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Objective: The purpose of this study was to investigate the effect of high-velocity low-amplitude techniques (HVLATs) on discogenic lumbosacral radicular syndrome (LSRS)., Methods: This was a systematic review of randomized controlled trials (RCTs). Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica Database (EMBASE), Physiotherapy Evidence Database (PEDro) and Web of Science (WoS) were searched from inception until 19 November 2023. Eligible RCTs involved adults with LSRS and compared HVLATs with other nonsurgical treatments, sham HVLATs or no intervention. Data related to pain, disability, health-related quality of life (HRQoL) and adverse events were extracted. The methodological quality was assessed with the 'Cochrane Risk of Bias (RoB) Tool 2.0' and the certainty of the evidence with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE)., Results: Three of the 415 retrieved records met the inclusion criteria. One study investigated acute LSRS, comparing HVLAT versus sham HVLAT. The second study investigated subacute and chronic LSRS, comparing the same intervention with the intervention group receiving 3 adjunctive sessions of HVLAT. The third study investigated chronic LSRS, comparing HVLATs to another manual therapy technique. Totally, 186 people were involved (n = 95 intervention group; n = 91 control group). The first study reported greater improvement in pain and disability in favor of HVLATs. The second study found no differences in pain in favor of HVLATs. The third study found greater improvement for pain, disability and HRQoL in the control group. No adverse events were reported. Two studies were at high RoB and highly heterogeneous; 1 was considered of some concern. The certainty of the evidence was "very low.", Conclusions: There is insufficient evidence to conclude whether HVLATs can be helpful in LSRS. Future high-quality RCTs are necessary., (Copyright © 2024. Published by Elsevier Inc.)

Background: Pulp pinch (PP) is a vital hand movement involving muscle strength and sensory integration. Previous research has primarily focused on Maximal Voluntary Contraction, but PP encompasses broader parameters., Purpose: This study aims to establish normative data for a comprehensive evaluation of thumb and index force control during PP, including endurance, precision, accuracy in unilateral PP, and force coordination in bilateral PP., Study Design: A cross-sectional study., Methods: Three hundred and twenty eight healthy Italian cis-gender participants (169 females, 159 males) were enrolled in a multiparametric force control evaluation of pinch grip, consisting in: sustained contraction (SC: ability to maintain a stable contraction at 40% MVC, measured as the time until exhaustion), dynamic contraction (DC: the ability to modulate precisely and accurately force output to follow a dynamic force trace), bimanual strength coordination (BSC: the ability to coordinate in-phase bimanual forces at different combined magnitudes) tasks. The sample was divided per sex and stratified in five age groups taking into account hand dominance. Differences in tasks' results between age, sex and hand-dominance were analysed., Results: Endurance (SC) was similar between younger and older adults (η 2 =0.047 (Females) and η 2 < 0.007 (Males)). Older adults exhibited lower precision (DC) and coordination (BSC) compared to young adults in both sexes (η 2 >0.16). Females demonstrated greater endurance (SC) but lower precision and coordination (BSC) compared to males (0.01 <η 2 <0.1). No hand dominance effect emerged in SC and DC., Conclusions: Force accuracy and precision to modulate pinch force to perform a visual feedback force-matching task (DC) and force coordination between hands (BSC) worsen at increasing age. Hand dominance did not influence either endurance or precision of pinch grip in visual-feedback guided task., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: We aimed to identify the factors influencing the success of Pain Neuroscience Education (PNE) in chronic musculoskeletal (MSK) pain from the perspective of those experiencing PNE first-hand., Materials and Methods: We conducted a meta-synthesis of qualitative studies. Articles were found on MEDLINE via Pubmed, EMBASE, Cochrane Library, CINHAL, and PsycINFO up to April 2023. Eligible qualitative studies focussed on adults (>16 years old) with a diagnosis of chronic primary or secondary MSK pain who performed PNE. Thematic synthesis by Thomas and Harden was followed. The Critical Appraisal Skills Programme (CASP) tool ensured the quality of the studies, while the Confidence in Evidence from the Reviews of Qualitative Research (CERQual) approach facilitated data confidence assessment., Results: Nine studies were included (188 participants). Three analytical themes were developed: (i) "Efficient Communication of Information", emphasising the importance of accurate content transmission; (ii) "Emotional Support and Well-being", recognising emotional aspects as integral to treatment; and (iii) "Empowerment Promotion", focusing on information retention and personal transformation. The studies showed good quality, with moderate confidence in the evidence., Conclusions: The perceived factors influencing the success of PNE are intricately related to the domain of communication, the emotional dimension of personal experience, and the capacity to be empowered.

Background: This study aimed to explore the awareness, experiences, and beliefs of individuals with osteoarthritis (OA) regarding their healthcare management, along with assessing their overall satisfaction levels., Methods: A cross-sectional online survey was conducted in Italy, Sweden, and Russia, rigorously developed based on OA international guidelines in collaboration with healthcare professionals and individuals with OA. Participants over 40 years of age with self-reported hip and/or knee OA were eligible. The analytical framework included descriptive analysis (assessment of awareness levels for 'recommended', 'optional', and 'not recommended' treatments), analysis of suggested treatments and taken treatments, exploration of beliefs, barriers and satisfaction analysis (0-100 scale)., Results: A total of 401 participants (mean age: 59.7, 78.3% female, 28% Italian, 49% Swedish, 23% Russian) contributed to the study. In Sweden, 57%-72% accurately identified recommended treatments, while in Russia, the range was 34%-91%, and in Italy, it was 35%-73%. The predominant suggested and taken treatments were oral anti-inflammatory drugs in Italy (87/81%) and Russia (97/97%) and specific exercise in Sweden (84/79%). Notably, only Sweden reached a consensus on the effectiveness of exercise for everyone, while Russia and Italy insisted on radiographic findings as a prerequisite for exercise. Mean satisfaction levels were 59.7 (Italy), 47.4 (Sweden), and 35.2 (Russia)., Conclusions: This study uncovered variations in awareness, treatment preferences, and beliefs among the three countries, underscoring the necessity for tailored education on OA management that accounts for regional differences across Europe., (© 2024 The Author(s). Musculoskeletal Care published by John Wiley & Sons Ltd.)

The "AT-hook" is a peculiar DNA-binding domain that interacts with DNA in the minor groove in correspondence to AT-rich sequences. This domain has been first described in the HMGA protein family of architectural factors and later in various transcription factors and chromatin proteins, often in association with major groove DNA-binding domains. In this review, using a literature search, we identified about one hundred AT-hook-containing proteins, mainly chromatin proteins and transcription factors. After considering the prototypes of AT-hook-containing proteins, the HMGA family, we review those that have been studied in more detail and that have been involved in various pathologies with a particular focus on cancer. This review shows that the AT-hook is a domain that gives proteins not only the ability to interact with DNA but also with RNA and proteins. This domain can have enzymatic activity and can influence the activity of the major groove DNA-binding domain and chromatin docking modules when present, and its activity can be modulated by post-translational modifications. Future research on the function of AT-hook-containing proteins will allow us to better decipher their function and contribution to the different pathologies and to eventually uncover their mutual influences.

