Traditional versus progressive robot-assisted gait training in people with multiple sclerosis and severe gait disability: study protocol for the PROGR-EX randomised controlled trial.

Gait disorders are the most frequent symptoms associated to multiple sclerosis (MS). Robot-assisted gait training (RAGT) in people with MS (PwMS) has been proposed as a possible effective treatment option for severe motor disability without significant superiority when compared to intensive overground gait training (OGT). Furthermore, RAGT at high intensity may enhance fatigue and spasticity. This study aims to evaluate the effects of a low-intensity RAGT at progressively increasing intensity compared to conventional RAGT and OGT in PwMS and moderate to severe walking impairment. 24 PwMS will be recruited and assigned to one of the three treatment groups: low-intensity RAGT at progressively increasing intensity, conventional RAGT and OGT. All participants will receive 3-weekly treatment sessions of 3 hours each for 4 weeks. In the first 2 hours of treatment, all participants will receive a rehabilitation programme based on stretching exercises, muscle strengthening and educational interventions. During the last hour, subjects will undergo specific gait training according to the assignment group. Outcomes will be assessed before and after treatment and at 3-month follow-up. The primary outcome is walking speed. Secondary outcomes include mobility and balance, psychological measures, muscle oxygen consumption, electrical and haemodynamic brain activity, urinary biomarkers, usability, and acceptability of robotic devices for motor rehabilitation. The results of this study will provide a safe, affordable and non-operator-dependent, intervention for PwMS. Results in terms of functional, psychological, neurophysiological and biological outcomes will confirm our hypothesis. The study's trial registration number: NCT06381440.

The Impact of Physical Exercise on microRNAs in Hemodialysis Patients: A Review and a Protocol for an Ancillary Study.

Physical inactivity is considered a significant risk factor for mortality and morbidity among chronic hemodialysis (HD) patients. Therefore, physical exercise is recommended in the treatment of HD patients. Although the beneficial effects of physical exercise in HD patients are well-described in the literature, the underlying physiological mechanisms still need to be fully understood. Recently, microRNAs (miRNAs) have emerged as potential mediators of the therapeutic effects of physical exercise in healthy individuals. miRNAs are short, single-stranded, noncoding RNAs involved in gene expression regulation. Specifically, upon forming the RNA-induced silencing complex, miRNAs selectively bind to specific miRNAs within cells, reducing gene expression. miRNAs can be secreted by cells in an accessible form or enclosed within exosomes or extracellular vesicles. They can be detected in various body fluids, including serum (circulating miRNAs), facilitating the study of their diverse expression. Currently, there is no available data regarding the impact of physical exercise on the expression of miRNAs involved in osteogenic differentiation, a fundamental mechanism in the development of vascular calcification, for HD patients. Therefore, we have designed an observational and longitudinal case-control study to evaluate the expression of miR-9 and miR-30b in HD patients participating in a 3-month interdialytic physical exercise program. This paper aims to present the study protocol and review the expression of circulating miRNAs in HD patients and their modulation through physical exercise.

A "test in-train out" program versus a "go home and walk" intervention for home-based exercise therapy in patients with peripheral artery disease: A randomized controlled trial.

OBJECTIVE: In this single-blinded randomized controlled trial, we compared the "Test in-Train Out" structured home-based exercise program (TiTo-SHB) with the traditional "go home and walk" exercise intervention in people with peripheral artery disease (PAD). METHODS: Peripheral artery disease patients at Leriche-Fontaine's stage II were randomized to receive TiTo-SHB or walking advice (C-WA). The TiTo-SHB group performed two daily 8-min sessions of pain-free interval walking at progressive low-to-moderate speed maintained with a metronome. The C-WA group was recommended to walk for 30 min at least three times per week and to endure claudication pain. Outcomes collected at baseline and at the end of the program (6 months) included: 6-min and pain-free walking distance (6MWD, PFWD), ankle-brachial index (ABI), 5-time sit-to-stand test (5STS), and health-related quality of life (HRQoL) by the VascuQoL-6 questionnaire. RESULTS: A total of 68 patients were randomized (males n = 50; aged 73 ± 9; TiTo-SHB n = 34). At the end of the program, patients in the TiTo-SHB group compared with the C-WA group had significantly improved 6MWD (Δ + 60 ± 32 m vs. Δ - 5 ± 37 m; p < 0.001) and PFWD (Δ + 140 ± 92 m vs. Δ - 7 ± 87 m; p < 0.001). A significant between-group difference in favor of the TiTo-SHB group was also recorded for all the secondary outcomes, including 5STS (Δ - 2.6 ± 1.8 s vs. Δ + 0.8 ± 2.6 s; p < 0.001), ABI of the more impaired limb (Δ + 0.10 ± 0.11 vs. Δ + 0.02 ± 0.08; p = 0.003), and VascuQoL-6 score (Δ +2 ± 2 vs. -1 ± 4; p < 0.001). CONCLUSION: In PAD patients with claudication, the pain-free in-home TiTo-SHB program was more effective in improving exercise capacity and HRQoL than the traditional walking advice recommendation.

