Comment on “early efficacy of intra-articular HYADD® 4 (Hymovis®) injections for symptomatic knee osteoarthritis”

We read with great interest the study by Priano titled“Early efficacy of intra-articular HYADD® 4 (Hymovis®) injections for symptomatic knee osteoarthritis.” 1 The author would like to explore the efficacy of intra-articular HYADD 4 (Hymovis) injections for symptomatic knee osteoarthritis. Results from this study are very interesting and promising from a clinical aspect; however, we believe that studying patient’sclinical status with visual analog scale and Western Ontario and McMaster Universities Arthritis Index scale should be supported by biomechanical information. From this point of view, to have more data that could influence the clinical practice, it is important to note the possible action that intraarticular injections of different kinds of hyaluronic acid could have on walking biomechanics using an objective measurement tool as gait analysis. In our opinion, the work by Priano1 is promising because it investigates the efficacy of a new formulation of hyaluronic acid. Nowadays, many hyaluronic acid formulations are approved for clinical use in Europe and the United States. Furthermore, hyaluronic acid injections’ efficacy has been demonstrated also in hip osteoarthritis. 2 However, even if these formulations differ in their chemical– physical properties, joint space half-life, rheological properties, and clinical efficacy, there are few studies that investigate hyaluronic acid’s possible action from a biomechanical point of view. 3,4 From this point of view, we believe that osteoarthritis management and rehabilitation should be prescribed after an objective analysis of functional walking alterations using gait analysis instrumentations. The use of gait analysis should be desirable during diagnosis and follow-up. In fact, it is capable to identify different walking patterns in patient with osteoarthritis of the lower limbs, whereas the radiology can evaluate the status of the joint’s structures

Cell death pathology: Perspective for human diseases

AbstractApoptosis, a genetically regulated form of cell death with distinct biochemical and morphological features, plays a relevant physiological and pathological role in the organism, being pivotal in the maintenance of tissue development and homeostasis in the adult as well as in the regulation of immune responses. Deregulation of this process causes several human disorders including cancer, autoimmune and neurodegenerative diseases. Thus, modulation of the apoptotic process and of cell death in general, is a potential therapeutic approach for the treatment of several human pathologies

La Neuromodulazione sacrale nelle disfunzioni del pavimento pelvico

La disfunzione vescico-uretrale rappresenta un importante problema nella pratica medica quotidiana a causa dei disturbi psicologici, i costi sociali e l’elevato impatto sulla qualità di vita. Recentemente, la neuromodulazione sacrale, cioè la stimolazione elettrica dei nervi sacrali, sembra rappresentare un’alternativa nei casi di iperattività vescicale idiomatica resistente alla terapia medica. Il meccanismo di azione è soltanto parzialmente noto, ma sembra coinvolgere la modulazione nel midollo spinale per via della stimolazione degli interneuroni inibitori. La prima tappa è rappresentata da un test di prova (PNE test). Comprende l’applicazione di un elettrodo monopolare temporaneo quale test diagnostico per determinare la sede migliore per l’impianto e per verificare, dopo un periodo di applicazione della neuromodulazione di 7-14 giorni la risposta clinica. Se il test di simulazione è efficace, viene impiantato un elettrodo quadripolare connesso ad un neuromodulatore definitivo. L’iperattività vescicale idiopatica rappresenta la principale indicazione per questa tecnica. I pazienti che hanno le minori probabilità di beneficiare da questa procedura sono coloro con lesioni spinali complete o quasi complete, mentre le lesioni spinali incomplete sembrano rappresentare una potenziale indicazione. Questa tecnica è attualmente indicata anche nei casi di ritenzione cronica non ostruttiva e nella sindrome del dolore pelvico cronico. Quando si effettua la selezione, oltre tre quarti dei pazienti hanno mostrato una risposta clinicamente significativa con una riduzione di almeno 50% nella frequenza di episodi di incontinenza, ma i risultati variano in base alla metodica di valutazione di ciascun Autore. Dal punto di vista economico, l’investimento iniziale per l’apparecchiatura è ammortizzato nel medio termine dalla riduzione dei costi legati alla disfunzione delle basse vie urinarie. Infine, questa tecnica richiede un attento follow-up ed adattamenti dei parametri elettrici per ottimizzare l’equilibrio tra i sistemi neurologiciVesico-urethral dysfunction is a major problem in daily medical practice due to its psychological disturbances, its social costs and its high impact on quality of life. Recently, sacral neuromodulation, namely the electrical stimulation of the sacral nerves, appears to have become an alternative for radical bladder surgery particularly in cases of idiopathic bladder over¬activity. The mechanism of action is only partially understood but it seems to involve a modulation in the spinal cord due to stimulation of inhibitory interneurons. Temporary sacral nerve stimulation is the first step. It comprises the temporary application of neuromodulation as a diagnostic test to deter¬mine the best location for the implant and to control the integrity of the sacral root. If test stimulation is successful, a permanent device is implanted. This procedure is safe in experienced hands. So-called idiopathic bladder overactivity still the major indication for this technique. Patients not likely to benefit from the procedure were those with complete or almost complete spinal lesions, but incomplete spinal lesions seemed to be a potential indication. This technique is now also indicated in the case of idiopathic chronic retention and chronic pelvic pain syndrome. When selection is performed, more than three-quarters of the patients showed a clinically significant response with 50% or more reduction in the frequency of incontinent episodes, but the results vary according to the author’s mode of evaluation. From the economic point of view, the initial investment in the device is amortized in the mid-term by savings related to lower urinary tract dysfunction. Finally, this technique requires an attentive follow-up and adjustments to the electric parameters so as to optimize the equilibrium between the neurological system

