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Background: The level of spinal cord injury affects the severity of respiratory impairment and the alteration of respiratory pattern and gas exchanges. Lesions at the C3-C5 level (phrenic nerve nucleus) cause disruption of descending input with paralysis of the main inspiratory muscle, often requiring tracheostomy and prolonged mechanical ventilation. Oxygen therapy is essential to switch from ventilatory support to removal of the endotracheal tube to correct residual difficulties in oxygenation management. Case Presentation: A 58-year-old man had tracheostomy and tetraparesis as complication of tonsillectomy and adenoidectomy treatment for a history of obstructive sleep apnea. A respiratory rehabilitation program with protocol of oxygen therapy with high flow cannula alternated with a low-flow system by Venturi mask during daytime hours only was started. The patient was constantly monitored with capillary partial oxygen saturation to obtain adequate oxygenation (> 94%) and registered every 15 minutes in the clinical chart. There was gradual improvement of respiratory function. Oxygen by Venturi mask was gradually reduced due to improvement of partial pressure oxygen values. Over the course of days, the optimal results of respiratory parameters led to a gradual weaning from the Venturi mask until the complete discontinuation of the low-flow system during daytime and decreased of the high-flow fraction of inspired oxygen to the maximal tolerated level during nighttime. Conclusions: Implementing a combined protocol of nighttime oxygen with high flow cannula and daytime Venturi mask improves intensive motor training of patients by promoting the acquisition of ability to perform chair/bed transitions and to be able to achieve standing and begin gait training. More research is needed whether or noted to determine the role of this promising approach in patients with severe SCI and in other critically ill patients.

Arctic seabirds are key bio-indicators of marine plastic pollution due to their transient movement and large populations. Although many studies have quantified the ingestion of microplastic particles (100 µm in size), 19 of which were analyzed for material composition using Fourier Transform Infrared Spectroscopy and Raman micro-spectroscopy. Of these, 13 particles were successfully matched to materials, with five as plastic. This produced an average concentration of 0.08 ± 0.28 microplastic particles per fecal sample, with no difference of occurrence between chicks and adults. Particle lengths ranged from 113 - 751 µm. The presence of microplastics larger than our lower limit of detectability of 100-µm suggests a need for analysis of smaller particles and microfibers in this species. We contribute to understanding how microplastics pass through little auks and characterize how this species interacts with the plastic pathways.

Abstract Urinary tract infections (UTIs) are the most common bacterial infections and uropathogenic Escherichia coli (UPEC) is the main etiological agent of UTIs. UPEC can persist in bladder cells protected by immunological defenses and antibiotics and intracellular behavior leads to difficulty in eradicating the infection. The aim of this paper is to design, prepare and characterize surfactant-based nanocarriers (niosomes) able to entrap antimicrobial drug and potentially to delivery and release antibiotics into UPEC-infected cells. In order to validate the proposed drug delivery system, gentamicin, was chosen as “active model drug” due to its poor cellular penetration. The niosomes physical–chemical characterization was performed combining different techniques: Dynamic Light Scattering Fluorescence Spectroscopy, Transmission Electron Microscopy. Empty and loaded niosomes were characterized in terms of size, ζ-potential, bilayer features and stability. Moreover, Gentamicin entrapped amount was evaluated, and the release study was also carried out. In addition, the effect of empty and loaded niosomes was studied on the invasion ability of UPEC strains in T24 bladder cell monolayers by Gentamicin Protection Assay and Confocal Microscopy. The observed decrease in UPEC invasion rate leads us to hypothesize a release of antibiotic from niosomes inside the cells. The optimization of the proposed drug delivery system could represent a promising strategy to significatively enhance the internalization of antimicrobial drugs.

In this article, we consider the role of ocean literacy in coastal communities as an approach that fosters relevant, community-based learning. We also propose solutions to challenges facing human-ocean relationships by cultivating common understanding and collective action. We present four examples of community-based ocean literacy in Mi'kma'ki/Atlantic Canada demonstrate how intersectional approaches to ocean literacy that are context-specific and responsive to community priorities can foster healthier human-ocean relationships: (1) Oceans Week Halifax's organization of community events to strengthen human-ocean relationships; (2) the Apoqnmatulti'k (Mi'kmaw: we help each other) project's partnerships between Mi'kmaq and local knowledge holders and academia; (3) Fishing For Success's (Newfoundland and Labrador) inclusive approaches to connecting marginalized communities to the ocean; and (4) the Co-Existing With North Atlantic Right Whale Project's protection of whales without jeopardizing coastal community livelihoods. Without denying there are barriers to bridging community learning with formal education, we focus on opportunities for collaborations and the importance of ocean optimism in guiding these urgently needed efforts to benefit future community-based, ocean-focused, and solutions-orientated initiatives.

