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Abstract Colorectal cancer (CRC) is a devastating disease, ranking as the second leading cause of cancer-related deaths worldwide. Immune checkpoint inhibitors (ICIs) have emerged as promising treatments; however, their efficacy is largely restricted to a subgroup of microsatellite instable (MSI) CRCs. In contrast, microsatellite stable (MSS) CRCs, which account for the majority of cases, exhibit variable and generally weaker response to ICIs, with only a subset demonstrating exceptional responsiveness. Identifying novel cancer-specific tissue (CST) markers predictive of immunotherapy response is crucial for refining patient selection and overcoming treatment resistance. In this study, we developed clinically relevant CRC organoids and autologous immune system interaction platforms to model ICI response. We conducted a comprehensive molecular characterization of both responder and non-responder models, identifying CST markers that predict ICI response. Validation of these findings was performed using an independent cohort of patient specimens through multiplex immunofluorescence. Furthermore, we demonstrated that knocking out a key gene from the identified predictive signature in resistant organoids restored immune sensitivity and induced T-cell-mediated apoptosis. Overall, our results provide novel insights into the mechanisms underlying immunotherapy resistance and suggest new markers for enhancing patient selection. These findings may pave the way for new therapeutic options in MSS patients, potentially broadening the cohort of individuals eligible for immunotherapy.

Abstract The NA48/2 experiment at CERN reports the first observation of the K ± → π 0 π 0 μ ± ν decay based on a sample of 2437 candidates with 15% background contamination collected in 2003–2004. The decay branching ratio in the kinematic region of the squared dilepton mass above 0.03 GeV2/c 4 is measured to be (0.65 ± 0.03) × 10 −6. The extrapolation to the full kinematic space, using a specific model, is found to be (3.45 ± 0.16) × 10 −6, in agreement with chiral perturbation theory predictions.

Abstract Dual‐energy X‐ray computed tomography consists of imaging objects using two incident X‐ray beams of different energy to distinguish the different compounds within a sample based on their density (electron density, ρe) and elemental composition (effective atomic number, Zeff). The stoichiometric calibration for dual‐energy X‐ray computed tomography was already successfully implemented to identify single and homogeneous minerals easily and non‐destructively. It is here applied for the first time to a more complex and heterogeneous sample, a varved sediment core with three distinct facies. The output of dual‐energy X‐ray computed tomography was compared against elemental geochemistry obtained at the same resolution using a micro‐XRF core scanner. The three individual facies can be successfully differentiated using dual‐energy X‐ray computed tomography because their range of ρe and Zeff values allow their discrimination. Correlations with elemental geochemistry are also discussed but are less conclusive, probably because of variations in grain size and porosity, and because these high resolution analyses were not performed at the exact same location. The paper not only eventually discusses the limitations when using dual‐energy X‐ray computed tomography on sediments but also demonstrates its potential to quantitatively study sediment cores in a non‐destructive way.

Colorectal cancer (CRC) is a devastating disease, ranking as the second leading cause of cancer-related deaths worldwide. Immune checkpoint inhibitors (ICIs) have emerged as promising treatments; however, their efficacy is largely restricted to a subgroup of microsatellite instable (MSI) CRCs. In contrast, microsatellite stable (MSS) CRCs, which account for the majority of cases, exhibit variable and generally weaker response to ICIs, with only a subset demonstrating exceptional responsiveness. Identifying novel cancer-specific tissue (CST) markers predictive of immunotherapy response is crucial for refining patient selection and overcoming treatment resistance. In this study, we developed clinically relevant CRC organoids and autologous immune system interaction platforms to model ICI response. We conducted a comprehensive molecular characterization of both responder and non-responder models, identifying CST markers that predict ICI response. Validation of these findings was performed using an independent cohort of patient specimens through multiplex immunofluorescence. Furthermore, we demonstrated that knocking out a key gene from the identified predictive signature in resistant organoids restored immune sensitivity and induced T-cell-mediated apoptosis. Overall, our results provide novel insights into the mechanisms underlying immunotherapy resistance and suggest new markers for enhancing patient selection. These findings may pave the way for new therapeutic options in MSS patients, potentially broadening the cohort of individuals eligible for immunotherapy., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: Informed consent was obtained from all subjects. The experimental protocol was approved by the local ethics committee (Fondazione Policlinico Gemelli IRCCs, Ethical Committee approval Prot. 8711/20) and followed EU regulations., (© 2024. The Author(s).)

A change in implicit behavioural tendencies toward foods may contribute to the maintenance of calorie restriction in Anorexia Nervosa (AN). To test this hypothesis, we assessed approach-avoidance tendencies toward different categories of stimuli using a novel mobile version of the approach-avoidance task (AAT). The sample included 66 patients with restrictive AN and 84 healthy controls, all females. All participants performed the AAT in which they were required to approach or avoid stimuli (high-calorie foods, low-calorie foods, and neutral objects) by respectively pulling their phone towards themselves of pushing it away. Both the response time and the force of each movement were collected by means of the smartphone's accelerometer. The results revealed that patients with AN had a reduced tendency to approach food stimuli compared to healthy controls, who instead presented faster and stronger movements in approaching rather than avoiding foods as compared to neutral objects. This finding was particularly pronounced in patients with greater levels of malnutrition. No differences were instead observed comparing high-calorie and low-calorie foods. The observed reduction in the natural tendency to approach food stimuli is consistent with patients' eating behaviour and may contribute to the maintenance of calorie restriction, thus representing a possible target for novel therapeutic approaches., Competing Interests: Declaration of competing interest The authors have no competing financial interests to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: Head and neck cancer surgery often requires postoperative monitoring in an intensive care unit (ICU) or intermediate care unit (IMC). With a variety of different risk scores, it is incumbent upon the investigator to plan a risk-adapted allocation of resources. Tumor surgery in the head and neck region itself offers a wide range of procedures in terms of resection extent and reconstruction methods, which can be stratified only vaguely by a cross-disciplinary score. Facing a variety of different risk scores we aimed to develop a new Tumor Risk Score (TRS) enabling anterograde preoperative risk evaluation, resource allocation and optimization of cost and outcome measurements in tumor surgery of the head and neck., Methods: A collective of 547 patients (2010-2021) with intraoral tumors was studied to develop the TRS by grading the preoperative tumor size and location as well as the invasiveness of the planned surgery by means of statistical modeling. Two postoperative complications were defined: (1) prolonged postoperative stay in IMC/ICU and (2) prolonged total length of stay (LOS). Each parameter was analyzed using TRS and all preoperative patient parameters (age, sex, preoperative hemoglobin, body-mass-index, preexisting medical conditions) using predictive modeling design. Established risk scores (Charlson Comorbidity Index (CCI), American Society of Anesthesiologists risk classification (ASA), Functional Comorbidity Index (FCI)) and Patient Clinical Complexity Level (PCCL) were used as benchmarks for model performance of the TRS., Results: The TRS is significantly correlated with surgery duration (p < 0.001) and LOS (p = 0.001). With every increase in TRS, LOS rises by 9.3% (95%CI 4.7-13.9; p < 0.001) or 1.9 days (95%CI 1.0-2.8; p < 0.001), respectively. For each increase in TRS, the LOS in IMC/ICU wards increases by 0.33 days (95%CI 0.12-0.54; p = 0.002), and the probability of an overall prolonged IMC/ICU stay increased by 32.3% per TRS class (p < 0.001). Exceeding the planned IMC/ICU LOS, overall LOS increased by 7.7 days (95%CI 5.35-10.08; p < 0.001) and increases the likelihood of also exceeding the upper limit LOS by 70.1% (95%CI 1.02-2.85; p = 0.041). In terms of predictive power of a prolonged IMC/ICU stay, the TRS performs better than previously established risk scores such as ASA or CCI (p = 0.031)., Conclusion: The lack of a standardized needs assessment can lead to both under- and overutilization of the IMC/ICU and therefore increased costs and losses in total revenue. Our index helps to stratify the risk of a prolonged IMC/ICU stay preoperatively and to adjust resource allocation in major head and neck tumor surgery., (© 2024. The Author(s).)

