webPDBinder: a server for the identification of ligand binding sites on protein structures

The webPDBinder (http://pdbinder.bio.uniroma2.it/PDBinder) is a web server for the identification of small ligand-binding sites in a protein structure. webPDBinder searches a protein structure against a library of known binding sites and a collection of control non-binding pockets. The number of similarities identified with the residues in the two sets is then used to derive a propensity value for each residue of the query protein associated to the likelihood that the residue is part of a ligand binding site. The predicted binding residues can be further refined using conservation scores derived from the multiple alignment of the PFAM protein family. webPDBinder correctly identifies residues belonging to the binding site in 77% of the cases and is able to identify binding pockets starting from holo or apo structures with comparable performances. This is important for all the real world cases where the query protein has been crystallized without a ligand and is also difficult to obtain clear similarities with bound pockets from holo pocket libraries. The input is either a PDB code or a user-submitted structure. The output is a list of predicted binding pocket residues with propensity and conservation values both in text and graphical format

Idiopathic facial palsy: umbrella review of systematic reviews and meta-analyses

Idiopathic facial palsy is the most common disease of the VII cranial nerve. There are many treatments to facilitate recovery from this condition: pharmacological, surgical, rehabilitative, but the effectiveness of some of these treatments, especially the latter, is still under discussion. The purpose of this umbrella review of systematic reviews is to analyse the literature in order to investigate the different rehabilitation interventions in patients suffering from idiopathic facial palsy. A scientific literature search was carried out from January 2009 until August 2019, using Mesh the terms "facial palsy", "Bell's Palsy", "idiopathic facial nerve palsy", combined with "rehabilitation" and "therapy". Initially all the systematic reviews and meta-analyses of the last 10 years concerning rehabilitation treatments for the recovery of injured functions in facial palsy were included. Given the heterogeneity of the studies in the literature, which do not differentiate the different causes of facial palsy, all the causes of idiopathic facial palsy were included in the review. The research resulted in 94 published systematic reviews but only 6 were considered in respect to the inclusion criteria. All studies agree on the lack of high-quality scientific work to be able to say that Bell's physiotherapy treatments for facial palsy are effective, in particular with regard to recovery times during the rehabilitation process. Future studies are needed, in order to highlight the therapeutic implications of the different rehabilitation methods, with standardized protocols, in patients suffering from facial palsy of different aetiology

Changes in spine alignment and postural balance after breast cancer surgery: a rehabilitative point of view

Breast cancer is the most common malignant tumor in female patients in developed countries. Recent articles indicate that one-sided mastectomy or minor breast surgery to treat breast cancer can have deleterious effects on posture and the musculoskeletal system. The purpose of this study was to investigate the alterations post-breast cancer surgery of the spine alignment associated to the balance not reported by the noninvasive instrumentation. We enrolled 30 women who had undergone treatment for breast cancer (BG) and were on a waiting-list for rehabilitation treatment and a control group of 30 healthy volunteer women (CG), matched by age and body mass index. The stabilometry was performed using a force platform (Kistler Instruments, Winterthur, Switzerland) test during quiet standing with closed-eyes (EC) and open-eyes (EO), recording the position of the center of pressure (CoP) for 51.2 sec. The stabilogram or the time plot of the two coordinates, X and Y, of the CoP was obtained, which represent anteroposterior and midlateral balance. Spinal posture was measured using the Formetric-4D rasterstereographic system (DIERS, International GmbH, Schlangenbad, Germany), and thoracic kyphotic angle, lumbar lordotic angle, and surface trunk rotation were evaluated. Sixty participants were analyzed (CG:30; BG:30). For the spine rasterstereography a statistically significant difference was shown with regard to anterior-posterior flexion of the trunk major in BG; pelvic inclination and twist of half-pelvis decreased in BG; normalized lumbosacral inversion point decreased in BG; surface rotation major in BG; and lateral deviation major in BG. Compared with the values for the stabilometry test with EO and EC, a statistically significant difference was observed, respectively, for ellipse length (mm; p = 0.04) and ellipse area (mm2; p = 0.04) with EO and in ellipse area (mm2) with EC (p = 0.05), increased in BG for both conditions. No difference was shown for CoP velocity and oscillations between the groups. Breast cancer survivors after prostheses or tissue expanders for mastectomy showed a spine's misalignment present both on the sagittal plane, both on the coronal and frontal plane, increased in BG regard to anterior-posterior flexion of the trunk, surface rotation, and lateral deviation. It is associated with greater energy expenditure for the postural balance control increased in BG with a major ellipse area in EO and EC conditions and major ellipse length in EC condition