Background/Objectives: Neuronal Ceroid Lipofuscinosis type 2 is a rare pathology affecting mainly the central nervous system (CNS) and retina, and is caused by variants in the gene encoding the lysosomal enzyme tripeptidyl peptidase 1. Therapy with enzyme replacement through the brain infusion of the orphan drug cerliponase alfa, a recombinant human tripeptidyl peptidase 1 enzyme replacement therapy delivered via intracerebroventricular infusion, has been approved for Neuronal Ceroid Lipofuscinosis type 2 disease. The safety profile of cerliponase alfa has been established based on pre-authorization studies; currently, no post-marketing investigation has been performed to confirm it. Here, a descriptive analysis of real-world spontaneous reporting data of suspected adverse reactions (SARs) to cerliponase alfa in the EudraVigilance database was performed to compile clear information on the safety profile. Methods: Suspected adverse reactions to cerliponase alfa reported in the data system EudraVigilance were analyzed for age, sex of the patient, adverse reactions, and the indication for use. Results: Cases with suspected adverse reactions to cerliponase alfa were found to be more frequent in female patients (58.1%) and in children aged 3–11 years. The most common adverse reactions were, in decreasing order, fever/pyrexia, device-related infection, vomiting, seizures/convulsions, pleocytosis, irritability, ventriculitis, and respiratory disorders. Conclusions: The results confirm the safety profile of cerliponase alfa established with pre-registration clinical studies but suggest the need for further studies to investigate the occurrence of adverse reactions, as possible predictive prognostic markers, in more depth.

The constellation fish, Valenciennellus tripunctulatus, is a small mesopelagic teleost typically found in equatorial and temperate waters worldwide, although the species has been also rarely recorded in the Mediterranean Sea (less than 20 specimens from the available literature since 1918). The Mediterranean records have been documented for the Strait of Messina, the southern Tyrrhenian Sea, the Ligurian Sea and the Adriatic Sea. The present paper offers an updated review on the occurrence of V. tripunctulatus in the Mediterranean basin and provides data on three new specimens, collected in the Strait of Messina between April 2010 and March 2024. Furthermore, we also report information from two individuals found in March 1992 and February 2017, respectively. Overall, the standard length of these specimens ranged from 24.1 to 28.2 mm, whereas weight varied from 0.18 g to 0.20 g. Morphometric and meristic data were reported, and this analysis revealed few differences between examined individuals in the number of PV (ventral series anterior to pelvic fin base) and AC (from anal fin origin to caudal fin base) photophore series. The relationship between total length and standard length (SL = 0.75 × TL + 2.98), total length and head length (HL = 0.17 × TL + 1.47) and standard length and head length (HL = 0.23 × SL + 0.88) showed high correlation values. Considering the lack of data on this species in the Mediterranean, updating morphometric, meristic, biological, ecological and distribution information is very important for taxonomic purposes and useful in understanding the characteristics of the regional population and eventual differences between Mediterranean stock(s) and those from other oceanic areas.

Introduction: Unlike the most common training approaches for bodybuilding, powerlifting programs are generally based on maximum and submaximal loads, putting enormous stresses on the lumbar spine. The flexion relaxation phenomenon evaluation is a clinical tool used for low back pain (LBP) assessment. This study aimed to evaluate the role of the flexion relaxation phenomenon in the analysis of LBP in the powerlifters. Methods: Healthy professional powerlifters participated in the study. In fact, we divided the participants into a LBP-low-risk group and a LBP-high-risk group, based on a prior history of LBP. Outcome measures included flexion relaxation ratio (FRR) and trough surface electromyography collected during trunk maximum voluntary flexion; furthermore, during a bench press lifting, we measured the height of the arched back (ARCH), using a camera and the Kinovea video editing software, to consider a potential correlation with the risk of LBP. Results: We included a group of 18 male (aged 24–39 y) powerlifters of 93 kg category. We measured a nonsignificant mean difference of ARCH between low-risk LBP group and high-risk LBP subjects. Curiously, maximum voluntary flexions were both above the threshold of 3.2 μV; therefore, with an absence of appropriate myoelectric silence, on the contrary, the FRR ratios were higher than 9.5, considering the presence of the phenomenon, exclusively for the low-risk group. The lumbar arched back measurement data did not report any association with the LBP risk, regarding the maximum voluntary flexion value, and even more than the FRR there is a relationship with the presence or the absence of LBP risk. Conclusions: FRR could be considered as a useful parameter for studying the risk of LBP in powerlifting. The FRR index not only refers to the possible myoelectric silence of the lumbar muscles in trunk maximum forward flexion but also takes into account the energy value delivered by the lumbar muscles during the flexion. Furthermore, we can indicate that the size of the powerlifter ARCH may not be a determining factor in the occurrence of LBP. [ABSTRACT FROM AUTHOR]