Conflict management is rarely explored among physiotherapists though they often work in teams. Hence, this study explored attitudes, perceived competencies, beliefs, training experiences, and needs in conflict management among Italian physiotherapists. We conducted a cross-sectional online survey study between June and September 2023 among Italian physiotherapists. The survey instrument comprised four sections. Section 1: Socio-Demographic and Professional Data: Explored participant profiles and conflict frequency. Section 2: Attitudes and Competences: assess conflict-related behaviours and management styles (Likert Scale). Section 3: Training Experiences and Needs: Evaluated training importance and conflict-related issues with other professionals (Likert Scale). Section 4: Beliefs About Factors: Participants rated (0-10) factors influencing conflict management and its impact on care and well-being. Descriptive analyses were performed, presenting continuous data as mean (SD) and categorical data as frequencies/percentages. Likert scale responses were dichotomised (agreement/disagreement), and consensus was defined as ≥70% agreement. Median, quartiles, and box-and-whisker plots depicted responses were used for 0-to-10 scales. Physiotherapists (n = 203; mean age: 39±10.40) generally leaned towards a constructive communication style, characterised by compromise and collaboration, viewing conflict management as an opportunity to grow. There was a disparity between their exhibited behaviours and self-assessment of appropriateness in conflict resolution. Only 27.6% considered their conflict resolution skills as satisfactory. However, 85.7% acknowledged the significance of being trained in conflict management. Challenges were evident in conflicts within interprofessional relationships and communication with superiors. Both personal and organisational factors were identified as influencing conflict management, with participants recognising the detrimental impact of conflicts on their well-being and patient care. This study highlighted educational gaps in conflict management among Italian physiotherapists, showing areas of improvement in their training. Our results suggested that physiotherapists might need additional training in conflict management to enhance workplace well-being and the quality of care provided., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Battista et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: The growing recognition of holistic patient care highlights the various factors shaping the quality of life of individuals with autoimmune and rheumatic diseases (AIRDs). Beyond the traditional disease measures, there is an emerging acknowledgment of the less-explored aspects, including subjective well-being, social determinants of health, comorbidities, mental health, and medication adherence. Moreover, digital health services have empowered patients to engage actively in decision-making alongside clinicians. To explore these domains within the context of AIRDs, the "Collating the Voice of People with Autoimmune Diseases" COVAD survey was conceived, a successor of the previous two COVAD surveys. In this document, we present the study protocol in comprehensive detail., Methods: The COVAD-3 survey is a cross-sectional patient self-reported e-survey incorporating multiple widely accepted scales/scores to assess various aspects of patients' lifestyles objectively. To ensure the survey's accuracy and usability across diverse regions, it will be translated into multiple languages and subjected to rigorous vetting and pilot testing. It will be distributed by collaborators via online platforms and data will be collected from patients with AIRDs, and healthy individuals over eight months. Data analysis will focus on outcome measures related to various social, demographic, economic, and psychological factors., Conclusion: With the increasing awareness to adopt a holistic treatment approach encompassing all avenues of life, the COVAD-3 survey aims to gain valuable insights into the impact of social, demographic, economic, and psychological determinants of health on the subjective well-being in patients with AIRDs, which will contribute to a better understanding of their overall health and well-being., (© 2024. The Author(s).)

Introduction: Hip and knee osteoarthritis (OA) are increasingly common with a significant impact on individuals and society. Non-pharmacological treatments are considered essential to reduce pain and improve function and quality of life. EULAR recommendations for the non-pharmacological core management of hip and knee OA were published in 2013. Given the large number of subsequent studies, an update is needed., Methods: The Standardised Operating Procedures for EULAR recommendations were followed. A multidisciplinary Task Force with 25 members representing 14 European countries was established. The Task Force agreed on an updated search strategy of 11 research questions. The systematic literature review encompassed dates from 1 January 2012 to 27 May 2022. Retrieved evidence was discussed, updated recommendations were formulated, and research and educational agendas were developed., Results: The revised recommendations include two overarching principles and eight evidence-based recommendations including (1) an individualised, multicomponent management plan; (2) information, education and self-management; (3) exercise with adequate tailoring of dosage and progression; (4) mode of exercise delivery; (5) maintenance of healthy weight and weight loss; (6) footwear, walking aids and assistive devices; (7) work-related advice and (8) behaviour change techniques to improve lifestyle. The mean level of agreement on the recommendations ranged between 9.2 and 9.8 (0-10 scale, 10=total agreement). The research agenda highlighted areas related to these interventions including adherence, uptake and impact on work., Conclusions: The 2023 updated recommendations were formulated based on research evidence and expert opinion to guide the optimal management of hip and knee OA., Competing Interests: Competing interests: TPMVV was the Vice president EULAR health professionals 2020–2022 and is part of the EULAR Advocacy Committee 2020–present. MG holds a leadership position in OpenReuma/Spanish Association of Health Professionals in Rheumatology (unpaid). CDM received Grants from Versus Arthritis, MRC, NIHR (paid to Keele University) and is the director of the NIHR School for Primary Care Research. SL received payment as scientific consultant from Arthro Therapeutics AB and received payment from AstraZeneca as a member of DSMB. DC received grants from Fundação para a Ciência e Tecnologia SFRH/BD/148420/2019 and Pfizer (ID 64165707). GZ received payment for expert testimony from Casa di Cura San Francesco, Verona and Support for attending meetings and/or travel from Orthotech and Jtech, payment for participation on a Data Safety Monitoring Board or Advisory Board from VIVENKO for Gruenenthal and Ethos for Angelini and holds other financial interests related to clinical practice as an orthopedic surgeon (performing total joint replacement, arthroscopies and other types of surgeries), either directly from private patients or indirectly from the health system or insurances acting as a private consultant. JEV has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Lilly Netherlands BV. TG has received paid honoraria for lectures by Abbvie, Novartis, Boehringer Ingelheim, UCB, Berlin-Chemie/A. Menarini Bulgaria, Sandoz and received support for attending meetings by Abbvie, Pfizer and UCB. DW is an International Advisory Board Member of DRFZ (Germany) 2019–current and was the EULAR PARE Chair 2015–2017and an EULAR Vice President representing PARE 2017–2021., (© European Alliance of Associations for Rheumatology, EULAR 2024. Re-use permitted under CC BY-NC-ND. No commercial re-use. No derivatives. See rights and permissions. Published by BMJ on behalf of EULAR.)

Objective: To examine income-related inequality changes in the outcomes of an osteoarthritis (OA) first-line intervention., Design: Retrospective cohort study., Setting: Swedish health care system., Participants: We included 115,403 people (age: 66.2±9.7 years; females 67.8%; N=115,403) with knee (67.8%) or hip OA (32.4%) recorded in the "Swedish Osteoarthritis Registry" (SOAR)., Interventions: Exercise and education., Main Outcome Measures: Erreygers' concentration index (E) measured income-related inequalities in "Pain intensity," "Self-efficacy," "Use of NSAIDs," and "Desire for surgery" at baseline, 3-month, and 12-month follow-ups and their differences over time. E-values range from -1 to +1 if the health variables are more concentrated among people with lower or higher income. Zero represents perfect equality. We used entropy balancing to address demographic and outcome imbalances and bootstrap replications to estimate confidence intervals for E differences over time., Results: Comparing baseline to 3 months, "pain" concentrated more among individuals with lower income initially (E=-0.027), intensifying at 3 months (difference with baseline: E=-0.011 [95% CI: -0.014; -0.008]). Similarly, the "Desire for surgery" concentrated more among individuals with lower income initially (E=-0.009), intensifying at 3 months (difference with baseline: E=-0.012 [-0.018; -0.005]). Conversely, "Self-efficacy" concentrated more among individuals with higher income initially (E=0.058), intensifying at 3 months (difference with baseline: E=0.008 [0.004; 0.012]). Lastly, the "Use of NSAIDs" concentrated more among individuals with higher income initially (E=0.068) but narrowed at 3 months (difference with baseline: E=-0.029 [-0.038; -0.021]). Comparing baseline with 12 months, "pain" concentrated more among individuals with lower income initially (E=-0.024), intensifying at 12 months (difference with baseline: E=-0.017 [-0.022; -0.012]). Similarly, the "Desire for surgery" concentrated more among individuals with lower income initially (E=-0.016), intensifying at 12 months (difference with baseline: E=-0.012 [-0.022; -0.002]). Conversely, "Self-efficacy" concentrated more among individuals with higher income initially (E=0.059), intensifying at 12 months (difference with baseline: E=0.016 [0.011; 0.021]). The variable 'Use of NSAIDs' was not recorded in the SOAR at 12-month follow-up., Conclusion: Our results highlight the increase of income-related inequalities in the SOAR over time., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: According to gender-differentiated attributions of failure in the STEM field, errors tend to be attributed to internal factors more to girls than to boys., Aims: This experimental study explored factors influencing gender-differentiated teachers' internal attributions of girls' and boys' errors and the consequent likelihood of teachers' hesitancy to offer educational robotics (ER) courses to them. The predictions were as follows: (1) the likelihood of teachers' hesitancy would be related to gender-differentiated internal attributions of errors based on expectations of a low natural aptitude for girls; and (2) teachers with high levels of gender stereotypes would be more hesitant about offering ER to girls than to boys via the mediation of internal attributions of errors as being due to girls' low levels of natural aptitude for ER., Sample and Methods: In this experimental study, 155 Italian teachers (M = 38.59 years, SD = 8.20) responded to a questionnaire at the end of a course on ER in 2022. Teachers randomly read one of two vignettes describing a girl's or a boy's error during an ER course., Results: Results of multiple regression and moderated mediation analyses confirmed both predictions., Conclusions: In order to reduce the gender STEM gap, the tendency to attribute girls' errors to internal and natural causes should be better inspected., (© 2024 The British Psychological Society.)

