Identifying discriminant factors between phantom limb pain, residual limb pain, and both in people with lower limb amputations: a cross-sectional study.

Postamputation pain is a common condition in patients with lower limb amputation (LLA), which compromises amputees' rehabilitation, use of the prosthesis, and quality of life. The aim of our study was to investigate the prevalence of phantom limb pain (PLP), residual limb pain (RLP), or both types of pain among individuals with LLA, and to identify the factors associated with the presence of one type of pain versus the other. Patients who underwent amputation for traumatic or vascular reasons and who reported on RLP or PLP were analyzed and divided into three groups: PLP, RLP, or a group of subjects that presented both pains. We searched for factors that affect the occurrence of limb pain using univariate analyses, followed by multinomial logistic regression. Among the 282 participants with transtibial and transfemoral amputations, 192 participants (150 male and 42 female) presented PLP, RLP, or both types of pain, while 90 participants declared to perceive no pain. The estimated prevalence of any type of pain after transfemoral and transtibial amputation was therefore 68% (27% PLP, 10% RLP, and 31% both). Among the studied characteristics, only amputation level was associated with the type of pain (P = 0.001). Multinomial logistic regression identified transfemoral amputation as the only statistically significant predictor for PLP (odds ratio = 2.8; P = 0.002). Hence, it was estimated that individuals with transfemoral amputation have nearly three times higher odds of experiencing PLP compared with those with transtibial amputation.

Predictive Prognostic Factors in Non-Calcific Supraspinatus Tendinopathy Treated with Focused Extracorporeal Shock Wave Therapy: An Artificial Neural Network Approach.

The supraspinatus tendon is one of the most involved tendons in the development of shoulder pain. Extracorporeal shockwave therapy (ESWT) has been recognized as a valid and safe treatment. Sometimes the symptoms cannot be relieved, or a relapse develops, affecting the patient's quality of life. Therefore, a prediction protocol could be a powerful tool aiding our clinical decisions. An artificial neural network was run, in particular a multilayer perceptron model incorporating input information such as the VAS and Constant-Murley score, administered at T0 and at T1 after six months. It showed a model sensitivity of 80.7%, and the area under the ROC curve was 0.701, which demonstrates good discrimination. The aim of our study was to identify predictive factors for minimal clinically successful therapy (MCST), defined as a reduction of ≥40% in VAS score at T1 following ESWT for chronic non-calcific supraspinatus tendinopathy (SNCCT). From the male gender, we expect greater and more frequent clinical success. The more severe the patient's initial condition, the greater the possibility that clinical success will decrease. The Constant and Murley score, Roles and Maudsley score, and VAS are not just evaluation tools to verify an improvement; they are also prognostic factors to be taken into consideration in the assessment of achieving clinical success. Due to the lower clinical improvement observed in older patients and those with worse clinical and functional scales, it would be preferable to also provide these patients with the possibility of combined treatments. The ANN predictive model is reasonable and accurate in studying the influence of prognostic factors and achieving clinical success in patients with chronic non-calcific tendinopathy of the supraspinatus treated with ESWT.

UVB-Aged Microplastics and Cellular Damage: An in Vitro Study.

Plastics are synthetic organic compounds whose widespread use generates enormous waste. Different processes, such as mechanical abrasion, microbiological activity, and UVB irradiation, can fragment the plastic material and generate microplastics (MPs). MPs are ubiquitous, and various organisms, including humans, can ingest or inhale them, with potential adverse health effects. The differences between UV-aged and virgin particles were studied to evaluate the genotoxic damage and oxidative stress induced by polystyrene MPs with 1 and 5 µm sizes on the monocyte-like cell line (THP-1). Fourier transform infrared spectroscopy and Ζ-potential measurements were used to characterise MP particles after UVB exposure. Cells exposed to MPs show a widespread change in the cellular environment with the generation of reactive oxidative species (ROS), as indicated by the increased malondialdehyde level. The occurrence of genotoxic damage is correlated to the smaller size and ageing state of the MPs. The biochemical and genomic alterations observed in this in vitro study suggest that MPs, ubiquitous pollutants, following natural degradation and oxidation processes can cause various adverse effects on the health of the exposed population, making it necessary to carry out further studies to better define the real risk.