Abstract Background People with nonspecific low back pain (NSLBP) can also experience overlapping symptoms of lumbar spinal stenosis (LSS), but the impact on treatment outcomes is unknown. This study investigated differences in treatment outcomes for disability, back pain intensity, and leg pain intensity following an education and exercise therapy program for NSLBP patients with and without comorbid LSS symptoms. Methods This was a longitudinal analysis of 655 Danish participants in the GLA:D® Back program; an education and exercise therapy program for people with persistent NSLBP. Participants were classified as having comorbid LSS symptoms based on self-report. Linear mixed models were used to assess differences in change in disability (Oswestry Disability Index [0-100]) and back and leg pain intensity (Numeric Rating Scale [0–10]) at 3-, 6-, and 12-months between those with and without LSS symptoms. Results 28% of participants reported LSS symptoms. No certain differences in change in disability or back pain intensity improvement were observed at any time-point between those with and without LSS symptoms. Participants with LSS symptoms had slightly greater improvement in leg pain intensity at 6- (-0.7, 95% CI -1.2 to -0.2) and 12-months (-0.6, 95% CI -1.2 to -0.1). Conclusion Compared to those without LSS symptoms, patients with persistent NSLBP and LSS symptoms can expect similar improvements in disability and back pain intensity, and slightly greater improvements in leg pain intensity with treatment. Therefore, education and exercise therapy programs designed for NSLBP are likely helpful for those also experiencing LSS symptoms.

Scapular dyskinesia, glenohumeral internal rotation deficit, upper posterior labral anterior tears, and rotator cuff injuries are common in athletes who play “overhead” sports due to their repetitive excessive movements. The aims of this study are to propose a new protocol with kinematic analysis coupled with sEMG and to objectively analyze the effect of a specific prevention exercise protocol. Thirty-two subjects (age: 22 ± 4 years, height: 183 ± 3.2 cm, BMI: 23 ± 0.96 kg/m2), including sixteen healthy subjects (Group A) and sixteen male water polo athletes (Group B), underwent a three-dimensional motion analysis based on optoelectronic and sEMG systems. A functional evaluation was performed on Group A and Group B to assess the reliability of the operator-dependent tasks and collect a series of normative data, before starting the prevention protocol (T0) and after 8 weeks (T1). The athletes performed a specific exercise protocol to prevent shoulder injuries. In Group B, the movements of abduction (T0: 111° ± 24°; T1: 140° ± 13°) and extension (T0: 72°± 10°; T1: 84° ± 2.8°) of the glenohumeral joint and the scapulothoracic joint (T0: 33° ± 8.36°; T1: 40.5° ± 10.6°) significantly improved. A significant reduction (in %) in the maximum voluntary contraction (MCV) at T1 of the upper trapezius, teres minor, and pectoralis major was observed. This protocol provides objective data in a simple and reliable way for the functional assessment of the shoulder in water polo players during the sport season.

In the global context, advancements in technology and science have rendered virtual, augmented, and mixed-reality technologies capable of transforming clinical care and medical environments by offering enhanced features and improved healthcare services. This paper aims to present a mixed reality-based system to control a robotic wheelchair for people with limited mobility. The test group comprised 11 healthy subjects (six male, five female, mean age 35.2 ± 11.7 years). A novel platform that integrates a smart wheelchair and an eye-tracking-enabled head-mounted display was proposed to reduce the cognitive requirements needed for wheelchair movement and control. The approach’s effectiveness was demonstrated by evaluating our system in realistic scenarios. The demonstration of the proposed AR head-mounted display user interface for controlling a smart wheelchair and the results provided in this paper could highlight the potential of the HoloLens 2-based innovative solutions and bring focus to emerging research topics, such as remote control, cognitive rehabilitation, the implementation of patient autonomy with severe disabilities, and telemedicine.

Most clinical isolates of both Staphylococcus aureus and Staphylococcus epidermidis show the capacity to adhere to abiotic surfaces and to develop biofilms resulting in a contribution to chronic human skin infections. Antibiotic resistance and poor biofilm penetration are the main causes of ineffective therapeutic treatment in killing bacteria within biofilms. A possible strategy could be represented by drug delivery systems, such as nanoemulsions (composed of bioactive oil, surfactant and water phase), which are useful for enhancing the drug permeation of a loaded drug inside the biofilm and its activity. Phytochemical characterization of Pistacia lentiscus oil (LO) by direct infusion Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS) allowed the identification of bioactive compounds with antimicrobial properties, including fatty acids and phenolic compounds. Several monoterpenes and sesquiterpenes have been also detected and confirmed by gas chromatography–mass spectrometric (GC-MS) analysis, together providing a complete metabolomic profiling of LO. In the present study, a nanoemulsion composed of LO has been employed for improving Levofloxacin water solubility. A deep physical–chemical characterization of the nanoemulsion including hydrodynamic diameter, ζ-potential, morphology, entrapment efficiency, stability release and permeation studies was performed. Additionally, the antimicrobial/antibiofilm activity of these preparations was evaluated against reference and clinical Staphylococcus spp. strains. In comparison to the free-form antibiotic, the loaded NE nanocarriers exhibited enhanced antimicrobial activity against the sessile forms of Staphylococcus spp. strains.