Vaccination policy and mortality from COVID-19 in the European Union

This paper estimates the dynamic effect of vaccination on mortality from COVID-19 using weekly data from 26 European Union countries during 2021. Our analysis relies on the double machine learning method to control for multiple confounders, including nonpharmaceutical interventions, climate variables, mobility factors, variants of concern, country- and week-specific shocks. In our baseline specification, we show that a 10-pp. increase in cumulative doses per 100 inhabitants averts 5.08 COVID-19 deaths per million inhabitants at the 8-week horizon and 26.41 deaths in the 8-week time window considered. The average reduction in mortality in this window is close to 50%. Further estimates reveal that the effect of doses administered to adults aged 18-59 does not statistically differ from that of doses received by people aged 60+. Finally, vaccine-specific estimates document that mRNA-1273 (Moderna) and Vaxzevria (AstraZeneca) are more cost-effective in saving lives than Comirnaty (Pfizer), while we are unable to demonstrate any effect of Ad26.COV2.S (J&J)

Bioinformatics analysis of the serine and glycine pathway in cancer cells

Serine and glycine are amino acids that provide the essential precursors for the synthesis of proteins, nucleic acids and lipids. Employing 3 subsequent enzymes, phosphoglycerate dehydrogenase (PHGDH), phosphoserine phosphatase (PSPH), phosphoserine aminotransferase 1 (PSAT1), 3-phosphoglycerate from glycolysis can be converted in serine, which in turn can by converted in glycine by serine methyl transferase (SHMT). Besides proving precursors for macromolecules, serine/glycine biosynthesis is also required for the maintenance of cellular redox state. Therefore, this metabolic pathway has a pivotal role in proliferating cells, including cancer cells. In the last few years an emerging literature provides genetic and functional evidences that hyperactivation of serine/glycine biosynthetic pathway drives tumorigenesis. Here, we extend these observations performing a bioinformatics analysis using public cancer datasets. Our analysis highlighted the relevance of PHGDH and SHMT2 expression as prognostic factor for breast cancer, revealing a substantial ability of these enzymes to predict patient survival outcome. However analyzing patient datasets of lung cancer our analysis reveled that some other enzymes of the pathways, rather than PHGDH, might be associated to prognosis. Although these observations require further investigations they might suggest a selective requirement of some enzymes in specific cancer types, recommending more cautions in the development of novel translational opportunities and biomarker identification of human cancers

Muscle activations during functional tasks in individuals with chronic ankle instability: a systematic review of electromyographical studies

Background: It has been reported that individuals with chronic ankle instability (CAI) show motor control ab-normalities. The study of muscle activations by means of surface electromyography (sEMG) plays a key role in understanding some of the features of movement abnormalities. Research question: Do common sEMG activation abnormalities and strategies exists across different functional movements? Methods: Literature review was conducted on PubMed, Web-of-Science and Cochrane databases. Studies pub-lished between 2000 and 2020 that assessed muscle activations by means of sEMG during any type of functional task in individuals with CAI, and used healthy individuals as controls, were included. Methodological quality was assessed using the modified Downs&Black checklist. Since the methodologies of different studies were hetero-geneous, no meta-analysis was conducted. Results: A total of 63 articles investigating muscle activations during gait, running, responses to perturbations, landing and hopping, cutting and turning; single-limb stance, star excursion balance task, forward lunges, ball- kicking, y-balance test and single-limb squatting were considered. Individuals with CAI showed a delayed activation of the peroneus longus in response to sudden inversion perturbations, in transitions between double- and single-limb stance, and in landing on unstable surfaces. Apparently, while walking on ground there are no differences between CAI and controls, walking on a treadmill increases the variability of muscles activations, probably as a “safety strategy” to avoid ankle inversion. An abnormal activation of the tibialis anterior was observed during a number of tasks. Finally, hip/spine muscles were activated before ankle muscles in CAI compared to controls. Conclusion: Though the methodology of the studies herein considered is heterogeneous, this review shows that the peroneal and tibialis anterior muscles have an abnormal activation in CAI individuals. These individuals also show a proximal muscle activation strategy during the performance of balance challenging tasks. Future studies should investigate whole-body muscle activation abnormalities in CAI individuals