Upregulation of cholesterol synthesis by lysosomal defects requires a functional mitochondrial respiratory chain.

Mitochondria and lysosomes are two organelles that carry out both signaling and metabolic roles in cells. Recent evidence has shown that mitochondria and lysosomes are dependent on one another, as primary defects in one cause secondary defects in the other. Although there are functional impairments in both cases, the signaling consequences of primary mitochondrial dysfunction and lysosomal defects are dissimilar. Here, we used RNA sequencing to obtain transcriptomes from cells with primary mitochondrial or lysosomal defects to identify the global cellular consequences associated with mitochondrial or lysosomal dysfunction. We used these data to determine the pathways affected by defects in both organelles, which revealed a prominent role for the cholesterol synthesis pathway. We observed a transcriptional upregulation of this pathway in cellular and murine models of lysosomal defects, while it is transcriptionally downregulated in cellular and murine models of mitochondrial defects. We identified a role for the posttranscriptional regulation of transcription factor SREBF1, a master regulator of cholesterol and lipid biosynthesis, in models of mitochondrial respiratory chain deficiency. Furthermore, we found that retention of Ca2+ in lysosomes of cells with mitochondrial respiratory chain defects contributes to the differential regulation of the cholesterol synthesis pathway in the mitochondrial and lysosomal defects tested. Finally, we verified in vivo, using a model of mitochondria-associated disease in Caenorhabditis elegans that normalization of lysosomal Ca2+ levels results in partial rescue of the developmental delay induced by the respiratory chain deficiency.

Ex vivo expansion in a clinical grade medium, containing growth factors from human platelets, enhances migration capacity of adipose stem cells.

Introduction: Adipose tissue mesenchymal stem/stromal cells (ASC) can be used as advanced therapy medicinal product in regenerative and cancer medicine. We previously demonstrated Supernatant Rich in Growth Factors (SRGF) can replace fetal bovine serum (FBS) to expand ASC by a clinical grade compliant protocol. The therapeutic potential of ASC is based also on their homing capacity toward inflammatory/cancer sites: oriented cell migration is a fundamental process in this scenario. We investigated the impact of SRGF on ASC migration properties. Methods: The motility/migration potential of ASC expanded in 5% SRGF was analyzed, in comparison to 10% FBS, by standard wound healing, bidimensional chemotaxis and transwell assays, and by millifluidic transwell tests. Mechanisms involved in the migration process were investigated by transient protein overexpression. Results: In comparison to standard 10% FBS, supplementation of the cell culture medium with 5% SRGF, strongly increased migration properties of ASC along the chemotactic gradient and toward cancer cell derived soluble factors, both in static and millifluidic conditions. We showed that, independently from applied migratory stimulus, SRGF expanded ASC were characterized by far lower expression of α-smooth muscle actin (αSMA), a protein involved in the cell migration machinery. Overexpression of αSMA induced a significant and marked decrease in migration capacity of SRGF expanded ASC. Discussion: In conclusion, 5% SRGF addition in the cell culture medium increases the migration potential of ASC, reasonably through appropriate downregulation of αSMA. Thus, SRGF could potentially improve the therapeutic impact of ASC, both as modulators of the immune microenviroment or as targeted drug delivery vehicles in oncology.

Aortopathy and aortic valve surgery in patients with bicuspid aortic valve with and without raphe.