Cardiac rehabilitation and acute aortic dissection: understanding and addressing the evidence GAP a systematic review.

Despite guideline recommendations, strategies for implementing cardiac rehabilitation (CR) in patients with acute aortic dissection (AAD) are not well established with little evidence to risk stratify prudent and effective guidelines for the many required variables. We conducted a systematic review of studies (2004-2023) reporting CR following type A (TA) and type B (TB) AAD. Our review is limited to open surgical repair for TA and medical treatment for TB. A total of 5 studies were included (4 TA-AAD and 1 TB-AAD) in the qualitative analysis. In general, observational data included 311 patients who had an overall favorable effect of CR in AAD consisting of a modestly improved exercise capacity and work load during cycle cardiopulmonary exercise test (TB-AAD), and improved quality of life (QoL). No adverse events were reported during symptom limited pre-CR treadmill or cycle exercise VO2 max or CR. Given the overall potential in this high risk population without adequate evidence for important variables such as safe time from post-op to CR, intensity of training, duration and frequency of sessions and followup it is time for a moderate sized well designed safe trial for patients' post-op surgery for TA-AAD and medically treated TB-AAD who are treated with standardized evidence based medical therapy and physical therapy from discharge randomized to CR versus usual care. PROSPERO registry ID: CRD42023392896.

Transcriptomic responses to location learning by honeybee dancers are partly mirrored in the brains of dance-followers.

The waggle dances of honeybees are a strikingly complex form of animal communication that underlie the collective foraging behaviour of colonies. The mechanisms by which bees assess the locations of forage sites that they have visited for representation on the dancefloor are now well-understood, but few studies have considered the remarkable backward translation of such information into flight vectors by dance-followers. Here, we explore whether the gene expression patterns that are induced through individual learning about foraging locations are mirrored when bees learn about those same locations from their nest-mates. We first confirmed that the mushroom bodies of honeybee dancers show a specific transcriptomic response to learning about distance, and then showed that approximately 5% of those genes were also differentially expressed by bees that follow dances for the same foraging sites, but had never visited them. A subset of these genes were also differentially expressed when we manipulated distance perception through an optic flow paradigm, and responses to learning about target direction were also in part mirrored in the brains of dance followers. Our findings show a molecular footprint of the transfer of learnt information from one animal to another through this extraordinary communication system, highlighting the dynamic role of the genome in mediating even very short-term behavioural changes.

Variations in Health-Related Quality of Life After Stroke: Insights From a Clinical Trial on Arm Rehabilitation With a Long-Term Follow-Up.

Despite rehabilitation, stroke patients continue to have impaired function and reduced health-related quality of life (HRQoL) even in a chronic stage. However, no clear information is available on long-term variations in HRQoL. In this study, we aimed to report the short- and long-term changes in HRQoL in a subacute stroke sample that was enrolled in a clinical trial on arm rehabilitation. Thirty-nine stroke survivors (62% male, mean age 68 years) were assessed using the Stroke Impact Scale Version 2.0 (SIS 2.0) pre and post rehabilitation and at 6 months and 6 years follow-up. Long-term changes in physical function were explored through clinically meaningful changes in the Stroke Impact Scale-16 (SIS-16). After rehabilitation (P < .001), an overall improvement was found in all SIS domains except the memory and thinking, emotions, and communication domains. The baseline SIS-16 score (P < .001), the presence of a sensory deficit, and rehabilitation setting (P < .05) were factors related to the SIS-16 domain scores at the end of rehabilitation and at 6 months follow-up. Patients showed the most deterioration in the mobility (P < .001), strength (P < .003), and hand function (P < .05) domains 6 years after stroke. Stroke severity, male gender, and age ⩾65 years are related with a long-term HRQoL reduction after stroke.