The role of noncoding RNAs in epithelial cancer

Funder: RCUK | Medical Research Council (MRC); doi: https://doi.org/10.13039/501100000265Funder: Fondazione Luigi Maria Monti IDI-IRCCS (RC)Abstract: Regulatory noncoding RNAs (ncRNAs) are a class of RNAs transcribed by regions of the human genome that do not encode for proteins. The three main members of this class, named microRNA, long noncoding RNA, and circular RNA play a key role in the regulation of gene expression, eventually shaping critical cellular processes. Compelling experimental evidence shows that ncRNAs function either as tumor suppressors or oncogenes by participating in the regulation of one or several cancer hallmarks, including evading cell death, and their expression is frequently deregulated during cancer onset, progression, and dissemination. More recently, preclinical and clinical studies indicate that ncRNAs are potential biomarkers for monitoring cancer progression, relapse, and response to cancer therapy. Here, we will discuss the role of noncoding RNAs in regulating cancer cell death, focusing on those ncRNAs with a potential clinical relevance

Rhythmic Auditory Stimulation (RAS) and motor rehabilitation in Parkinson\u2019s disease: New frontiers in assessment and intervention protocols

Previous studies have demonstrated that physical therapy accompanied by Rhythmic Auditory Stimulation (RAS) can improve the motor skills of patients with Parkinson\u2019s disease and, in particular, their gait disturbances. In the present work we describe the neurological bases and perceptual-motor deficits generally associated with Parkinson\u2019s disease, with a specific focus on gait disturbances. Within this framework, we review the role of auditory cueing in the modulation of patients\u2019 gait, addressing this issue from the cognitive, neurological and biomechanical perspectives. In particular, we focus on the new frontiers of both assessment and intervention. With regards to the assessment, we describe the advantages of the three-dimensional quantitative multifactorial gait analysis. As concerns the intervention, we illustrate the potential impact of the administration of ecological footstep sounds as rhythmic cues

Effects of physical rehabilitation integrated with rhythmic auditory stimulation on spatio-temporal and kinematic parameters of gait in parkinsons's disease

Movement rehabilitation by means of physical therapy represents an essential tool in the management of gait disturbances induced by Parkinson’s disease (PD). In this context, the use of Rhythmic Auditory Stimulation (RAS) has been proven useful in improving several spatio-temporal parameters, but concerning its effect on gait patterns scarce information is available from a kinematic viewpoint. In this study we used three-dimensional gait analysis based on optoelectronic stereophotogrammetry to investigate the effects of 5 weeks of intensive rehabilitation, which included gait training integrated with RAS on 26 individuals affected by PD (age 70.4±11.1, Hoehn & Yahr 1-3). Gait kinematics was assessed before and at the end of the rehabilitation period and after a three-month follow-up, using concise measures (Gait Profile Score and Gait Variable Score, GPS and GVS, respectively), which are able to describe the deviation from a physiologic gait pattern. The results confirm the effectiveness of gait training assisted by RAS in increasing speed and stride length, in regularizing cadence and correctly reweighting swing/stance phase duration. Moreover, an overall improvement of gait quality was observed, as demonstrated by the significant reduction of the GPS value, which was created mainly through significant decreases in the GVS score associated with the hip flexion-extension movement. Future research should focus on investigating kinematic details to better understand the mechanisms underlying gait disturbances in people with PD and the effects of RAS, with the aim of finding new or improving current rehabilitative treatments

Effects of Physical Rehabilitation Integrated with Rhythmic Auditory Stimulation on Spatio-Temporal and Kinematic Parameters of Gait in Parkinson's Disease

Movement rehabilitation by means of physical therapy represents an essential tool in the management of gait disturbances induced by Parkinson's disease (PD). In this context, the use of rhythmic auditory stimulation (RAS) has been proven useful in improving several spatio-temporal parameters, but concerning its effect on gait patterns, scarce information is available from a kinematic viewpoint. In this study, we used three-dimensional gait analysis based on optoelectronic stereophotogrammetry to investigate the effects of 5\u2009weeks of supervised rehabilitation, which included gait training integrated with RAS on 26 individuals affected by PD (age 70.4\u2009\ub1\u200911.1, Hoehn and Yahr 1-3). Gait kinematics was assessed before and at the end of the rehabilitation period and after a 3-month follow-up, using concise measures (Gait Profile Score and Gait Variable Score, GPS and GVS, respectively), which are able to describe the deviation from a physiologic gait pattern. The results confirm the effectiveness of gait training assisted by RAS in increasing speed and stride length, in regularizing cadence and correctly reweighting swing/stance phase duration. Moreover, an overall improvement of gait quality was observed, as demonstrated by the significant reduction of the GPS value, which was created mainly through significant decreases in the GVS score associated with the hip flexion-extension movement. Future research should focus on investigating kinematic details to better understand the mechanisms underlying gait disturbances in people with PD and the effects of RAS, with the aim of finding new or improving current rehabilitative treatments