The classification of tumors into subtypes, characterized by phenotypes determined by specific differentiation pathways, aids diagnosis and directs therapy towards targeted approaches. However, with the advent and explosion of next-generation sequencing, cancer phenotypes are turning out to be far more heterogenous than initially thought, and the classification is continually being updated to include more subtypes. Tumors are indeed highly dynamic, and they can evolve and undergo various changes in their characteristics during disease progression. The picture becomes even more complex when the tumor responds to a therapy. In all these cases, cancer cells acquire the ability to transdifferentiate, changing subtype, and adapt to changing microenvironments. These modifications affect the tumor's growth rate, invasiveness, response to treatment, and overall clinical behavior. Studying tumor subtype transitions is crucial for understanding tumor evolution, predicting disease outcomes, and developing personalized treatment strategies. We discuss this emerging hallmark of cancer and the molecular mechanisms involved at the crossroads between tumor cells and their microenvironment, focusing on four different human cancers in which tissue plasticity causes a subtype switch: breast cancer, prostate cancer, glioblastoma, and pancreatic adenocarcinoma.

Significance: Metabolic end products and intermediates can exert signaling functions as chemical sources for histone posttranslational modifications, which remodel chromatin and affect gene expression. Among them, lactic acid is responsible for histone lactylation, a recently discovered histone mark that occurs in high lactate conditions, such as those resulting from the Warburg effect in cancer cells. Recent Advances: Late-breaking studies have advanced the knowledge on the mechanisms involved in histone lactylation, requiring independent nonenzyme and enzyme-dependent reactions, which is emerging as an important hallmark of cancer cells linking metabolic changes to gene expression reprogramming. Critical Issues: In this study, we give an overview about this new epigenetic modification, focusing on its mechanism of action in tumors and tumor microenvironment. Future Directions: Further investigation on the competition mechanism between lactylation and acetylation, as well as on the mechanisms by which lactate fluctuation can control a specific gene set in a given tissue, is needed in the coming years to exploit new anticancer therapeutic approaches. Antioxid. Redox Signal. 40, 236-249.

Objective: To explore sex and age differences in Patient-Reported Outcomes Measures (PROMs) and adherence to digital osteoarthritis (OA) self-management intervention., Methods: A register-based study with data from an OA digital self-management intervention. PROMs and adherence were collected at baseline and/or 3 ​month follow-up: 'pain intensity' in hip/knee (best/worst: 0-10), 'activity impairments' (best/worst: 0-10), 'overall health' perception (worst/best: 0-10), 'physical function' (30-s chair stand test), 'health-related quality of life' (EQ-5D-5L index score; worst/best: 0.243-0.976), the subscales and total scores of the Knee Injury/Hip Disability and Osteoarthritis Outcome Score (KOOS/HOOS-12; worst/best: 0-100), 'fear of movement' (yes/no), 'walking difficulties' (yes/no), 'programme adherence' (0-100 ​% and ≥80 ​% [yes/no]), 'patient acceptable symptom state' (PASS; yes/no), and 'treatment failure' (those who answered no to PASS question and thought the treatment failed [yes/no]). We used linear/logistic regression to calculate mean/risk differences in the PROMs and adherence levels among sex and age groups at 3-month follow-up. We employed entropy balancing to explore the contributions of baseline characteristics and different covariates to the sex/age differences., Results: We included 14,610 participants (mean (SD) age: 64.1 (9.1), 75.5 ​% females). Females generally reported better outcomes than males. Participants aged ≥70 had greater activity impairments, lower KOOS/HOOS-pain/function scores, more walking difficulties, less fear of movement and higher adherence than those <70. However, these differences were small and not likely clinically relevant., Conclusion: No clinically relevant differences in PROMs and adherence were found among sex/age groups in this digital OA programme, suggesting that sex/age seemed not to impact the outcomes of this intervention., Competing Interests: AK and LSL act as part-time advisors for Joint Academy®; LED is the founder and chief medical officer at Joint Academy®. The other authors do not have any conflict of interest to declare., (© 2024 The Author(s).)

Background and Aims: The diagnostic and prognostic performance of soluble Suppression of Tumorigenicity 2 (sST2) in suspected septic patients presenting to the Emergency Department (ED) is largely unknown., Materials and Methods: Patients were included in this prospective study if there was high suspicion of sepsis. The plasma level of sST2 was measured during initial ED evaluation. Outcomes were the evaluation of (1) sST2 diagnostic performance (alone and in combination with procalcitonin [PCT]), and (2) sST2 ability to predict 30-day and 90-day all-cause mortality., Results: Among 569 patients included, 481 (84.5 %) had sepsis or septic shock. Plasma sST2 levels were more elevated in septic patients (159 [71-331] vs 50 [31-103] ng/mL, P < 0.001). The AUC of sST2 for sepsis diagnosis was lower than the AUC of PCT (0.76 vs 0.85, P = 0.03). The best cut-off for sST2 was 61.7 ng/mL, with a sensitivity of 79.9 % and a specificity of 70.6 %. sST2 was able to correctly reclassify septic patients with PCT <0.5 (NRI 28.9 % [P = 0.02]). sST2 level was an independent predictor of 30-day mortality in a model including clinical variables (aHR 2.03 [1.24-3.33], C-index 0.69)., Conclusion: sST2 could be a useful adjunct in diagnosing sepsis and in all-cause mortality prediction., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Physiotherapy is gaining a central role in oncology. However, the training and competencies needed by physiotherapists in oncology rehabilitation are still unclear. This study aims to articulate the training trajectory of physiotherapists in oncology rehabilitation from entry-level education to advanced education degrees., Methods: Qualitative focus group study following a 'Reflexive Thematic Analysis' for data analysis. Participants were Italian physiotherapists with expertise in Oncology Rehabilitation (either clinically or academically) and Physiotherapy Bachelor of Science (BSc) course leaders, selected through purposive sampling., Results: Two focus groups were conducted with 14 participants. Six themes were developed: 1. 'Entry-Level Education in Oncology Rehabilitation: Let's Have a Taste', as the BSc introduces oncology rehabilitation. 2. 'Basic Knowledge: Building up the Library' as students acquire basic knowledge on oncology rehabilitation during their BSc; 3. 'Learning by Experience: The Relevance of the Placement' to answer the question "Is this the right road for me?"; 4. 'Clinical Reasoning and Competencies in Oncology Rehabilitation Embedded in Uncertainty' because oncology physiotherapists need to deal with the uncertainty of their patients' status; 5. 'Advanced Education Degree Skills: from Appetiser to the Main Course', as advanced education degree courses allow for becoming an expert in the field; 6. 'A Call to Action for Physiotherapists: Prevention-Diagnosis-Survivorship & End of Life', to realise their critical role in all the phases of the oncology path., Conclusions: The BSc in Physiotherapy provides a foundation for future physiotherapists to understand oncology rehabilitation, but advanced education is necessary for expertise. The findings of this study have important implications for creating a shared physiotherapy curriculum in oncology rehabilitation., Implication for Physiotherapy Practice: This study has significant implications for improving physiotherapy curricula in oncology rehabilitation, positively impacting the skills and competencies of practitioners in this paramount field., (© 2023 The Authors. Physiotherapy Research International published by John Wiley & Sons Ltd.)

