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STUDY DESIGN: Cross-sectional survey. OBJECTIVE: Currently there is limited evidence and guidance on the management of mild degenerative cervical myelopathy (DCM) and asymptomatic spinal cord compression (ASCC). Anecdotal evidence suggest variance in clinical practice. The objectives of this study were to assess current practice and to quantify the variability in clinical practice. METHODS: Spinal surgeons and some additional health professionals completed a web-based survey distributed by email to members of AO Spine and the Cervical Spine Research Society (CSRS) North American Society. Questions captured experience with DCM, frequency of DCM patient encounters, and standard of practice in the assessment of DCM. Further questions assessed the definition and management of mild DCM, and the management of ASCC. RESULTS: A total of 699 respondents, mostly surgeons, completed the survey. Every world region was represented in the responses. Half (50.1%, n = 359) had greater than 10 years of professional experience with DCM. For mild DCM, standardised follow-up for non-operative patients was reported by 488 respondents (69.5%). Follow-up included a heterogeneous mix of investigations, most often at 6-month intervals (32.9%, n = 158). There was some inconsistency regarding which clinical features would cause a surgeon to counsel a patient towards surgery. Practice for ASCC aligned closely with mild DCM. Finally, there were some contradictory definitions of mild DCM provided in the form of free text. CONCLUSIONS: Professionals typically offer outpatient follow up for patients with mild DCM and/or asymptomatic ASCC. However, what this constitutes varies widely. Further research is needed to define best practice and support patient care.

Abstract We provide an update regarding the differences between men and women in short-term postoperative mortality after coronary artery bypass grafting (CABG) and highlight the differences in postoperative risk of stroke, myocardial infarction, and new onset atrial fibrillation. We included 23 studies, with a total of 3,971,267 patients (70.7% men, 29.3% women), and provided results for groups of unbalanced studies and propensity matched studies. For short-term mortality, the pooled odds ratio (OR) from unbalanced studies was 1.71 (with 95% CI 1.69–1.74, I2 = 0%, p = 0.7), and from propensity matched studies was 1.32 (95% CI 1.14–1.52, I2 = 76%, p

Abstract Objective Biallelic mutations in PRDX3 have been linked to autosomal recessive spinocerebellar ataxia type 32. In this study, which aims to contribute to the growing body of knowledge on this rare disease, we identified two unrelated patients with mutations in PRDX3. We explored the impact of PRDX3 mutation in patient skin fibroblasts and the role of the gene in neurodevelopment. Methods We performed trio exome sequencing that identified mutations in PRDX3 in two unrelated patients. We also performed functional studies in patient skin fibroblasts and generated a “crispant” zebrafish (Danio rerio) model to investigate the role of the gene during nervous system development. Results Our study reports two additional patients. Patient 1 is a 19‐year‐old male who showed a novel homozygous c.525_535delGTTAGAAGGTT (p. Leu176TrpfsTer11) mutation as the genetic cause of cerebellar ataxia. Patient 2 is a 20‐year‐old male who was found to present the known c.425C>G/p. Ala142Gly variant in compound heterozygosity with the p. Leu176TrpfsTer11 one. While the fibroblast model failed to recapitulate the pathological features associated with PRDX3 loss of function, our functional characterization of the prdx3 zebrafish model revealed motor defects, increased susceptibility to reactive oxygen species‐triggered apoptosis, and an impaired oxygen consumption rate. Conclusions We identified a new variant, thereby expanding the genetic spectrum of PRDX3‐related disease. We developed a novel zebrafish model to investigate the consequences of prdx3 depletion on neurodevelopment and thus offered a potential new tool for identifying new treatment opportunities.

