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BACKGROUND: Robot-assisted arm therapy (RAT) has been used mainly in stroke rehabilitation in the last 20 years with rising expectations and growing evidence summarized in systematic reviews (SRs). OBJECTIVE: The aim of this study is to provide an overview of SRs about the effectiveness, within the ICF domains, and safety of RAT in the rehabilitation of adult with stroke compared to other treatments. METHODS: The search strategy was conducted using search strings adapted explicitly for each database. A screening base on title and abstract was realized to find all the potentially relevant studies. The methodological quality of the included SRs was assessed using AMSTAR-2. A pre-determined standardized form was used to realize the data extraction. RESULTS: 18 SRs were included in this overview. Generally, positive effects from the RAT were found for motor function and muscle strength, whereas there is no agreement for muscle tone effects. No effect was found for pain, and only a SR reported the positive impact of RAT in daily living activity. CONCLUSION: RAT can be considered a valuable option to increase motor function and muscle strength after stroke. However, the poor quality of most of the included SRs could limit the certainty around the results.

Rehabilitation focuses on impairments, activity limitations and participation restrictions being informed by the underlying health condition. In the current absence of direct "evidence on" rehabilitation interventions for people with post-COVID-19 condition (PCC), we can search and synthesize the indirect "evidence relevant to" coming from interventions effective on the symptoms of PCC in other health conditions. The World Health Organization (WHO) required this information to inform expert teams and provide specific recommendations in its Guidelines. With this overview of reviews with mapping we aimed to synthesize the Cochrane evidence relevant to rehabilitation for arthralgia due to PCC in a map.We searched the last five years' Cochrane Systematic Review (CSRs) using the terms "arthralgia," "joint pain," and "rehabilitation" and their synonyms in the Cochrane Library. We extracted and summarized all the available evidence using a map. We grouped the included CSRs for health conditions and interventions, indicating the effect and the quality of evidence.We found 200 CSRs published between 2016 and 2021, and included 11 in this overview. They provided data from 7 health conditions, with osteoarthritis (5 studies) being the most studied. Effective rehabilitation interventions included exercise training, transcranial magnetic stimulation, different types of electrical stimulation and Tai chi. The overall quality of evidence was mainly low to very low, and moderate in a few cases.These results provided the requested information to the WHO and served as the basis for one recommendation on treatments for arthralgia due to PCC in the current Guidelines for clinical practice. These results should be interpreted as a first step of indirect evidence able to generate helpful hypotheses for future research.

Upper extremities limitation is a common functional impairment in patients with Multiple Sclerosis (PwMS). Novel technological devices are increasingly used in neurorehabilitation to support motor function improvement and the quantitative assessment of motor performance during training in patients with neurological diseases. In this review, we systematically report the evidence on clinical applications and robotic-assisted arm training (RAT) in functional recovery in PwMS. PubMed/MEDLINE, the Cochrane Library, and the Physiotherapy Evidence Database (PEDro) databases were systematically searched from inception to March 2021. The 10-item PEDro scale assessed the study quality for the RCT, and the AMSTAR-2 was used to assess the quality of the systematic review. The 5-item Oxford CEBM scale was used to rate the level of evidence. A total of 10 studies (161 subjects) were included. The selected studies included one systematic review, four RCTs, one randomized crossover, and four case series. The RCTs were scored as high-quality studies, while the systematic review was determined to be of low quality. Shoulder range of motion, handgrip strength, and proximal arm impairment improved after RAT. Manual dexterity, arm function, and use in daily life also ameliorated arm function. The high clinical heterogeneity of treatment programs and the variety of robot devices affects the generalizability of the study results; therefore, we emphasize the need to standardize the intervention type in future studies that evaluate the role of robotic-assisted training in PwMS. Robot-assisted treatment seems safe and useful to increase manual dexterity and the quality of movement execution in PwMS with moderate to severe disability. Additional studies with an adequate sample size and methodological rigour are warranted to drive definite conclusions.