Aims: In the DESTINY-Gastric01 trial, a novel HER2-targeted antibody-drug conjugate trastuzumab deruxtecan proved to be effective in HER2-low gastro-oesophageal adenocarcinomas. The aim of our study is to investigate the clinicopathological and molecular features of HER2-low gastric/gastro-oesophageal junction cancers in the real-world setting of a large multi-Institutional series., Methods: We retrospectively evaluated 1210 formalin-fixed paraffin-embedded samples of gastro-oesophageal adenocarcinomas which were analysed by immunohistochemistry for HER2 protein expression in 8 Italian surgical pathology units from January 2018 to June 2022. We assessed the prevalence of HER2-low (ie, HER2 1+ and HER2 2+ without amplification) and its correlation with clinical and histopathological features, other biomarkers' status, including mismatch repair/microsatellite instability status, Epstein-Barr encoding region (EBER) and PD-L1 Combined Positive Score., Results: HER2 status could be assessed in 1189/1210 cases, including 710 HER2 0 cases, 217 HER2 1+, 120 not amplified HER2 2+, 41 amplified HER2 2+ and 101 HER2 3+. The estimated prevalence of HER2-low was 28.3% (95% CI 25.8% to 31.0%) overall, and was higher in biopsy specimens (34.9%, 95% CI 31.2% to 38.8%) compared with surgical resection specimens (21.0%, 95% CI 17.7% to 24.6%) (p<0.0001). Moreover, HER2-low prevalence ranged from 19.1% to 40.6% among centres (p=0.0005)., Conclusions: This work shows how the expansion of the HER2 spectrum might raise problems in reproducibility, especially in biopsy specimens, decreasing interlaboratory and interobserver concordance. If controlled trials confirm the promising activity of novel anti-HER2 agents in HER2-low gastro-oesophageal cancers, a shift in the interpretation of HER2 status may need to be pursued., Competing Interests: Competing interests: MF has been involved in consulting/advisory roles in Astellas Pharma, Pierre Fabre, MSD, GlaxoSmithKline, Amgen, Novartis and Roche, and received research funding from Astellas Pharma, QED Therapeutics, Diaceutics and Macrophage Pharma., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To explore how lifestyle and demographic, socioeconomic, and disease-related factors are associated with supervised exercise adherence in an osteoarthritis (OA) management program and the ability of these factors to explain exercise adherence., Methods: A cohort register-based study on participants from the Swedish Osteoarthritis Registry who attended the exercise part of a nationwide Swedish OA management program. We ran a multinomial logistic regression to determine the association of exercise adherence with the abovementioned factors. We calculated their ability to explain exercise adherence with the McFadden R 2 ., Results: Our sample comprises 19,750 participants (73% female, mean ± SD age 67 ± 8.9 years). Among them, 5,862 (30%) reached a low level of adherence, 3,947 (20%) a medium level, and 9,941 (50%) a high level. After a listwise deletion, the analysis was run on 16,685 participants (85%), with low levels of adherence as the reference category. Some factors were positively associated with high levels of adherence, such as older age (relative risk ratio [RRR] 1.01 [95% confidence interval (95% CI) 1.01-1.02] per year), and the arthritis-specific self-efficacy (RRR 1.04 [95% CI 1.02-1.07] per 10-point increase). Others were negatively associated with high levels of adherence, such as female sex (RRR 0.82 [95% CI 0.75-0.89]), having a medium (RRR 0.89 [95% CI 0.81-0.98] or a high level of education (RRR 0.84 [95% CI 0.76-0.94]). Nevertheless, the investigating factors could explain 1% of the variability in exercise adherence (R 2 = 0.012)., Conclusion: Despite the associations reported above, the poorly explained variability suggests that strategies based on lifestyle and demographic, socioeconomic, and disease-related factors are unlikely to improve exercise adherence significantly., (© 2023 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Liposomes are promising drug carriers for a wide range of central nervous system disorders, such as Parkinson's disease (PD), since they can protect active substances from degradation and could be administered intranasally, ensuring a direct access to the brain. Levodopa (LD), the drug commonly used to treat PD, spontaneously oxidizes in aqueous solutions and thus needs to be stabilized. Our investigation focuses on the preparation and the physico-chemical characterization of mixed liposomes to vehiculate LD and two natural substances (L-ascorbic acid and quercetin) that can prevent its oxidation and contribute to the treatment of Parkinson's disease. These co-loaded vesicles were prepared using a saturated phospholipid and structurally related cationic or analogue N-oxide surfactants and showed different properties, based on their composition. In particular, ex-vivo permeability tests using porcine nasal mucosa were performed, denoting that subtle variations of the lipids structure can significantly affect the delivery of LD to the target site., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To explore the experience of using audience response systems (ARS) in postgraduate physiotherapy training., Design: Qualitative interview study following the 'reflexive thematic analysis' by Braun and Clarke., Setting: Higher education university., Participants: Ten Italian students (60% men, N=6; 40% women, N=4) agreed to partake in the interviews., Results: We generated four themes. Specifically, the ARS were perceived: (1) as a 'Shared Compass' (theme 1) between the student and the lecturers to monitor and modify the ongoing students' learning journey; (2) useful to 'Come Out of Your Shell' (theme 2) as they help students to overcome shyness and build a team with peers; (3) as 'A Square Peg in a Round Hole' (theme 3) as they should not be used in situations that do not suit them; (4) as 'Not Everyone's Cup of Tea' (theme 4) as mixed opinions among ARS' utilities were found under some circumstances (eg, memorisation process and clinical reasoning)., Conclusion: Physiotherapy lecturers must use ARS critically, respecting when (eg, not at the end of the lesson) and how to propose them, keeping in mind that some skills (eg, practical ones) might not benefit from their use. Moreover, they need to consider that the ARS are not a tool for everyone, so ARS must be integrated into a multimodal teaching paradigm., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Clinical Record (CR) writing is a fundamental skill for healthcare professionals, but the best e-learning methods for teaching it remain unstudied. Therefore, we investigated speech therapy students' differences in the quality production of CR at the placement and their experience after following asynchronous or synchronous e-learning courses., Methods: A multi-method randomised controlled trial. Fifty speech therapist students were equally and randomly divided into two groups attending asynchronous or synchronous e-learning classes to learn how to write a CR. The quality of the CR was tested through an ad hoc checklist (score 0-32) and the groups' scores were compared. The assessors and the statistician were blinded to students' group assignment. Students' experience was assessed through semi-structured interviews analysed with a reflexive thematic analysis., Results: No score differences between the two groups were found (Cohen's d = 0.1; 95% Confidence Interval [-0.6; 0.7]). Four themes were generated: (1) 'Different Forms of Learning Interaction', as the synchronous group reported a positive experience with being fed back immediately by the lecturer, whereas the asynchronous group reported that pushing back the question time allows for reflecting more on the learning experience; (2) 'Different Ways to Manage the Time', as the synchronous group had to stick to the lecturer's schedule and the asynchronous group felt the possibility to manage its time; (3) 'To Be or Not To Be (Present)?' due to the different experiences of having (or not) the lecturer in front of them; (4) 'Inspiring Relationships With The Peers', where both groups preferred a peer-to-peer discussion instead of contacting the lecturer., Discussion: Asynchronous and synchronous e-learning courses appeared equally effective in teaching CR writing. However, students perceive and experience these methods differently. The choice or blend of these methods should be based on students' needs and preferences, teacher input, as well as organisational requirements rather than solely on students' attended performance., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: In education, lecturers play a crucial role in facilitating students' learning process. However, only a few studies explored which lecturers' characteristics can facilitate this process in higher education for rehabilitation healthcare professionals. Starting from students' perspectives, our qualitative study investigated the lecturers' characteristics that facilitate students' learning process in the rehabilitation sciences., Methods: A qualitative interview study. We enrolled students attending the 2nd year of the Master of Science (MSc) degree in 'Rehabilitation Sciences of Healthcare Professions'. Different themes were generated following a 'Reflexive Thematic Analysis'., Results: Thirteen students completed the interviews. From their analysis, we generated five themes. Specifically, a lecturer that facilitates students' learning process should be: 1) 'A Performer who Interacts with the Classroom', 2) A Flexible Planner who Adopts Innovative Teaching Skills', 3) 'A Motivator who Embraces Transformational Leadership', 4) 'A Facilitator Who Encourages a Constructive Learning Context' and 5) 'A Coach who Devises Strategies to Reach Shared Learning Goals'., Conclusions: The results of this study underscore the importance for lecturers in rehabilitation to cultivate a diverse set of skills drawn from the arts and performance, education, team building and leadership to facilitate students' learning process. By developing these skills, lecturers can design lessons that are worth attending not only for their relevant content but also for their value in human experience., (© 2023. The Author(s).)