Abstract Background Migraine lacks biomarkers that can trace the biological pathways of the disease and predict the effectiveness of treatments. Monoclonal antibodies targeting calcitonin gene-related peptide pathway – including erenumab – offer the opportunity of investigating potential migraine biomarkers due to their specific mechanism of action in preventing both episodic (EM) and chronic (CM) migraine. Our study aims at evaluating the expression levels of circulating microRNAs (miRNAs) according to migraine type, before and after treatment with erenumab and based on treatment response, in order to identify miRNAs with potential role as epigenetic biomarkers. Methods The study included women aged 25–50 years with EM or CM treated with erenumab according to clinical indications. MiRNAs expression levels were assessed before (baseline) and after a 16-week treatment with erenumab, 140 mg every four weeks (post-treatment). An extensive miRNAs profiling was performed by qRT-PCR in small, pooled groups of ≤ 8 women each, classified according to migraine frequency (EM and CM) and the degree of response to erenumab. The expression levels of selected miRNAs were also validated using single miRNA assays in each woman with EM and CM. Results During the study, 36 women with migraine (19 with EM and 17 with CM) out of 40 who were initially screened, performed the assessment of miRNA expression at baseline and post-treatment, Erenumab treatment significantly improved migraine burden in both EM and CM. MiRNA profiling revealed differential expression levels of a wide set of miRNAs (hsa-let-7d-3p, hsa-miR-106b-3p, hsa-miR-122-5p, hsa-miR-143-3p, hsa-miR-144-3p, hsa-miR-16-5p, hsa-miR-181a-5p, hsa-miR-221-3p, hsa-miR-25-3p, hsa-miR-29b-2-5p, hsa-miR-326, miR-363-3p, hsa-miR-424-5p, hsa-miR-485-3p, hsa-miR-532-5p, hsa-miR-543, hsa-miR-629-5p, hsa-miR-660-5p, hsa-miR-92a-3p) depending on treatment response. Among them, single miRNA assays confirmed the progressive decrease of hsa-miR-143-3p expression levels in relation to increasing response to erenumab in women with EM (7 with low, 6 with medium, and 6 with high response; p = 0.02). Additionally, single assays showed higher hsa-miR-34a-5p and hsa-miR-382-5p expression levels at baseline in women with CM compared with those with EM (p = 0.0002 and p = 0.0007, respectively), as well as their expression level decrease in women with CM from baseline to follow-up (p = 0.04 and p = 0.02, respectively). Conclusions Our study suggests that targeting the CGRP pathway in migraine changes the expression levels of certain miRNAs. These miRNA levels are linked to the levels of response to CGRP receptor blockage. Future research challenges include assigning specific functions to the modulated miRNAs to unravel pathways modulated by the disease and the treatment. Trial registration The study was registered in clinicaltrials.gov with code NCT04659226 and in the Novartis database with code CAMG334AIT05T.

IntroductionThe COVID-19 pandemic brought about unprecedented problems for contemporary society. Among the numerous challenges faced following the spread of the virus, the need to provide assessment tools and remote psychological assistance certainly deserves particular attention. Indeed, this profound paradigm shift in psychological assessment and care occurred during a period of fragility for people already suffering from the restrictions imposed to stem the spread of the virus. One population particularly affected by the pandemic was students, including university students. The latter faced the pandemic in a particularly critical formative period.MethodsFor these reasons, our systematic review has two main objectives: (i) identify the assessment tools and psychological dimensions most used/investigated during the pandemic in Italian university students; (ii) systematize and deepen our knowledge about the impact of the pandemic on the psychological wellbeing of Italian university students. Our search used PRISMA 2020 guidelines on Web of Science, Pubmed, Scopus, and EBSCOHost.ResultsThe results indicated that the psychological dimensions most investigated in university students during the pandemic were anxiety and depression. At the same time, the most used assessment instruments were the State-Trait Anxiety Inventory (STAI-Y) and the Beck Depression Inventory-II (BDI-II). Furthermore, it is clear from the results that the pandemic has harmed the psychological wellbeing of university students. Finally, we dedicated a section to discuss the interventions implemented by university counseling services during the pandemic.DiscussionThis review could improve the work of university counseling services in this post-pandemic period and contribute to developing specific screening and assessment programs for future emergencies.

