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Background Tumour relapse is recognized to be the prime fatal burden in patients affected by head and neck squamous cell carcinoma (HNSCC), but no discrete molecular trait has yet been identified to make reliable early predictions of tumour recurrence. Expression of cell surface proteoglycans (PGs) is frequently altered in carcinomas and several of them are gradually emerging as key prognostic factors. Methods A PG expression analysis at both mRNA and protein level, was pursued on primary lesions derived from 173 HNSCC patients from whom full clinical history and 2 years post-surgical follow-up was accessible. Gene and protein expression data were correlated with clinical traits and previously proposed tumour relapse markers to stratify high-risk patient subgroups. Results HNSCC lesions were indeed found to exhibit a widely aberrant PG expression pattern characterized by a variable expression of all PGs and a characteristic de novo transcription/translation of GPC2, GPC5 and NG2/CSPG4 respectively in 36%, 72% and 71% on 119 cases. Importantly, expression of NG2/CSPG4, on neoplastic cells and in the intralesional stroma (Hazard Ratio [HR], 6.76, p  = 0.017) was strongly associated with loco-regional relapse, whereas stromal enrichment of SDC2 (HR, 7.652, p  = 0.007) was independently tied to lymphnodal infiltration and disease-related death. Conversely, down-regulated SDC1 transcript (HR, 0.232, p  = 0.013) uniquely correlated with formation of distant metastases. Altered expression of PGs significantly correlated with the above disease outcomes when either considered alone or in association with well-established predictors of poor prognosis (i.e. T classification, previous occurrence of precancerous lesions and lymphnodal metastasis). Combined alteration of all three PGs was found to be a reliable predictor of shorter survival. Conclusions An unprecedented PG-based prognostic portrait is unveiled that incisively diversifies disease course in HNSCC patients beyond the currently known clinical and molecular biomarkers.

Penetrating wounds of the neck with foreign bodies retention are frequent and often life-threatening events, and their management has changed in recent years from an open approach to a conservative approach thanks to the possibility of performing minimally invasive radiologically guided surgery. We present a case of penetrating glass injury to zone III of the neck in which the foreign body go through the parotid region passing near, but without injuring, the facial nerve and the external and internal carotid arteries.

Background: Locoregionally advanced head and neck squamous cell carcinoma (HNSCC) patients have high relapse and mortality rates. Imaging-based decision support may improve outcomes by optimising personalised treatment, and support patient risk stratification. We propose a multifactorial prognostic model including radiomics features to improve risk stratification for advanced HNSCC, compared to TNM eighth edition, the gold standard. Patient and methods: Data of 666 retrospective- and 143 prospective-stage III-IVA/B HNSCC patients were collected. A multivariable Cox proportional-hazards model was trained to predict overall survival (OS) using diagnostic CT-based radiomics features extracted from the primary tumour. Separate analyses were performed using TNM8, tumour volume, clinical and biological variables, and combinations thereof with radiomics features. Patient risk stratification in three groups was assessed through Kaplan–Meier (KM) curves. A log-rank test was performed for significance (p-value < 0.05). The prognostic accuracy was reported through the concordance index (CI). Results: A model combining an 11-feature radiomics signature, clinical and biological variables, TNM8, and volume could significantly stratify the validation cohort into three risk groups (p < 0∙01, CI of 0.79 as validation). Conclusion: A combination of radiomics features with other predictors can predict OS very accurately for advanced HNSCC patients and improves on the current gold standard of TNM8.

Soil is one of the most important reservoirs of antibiotic resistance, global threat that needs to be addressed with the One Health approach. Despite urban parks playing a fundamental role in urban ecosystems, the diffusion, maintenance, and human impact of antibiotic-resistance genes in this substrate are still poorly addressed. To fill in this gap, we adopted a molecular and culturomics approach to study antibiotic resistance in urban parks, accounting for the environmental matrix and the level of urbanization. A higher abundance of efflux-mediated mechanisms in undisturbed environments was observed, while antibiotic alteration or inactivation, and target replacement were more abundant in areas with a higher level of urbanization, also confirmed by significant correlations with anthropogenic features of the environmental matrix. Overall, this study highlights the crucial need to monitor antibiotic resistance in urban parks’ soil through a dual molecular and culturomics approach to fully understand and fight antibiotic resistance diffusion.

