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The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19), resulting in acute respiratory disease, is a worldwide emergency. Because recently it has been found that SARS-CoV is dependent on host transcription factors (TF) to express the viral genes, efforts are required to understand the molecular interplay between virus and host response. By bioinformatic analysis, we investigated human TF that can bind the SARS-CoV-2 sequence and can be involved in viral transcription. In particular, we analysed the key role of TF involved in interferon (IFN) response. We found that several TF could be induced by the IFN antiviral response, specifically some induced by IFN-stimulated gene factor 3 (ISGF3) and by unphosphorylated ISGF3, which were found to promote the transcription of several viral open reading frame. Moreover, we found 22 TF binding sites present only in the sequence of virus infecting humans but not bat coronavirus RaTG13. The 22 TF are involved in IFN, retinoic acid signalling and regulation of transcription by RNA polymerase II, thus facilitating its own replication cycle. This mechanism, by competition, may steal the human TF involved in these processes, explaining SARS-CoV-2's disruption of IFN-I signalling in host cells and the mechanism of the SARS retinoic acid depletion syndrome leading to the cytokine storm. We identified three TF binding sites present exclusively in the Brazilian SARS-CoV-2 P.1 variant that may explain the higher severity of the respiratory syndrome. These data shed light on SARS-CoV-2 dependence from the host transcription machinery associated with IFN response and strengthen our knowledge of the virus's transcription and replicative activity, thus paving the way for new targets for drug design and therapeutic approaches.

Ad oggi l'origine dei fibroblasti, le principali cellule responsabili dello sviluppo della fibrosi renale, è ancora incerta. In un recente lavoro pubblicato da Asada e colleghi, gli Autori dimostrano che la maggior parte dei fibroblasti secernenti eritropoietina nel rene normale hanno un'origine extra renale e provengono da cellule della Cresta Neurale. Durante lo sviluppo della fibrosi renale, queste cellule trans-differenziano in miofibroblasti, perdendo la loro capacità intrinseca di produrre eritropoietina. Questi interessanti dati potrebbero rappresentare il punto di partenza per lo sviluppo di nuovi farmaci capaci da un lato di ridurre la fibrosi renale e dall'altro di preservare la produzione di eritropoietina.

Liquid biopsy is a valuable emerging alternative to tissue biopsy with great potential in the noninvasive early diagnostics of cancer. Liquid biopsy based on single cell analysis can be a powerful approach to identify circulating tumor cells (CTCs) in the bloodstream and could provide new opportunities to be implemented in routine screening programs. Since CTCs are very rare, the accurate classification based on high-throughput and highly informative microscopy methods should minimize the false negative rates. Here, we show that holographic flow cytometry is a valuable instrument to obtain quantitative phase-contrast maps as input data for artificial intelligence (AI)-based classifiers. We tackle the problem of discriminating between A2780 ovarian cancer cells and THP1 monocyte cells based on the phase-contrast images obtained in flow cytometry mode. We compare conventional machine learning analysis and deep learning architectures in the non-ideal case of having a dataset with unbalanced populations for the AI training step. The results show the capacity of AI-aided holographic flow cytometry to discriminate between the two cell lines and highlight the important role played by the phase-contrast signature of the cells to guarantee accurate classification.

We show how reflectarray antenna synthesis can take profit from parallel computing on Graphics Processing Units (GPUs). The presented approach uses an implementation of Particle Swarm Optimization in CUDA language and accelerates the computation of the field radiated by the reflectarray using a GPU- mplemented Non-Uniform FFT routine. Numerical results show how computing time can be kept convenient for the application at hand.

We compare the computational performance of the Fast Marching Method, the Fast Sweeping Method and the Fast Iterative Method to determine a numerical solution to the eikonal equation. We point out how the Fast Iterative Method outperforms the other two thanks to its parallel processing capabilities.

Objective: Vulvodynia is a chronic clinical condition characterized by provoked or non-provoked vulvar pain for at least 3 months of unknown etiology. The onset of vulvodynia involves a complex interplay of peripheral and central pain mechanisms, such as pelvic floor muscle and autonomic dysfunction, and interpersonal factors. A stepwise approach of pelvic floor physical therapy as medical management is suggested. In this scenario, by this meta-analysis of randomized controlled trials, we aimed to evaluate the efficacy of rehabilitation interventions in patients with vulvodynia., Methods: On October 13, 2022, PubMed, Scopus, and Web of Science were systematically searched for randomized controlled trials that assessed the efficacy of the rehabilitative approach to pain during intercourse in patients with vulvodynia. The quality assessment was performed with the Cochrane risk-of-bias tool for randomized trials. The trial registration number is CRD42021257449. At the end of the search, 9 studies were included for a total of 332 patients. A pairwise meta-analysis was performed to highlight the efficacy of rehabilitative approaches for reducing pain during intercourse, as measured with a visual analog scale or a numerical rating scale., Results: Meta-analysis showed that all these rehabilitative approaches had an overall effect size of -1.43 (95% CI = -2.69 to -0.17) in decreasing vulvodynia pain in terms of the visual analog scale. In the subgroup analysis, a significant effect size in acupuncture (effect size = -2.36; 95% CI = -3.83 to -0.89) and extracorporeal shockwave therapy (effect size = -2.94; 95% CI = -4.31 to -1.57; I2 = 58%) was observed. According to the Cochrane risk-of-bias tool, a low risk of bias for outcome selection in 89% of studies., Conclusion: Findings from this meta-analysis suggested that the physical agent modalities and complementary medicine techniques in people with vulvodynia appear to be more effective than placebo, sham, or waiting list. Further evidence on physical agent modalities and complementary therapies are warranted in the future., Impact: This was the first systematic review and meta-analysis of randomized controlled trials to provide evidence on the efficacy of rehabilitation interventions in patients with vulvodynia., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Malignant pleural mesothelioma (MPM) represents a significant health burden, with limited treatment options and poor prognosis. Despite advances in pharmacological and surgical interventions, the role of rehabilitation in MPM management remains underexplored. This study aims to assess the feasibility of a tailored pulmonary rehabilitation intervention addressing physical and respiratory function in MPM patients. A prospective pilot study was conducted on surgically treated MPM patients referred to a cardiopulmonary rehabilitation service. The intervention comprised multidisciplinary educational sessions, physical rehabilitation, and respiratory physiotherapy. Feasibility was evaluated based on dropout rates, adherence to the rehabilitation program, safety, and patient-reported outcomes. Twelve patients were initially enrolled, with seven completing the study. High adherence to physical (T1: 93.43%, T2: 82.56%) and respiratory (T1: 96.2%, T2: 92.5%) rehabilitation was observed, with minimal adverse events reported. Patient satisfaction remained high throughout the study (GPE scores at T1: 1.83 ± 1.17; T2: 2.0 ± 1.15), with improvements noted in physical function, pain management, and health-related quality of life. However, some issues, such as time constraints and lack of continuous supervision, were reported by participants. This pilot study demonstrates the feasibility and potential benefits of a tailored pulmonary rehabilitation intervention in MPM patients. Despite its promising outcomes, further research with larger samples is warranted to validate its efficacy and integrate rehabilitation as a component into the multidisciplinary management of MPM.