Abstract Superficial infections with Streptococcus pyogenes (Strep A), pharyngitis and impetigo can induce acute rheumatic fever, an autoimmune sequela manifesting mostly with arthritis and rheumatic carditis. Valvular heart damage can persist or advance following repeated episodes of acute rheumatic fever, causing rheumatic heart disease. Acute rheumatic fever and rheumatic heart disease disproportionately affect children and young adults in developing countries and disadvantaged communities in developed countries. People living with rheumatic heart disease are at risk of experiencing potentially fatal complications such as heart failure, bacterial endocarditis or stroke. Transthoracic echocardiography plays a central role in diagnosing both rheumatic carditis and rheumatic heart disease. Despite the obvious medical need, no licensed Strep A vaccines are currently available, as their clinical development process faces several challenges, including concerns for cardiac safety. However, the development of Strep A vaccines has been recently relaunched by many vaccine developers. In this context, a reliable and consistent safety evaluation of Strep A vaccine candidates, including the use of transthoracic echocardiography for detecting cardiac adverse events, could greatly contribute to developing a safe and efficacious product in the near future. Here, we propose a framework for the consistent use of transthoracic echocardiography to proactively detect cardiac safety events in clinical trials of Strep A vaccine candidates.

AbstractBackground Oral levodopa remains the mainstay of treatment for Parkinson’s disease (PD). However, as PD progresses, response to treatment may fluctuate. Managing fluctuations can be demanding for clinicians and patients. There is a paucity of real-world studies reporting on PD management in patients with fluctuations in treatment response, especially in patients with advanced stages of PD. The multicentre, observational Parkinson’s Disease Fluctuations treatment PAthway (PD-FPA) study describes the real-life management of response fluctuations in Italian patients with advanced PD.Patients and Methods PD-FPA had a retrospective and prospective phase; herein, retrospective results are presented. Ten Italian centres enrolled patients with a PD diagnosis from 10–15 years prior to study entry (T0) and who had ≥2-year history of fluctuations. Data on patient demographics, medical history, PD stage, fluctuation characteristics, symptoms, and prescribed treatments were collected at T0 and retrospectively (2 years prior to T0) via patient chart review/interview.Results Overall, 296 patients (60% male, mean age 68 years, 84% with Hoehn and Yahr scores 2–3) were enrolled. At T0, most patients (99.3%) were on oral levodopa therapy. All patients used dopaminergic medications; adjunctive medications included dopamine agonists (56%) and monoamine oxidase B (60%) and catechol-O-methyltransferase enzyme inhibitors (41%). At T0, 51% of patients had changed therapy, with response fluctuations being the most common reason (74%); wearing-off was the most common fluctuation (83%).Conclusion This interim analysis of PD-FPA suggests that adequate levodopa dosing and adjunctive medications can stabilize advanced PD and provide patients with a good quality of life.

UNESCO has indicated the need for more research to test the effectiveness of education for sustainable development (ESD). This study analyzes how ESD is included in the Finnish national core curriculum and examines four environmental indicators to determine if a correlation exists between ESD and a cleaner physical environment in Finland. The study's results indicate that increased environmental consciousness through ESD does not completely correlate to a cleaner physical environment. Two of the environmental indicators, total CO[subscript 2] and greenhouse gas emissions from household fuel combustion, reduced after the United Nations Decade of Education for Sustainable Development (DESD); however, it could not be determined if ESD or government policies are responsible for these reductions. The other two environmental indicators, municipal waste and electricity consumption, increased post-DESD. This study concludes by recommending that ESD be institutionalized in teacher education programs alongside ecopedagogy throughout the Finnish education system.

IntroductionThe successful combination of a sports career and education, known as the dual career, requires cooperation and a multi-dimensional approach. Although extensive research has been conducted on dual career programs and services in developed countries, there is limited information available on the dual-career phenomenon in developing countries. This study aimed to explore the dual career experiences of university student-athletes in the Republic of Kosovo.Materials and methodsA 30-item online survey was distributed to student-athletes, addressing various aspects of the dual career. A total of 121 student-athletes (males: 63.6%; females: 36.4%) voluntarily participated in the survey.ResultsThese student-athletes represented 13 different sports, with 102 (84.3%) participating in team and 19 (15.7%) in individual sports. Between individual and team sports no significant differences were found regarding university and sports engagement, and the time required to travel from the university to the training venue, whereas a significant difference (p = 0.019) emerged for the time needed to travel from home to the training venue. Significant differences (p

