Molecular Simulations Matching Denaturation Experiments for N-6-Methyladenosine

Post-transcriptional modifications are crucial for RNA function and can affect its structure and dynamics. Force-field-based classical molecular dynamics simulations are a fundamental tool to characterize biomolecular dynamics, and their application to RNA is flourishing. Here, we show that the set of force-field parameters for N-6-methyladenosine (m(6)A) developed for the commonly used AMBER force field does not reproduce duplex denaturation experiments and, specifically, cannot be used to describe both paired and unpaired states. Then, we use reweighting techniques to derive new parameters matching available experimental data. The resulting force field can be used to properly describe paired and unpaired m(6)A in both syn and anti conformation, which thus opens the way to the use of molecular simulations to investigate the effects of N-6 methylations on RNA structural dynamics

Molecular Dynamics of Solids at Constant Pressure and Stress Using Anisotropic Stochastic Cell Rescaling

Molecular dynamics simulations of solids are often performed using anisotropic barostats that allow the shape and volume of the periodic cell to change during the simulation. Most existing schemes are based on a second-order differential equation that might lead to undesired oscillatory behaviors and should not be used in the equilibration phase. We recently introduced stochastic cell rescaling, a first-order stochastic barostat that can be used for both the equilibration and production phases. Only the isotropic and semi-isotropic variants have been formulated and implemented so far. In this paper, we develop and implement the equations of motion of the fully anisotropic variant and test them on Lennard-Jones solids, ice, gypsum, and gold. The algorithm has a single parameter that controls the relaxation time of the volume, results in the exponential decay of correlation functions, and can be effectively applied to a wide range of systems

Computational drug discovery under RNA times

RNA molecules play many functional and regulatory roles in cells, and hence, have gained considerable traction in recent times as therapeutic interventions. Within drug discovery, structure-based approaches have successfully identified potent and selective small-molecule modulators of pharmaceutically relevant protein targets. Here, we embrace the perspective of computational chemists who use these traditional approaches, and we discuss the challenges of extending these methods to target RNA molecules. In particular, we focus on recognition between RNA and small-molecule binders, on selectivity, and on the expected properties of RNA ligands

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

Effects of hyaluronic acid injections on pain and functioning in patients affected by tendinopathies: a narrative review

BACKGROUND: Tendinopathies are overuse tendon injuries showing load-dependant pain, stiffness, weakness of movement in the affected area, and impairment in the movements. The scientific interest on the role of Hyaluronic Acid (HA) for the management of tendinopathies has been increased due to its anti-inflammatory and lubricative properties. OBJECTIVE: To collect evidence regarding the effectiveness and safety of HA injections in reducing pain in patients affected by tendinopathies. METHODS: A scientific literature search was conducted using the PubMed, Medline and PEDro electronic databases. The databases were searched since their inception until July 2021. The search was limited to English language articles. Different combinations of the terms and MeSH terms 'tendinopathy', 'tendinosis', 'tendinitis', 'hyaluronic acid', 'hyaluronate', 'infiltration', 'hyaluronic injections', 'viscosupplementation' connected with various boolean operators were used for other electronic databases. RESULTS: One hundred and one records were identified from the selected databases plus three additional papers identified by the authors through other sources. After removing duplicated papers and title/abstract screening, 19 studies were included in our review (eight papers on shoulder, three on elbow, four on hand, one on knee, and three on ankle). CONCLUSION: The results showed that none of the studies report severe adverse effects and most of them support the use of HA injections in tendinopathies, with a special attention to pain reduction and functional assessment. Further studies are warranted to better investigate effects and methods of administration of HA in tendinopathies

Financial analysis of acorns chain for food production

This study presents a decision support system for the financial analysis of an acorn chain used in food production. The application of these fruits, in fact, shows potential in human nutrition and valorization of rural and marginal areas. A multi-step production process is hypothesised with a different potential organizational structure of each phase and products to be sold. The net present value, pay-back period, safety margins, and internal rate of return are computed for the implemented scenario. The research was grounded on Italian-based data but can be easily transferred to other case studies. The results highlight potential economic suitability of the chain, although subject to a minimal value of prices and productivity. Future improvements and further integration of this study, such as the analysis of fluctuation’s risk of annual production or the need to investigate sensorial properties of acorns, are suggested and discussed

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

A rehabilitative approach beyond the acute stroke event: a scoping review about functional recovery perspectives in the chronic hemiplegic patient

Background: Stroke is a main cause of disability worldwide and its neuro-rehabilitative management is not limited to the acute phase but requires continuity in the rehabilitation approach especially in the chronic phase. The aim of this scoping review was to highlight the different treatment opportunities available in neurorehabilitation, effective for patients with chronic stroke sequelae, not only in terms of maintaining motor function but also improving it. Methods: The literature search was conducted using the following databases: MEDLINE (PubMed), PEDro, Scopus, Web of Science (WOS), Cochrane from 2012 to February 2023. We selected Randomized Clinical Trials in English dealing with neurorehabilitation strategies in chronic hemiplegic patients after stroke focusing on motor function, muscular strength, gait, postural balance, spasticity, and quality of life. Results: According to the inclusion criteria, 47 articles were selected for our review. All of them were analyzed following the primary outcome and the rehabilitation technique used. Despite the different protocols used within the same technique and despite the chronicity of the disease, all studies report an improvement after the rehabilitation treatment of motor function and quality of life. Conclusion: The literature analyzed invites us to reflect respect to neurorehabilitation approach to the patient with chronic stroke sequelae often considered to have as its objective the maintenance of the present motor function and contain disability: instead, the review reports how, even in chronicity, the patient always reports margins of statistically and clinically significant improvement. The chronic stroke rehabilitation over 6 months has been proved effective in obtaining recovery in different settings

Oxygen–ozone therapy in the rehabilitation field: state of the art on mechanisms of action, safety and effectiveness in patients with musculoskeletal disorders

In recent years, the interest in oxygen–ozone (O2O3) therapy application has considerably increased in the field of rehabilitation. Despite its widespread use in common clinical practice, the biochemical effects of O2O3 are still far from being understood, although its chemical properties seem to play a pivotal role in exerting its positive effects on different pathological conditions. Indeed, the effectiveness of O2O3 therapy might be partly due to the moderate oxidative stress produced by O3 interactions with biological components. O2O3 therapy is widely used as an adjuvant therapeutic option in several pathological conditions characterized by chronic inflammatory processes and immune over‐activation, and most musculoskeletal disorders share these pathophysiological processes. The present comprehensive review depicts the state‐of‐the‐art on the mechanisms of action, safety and effectiveness of O2O3 therapy in the complex scenario of the management of musculoskeletal disorders. Taken together, our findings suggest that O2O3 therapy seems to reduce pain and improve functioning in patients affected by low back pain and knee osteoarthritis, as reported by several studies in the literature. However, to date, further studies are warranted to clearly investigate the therapeutic effects of this promising therapy on other musculoskeletal disorders in the field of rehabilitation