Serious Games for Wrist Rehabilitation in Juvenile Idiopathic Arthritis

Rehabilitation is a painful and tiring process involving series of exercises that patients must repeat over a long period. Unfortunately, patients often grow bored, frustrated, and lose motivation making rehabilitation less effective. In the recent years video games have been widely used to implement rehabilitation protocols so as to make the process more entertaining, engaging and to keep patients motivated. In this paper, we present an integrated framework we developed for the wrist rehabilitation of patients affected by Juvenile Idiopathic Arthritis (JIA) following a therapeutic protocol at the Clinica Pediatrica G. e D. De Marchi. The framework comprises four video games and a set modules that let the therapists tune and control the exercises the games implemented, record all the patients actions, replay and analyze the sessions. We present the result of a preliminary validation we performed with four poliarticular JIA patients at the clinic under the supervision of the therapists. Overall, we received good feedback both from the young patients, who enjoyed performing known rehabilitation exercises using video games, and therapists who were satisfied with the framework and its potentials for engaging and motivating the patients

Ultramicronized palmitoylethanolamide reduces viscerovisceral hyperalgesia in a rat model of endometriosis plus ureteral calculosis: role of mast cells.

The effects of ultramicronized palmitoylethanolamide were evaluated on pain behaviours and markers of mast cell (MC) activity in 'a rat model of endometriosis plus ureteral calculosis (ENDO+STONE)-induced viscerovisceral hyperalgesia (VVH). Female Sprague-Dawley rats that underwent surgical induction of endometriosis were randomly assigned to receive active (ultramicronized palmitoylethanolamide 10 mg·kg-1 ·d-1, orally) or placebo treatment for 25 days. At day 21, they underwent ureteral stone formation and were video-recorded till day 25 to evaluate ureteral and uterine pain behaviours. At autopsy (day 25), ureteral condition and number and diameter of endometrial cysts were evaluated. The following were then measured: number and percentage of degranulating MCs, number of vessels, chymase, nerve growth factor (NGF), vascular endothelial growth factor (VEGF), and Flk-1 (VEGF receptor) in cysts, and NGF in dorsal root ganglia (DRG). Ultramicronized palmitoylethanolamide-treated vs placebo-treated rats showed significantly lower number, duration and complexity of ureteral crises, shorter duration of uterine pain, and smaller cyst diameter (0.0001 < P < 0.004); a significantly higher percentage of expelled stones (P < 0.0001); significantly lower MC number (P<0.01), vessel number (P< 0.01), chymase (P< 0.05), NGF (P<0.05), VEGF (P< 0.01), and Flk-1 (P< 0.01) expression in cysts and NGF expression in DRG (P< 0.01). In all animals, the global duration of ureteral crises correlated linearly and directly with cyst diameter, MC number and chymase in cysts, and NGF in cysts and DRG (0.02 < P < 0.0002). Ultramicronized palmitoylethanolamide significantly reduces VVH from ENDO+STONE, probably by modulating MC expression/activity in cysts, thus reducing central sensitization due to noxious signals from endometriotic lesions. The results suggest potential utility of the compound for VVH in clinics

Fascial Manipulation® for chronic aspecific low back pain: a single blinded randomized controlled trial [version 2; referees: 2 approved]

Background: The therapeutic approach to chronic aspecific low back pain (CALBP) has to consider the multifactorial aetiology of the disorder. International guidelines do not agree on unequivocal treatment indications. Recommendations for fascial therapy are few and of low level evidence but several studies indicate strong correlations between fascial thickness and low back pain. This study aims at comparing the effectiveness of Fascial Manipulation® associated with a physiotherapy program following guidelines for CALBP compared to a physiotherapy program alone. Methods: 24 subjects were randomized into two groups, both received eight treatments over 4 weeks. Outcomes were measured at baseline, at the end of therapy and at a 1 month and a 3 months follow-up. Pain was measured with the visual analogue scale (VAS) and the brief pain inventory (BPI), function with the Rolland-Morris disability questionnaire (RMDQ), state of well-being with the short-form 36 health-survey (SF-36). The mean clinical important difference (MCID) was also measured. Results: Patients receiving Fascial Manipulation® showed statistically and clinically significant improvements at the end of care for all outcomes, in the short (RMDQ, VAS, BPI) and medium term for VAS and BPI compared to manual therapy. The MCID show significant improvements in the means and percentage of subjects in groups in all outcomes post-treatment, in the short and medium term. Conclusion: Fascial tissues were implicated in the aetiology of CALBP and treatment led to decreased symptomatic, improved functional and perceived well-being outcomes that were of greater amplitude compared to manual therapy alone

Facilitating accessible, rapid, and appropriate processing of ancient metagenomic data with AMDirT [version 1; peer review: 1 approved, 1 approved with reservations]

