imbalance in the muscle-gut axis are just a few of the factors that can lead to sarcopenia. Supplementing the diet with antioxidants, polyunsaturated fatty acids, vitamins, probiotics, prebiotics, proteins, kefir, and short-chain fatty acids could be potential nutritional therapies against sarcopenia. Finally, a personalized integrated strategy to counteract sarcopenia and maintain the health of skeletal muscles is suggested in this review.

Movement and health beyond care, MoviS: study protocol for a randomized clinical trial on nutrition and exercise educational programs for breast cancer survivors.

BACKGROUND: Breast cancer (BC) is the most common invasive cancer in women, and exercise can significantly improve the outcomes of BC survivors. MoviS (Movement and Health Beyond Care) is a randomized controlled trial aimed to evaluate the potential health benefits of exercise and proper nutritional habits. This study aims to assess the efficacy of aerobic exercise training in improving quality of life (QoL) and health-related factors in high-risk BC. METHODS: One hundred seventy-two BC survivor women, aged 30-70 years, non-metastatic, stage 0-III, non-physically active, 6-12 months post-surgery, and post chemo- or radiotherapy, will be recruited in this study. Women will be randomly allocated to the intervention arm (lifestyle recommendations and MoviS Training) or control arm (lifestyle recommendations). The MoviS training consists of 12 weeks of aerobic exercise training (2 days/week of supervised and 1 day/week of unsupervised exercise) with a progressive increase in exercise intensity (40-70% of heart rate reserve) and duration (20-60 min). Both arms will receive counseling on healthy lifestyle habits (nutrition and exercise) based on the World Cancer Research Fund International (WCRF) 2018 guidelines. The primary outcome is the improvement of the QoL. The secondary outcomes are improvement of health-related parameters such as Mediterranean diet adherence, physical activity level, flexibility, muscular fitness, fatigue, cardiorespiratory fitness (estimated maximal oxygen uptake), echocardiographic parameters, heart rate variability (average of the standard deviations of all 5 min normal to normal intervals (ASDNN/5 min) and 24 h very low and low frequency), and metabolic, endocrine, and inflammatory serum biomarkers (glycemia, insulin resistance, progesterone, testosterone, and high-sensitivity C-reactive protein). DISCUSSION: This trial aims to evaluate if supervised exercise may improve QoL and health-related factors of BC survivors with a high risk of recurrence. Findings from this project could provide knowledge improvement in the field of exercise oncology through the participation of a multidisciplinary team that will provide a coordinated program of cancer care to improve healthcare quality, improve prognosis, increase survival times and QoL, and reduce the risk of BC recurrence. TRIAL REGISTRATION: ClinicalTrials.gov  NCT04818359 . Retrospectively registered on March 26, 2021.

Effect of individual characteristics and aerobic training on the %HRR-%V̇O2R relationship.

This study aimed to assess if, during incremental exercise, considering individual characteristics can make the relationship between the percentages of heart rate (HRR) and oxygen uptake (V̇O2R) reserve either 1:1 or more accurate. Cycle ergometer data of the maximal incremental exercise tests performed by 450 healthy and sedentary participants (17-66 years) of the HERITAGE Family Study, grouped for sex, ethnicity, age, body fat, resting HR, and V̇O2max, were used to calculate the individual linear regressions between %HRR and %V̇O2R. The mean slope and intercept of the individual linear regressions of each subgroup were compared with 1 and 0 (identity line), respectively, using Hotelling tests followed by post-hoc one-sample t-tests. Two multiple linear regressions were also performed, using either the slopes or intercepts of the individual linear regressions as dependent variables and sex, age, resting HR, and V̇O2max as independent variables. The mean %HRR-%V̇O2R relationships of all subgroups differed from the identity line. Moreover, individual linear regression intercepts (8.9 ± 16.0) and slopes (0.971 ± 0.190) changed (p < 0.001) after 20 weeks of aerobic training (13.1 ± 11.1 and 0.891 ± 0.122). The multiple linear regressions could explain only 3.8% and 1.3% of the variance in the intercepts and slopes, whose variability remained high (standard error of estimate of 15.8 and 0.189). In conclusion, the %HRR-%V̇O2R relationship differs from the identity line regardless of individual characteristics and their difference increased after aerobic training. Moreover, due to the high interindividual variability, using a single equation for the whole population seems not suitable for representing the %HRR-%V̇O2R relationship of a given subject, even when several individual characteristics are considered.HighlightsThe association between %HRR and %V̇O2R is not 1:1 even when individuals are grouped by age, sex, ethnicity, body composition, HRrest, and V̇O2max.Using several subject characteristics to identify the individual's %HRR-%V̇O2R relationship does not meaningfully increase its prediction accuracy or reduce the interindividual variability of %HRR-%V̇O2R relationshipsUsing a single equation for the whole population is not suitable for representing the relationship of a given subject; hence, individual relationships should be preferred when prescribing the intensity of aerobic exercise.The individual %HRR-%V̇O2R relationship should be periodically assessed due to the potential training induced changes in the relationship.