This perspective explains why the lack of regulation around bioplastics remains a hurdle for the successful development and implementation of a legally binding agreement (the Global Plastics Treaty) by the United Nations Environment Assembly to curb plastic pollution by 2024. For example, bioplastics have been marketed to consumers as the panacea solution to our plastic waste crisis. Of the >400 million tonnes of plastics produced each year,

Abstract Background Previous studies have found that lumbar spinal stenosis (LSS) often co-occurs with knee or hip OA and can impact treatment response. However, it is unclear what participant characteristics may be helpful in identifying individuals with these co-occurring conditions. The aim of this cross-sectional study was to explore characteristics associated with comorbid symptoms of lumbar spinal stenosis (LSS) in people with knee or hip osteoarthritis (OA) enrolled in a primary care education and exercise program. Methods Sociodemographic, clinical characteristics, health status measures, and a self-report questionnaire on the presence of LSS symptoms was collected at baseline from the Good Life with osteoArthritis in Denmark primary care program for knee and hip OA. Cross-sectional associations between characteristics and the presence of comorbid LSS symptoms were assessed separately in participants with primary complaint of knee and hip OA, using domain-specific logistic models and a logistic model including all characteristics. Results A total of 6,541 participants with a primary complaint of knee OA and 2,595 participants with a primary complaint of hip OA were included, of which 40% and 50% reported comorbid LSS symptoms, respectively. LSS symptoms were associated with similar characteristics in knee and hip OA. Sick leave was the only sociodemographic variable consistently associated with LSS symptoms. For clinical characteristics, back pain, longer symptom duration and bilateral or comorbid knee or hip symptoms were also consistently associated. Health status measures were not consistently related to LSS symptoms. Conclusion Comorbid LSS symptoms in people with knee or hip OA undergoing a primary care treatment program of group-based education and exercise were common and associated with a similar set of characteristics. These characteristics may help to identify people with co-occurring LSS and knee or hip OA, which can be used to help guide clinical decision-making.

Spasticity is a very common sign in the neurological field. It can be defined as “a motor disorder marked by a velocity-dependent increase in muscle tone or tonic stretch reflexes” associated with hypertonia. It leads to a high risk of limb deformities and pain that prejudices residual motor function, impairing quality of life”. The treatment of spasticity depends on its severity and its location and, in general, it is based on rehabilitation, oral therapies (the gamma-aminobutyric acid b agonist baclofen) and injectable medications (i.e., botulin toxins, acting on polysynaptic reflex mechanisms). The botulin toxin type A (BoNT-A) injection has been effectively used to improve different types of spasticity. However, when BoNT-A is not sufficient, a combination of nonpharmacological approaches could be attempted. Therefore, additional intervention, such as conventional physical therapy by itself or further combined with robotic gait training, may be needed. Indeed, it has been shown that combination of BoNT-A and robotics has a positive effect on activity level and upper limb function in patients with stroke, including those in the chronic phase. The aim of this review is to evaluate the efficacy of pharmacological or nonpharmacological treatment in combination with BoNT-A injections on spasticity. The combined therapy of BoNT with conventional or adjunct activities or robot-assisted training, especially with end-effectors, is a valid tool to improve patients’ performance and outcomes. The combined strategies might rise the toxin’s effect, lowering its dosages of botulinum and reducing side effects and costs.

Although rehabilitation medicine emphasizes a holistic health approach, there is still a large gap of knowledge about potential interventions aimed at improving overall wellbeing through cosmetic interventions. Therefore, this narrative review investigates the role of different rehabilitative techniques in enhancing aesthetics, quality of life, and psychosocial wellbeing for patients with disabilities. The study follows the SANRA framework quality criteria for a narrative review. Literature searches across PubMed/Medline, Web of Science, and Scopus identified articles focusing on rehabilitation strategies within the aesthetic rehabilitation domain. The review identified evidence supporting injection procedures, such as Botulinum Toxin, Platelet-Rich Plasma, Hyaluronic Acid, Ozone, and Carboxytherapy, and assessing their applications in several disabling disorders. Additionally, physical therapies like Extracorporeal Shock Wave Therapy, Laser Therapy, Microcurrent Therapy, Tecar Therapy, and physical exercises were explored for their impact on cutaneous microcirculation, cellulite treatment, wound healing, and scar appearance improvement. Lastly, the manuscript underlines the role of manual therapy techniques in addressing both physical discomfort and aesthetic concerns, discussing their effectiveness in adipose tissue therapy, scar tissue mobilization, and regional fat thickness reduction. Taken together, this review emphasizes the role of a multidisciplinary approach, aiming to provide valuable insights into potential benefits for both functional and aesthetic outcomes.