Effects of Exercise, Rehabilitation, and Nutritional Approaches on Body Composition and Bone Density in People with Multiple Sclerosis: A Systematic Review and Meta-Analysis.

People with multiple sclerosis (pwMS) are affected by a wide range of disabilities, including a decrease in bone mineral density (BMD) and a worsening of body composition (BC), which negatively impact their quality of life quality. This study aims to analyze the effects of nonpharmacological interventions-in particular, physical activity, nutritional approaches, and rehabilitation-on BC and BMD in pwMS. This systematic review and meta-analysis was performed following the updated version of the PRISMA guidelines. In July 2022, five databases (MEDLINE, Embase, The Cochrane Library, Google Scholar, Web of Science) and gray literature were screened. Relevant articles published between 1 January 1990 and 1 September 2022 in any language were included. Outcomes of interest were anthropometric, BC measures, and BMD. The RoB 2.0 tool was used to assess the risk of bias. After duplicates elimination, 1120 records were screened, and 36 studies were included. A total of 25 articles were focused on physical activity and rehabilitation, 10 on nutrition, and 1 on multimodal intervention. One-third of the studies were judged to be at high risk of bias. The meta-analysis showed a high degree of heterogeneity due to the high variability in disease severity and intervention duration, intensity, frequency, and type. In general, no intervention showed consistent positive effects on BC. However, the most promising interventions seemed to be high-intensity training and ketogenic diets. Only a few studies considered BMD, and the results are inconsistent. Nevertheless, more studies are needed in order to confirm these results.

Foot Temperature by Infrared Thermography in Patients with Peripheral Artery Disease before and after Structured Home-Based Exercise: A Gender-Based Observational Study.

Decreased arterial perfusion is a typical condition of patients with peripheral artery disease (PAD), with the microvascular picture particularly present among women. This observational study aimed to detect foot perfusion changes by infrared thermography (IRT) after a home-based exercise program in both sexes. A total of 76 PAD patients with claudication (72 ± 4 years; 52 males) were enrolled in a structured in-home exercise program composed of two daily 8 min interval walking sessions (1:1 walk:rest ratio) with progressively increasing speed. Outcome measures collected at baseline (T0) and at each hospital visit after 5 weeks, 12 weeks and 20 weeks included foot temperature measured by IRT (anterior tibial, posterior tibial, dorsalis pedis and arcuate artery regions), ankle brachial index and the 6 min walking test. After 20 weeks, foot temperature in both limbs showed a significant increasing trend, with a mean variation of 1.3 °C for the more impaired limb and 0.9 °C for the contralateral limb (t = 8.88, p < 0.001 and t = 5.36; p < 0.001, respectively), with significant changes occurring after 5 weeks of training. The sex-oriented analysis did not highlight any significant difference, with an improvement of mean foot temperature of 1.5 ± 0.6 °C in females versus 1.2 ± 0.5 °C in males (p = 0.42). Ankle brachial index and performance also significantly improved over time (p < 0.001) without gender differences. In patients with PAD, a structured low-intensity exercise program significantly improved foot temperature and exercise capacity without any sex-related difference.

Quantitative Comparison of Hand Kinematics Measured with a Markerless Commercial Head-Mounted Display and a Marker-Based Motion Capture System in Stroke Survivors.