This study aimed to explore the views of judo coaches on their perceived knowledge (PK) and needs for education (NE) for training older practitioners. In total, 470 international (Europe = 48%, Americas = 22%, Africa = 23%, Asia = 5% and Oceania = 2%) judo coaches (IJF: level 1 = 55,3%, level 2 = 33%; judo black belt: 3,4 ± 1,7 dan; F = 15%; university education: 68% >BA) responded an online survey encompassing demographic information and 35 items relevant to training older adults (Aging process; Safety and First Aid; Organization & Environment; Physiology and Fitness; Psychology & Mental Health; Teaching & Training) to be rated on a 7-point Likert scale for PK and NE. Non parametric statistics (p > 0.05) was applied to ascertain differences and relationships between PK and NE, respectively. A bivariate go-zone plot was used to highlight items with the lowest PK and the highest NE mean values. The coaches reported high PK (4.5 ± 0.3 pt) and NE (4.7 ± 0.1 pt) values, with significant higher PK values emerging for high education levels and judo experience. In considering their unique needs and special role, the judo coaches presented valuable insights to develop a sustainable educational curriculum tailored to train older judo practitioners.

To improve soccer performance, coaches should be able to replicate the match’s physical efforts during the training sessions. For this goal, small-sided games (SSGs) are widely used. The main purpose of the current study was to develop similarity and overload scores to quantify the degree of similarity and the extent to which the SSG was able to replicate match intensity. GPSs were employed to collect external load and were grouped in three vectors (kinematic, metabolic, and mechanical). Euclidean distance was used to calculate the distance between training and match vectors, which was subsequently converted into a similarity score. The average of the pairwise difference between vectors was used to develop the overload scores. Three similarity (Sim kin , Sim met , Sim mec ) and three overload scores (OVER kin , OVER met , OVER mec ) were defined for kinematic, metabolic, and mechanical vectors. Sim met and OVER met were excluded from further analysis, showing a very large correlation ( r > 0.7, p < 0.01) with Sim kin and OVER kin . The scores were subsequently analysed considering teams’ level (First team vs. U19 team) and SSGs’ characteristics in the various playing roles. The independentsample t -test showed ( p < 0.01) that the First team presented greater Sim kin ( d = 0.91), OVER kin ( d = 0.47), and OVER mec ( d = 0.35) scores. Moreover, a generalized linear mixed model (GLMM) was employed to evaluate differences according to SSG characteristics. The results suggest that a specific SSG format could lead to different similarity and overload scores according to the playing position. This process could simplify data interpretation and categorize SSGs based on their scores.

Abstract Background Klippel–Feil syndrome is a rare condition described in 1912 by Maurice Klippel and André Feil. It is defined as a congenital cervical fusion of at least two vertebrae, associated with a classical triad of clinical signs: short neck, low posterior hairline, and limited range of movement. However, Klippel–Feil syndrome manifests with a vast spectrum of phenotypes, ranging from no symptoms to complete triad, with or without other associated malformations. Most commonly, CCF results from sporadic mutations, even though autosomal recessive, autosomal dominant, or even X-linked inheritance can be detected. The ATP-binding cassette subfamily B member 4 is only expressed in the liver and is involved in biliary phospholipid secretion. The clinical spectrum includes various hepatobiliary pathologies, including low phospholipid-associated cholelithiasis, and has never been associated with musculoskeletal anomalies. Case presentation A 55-year-old male Caucasian patient presenting with low phospholipid-associated cholelithiasis syndrome with ATP-binding cassette subfamily B member 4 mutation and liver cirrhosis was referred to our clinic for a liver transplant. A period of 6 months before, the patient underwent a T7–T9 posterior fixation for a T8 osteoporotic fracture. Postoperatively, he was tetraparetic, whereas he was neurologically intact before the operation. At admission to our hospital, he was still tetraparetic and presented with clinical signs of cervical myelopathy. Moreover, he suffered a limitation of cervical range of motion in all directions, short neck, and low posterior hairline. Imaging showed multiple cervical and thoracic vertebral bodies fusion, as well as cervical spine stenosis. Based on the available data, we diagnosed a type 3 Klippel–Feil syndrome according to Samartzis’ classification. Conclusions The heterogeneity of KFS and the various potential hereditary links that are known indicate that it is important to highlight all potential cases related to known genetic defects. At present, no association between ATP-binding cassette subfamily B member 4 mutation and congenital cervical fusions has been reported. The other important clinical focus of this case is the appearance of spontaneous tetraparesis after thoracic spine surgery. This mechanism remains unclear, but considering different spinal anatomy it might have been due to difficult intubation and patient’s positioning during his previous operation.