Abstract Psoriasis is a chronic inflammatory skin disease characterized by plaque formation. Interleukin (IL)‐23 is upregulated in psoriatic lesions and is thought to be a major regulator of the Th17 pathway in psoriasis pathogenesis. Three monoclonal antibodies targeting the IL‐23p19 subunit, guselkumab, tildrakizumab, and risankizumab, have been approved for psoriasis therapy. The balance between cytokines IL‐23 and IL‐12 can affect antitumor and pro‐tumor immune activities, and patients with psoriasis may have higher rates of cancer than the general population. Moreover, a chronic inflammatory state typical of psoriasis may induce protumorigenic effects, however, the potential risk of malignancy in patients taking these drugs remains largely unknown. This study investigated the occurrence of malignancies as suspected adverse reactions (SARs) potentially associated with IL‐23 inhibitors by analyzing real‐world data from the European EudraVigilance database. Although indicatory, these real‐world data seem to confirm the potential association between the IL‐23 inhibitors risankizumab and tildrakizumab, and the occurrence of SARs linked to cancer in patients with psoriasis and, according to a gender perspective, they show that this relationship is asymmetrically distributed between women and men, with a clear prevalence of oncologic SARs in men.

Federica Rinaldi,1,* Patrizia Nadia Hanieh,1,* Linda Maurizi,2 Catia Longhi,2 Daniela Uccelletti,3 Emily Schifano,3 Elena Del Favero,4 Laura Cantù4 ,† Caterina Ricci,4 Maria Grazia Ammendolia,5 Donatella Paolino,6 Francesca Froiio,6 Carlotta Marianecci,1 Maria Carafa1 1Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, Rome, Italy; 2Dipartimento di Sanità pubblica e Malattie infettive, Sapienza Università di Roma, Rome, Italy; 3Dipartimento di Biologia e Biotecnologie Charles Darwin, Sapienza Università di Roma, Rome, Italy; 4Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università di Milano, Milan, Italy; 5Centro Nazionale Tecnologie Innovative in Sanità Pubblica, Istituto Superiore di Sanità, Rome, Italy; 6Dipartimento di Medicina Sperimentale e Clinica, Università Magna Graecia di Catanzaro, Campus Universitario “S. Venuta”, Catanzaro, Italy*These authors contributed equally to this work†Professor Laura Cantù passed away on August 05, 2022Correspondence: Maria Carafa; Carlotta Marianecci, Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, Piazzale Aldo Moro 5, Roma, 00185, Italy, Tel +390649913603 ; +390649913970, Fax +39064913133, Email maria.carafa@uniroma1.it; carlotta.marianecci@uniroma1.itPurpose: Vitamin E (VitE) may be classified in “the first line of defense” against the formation of reactive oxygen species. Its inclusion in nanoemulsions (NEs) is a promising alternative to increase its bioavailability. The aim of this study was to compare O/W NEs including VitE based on Almond or Neem oil, showing themselves antioxidant properties. The potential synergy of the antioxidant activities of oils and vitamin E, co-formulated in NEs, was explored.Patients and Methods: NEs have been prepared by sonication and deeply characterized evaluating size, ζ-potential, morphology (TEM and SAXS analyses), oil nanodroplet feature, and stability. Antioxidant activity has been evaluated in vitro, in non-tumorigenic HaCaT keratinocytes, and in vivo through fluorescence analysis of C. elegans transgenic strain. Moreover, on healthy human volunteers, skin tolerability and anti-inflammatory activity were evaluated by measuring the reduction of the skin erythema induced by the application of a skin chemical irritant (methyl-nicotinate).Results: Results confirm that Vitamin E can be formulated in highly stable NEs showing good antioxidant activity on keratinocyte and on C. elegans. Interestingly, only Neem oil NEs showed some anti-inflammatory activity on healthy volunteers.Conclusion: From the obtained results, Neem over Almond oil is a more appropriate candidate for further studies on this application.Graphical Abstract: Keywords: O/W nanodispersion, α-tocopherol, anti-inflammatory activity, HaCaT, C. elegans, healthy volunteers

Neutrophils are essential for host defense against Staphylococcus aureus (S. aureus). The neuro-repellent, SLIT2, potently inhibits neutrophil chemotaxis, and might, therefore, be expected to impair antibacterial responses. We report here that, unexpectedly, neutrophils exposed to the N-terminal SLIT2 (N-SLIT2) fragment kill extracellular S. aureus more efficiently. N-SLIT2 amplifies reactive oxygen species production in response to the bacteria by activating p38 mitogen-activated protein kinase that in turn phosphorylates NCF1, an essential subunit of the NADPH oxidase complex. N-SLIT2 also enhances the exocytosis of neutrophil secondary granules. In a murine model of S. aureus skin and soft tissue infection (SSTI), local SLIT2 levels fall initially but increase subsequently, peaking at 3 days after infection. Of note, the neutralization of endogenous SLIT2 worsens SSTI. Temporal fluctuations in local SLIT2 levels may promote neutrophil recruitment and retention at the infection site and hasten bacterial clearance by augmenting neutrophil oxidative burst and degranulation. Collectively, these actions of SLIT2 coordinate innate immune responses to limit susceptibility to S. aureus.