Regular physical activity is associated with healthier brains and improved cognition among older adults. Yet, the impact of a short bout of exercise on older adults' cognition still is not fully clarified. The present study explored the effects of 20 min of moderate-intensity aerobic exercise (on a cycle ergometer) on cognition. Forty-eight healthy older adults were randomly assigned to an exercise or a control group and completed four cognitive tests: Affective Go/No-Go (AGN), Simple Reaction Time (SRT), Spatial Working Memory (SWM) and a Backward Counting task. Tests were administered prior to and immediately after 20 min of cycling (exercise group) or rest (control group). Mixed-design 2 × 2 ANOVAs indicated a significant interaction of Group x Session, for commission errors on the positive valence of the Affective Go/No-go task, indicating that the exercise group performed better on one aspect of this inhibition test after cycling (p = 0.004), while the control group's performance declined after rest. A similar pattern was found for the SWM, with the exercise group showing a significantly better performance after the exercise both for total error (p = 0.027) and the strategy (p = 0.002), while no improvement was observed after rest (controls). The study suggests that inhibitory control functions and working memory may be improved by a single relatively short bout of moderate exercise. However, the null effects of exercise on the other cognitive measures indicate that the neurocognitive benefits of acute exercise for older adults may be selectively sensitive to exercise parameters and to specific aspects of cognition., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background/Objectives : Anorexia nervosa (AN) has a high mortality rate frequently related to suicidality; however, there are few studies on suicide attempts (SAs) and non-suicidal self-injuries (NSSIs) in adult inpatients with AN. This study aims to describe SA and NSSI prevalence and related clinical and sociodemographic factors in adult inpatients with AN. Methods : We retrospectively analyzed data on 298 inpatients hospitalized between 2014 and 2023. Suicidality and clinical and sociodemographic data were collected by experienced psychiatrists; then, the patients completed a battery of self-report questionnaires investigating eating-related and general psychopathology. Results : A total of 9.7% of the inpatients reported an SA in their lifetime, and 13.4% reported NSSI. The percentages were lower among patients with restricter-type AN (5.6% SA and 6.6% NSSI) and higher among patients with binge-purging AN (18% SA and 27% NSSI). SAs were associated with unemployment, binge-purging AN, personality disorders, and lifetime sexual abuse; NSSIs were correlated with family psychiatric disorders, binge-purging AN, personality disorders, body dissatisfaction, restriction, and eating-related concerns. No differences emerged in the frequency of reported suicidality between patients tested before and after the COVID-19 pandemic. Conclusions : Suicidality is a relevant issue in AN. Many factors in the history of the patients and their eating-related pathologies should be considered as potentially associated with SA and NSSI and carefully assessed.

Summary: The aim of this contribution was to highlight the "favorable" and "unfavorable" roles of domestic and non-domestic animals on airway sensitization processes and on the type/severity of the clinical symptoms induced by their exposure. We performed a literature research in MEDLINE for allergic manifestations and animals. Pets can be "allergy friends" through mechanisms related to hygiene hypothesis and translational aspects, the dual role of IgG4 antibodies for pets, and their promising role as healthcare service animals (dogs). On the contrary, animals can be "allergy enemies" when inducing allergic sensitization and  respiratory symptoms (sometimes leading to severe reactions), and also due to cross reactivity with other pets allergens, indirect exposure and ubiquity of their allergens, cross reactivity between Can f 5 and human prostate-specific antigen (PSA). Moreover, in some cases they can trigger anaphylaxis, induce occupational asthma, and act as pests. Finally, we must outline the modest efficacy of allergen immunotherapy (AIT) for their allergens. From a strictly allergological perspective, it is evident that the "negative" aspects resulting from exposure to domestic / non-domestic animals outweigh the "positive" aspects. As a consequence, it is up to humans to seek new ways to balance the pros and cons by exploring research areas that can allow the best possible coexistence with subjects at risk of allergy with domestic and non-domestic animals.

Objectives: To investigate seasonality, epidemiologic characteristics, and clinical severity variations of respiratory syncytial virus (RSV)-associated hospitalizations following the easing of COVID-19 restrictions in Tuscany, Italy, up to the 2022-2023 season., Methods: From 2017 to 2023, a dynamic cohort consisting of all resident children aged ≤2 years was followed up in regional registries. The person-time incidence rate of RSV-associated hospitalizations per 1,000 person-years and risk of severe hospitalization (intensive care unit, continuous positive airway pressure, or mechanical ventilation) per 100 RSV hospitalizations were calculated. RSV seasonality was investigated with retrospective methods., Results: A total of 193,244 children were followed up. After the easing of restrictions, RSV epidemics showed earlier seasonality and shorter duration compared with pre-pandemic (2017 to 2019), with this deviation decreased in 2022-2023. In 2021-2022 and 2022-2023, the incidence rate of RSV-associated hospitalizations significantly increased compared with pre-pandemic (2022-2023 risk ratio 3.6, 95% confidence interval 3.3-4.0), with larger increases among older age groups. Among hospitalized children, only those aged ≥12 months showed an increased risk of severe hospitalization, particularly during 2021-2022 (risk ratio 4.7, 95% confidence interval 1.5-24.3)., Conclusions: Our findings suggest a gradual return of RSV epidemics to the pre-pandemic pattern, although relevant increases in disease incidence persist. Reduced regular RSV exposure among older children may lead to declining immunity and increased severe outcome risks., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Telerehabilitation has been suggested to be equally effective than in-person rehabilitation, and could be helpful to increase participation and reduce barriers. People with multiple sclerosis (MS) often present urogenital dysfunctions, impairing independence and quality of life (QoL). Since the different available telerehabilitation protocols, the present study aimed to compare a live video urogenital rehabilitation intervention protocol (REMOTE) with a home-based pre-recorded video protocol (SELF). A randomized-controlled trial was performed, with 14 females with MS being allocated in the REMOTE group (36 ± 9 y) and 14 females in the SELF group (37 ± 7 y). Both telerehabilitation protocols were identical in terms of contents (including pelvic floor training and relaxation exercises), frequency and duration, consisting of 10 sessions of 45 min each, every 5 days. Questionnaires were administered at the beginning and the end of the study: Short Form Health Survey 36 (SF-36), Beck Depression Inventory (BDI), Female Sexual Function Index (FSFI), International Consultation on Incontinence Questionnaire (ICIQ) symptoms and related QoL, the main outcome being ICIQ incontinence score. Despite most of the outcomes improved in both groups, REMOTE was found to be more effective than SELF in most of the SF-36 domains (from p < 0.001 pη 2 0.555 to p = 0.044 pη 2 0.147), FSFI (p = 0.001 pη 2 0.373), ICIQ (p = 0.003 pη 2 0.291). Despite the home-based pre-recorded videos could be effective in improving urogenital symptoms, live video urogenital rehabilitation results in larger improvements. Telerehabilitation should be encouraged for urogenital dysfunctions in females with MS, and pre-recorded videos could represent an alternative when live sessions are not available. Clinical trial registration This randomized controlled trial was registered on ClinicalTrials.gov with the number NCT05984095., (© 2024. The Author(s).)