Effect of steady-state aerobic exercise intensity and duration on the relationship between reserves of heart rate and oxygen uptake.

Background: The percentages of heart rate (%HRR) or oxygen uptake (%V̇O2R) reserve are used interchangeably for prescribing aerobic exercise intensity due to their assumed 1:1 relationship, although its validity is debated. This study aimed to assess if %HRR and %V̇O2R show a 1:1 relationship during steady-state exercise (SSE) and if exercise intensity and duration affect their relationship. Methods: Eight physically active males (age 22.6 ± 1.2 years) were enrolled. Pre-exercise and maximal HR and V̇O2 were assessed on the first day. In the following 4 days, different SSEs were performed (running) combining the following randomly assigned durations and intensities: 15 min, 45 min, 60% HRR, 80% HRR. Post-exercise maximal HR and V̇O2 were assessed after each SSE. Using pre-exercise and post-exercise maximal values, the average HR and V̇O2 of the last 5 min of each SSE were converted into percentages of the reserves (%RES), which were computed in a 3-way RM-ANOVA (α = 0.05) to assess if they were affected by the prescription parameter (HRR or V̇O2R), exercise intensity (60% or 80% HRR), and duration (15 or 45 min). Results: The %RES values were not affected by the prescription parameter (p = 0.056) or its interactions with intensity (p = 0.319) or duration and intensity (p = 0.117), while parameter and duration interaction was significant (p = 0.009). %HRRs and %V̇O2Rs did not differ in the 15-min SSEs (mean difference [MD] = 0.7 percentage points, p = 0.717), whereas %HRR was higher than %V̇O2R in the 45-min SSEs (MD = 6.7 percentage points, p = 0.009). Conclusion: SSE duration affects the %HRR-%V̇O2R relationship, with %HRRs higher than %V̇O2Rs in SSEs of longer duration.

Nutraceuticals and Physical Activity as Antidepressants: The Central Role of the Gut Microbiota.

Major depressive disorder (MDD) is a common mental illness. Evidence suggests that the gut microbiota play an essential role in regulating brain functions and the pathogenesis of neuropsychiatric diseases, including MDD. There are numerous mechanisms through which the gut microbiota and brain can exchange information in a continuous, bidirectional communication. Current research emphasizes the interexchange of signals influenced by the gut microbiota that are detected and transduced in information from the gut to the nervous system involving neural, endocrine, and inflammatory mechanisms, suggesting a relationship between oxidative stress and the pathophysiology of MDD via the hyperactivation of inflammatory responses. Potential sources of inflammation in the plasma and hippocampus of depressed individuals could stem from increases in intestinal permeability. Some nutraceuticals, such as specific probiotics, namely psychobiotics, polyphenols, carotenoids, butyrate, and prebiotics, have been demonstrated to exert an antidepressant activity, but most of them need to be metabolized and activated by gut microorganisms. By inducing changes in the gut microbiota composition, physical exercise might also exert a role in alleviating depression-like symptoms. The mutual relationships among nutraceuticals, exercise, and depression will be discussed, and the potential role of the gut microbiota as a therapeutic target to treat depression will be explored.

Defective IGF-1 prohormone N-glycosylation and reduced IGF-1 receptor signaling activation in congenital disorders of glycosylation.