Musculoskeletal disorders (MSD) are a crucial issue in current literature due to their impact on physical function, social, and economic costs. Rehabilitation plays a pivotal role in the therapeutic management of these disabling conditions with growing evidence underlining positive effects in improving functional outcomes. However, to date, several questions are still open about the mechanisms underpinning functional improvements while recent research is now focusing on a deeper understanding of the biophysical processes underpinning the macroscopical effects of these treatments. Thus, this narrative review aims at providing a comprehensive overview about the state of the art of biophysical dimensions of currently available treatments for MSD. PubMed, Scopus, CENTRAL, PEDro, and Web of Science were searched between March 2022 and October 2022 for in vitro and in vivo studies, clinical trials, systematic reviews, and meta-analysis addressing the issue of biophysics-based approach in rehabilitation of MSD. Our findings showed that a biophysical approach might be integrated into regenerative rehabilitation, aiming at enhancing regenerative processes by mechanical and biophysical stimuli. In addition, a biophysical-based approach has been proposed to improve knowledge about several instrumental physical therapies, including shock wave therapies, low-level laser therapy, ultrasound, short-wave diathermy, electrical stimulation, pulsed electromagnetic field, and vibration therapy. In accordance, emerging research is now focusing on the biophysical properties of several medical procedures to improve pain management in patients with MSD. Taken together, our results showed promising results of the integration of a biophysical-based approach in rehabilitation, albeit several limitations currently limit its implementation in routine clinical setting. Unfortunately, the state of the art is still inconclusive, and the low quality of clinical studies based on the biophysical approach did not provide clear treatment protocols. Further studies are needed to promote a precise rehabilitation approach targeting biological modification and enhancing the functional improvement of patients with MSDs.

Background: Evolocumab is a humanized immunoglobulin G2 monoclonal antibody, directed against Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9), prescribed in hypercholesterolemic patients. The safety profile of this drug is currently defined by the data of pre-authorization clinical trials. The purpose of this study is to update knowledge of the safety of evolocumab through an analysis of post-marketing real-world data on suspected adverse reactions (SARs), reported by the EudraVigilance database system. Methods: The public version of the EudraVigilance database has been used, and only serious SARs signals were included. Results: Musculoskeletal system disorders, flu-like symptoms, injection-site reactions, skin reactions, and metabolism and nutrition disorders are observed in the post-marketing surveillance, as well as being found in the pre-authorization studies. Not previously signaled in the pre-marketing studies, diarrhea was reported. Furthermore, signals related to cardiac adverse reactions, more frequently at the expense of adults in comparison to elders, were found. Conclusions: The post-marketing safety profile of evolocumab emerging from an analysis of the EudraVigilance data system indicates it is sufficiently safe but suggests the necessity for caution when it is prescribed to hyperlipidemic patients affected by heart diseases.

Background: Chronic post-surgical pain is a condition persisting for not less than 3 months after surgical intervention. It is evaluated that 25–60% of women who underwent breast cancer excision suffer from post-mastectomy pain syndrome, and anxiety, depression, sleep disturbance, and catastrophizing. Physical activity can reduce the risk of chronic diseases and has a good impact on mood and cognitive function. The aim of this study was to estimate the influence of physical activity on the intensity of pain, depression, and anxiety in women who underwent mastectomy for breast cancer removal. Methods: A prospective observational unicentric cohort study was performed. Patients were females who underwent unilateral or bilateral mastectomy. The Numerical Rating Scale (NRS) was used to measure pain intensity, Beck’s Depression Inventory (BDI) for depression, and Generalized Anxiety Disorders-7 (GAD-7) for anxiety evaluation. Physical activity was assessed by the International Physical Activity Questionnaire (IPAQ). Interleukin (IL)-17, IL-1β, cortisol, adrenocorticotropic hormone (ACTH), and brain-derived neurotrophic factor (BDNF) were also evaluated in the blood of patients. All evaluations were assessed 3 and 6 months after the surgery. Results: Adequate physical activity reduced the intensity of pain, depression, and anxiety symptoms in women affected by post-mastectomy pain syndrome. Moreover, adequately active women showed a reduction in biomarkers of inflammation, cortisol, ACTH, and an increase of BDNF. Conclusions: Our results suggest that physical activity can improve the quality of life, reduce the intensity of pain and inflammatory markers, and be useful in the reduction of associated anxiety and depression.