Autophagy is a biological process that facilitates the degradation and removal of damaged structures and macromolecules. In neoplasms, autophagy has been proposed to play a dual role, functioning either as a tumor promoter or a tumor suppressor. To date, no comprehensive analysis of autophagy, primarily through immunohistochemical investigation of autophagy-related proteins (ATGs), has been conducted in chordomas (CHs), which are rare bone tumors that arise from remnants of the notochord. The present study aimed to investigate the immunoexpression of several ATGs, including microtubule-associated protein 1 light chain 3 (LC3A/B), Sequestosome-1 (p62) and autophagy and Beclin 1 regulator 1 (AMBRA-1) in a series of sporadic adult conventional clival CHs collected from a single neuropathological center in southern Italy. Immunohistochemical analysis revealed that LC3A/B, p62 and AMBRA-1 were exclusively found in neoplastic cells, with no expression detected in the surrounding stromal cells. Both LC3A/B and p62 were expressed in the cytoplasm and nucleus of neoplastic cells, while AMBRA-1 was predominantly localized in the cytoplasm. In all cases of CHs, p62 was consistently and highly expressed, whereas a similarly high expression of LC3A/B was observed in five cases, four of which were characterized by neoplastic recurrence and partial resection. Low immunoreactivity was noted in seven out of 10 cases (70%), while three recurrent cases exhibited high levels of AMBRA-1 immunostaining. Statistical analysis using Fisher's exact test revealed significant P-values for LC3A/B (P=0.048), AMBRA-1 (P=0.033), Ki-67 (P=0.048) and surgical treatment (P=0.048). Consequently, a negative prognostic role for these two ATGs may be hypothesized in the development of CHs., Competing Interests: No competing interests have been declared., (Copyright © 2024, Spandidos Publications.)

Objective: Axitinib is a tyrosine kinase inhibitor characterized by a strong affinity for Vascular Endothelial Growth Factor Receptors (VEGFRs). It was approved in 2012 by Food and Drug Administration and European Medicines Agency as a second line treatment for advanced renal cell carcinoma and is currently under evaluation in clinical trial for the treatment of other cancers. Glioblastoma IDH-wild type (GBM) is a highly malignant brain tumor characterized by diffusely infiltrative growth pattern and by a prominent neo-angiogenesis. In GBM, axitinib has demonstrated a limited effectiveness as a monotherapy, while it was recently shown to significantly improve its efficacy in combination treatments. In preclinical models, axitinib has been reported to trigger cellular senescence both in tumor as well as in normal cells, through a mechanism involving intracellular reactive oxygen species (ROS) accumulation and activation of Ataxia Telangiectasia Mutated kinase (ATM). Limiting axitinib-dependent ROS increase by antioxidants prevents senescence specifically in normal cells, without affecting tumor cells., Methods: We used brain tumor xenografts obtained by engrafting Glioma Stem Cells (GSCs) into the brain of immunocompromised mice, to investigate the hypothesis that the antioxidant molecule N-Acetyl-L-Cysteine (NAC) might be used to reduce senescence-associated adverse effects of axitinib treatment without altering its anti-tumor activity., Results: We demonstrate that the use of the antioxidant molecule N-Acetyl-Cysteine (NAC) in combination with axitinib stabilizes tumor microvessels in GBM tumor orthotopic xenografts, eventually resulting in vessel normalization, and protects liver vasculature from axitinib-dependent toxicity., Conclusion: Overall, we found that NAC co-treatment allows vessel normalization in brain tumor vessels and exerts a protective effect on liver vasculature, therefore minimizing axitinib-dependent toxicity., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

The melanocortin receptor 4 (MC4R) belongs to the melanocortin receptor family of G-protein coupled receptors and is a key switch in the leptin-melanocortin molecular axis that controls hunger and satiety. Brain-produced hormones such as α-melanocyte-stimulating hormone (agonist) and agouti-related peptide (inverse agonist) regulate the molecular communication of the MC4R axis but are promiscuous for melanocortin receptor subtypes and induce a wide array of biological effects. Here, we use a chimeric construct of conformation-selective, nanobody-based binding domain (a ConfoBody Cb80) and active state-stabilized MC4R-β2AR hybrid for efficient de novo discovery of a sequence diverse panel of MC4R-specific, potent and full agonistic nanobodies. We solve the active state MC4R structure in complex with the full agonistic nanobody pN162 at 3.4 Å resolution. The structure shows a distinct interaction with pN162 binding deeply in the orthosteric pocket. MC4R peptide agonists, such as the marketed setmelanotide, lack receptor selectivity and show off-target effects. In contrast, the agonistic nanobody is highly specific and hence can be a more suitable agent for anti-obesity therapeutic intervention via MC4R., (© 2024. The Author(s).)

Heart failure (HF) remains a critical global health challenge, necessitating advancements in diagnostic and therapeutic strategies. This review explores the evolution of imaging technologies and their impact on HF management, focusing on three-dimensional echocardiography (3DE), myocardial strain imaging, and vortex dynamics imaging. Three-dimensional echocardiography enhances traditional echocardiography by providing more accurate assessments of cardiac structures, while myocardial strain imaging offers the early detection of subclinical myocardial dysfunction, crucial in conditions such as chemotherapy-induced cardiotoxicity and ischemic heart disease. Vortex dynamics imaging, a novel technique, provides insights into intracardiac flow patterns, aiding in the evaluation of left ventricular function, valve diseases, and congenital heart anomalies. The integration of these advanced imaging modalities into clinical practice facilitates personalized treatment strategies, enabling the earlier diagnosis and more precise monitoring of disease progression. The ongoing refinement of these imaging techniques holds promise for improving patient outcomes and advancing the field of precision medicine in HF care.

Thyroid nodules are a common, benign condition with a higher prevalence in women, individuals with iodine deficiency, and radiation exposure. Treatment options for benign thyroid nodules include pharmaceutical therapy, thyroidectomy, and thermal ablation (TA). TA, including laser ablation (LA), radiofrequency ablation (RFA), and microwave ablation (MWA), is a procedure that uses heat to cause tissue necrosis. It is commonly used for large, firm, benign, non-functioning thyroid nodules that cause severe symptoms or pain when surgery is not recommended or desired. When thyroid nodules do not respond to TA, they undergo surgery to resolve the symptoms and clarify the diagnosis. This study aims to analyze the histological alterations found in surgically excised TA-treated thyroid nodules and to evaluate the morphological criteria of differential diagnosis between benign and malignant nodules, establishing whether the alterations observed on the histological sample are a consequence of TA or indicative of neoplastic disease. For this purpose, the adoption of ancillary methods, such as immunohistochemistry, is fundamental to distinguish the artifacts induced by TA from the typical morphological characteristics of malignant neoplasms.