Upper-limb paresis is common after stroke. An important tool to assess motor recovery is to use marker-based motion capture systems to measure the kinematic characteristics of patients' movements in ecological scenarios. These systems are, however, very expensive and not readily available for many rehabilitation units. Here, we explored whether the markerless hand motion capabilities of the cost-effective Oculus Quest head-mounted display could be used to provide clinically meaningful measures. A total of 14 stroke patients executed ecologically relevant upper-limb tasks in an immersive virtual environment. During task execution, we recorded their hand movements simultaneously by means of the Oculus Quest's and a marker-based motion capture system. Our results showed that the markerless estimates of the hand position and peak velocity provided by the Oculus Quest were in very close agreement with those provided by a marker-based commercial system with their regression line having a slope close to 1 (maximum distance: mean slope = 0.94 ± 0.1; peak velocity: mean slope = 1.06 ± 0.12). Furthermore, the Oculus Quest had virtually the same sensitivity as that of a commercial system in distinguishing healthy from pathological kinematic measures. The Oculus Quest was as accurate as a commercial marker-based system in measuring clinically meaningful upper-limb kinematic parameters in stroke patients.

Exercise-based functional recovery from severe upper extremity arterial disease due to bilateral subclavian artery obstruction in a person with giant cell arteritis.

We report the case of a 71-year-old woman diagnosed with giant cell arteritis with bilateral subclavian and axillary obstruction and severe arm claudication that occurred 3 months earlier and was non-regressed after corticosteroids. Before possible revascularization, the patient was initiated to a personalized home-based graded exercise program including walking, hand-bike pedaling, and muscle strength training. During the 9 months of treatment, the patient progressively improved radial pressure values (10 to 85 mmHg), hand temperature values by infrared-thermography (+2.1 °C), arm endurance, and forearm muscle oxygenation by near-infrared spectroscopy. Home-based graded exercise proved to be a noninvasive option for upper limb claudication.

Lower All-Cause Mortality Risk in Females and Males with Peripheral Artery Disease following Pain-Free Home-Based Exercise: A 7-Year Observational Study.

We evaluated the sex-specific difference in response upon participation in an exercise program with respect to the risk of adverse clinical outcomes among patients with peripheral artery disease (PAD) and claudication. The records of 400 PAD patients were assessed between 2012 and 2015. Two hundred of them were addressed to a walking program prescribed at the hospital and executed at home at symptom-free walking speed (Ex), while the remaining 200 acted as a control group (Co). The number and date of deaths, all-cause hospitalizations, and amputations for a 7-year period were collected from the regional registry. At baseline, no differences were observed (MEXn = 138; FEXn = 62; MCOn = 149; FCOn = 51). The 7-year survival rate was significantly higher in FEX (90%) than in MEX (82% hazard ratio, HR: 0.542 95% CI 0.331-0.885), FCO (45%, HR: 0.164 95% CI 0.088-0.305), and MCO (44%; HR: 0.157 95% CI 0.096-0.256). A significantly lower rate of hospitalization (p < 0.001) and amputations (p = 0.016) was observed for the Ex group compared to the Co group, without differences by sex. In conclusion, in PAD patients, active participation in a home-based pain-free exercise program was associated with a lower rate of death and better long-term clinical outcomes, particularly among women.

Inspiratory-Expiratory Muscle Training Improved Respiratory Muscle Strength in Dialysis Patients: A Pilot Randomised Trial.

End-stage kidney disease (ESKD) exposes patients to progressive physical deconditioning involving the respiratory muscles. The aim of this pilot randomized controlled trial was to determine the feasibility and effectiveness of low-intensity respiratory muscle training (RMT) learned at the hospital and performed at home. A group of ESKD patients (n = 22) were randomized into RMT or usual care (control group, CON) in a 1:1 ratio. The respiratory training was performed at home with an inspiratory-expiratory system for a total of 5 min of breathing exercises in a precise rhythm (8 breaths per minute) interspersed with 1 min of rest, two times per day on nondialysis days for a total of 4 weeks, with the air resistance progressively increasing. Outcome measures were carried out every 4 weeks for 3 consecutive months, with the training executed from the 5th to the 8th week. Primary outcomes were maximal inspiratory and expiratory pressure (MIP, MEP), while secondary outcomes were lung capacity (FEV1, FVC, MVV). Nineteen patients without baseline between-group differences completed the trial (T: n = 10; Age: 63 ± 10; Males: n = 12). Both MIP and MEP significantly improved at the end of training in the T group only, with a significant difference of MEP of 23 cmH2O in favor of the RMT group (p = 0.008). No significant variations were obtained for FVC, FEV1 or MVV in either group, but there was a greater decreasing trend over time for the CON group, particularly for FVC (t = -2.00; p = 0.046). Low-fatiguing home-based RMT, with a simple device involving both inspiratory and expiratory muscles, may significantly increase respiratory muscle strength.