Background: The thoracic area has mainly been neglected in research compared to the lumbar and cervical regions. No clinical practice guidelines (CPGs) for non-specific thoracic spine pain (TSP) have been compiled. Therefore, it can be argued that the absence of specific CPGs raises questions about the management of non-specific TSP. Hence, this study aimed at determining the management of non-specific TSP among physiotherapists in Italy., Methods: A web cross-sectional survey investigating physiotherapists' management of non-specific TSP was conducted. The survey instrument was divided into three sections. The first section obtained participants' characteristics. The second section determined participants' agreement with 29 statements regarding the clinical management of non-specific TSP utilising a five-point Likert scale. Participants who partially or completely agreed (scores 4-5) were considered to agree with the statements. A ≥ 70% of agreement with a statement was considered as consensus according to previous literature. The third section asked the participants to indicate how often they adopted several treatments to manage non-specific TSP with a 5-point scale (always - often - sometimes - rarely - never). The frequencies of answers were calculated, and a visual representation through a bar chart was reported. The online version of the survey instrument was delivered through the newsletter of the Italian Association of Physiotherapists and the postgraduate master's degree in Rheumatic and Musculoskeletal Rehabilitation of the University of Genova (Genova, Italy)., Results: In total, 424 physiotherapists (mean age (SD): 35.1 years (10.5); 50% female) completed the survey. In the second section, physiotherapists achieved consensus for 22/29 statements. Those statements addressed the importance of psychosocial factors, exercise, education, and manual therapy techniques in managing non-specific TSP. In the third section, 79.7% of participants indicated they would always adopt a multimodal treatment (education, therapeutic exercise, manual therapy), followed by education and information (72.9%), therapeutic exercise (62.0%), soft tissue manual therapy (27.1%), and manual therapy (16.5%)., Conclusions: Study participants considered fundamentally using a multimodal programme based on education, exercise and manual therapy to manage non-specific TSP. This approach aligns with the CPGs for other chronic musculoskeletal pain than non-specific TSP., (© 2023. The Author(s).)

Non-small cell lung cancer (NSCLC), the leading cause of cancer death worldwide, is still an unmet medical problem due to the lack of both effective therapies against advanced stages and markers to allow a diagnosis of the disease at early stages before its progression. Immunotherapy targeting the PD-1/PD-L1 checkpoint is promising for many cancers, including NSCLC, but its success depends on the tumor expression of PD-L1. PATZ1 is an emerging cancer-related transcriptional regulator and diagnostic/prognostic biomarker in different malignant tumors, but its role in lung cancer is still obscure. Here we investigated expression and role of PATZ1 in NSCLC, in correlation with NSCLC subtypes and PD-L1 expression. A cohort of 104 NSCLCs, including lung squamous cell carcinomas (LUSCs) and adenocarcinomas (LUADs), was retrospectively analyzed by immunohistochemistry for the expression of PATZ1 and PD-L1. The results were correlated with each other and with the clinical characteristics, showing on the one hand a positive correlation between the high expression of PATZ1 and the LUSC subtype and, on the other hand, a negative correlation between PATZ1 and PD-L1, validated at the mRNA level in independent NSCLC datasets. Consistently, two NSCLC cell lines transfected with a PATZ1-overexpressing plasmid showed PD-L1 downregulation, suggesting a role for PATZ1 in the negative regulation of PD-L1. We also showed that PATZ1 overexpression inhibits NSCLC cell proliferation, migration, and invasion, and that Patz1-knockout mice develop LUAD. Overall, this suggests that PATZ1 may act as a tumor suppressor in NSCLC.

The objective of the present study was to evaluate the effect of GnRH dose administered at initiation (GnRH-1) of a 5-day CO-Synch + P4 protocol on ovulatory response, expression of estrus, and fertility in suckled beef cows. Suckled beef cows (n = 1101) at four locations were randomized to receive either 100 or 200 µg of gonadorelin acetate at initiation (D-8) of a 5-day CO-Synch + P4 protocol concurrently with insertion of an intravaginal progesterone (P4) device. On D-3 the P4 device was removed, two doses of prostaglandin F2α were administered concurrently and a patch was applied to evaluate expression of estrus. Artificial insemination was performed 72 h after P4 device removal (D0) simultaneously with the administration of 100 µg of gonadorelin acetate (GnRH-2). Increasing GnRH dose at initiation of a 5-day CO-Synch + P4 did not enhance ovulatory response (P = 0.57) to GnRH-1, expression of estrus (P = 0.79), nor pregnancies per AI (P/AI; P = 0.91). Both follicle size (quadratic) and circulating P4 (linear) affected (P < 0.01) ovulatory response to GnRH-1 independent of dose. Cows that had ovulation to GnRH-1 had smaller (P < 0.001) follicle size on D-3 and reduced (P = 0.05) expression of estrus compared to cows that did not have ovulation to GnRH-1, however, P/AI did not differ (P = 0.75). In conclusion, increasing the dose of GnRH-1 in the 5-day CO-Synch + P4 protocol did not enhance ovulatory response, expression of estrus, or P/AI in suckled beef cows., Competing Interests: Competing interests None of the authors of the above manuscript has declared any conflict of interest which may arise from being an author on the manuscript. The authors declare no financial or personal competing interests that may influence data interpretation or presentation of information in relation to this manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The DNA mismatch repair (MMR) system is a highly preserved protein complex recognizing short insertions, short deletions, and single base mismatches during DNA replication and recombination. MMR protein status is identified using immunohistochemistry. Deficit in one or more MMR proteins, configuring deficient MMR status (dMMR), leads to frameshift mutations particularly clustered in microsatellite repeats. Thus, microsatellite instability (MSI) is the epiphenomenon of dMMR. In colorectal cancer (CRC), MMR/MSI status is a biomarker with prognostic and predictive value of resistance to 5-fluorouracil and response to immune checkpoint inhibitor therapy., Summary: In this Review, we describe the challenges the practicing pathologist may face in relation to the assessment of MMR/MSI status and any open issues which still need to be addressed, focusing on pre-analytic issues, pitfalls in the interpretation, and technical aspects of the different assays., Key Messages: The current methods of detecting dMMR/MSI status have been optimized for CRCs, and whether these techniques can be applied to all tumor and specimen types is still not fully understood. Following the Food and Drug Administration (FDA), tissue/site agnostic drug approval of pembrolizumab for advanced/metastatic MSI tumors, MMR/MSI status in gastrointestinal tract is a common request from the oncologist. In this setting, several issues still need to be addressed, including criteria for sample adequacy., (© 2023 S. Karger AG, Basel.)