BACKGROUND: Robot-assisted Arm Therapy (RAT) has been increasingly applied in the last years for promoting functional recovery in patients with disabilities related to neurological health conditions. Evidence of a knowledge-to-action gap for applying robot-assisted technologies in the rehabilitation of patients with neurological health conditions and the difficulty to apply and tailor the knowledge to the local contexts solicited the need for a national consensus conference on these interventions. AIM: The aim of this paper was to explain the methodology used by the working group dedicated to synthesizing evidence on the effectiveness of RAT in neurological health conditions in the context of the CICERONE Italian Consensus Conference. DESIGN: The methodological approach of the working group. SETTING: All rehabilitation settings. POPULATION: Patients with disability following a neurological health condition. METHODS: Following the indications proposed by the Methodological Manual published by the Italian National Institute of Health, a Promoting Committee and a Technical Scientific Committee have been set up. Six working groups (WGs) have been composed to collect evidence on different questions, among which WG2.2 was focused on the effectiveness of RAT in neurological health conditions. RESULTS: WG2.2 started its work defining the specific research questions. It was decided to adopt the ICF as the reference framework for the reporting of all outcomes. Literature search, data extraction and qualitative assessment, evidence analysis and synthesis have been performed. CONCLUSIONS: This paper summarized the methodological approaches used by the WG2.2 of the CICERONE Italian Consensus Conference to define the effectiveness of RAT in the management of patients with neurological health conditions. CLINICAL REHABILITATION IMPACT: WG2.2 synthesis might help clinicians, researchers, and all rehabilitation stakeholders to address the use of RAT in the Individualized Rehabilitation Plan, to guide the allocation of resources and define clinical protocols and indications for the management of patients with different neurological health conditions.

Introduction COVID-19 infection significantly increased mortality risk and the burden of disability in most survivors, regardless of symptom severity at onset. The rehabilitation needs of people infected are receiving growing attention, as evidenced by the increasing number of publications, including those addressing the chronic consequences of infection. This rapid living systematic review reports the evidence published in November and December 2020 and summarises the entire body of literature on rehabilitation in COVID-19 patients published in 2020. Evidence acquisition This update was performed using the methodology reported by the second edition conducted by Cochrane Rehabilitation REH-COVER Action. We searched PubMed, Embase, CINAHL, Scopus, Web of Science, and Pedro databases. Papers related to COVID-19 and rehabilitation were retrieved and summarised descriptively. Evidence synthesis The search retrieved 4441 studies. After the removal of duplicates and the screening for title and abstract, we retained 105 studies. Of these, we included 54 in the qualitative synthesis of this update. According to OCEBM 2011 levels of evidence table, most studies (64.8%) fall within the category of level 4 evidence. Up to 40.7% of papers included COVID-19 patients in the postacute phase. In 2020, our rapid living systematic review included 230 studies; most of these (73.9%) were level 4 studies, 25.7% were level 3, and only one study was level 2. The evidence level improved over time. While most studies (44.8%) included patients with acute COVID-19, we observed a gradual increase in the number of reports about chronic symptoms and the long-term consequences of the infection. Conclusions The update of the rapid living systematic review by Cochrane Rehabilitation Field demonstrates an increase in the level of evidence of studies addressing the rehabilitation needs associated with COVID-19 infection. Although most studies are still case reports/series, there is a trend towards conducting prospective investigations of the early natural history of the disease (first months post onset). High-quality-level studies on the efficacy of rehabilitation, and long-term monitoring of the disease and its sequelae are yet to emerge.

Background: Cochrane Rehabilitation (CR) is working on the production of an Ebook to systematically present all the relevant evidence of rehabilitation interest included in the Cochrane Systematic Reviews (CSRs). In line with the Cochrane Knowledge Translation (KT) strategy, the Ebook aims to fill the knowledge practice gap addressing four different audiences producing one different summary for each of them, structured to meet the needs of the different end-users according to their different knowledge skills, and outcomes of interest: clinicians, medical and health professional students, policy decision-makers and rehabilitation health care managers, patients and caregivers (consumers). Objectives: To present the CR Ebook project. Methods: After identifying all the CSRs relevant to rehabilitation, residents from two Italian universities have been involved and instructed on how to write the different summaries, using a structured template, based on the Cochrane’s Dissemination checklist, and following the Cochrane Norway language guidelines. Two Physical and Rehabilitation Medicine (PRM) physicians (AM, MGC) revised them, a second revision was provided by a member of CR and a third by at least two among a group of international editors coming from the European Physical and Rehabilitation Medicine (PRM) Bodies supporting and co-authoring the ebook. A last check was then performed by the another PRM physician (FG), before the final decision by the European PRM Bodies took place. Results: To date, we have identified 375 CSRs published between 2014 and August 2019. Of these, 145 (3 for 2018, 68 for 2017, 60 for 2016 and 14 for 2015) have been assigned to and summarized by the residents. Ninety-six of them (45 for 2017, 48 for 2016 and 3 for 2015) have been finally approved and uploaded on the Ebook website. The remaining ones are undergoing one of the two processes of revision. Conclusions: The CR Ebook will be officially launched in the European Bodies Meeting, postponed from March to September 2020, and will be progressively filled with a new set of summaries completed and approved. The process started with the CSRs published in 2016 and 2017, and is now proceeding simultaneously onwards and backwards. The project is continuous: the number of CSRs to be summarized is meant to increase every time a CSR is tagged as relevant to rehabilitation, making the Ebook a “live” and updated source of evidence. CR is also planning to translate the summaries into different languages, as is already done for other KT products (i.e. blogshots), in order to reach the widest possible audience. Patient or healthcare consumer involvement: Patients or healthcare consumers have not been directly involved in the project, but represents one of the different audiences the Ebook addresses.