Objectives: This systematic review aimed at evaluating the reliability of dental maturation (DM) according to Demirjian method compared to hand and wrist maturation (HWM) to assess skeletal maturity (SM) in growing subjects, to identify the teeth and the corresponding mineralisation stages related to the pubertal growth spurt (PGS)., Materials and Methods: PubMed, Scopus, and Web of Science were systematically searched until January 5th, 2024, to identify observational cross-sectional studies that assessed the reliability of Demirjian method compared to the HWM methods (i.e., Grave and Brown and Fishman) in growing subjects. The quality assessment was evaluated using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist., Results: Out of 136 papers suitable for title/abstract screening, 19 included studies. Of them, 17 papers showed the reliability of Demirjian DM method compared to HWM Fishman and Grave and Brown methods to assess SM in growing subjects. According to JBI Critical Appraisal Checklist, 12 papers were high-quality studies and 7 papers were medium-quality studies.  Conclusions: The mandibular second molar might be considered as the best indicator compared to other teeth and that the peak of growth occurs no earlier than stage F in females and stage G in males according to Demirjian method. Also, the mandibular canine might be analysed as indicator of SM in males, and results suggest that the peak of growth occurs no earlier than maturation stage F according to Demirjian method, only in male subjects. Further studies are needed to confirm these findings.

Although rehabilitation medicine emphasizes a holistic health approach, there is still a large gap of knowledge about potential interventions aimed at improving overall wellbeing through cosmetic interventions. Therefore, this narrative review investigates the role of different rehabilitative techniques in enhancing aesthetics, quality of life, and psychosocial wellbeing for patients with disabilities. The study follows the SANRA framework quality criteria for a narrative review. Literature searches across PubMed/Medline, Web of Science, and Scopus identified articles focusing on rehabilitation strategies within the aesthetic rehabilitation domain. The review identified evidence supporting injection procedures, such as Botulinum Toxin, Platelet-Rich Plasma, Hyaluronic Acid, Ozone, and Carboxytherapy, and assessing their applications in several disabling disorders. Additionally, physical therapies like Extracorporeal Shock Wave Therapy, Laser Therapy, Microcurrent Therapy, Tecar Therapy, and physical exercises were explored for their impact on cutaneous microcirculation, cellulite treatment, wound healing, and scar appearance improvement. Lastly, the manuscript underlines the role of manual therapy techniques in addressing both physical discomfort and aesthetic concerns, discussing their effectiveness in adipose tissue therapy, scar tissue mobilization, and regional fat thickness reduction. Taken together, this review emphasizes the role of a multidisciplinary approach, aiming to provide valuable insights into potential benefits for both functional and aesthetic outcomes.

Catheter-based revascularization procedures were developed as an alternative to systemic thrombolysis for patients with intermediate-high- and high-risk pulmonary embolisms. USAT IH-PE is a retrospective and prospective multicenter registry of such patients treated with ultrasound-facilitated, catheter-directed thrombolysis, whose preliminary results are presented in this study. The primary endpoint was the incidence of pulmonary hypertension (PH) at follow-up. Secondary endpoints were short- and mid-term changes in the echocardiographic parameters of right ventricle (RV) function, in-hospital and all-cause mortality, and procedure-related bleeding events. Between March 2018 and July 2023, 102 patients were included. The majority were at intermediate-high-risk PE (86%), were mostly female (57%), and had a mean age of 63.7 ± 14.5 years, and 28.4% had active cancer. Echocardiographic follow-up was available for 70 patients, and in only one, the diagnosis of PH was confirmed by right heart catheterization, resulting in an incidence of 1.43% (CI 95%, 0.036-7.7). RV echocardiographic parameters improved both at 24 h and at follow-up. In-hospital mortality was 3.9% (CI 95%, 1.08-9.74), while all-cause mortality was 11% (CI 95%, 5.4-19.2). Only 12% had bleeding complications, of whom 4.9% were BARC ≥ 3. Preliminary results from the USAT IH-PE registry showed a low incidence of PH, improvement in RV function, and a safe profile.