The reaching movement in breast cancer survivors. attention to the principles of rehabilitation

Introduction: Breast-cancer is leading cause of morbidity and mortality in women. The prognosis and survival rate of women with breast-cancer have significantly improved worldwide; more attention needs to be paid to rehabilitative interventions after surgery. This paper describes use of reaching movement to assess upper limb motorcontrol and functional ability after breast-cancer surgery (BC). Material and methods: We conducted a cross-sectional observational study consisting of biomechanical evaluation of upper limb limitations in women BC, versus a controlgroup (CG). Thirty breast-cancer survivors and thirty healthy women participated in this study. Both groups were subjected to clinical evaluation of the shoulder joint ROM on the operated side, as an assessment of the muscular-strength of the shoulder with the MRC-scale. The Functional-Assessment was evaluated by the DASH and Constant-Murley-Score. The EORTC QLQ-C30 and VAS were used to measure the quality of life assessment and pain respectively. A Biomechanical evaluation was performed, using Reaching-Task and Surface-EMG. Results: Normal Jerk for BC was higher than CG. Target approaching velocity and movement duration BC was lower than CG. Synergy Anterior Deltoid/Triceps Brachii muscles in CG was higher than BC

Rehabilitative good practices in the treatment of sarcopenia: a narrative review

ABSTRACT: To date, rehabilitative good practices that analyze all aspects of the rehabilitation management of the patient with sarcopenia are absent in the literature. The purpose of this article is to carry out research and evaluation of the evidence, good practice, and recommendations in the literature relating to the rehabilitative treatment of disabilities associated with sarcopenia. Bibliographic research was conducted on Medline, PEDro, Cochrane Database, and Google Scholar. All articles published in the last 10 yrs were analyzed. The results of this research generated three guidelines, eight meta-analyses, five systematic reviews, a Cochrane review, 17 reviews, and seven consensus conferences. From the analysis of the literature, it seems that most of the works agree in affirming that exercise and diet supplementation are the cornerstones of rehabilitation treatment of patients with sarcopenia. The practice of an adequate lifestyle received numerous high-grade recommendations in the included guidelines. Based on the data obtained, the rehabilitation management of the patient with sarcopenia must be personalized and must include exercise and nutritional supplementation. These factors are important in increasing the autonomy of the elderly essential for safe walking without neglecting stretching exercises that are important for flexibility and balance and coordination exercises

Efficacy of hyaluronate injections in rotator cuff disorders: a level-I meta-analysis