Abstract Background Diagnostic imaging is useful for assessing low back pain (LBP) when a clinician suspects a specific underlying pathology. Evidence-based imaging guidelines assist clinicians in appropriately determining the need for imaging when assessing LBP. A previous study reported high adherence to three clinical guidelines, with utilization rate of 12.3% in imaging of LBP patients attending a chiropractic teaching clinic. A new imaging guideline for spinal disorders has been published and used in teaching. Thus, the aims of our study were to assess the adherence to the new guideline and X-ray utilization in new episodes of LBP. Methods We conducted a historical clinical cohort study using patient electronic health record audits at seven teaching clinics over a period of 20 months. Records of patients who were at least 18 years of age, presented with a new onset of LBP, and consented to data collection were included. Abstracted data included patient demographics, the number and type of red flags, and the decision to image. Rate of guideline adherence (proportion of those not recommended for imaging, given no red flags) and rate of image utilization were descriptively analyzed. Results We included 498 patients in this study. At least 81% of included patients had one or more red flags reported. The most commonly reported individual red flag was age ≥ 50 (43.8%) followed by pain at rest (15.7%). In those referred for imaging, age ≥ 50 (93.3%) was the most frequently reported red flag. No red flag(s) were identified in 93 patient records, and none were referred for imaging of their LBP, yielding an adherence rate of 100% (95% CI 96, 100%). A total of 17 of 498 patients were recommended for imaging for their low back pain, resulting in an imaging utilization rate of 3.4% (95% CI 1.8, 5.0%). Conclusion The imaging utilization rate was 3.4%, lower than 12.3% previously reported at a chiropractic teaching clinic. None without red flags were referred for imaging, yielding a 100%, adherence rate to current LBP imaging guidelines. Future research should consider currency of guideline, accuracy of red flags and factors influencing clinicians’ decision, when assessing imaging adherence rates.

Alessandro de Sire,1 Francesco Agostini,2 Andrea Bernetti,2 Massimiliano Mangone,2 Marco Ruggiero,2 Stefano Dinatale,2 Alessandro Chiappetta,2 Marco Paoloni,2 Antonio Ammendolia,1 Teresa Paolucci3 1Department of Medical and Surgical Sciences, University of Catanzaro “Magna Graecia”, Catanzaro, Italy; 2Department of Anatomical and Histological Sciences, Legal Medicine and Orthopedics, Sapienza University, Rome, Italy; 3Department of Medical, Oral and Biotechnological Sciences, G. D’Annunzio University of Chieti-Pescara, Chieti, ItalyCorrespondence: Francesco Agostini, Department of Anatomical and Histological Sciences, Legal Medicine and Orthopedics, Sapienza University, Rome, Italy, Email francescoagostini.ff@gmail.comBackground: Frozen shoulder (FS) is a painful condition characterized by progressive loss of shoulder function with passive and active range of motion reduction. To date, there is still no consensus regarding its rehabilitative treatment for pain management.Purpose: The aim of this umbrella review of systematic reviews was to analyze the literature, investigating the effects of non-surgical and rehabilitative interventions in patients suffering from FS.Patients and Methods: A review of the scientific literature was carried out from 2010 until April 2020 using the following search databases: PubMed, Medline, PEDro, Scopus and Cochrane Library of Systematic Reviews. A combination of terms was used for the search: frozen shoulder OR adhesive capsulitis AND systematic review OR meta-analysis AND rehabilitation NOT surgery NOT surgical intervention. We included systematic reviews that specifically dealt with adults with FS, treated with non-surgical approaches. All the systematic reviews and meta-analyses included in the study that met the inclusion criteria were assessed using the Assessment of Multiple Systematic Reviews as a quality assessment tool.Results: Out of 49 studies, only 14 systematic reviews respected the eligibility criteria and were included in this study. Their results showed an important heterogeneity of the studies and all of them agree on the lack of high-quality scientific work to prove unequivocally which rehabilitative treatment is better than the other. Due to this lack of gold standard criteria, there may be also a heterogeneity in the diagnosis of the reviews analyzed.Conclusion: Non-surgical and rehabilitative interventions are undoubtedly effective in treating FS, but there is no evidence that one approach is more effective than the other regarding the methods reported. Future high-quality RCTs are needed to standardize the treatment modalities of each physiotherapy intervention to provide strong recommendations in favor.Keywords: adhesive capsulitis, frozen shoulder, pain control, pain management, rehabilitation, non-surgical interventions