Silvia Carloni,1 Giulia Gallerani,1 Anna Tesei,1 Emanuela Scarpi,2 Giorgio Maria Verdecchia,3 Salvatore Virzì,4 Francesco Fabbri,1 Chiara Arienti1 1Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, 2Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, 3Department of Surgery and Advanced Cancer Therapies, Morgagni-Pierantoni Hospital, Forlì, 4Department of Surgery, Bentivoglio Hospital, Bologna, Italy Objective: We investigated the correlation between ploidy or S-phase fraction (SPF) and the clinical pathological characteristics of patients with peritoneal carcinomatosis from ovarian cancer. We also assessed their relation with the in vivo and in vitro response to several chemotherapeutic agents. Patients and methods: Fifty-three patients with peritoneal carcinomatosis from ovarian cancer were enrolled. Frozen tumor tissue was dissociated by a detergent–trypsin method, and the resulting cell suspension was stained with RNase A and propidium iodide. Samples were then analyzed for ploidy and SPF by flow cytometry. Fresh tumor tissue was dissociated by enzymatic digestion, and cells were exposed to different concentrations of cisplatin, adriamycin, carboplatin, gemcitabine and taxol for 72 hours. In vitro drug sensitivity was then measured using the sulforhodamine B assay.Results: No significant correlation was found between ploidy or SPF and patient characteristics, even though primary carcinomas were mainly hyperdiploid and more proliferative than recurrent tumors. SPF differed significantly among ploidy categories (P=0.01), and high SPF was associated with short-term survival (P=0.48). Patients with multiploid tumors were the most resistant to platinum-based chemotherapy, whereas those with hyperdiploid tumors were the most responsive. In vitro multiploid tumors were the least sensitive, while hypodiploid samples showed the highest sensitivity to the tested drugs. Sensitivity to adriamycin was significantly correlated with ploidy (P=0.03), whereas sensitivity to taxol was correlated with SPF (P=0.04).Conclusion: Our results indicate that ploidy and SPF could facilitate the choice of therapy for patients with peritoneal carcinomatosis. Keywords: DNA index, aneuploidy, SPF, chemotherapeutic agent, in vitro sensitivity, in vivo response&nbsp

Studies on cyclopentenone prostaglandins (CPPGs), clavulones and other cyclopentenones have shown that these compounds have a significant anticancer activity mediated by their cyclopentenone (CP) chemical moiety. In this study the cytotoxicity against cancer cells of the model compound cyclopent-2-en-1-one (2CP) was investigated. Being a highly water soluble small molecule, 2CP could be an ideal candidate to overcome pharmacological issues related to drug delivery and penetration. Its cytotoxic activity was tested on various melanoma and lung cancer cells. Interestingly, 2CP was both cytotoxic and pro-apoptotic, more pronounced on melanoma cells, at concentrations in the sub-micromolar range. On melanoma cells its mechanism of action was mediated by the mitochondria and the activation of caspase 3.

Tumors are complex and heterogeneous diseases characterized by an intricate milieu and dynamically in connection with surrounding and distant tissues. In the last decades, great efforts have been made to develop novel preclinical models able to recapitulate the original features of tumors. However, the development of an in vitro functional and realistic tumor organ is still utopic and represents one of the major challenges to reproduce the architecture of the tumor ecosystem. A strategy to decrypt the whole picture and predict its behavior could be started from the validation of simplified biomimetic systems and then proceed with their integration. Variables such as the cellular and acellular composition of tumor microenvironment (TME) and its spatio-temporal distribution have to be considered in order to respect the dynamic evolution of the oncologic disease. In this perspective, we aim to explore the currently available strategies to improve and integrate in vitro and in vivo models, such as three-dimensional (3D) cultures, organoids, and zebrafish, in order to better understand the disease biology and improve the therapeutic approaches.