Background: Rotator cuff disease is the most common cause of shoulder pain and weakness. Conservative treatment is the first choice of shoulder pain management. Viscosupplementation of hyaluronic acid (HA) seems to be effective for management of tendon disorders. The objective of this study was to evaluate the scientific evidence reported in literature according to HA shoulder injection in rotator cuff disorders treatment. Methods: An English-language systematic literature search was performed by two independent researchers; data sources included the following databases: MEDLINE, Embase, CINAHL, Google scholar web, Ovid database, Physiotherapy Evidence Database (PEDro), and the Cochrane Library. We performed a broad research for relevant study up to February 2017. Articles were included if they reported data on clinical and functional outcomes in patients who had undergone HA injection for management of rotator cuff pathology compared to placebo, corticosteroid injection and/or physical therapies. Methodological quality was assessed with the PEDro rating scale. The outcomes were improvement of symptoms (assessed by VAS scale) and shoulder function (assessed through DASH and ASES Score). Results: 5 RCTs studies (990 patients) were pooled in the Meta-analysis. The PEDro rating scale ranged from 2 to 8. Two studies compared HA injection with corticosteroid injections, patients were injected once a week for three weeks. Four studies compared HA injection with placebo injection, of which two used 3 weekly injections and two used 5 weekly injections. Significant difference was found in pain reduction between HA and placebo group at 26 weeks follow-up (MD= -0.51, 95% CI -0.96 to -0.07), p=0.02. Conclusion: HA injections might be a valuable safe alternative to other conservative methods for the treatment of rotator cuff disorders. Nowadays, few and low quality randomized controlled trials have been published. Therefore, to reach an overall conclusion about the effect of HA injection in rotator cuff we need more high quality studies. Level of evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence. Study design: Meta-analys

Gait analysis advancements: rehabilitation value and new perspectives from forensic application

The clinical and rehabilitation value of gait analysis is remarkable and indisputable and poised to grow as technological advancements unfold. This article aims to shed light on the advances in how gait is assessed, enabling those who have suffered an injury impairing their motor skills to be diagnosed more accurately and efficiently as well as to compare the hallmarks of rehabilitative and forensic gait analysis. The authors have conducted an analysis of relevant papers (published between 1967 and 2020) from a medicolegal perspective, cited in PubMed, MEDLINE, Cochrane Library, EMBASE, and available recommendations for the legal application of such techniques. Moreover, considering the use of gait analysis as a forensic tool, this study broadens the scope of research by including search engines, legal databases, and court filings (DeJure, Lexis Nexis, Justia) between 2000 and 2022. The instrumental assessment of movement (Gait Analysis) has come to constitute an essential analytical tool for the biomedical sector to objectively and accurately assess human movement and posture. The article is also aimed at elaborating differences and similarities between clinical and forensic gait analysis. When it comes to the forensic applicability of gait analysis and its evidentiary value, however, there is a pressing need for a review of its scientific basis. Therefore, it is necessary to conduct a thorough evaluation of its use in legal practice, as stressed in scientific literature and surveys. It is of utmost importance to highlight the procedural and assessment standards currently applied to forensic gait analysis, to evaluate its strengths and weaknesses, and to achieve standardized guidelines based on broad scientific consensus

Integration of focal vibration and intra-articular oxygen–ozone therapy in rehabilitation of painful knee osteoarthritis

Objective: To examine the pain-reducing effects of intra-articular oxygen–ozone (O2O3) injections and mechanical focal vibration (mFV) versus O2O3 injections alone in patients with knee osteoarthritis. Methods: Patients with chronic pain (>6 weeks) due to knee osteoarthritis (II–III on the Kellgren–Lawrence scale) were consecutively enrolled and divided into two groups: O2O3 (n = 25) and O2O3-mFV (n = 24). The visual analog scale (VAS), Knee Injury and Osteoarthritis Outcome Score (KOOS), and Medical Research Council (MRC) Manual Muscle Testing scale were administered at baseline (before treatment), after 3 weeks of treatment, and 1 month after the end of treatment. Patients received three once-weekly intra-articular injections of O2O3 into the knee (20 mL O3, 20 μg/mL). The O2O3-mFV group also underwent nine sessions of mFV (three sessions per week). Results: The VAS score, KOOS, and MRC score were significantly better in the O2O3-mFV than O2O3 group. The within-group analysis showed that all scores improved over time compared with baseline and were maintained even 1 month after treatment. No adverse events occurred. Conclusion: An integrated rehabilitation protocol involving O2O3 injections and mFV for 3 weeks reduces pain, increases autonomy in daily life activities, and strengthens the quadriceps femoris

Modificaciones histológicas foliares causadas por organismos fúngicos en tres especies de Myrtaceae.