AIM: To evaluate the association between raphe in bicuspid aortic valve (BAV) patients and valve dysfunction, aortopathy and aortic valve surgery in the REBECCA registry [REgistro della valvola aortica Bicuspide della Società Italiana di ECocardiografia e CArdiovascular Imaging (SIECVI)]. METHODS: Prevalence of aortic valve dysfunction and aortopathy was investigated in BAV patients with and without raphe. Aortic valve dysfunction (regurgitation or stenosis) was categorized as mild, moderate and severe. Aortopathy was defined as annulus ≥14 mm/m2; root ≥20 mm/m2; sinotubular junction ≥16 mm/m2; ascending aorta ≥17 mm/m2, and classified in Type A, isolated ascending aorta dilatation; Type B, aortic root and ascending aorta dilatation; and Type C, isolated aortic root dilatation. RESULTS: Overall, 695 patients with BAV were enrolled; 520 (74.8%) with raphe and 175 (25.2%) without raphe. BAV patients with raphe presented more frequently with moderate or severe aortic stenosis than BAV patients without raphe (183 [35.2%] vs 34 [19.4%], p < 0.001). A higher prevalence of aortopathy, particularly Type B, was observed in patients with vs without raphe. At multivariable analysis, raphe was a predictor of aortic valve surgery at three-year follow-up (odds ratio 2.19, 95% confidence interval 1.08-4.44, p < 0.001). CONCLUSIONS: Patients with BAV and raphe have a higher prevalence of significant aortic stenosis, aortopathy, especially Type B, and a higher risk of undergoing aortic valve surgery at three-year follow-up.

Efficacy of Rehabilitative Techniques on Pain Relief in Patients With Vulvodynia: A Systematic Review and Meta-Analysis.

OBJECTIVE: Vulvodynia is a chronic clinical condition characterized by provoked or non-provoked vulvar pain for at least 3 months of unknown etiology. The onset of vulvodynia involves a complex interplay of peripheral and central pain mechanisms, such as pelvic floor muscle and autonomic dysfunction, and interpersonal factors. A stepwise approach of pelvic floor physical therapy as medical management is suggested. In this scenario, by this meta-analysis of randomized controlled trials, we aimed to evaluate the efficacy of rehabilitation interventions in patients with vulvodynia. METHODS: On October 13, 2022, PubMed, Scopus, and Web of Science were systematically searched for randomized controlled trials that assessed the efficacy of the rehabilitative approach to pain during intercourse in patients with vulvodynia. The quality assessment was performed with the Cochrane risk-of-bias tool for randomized trials. The trial registration number is CRD42021257449. At the end of the search, 9 studies were included for a total of 332 patients. A pairwise meta-analysis was performed to highlight the efficacy of rehabilitative approaches for reducing pain during intercourse, as measured with a visual analog scale or a numerical rating scale. RESULTS: Meta-analysis showed that all these rehabilitative approaches had an overall effect size of -1.43 (95% CI = -2.69 to -0.17) in decreasing vulvodynia pain in terms of the visual analog scale. In the subgroup analysis, a significant effect size in acupuncture (effect size = -2.36; 95% CI = -3.83 to -0.89) and extracorporeal shockwave therapy (effect size = -2.94; 95% CI = -4.31 to -1.57; I2 = 58%) was observed. According to the Cochrane risk-of-bias tool, a low risk of bias for outcome selection in 89% of studies. CONCLUSION: Findings from this meta-analysis suggested that the physical agent modalities and complementary medicine techniques in people with vulvodynia appear to be more effective than placebo, sham, or waiting list. Further evidence on physical agent modalities and complementary therapies are warranted in the future. IMPACT: This was the first systematic review and meta-analysis of randomized controlled trials to provide evidence on the efficacy of rehabilitation interventions in patients with vulvodynia.

Up-regulation of cholesterol synthesis by lysosomal defects requires a functional mitochondrial respiratory chain.

Mitochondria and lysosomes are two organelles that carry out both signaling and metabolic roles in the cells. Recent evidence has shown that mitochondria and lysosomes are dependent on one another, as primary defects in one cause secondary defects in the other. Nevertheless, the signaling consequences of primary mitochondrial malfunction and of primary lysosomal defects are not similar, despite in both cases there are impairments of mitochondria and of lysosomes. Here, we used RNA sequencing to obtain transcriptomes from cells with primary mitochondrial or lysosomal defects, to identify what are the global cellular consequences that are associated with malfunction of mitochondria or lysosomes. We used these data to determine what are the pathways that are affected by defects in both organelles, which revealed a prominent role for the cholesterol synthesis pathway. This pathway is transcriptionally up-regulated in cellular and mouse models of lysosomal defects and is transcriptionally down-regulated in cellular and mouse models of mitochondrial defects. We identified a role for post-transcriptional regulation of the transcription factor SREBF1, a master regulator of cholesterol and lipid biosynthesis, in models of mitochondrial respiratory chain deficiency. Furthermore, the retention of Ca 2+ in the lysosomes of cells with mitochondrial respiratory chain defects contributes to the differential regulation of the cholesterol synthesis pathway in the mitochondrial and lysosomal defects tested. Finally, we verified in vivo , using models of mitochondria-associated diseases in C. elegans , that normalization of lysosomal Ca 2+ levels results in partial rescue of the developmental arrest induced by the respiratory chain deficiency.