Charcot-Marie-Tooth (CMT) disease is one of the most common inherited neuropathies and can lead to progressive muscular weakness, pes cavus, loss of deep tendon reflexes, distal sensory loss, and gait impairment. There are still no effective drugs or surgical therapies for CMT, and supportive treatment is limited to rehabilitative therapy and surgical treatment of skeletal deformities. Many rehabilitative therapeutic approaches have been proposed, but timing and cadence of rehabilitative intervention are not clearly defined, and long-term follow-up is lacking in literature. The aim of this real-practice retrospective study was to assess the effectiveness of an intensive neurorehabilitation protocol on muscle strength and functioning in CMT patients. We analyzed data of patients with diagnosis of mild to moderate CMT. The rehabilitation program lasted 2-4 h a day, 5 days a week, for 3 weeks and consisted of manual treatments, strengthening exercises, stretching, core stability, balance and resistance training, aerobic exercises, and tailored self-care training. Data were collected at baseline (T 0 ), after treatment (T 1 ), and at the 12-month mark (T 2 ) in terms of the following outcome measures: muscle strength, pain, fatigue, cramps, balance, walking speed, and ability. We included 37 CMT patients with a median age of 50.72 ± 13.31 years, with different forms: demyelinating (n = 28), axonal (n = 8), and mixed (n = 1). After intensive rehabilitation treatment, all outcomes significantly improved. This improvement was lost at the 1-year mark. Taken together, these findings suggest that an intensive rehabilitation program improves short-term symptoms and functional outcomes in a cohort of inpatients affected by mild to moderate CMT., (© 2023. The Author(s).)

Background: Immunoglobulin A nephropathy (IgAN) is the most frequent primary glomerulonephritis and the role of IL-6 in pathogenesis is becoming increasingly important. A recent whole genome DNA methylation screening in IgAN patients identified a hypermethylated region comprising the non-coding RNA Vault RNA 2-1 (VTRNA2-1) that could explain the high IL-6 levels., Methods: The pathway leading to IL-6 secretion controlled by VTRNA2-1, PKR, and CREB was analyzed in peripheral blood mononuclear cells (PBMCs) isolated from healthy subjects (HS), IgAN patients, transplanted patients with or without IgAN. The role of double and single-strand RNA in controlling the pathway was investigated., Results: VTRNA2-1 was downregulated in IgAN compared to HS and in transplanted IgAN patients (TP-IgAN) compared to non-IgAN transplanted (TP). The loss of the VTRNA2-1 natural restrain in IgAN patients caused PKR hyperphosphorylation, and consequently the activation of CREB by PKR, which, in turn, led to high IL-6 production, both in IgAN and in TP-IgAN patients. IL-6 levels could be decreased by the PKR inhibitor imoxin. In addition, PKR is normally activated by bacterial and viral RNA, and we found that both the RNA poly(I:C), and the COVID-19 RNA-vaccine stimulation significantly increased the IL-6 levels in PBMCs from HS but had an opposite effect in those from IgAN patients., Conclusion: The discovery of the upregulated VTRNA2-1/PKR/CREB/IL-6 pathway in IgAN patients may provide a novel approach to treating the disease and may be useful for the development of precision nephrology and personalized therapy by checking the VTRNA2-1 methylation level in IgAN patients., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: This narrative review aims to provide a comprehensive overview of the current prehabilitation and rehabilitation strategies for thyroid cancer survivors to optimize functional outcomes and enhance their quality of life., Methods: The review follows the SANRA quality criteria and includes an extensive literature search conducted in PubMed/Medline, Web of Science, and Scopus., Results: The review emphasizes the role of a comprehensive rehabilitation approach in targeting the different domains that generate disability in thyroid cancer patients. In this context, physical activity, range of motion exercises, myofascial release, joint mobilization, and postural exercises are crucial for improving functional outcomes and reducing treatment-related discomfort and disability. Moreover, tailored rehabilitative management addressing dysphonia and dysphagia might have a positive impact on the quality of life of these patients. Despite these considerations, several barriers still affect the implementation of a multimodal rehabilitative approach in common clinical practice. Thus, sustainable and effective strategies like digital innovation and patient-centered approaches are strongly needed in order to implement the rehabilitative treatment framework of these subjects., Conclusions: This narrative review provides valuable insights into the current prehabilitation and rehabilitation strategies to treat thyroid cancer survivors, addressing physical, psychological, and vocational needs to optimize functional outcomes and enhance their quality of life.

The surgical intervention rate and the subsequent rehabilitation plan for anterior cruciate ligament (ACL) injury was crucially affected by the COVID-19 pandemic due to the necessity in the face of the emergency. This review aimed to evaluate potential persistent and residual symptoms after COVID-19 disease, including fatigue and neuromuscular disorders. A scoping review design and methodology were used due to the exploratory nature of the research question, according to literature searches on PubMed/Medline, Scopus, Web of Science (WoS), and Physiotherapy Evidence Database (PEDro) electronic databases using the following keywords: "Anterior Cruciate Ligament", "ACL", "SARS-CoV-2", and "COVID-19". Undertraining and muscular knee imbalance might cause inefficient movement strategies, lack of knee stability, and increasing load with negative implications in ACL injuries. In the post-surgery period, during COVID-19, telerehabilitation approaches appeared to be successfully applied to maintain strength and range of motion in this condition. However, no definitive data are available regarding the most effective interventions. This scoping review showed the influence of the COVID-19 pandemic and associated restrictions on postoperative and rehabilitative care of ACL injuries.