The insulin-like growth factor-1 (IGF-1) signaling pathway is crucial for the regulation of growth and development. The correct processing of the IGF-1Ea prohormone (proIGF-1Ea) and the IGF-1 receptor (IGF-1R) peptide precursor requires proper N-glycosylation. Deficiencies of N-linked glycosylation lead to a clinically heterogeneous group of inherited diseases called Congenital Disorders of Glycosylation (CDG). The impact of N-glycosylation defects on IGF-1/IGF-1R signaling components is largely unknown. In this study, using dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1)], we analyzed the glycosylation pattern of the proIGF-1Ea, IGF-1 secretion efficiency and IGF-1R signaling activity. ALG3-CDG, ALG8-CDG, GMPPB-CDG and some PMM2-CDG fibroblasts showed hypoglycosylation of the proIGF-1Ea and lower IGF-1 secretion when compared with control (CTR). Lower IGF-1 serum concentration was observed in ALG3-CDG, ALG8-CDG and in some patients with PMM2-CDG, supporting our in vitro data. Furthermore, reduced IGF-1R expression level was observed in ALG3-CDG, ALG8-CDG and in some PMM2-CDG fibroblasts. IGF-1-induced IGF-1R activation was lower in most PMM2-CDG fibroblasts and was associated with decreased ERK1/2 phosphorylation as compared to CTR. In general, CDG fibroblasts showed a slight upregulation of Endoplasmic Reticulum (ER) stress genes compared with CTR, uncovering mild ER stress in CDG cells. ER-stress-related gene expression negatively correlated with fibroblasts IGF-1 secretion. This study provides new evidence of a direct link between N-glycosylation defects found in CDG and the impairment of IGF-1/IGF-1R signaling components. Further studies are warranted to determine the clinical consequences of reduced systemic IGF-1 availability and local activity in patients with CDG.

Interventions on Gut Microbiota for Healthy Aging.

In recent years, the improvement in health and social conditions has led to an increase in the average lifespan. Since aging is the most important risk factor for the majority of chronic human diseases, the development of therapies and intervention to stop, lessen or even reverse various age-related morbidities is an important target to ameliorate the quality of life of the elderly. The gut microbiota, that is, the complex ecosystem of microorganisms living in the gastrointestinal tract, plays an important role, not yet fully understood, in maintaining the host's health and homeostasis, influencing metabolic, oxidative and cognitive status; for this reason, it is also named "the forgotten endocrine organ" or "the second brain". On the other hand, the gut microbiota diversity and richness are affected by unmodifiable factors, such as aging and sex, and modifiable ones, such as diet, pharmacological therapies and lifestyle. In this review, we discuss the changes, mostly disadvantageous, for human health, induced by aging, in microbiota composition and the effects of dietary intervention, of supplementation with probiotics, prebiotics, synbiotics, psychobiotics and antioxidants and of physical exercise. The development of an integrated strategy to implement microbiota health will help in the goal of healthy aging.

Nine weeks of high-intensity indoor cycling training induced changes in the microbiota composition in non-athlete healthy male college students.

BACKGROUND: The gut microbiota constitutes a dynamic microbial system constantly challenged by environmental conditions, including physical exercise. Limited human studies suggest that exercise could play a beneficial role for gut health, increasing microbial diversity, even if the effects of exercise on gut microbial microorganisms depends on its intensity and duration. This study aimed to investigate the effects of nine weeks of high-intensity interval exercise on gut microbiota composition in healthy young adults. METHODS: The gut microbiota composition of seventeen healthy male college students was analysed before and after nine weeks of high-intensity interval cycling training by 16S rRNA amplicon sequencing. PERMANOVA for repeated measures was used to test pre-post differences in the relative abundance of all taxonomic levels, and correlations between variations in microbial composition and physical and dietary features were also assessed. RESULTS: Physical exercise induced changes in microbiota composition, at all taxonomic levels analysed (phyla: F [1, 32]=3.97, p=0.029; classes: F [1, 32]=3.39, p=0.033, orders: F [1, 32]=3.17, p=0.044, families: F [1, 32]=1.54, p=0.037, genera: F [1, 32]=1.46, p=0.015, species: F [1, 32]=1.38, p=0.007). Conversely, no differences were found between pre and post-training conditions for microbial community richness (Chao1: V=105, p=0.06) or diversity (Shannon index: V=62, p=0.52; Simpson index: V=59, p=0.43). Changes in the relative abundance of eighteen genera were correlated to changes of twenty environmental factors grouped in physical features, sport-related features, and dietary features. CONCLUSIONS: Nine weeks of high-intensity exercise induced modifications in gut microbiota composition in healthy male college students, shifting the gut microbial population towards a healthier microbiome with benefit to human health in general.