The Issue of Gender Bias Represented in Authorship in the Fields of Exercise and Rehabilitation: A 5-Year Research in Indexed Journals.

Despite progress made in recent decades, gender bias is still present in scientific publication authorship. The underrepresentation of women and overrepresentation of men has already been reported in the medical fields but little is known in the fields of exercise sciences and rehabilitation. This study examines trends in authorship by gender in this field in the last 5 years. All randomized controlled trials published in indexed journals from April 2017 to March 2022 through the widely inclusive Medline dataset using the MeSH term "exercise therapy" were collected, and the gender of the first and last authors was identified through names, pronouns and photographs. Year of publication, country of affiliation of the first author, and ranking of the journal were also collected. A chi-squared test for trends and logistic regression models were performed to analyze the odds of a woman being a first or last author. The analysis was performed on a total of 5259 articles. Overall, 47% had a woman as the first author and 33% had a woman as the last author, with a similar trend over five years. The trend in women's authorship varied by geographical area, with the higher representation of women authors in Oceania (first: 53.1%; last: 38.8%), North-Central America (first: 45.3%; last: 37.2%), and Europe (first: 47.2%; last: 33.3%). The logistic regression models (p < 0.001) indicated that women have lower odds of being authors in prominent authorship positions in higher-ranked journals. In conclusion, over the last five years, in the field of exercise and rehabilitation research, women and men are almost equally represented as first authors, in contrast with other medical areas. However, gender bias, unfavoring women, still exists, especially in the last authorship position, regardless of geographical area and journal ranking.

SARS-COV-2 Pandemic for Patients with Chronic Obstructive Peripheral Arterial Disease: Impact of Interruption to Access According to Gender in a Single Center Experience.

BACKGROUND: This retrospective study aims to evaluate the impact of interrupted services for peripheral arterial disease (PAD) patients and especially women in a single north-eastern Italian center over a period of 3 months prior to the pandemic, during the first (2020) and the second (2021) wave of contagion in northern Italy. METHODS: Patients with PAD at Rutherford stages 3 to 6 that required revascularization between March 2019 and March 2021 were classified into 3 groups, according to the period of treatment: the prepandemic period, the pandemic-20 period, and the pandemic-21 period. RESULTS: Twenty-eight patients were treated in the prepandemic period, 21 in the pandemic-20 period, and 39 in the pandemic-21 period. It was observed that in the both pandemic periods patients presented with more severe stages of limb ischemia, Rutherford 5 and 6 stages. During pandemic-20, patients underwent mostly open surgery, followed by hybrid procedures. No differences were observed between the 3 groups in major amputations, length of hospital stay, type of discharge, limb salvage and mortality. During long-term follow-up, limb salvage appeared to be significantly better in the pandemic-21 group. The gender analysis revealed a significantly reduced female proportion of overall treated patients in 2020 and 2021 compared to the prepandemic period. In the pandemic-20 this difference appears even more evident since treatments on females represented 19% of the total while in the same period of the previous year the male/female percentage was comparable (54% vs. 46%). The women admitted presented higher stages of disease and tended to have a longer hospital stay than men. At 12-month follow-up, limb salvage was similar between the 2 genders but was slightly worse in women. CONCLUSIONS: An efficient reorganization of the vascular surgery services during the pandemic period guaranteed the quality and standard of treatment offered in the preceding periods. Among patients suffering from PAD the impact of the pandemic was greater for the female gender. It is therefore important that in addition to a reorganization of hospital services to provide adequate care for patients with ACOP in the pandemic period, greater information and awareness of women.

Anti-Inflammatory and Cortical Responses after Transcranial Direct Current Stimulation in Disorders of Consciousness: An Exploratory Study.