Introduction: Metastasis from melanoma in the gastro-intestinal tract is a frequent event but, in the absence of an adequate clinical context and oncological anamnesis, it could be misdiagnosed by the pathologists. Moreover, amelanotic and/or poorly differentiated metastasis from melanoma in the gastro-intestinal tract can be easily underestimated., Materials and Methods: We describe the histological features of gastro-intestinal metastasis from melanoma in a multi-centric cohort of 49 patients. In 24/49 patients, we were able to compare histological findings such as the growth pattern and the melanotic pigment also in the primary melanoma., Results: The epithelioid pattern is the most common growth pattern observed in gastro-intestinal metastasis (57 %), followed by the mixed pattern (41 %) and the spindled pattern (2 %). We documented a discordant growth pattern between metastasis and primary in 9/24 cases and the absence of melanotic pigment in 8/49 cases., Discussion: Our experience highlights that pathologists should take into account the possibility of gastro-intestinal metastasis from melanoma also in cases with spindled-cells/amelanotic lesions, without a previous anamnesis of melanoma asportation, and in cases of a discordant growth pattern with the primary. A correct clinical integration and an aware immunohistochemical approach are imperative to best manage the bioptic sample in order to investigate the biological profiling and therefore plan a personalizated therapy., Competing Interests: Conflicts of Interest The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Study Design: Cross-sectional study., Introduction: Flexion (Palmar Pinch, PP-MVC and Tip Pinch, TP-MVC) and extension (E-MVC) maximal voluntary contraction (MVC) of the index-thumb system offers a quick way to estimate the level of hands' impairment in several musculoskeletal and neurologic conditions., Purpose of the Study: This study established normative data of PP-MVC, TP-MVC, E-MVC in the Italian population and evaluated their correlation with hand dominance, anthropometric factors, dexterity and workload level., Methods: In our study, 303 healthy people (150F, 153M) were recruited. Participants performed PP-MVC, TP-MVC and E-MVC tests per hand, conducted by using a pinch-gauge. T-test was used to analyze MVC means between sexes and between hands. One-way ANOVA was conducted to compare MVC means in male and female samples stratified by age (18-29, 30-44, 45-59, 60-74, +75). Spearman's correlation analysis was performed to determine anthropometric variables, dexterity and workload level effects on MVCs., Results: Medium-to-large effect sizes of age were shown in the majority of tasks. The 30 to 44 years and then +75 years age groups showed the highest and the lowest values, respectively, for both sex and both hands. Men were meanly 50% stronger, and the dominant hand showed higher values (6-10%). MVC-tests correlated moderately with weight and height weakly with dexterity and workload level., Conclusions: After 30 to 44 years, hand strength declines in line with the normal process of aging that also entails muscle fibers and the reduction of daily activities in older adults. In relative terms, E-MVC showed the highest strength loss in the over 75 seconds. The difference between sexes was higher in E-MVC than in flexion MVCs. E-MVC seems to depend more on musculoskeletal architecture that differs from women to men, according to the highest correlation between E-MVC and anthropometric variables. Only high workload levels impacted hand strength. In heaviest occupations, no PP-MVCs differences were observed between hands., (Copyright © 2021. Published by Elsevier Inc.)

Research found that those who believe sexual orientation is inborn have generally positive attitudes toward gay men and lesbian women. However, other studies have also found that these beliefs could include negative eugenic ideas. This study aims to investigate the role of people's beliefs about the aetiology of sexual orientation in attitudes toward adoption for both gay and lesbian couples in Italy. We hypothesized that this relationship would be mediated by sexual prejudice. To test the predictions, 256 Italian heterosexual participants were asked to answer questions on a scale about their beliefs regarding the aetiology of sexual orientation, sexual prejudice, and attitudes toward adoption by same-sex couples. Results confirmed that the relationship between aetiology beliefs and support for adoption by gay and lesbian couples was fully mediated by sexual prejudice. These results suggest that the belief that sexual orientation is controllable may serve to justify one's prejudice and, in turn, result in a lower support for same-sex couples' adoption., Competing Interests: The authors have declared that no competing interests exist.

Study Design: A cross-sectional study based on an online questionnaire., Objective: The aim was to investigate the prevalence and intensity of low back pain (LBP) in people with lower limb amputation (LLA) and to analyze the association factors that can influence the genesis of LBP., Summary of Background Data: It is still unclear whether LBP is more prevalent in the amputated population than in its nonamputated counterpart. Given the multifactorial nature of LBP, it is necessary to explore possible factors that can influence its presence and intensity, to build a solid background to define a better rehabilitation pathway for the management of these people., Methods: The online questionnaire included six sections: informed consent of the study, demographic information, comorbid conditions, history of LLA, history of LBP, and acceptance of the amputation., Results: Between March and June 2021, 239 participants [mean age (SD): 49.2 (11.5); female 11%] completed the survey (response rate: 32%). From the results of this study, LBP in LLA showed a prevalence of 82% postamputation and 70% in the last year. A logistic regression with a backward method showed that participants who had problems in the not affected leg presented 1.58 (95% confidence interval: 0.70; 2.45) times higher odds to have LBP after the amputation., Conclusion: This study shows that the prevalence of LBP in lower limb amputees appears to be higher than in the general population, with similar levels of pain intensity and frequency. The highest percentage of people with a sedentary lifestyle not practicing any kind of sports emphasizes the importance of educating this population on the importance of physical activity. New strategies to invest in the education of this population in terms of physical activity are needed., Level of Evidence: Level 4., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Lateral ankle sprain (LAS) is a common and burdensome injury. However, the quality of its management is scant. Nowadays, physiotherapy management of musculoskeletal diseases seems to be generally not based on research evidence. Studies that investigated the knowledge-to-practice gap in LAS management are yet to be carried out. Therefore, this research investigated physiotherapists' knowledge of and adherence to LAS Clinical Practice Guidelines (CPGs) and recommendations., Methods: A cross-sectional study based on an online survey structured in three sections. The first section collected demographic data. The second section showed two clinical cases (with positive and negative Ottawa Ankle Rules (OAR), respectively). The participants indicated which treatments they would adopt to manage them. Participants were classified as 'following', 'partially following', 'partially not following' and 'not following' the CPGs and recommendations. In the third section, participants expressed their agreement with different CPG and recommendation statements through a 1-5 Likert scale., Results: In total, 483 physiotherapists (age: 34 ± 10; female 38%, male 61.5%, other 0.5%) answered the survey: 85% completed the first two sections, 76% completed all three sections. In a case of acute LAS with negative OAR, 4% of the participants were considered as 'following' recommended treatments, 68% as 'partially following', 23% as 'partially not following', and 5% as 'not following'. In a case of acute LAS with positive OAR, 37% were considered 'following' recommended treatments, 35% as 'partially following', and 28% as 'not following'. In the third section, the consensus was achieved for 73% of the statements., Conclusion: This study showed that although there is a good knowledge about first-line recommended treatments, a better use of CPGs and recommendations should be fostered among physiotherapists. Our results identify an evidence-to-practice gap in LAS management, which may lead to non-evidence-based practice behaviors., (© 2022. The Author(s).)

Diet and lifestyle factors greatly affect health and susceptibility to diseases, including cancer. Stem cells' functions, including their ability to divide asymmetrically, set the rules for tissue homeostasis, contribute to health maintenance, and represent the entry point of cancer occurrence. Stem cell properties result from the complex integration of intrinsic, extrinsic, and systemic factors. In this context, diet-induced metabolic changes can have a profound impact on stem cell fate determination, lineage specification and differentiation. The purpose of this review is to provide a comprehensive description of the multiple "non-metabolic" effects of diet on stem cell functions, including little-known effects such as those on liquid-liquid phase separation and on non-random chromosome segregation (asymmetric division). A deep understanding of the specific dietetic requirements of normal and cancer stem cells may pave the way for the development of nutrition-based targeted therapeutic approaches to improve regenerative and anticancer therapies.

Introduction: Despite the publication of clinical practice guidelines, the quality of the care process as experienced by patients with osteoarthritis (OA) appears suboptimal. Hence, this study investigates how patients with OA experience their disease and care process, highlighting potential elements that can enhance or spoil it, to optimise their quality of care., Methods: A qualitative study based on semi-structured interviews. Patients with hip and knee OA in Italy were interviewed. The interview guide was created by a pool of health professionals and patients. The interviews were analysed through a theme-based analysis following a philosophy of descriptive phenomenological research., Results: Our analysis revealed seven main themes: (1) Experiencing a sense of uncertainty, as interviewees perceived treatment choices not to be based on medical evidence; (2) Establishing challenging relationships with the self and the other, as they did not feel understood and felt ashamed or hopeless about their condition; (3) Being stuck in one's own or the health professionals' beliefs about the disease management, as a common thought was the perception of movement as something dangerous together with a frequent prescription of passive therapies; (4) Dealing with one's own attitudes towards the disease; Understanding (5) the barriers to and (6) the facilitators of the adherence to therapeutic exercise, which revolve around the therapy cost, the time needed and the patients' willingness to change their life habits and (7) Developing an uneasy relationship with food since the diet was considered as something that "you force yourself to follow" and overeating as a way "to eat your feelings"., Conclusion: The lack of clear explanations and a negative attitude towards first-line nonsurgical treatments (mainly physical exercise), which are considered as a way to fill the time while waiting for surgery, underlines the importance of providing patients with adequate information about OA treatments and to better explain the role of first-line intervention in the care of OA. This will enhance patient-centred and shared decision-making treatments., Patient Contribution: Patients with hip and knee OA participated in creating the interview and contributed with their experience of their care process., (© 2022 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