Aortic stenosis (AS) is the most prevalent valvular heart disease in Europe and North America, with transcatheter aortic valve implantation (TAVI) revolutionizing its management. Hypertrophic left ventricle (HLV) frequently coexists with AS, complicating treatment due to the associated risk of left ventricular outflow tract (LVOT) obstruction, heart failure, and sudden death. A rare but severe post-aortic valve replacement (AVR) complication, termed "suicide left ventricle" (SLV), has emerged, necessitating further study. This report synthesizes current literature on SLV, its pathophysiology, and management strategies, alongside four patient case studies. The patients aged 79-87 years, underwent AVR for symptomatic AS with HLV. Post-AVR, all experienced severe complications, including dynamicLVOT gradients, systolic anterior motion (SAM) of the mitral valve, and severe hypotension, leading to death in two cases. One patient survived following surgical aortic valve replacement (SAVR) with surgical myectomy. One patient survived after TAVI. These cases highlight the critical importance of multidisciplinary Heart Team evaluations and personalized treatment plans in managing SLV. Despite advancements in AVR, SLV remains a complex, life-threatening condition, requiring an exhaustive and multifaceted approach for optimal patient outcomes. This report offers valuable insights into SLV occurrence and management from a clinical perspective.

Background/Objectives: Bladder cancer is a prevalent urinary system malignancy and urinary cytology is widely used for its screening and follow-up. A novel diagnostic tool called Bladder Epicheck ® (BE) is increasingly being used for monitoring the recurrence of non-muscle-invasive bladder cancer (NMIBC). The simultaneous use of BE and urinary cytology can increase the diagnostic performances in the follow-up of bladder neoplasms. Methods: In this multicenter study, we retrospectively evaluated the data of 322 patients in follow-up for a high-grade bladder carcinoma over a six-year period (from January 2018 to March 2024). The diagnostic performances of both cytology and BE and their combination were calculated using histology as gold standard. Results: Recurrences were diagnosed as high-grade urothelial carcinoma NMIBC in 18 cases, low-grade papillary NMIBC in 8 cases, and carcinoma in situ (CIS) in 4 cases. Cytological analysis correctly identified 26 out of 30 carcinomas, while 286 were correctly diagnosed as negative results. BE correctly identified 25 out of 30 carcinomas, 285 were correctly diagnosed as negative results. The combination of BE and urinary cytology correctly identified 29 out of 30 carcinomas, while 289 were correctly diagnosed as negative results. Conclusions: The combination of BE and cytology could be the most effective approach for follow-up diagnosis in patients with high-grade NMIBC, reducing unnecessary invasive procedures.

Background/objectives: The previous literature on purging behavior in eating disorders (EDs) suggests an overall more complicated clinical picture for individuals with this symptomatology. So far, no studies have analyzed the possible differences between the specific types of purging among ED inpatients., Methods: A clinical sample of 302 inpatients with EDs was classified according to no purging behaviors, vomiting, the abuse of laxatives, and both vomiting and the abuse of laxatives. Participants completed the following questionnaires: the Eating Disorder Examination Questionnaire (EDE-Q), Frost Multidimensional Perfectionism Scale (F-MPS), State-Trait Anxiety Inventory (STAI), and Beck Depression Inventory (BDI). Clinical information was collected for each individual., Results: Significant differences in the four groups were evidenced in age ( p < 0.001), years of illness ( p < 0.001), BMI at discharge ( p < 0.001), STAI state anxiety ( p < 0.001), STAI trait anxiety ( p < 0.001), BDI ( p < 0.001), EDE-Q eating concerns ( p < 0.001), EDE-Q shape concerns ( p < 0.001), EDE-Q weight concerns ( p < 0.001), EDE-Q global score ( p < 0.001), and F-MPS parental criticism ( p < 0.001). ED inpatients with purging behaviors were older, had a longer duration of illness, higher parental criticism, and worse general and eating psychopathology. No differences emerged between the specific types of purging behavior., Conclusions: Purging behavior is a marker of severity in EDs independently of the specific type of purging. The appearance of any purging behavior must be regarded as a considerable red flag and be followed by an intensification of the cure.

Mycobacterium chimaera (MC), a member of the Mycobacterium avium complex, can cause infections in patients after open-heart surgery due to contaminated heater-cooler units (HCUs). The transmission route of HCU-related MC infection is non-inhalational, and infection can occur in patients without previously known immune deficiency. Patients may develop endocarditis of the prosthetic valve, infection of the vascular graft, and/or manifestations of disseminated mycobacterial infection (splenomegaly, arthritis, hepatitis, nephritis, myocarditis, etc.). MC infections have serious outcomes (30-50% recurrence rate, 20-67% mortality rate). In 2015, an international outbreak of M. chimaera infections among patients undergoing cardiothoracic surgeries was associated with exposure to contaminated LivaNova 3T HCUs (formerly Stöckert 3T heater-cooler system, London, United Kingdom). In response to the global outbreak, many international agencies have issued directives and recommendations in order to reduce the risk of MC infection in cardiac surgery. Whole-genome sequencing (WGS) technology can be used to describe the global spread and dynamics of MC infections, to characterize local outbreaks, and also to identify sources of infection in hospital settings. In order to minimize the risk of contamination of HCUs and reduce the risk of patient infection, it is imperative that healthcare facilities establish a program of regular cleaning and disinfection maintenance procedures as well as monitoring of the water used and the air in the operating room, in accordance with the manufacturer's procedure.

Trachoma is one of the oldest known causes of blindness in humans and it is caused by the intracellular Gram-negative bacterium Chlamydia trachomatis serovars A, B, Ba and C. Its transmission has historically been related to poorness, overcrowded housing and scarce hygiene. We have traced the history of trachoma in Italy in the 19th and 20th centuries, among people living in Italy, those who immigrated to America and the population in the colonies, with a focus on Libya (1912-1943). Trachoma knowledge and perception in Italy and in its colonies was ambiguous during the 19th and 20th centuries. Trachoma was responsible for a great morbidity on both sides of the Mediterranean, in Italy as well as in Libya. Trachoma is still one of the leading infectious causes of preventable blindness worldwide and it was widespread in Italy and the Italian colonies in the first half of the last century.

Introduction: The article aims to outline the features of the efforts for smallpox eradication within the pre-unitary context of the Kingdom of Sardinia, characterized by a long tradition in medical-health prevention. This tradition is partly inherited from the health magistracies of the Italian states during the ancient regime and partly adopted from policies initially outlined by Napoleon and later by other European states. In addition to prevention activities, authorities also engage in a vigorous information and awareness campaign aimed at eliminating common prejudices and doubts about vaccination among the population., Methods: In analyzing the authorities' achievements in combating smallpox, this study examines the two epidemic waves (1829-30 and 1852-54), along with the legislative developments before, during, and after these periods. It also compares these regulatory changes with those in other European contexts., Discussion: The epidemiological situation turned out to be more complex to manage than the authorities had anticipated, as evidenced by the increasing controls imposed. Scientific and political communities, both in the Kingdom of Sardinia and in other European nations, found themselves divided on the legitimacy of proposing restrictive measures by the state. Some advocated for restricted access to public places and imposed mandatory vaccination for vulnerable individuals., Conclusions: The comparison with smallpox resulted in a gradual improvement in of health security levels, although vaccination coverage did not reach the desired targets. Several factors contributed to this failure, including the limited expertise and reluctance of medical personnel, who were burdened with much of the operation's costs. Additionally, particularly in rural areas, there was widespread mistrust among the population towards doctors. Despite these challenges, the fight against smallpox enabled authorities to develop population control tools in the name of public health protection. However, it was not until 1888 that mandatory vaccination was introduced., 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., (©2024 Pacini Editore SRL, Pisa, Italy.)