Effects of a Home-Based Lifestyle Intervention Program on Cardiometabolic Health in Breast Cancer Survivors during the COVID-19 Lockdown.

This study aimed to evaluate the cardiometabolic effects of a home-based lifestyle intervention (LI) in breast cancer survivors (BCSs) during the COVID-19 lockdown. In total, 30 BCSs (women; stages 0-II; non-metastatic; aged 53.5 ± 7.6 years; non-physically active; normal left ventricular systolic function) with a risk factor for recurrence underwent a 3-month LI based on nutrition and exercise. Anthropometrics, Mediterranean diet adherence, physical activity level (PAL), cardiorespiratory fitness (VO2max), echocardiographic parameters, heart rate variability (average standard deviation of NN intervals (ASDNN/5 min) and 24 h very- (24 hVLF) and low-frequency (24 hLF)), and metabolic, endocrine, and inflammatory serum biomarkers (glycemia, insulin resistance, progesterone, testosterone, and high-sensitivity C-reactive protein (hs-CRP)) were evaluated before (T0) and after (T1) the LI. After the LI, there were improvements in: body mass index (kg/m2: T0 = 26.0 ± 5.0, T1 = 25.5 ± 4.7; p = 0.035); diet (Mediet score: T0 = 6.9 ± 2.3, T1 = 8.8 ± 2.2; p < 0.001); PAL (MET-min/week: T0 = 647 ± 547, T1 = 1043 ± 564; p < 0.001); VO2max (mL·min-1·kg-1: T0 = 30.5 ± 5.8, T1 = 33.4 ± 6.8; p < 0.001); signs of diastolic dysfunction (participants: T0 = 15, T1 = 10; p = 0.007); AS-DNN/5 min (ms: T0 = 50.6 ± 14.4, T1 = 55.3 ± 16.7; p = 0.032); 24 hLF (ms2: T0 = 589 ± 391, T1 = 732 ± 542; p = 0.014); glycemia (mg/dL: T0 = 100.8 ± 11.4, T1 = 91.7 ± 11.0; p < 0.001); insulin resistance (HOMA-IR score: T0 = 2.07 ± 1.54, T1 = 1.53 ± 1.11; p = 0.005); testosterone (ng/mL: T0 = 0.34 ± 0.27, T1 = 0.24 ± 0.20; p = 0.003); hs-CRP (mg/L: T0 = 2.18 ± 2.14, T1 = 1.75 ± 1.74; p = 0.027). The other parameters did not change. Despite the home-confinement, LI based on exercise and nutrition improved cardiometabolic health in BCSs.

Are there sex differences in physiological parameters and reaction time responses to overload in firefighters?

Male and female firefighters work side-by-side in the same in strenuous and risky conditions. Anthropometrics, physiological, and reaction time (mean of reaction time -MRT-, and errors made -E) parameters of 12 Female and 13 Male firefighters were compared. Effect of overload (step test with and without equipment) on the MRT and E were analyzed on 3 trials (T1 = 1-1s, T2 = 0.5-1s, T3 = 0.5-0.5s), compared with a pre-test condition (basal). T-test between males and females was applied to assess differences (p<0.05) in all parameters. ANOVA with repeated measures and Bonferroni on 3 conditions of step test between males and females was applied in reaction time variables. Between MRT and E, in T1, T2 and T3 trials and the 3 test conditions, ANCOVA models with interactions were used. Differences (p<0.05) in anthropometric, physiological and reaction time data emerged across groups, and on the 3rd trials (T3 vs T1 and T2) in reaction time parameters of each group. ANCOVA showed differences (p<0.001) in E among trials. Post hoc showed significant differences in T1vsT3 and T1vsT2. MRT x trial interaction was extremely significant (P<0.001). Implementing fitness and reaction time exercise programs is important to decrease the injury risk and increase work capacity in firefighters with reference to female workers.

Treatment of Achilles Tendinopathy in Recreational Runners with Peritendinous Hyaluronic Acid Injections: A Viscoelastometric, Functional, and Biochemical Pilot Study.