The pandemic of COVID-19 is continuously spreading, becoming a worldwide emergency. Early and fast identification of subjects with a current or past infection must be achieved to slow down the epidemiological widening. Here we report a Raman-based approach for the analysis of saliva, able to significantly discriminate the signal of patients with a current infection by COVID-19 from healthy subjects and/or subjects with a past infection. Our results demonstrated the differences in saliva biochemical composition of the three experimental groups, with modifications grouped in specific attributable spectral regions. The Raman-based classification model was able to discriminate the signal collected from COVID-19 patients with accuracy, precision, sensitivity and specificity of more than 95%. In order to translate this discrimination from the signal-level to the patient-level, we developed a Deep Learning model obtaining accuracy in the range 89–92%. These findings have implications for the creation of a potential Raman-based diagnostic tool, using saliva as minimal invasive and highly informative biofluid, demonstrating the efficacy of the classification model.

Current literature agrees on the notion that efficient DNA repair favors longevity across evolution. The DNA damage response machinery activates inflammation and type I interferon signaling. Both pathways play an acknowledged role in the pathogenesis of a variety of age-related diseases and are expected to be detrimental for human longevity. Here, we report on the anti-inflammatory molecular make-up of centenarian’s fibroblasts (low levels of IL-6, type 1 interferon beta, and pro-inflammatory microRNAs), which is coupled with low level of DNA damage (measured by comet assay and histone-2AX activation) and preserved telomere length. In the same cells, high levels of the RNAseH2C enzyme subunit and low amounts of RNAseH2 substrates, i.e. cytoplasmic RNA:DNA hybrids are present. Moreover, RNAseH2C locus is hypo-methylated and RNAseH2C knock-down up-regulates IL-6 and type 1 interferon beta in centenarian’s fibroblasts. Interestingly, RNAseH2C locus is hyper-methylated in vitro senescent cells and in tissues from atherosclerotic plaques and breast tumors. Finally, extracellular vesicles from centenarian’s cells up-regulate RNAseH2C expression and dampen the pro-inflammatory phenotype of fibroblasts, myeloid, and cancer cells. These data suggest that centenarians are endowed with restrained DNA damage-induced inflammatory response, that may facilitate their escape from the deleterious effects of age-related chronic inflammation.

during its fourth year of existence, cochrane rehabilitation went on to promote evidence-informed health decision-making in rehabilitation. in 2020, the outbreak of the coVid-19 pandemic has made it necessary to alter priorities. in these challenging times, cochrane rehabilitation has firstly changed its internal organisation and established a new relevant project in line with pandemic needs: the REH-COVER (Rehabilitation – coVid-19 evidence-based response) action. the aim was to focus on the timely collection, review and dissemination of summarised and synthesised evidence relating to COVID-19 and rehabilitation. Cochrane Rehabilitation REH-COVER action has included in 2020 five main initiatives: 1) rapid living systematic reviews on rehabilitation and coVid-19; 2) interactive living evidence map on rehabilitation and coVid-19; 3) definition of the research topics on “rehabilitation and COVID-19” in collaboration with the World Health Organization (WHO) rehabilitation programme; 4) Cochrane Library special collection on Coronavirus (COVID-19) rehabilitation; and 5) collaboration with COVID-END for the topics “rehabilitation” and “disability.” Furthermore, we are still carrying on five different special projects: Be4rehab; RCTRACK; definition of rehabilitation for research purposes; ebook project; and a prioritization exercise for Cochrane Reviews production. The Review Working Area continued to identify and “tag” the rehabilitation-relevant reviews published in the cochrane library; the publication Working area went on to publish Cochrane Corners, working more closely with the Cochrane Review Groups (CRGs) and Cochrane Networks, particularly with Cochrane Musculoskeletal, oral, skin and sensory Network; the Education Working area, the most damaged in 2020, tried to continue performing educational activities such as workshops in different online meetings; the Methodology Working area organized the third and fourth cochrane Rehabilitation Methodological (CRM) meetings respectively in Milan and Orlando; the Communication Working Area spread rehabilitation evidences through different channels and translated the contents in different languages.

Despite the fact that significant advances in treatment of common cancers have been achieved over the years, orphan tumors still represent an important unmet medical need. Due to their complex multifactorial origin and limited number of cases, such pathologies often have very limited treatment options and poor prognosis. In the search for new anticancer agents, our group recently identified RC-106, a Sigma receptor modulator endowed with proteasome inhibition activity. This compound showed antiproliferative activity toward different cancer cell lines, among them glioblastoma (GB) and multiple myeloma (MM), two currently unmet medical conditions. In this work, we directed our efforts toward the exploration of chemical space around RC-106 to identify new active compounds potentially useful in cancer treatment. Thanks to a combinatorial approach, we prepared 41 derivatives of the compound and evaluated their cytotoxic potential against MM and GB. Three novel potential anticancer agents have been identified.