Histological changes in leaves caused by fungi in three species of Myrtaceae. The family Myrtaceae is one of the largest in Argentina. In the province of Tucumán, eleven native species inhabit, three of them, Blepharocalyx salicifolius (Kunth) O. Berg, Eugenia uniflora L. and Myrcianthes pungens (O. Berg) D. Legrand have medicinal, alimentary and forestry importance. Information about fungal species and histological foliar changes produced by them is limited. So the objective of this research is to identify the species of fungi present in leaves of these three tree species; and evaluate the anatomical changes caused by the presence of them. Conventional techniques and stains were used. Twelve fungal species were identified in the three arboreal hosts studied. Ten species were cited for the first time for Argentina. Puccinia psidii and Alternaria sp. were found more frequently. The most affected leaf tissues were the palisade and spongy parenchyma. The most significant lesion was that one observed in the leaf of E. uniflora, it was produced by Microsphaerospis arundinis. Fungal identified species increases the knowledge of the diversity of fungi associated with leaves in native tree species from province of Tucuman.La familia Myrtaceae es una de las más numerosas en Argentina. En la provincia de Tucumán habitan 11 especies nativas, de las cuales Blepharocalyx salicifolius (Kunth) O. Berg, Eugenia uniflora L. y Myrcianthes pungens (O.Berg) D. Legrand presentan importancia medicinal, alimenticia y forestal. La información sobre las especies fúngicas y las modificaciones histológicas foliares que ellos producen es escasa. Por lo tanto, el objetivo de la presente investigación fue identificar las especies de hongos en hojas de las tres especies arbóreas y describir las modificaciones anatómicas causadas por la presencia de los mismos. Se trabajó con material fresco al que se aplicó técnicas y tinciones convencionales para su estudio. Se identificaron 12 especies fúngicas, 10 de ellas se citan por primera vez para la Argentina, en los tres hospedantes arbóreos estudiados. Puccinia psidii y Alternaria sp. se encontraron con mayor frecuencia. Los tejidos foliares más afectados fueron el parénquima esponjoso y el parénquima en empalizada. La lesión más significativa en la lámina foliar se observó en E. uniflora, producida por Microsphaerospis arundinis. Las especies fúngicas identificadas amplían el conocimiento de la diversidad de hongos asociados a hojas en especies arbóreas nativas de la provincia de Tucumán

Generation of pralatrexate resistant T-cell lymphoma lines reveals two patterns of acquired drug resistance that is overcome with epigenetic modifiers

While pralatrexate (PDX) has been successfully developed for the treatment of T-cell lymphoma, the mechanistic basis for its T-cell selectivity and acquired resistance remains elusive. In an effort to potentially identify synergistic combinations that might circumnavigate or delay acquired PDX resistance, we generated resistant cells lines over a broad concentration range. PDX-resistant cell lines H9-12 and H9-200 were developed, each exhibiting an IC50 of 35 and over 1000 nM, respectively. These lines were established in vitro from parental H9 cells. Expression analysis of the proteins known to be important determinants of antifolate pharmacology revealed increase expression of dihydrofolate reductase (DHFR) due to gene amplification, and reduced folate carrier1 downregulation, as the putative mechanisms of resistance in H9-12 and H9-200 cells. Cross resistance was only seen with methotrexate but not with romidepsin, azacitidine (AZA), decitabine, gemcitabine, doxorubicin, or bortezomib. Resistance to PDX was reversed by pretreatment with hypomethylating agents in a concentration-dependent fashion. Comparison of gene expression profiles of parental and resistant cell lines confirmed markedly different patterns of gene expression, and identified the dual specificity phosphatase four (DUSP4) as one of the molecular target of PDX activity. Reduced STAT5 phosphorylation following exposure to PDX was observed in the H9 but not in the H9-12 and H9-200 cells. These data suggest that combination with hypomethylating agents could be potent, and that DUSP4 and STAT5 could represent putative biomarkers of PDX activity