Physical therapy is strongly recommended for patients with neurological disorders. Tai Chi-based treatments seem to improve physical functions like gait speed and balance. However, assessments after treatment rely on semi-quantitative clinical scales affected by subjectivity with controversial results. This study aims at investigating whether Tai Chi could be a valid alternative to traditional physiotherapy rehabilitation. We propose a wearable system composed of two inertial devices able to objectively measure the effect of the rehabilitation treatment on the range of movement of the trunk. Seventeen patients with Parkinson's Disease (PD) were recruited and assessed. They have been randomly divided into two groups: group 1 followed a Tai Chi-based treatment, while group 2 underwent a traditional physiotherapy rehabilitation. The two groups have been assessed before (t0) and after the treatment (t1). No statistical differences have been found in the relative range of motion between the upper and lower sensors between the two groups at the baseline. Both treatments resulted in a significant improvement in the trunk range of movement (on the right side). Notably, the improvement in the effect size of the treatment was greater in group 1 than in group 2. In fact, even if both the groups benefited from their treatment group 1 gained larger mobility of the trunk if compared to group 2. Interestingly, no differences have been accounted adopting the traditional UPDRS III for motor symptoms of PD, strengthening the idea that objective measurement coming from wearable biomedical sensors could detect information otherwise neglected by traditional clinical tools.Clinical Relevance- This study preliminary confirms that beneficial motor effects after a Tai Chi rehabilitation program are comparable and quite better than after traditional physiotherapy, promoting Tai Chi as a valid alternative treatment for PD patients.

Cisplatin is one of the most effective chemotherapeutic agents strongly associated with nephrotoxicity. Tubular adult renal progenitor cells (tARPC) can regenerate functional tubules and participate in the repair processes after cisplatin exposition. This study investigated the molecular mechanisms underlying the protective effect of tARPC on renal epithelium during cisplatin nephrotoxicity. By performing a whole-genome transcriptomic analysis, we found that tARPC, in presence of cisplatin, can strongly influence the gene expression of renal proximal tubular cell [RPTEC] by inducing overexpression of CYP1B1, a member of the cytochrome P450 superfamily capable of metabolizing cisplatin and of hypoxia/cancer-related lncRNAs as MIR210HG and LINC00511. Particularly, tARPC exerted renoprotection and regeneration effects via extracellular vesicles (EV) enriched with CYP1B1 and miR-27b-3p, a well-known CYP1B1 regulatory miRNA. The expression of CYP1B1 by tARPC was confirmed by analyzing biopsies of cisplatin-treated renal carcinoma patients that showed the colocalization of CYP1B1 with the tARPC marker CD133. CYP1B1 was also overexpressed in urinary EV purified from oncologic patients that presented nephrotoxicity episodes after cisplatin treatment. Interestingly CYP1B1 expression significantly correlated with creatinine and eGFR levels. Taken together, our results show that tARPC are able to counteract cisplatin-induced nephrotoxicity via CYP1B1 release through EV. These findings provide a promising therapeutic strategy for nephrotoxicity risk assessment that could be related to abundance of renal progenitors.

Background: Several technological advances and digital solutions have been proposed in the recent years to face the emerging need for tele-monitoring older adults with Chronic Obstructive Pulmonary Disease (COPD). However, several challenges have negatively influenced an evidence-based approach to improve Health-Related Quality of Life (HR-QoL) in these patients., Aim: To assess the effects of tele-monitoring devices on HR-QoL in older adults with COPD., Methods: On November 11, 2022, PubMed, Scopus, Web of Science, and Cochrane were systematically searched for randomized controlled trials (RCTs) consistent with the following PICO model: older people with COPD as participants, tele-monitoring devices as intervention, any comparator, and HR-QoL as the primary outcome. Functional outcomes, sanitary costs, safety, and feasibility were considered secondary outcomes. The quality assessment was performed in accordance with the Jadad scale., Results: A total of 1845 records were identified and screened for eligibility. As a result, 5 RCTs assessing 584 patients (423 males and 161 females) were included in the systematic review. Tele-monitoring devices were ASTRI telecare system, WeChat social media, Pedometer, SweetAge monitoring system, and CHROMED monitoring platform. No significant improvements in terms of HR-QoL were reported in the included studies. However, positive effects were shown in terms of the number of respiratory events and hospitalization in patients telemonitored by SweetAge system and CHROMED platform., Discussion: Although a little evidence supports the role of tele-monitoring devices in improving HR-QoL in older patients, positive effects were reported in COPD exacerbation consequences and functional outcomes., Conclusion: Tele-monitoring solutions might be considered as sustainable strategies to implement HR-QoL in the long-term management of older patients with COPD., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Blood flow restriction (BFR) training improves muscle strength and functional outcomes, but the proprioceptive implications of this technique in the rehabilitation field are still unknown., Objective: The present study aimed at assessing the effects of BFR in terms of stabilometric and balance performance., Methods: In this pilot randomized cross-over study, healthy young adults were included and randomly assigned to Groups A and B. Both groups underwent a postural assessment with and without wearing a BFR device. Study participants of Group A underwent postural baseline assessment wearing BFR and then removed BFR for further evaluations, whereas subjects in Group B performed the baseline assessment without BFR and then with BFR. Stabilometric and balance performance were assessed by the robotic platform Hunova, the Balance Error Scoring System (BESS), the self-reported perceived balance (7-point Likert scale), and discomfort self-rated assessment. Moreover, the safety profile was recorded., Results: Fourteen subjects were included and randomly assigned to Group A (n: 7) and Group B (n: 7). Significant differences were shown in balance tests in static conditions performed on the Hunova robot platform in terms of average distance RMS (root-mean-square) with open eyes (OE), anteroposterior (AP) trunk oscillation range with OE, mediolateral (ML) average speed of oscillation with OE, and total excursion AP range with closed eyes (CE) (BFR: 3.44 ± 1.06; without BFR: 2.75 ± 0.72; p= 0.041). Moreover, elastic balance test showed differences in Romberg index (BFR: 0.16 ±0.16; without BFR: 0.09 ± 0.07; p= 0.047). No adverse events were reported., Conclusion: Taken together, our data showed that BFR affects balance performance of healthy subjects. Further studies are needed to better characterize the possible role of BFR treatment in the context of a specific rehabilitation protocol.