Disorders of consciousness (DoC) due to severe traumatic brain injury (TBI) are associated with severe disability and an alteration of cortical activation, angiogenesis, and inflammation, which are crucial elements for behavioural recovery. This exploratory study aimed to evaluate anti-inflammatory and cortical responses after transcranial direct current stimulation (tDCS) in traumatic prolonged disorders of consciousness. Ten minimally conscious state (MCS) patients underwent ten sessions of anodal tDCS (five sessions/week, two weeks, 40 min/session) on the primary motor cortex bilaterally. Clinical evaluations were performed using the Coma Recovery Scale-Revised (CRS-R) pre- and post-treatment. In contrast, after single and multiple tDCS sessions, the haemodynamic cortical response was obtained with functional near-infrared spectroscopy (fNIRS). Moreover, angiogenesis (angiopoietin-2, BMP9, endoglin, HbEFG, HGF, IL8, Leptin, PLGF, VEGF-A, and VEGF-C) and inflammation (GM-CSF, IFNg, IP10, MCP1, and TNFα) circulating biomarkers were collected. A significant haemodynamic response was observed after a single tDCS session, with an increased activation from 4.4 (3.1-6.1) to 7.6 (2.9-15.7) a.u. (p = 0.035). After ten tDCS sessions, a significant reduction of angiopoietin-2, VEGF-C, and IP-10 was detected. Moreover, a correlation between behavioural (CRS-R), TNFα (r = 0.89; p = 0.007), and IP10 (r = 0.81; p = 0.014) variation was found. In conclusion, a single tDCS session can increase the cortical activation in MCS patients. Moreover, multiple tDCS sessions showed an anti-inflammatory effect related to behavioural improvement.

The Value of Infrared Thermography to Assess Foot and Limb Perfusion in Relation to Medical, Surgical, Exercise or Pharmacological Interventions in Peripheral Artery Disease: A Systematic Review.

Infrared thermography (IRT) is a promising imaging method in patients with peripheral artery disease (PAD). This systematic review aims to provide an up-to-date overview of the employment of IRT as both a diagnostic method and an outcome measure in PAD patients in relation to any kind of intervention. On September 2022, MEDLINE, EMBASE, CENTRAL, Google Scholar, Web of Science, and gray literature were screened. Eligible articles employing IRT in PAD were screened for possible inclusion. The RoB 2.0 tool was used to assess the risk of bias. Twenty-one eligible articles were finally included, recruiting a total of 1078 patients. The IRT was used for PAD diagnosis/monitoring in 11 studies or to assess the effect of interventions (revascularization, pharmacological therapy, or exercise rehabilitation) in 10 studies. The analysis of the included papers raised high concerns about the overall quality of the studies. In conclusion, IRT as a noninvasive technique showed promising results in detecting foot perfusion in PAD patients. However, limits related to devices, points of reference, and measurement conditions need to be overcome by properly designed trials before recommending its implementation in current vascular practice.

Effect of physical activity interventions on quality of life in older adults: A protocol for systematic review and meta-analysis.

INTRODUCTION: Quality of life (QoL) has been acknowledged as a fundamental concept in the field of health and is favorably improved by physical activity (PA). This systematic review aims to assess the benefits and harms of different types of PA to improve health-related QoL in both community-dwelling and diseased older adults to provide a recommendation for the minimum amount of PA needed to obtain measurable QoL benefits. METHODS AND ANALYSIS: We will search MEDLINE, Cochrane Central Register of Controlled Trials, CINHAL, Epistemonikos, Web of Science and gray literature. Randomized controlled trials enrolling healthy or diseased older adults aged > 65 years, providing any kind of physical activity intervention and having quality of life as an outcome will be included. There will be no language restriction. Two independent reviewers will screen the papers, and a third reviewer will resolve the conflicts. The quality of the included studies will be assessed through the Risk of Bias 2.0 tool. Finally, data will be extracted to create proper meta-analyses of comparisons between the different kinds of physical activity interventions or to control groups. ETHICS AND DISSEMINATION: This review does not require approval from the Ethics Committee. The results will be disseminated in peer-reviewed journals and at international conferences; moreover, the findings will be shared on social media using an accessible language.