A hundred years ago, Achille Sclavo (1861-1930) published his book entitled "Per la Propaganda igienica. Scuola e Igiene" (The Propagation of Hygiene. Schools and Hygiene) which he dedicated "To elementary teachers, from whom Italy expects the most effective propaganda in favor of hygiene". The words of the dedication were profoundly felt by Sclavo and reveal a precise choice by the great hygienist. Sclavo was then at an advanced age and had devoted his whole life to studying hygiene and disseminating its basic concepts, to promote a healthier life for all. Nowadays, Sclavo's book "The Propagation of Hygiene. Schools and Hygiene" still remains an important statement to the commitment of the great hygienist to spreading a culture of hygiene, and public health in Italy. This was a commitment that Sclavo clearly felt throughout his life, as a teacher, as a scholar, as the entrepreneur who founded the Serotherapy and Vaccinogenic Institute in 1904, and mainly as a policymaker who spoke to all citizens, especially young people., 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., (©2024 Pacini Editore SRL, Pisa, Italy.)

Diagnostic accuracy of arteriovenous malformations (AVMs) is imperative for delineating management. The current standard is digital subtraction angiography (DSA). Arterial spin labeling (ASL) is an understudied noninvasive, non-contrast technique that allows angioarchitecture visualization and additionally quantifies cortical and AVM cerebral blood flow and hemodynamics. This meta-analysis aims to compare ASL and DSA imaging in detecting and characterizing cerebral AVMs. EMBASE, Medline, Scopus, and Cochrane databases were queried from inception to July 2022 for reports of AVMs evaluated by DSA and ASL imaging. Fourteen studies with 278 patients evaluated using DSA and ASL imaging prior to intervention were included; pCASL in 11 studies (n = 239, 85.37%) and PASL in three studies (n = 41, 14.64%). The overall AVM detection rate on ASL was 99% (CI 97-100%); subgroup analysis revealed no difference between pCASL vs. PASL (99%; CI 96-100% vs. 100%; CI 95-100% respectively, p = 0.42). The correlation value comparing ASL and DSA nidus size was 0.99. DSA and ASL intermodality agreement Cohen's k factor for Spetzler Martin Grading (SMG) was reported at a median of 0.98 (IQR 0.73-0.1), with a 1.0 agreement on SMG classification. A median of 25 arteries were detected by DSA (IQR 14.5-27), vs. 25 by ASL (IQR 14.5-27.5) at a median 0.92 k factor. ASL provides angioarchitectural visualization noninferior to DSA and additionally quantifies CBF. Our study suggests that ASL should be considered in the detection of AVMs, especially in patients with contrast contraindications or apprehension towards an invasive assessment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Abstract: Peyronie's disease (PD) presents a multifaceted challenge in contemporary urological practice, marked by penile deformity, pain, and the potential for erectile dysfunction. We meticulously explored the existing literature of intralesional/topical interventions, aiming to provide clinicians with a nuanced understanding of available options for comprehensive PD management. To conduct this review, we performed a systematic search using the PubMed, Scopus, and ScienceDirect databases, including the keywords of combination of the "Peyronie's disease/plastic induration of the penis (PIP) and intralesional/topical treatments". The study selection was based on adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, resulting in the inclusion of 16 articles. We delve into the effectiveness and safety profiles of collagenase Clostridium histolyticum (CCH), interferon, platelet-rich plasma (PRP), hyaluronic acid, botulinum toxin, stem cell, extracorporeal shock wave therapy (ESWT), and traction therapy, assessing their impact on penile curvature, length improvement, and patient-reported symptoms and outcomes. The best options evaluated are intralesional injections of CCH and penile traction devices, alone or in combination. Despite PD remains a challenge for urologists, the objective of this review is to contribute to the evolving landscape of PD management, fostering informed decision-making, and personalized care for individuals grappling with this challenging condition., (Copyright © 2024 Copyright: ©The Author(s)(2024).)

Among autophagic-related proteins, p62/SQSTM1/Sequestosome-1 represents a relevant actor in cellular proliferation and neoplastic growth. Although, recently, p62 expression has been analyzed in different neurodegenerative and glial neoplastic diseases, no available information have been reported in meningiomas, which have an high epidemiological relevance being the second most common category of intracranial tumors after gliomas. Generally meningiomas have a benign behavior, but their recurrence is not uncommon mainly when atypical or anaplastic varieties occur. However, intranuclear vacuoles have been ultrastructurally observed in meningiomas, and they were labelled by p62 antibodies. Therefore, in the present study, we have investigated p62 immunohistochemical pattern in a cohort of 133 cases representative of low- and high-grade meningiomas, to verify if p62 expression may be related to clinicopathological data, thus achieving a potential prognostic role. The p62 immunoexpression was frequently found in the nucleus and cytoplasm of neoplastic elements, and utilizing an intensity-distribution score, 55 (41.3%) cases were considered as high expressors while 78 (58.7%) cases were instead recorded as low expressors. Fifteen cases exhibited recurrences of the disease, 14 of which were codified as high expressors. Moreover, a direct relationship between p62 and Mib-1 immunoexpression as well as between p62 and neoplastic grade have been documented. Finally, we suggest that impaired autophagic flux with an increase in p62 expression may be involved in the activation of NRF2 also contributing in the development of recurrence in meningioma patients., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Antonio Ieni et al.)

Objective: The uPath PD-L1 (SP263) is an AI-based platform designed to aid pathologists in identifying and quantifying PD-L1 positive tumor cells in non-small cell lung cancer (NSCLC) samples stained with the SP263 assay., Methods: In this preliminary study, we explored the diagnostic performance of the uPath PD-L1 algorithm in defining PD-L1 tumor proportion score (TPS) and predict clinical outcomes in a series of patients with advanced stage NSCLC treated with single agent PD-1/PD-L1 checkpoint blockade previously assessed with the SP263 assay in clinical practice., Results: 44 patients treated from August 2015 to January 2019 were included, with baseline PD-L1 TPS of ≥ 50%, 1-49% and < 1% in 38.6%, 25.0% and 36.4%, respectively. The median uPath PD-L1 score was 6 with a significant correlation with the baseline PD-L1 TPS (r: 0.83, p < 0.01). However, only 27 cases (61.4%) were scored within the same clinically relevant range of expression (≥ vs < 50%). In the study population the baseline PD-L1 TPS was not significantly associated with clinical outcomes, while the uPath PD-L1 score showed a good diagnostic ability for the risk of death at the ROC curve analysis [AUC: 0.81 (95%CI: 0.66-0.91), optimal cut-off of ≥ 3.2], resulting in 19 patients (43.2%) being u-Path low and 25 patients (56.8%) being uPath high. The objective response rate in uPath high and low was 51.6% and 25.0% (p = 0.1), respectively, although the uPath was significantly associated with overall survival (OS, HR 2.45, 95%CI: 1.19-5.05) and progression free survival (PFS, HR 3.04, 95%CI: 1.51-6.14). At the inverse probability of treatment weighting analysis used to balance baseline covariates, the uPath categories confirmed to be independently associated with OS and PFS., Conclusions: This preliminary analysis suggests that AI-based, digital pathology tools such as uPath PD-L1 (SP263) can be used to optimize already available biomarkers for immune-oncology treatment in patients with NSCLC., (Copyright © 2024 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)