Background: Temporomandibular disorders (TMD) are musculoskeletal conditions involving masticatory muscles and temporomandibular joints. Bibliometric analysis has been introduced as a new method for collecting and analyzing information on scientific articles., Objective: The aim of this study was to identify the 50 most cited articles on TMD, performing a bibliometric analysis of the identified papers to favor research and clinical practice., Methods: On December 17, 2021 a systematic research was performed to find all papers on TMD published in the literature. The Incites Journal Citation Reports dataset and Scopus database was used to obtain bibliometric indexes of the authors and metrics data of the journals, including Impact Factor, Eigenfactor Score, and Normalized Eigenfactor. VOSviewer was used to visualize the keyword mapping networking, with the nodes standing for keywords and the edges for keyword relationships., Results: Out of 24372 papers obtained by the search strategy, the 50 most cited articles on TMD were analyzed. The paper with the highest number of citations (n= 3020) was on TMD research diagnostic criteria. Rate of citations per year collected by the 50 most cited articles on TMD has been increasing over time (from 627 in 2006 to 1483 in 2021). Most of them were cross-sectional studies (n= 20; 40.0%) and narrative reviews (n= 14; 28.0%)., Conclusion: This bibliometric study showed an increasing number of citations for articles on TMD, testifying a high interest in the last years. Starting from this analysis, future studies might provide high-quality evidence on TMD management.

Background: Despite the fact that weaning from mechanical ventilation (MV) is one of the main rehabilitation goals in patients with spinal cord injury (SCI), controversies are still open about the optimal rehabilitation approach., Objective: This systematic review aimed at characterizing the rehabilitation interventions currently available to optimize weaning from MV in SCI patients., Methods: On April 12nd, 2022, a systematic literature search was performed in PubMed, Scopus, Web of Science, Cochrane, and PEDro, identifying studies assessing MV patients with SCI undergoing pulmonary rehabilitation. The primary outcomes were weaning duration, MV duration, and weaning success rate. Secondary outcomes were pulmonary function, extubation or decannulation time, length of stay, and safety., Results: Out of 413 records, 14 studies were included (2 randomized controlled trials, 7 observational studies, and 5 case reports). Most of the studies assessed a comprehensive rehabilitation approach, including high tidal volume ventilation, positioning, mechanical lung recruitment maneuvers, secretion management strategies, respiratory muscle training, and electrical stimulation., Conclusion: Our findings suggested that a comprehensive rehabilitation intervention might have a role in reducing MV duration in patients with SCI. Further studies are needed to better characterize the optimal rehabilitation strategies for enhancing functional recovery of patients with SCI.

Background: Various tools have been created to measure physical function during intensive care unit (ICU) stay and after ICU discharge, but those have not been validated in coronavirus 2019 (COVID-19) patients. There is a need for a reliable, valid and feasible tool to define the rehabilitation needs of post-ICU COVID-19 patients entering the acute wards and then rehabilitation clinics., Objective: This study aims to investigate the validity, inter-rater reliability and feasibility of Chelsea Physical Assessment Tool (CPAx) in assessing the functional status of COVID-19 patients after discharge from the ICU., Methods: Demographic and clinical characteristics of the patients were recorded. Patients were evaluated using the modified Medical Research Council (MRC) dyspnea scale, Functional Oral Intake Scale, Glasgow Coma Scale, CPAx, Barthel Index, Katz Index and MRC sum score, measurements of grip strength obtained by dynamometer, the 5 time sit-to-stand test and 30 seconds and sit-to-stand test. CPAx and the other functional assessment tools were administered to 16 patients within 48 hours following ICU discharge. For inter-rater reliability, another physiatrist independently re-assessed the patients. MRC sum score, Barthel and Katz indexes were used to assess construct validity of CPAx. The discriminative validity of CPAx was determined by its ability to differentiate between patients with and without ICU acquired muscle weakness based on MRC sum score. The intra-class correlation coefficients (ICC) were calculated to determine inter-rater reliability for total scores of the functional assessment tools. Cohen's Kappa (κ) coefficient and weighed Kappa (κw) were calculated to determine inter-rater reliability of individual CPAx items. Ceiling and flooring effects were calculated by percentage frequency of lowest or highest possible score achieved. The number and percentages of the patients who were able to complete each tool were calculated to assess feasibility. The CPAx score was strongly correlated with MRC sum score (rho: 0.83), Barthel Index (rho: 0.87) and Katz Index (rho: 0.89) (p< 0.001) showing construct validity. Area under the ROC curve demonstrated that cut off score for CPAx was ⩽ 12 to discriminate patients with MRC sum score < 48, with a sensitivity and a specificity of 100% and 63%, respectively (AUC = 0.859, p< 0.001). ICC was high for CPAx, MRC sum score, Barthel and Katz indexes, Glasgow Coma Scale, and hand grip strength measurement, with the highest value observed for CPAx (ICC, 0.96; 95% confidence interval (CI), 0.71-0.98). κ and κw analysis showed good to excellent inter-rater reliability for individual CPAx items. No floor or ceiling effect was observed at CPAx while floor effect was observed at Barthel Index scores (25%) and Katz Index scores (37.5%). All patients could be evaluated using CPAx while less were physically able to complete the 5 time sit-to-stand, 30 seconds sit-to-stand tests (n= 4) and MRC sum score (n= 14)., Conclusion: CPAx is a valid, reliable, and feasible tool to assess the physical functional state in COVID-19 patients following discharge from the ICU.