BACKGROUND: Achilles tendinopathy (AT) affects ca. 10 million recreational runners in Europe; the practice of hyaluronic acid (HA) infiltration is being increasingly adopted. The aim of this pilot study was to monitor the effects of a three-local time-spaced injections regimen of HA in the treatment of AT in middle-aged runners combining for the first time viscoelastometric, biochemical, and functional methodologies with routine clinical examinations. METHODS: Eight male runners (Age 49.3 ± 3.9), diagnosed for unilateral AT, were given three ultrasound (US) guided peritendinous HA injections at the baseline (T0) and every fifteenth day with a follow-up on the forty-fifth day (T1, T2, and T3). At all-time points patients were assessed for viscoelastic tone and stiffness, maximal voluntary isometric contraction (MVIC), and pain level (Likert scale 0-5). The peritendinous effusions of the injured tendon were collected at T0 and T2 to quantify the volume variations and the IL-1ß and MMP-3 levels. RESULTS: At T0 MVIC and pain score were significantly lower and higher, respectively, in injured tendons. The volume, IL-1ß and MMP-3 levels decreased in the course of treatment and the clinical endpoints ameliorated over time. Tone, stiffness, and functional performance also varied significantly at T2 and T3, as compared to T0. CONCLUSIONS: The sequential peritendinous injections of HA were effective in the amelioration of the clinical symptoms, as well as of the functional and viscoelastic state associated with AT. The determination of the viscoelastometric state may help to precisely evaluate the healing process in AT patients.

Current Methods for the Isolation of Urinary Extracellular Vesicles.

Extracellular vesicles (EVs) are small membrane-bound particles released into extracellular space by almost all cell types, and found in body fluids like blood, urine, and saliva. Mounting evidence has demonstrated the clinical potential of EVs as diagnostic and therapeutic tools to analyse physiological/pathological processes due to their ability to transport biomolecules secreted from diverse tissues of an individual.For example, the urinary EVs (uEVs), released from all regions of the kidney's nephron and from other cells that line the urinary tract, retain proteomic and transcriptomic markers specific to their cell of origin representing a valuable tool for kidney disease diagnosis.Despite the numerous efforts in developing suitable methods to separate EVs from biofluids, providing material of high purity and low variability poses a limit to clinical translation.This chapter focuses on advantages and disadvantages of several EV isolation methodologies, and provides examples of uEV isolation protocols based on time, cost, and equipment considerations, as well as the sample requirements for any downstream analyses.

An ultracentrifugation - hollow-fiber flow field-flow fractionation orthogonal approach for the purification and mapping of extracellular vesicle subtypes.

In the course of their life span, cells release a multitude of different vesicles in the extracellular matrix (EVs), constitutively and/or upon stimulation, carrying signals either inside or on their membrane for intercellular communication. As a natural delivery tool, EVs present many desirable advantages, such as biocompatibility and low toxicity. However, due to the complex biogenesis of EVs and their high heterogeneity in size distribution and composition, the characterization and quantification of EVs and their subpopulations still represents an enticing analytical challenge. Centrifugation methods allow to obtain different subpopulations in an easy way from cell culture conditioned medium and biological fluids including plasma, amniotic fluid and urine, but they still present some drawbacks and limitations. An unsatisfactory isolation can limit their downstream analysis and lead to wrong conclusions regarding biological activities. Isolation and characterization of biologically relevant nanoparticles like EVs is crucial to investigate specific molecular and signaling patterns and requires new combined approaches. Our work was focused on HF5 (miniaturized, hollow-fiber flow field-flow fractionation), and its hyphenation to ultracentrifugation techniques, which are the most assessed techniques for vesicle isolation. We exploited model samples obtained from culture medium of murine myoblasts (C2C12), known to release different subsets of membrane-derived vesicles. Large and small EVs (LEVs and SEVs) were isolated by differential ultracentrifugation (UC). Through an HF5 method employing UV, fluorescence and multi-angle laser scattering as detectors, we characterized these subpopulations in terms of size, abundance and DNA/protein content; moreover, we showed that microvesicles tend to hyper-aggregate and partially release nucleic matter. The quali-quantitative information we obtained from the fractographic profiles was improved with respect to Nano Tracking Analysis (NTA) estimation. The SEV population was then further separated using density gradient centrifugation (DGC), and four fractions were submitted again to HF5-multidetection. This technique is based on a fully orthogonal principle, since F4 does not separate by density, and provided uncorrelated information for each of the fractions processed. The "second dimension" achieved with HF5 showed good promise in sorting particles with both different size and content, and allowed to identify the presence of fibrilloid nucleic matter. This analytical bidimensional approach proved to be effective for the characterization of highly complex biological samples such as mixtures of EVs and could provide purified fractions for further biological characterization.