Safety and Efficacy of Ultrasound-Guided Perineural Hydrodissection as a Minimally Invasive Treatment in Carpal Tunnel Syndrome: A Systematic Review.

Ultrasound-guided perineural hydrodissection (HD) is a novel technique that has been found to be effective in providing mechanical release of perineural adhesions and decompression of the nerve, reducing inflammation and edema and restoring its physiological function. It has a significant impact on chronic neuropathic pain (20 ± 4 weeks with VAS < 5 or VAS diminished by 2 points after the procedure). Carpal tunnel syndrome (CTS) is a common entrapment mononeuropathy, and its distribution is typically innervated by the median nerve. Patients with mild or moderate CTS may benefit from nonsurgical treatments or conservative therapies. This review was conducted following the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement guidelines. Four investigators assessed each title, abstract, and full-text article for eligibility, with disagreements being resolved by consensus with two experienced investigators. The qualitative assessment of the studies was carried out using the modified Oxford quality scoring system, also known as the modified Jadad score. Furthermore, risk of possible biases was assessed using the Cochrane collaboration tool. The results of this review suggest that US-guided HD is an innovative, effective, well-tolerated, and safe technique (11 out of 923 patients had collateral or side effects after the procedure). However, further studies comparing all drugs and with a larger sample population are required to determine the most effective substance.

Role of vitamin D for orthodontic tooth movement, external apical root resorption, and bone biomarker expression and remodeling: A systematic review.

Objective: : This systematic review aimed to evaluate the correlation between vitamin D levels and the rate of tooth movement, external apical root resorption, bone biomarker expression, and bone remodeling. Methods: : Three databases (PubMed, Scopus, and Web of Science) were systematically searched from inception until 14th March 2023 to identify studies investigating the correlation between orthodontic tooth movement and vitamin D in animals and humans. The quality assessment was made in accordance with the Joanna Briggs Institute Critical Appraisal Checklist. Results: : Overall, 519 records were identified, and 19 were selected for the qualitative synthesis. Eleven studies investigated the effect of local administration (injections in the periodontal ligament, to the gingiva distal to the teeth, or submucosae palatal area) and systemic administration (oral supplementation) of vitamin D on tooth movement, external apical root movement, pro-inflammatory cytokines, and bone remodeling factors. The remaining eight studies investigated the correlation between serum vitamin D levels and salivary vitamin D levels on bone turnover markers and tooth movement. Conclusions: : The findings of this systematic review support that vitamin D3 local injections might increase the rate of tooth movement via the receptor activator of the nuclear factor-kB/osteoprotegerin axis. However, the non-uniform study designs and the different protocols and outcome methods make it challenging to draw reliable conclusions.

Postural Analysis Using Rasterstereography and Inertial Measurement Units in Volleyball Players: Different Roles as Indicators of Injury Predisposition.

Background and Objectives: Acute and chronic injuries are frequent in volleyball. Biomechanics of sport-specific tasks can influence the risk of injury, which is also related to specific court positions. We investigated posture at raster-stereography, balance, and dynamic tasks using inertial motion units to find differences between roles, which can be predictive of a higher risk of injury. Materials and Methods: We cross-sectionally evaluated amateur volleyball athletes. Participants were divided into roles as outside hitters, setters, middle blockers, and opposite hitters. We excluded the "libero" position from our analysis. Results: Sixteen players were included in the analysis. A statistically significant difference was found in left lower limb stiffness among the outside hitter and setter groups. Conclusions: Differences in stiffness might be related to the different training and the different abilities among the two groups. Raster-stereography is extending its indications and should be implemented for non-invasive postural analysis. The use of inertial motion units provides objective measurements of variables that could go unrecognized within a clinical evaluation; its use should be considered in injury preventive programs.