Background: Spinal cord injury (SCI) is a disabling condition characterized by multilevel skeletal muscle impairment and rapid cortical and trabecular bone loss. Rehabilitation is a cornerstone of the long-term management of patients with SCI; however, the optimal rehabilitation strategy for improving bone health has not been fully characterized., Objective: To characterize the current evidence supporting different rehabilitation interventions improving bone health in patients with SCI., Methods: On November 17th, 2022, five databases (PubMed, Scopus, Web of Science, Cochrane, and PEDro) were systematically searched for randomized controlled trials (RCTs) assessing SCI patients undergoing rehabilitation interventions. The primary outcomes were bone macroscopical effects. Secondary outcomes were changes in bone metabolisms and functional outcomes., Results: Out of 499 records, 11 RCTs met the eligibility criteria and were included. Electrical stimulation combined with physical exercise was assessed by 5 studies, standing intervention was assessed by 3 studies, vibration was assessed by 1 study, ultrasound therapy was assessed by 1 study, and electroacupuncture combined with a pulsed magnetic field was assessed by 1 study. The rehabilitation intervention was administered combined with pharmacological treatment (3 studies) or alone (8 studies). Positive effects in terms of BMD were reported by 3 studies. The quality assessment revealed some concerns in 9 out of 11 studies, in accordance with the Cochrane Risk of Bias assessment - version 2., Conclusion: Our data suggest that multicomponent interventions including rehabilitation might be considered a suitable option to improve bone health management in SCI patients. Further studies are mandatory to characterize the optimal combination of non-pharmacological interventions reducing bone loss and improving the risk of fractures in patients with SCI.

Background: Spinal cord injury (SCI) leads to spinal nerve fiber tract damage resulting in functional impairments. Volumetric muscle loss (VML), a skeletal muscle volume abnormal reduction, is represented by atrophy below the injury level. The strategies for VML management included personalized approaches, and no definite indications are available., Objective: To identify the rehabilitation effects of VML in subjects with SCI (humans and animals)., Methods: PubMed, Scopus, and Web of Science databases were systematically searched to identify longitudinal observational studies with individuals affected by traumatic SCI as participants; rehabilitation treatment as intervention; no control, sham treatment, and electrical stimulation programs as control; total lean body and lower limb lean mass, cross-sectional area, functional gait recovery, muscle thickness, and ultrasound intensity, as outcome., Results: Twenty-four longitudinal observational studies were included, evaluating different rehabilitation approaches' effects on the VML reduction in subjects affected by SCI. The data showed that electrical stimulation and treadmill training are effective in reducing the VML in this population., Conclusion: This systematic review underlines the need to treat subjects with traumatic SCI (humans and animals) with different rehabilitation approaches to prevent VML in the subacute and chronic phases. Further clinical observations are needed to overcome the bias and to define the intervention's timing and modalities.

Introduction: In recent years, growing attention is rising to virtual reality (VR) tools and exergaming in rehabilitation management of patients with Parkinson disease (PD). However, no strong evidence supports the effectiveness of these cutting-edge technologies on cognitive function and the integration of these promising tool in the rehabilitation framework of PD patients is still challenging. Therefore, the present systematic review of randomized controlled trials (RCTs) aimed at assessing the effects of VR and exergames/telerehabilitation in the cognitive rehabilitation management of patients with PD., Evidence Acquisition: PubMed, Scopus and Web of Science databases were systematically searched up to February 14 th , 2022, to identify RCTs assessing patients with PD undergoing cognitive rehabilitation including VR or exergames/telerehabilitation. The intervention was compared to conventional rehabilitation protocols. The primary outcome was cognitive function. The quality assessment was performed following the Version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). PROSPERO registration code: CRD42022319788., Evidence Synthesis: Out of 1419 identified studies, 66 articles were assessed for eligibility, and, at the end of the screening process, 10 studies were included in the present systematic review. Five RCTs (50%) assessed the exergaming devices, reporting significant positive results on cognitive outcomes scales (Trail Making test scale, Digit Span backward, MoCA, and MyCQ score). The other 5 RTCs (50%) assessed VR approaches, reporting significant improvement in executive functions. The RoB 2 showed an overall high risk of bias for the 40% of studies included., Conclusions: Exergaming and VR might be considered promising rehabilitation interventions in the cognitive rehabilitation framework of PD patients. Further high-quality studies are needed to define the role of exergames and VR in a comprehensive rehabilitation approach aiming at improving the multilevel cognitive impairment characterizing patients with PD.