The main aim of this study was to investigate the efficacy of a dual task protocol in people with episodic migraine with respect to both active exercises only and cognitive task only treatments, concerning some neurophysiological and clinical outcomes. A randomized control trial was adopted in people with episodic migraine without aura. Some neurophysiological and clinical outcomes were collected (t0): resting motor threshold (rMT), short intracortical inhibition (SICI) and facilitation (ICF), pressure pain threshold (PPT), trail making test (TMT), frontal assessment battery (FAB), headache-related disability (MIDAS) and headache parameters. Then, participants were randomized into three groups: active exercise only (n = 10), cognitive task only (n = 10) and dual task protocol (n = 10). After 3 months of each treatment and after 1-month follow-up the same neurophysiological and clinical outcomes were revaluated. A significant time x group effect was only found for the trapezius muscle (p = 0.012, pη2 = 0.210), suggesting that PPT increased significantly only in active exercise and dual task protocol groups. A significant time effect was found for rMT (p < 0.001, pη2 = 0.473), MIDAS (p < 0.001, pη2 = 0.426), TMT (p < 0.001, pη2 = 0.338) and FAB (p < 0.001, pη2 = 0.462). A repeated measures ANOVA for SICI at 3 ms highlighted a statistically significant time effect for the dual task group (p < 0.001, pη2 = 0.629), but not for the active exercises group (p = 0.565, pη2 = 0.061), and for the cognitive training (p = 0.357, pη2 = 0.108). The dual task protocol seems to have a more evident effect on both habituation and sensitization outcomes than the two monotherapies taken alone in people with migraine., (© 2024. The Author(s).)

Background: Central and peripheral sensitization are characterized by widespread hyperalgesia that is manifested by larger pain extent area and reduction in pressure pain threshold (PPT). PPT decreases in patients with migraine not only over the trigeminal cervical complex but also throughout the body., Methods: A cross-sectional study was adopted to assess the local and widespread hyperalgesia in chronic and episodic migraine patients respect to healthy controls. The guidelines of Andersen's were used to evaluate the PPT bilaterally over 3 muscles in the trigemino-cervical complex (temporalis, sub-occipitalis, trapezius) and over 1 muscle far from this area (tensor fasciae latae)., Results: Thirty subjects with episodic migraine (35.8 ± 2.82 years), 30 with chronic migraine (53.03 ± 19.79 years), and 30 healthy controls (29.06 ± 14.03 years) were enrolled. The interaction effect was present for the trapezius muscle with a significant difference between the right and the left side in episodic group (p = 0.003). A group effect was highlighted in all four muscles analyzed such as suboccipital (p < 0.001), temporalis (p > 0.001), trapezius (p < 0.001), and TFL (p < 0.001). PPT was usually higher in the control group than in the episodic group which in turn was characterized by higher PPT values than the chronic group., Conclusions: People with chronic and episodic migraine presented lower PPT than healthy controls both in the trigeminal and in the extra-trigeminal area. People with chronic migraine presented lower PPT than episodic migraine only in the trigeminal area. Temporalis and sub-occipitalis are the most sensitive muscles in people with chronic and episodic migraine., (© 2024. The Author(s).)

Arrhythmogenic Cardiomyopathy (AC), an inherited cardiac disorder characterized by myocardial fibrofatty replacement, carries a significant risk of sudden cardiac death (SCD) due to ventricular arrhythmias. A comprehensive multimodality imaging approach, including echocardiography, cardiac magnetic resonance imaging (CMR), and cardiac computed tomography (CCT), allows for accurate diagnosis, effective risk stratification, vigilant monitoring, and appropriate intervention, leading to improved patient outcomes and the prevention of SCD. Echocardiography is primary tool ventricular morphology and function assessment, CMR provides detailed visualization, CCT is essential in early stages for excluding congenital anomalies and coronary artery disease. Echocardiography is preferred for follow-up, with CMR capturing changes over time. The strategic use of these imaging methods aids in confirming AC, differentiating it from other conditions, tracking its progression, managing complications, and addressing end-stage scenarios., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Insect stings can cause large local reactions (LLRs) that are IgE-mediated and associated with considerable morbidity. A risk for systemic reactions including anaphylaxis to subsequent stings has been reported and is often noted by patients and health care providers. Guidelines do not recommend venom immunotherapy (VIT) for LLRs based on the relatively low risk of anaphylaxis, but this is debated in this review. On the pro side: the risk of anaphylaxis may be higher than reported in the limited literature, especially in patients who had only 1 LLR; new species with more potent stings are spreading into new areas; the quality of life can be markedly impaired by LLRs; and VIT is generally safe and highly effective. On the con side: LLRs are benign, stings occur infrequently, VIT has significant cost, systemic reactions occur more often to VIT than to stings in patients with LLRs, and Food and Drug Administration approval and published guidelines do not recommend VIT for LLRs. In practice, shared decision-making is appropriate to incorporate knowledge of the natural history and known high-risk factors in the context of the patient's personal values and preferences., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

In the evaluation of cardiomyopathies, cardiac computed tomography (CCT) is predominantly used for assessing congenital or acquired coronary artery diseases as a potential etiology underlying the observed myocardial abnormalities. However, its utility is expected to expand. We present a case of an asymptomatic patient with claustrophobia who sought medical attention due to frequent ventricular beats. The resting electrocardiogram revealed repolarization abnormalities characterized by flattened T-waves in the lateral leads and low QRS voltages in the peripheral leads, whereas transthoracic echocardiography was normal. CCT accurately identified hypodense areas indicative of fibrofatty infiltration within the inferolateral and anterior walls of the left ventricle. Furthermore, late iodine contrast-phase imaging revealed subepicardial late enhancement striae in the same regions. These imaging findings were pivotal in establishing a diagnosis of left-dominant arrhythmogenic cardiomyopathy. This clinical vignette underscores the potential of CCT in tissue characterization, particularly when cardiac magnetic resonance imaging is contraindicated or unavailable., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Cardiovascular Echography.)

Objectives: This study investigates peripersonal space (PPS) modulation in patients with anorexia nervosa (AN) versus healthy controls (HCs) and explores associations between PPS, eating-related, and general psychopathology., Method: Forty-six patients and 42 HCs completed a computer-based task observing videos of an approaching actor (male or female) displaying different facial expressions along with a non-social condition. Then, participants completed self-report questionnaires assessing eating-related and general psychopathology., Results: Mixed-models revealed that both groups adjusted PPS based on task conditions, with a gender effect favoring closer proximity to female actor. HCs reduced PPS amplitude progressively during the task, while patients did not show this effect. In patients, wider PPS correlated with lower self-esteem and facial expression identification accuracy, while in HCs, PPS was associated to body dissatisfaction and anxiety symptoms., Conclusion: These findings enhance understanding of bodily self-consciousness, suggesting PPS consideration in therapeutic interactions with patients with AN and as a potential target in treatments addressing social impairment., Competing Interests: The authors have no conflict of interests to declare., (© 2024 The Authors. Published by Elsevier B.V.)

Summary: Dogs and cats are the most common pets worldwide. In Italy, the prevalence of allergic sensitization to cats and dogs is 16% and 9% respectively. The limited standardization of allergenic extracts, especially for dogs, emphasizes the importance of Component Resolved Diagnosis (CRD) for accurate diagnosis and subsequent prescription of allergen immunotherapy (AIT). However, this low standardization is the main factor contributing to the unsatisfactory clinical efficacy of traditional AIT, AIT with modified allergens, and intralymphatic allergen-specific immunotherapy (ILAIT). Emerging immunological approaches, particularly for controlling the primary cat allergen, show promise but are hindered by high costs (e.g., use of anti-Fel d 1 monoclonal antibodies in humans) or by exclusively targeting Fel d 1 produced by one's own animal (e.g., immunizing cats to induce neutralizing antibodies against Fel d 1 or including an egg product with anti Fel d 1 IgY antibodies in feline diet). Further studies are imperative for standardizing pet allergens, enhancing the efficacy of various AIT modalities, and exploring other immunological approaches, to optimize the relationship between pets and their owners and prevent distressing "forced removals".