The efficacy of the treatment of bacterial infection is seriously reduced because of antibiotic resistance; thus, therapeutic solutions against drug-resistant microbes are necessary. Nanoparticle-based solutions are particularly promising for meeting this challenge because they can offer intrinsic antimicrobial activity and sustained drug release at the target site. Herein, we present a newly developed nanovesicle system of the quatsome family, composed of l-prolinol-derived surfactants and cholesterol, which has noticeable antibacterial activity even on Gram-negative strains, demonstrating great potential for the treatment of bacterial infections. We optimized the vesicle stability and antibacterial activity by tuning the surfactant chain length and headgroup charge (cationic or zwitterionic) and show that these quatsomes can furthermore serve as nanocarriers of pharmaceutical actives, demonstrated here by the encapsulation of (+)-usnic acid, a natural substance with many pharmacological properties., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Background: The direction and the magnitude of verbal suggestions have been shown to be strong modulators of nocebo hyperalgesia, while little attention has been given to the role of their temporal content. Here, we investigate whether temporal suggestions modulate the timing of nocebo hyperalgesia in an experimental model of sustained pain., Methods: Fifty-one healthy participants were allocated to one of three groups. Participants received an inert cream and were instructed that the agent had either hyperalgesic properties setting in after 5 (Nocebo 5, N5) or 30 (Nocebo 30, N30) minutes from cream application, or hydrating properties (No Expectation Group, NE). Pain was induced by the Cold Pressure Test (CPT) which was repeated before cream application (baseline) and after 10 (Test10) and 35 (Test35) minutes. Changes in pain tolerance and in HR at each test point in respect to baseline were compared between the three groups., Results: Tolerance change at Test 10 (Δ10) was greater in N5 (MED = -36.8; IQR = 20.9) compared to NE (MED = -5.3; IQR = 22.4; p < 0.001) and N30 (MED = 0.0; IQR = 23.1; p < 0.001), showing that hyperalgesia was only present in the group that expected the effect of the cream to set in early. Tolerance change at Test 35 (Δ35) was greater in N5 (MED = -36.3; IQR = 35.3; p = 0.002) and in N30 (MED = -33.3; IQR = 34.8; p = 0.009) compared to NE, indicating delayed onset of hyperalgesia in N30, and sustained hyperalgesia in N5. No group differences were found for HR., Conclusions: Our study demonstrated that temporal expectations shift nocebo response onset in a model of sustained pain., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Camerone, Battista, Benedetti, Carlino, Sansone, Buzzatti, Scafoglieri and Testa.)

Background and Aims: A hybrid technique may be a reasonable compromise to make endoscopic mucosal resection (EMR) more reliable for lesions ≥ 20 mm and a good way of approaching to endoscopic submucosal dissection (ESD). The aim of this study was to assess the efficacy and safety of a novel hybrid EMR technique, triple-anchoring EMR (T-EMR) for colorectal lesions 20-30 mm., Methods: Fifteen patients have been prospectively enrolled to T-EMR from December 2019 to April 2020 in two Endoscopy Units: Policlinico A. Gemelli, Rome, and University Hospital of Udine, Italy. Patients eligible for the study were ≥18 years old with superficial colorectal lesions 20-30 mm, morphologically liable to endoscopic treatment based on chromoendoscopy. The primary endpoint was assessment of the "en bloc" and the free resection margins (R0) rates. The secondary endpoints were resected specimen size, procedure time, complication rate, and recurrence rate at 6 months., Results: Among the 15 patients enrolled, 12 were males (80%), mean age 68.73±11.04 years. The mean size of the lesions was 24.93±2.89 mm. Mean procedure time was 22.13±4.31 min. T-EMR was performed en bloc in 14/15 patients (93.3%) with R0 in 13/15 patients (86.7%). No major intra-/peri-procedural or delayed complications occurred. At histological analysis, 13/15 lesions (86.7%) were adenomas, while 2 were early colorectal cancer. At a 6-month follow-up colonoscopy, only one patient (6.7%) had a recurrence of adenoma., Conclusions: T-EMR seems to be an effective and safe option to treat colorectal lesions between 20 and 30 mm, with a short procedure time and low costs.

The prognostic value of mid-regional proADM (MR-proADM) in septic patients presenting to the emergency department (ED) is not well established. In this prospective observational study enrolling septic patients evaluated in two EDs, MR-proADM was measured at arrival (t0) and after 72 h (t72). MR-proADM %change was calculated as follows: (MR-proADM t72h - MR-proADM t0 )/MR-proADM t0 . In total, 147 patients were included in the study, including 109 with a final diagnosis of sepsis and 38 with septic shock, according to the Sepsis-3 criteria. The overall 28-day mortality (outcome) rate was 12.9%. The AUC for outcome prognostication was 0.66 (95% CI 0.51-0.80) for MR-proADM t0 , 0.77 (95% CI 0.63-0.92) for MR-proADM t72 and 0.74 (95% CI 0.64-0.84) for MR-proADM %change . MR-proADM t0 ≥ 2.78 nmol/L, MR-proADM t72 ≥ 2.7 nmol/L and MR-proADM %change ≥ -15.2% showed statistically significant log-rank test results and sensitivity/specificity of 81/65%, 69/80% and 75/70% respectively. In regression analysis, MR-proADM %change was a significant outcome predictor both in univariate and multivariate analysis, after adjustment for age, SOFA and APACHEII scores, providing up to 80% of added prognostic value. In conclusion, time trends of MR-proADM may provide additional insights for patient risk stratification over single sampling. MR-proADM levels sampled both at presentation and after 72 h predicted 28-day survival in septic patients presenting to the ED.

Preneoplastic lesions represent a useful target for early diagnosis and follow-up of gastrointestinal malignancies. hERG1 channel expression was tested by immunohistochemistry (IHC) in a cohort of colorectal adenoma samples belonging to Italian subjects. Overall, hERG1 was expressed in 56.5% of cases with both high staining intensity and a high percentage of positive cells. Moreover, hERG1 was expressed in a higher percentage of dysplastic adenomas with respect to hyperplastic lesions, and the proportion of positive samples further increased in patients with high-grade dysplasia. Comparing hERG1 expression in other preneoplastic lesions of the GI tract (gastric dysplasia and Barrett's esophagus), it emerged that in all the conditions, hERG1 was expressed with a diffused pattern, throughout the cell, with variable staining intensity within the samples. The highest expression was detected in gastric dysplasia samples and the lowest in Barrett's esophagus at similar levels observed in colorectal adenomas. Our results show that hERG1 is aberrantly expressed in human preneoplastic lesions of the gastrointestinal tract and has a different pattern of expression and role in the different sites. Overall, the detection of hERG1 expression in preneoplastic lesions could represent a novel diagnostic or prognostic marker of progression in the gastrointestinal tract.

Although liposomes are largely investigated as drug delivery systems, they can also exert a pharmacological activity if devoid of an active principle as a function of their composition. Specifically, charged liposomes can electrostatically interact with bacterial cells and, in some cases, induce bacterial cell death. Moreover, they also show a high affinity toward bacterial biofilms. We investigated the physicochemical and antimicrobial properties of liposomes formulated with a natural phospholipid and four synthetic l-prolinol-derived surfactants at 9/1 and 8/2 molar ratios. The synthetic components differ in the nature of the polar headgroup (quaternary ammonium salt or N -oxide) and/or the length of the alkyl chain (14 or 16 methylenes). These differences allowed us to investigate the effect of the molecular structure of liposome components on the properties of the aggregates and their ability to interact with bacterial cells. The antimicrobial properties of the different formulations were assessed against Gram-negative and Gram-positive bacteria and fungi. Drug-drug interactions with four classes of available clinical antibiotics were evaluated against Staphylococcus spp. The target of each class of antibiotics plays a pivotal role in exerting a synergistic effect. Our results highlight that the liposomal formulations with an N -oxide moiety are required for the antibacterial activity against Gram-positive bacteria. In particular, we observed a synergism between oxacillin and liposomes containing 20 molar percentage of N -oxide surfactants on Staphylococcus haemolyticus , Staphylococcus epidermidis , and Staphylococcus aureus . In the case of liposomes containing 20 molar percentage of the N -oxide surfactant with 14 carbon atoms in the alkyl chain for S. epidermidis , the minimum inhibitory concentration was 0.125 μg/mL, well below the breakpoint value of the antibiotic.