Chronic obstructive pulmonary disease (COPD) is a burdensome condition affecting a growing number of people worldwide, frequently related to major comorbidities and functional impairment. In these patients, several factors might have a role in promoting both bone and muscle loss, including systemic inflammation, corticosteroid therapies, sedentary behaviours, deconditioning, malnutrition, smoking habits, and alcohol consumption. On the other hand, bone and muscle tissues share several linkages from functional, embryological, and biochemical points of view. Osteosarcopenia has been recently defined by the coexistence of osteoporosis and sarcopenia, but the precise mechanisms underpinning osteosarcopenia in patients with COPD are still unknown. In this scenario, a deeper understanding of the molecular basis of osteosarcopenia might guide clinicians in a personalized approach integrating skeletal muscle health with the pulmonary rehabilitation framework in COPD. Taken together, our results summarized the currently available evidence about the multilevel interactions between osteosarcopenia and COPD to pave the way for a comprehensive approach targeting the most common risk factors of these pathological conditions. Further studies are needed to clarify the role of modern clinical strategies and telemedicine solutions to optimize healthcare delivery in patients with COPD, including osteopenia, osteoporosis, and sarcopenia screening in these subjects.

Background: To date, the mitochondrial function has been related to several pathways involved in the cellular aging process. Dietary supplements might have reciprocal and multilevel interactions with mitochondria network; however, no systematic review assessed the role of different nutraceuticals in mitochondria modification of healthy older adults., Aim: To assess the effects of different dietary supplements on mitochondria modifications in older adults., Methods: On February 22, 2022, PubMed, Scopus, Web of Science, and Cochrane were systematically searched from inception for randomized controlled trials (RCTs). According to PICO model, we considered healthy older adults as participants, nutraceutical treatment as intervention, any treatment as comparator, mitochondrial modifications as outcome. Jadad scale was used for the quality assessment., Results: Altogether, 8489 records were identified and screened until 6 studies were included. A total of 201 healthy older adults were included in the systematic review (mean age ranged from 67.0 ± 1.0 years to 76.0 ± 5.6 years). The dietary supplements assessed were sodium nitrite, N-3 polyunsaturated fatty acids, hydrogen-rich water, nicotinamide riboside, urolithin A, and whey protein powder. Positive effects were reported in terms of mitochondrial oxidative and antioxidant capacity, volume, bioenergetic capacity, and mitochondrial transcriptome based on the nutritional supplements. The quality assessment underlined that all the studies included were of good quality., Discussion: Although dietary supplements might provide positive effects on mitochondria modifications, few studies are currently available in this field., Conclusion: Further studies are needed to better elucidate the reciprocal and multilevel interactions between nutraceuticals, mitochondria, and environmental stressors in healthy older adults., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The long non-coding RNAs (lncRNA) play an important role in several biological processes, including some renal diseases. Nevertheless, little is known about lncRNA that are expressed in the healthy kidneys and involved in renal cell homeostasis and development, and even less is known about lncRNA involved in the maintenance of human adult renal stem/progenitor cells (ARPCs) that have been shown to be very important for renal homeostasis and repair processes. Through a whole-genome transcriptome screening, we found that the HOTAIR lncRNA is highly expressed in renal progenitors and potentially involved in cell cycle and senescence biological processes. By CRISPR/Cas9 genome editing, we generated HOTAIR knockout ARPC lines and established a key role of this lncRNA in ARPC self-renewal properties by sustaining their proliferative capacity and limiting the apoptotic process. Intriguingly, the HOTAIR knockout led to the ARPC senescence and to a significant decrease in the CD133 stem cell marker expression which is an inverse marker of ARPC senescence and can regulate renal tubular repair after the damage. Furthermore, we found that ARPCs expressed high levels of the α-Klotho anti-aging protein and especially 2.6-fold higher levels compared to that secreted by renal proximal tubular cells (RPTECs). Finally, we showed that HOTAIR exerts its function through the epigenetic silencing of the cell cycle inhibitor p15 inducing the trimethylation of the histone H3K27. Altogether, these results shed new light on the mechanisms of regulation of these important renal cells and may support the future development of precision therapies for kidney diseases., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Study Design: Double-blind randomized controlled trial., Introduction: Carpal tunnel syndrome (CTS) is a common mononeuropathy that causes pain and disability in the affected hand. Kinesio taping (KT) has been recently proposed as a promising conservative approach in CTS patients., Purpose of the Study: To investigate the effectiveness of KT compared to a sham taping on symptoms and hand function in patients affected by mild CTS., Methods: Patients affected by mild CTS with symptoms for at least 8 weeks were enrolled and randomly allocated into two groups: KT group, according to the technique proposed by Kase plus specific exercises; control group, undergoing a sham taping plus specific exercise. All patients performed 2 sessions/week for 5 weeks of exercises of mobilization of fingers and carpal joint. At the baseline, after 5 weeks (T1), and after 6 months (T2), a physician unaware of patients' allocation assessed the Boston Carpal Tunnel Questionnaire (BCTQ) symptom (BCTQ-S) and functional (BCTQ-F) subscales., Results: Forty-two patients (mean age:54.3 ± 15.0 y) were randomly allocated into KT (n = 21) and control group (n = 21). At T1, in both groups we found a significant improvement in hand function and symptoms, as showed by BCTQ-F (KT:4.2 ± 0.7 vs 3.0 ± 0.6, P < .001; sham: 2.2 ± 0.3 vs 1.7 ± 0.3, P = .012) and by BCTQ-S (KT: 2.2 ± 0.3 vs 1.7 ± 0.3, P < .001; sham: 2.3 ± 0.4 vs 1.9 ± 0.5, P = .007). At T2, only in the KT group there was a significant difference in both sub-items of primary outcome. There were significantly better results in the KT group at T1 and T2., Discussion: The present study showed that KT compared to a sham taping might be more effective in reducing perceived symptoms in mild CTS patients, reporting a clinically significant difference., Conclusion: KT might be considered as an effective technique combined to rehabilitative treatment in terms of hand function and symptoms in patients affected by mild CTS., (Copyright © 2021. Published by Elsevier Inc.)