Background: Acute lateral ankle sprains are common injuries among athletes, but the optimal treatment strategies in elite athletes are still debated. This proof-of-concept study aimed to assess the impact of cryo-ultrasound therapy on the short-term recovery of football players with acute lateral ankle sprains. Methods: Semi-professional football players with grade I or II lateral ankle sprains were randomly assigned to the experimental group (receiving cryo-ultrasound therapy combined with conventional physical therapy) or control group (sham cryo-ultrasound therapy combined with conventional physical therapy). Pain intensity and physical functioning were assessed by the Numeric Rating Scale (NRS) and Foot and Ankle Disability Index (FADI) at baseline (T0) at the end of treatment (T1), after one month (T2), and two months after treatment (T3). Results: After the study intervention, significant between groups differences were reported in terms of pain relief (NRS: 4.08 ± 1.29 vs. 5.87 ± 1.19; p = 0.003) and physical function (FADI: 50.9 ± 10.3 vs. 38.3 ± 11.5; p = 0.021). However, no significant between group differences were reported at T2 and T3. No adverse effects were reported. Conclusions: Cryo-ultrasound therapy combined with conventional physical therapy can accelerate recovery and early return to sport in elite football players with acute lateral ankle sprains. While this study contributes valuable insights into the potential benefits of cryo-ultrasound therapy, further investigations with a longer follow-up are needed to validate and optimize the application of physical agent modalities in the management of ankle injuries.

Abstract Background Lumbar spinal stenosis (LSS) is a common degenerative spinal condition in older adults associated with disability, diminished quality of life, and substantial healthcare costs. Individual symptoms and needs vary. With sparse and sometimes inconsistent evidence to guide clinical decision-making, variable clinical care may lead to unsatisfactory patient outcomes and inefficient use of healthcare resources. Methods A three-phase modified Delphi study comprising four consensus rounds was conducted on behalf of the International Taskforce for the Diagnosis and Management of LSS to develop a treatment algorithm based on multi-professional international expert consensus. Participants with expertise in the assessment and management of people with LSS were invited using an international distribution process used for two previous Delphi studies led by the Taskforce. Separate treatment pathways for patients with different symptom types and severity were developed and incorporated into a proposed treatment algorithm through consensus rounds 1 to 3. Agreement with the proposed algorithm was evaluated in the final consensus round. Results The final algorithm combines stratified and stepped approaches. When indicated, immediate investigation and surgery is advocated. Otherwise, a stepped approach is suggested when self-directed care is unsatisfactory. This starts with tailored rehabilitation, then more complex multidisciplinary care, investigations and surgery options if needed. Treatment options in each step depend on clinical phenotype and symptom severity. Treatment response guides pathway entrance and exit points. Of 397 study participants, 86% rated their agreement ≥ 4 for the proposed algorithm on a 0–6 scale, of which 22% completely agreed. Only 7% disagreed. Over 70% of participants felt that the algorithm would be useful for clinicians in public healthcare (both primary care and specialist settings) and in private healthcare settings, and that a simplified version would help patients in shared decision-making. Conclusions International and multi-professional agreement was achieved for a proposed LSS treatment algorithm developed through expert consensus. The algorithm advocates different pathway options depending on clinical indications. It is not intended as a treatment protocol and will require evaluation against current care for clinical and cost-effectiveness. It may, however, serve as a clinical guide until evidence is sufficient to inform a fully stratified care model.

Background/Objectives: Neuronal Ceroid Lipofuscinosis type 2 is a rare pathology affecting mainly the central nervous system (CNS) and retina, and is caused by variants in the gene encoding the lysosomal enzyme tripeptidyl peptidase 1. Therapy with enzyme replacement through the brain infusion of the orphan drug cerliponase alfa, a recombinant human tripeptidyl peptidase 1 enzyme replacement therapy delivered via intracerebroventricular infusion, has been approved for Neuronal Ceroid Lipofuscinosis type 2 disease. The safety profile of cerliponase alfa has been established based on pre-authorization studies; currently, no post-marketing investigation has been performed to confirm it. Here, a descriptive analysis of real-world spontaneous reporting data of suspected adverse reactions (SARs) to cerliponase alfa in the EudraVigilance database was performed to compile clear information on the safety profile. Methods: Suspected adverse reactions to cerliponase alfa reported in the data system EudraVigilance were analyzed for age, sex of the patient, adverse reactions, and the indication for use. Results: Cases with suspected adverse reactions to cerliponase alfa were found to be more frequent in female patients (58.1%) and in children aged 3–11 years. The most common adverse reactions were, in decreasing order, fever/pyrexia, device-related infection, vomiting, seizures/convulsions, pleocytosis, irritability, ventriculitis, and respiratory disorders. Conclusions: The results confirm the safety profile of cerliponase alfa established with pre-registration clinical studies but suggest the need for further studies to investigate the occurrence of adverse reactions, as possible predictive prognostic markers, in more depth. [ABSTRACT FROM AUTHOR]