Comparison of Early versus Traditional Rehabilitation Protocol after Rotator Cuff Repair: An Umbrella-Review.

Rehabilitation after rotator cuff repair is crucial for functional recovery and for minimizing the risk of retear. There are two rehabilitation protocols (early and traditional) and the debate about which is the best is open. This umbrella review aimed to compare the effect of these rehabilitation protocols in terms of reduction in pain, functional recovery, and retear risk. We selected systematic reviews and meta-analyses published between 2012 and 2022 dealing with the aim. Nineteen systematic reviews were included. No significant differences were found between early and traditional protocols in terms of pain reduction. Early rehabilitation provided better short-term results regarding Range of Motion improvement, but long-term functional outcomes were similar. Retear risk remains a significant concern for the early protocol. We found major differences between the analyzed protocols. This review suggests that both protocols are useful to recover global shoulder function, but the standard protocol has a greater safety profile for larger tears. On the other hand, the early protocol may be preferable for smaller lesions, allowing a faster recovery and having less impact on medical costs. Further research is needed to identify optimal rehabilitation strategies tailored to the individual patient's needs and characteristics.

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.

Could Hyaluronic Acid Be Considered as a Senomorphic Agent in Knee Osteoarthritis? A Systematic Review.

BACKGROUND: Knee osteoarthritis (KOA) is one of the most common causes of disability in elderly patients and tends to be a major burden on social and health care spending. Despite its severe socioeconomic impact, KOA remains, to date, an incurable disease. Due to its proper characteristics, KOA represents a favorable disease model for experimenting with senotherapeutics, a group of treatments that counteract the development of age-related disorders and chronic diseases. In recent years, the use of intra-articular hyaluronic acid (IAHA) in the treatment of diseases related to the wear and tear of the articular cartilage has been gaining popularity. Given its ability in joint lubrification, shock absorption, and cell signaling, our aim is to investigate, through the existing scientific literature, its potential role as a senomorphic agent, emphasizing its crucial function in KOA patients. Indeed, senomorphics are a particular group of senotherapeutics capable of modulating the functions and morphology of senescent cells to those of young cells or delaying the progression of young cells to senescent cells in tissues. METHODS: A search in the scientific literature (PubMed, Cochrane Library, and Google Scholar) was carried out from 2019 to 2023, thus the last 5 years. RESULTS: One hundred thirty-eight articles were found concerning the role of hyaluronic acid injections in KOA patients. In these studies, its therapeutic efficacy, its anti-inflammatory properties, and its low risk of side effects emerged. CONCLUSION: IAHA injections are a valuable treatment option for KOA while they can provide pain relief, improve joint function, and slow the progression of joint degeneration. The inhibitory effect of HA on MMP13 and its action as a senomorphic agent suggests that it may have additional benefits beyond its lubricating and shock-absorbing properties. In order to clarify its mechanisms of action and to optimize its clinical use, further studies are definitely needed.

Impact of COVID-19 Era on the Anterior Cruciate Ligament Injury Rehabilitation: A Scoping Review.

The surgical intervention rate and the subsequent rehabilitation plan for anterior cruciate ligament (ACL) injury was crucially affected by the COVID-19 pandemic due to the necessity in the face of the emergency. This review aimed to evaluate potential persistent and residual symptoms after COVID-19 disease, including fatigue and neuromuscular disorders. A scoping review design and methodology were used due to the exploratory nature of the research question, according to literature searches on PubMed/Medline, Scopus, Web of Science (WoS), and Physiotherapy Evidence Database (PEDro) electronic databases using the following keywords: "Anterior Cruciate Ligament", "ACL", "SARS-CoV-2", and "COVID-19". Undertraining and muscular knee imbalance might cause inefficient movement strategies, lack of knee stability, and increasing load with negative implications in ACL injuries. In the post-surgery period, during COVID-19, telerehabilitation approaches appeared to be successfully applied to maintain strength and range of motion in this condition. However, no definitive data are available regarding the most effective interventions. This scoping review showed the influence of the COVID-19 pandemic and associated restrictions on postoperative and rehabilitative care of ACL injuries.