Abstract The naked mole rat (NMR), Heterocephalus glaber, the longest-living rodent, provides a unique opportunity to explore how evolution has shaped adult stem cell (ASC) activity and tissue function with increasing lifespan. Using cumulative BrdU labelling and a quantitative imaging approach to track intestinal ASCs (Lgr5 + ) in their native in vivo state, we find an expanded pool of Lgr5 + cells in NMRs, and these cells specifically at the crypt base (Lgr5 +CBC ) exhibit slower division rates compared to those in short-lived mice but have a similar turnover as human LGR5 +CBC cells. Instead of entering quiescence (G0), NMR Lgr5 +CBC cells reduce their division rates by prolonging arrest in the G1 and/or G2 phases of the cell cycle. Moreover, we also observe a higher proportion of differentiated cells in NMRs that confer enhanced protection and function to the intestinal mucosa which is able to detect any chemical imbalance in the luminal environment efficiently, triggering a robust pro-apoptotic, anti-proliferative response within the stem/progenitor cell zone.

Abstract Background Machine learning (ML) represents a powerful tool to capture relationships between molecular alterations and cancer types and to extract biological information. Here, we developed a plain ML model aimed at distinguishing cancer types based on genetic lesions, providing an additional tool to improve cancer diagnosis, particularly for tumors of unknown origin. Methods TCGA data from 9,927 samples spanning 32 different cancer types were downloaded from cBioportal. A vector space model type data transformation technique was designed to build consistently homogeneous new datasets containing, as predictive features, calls for somatic point mutations and copy number variations at chromosome arm-level, thus allowing the use of the XGBoost classifier models. Considering the imbalance in the dataset, due to large difference in the number of cases for each tumor, two preprocessing strategies were considered: i) setting a percentage cut-off threshold to remove less represented cancer types, ii) dividing cancer types into different groups based on biological criteria and training a specific XGBoost model for each of them. The performance of all trained models was mainly assessed by the out-of-sample balanced accuracy (BACC) and the AUC scores. Results The XGBoost classifier achieved the best performance (BACC 77%; AUC 97%) on a dataset containing the 10 most represented tumor types. Moreover, dividing the 18 most represented cancers into three different groups (endocrine-related carcinomas, other carcinomas and other cancers),such analysis models achieved 78%, 71% and 86% BACC, respectively, with AUC scores greater than 96%. In addition, the model capable of linking each group to a specific cancer type reached 81% BACC and 94% AUC. Overall, the diagnostic potential of our model was comparable/higher with respect to others already described in literature and based on similar molecular data and ML approaches. Conclusions A boosted ML approach able to accurately discriminate different cancer types was developed. The methodology builds datasets simpler and more interpretable than the original data, while keeping enough information to accurately train standard ML models without resorting to sophisticated Deep Learning architectures. In combination with histopathological examinations, this approach could improve cancer diagnosis by using specific DNA alterations, processed by a replicable and easy-to-use automated technology. The study encourages new investigations which could further increase the classifier’s performance, for example by considering more features and dividing tumors into their main molecular subtypes.

Dual-Energy computed tomography (DECT) with its various advanced techniques, including Virtual Non-Contrast (VNC), effective atomic number (Z-eff) calculation, Z-maps, Iodine Density Index (IDI), and so on, holds great promise in the diagnosis and management of urogenital tumours. In this narrative review, we analyze the current status of knowledge of this technology to provide better lesion characterization, improve the staging accuracy, and give more precise treatment response assessments in relation to urological tumours.