The transition between epithelial and mesenchymal phenotype is emerging as a key determinant of tumor cell invasion and metastasis. It is a plastic process in which epithelial cells first acquire the ability to invade the extracellular matrix and migrate into the bloodstream via transdifferentiation into mesenchymal cells, a phenomenon known as epithelial-mesenchymal transition (EMT), and then reacquire the epithelial phenotype, the reverse process called mesenchymal-epithelial transition (MET), to colonize a new organ. During all metastatic stages, metabolic changes, which give cancer cells the ability to adapt to increased energy demand and to withstand a hostile new environment, are also important determinants of successful cancer progression. In this review, we describe the complex interaction between EMT and metabolism during tumor progression. First, we outline the main connections between the two processes, with particular emphasis on the role of cancer stem cells and LncRNAs. Then, we focus on some specific cancers, such as breast, lung, and thyroid cancer.

Dynamic computer tomography (CT) is an emerging modality to analyze in-vivo joint kinematics at the bone level, but it requires manual bone segmentation and, in some instances, landmark identification. The objective of this study is to present an automated workflow for the assessment of three-dimensional in vivo joint kinematics from dynamic musculoskeletal CT images. The proposed method relies on a multi-atlas, multi-label segmentation and landmark propagation framework to extract bony structures and detect anatomical landmarks on the CT dataset. The segmented structures serve as regions of interest for the subsequent motion estimation across the dynamic sequence. The landmarks are propagated across the dynamic sequence for the construction of bone embedded reference frames from which kinematic parameters are estimated. We applied our workflow on dynamic CT images obtained from 15 healthy subjects on two different joints: thumb base ( n = 5) and knee ( n = 10). The proposed method resulted in segmentation accuracies of 0.90 ± 0.01 for the thumb dataset and 0.94 ± 0.02 for the knee as measured by the Dice score coefficient. In terms of motion estimation, mean differences in cardan angles between the automated algorithm and manual segmentation, and landmark identification performed by an expert were below 1°. Intraclass correlation (ICC) between cardan angles from the algorithm and results from expert manual landmarks ranged from 0.72 to 0.99 for all joints across all axes. The proposed automated method resulted in reproducible and reliable measurements, enabling the assessment of joint kinematics using 4DCT in clinical routine.

Background: Low back pain (LBP) is a burdensome problem affecting amateur cyclists. This cross-sectional study analysed Italian amateur cycling cohort's demographic and sport-specific characteristics, the prevalence and characteristics of LBP among this population, its possible association factors, the management strategies adopted to deal with LBP and the sample's beliefs among possible LBP triggers. A web-based cross-sectional survey was created. The questionnaire included 56 questions divided into six sections, querying the sample's demographic, clinical, and cycling characteristics. Binomial logistic regression with a Wald backward method was performed to ascertain the effects of some covariates ("Sex", "Age", "Body Mass Index", "Sleep hours", "Work type", "Cycling year", "Number of training sessions per week", "Stretching sessions", "Being supervised by a coach or following a scheduled training", "Other sports practised regularly", "Number of cycling competitions per year", "Past biomechanic visits", "Specific pedal training", "LBP before cycling") on the likelihood of developing LBP in the last 12 months., Results: A total of 1274 amateur cyclists answered the survey. The prevalence of LBP appeared to be 55.1%, 26.5% and 10.8% in life, in the last 12 months and the last 4 weeks, respectively. The final model of the logistic regression included the covariates "Sex", "Work type", "Cycling year", "Being supervised by a coach or following a scheduled training", "Other sports practised regularly", "Specific pedal training", "LBP before cycling", among which "Cycling year" (variable "Between 2 and 5 years" vs. "Less than 2 years", OR 0.48, 95% CI [0.26-0.89]), "Being supervised by a coach or following a scheduled training" (OR 0.53, 95% CI [0.37-0.74]), "Specific pedal training" (OR 0.69, 95% CI [0.51-0.94]), and "LBP before cycling" (OR 4.2, 95% CI [3.21-5.40]) were found to be significant., Conclusions: The prevalence of LBP among Italian amateur cyclists seems to be less frequent compared to the general population. Moreover, undergoing previous specific pedal training and being supervised by a coach or following scheduled training drew a negative association with LBP development. This evidence highlights the importance of being overseen by specific sport figures that could offer a tailored evidence-based training to reach good physical level and to practise sports safely., (© 2021. The Author(s).)

Objective: To examine the experience of the COVID-19 pandemic as lived by people with hip and knee osteoarthritis (OA), in Italy., Design: A qualitative study based on semi-structured interviews., Setting: Urban and suburban areas in northern Italy., Participants: A total of 11 people with OA were enrolled through a purposeful sampling and completed the study., Primary Outcome Measure: The experience of Italian people with OA during the COVID-19 pandemic., Results: Four themes were brought to the forefront from the analysis of the interviews. (1) Being Stressed for the Limited Social Interactions and for the Family Members at High Risk of Infection, as the interviewees were frustrated because they could not see their loved ones or felt a sense of apprehension for their relatives. (2) Recurring Strategies to Cope with the Pandemic such as an active acceptance towards the situation. (3) Being Limited in the Possibility of Undergoing OA Complementary Treatments and Other Routine Medical Visits. (4) Being Unaware of the Importance of Physical Activity as First-Line Interventions which was an attitude already present before the pandemic., Conclusion: The COVID-19 pandemic and related restrictions impacted the quality of life and the care of individuals with hip and knee OA. The social sphere seemed to be the most hindered. However, the interviewees developed a good level of acceptance to deal with the pandemic. When it came to their care, they faced a delay of routine medical visits not related to OA and of other complementary treatments (eg, physical therapies) to manage OA. Finally, a controversial result that emerged from these interviews was that first-line interventions for OA (ie, therapeutic exercise) was not sought by the interviewees, regardless of the restrictions dictated by the pandemic. Policy-making strategies are thus necessary to support the awareness of the importance of such interventions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Several studies have investigated the effect of botulinum toxin A (BoNT-A) for managing chronic musculoskeletal pain, bringing contrasting results to the forefront. Thus far, however, there has been no synthesis of evidence on the effect of BoNT-A as an adjunctive treatment within a multimodal approach. Hence, Medline via PubMed, EMBASE, and the Cochrane Library-CENTRAL were searched until November 2020 for randomised controlled trials (RCTs) that investigated the use of BoNT-A as an adjunctive therapy for chronic musculoskeletal pain. The risk of bias (RoB) and the overall quality of the studies were assessed through RoB 2.0 and the GRADE approach, respectively. Meta-analysis was conducted to analyse the pooled results of the six included RCTs. Four were at a low RoB, while two were at a high RoB. The meta-analysis showed that BoNT-A as an adjunctive therapy did not significantly decrease pain compared to the sole use of traditional treatment (SDM -0.89; 95% CI -1.91; 0.12; p = 0.08). Caution should be used when interpreting such results, since the studies displayed very high heterogeneity (I = 94%, p < 0.001). The overall certainty of the evidence was very low. The data retrieved from this systematic review do not support the use of BoNT-A as an adjunctive therapy in treating chronic musculoskeletal pain.

The knowledge of the English language is fundamental for the application of evidence-based practice. Hence, this study explores, through an online survey, the (1) perceived and (2) actual level of Scientific English among Italian undergraduate (UGs) and postgraduate (PGs) physiotherapists. As for (1), the participants expressed their agreement with 10 statements regarding the attitude towards Scientific English through a 1-4 Likert-type scale, with consensus set at ≥70%. As for (2), an ad-hoc 10-point questionnaire was developed through a Delphi procedure, with a pass score set at ≥60%. The survey was completed by 421 participants (UG: 47%; PG: 53%). As for (1), consensus was achieved in both groups in 4 out of 10 statements, specifically the ones addressing the capability to fully understand a scientific paper and physiotherapy-specific language in English. As for (2), the mean score reached by both groups was below 60%. The participants who had studied or were studying at a university in southern Italy presented 2.56 [1.54; 4.24] times higher odds to fail the test. New strategies to bridge the gap in the knowledge of Scientific English in Italy should be developed, through the creation of a unique syllabus tailored to the needs of future physiotherapists.