Background: Access to sample-level metadata is important when selecting public metagenomic sequencing datasets for reuse in new biological analyses. The Standards, Precautions, and Advances in Ancient Metagenomics community (SPAAM, https://spaam-community.github.io) has previously published AncientMetagenomeDir, a collection of curated and standardised sample metadata tables for metagenomic and microbial genome datasets generated from ancient samples. However, while sample-level information is useful for identifying relevant samples for inclusion in new projects, Next Generation Sequencing (NGS) library construction and sequencing metadata are also essential for appropriately reprocessing ancient metagenomic data. Currently, recovering information for downloading and preparing such data is difficult when laboratory and bioinformatic metadata is heterogeneously recorded in prose-based publications. Methods: Through a series of community-based hackathon events, AncientMetagenomeDir was updated to provide standardised library-level metadata of existing and new ancient metagenomic samples. In tandem, the companion tool 'AMDirT' was developed to facilitate automated metadata curation and data validation, as well as rapid data filtering and downloading. Results: AncientMetagenomeDir was extended to include standardised metadata of over 5000 ancient metagenomic libraries. The companion tool 'AMDirT' provides both graphical- and command-line interface based access to such metadata for users from a wide range of computational backgrounds. We also report on errors with metadata reporting that appear to commonly occur during data upload and provide suggestions on how to improve the quality of data sharing by the community.Conclusions: Together, both standardised metadata and tooling will help towards easier incorporation and reuse of public ancient metagenomic datasets into future analyses.Bioarchaeolog

A blood atlas of COVID-19 defines hallmarks of disease severity and specificity.

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description of specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying COVID-19 severity in an integrated comparison with influenza and sepsis patients versus healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity involved cells, their inflammatory mediators and networks, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism, and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Systems-based integrative analyses including tensor and matrix decomposition of all modalities revealed feature groupings linked with severity and specificity compared to influenza and sepsis. Our approach and blood atlas will support future drug development, clinical trial design, and personalized medicine approaches for COVID-19

Novel factor Xa inhibitors: a patent review

IMPORTANCE OF THE FIELD: New oral anticoagulants with favorable safety profiles and fixed doses are required for the management of thromboembolism and stroke prevention in patients with atrial fibrillation. Among them, fXa inhibitors (the so-called xabans) are attractive options that can overcome limitations (e.g., bleeding) of the current oral antithrombotic therapy. The rational design of small-molecule direct fXa inhibitors, whose importance is testified by the growing number of publications and patents recently registered, has been fully supported by the X-ray crystallography of enzyme-ligand complexes. AREAS COVERED IN THIS REVIEW: Pubmed, SciFinder Scholar, ISI web of knowledge(SM), http://ep.espacenet.com/ and Google websites were used as the main sources for literature retrieving, and &gt; 100 patents filed between 2006 and April 2009, reviewed and discussed herein, highlight the variety among the P1 and P4 moieties on suitable scaffolds. WHAT THE READER WILL GAIN: The replacement of the benzamidine P1 moiety, which characterizes the first generation, with less basic bioisosteric or nonpolar neutral P1 groups led to the disclosure of numerous fXa inhibitors with high potency, selectivity and oral bioavailability. Novel selective fXa inhibitors with stable pharmacokinetics, better therapeutic windows and ease-of-use than the existing anticoagulants are currently under advanced stage clinical trials. TAKE-HOME MESSAGE: Available data from Phase II and Phase III studies reflect the drive towards fXa inhibitors as potentially more effective and safer antithrombotic drugs. Their development is expected to address two major needs for anticoagulation, namely safety and ease-of-use, and to significantly affect the anticoagulant market

Fascial Manipulation® for chronic aspecific low back pain: a single blinded randomized controlled trial [version 1; referees: 2 approved]

Background: The therapeutic approach to chronic aspecific low back pain (CALBP) has to consider the multifactorial aetiology of the disorder. International guidelines do not agree on unequivocal treatment indications. Recommendations for fascial therapy are few and of low level evidence but several studies indicate strong correlations between fascial thickness and low back pain. This study aims at comparing the effectiveness of Fascial Manipulation® associated with a physiotherapy program following guidelines for CALBP compared to a physiotherapy program alone. Methods: 24 subjects were randomized into two groups, both received eight treatments over 4 weeks. Outcomes were measured at baseline, at the end of therapy and at a 1 month and a 3 months follow-up. Pain was measured with the visual analogue scale (VAS) and the brief pain inventory (BPI), function with the Rolland-Morris disability questionnaire (RMDQ), state of well-being with the short-form 36 health-survey (SF-36). The mean clinical important difference (MCID) was also measured. Results: Patients receiving Fascial Manipulation® showed statistically and clinically significant improvements at the end of care for all outcomes, in the short (RMDQ, VAS, BPI) and medium term for VAS and BPI compared to manual therapy. The MCID show significant improvements in the means and percentage of subjects in groups in all outcomes post-treatment, in the short and medium term. Conclusion: Fascial tissues were implicated in the aetiology of CALBP and treatment led to decreased symptomatic, improved functional and perceived well-being outcomes that were of greater amplitude compared to manual therapy alone