Hyaluronic acid injections for pain relief and functional improvement in patients with temporomandibular disorders: An umbrella review of systematic reviews.

BACKGROUND: Temporomandibular disorders (TMD) are the main cause of chronic facial pain, and intra-articular (IA) injections of hyaluronic acid (HA) are commonly performed. OBJECTIVES: This umbrella review of systematic reviews aimed at analysing the effectiveness of HA injections on pain and functional outcomes in patients affected by TMD. METHODS: PubMed, Cochrane Library and PEDro were systematically searched from inception until 17 January 2023 to identify systematic reviews evaluating the effects on pain and functional outcomes of HA IA injections. PROSPERO registration number: CRD42022382586. RESULTS: Out of 316 papers suitable for title/abstract screening, 18 articles were included in the umbrella review. Thirteen studies included only randomized controlled clinical trials (RCTs). The included systematic reviews reported no statistically significant differences between HA and corticosteroids, whereas platelet derivates seem to have good results in pain relief. The literature did not show severe adverse events, except for mild pain in the site of injection. Concerning the quality assessment of the 18 systematic reviews, 2 (11.11%) had a high quality, 3 (16.67%) a moderate quality, 7 (38.89%) a low quality and 6 (33.33%) a critically low quality. CONCLUSIONS: Taken together, findings of this umbrella review showed intriguing effects of IA HA injections in terms of reduction of pain intensity and improvement of functioning in patients affected by TMD. Furthermore, there is no agreement on the effectiveness of a combination of arthrocentesis or arthroscopy with IA HA injections. Although the literature showed these positive results after IA HA injections, the overlapping of primary studies in the systematic reviews included might have affect our results, such as the very low quality of the papers. Thus, further RCTs are needed to confirm the efficacy of IA injections of HA on pain relief in patients with TMD.

IRE1a-Induced FilaminA Phosphorylation Enhances Migration of Mesenchymal Stem Cells Derived from Multiple Myeloma Patients.

Multiple myeloma (MM) is an aggressive malignancy that shapes, during its progression, a pro-tumor microenvironment characterized by altered protein secretion and the gene expression of mesenchymal stem cells (MSCs). In turn, MSCs from MM patients can exert an high pro-tumor activity and play a strong immunosuppressive role. Here, we show, for the first time, greater cell mobility paralleled by the activation of FilaminA (FLNA) in MM-derived MSCs, when compared to healthy donor (HD)-derived MSCs. Moreover, we suggest the possible involvement of the IRE1a-FLNA axis in the control of the MSC migration process. In this way, IRE1a can be considered as a good target candidate for MM therapy, considering its pro-survival, pro-osteoclast and chemoresistance role in the MM microenvironment. Our results suggest that IRE1a downregulation could also interfere with the response of MSCs to MM stimuli, possibly preventing cell-cell adhesion-mediated drug resistance. In addition, further investigations harnessing IRE1a-FLNA interaction could improve the homing efficiency of MSC as cell product for advanced therapy applications.

Linking ROS Levels to Autophagy: The Key Role of AMPK.

Oxygen reactive species (ROS) are a group of molecules generated from the incomplete reduction of oxygen. Due to their high reactivity, ROS can interact with and influence the function of multiple targets, which include DNA, lipids, and proteins. Among the proteins affected by ROS, AMP-activated protein kinase (AMPK) is considered a major sensor of the intracellular energetic status and a crucial hub involved in the regulation of key cellular processes, like autophagy and lysosomal function. Thanks to these features, AMPK has been recently demonstrated to be able to perceive signals related to the variation of mitochondrial dynamics and to transduce them to the lysosomes, influencing the autophagic flux. Since ROS production is largely dependent on mitochondrial activity, through the modulation of AMPK these molecules may represent important signaling agents which participate in the crosstalk between mitochondria and lysosomes, allowing the coordination of these organelles' functions. In this review, we will describe the mechanisms through which ROS activate AMPK and the signaling pathways that allow this protein to affect the autophagic process. The picture that emerges from the literature is that AMPK regulation is highly tissue-specific and that different pools of AMPK can be localized at specific intracellular compartments, thus differentially responding to altered ROS levels. For this reason, future studies will be highly advisable to discriminate the specific contribution of the activation of different AMPK subpopulations to the autophagic pathway.