Background Since its discovery in the late 19th century, radiotherapy has been one of the most important medical treatments in oncology. Recently, fasting or short-term starvation (STS) in cancer patients undergoing chemotherapy has been studied to determine its potential for enhancing the therapeutic index and for preventing side- effects, but no data are available in the radiotherapy setting. We thus decided to investigate the effects in vitro of STS in combination with radiotherapy in metastatic cancer cells and non-cancer cells. Methods Cells were incubated in short-term starvation medium (STS medium, 0·5 g/L glucose + 1% FBS) or in control medium (CM medium, 1 g/L glucose + 10 % FBS) for 24 h and then treated with single high-dose radiation. A plexiglass custom-built phantom was used to irradiate cells. DNA damage was evaluated using alkaline comet assay and theCometAnalyser software. The cell surviving fraction was assessed by clonogenic assay. Finding STS followed by single high-dose radiation significantly increased DNA damage in metastatic cancer cell lines but not in normal cells. Furthermore, STS reduced the surviving fraction of irradiated tumor cells, indicating a good radio-sensitizing effect on metastatic cell lines. This effect was not observed in non-tumor cells. Interpretation Our results suggest that STS may alter cellular processes, enhancing the efficacy of radiotherapy in metastatic cancer cellsin vitro. Interestingly, STS has radioprotective effect on the survival of healthy cells.

During its third year of existence, Cochrane Rehabilitation goals included to point out the main methodological issues in rehabilitation research, and to increase the Knowledge Translation activities. This has been performed through its committees and specific projects. In 2019, Cochrane Rehabilitation worked on five different special projects at different stages of development: 1) a collaboration with the World Health Organization to extract the best evidence for Rehabilitation (Be4rehab); 2) the development of a reporting checklist for Randomised Controlled Trials in rehabilitation (RCTRACK); 3) the definition of what is the rehabilitation for research purposes; 4) the ebook project; and 5) a prioritization exercise for Cochrane Reviews production. The Review Committee finalized the screening and "tagging" of all rehabilitation reviews in the Cochrane library; the Publication Committee increased the number of international journals with which publish Cochrane Corners; the Education Committee continued performing educational activities such as workshops in different meetings; the Methodology Committee performed the second Cochrane Rehabilitation Methodological Meeting and published many papers; the Communication Committee spread the rehabilitation evidence through different channels and translated the contents in different languages. The collaboration with several National and International Rehabilitation Scientific Societies, Universities, Hospitals, Research Centers and other organizations keeps on growing.

Introduction: Despite the increasing financial outlay on cancer research and drug discovery, many advanced cancers remain incurable. One possible strategy for increasing the approval rate of new anticancer drugs for use in clinical practice could be represented by three-dimensional (3D) tumor models on which to perform in vitro drug screening. There is a general consensus among the scientific community that 3D tumor models more closely recapitulate the complexity of tumor tissue architecture and biology than bi-dimensional cell cultures. In a 3D context, cells are connected to each other through tissue junctions and show proliferative and metabolic gradients that resemble the intricate milieu of organs and tumors. Areas covered: The present review focuses on available techniques for generating tumor spheroids and discusses current and future applications in the field of drug discovery. The article is based on literature obtained from PubMed. Expert opinion: Given the relative simplicity of spheroid models with respect to clinical tumors, we must be careful not to overestimate the reliability of their drug-response prediction capacity. The next challenge is to combine our knowledge of co-culture methodologies with high-content imaging and advanced microfluidic technologies to improve the readout and biomimetic potential of spheroid-based models.

During its second year of existence, Cochrane Rehabilitation worked hard to accomplish new and old goals. The Review Committee completed the massive task of identifying and "tagging" all rehabilitation reviews in the Cochrane library. The Publication Committee signed agreements with several international journals and started the publication of Cochrane Corners. The Education Committee performed educational activities such as workshops in International Meetings. The Methodology Committee has completed a two days Cochrane Rehabilitation Methodological Meeting in Paris of which the results will soon be published. The Communication Committee reaches almost 5,000 rehabilitation professionals through social media, and is working on the translation of contents in Italian, Spanish, French, Dutch, Croatian and Japanese. Memoranda of Understanding have been signed with several National and International Rehabilitation Scientific Societies, Universities, Hospitals, Research Centres and other organizations. The be4rehab (best evidence for rehabilitation) project has been started with the World Health Organisation (WHO) to extract from Cochrane reviews and clinical guidelines the best currently available evidence to produce the WHO Minimum Package of Rehabilitation Interventions. The Cochrane Rehabilitation ebook is under development as well as a priority setting exercise with 39 countries from all continents.