Context: Shoulder muscles are active during front-crawl swimming to provide propulsion and stabilize the glenohumeral and scapulothoracic joints. Researchers have proposed that fatigue might contribute to altered activation of these muscles and represent a risk factor for injuries. Tensiomyography (TMG) might function as a noninvasive tool to detect changes in contractile measures of the skeletal muscles due to exercise-induced neuromuscular fatigue, though it has not yet been used in the shoulder muscles of swimmers., Objective: To assess the effects of a fatiguing swimming protocol on shoulder muscle TMG measures and isometric strength in competitive swimmers., Design: Cross-sectional study., Setting: Swimming pool facility., Patients or Other Participants: A total of 14 young front-crawl competitive swimmers (11 males and 3 females; age = 21 ± 3 years [range, 17-26 years], height = 1.78 ± 0.06 m, mass = 73.1 ± 9.2 kg)., Main Outcome Measure(s): Participants completed TMG and isometric strength assessments before and after 30-minute, high-intensity swim training. The TMG assessment was performed on 7 muscles of the shoulder according to front-crawl biomechanics and the applicability of the technique to obtain data, such as time to contraction and muscle-belly radial displacement. Isometric strength was assessed using a digital handheld dynamometer during shoulder flexion, extension, external rotation, and internal rotation., Results: Fatigue induced a smaller radial displacement, mostly observable in latissimus dorsi (-1.0 mm; 95% CI = -1.7, -0.3 mm; P = .007) and pectoralis major muscles (-1.4 mm; 95% CI = -2.4, -0.4 mm; P = .007). Only shoulder extension showed an isometric strength reduction after the fatiguing protocol (-0.03 N/kg; 95% CI = -0.05, -0.01 N/kg; F1,13 = 4.936; P = .045; ηp2 = 0.275)., Conclusions: This study provides preliminary evidence for the usefulness of TMG to detect fatigue-induced changes in contractile properties of the shoulder muscles in swimmers, in particular the latissimus dorsi and pectoralis major., (© by the National Athletic Trainers’ Association, Inc.)

The management of advanced bladder carcinoma involves a multidisciplinary approach, but the prognosis remains poor for many patients. The immune system plays a crucial role in this disease, influencing both tumor development and response to treatment, and exploiting the immune system against the tumor can be a valuable strategy to destroy neoplastic cells. This is the biological principle underlying Bacillus Calmette-Guérin (BCG) use and, more recently, immune checkpoint inhibitors (ICIs), like PD-1 (programmed death-1)/PD-L1 (programmed death-ligand 1) inhibitors. In fact, one of the best studied immune checkpoints is represented by the PD-1/PD-L1 axis, which is a well-known immune escape system adopted by neoplastic bladder cells. PD-L1 expression has been associated with a higher pathologic stage and has shown prognostic value in bladder carcinoma. Interestingly, high-grade bladder cancers tend to express higher levels of PD-1 and PD-L1, suggesting a potential role of such an axis in mediating disease progression. Immunotherapy with PD-1 and PD-L1 inhibitors has therefore emerged as a valuable treatment option and has shown efficacy in advanced bladder cancer patients, with high PD-L1 expression levels associated with better treatment responses. Our review aims to provide a comprehensive overview of the role of PD-L1 in advanced bladder cancer, focusing on its implications for treatment decisions and the prediction of treatment response. Overall, our work aims to contribute to the understanding of PD-L1 as a predictive biomarker and highlight its role in shaping therapeutic approaches for advanced bladder cancer.

Cold water immersion (CWI) and percussive massage therapy (PMT) are commonly used recovery techniques in team sports. In particular, despite its wide use, PMT has been scarcely investigated in the literature, especially regarding neuromuscular measures and in comparison with other techniques. This study aimed to evaluate and compare the acute and short-term effects (24 h) of CWI and PMT on muscle strength, contractile properties, and soreness after exercise. A randomized crossover study was performed on sixteen male soccer players (22 years, 20-27) who participated in three experimental sessions involving a fatiguing protocol consisting of a Yo-Yo Intermittent Endurance Test followed by 3 × 10 squat jumps and a wall sit for 30 s, and 12 min of recovery including CWI (10 °C water), bilateral PMT on the anterior and posterior thigh, or passive resting. Outcomes were assessed immediately after the exercise protocol, after the recovery intervention, and at 24 h. Isometric knee extension (IKE) and flexion (IKF) and tensiomyography (TMG) were assessed. Muscle soreness and fatigue were scored from 0 to 10. PMT increased strength after the treatment ( p = 0.004) and at 24 h ( p = 0.007), whereas no significant differences were found for the other two recovery modalities. At post-recovery, compared to CON, CWI resulted in a longer TMG contraction time ( p = 0.027). No significant differences were found at 24 h. Finally, PMT and CWI enhanced muscle soreness recovery compared to passive rest (F 4,60 = 3.095, p = 0.022, p η 2 = 0.171). Preliminary results from this study suggest that PMT might improve isometric strength after strenuous exercise, and both PMT and CWI reduce muscle soreness perception, while the effects on TMG parameters remain controversial.

Dilated cardiomyopathy (DCM) is a common cause of heart failure (HF) and heart transplantation (HTx), with genetic factors playing a significant role. In recent years, the RNA-binding protein motif 20 ( RBM20 ), which affects the gene splicing of various proteins with different cellular functions, was identified as the first DCM gene with regulatory properties. Variants of RBM20 have been associated with severe forms of DCM. The aim of this critical systematic review was to analyse RBM20 cardiomyopathy clinical features and outcomes. According to PRISMA guidelines, a search was run in the PubMed, Scopus and Web of Science electronic databases using the following keywords: " RBM20 "; "cardiomyopathy"; "arrhythmias"; "heart failure". A total of 181 records were screened, of which 27 studies were potentially relevant to the topic. Through the application of inclusion and exclusion criteria, eight papers reporting 398 patients with RBM20 pathogenic variants were analysed. The mean age at presentation was 41 years. Familiarity with cardiomyopathy was available in 59% of cases, with 55% of probands reporting a positive family history. Imaging data indicated a mild reduction of left ventricular ejection fraction (mean LVEF 40%), while tissue characterization was reported in 24.3% of cases, showing late gadolinium enhancement in 33% of patients. Composite outcomes of sustained monomorphic ventricular tachycardia or ventricular fibrillation occurred in 19.4% of patients, with 12% undergoing HTx. There were no gender differences in arrhythmic outcomes, while 96.4% of patients who underwent HTx were male. In conclusion, RBM20 cardiomyopathy exhibits a severe phenotypic expression, both in terms of arrhythmic burden and HF progression.