Botulinum toxin type A for spasticity in cerebral palsy patients: Which impact on popliteal angle to hamstring length? A proof-of-concept study.

BACKGROUND: Cerebral palsy (CP) is the most common physical disability in childhood. It is a heterogeneous condition in terms of etiology, motor type and severity of impairments. Clinical impairments, such as increased muscle tone (spasticity), muscle weakness and joint stiffness contribute to the abnormal development of functional activities, including gait. OBJECTIVE: The objective of this study was to investigate the popliteal angle to hamstring length after ultrasound guided Incobotulinum toxin A injections for spasticity in CP patients. METHODS: In this proof-of-concept study, we included outpatients with CP and crouch gait correlated to hamstrings spasticity referred to the Pediatric Rehabilitation outpatient clinic of Umberto I University Hospital, Sapienza University of Rome, in the period between February and October 2018. METHODS: Modified Ashworth Scale (MAS) of hamstring muscles, Popliteal Angle and Modified Popliteal Angle, Passive Knee Extension and 10 Meter Walk Test (10MWT) were assessed at baseline (T0) and three weeks after ultrasound guided injection (T1) of Incobotulinum Toxin A (dose weight and site dependent). RESULTS: Thirteen patients (5 male and 8 female), mean aged 9.91 ± 3.59, were included. The clinical evaluation at T0 showed hamstring muscles spasticity, with MAS of 2.4 ± 0.6, popliteal angle -51.7∘± 11.0∘, modified popliteal angle of -39.5∘± 11.0∘, passive knee extension of -14.0∘± 8.7∘ and 10MWT of 14.3 ± 4.6 seconds. At T1, hamstring muscles MAS mean value was 1.7 ± 0.6 (p< 0.01), popliteal angle 41.3∘± 7.0∘ (p< 0.001), modified popliteal angle -32.9∘± 10.4∘ (p< 0.001), passive knee extension -4.0∘± 4.2∘ (p< 0.05) and 10MWT 12.6 ± 4.8 seconds (p< 0.05). None of the treated patients reported any adverse event related to Incobotulinum Toxin A injection. CONCLUSION: Incobotulinum toxin A treatment has been proven to be safe and effective for hamstring muscles spasticity management in CP patients. Further studies with larger samples and longer follow-up are warranted to assess the efficacy of this treatment on the popliteal angle.

Comet-FISH analysis of urothelial cells. A screening opportunity for bladder cancer?

INTRODUCTION: Bladder cancer (BCa) is the most frequent cancer of the urinary tract, with more than 500,000 reported cases and nearly 200,000 related deaths yearly. Cystoscopy is the standard examination used for the initial diagnosis and follow-up of BCa in the noninvasive stage. However, the American Cancer Society does not include BCa screening in its list of recommended cancer screenings. AREAS COVERED: Recently, several urine-based bladder tumor markers (UBBTMs) that identify genomic, transcriptomic, epigenetic, or protein alterations have been introduced, some of which have been approved by the Food and Drug Administration (FDA) to improve its diagnosis and surveillance. Several biomarkers have been found in the tissues and blood of individuals with BCa or predisposed to develop the disease, further enriching our information. EXPERT OPINION: From a prevention perspective, alkaline Comet-FISH could be a valuable tool with broad potential for clinical application. Furthermore, a comet assay could be more beneficial for diagnosing and monitoring bladder cancer and determining individual susceptibility. Thus, we recommend further studies to understand the potential of this combined assay in the general population as a potential screening test and in patients initiated into the diagnostic process.