Background: Previous evidence showed that cellular aging is a multifactorial process that is associated with decline in mitochondrial function. Physical exercise has been proposed as an effective and safe therapeutical intervention to improve the mitochondria network in the adult myocytes., Aims: The aim of this systematic review of randomized controlled trials (RCTs) was to assess the exercise-induced muscle mitochondria modifications in older adults, underlining the differences related to different exercise modalities., Methods: On November 28th, 2021, five databases (PubMed, Scopus, Web of Science, Cochrane, and PEDro) were systematically searched for RCTs to include articles with: healthy older people as participants; physical exercise (endurance training (ET), resistance training (RT), and combined training (CT)) as intervention; other different exercise modalities or physical inactivity as comparator; mitochondrial modifications (quality, density and dynamics, oxidative, and antioxidant capacity) as outcomes. The quality assessment was performed according to the PEDro scale; the bias risk was evaluated by Cochrane risk-of-bias assessment tool., Results: Out of 2940 records, 6 studies were included (2 assessing ET, 2 RT, 1 CT, and 1 both ET and RT). Taken together, 164 elderly subjects were included in the present systematic review. Significant positive effects were reported in terms of mitochondrial quality, density, dynamics, oxidative and antioxidant capacity, even though with different degrees according to the exercise type. The quality assessment reported one good-quality study, whereas the other five studies had a fair quality., Discussion: The overall low quality of the studies on this topic indicate that further research is needed., Conclusion: RT seems to be the most studied physical exercise modality improving mitochondrial density and dynamics, while ET have been related to mitochondrial antioxidant capacity improvements. However, these exercise-induced specific effects should be better explored in older people., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

There is still a gap in the scientific knowledge on the linkage between craniofacial structure and spinal postural control in temporomandibular disorder (TMD) patients. This systematic review aimed to assess the role of occlusal splints on spinal posture of TMD patients. PubMed, Web of Science, and Scopus were systematically searched from inception until 5 January 2022 to identify observational studies with a longitudinal study design presenting: patients with diagnosis of TMD according to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD); occlusal splint therapy as intervention; postural assessment as outcome. Out of 133 records identified, 104 were suitable for data screening, and only 7 articles were included satisfying the eligibility criteria. We found that occlusal splints might have a positive effect on posture in TMD patients, albeit there is little evidence of appropriate investigation for postural assessment. This systematic review suggested that the occlusal splint might be considered a non-invasive therapeutic approach for patients with TMD. However, the low number of studies with high-quality methodology in these patients showed an urgent need for further research using combined force platform stabilometry and kinematic evaluation of the spine to investigate the impact of occlusal splints on posture.

Our immune system actively fights bacteria and viruses, and it must strike a delicate balance between over- and under-reaction, just like Daedalus and Icarus in Greek mythology, who could not escape their imprisonment by flying too high or too low. Both human amniotic epithelial and mesenchymal stromal cells and the conditioned medium generated from their culture exert multiple immunosuppressive activities. They have strong immunomodulatory properties that are influenced by the types and intensity of inflammatory stimuli present in the microenvironment. Notably, very recently, the immunomodulatory activity of human adult renal stem/progenitor cells (ARPCs) has been discovered. ARPCs cause a decrease in Tregs and CD3 + CD4 - CD8 - (DN) T cells in the early stages of inflammation, encouraging inflammation, and an increase in the late stages of inflammation, favoring inflammation quenching. If the inflammatory trigger continues, however, ARPCs cause a further increase in DN T cells to avoid the development of a harmful inflammatory state. As in the flight of Daedalus and Icarus, who could not fly too high or too low to not destroy their wings by the heat of the sun or the humidity of the sea, in response to an inflammatory environment, stem cells seem to behave by paying attention to regulating T cells in the balance between immune tolerance and autoimmunity. Recognizing the existence of both suppressive and stimulatory properties, and the mechanisms that underpin the duality of immune reaction, will aid in the development of active immunotherapeutic approaches that manipulate the immune system to achieve therapeutic benefit., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Picerno, Castellano, Curci, Kopaczka, Stasi, Pertosa, Sabbà, Gesualdo, Gramignoli and Sallustio.)

Osteoporosis is characterized by an alteration of bone microstructure with a decreased bone mineral density, leading to the incidence of fragility fractures. Around 200 million people are affected by osteoporosis, representing a major health burden worldwide. Several factors are involved in the pathogenesis of osteoporosis. Today, altered intestinal homeostasis is being investigated as a potential additional risk factor for reduced bone health and, therefore, as a novel potential therapeutic target. The intestinal microflora influences osteoclasts' activity by regulating the serum levels of IGF-1, while also acting on the intestinal absorption of calcium. It is therefore not surprising that gut dysbiosis impacts bone health. Microbiota alterations affect the OPG/RANKL pathway in osteoclasts, and are correlated with reduced bone strength and quality. In this context, it has been hypothesized that dietary supplements, prebiotics, and probiotics contribute to the intestinal microecological balance that is important for bone health. The aim of the present comprehensive review is to describe the state of the art on the role of dietary supplements and probiotics as therapeutic agents for bone health regulation and osteoporosis, through gut microbiota modulation.