Manipulation of host behaviour by parasites to enhance transmission to the next host is a fascinating phenomenon that has interested scientists since the 1970s. It has been proposed that infection with the cestode Echinococcus multilocularis produces an impairment of the antipredatory behaviour in the rodent intermediate host common vole, Microtus arvalis , which may facilitate transmission of the tapeworm to the canid final host. In this study, we observed the behaviour of infected common voles at 12 weeks post-infection, when protoscoleces production and maturation commonly occurs, in order to assess behavioural changes compared to uninfected controls, that might ease predation in the wild. Infected and uninfected voles were monitored for 24 h to observe their spontaneous activity. In addition, the next day, both infected and uninfected voles were subjected to 4 different behavioural tests: open field test, barrier test, platform test and air-puff test in a running wheel. No significant difference between uninfected and infected voles emerged during the behavioural tests. However, observation of spontaneous activity revealed that infected voles increased their feeding frequency and spent significantly more time above bedding even when not eating, compared to the uninfected controls. In the wild, these behavioural changes increase the animals exposure to predators, raising their chance of becoming prey. These findings are the first direct evidence consistent with behavioural manipulation by E. multilocularis on common voles.

Background: Trunk muscles' function and characteristics are of great importance for both static and dynamic tasks in different sports, and abnormalities of trunk flexors and extensors might be associated with low back pain (LBP). The aim of this study was to provide a comprehensive evaluation of the functional, morphological and contractile properties in trunk flexors and extensors of young gymnasts with and without LBP., Methods: Young gymnasts (14/25 females, 14-18 y) were screened for the presence of chronic LBP. Abdominal and lumbar muscles were tested for function (McGill's endurance tests), thickness (ultrasound), and contractile responses (tensiomyography). An 8-sessions physiotherapy intervention including postural reeducation was performed by a subsample of 10 subjects with LBP., Results: LBP was found to be associated to higher flexors-to-extensors endurance ratio (OR 11.250, 95% CI: 1.647-76.849, p  = 0.014), reduced mean lumbar multifidus thickness (OR 16.500, 95% CI: 2.246-121.228, p  = 0.006), and reduced mean erector spinae radial displacement (OR 16.500, 95% CI: 2.246-121.228, p  = 0.006). The physiotherapy intervention was found to reduce LBP symptoms and it was associated with a significant improvement in the flexors-to-extensors ratio ( p  < 0.001)., Conclusions: This study provides preliminary evidence of functional, morphological, and contractile trunk muscles' alterations associated with chronic LBP in young gymnasts, and presents the effects of a postural reeducation program on symptoms and muscles' functional properties.

Objective: To compare the prognostic power of Hounsfield units (HU) and Vertebral Bone Quality (VBQ) score for predicting proximal junctional kyphosis (PJK) following long-segment thoracolumbar fusion to the upper thoracic spine (T1-T6)., Methods: Vertebral bone quality around the upper instrumented vertebrae (UIV) was measured using HU on preoperative CT and VBQ on preoperative MRI. Spinopelvic parameters were also categorized according to the Scoliosis Research Society-Schwab classification. Univariable analysis to identify predictors of the occurrence of PJK and survival analyses with Kaplan-Meier method and Cox regression were performed to identify predictors of time to PJK (defined as ≥10° change in Cobb angle of UIV+2 and UIV). Sensitivity analyses showed thresholds of HU < 164 and VBQ > 2.7 to be most predictive for PJK., Results: Seventy-six patients (mean age 66.0 ± 7.0 years; 27.6% male) were identified, of whom 15 suffered PJK. Significant predictors of PJK were high postoperative pelvic tilt (P = 0.038), high postoperative T1-pelvic angle (P = 0.041), and high postoperative PI-LL mismatch (P = 0.028). On survival analyses, bone quality, as assessed by the average HU of the UIV and UIV+1 was the only significant predictor of time to PJK (odds ratio [OR] 3.053; 95% CI 1.032-9.032; P = 0.044). VBQ measured using the UIV, UIV+1, UIV+2, and UIV-1 vertebrae approached, but did not reach significance (OR 2.913; 95% CI 0.797-10.646; P = 0.106)., Conclusions: In larger cohorts, VBQ may prove to be a significant predictor of PJK following long-segment thoracolumbar fusion. However, Hounsfield units on CT have greater predictive power, suggesting preoperative workup for long-segment thoracolumbar fusion benefits from computed tomography versus magnetic resonance imaging alone to identify those at increased risk of PJK., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive form of pancreatic cancer, known for its challenging diagnosis and limited treatment options. The focus on metabolic reprogramming as a key factor in tumor initiation, progression, and therapy resistance has gained prominence. In this review we focus on the impact of metabolic changes on the interplay among stromal, immune, and tumor cells, as glutamine and branched-chain amino acids (BCAAs) emerge as pivotal players in modulating immune cell functions and tumor growth. We also discuss ongoing clinical trials that explore metabolic modulation for PDAC, targeting mitochondrial metabolism, asparagine and glutamine addiction, and autophagy inhibition. Overcoming challenges in understanding nutrient effects on immune-stromal-tumor interactions holds promise for innovative therapeutic strategies., Competing Interests: Declaration of interests B.B. reports research funding from Agenus Inc and NanoView Biosciences, travel expenses from Erytech Pharma, and advisory board and consulting from Blueprint Medicines, BioLineRx, and Enlivex. E.H. is a founder of Kither Biotech, a company involved in the development of PI3K inhibitors. The other authors declare no potential conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Few studies used thermal quantitative sensory testing to assess the effects of repeated capsaicin gel administration in the oral cavity. This study aimed to investigate thermal sensory and pain thresholds before and after repeated capsaicin gel administration., Subjects and Methods: Ten healthy females (22 ± 2 years) applied a capsaicin gel on the gingival mucosa twice daily for 14 days, and heat pain threshold, warm detection threshold, cold pain threshold, and cold detection threshold were assessed on the oral mucosa. Measurements were performed before and after the 14 days and were compared to a control sample (n = 10, all females, 23 ± 3 years)., Results: Capsaicin increased heat pain threshold in the anterior maxilla by 2.9°C (95% CI: 1.6-4.2) (p < 0.001) and in the anterior mandible by 2.2°C (95% CI: 1.0-3.4) (p = 0.001), similar to warm detection threshold that increased by Δ1.1°C (95% CI: 0.3-1.9) (p = 0.009). No significant changes were found in the controls., Conclusions: These findings encourage the use of thermal quantitative sensory testing in the oral cavity to assess thermal sensation, which might be useful for assessing the effects of therapies aimed at reducing pain., (© 2024 Wiley Periodicals LLC.)

The choice of a refeeding strategy is essential in the inpatient treatment of Anorexia Nervosa (AN). Oral nutrition is usually the first choice, but enteral nutrition through the use of a Nasogastric Tube (NGT) often becomes necessary in hospitalized patients. The literature provides mixed results on the efficacy of this method in weight gain, and there is a scarcity of studies researching its psychological correlates. This study aims to analyze the effectiveness of oral versus enteral refeeding strategies in inpatients with AN, focusing on Body Mass Index (BMI) increase and treatment satisfaction, alongside assessing personality traits. We analyzed data from 241 inpatients, comparing a group of treated vs. non-treated individuals, balancing confounding factors using propensity score matching, and applied regression analysis to matched groups. The findings indicate that enteral therapy significantly enhances BMI without impacting treatment satisfaction, accounting for the therapeutic alliance. Personality traits showed no significant differences between patients undergoing oral or enteral refeeding. The study highlights the clinical efficacy of enteral feeding in weight gain, supporting its use in severe AN cases when oral refeeding is inadequate without adversely affecting patient satisfaction or being influenced by personality traits.