Objective Multiple sclerosis (MS) is a chronic neurological condition causing motor and cognitive impairments. Evidence indicates that multimodal rehabilitation, including high-intensity interval training (HIIT), balance, and strength exercises can improve balance, walking ability, and cognition while reducing fatigue in People with MS (PwMS). This study aims to evaluate the effects of high-intensity multimodal functional training on improvements in balance, walking, and cognitive function and fatigue reduction in PwMS. Materials and Methods This pilot randomized controlled, assessor-blinded, multicenter trial will include PwMS with an Expanded Disability Status Scale score ≥ 2 and ≤ 5.5 points. Participants will be randomized to an experimental group receiving high-intensity multimodal training (aerobic HIIT, balance, and strength exercises) or a control group (conventional rehabilitation). The intervention will consist of 16 sessions over 8 weeks. Participants will undergo an extensive evaluation at baseline (T0), post-intervention (T1), and after 2 months at the follow-up (T2). The assessment will include a fatiguing walking test, standing balance evaluation, and cognitive performance tests. Primary outcomes will focus on walking velocity during a fatiguing walking test, while secondary outcomes will evaluate balance, fatigue, and cognitive functions using wearable sensors and clinical scales. Results Expected results will be a higher effect on walking (primary outcome), balance, fatigue, and cognition (secondary outcomes) for the experimental group (high-intensity multimodal functional training) compared to the control group (conventional rehabilitation). Conclusion This study introduces a time-efficient, high-intensity multimodal rehabilitation protocol targeting motor and non-motor symptoms in PwMS. By promoting neuroplasticity, the intervention could enhance independence, quality of life, and inform future rehabilitation strategies for MS.

Clostridium difficile causes nosocomial/antibiotic-associated diarrhoea and pseudomembranous colitis. The major virulence factors are toxin A and toxin B (TcdB), which inactivate GTPases by monoglucosylation, leading to cytopathic (cytoskeleton alteration, cell rounding) and cytotoxic effects (cell-cycle arrest, apoptosis). C. difficile toxins breaching the intestinal epithelial barrier can act on underlying cells, enterocytes, colonocytes, and enteric neurons, as described in vitro and in vivo, but until now no data have been available on enteric glial cell (EGC) susceptibility. EGCs are crucial for regulating the enteric nervous system, gut homeostasis, the immune and inflammatory responses, and digestive and extradigestive diseases. Therefore, we evaluated the effects of C. difficile TcdB in EGCs. Rat-transformed EGCs were treated with TcdB at 0.1–10 ng/ml for 1.5–48 h, and several parameters were analysed. TcdB induces the following in EGCs: (1) early cell rounding with Rac1 glucosylation; (2) early G2/M cell-cycle arrest by cyclin B1/Cdc2 complex inactivation caused by p27 upregulation, the downregulation of cyclin B1 and Cdc2 phosphorylated at Thr161 and Tyr15; and (3) apoptosis by a caspase-dependent but mitochondria-independent pathway. Most importantly, the stimulation of EGCs with TNF-α plus IFN-γ before, concomitantly or after TcdB treatment strongly increased TcdB-induced apoptosis. Furthermore, EGCs that survived the cytotoxic effect of TcdB did not recover completely and showed not only persistent Rac1 glucosylation, cell-cycle arrest and low apoptosis but also increased production of glial cell-derived neurotrophic factor, suggesting self-rescuing mechanisms. In conclusion, the high susceptibility of EGCs to TcdB in vitro, the increased sensitivity to inflammatory cytokines related to apoptosis and the persistence of altered functions in surviving cells suggest an important in vivo role of EGCs in the pathogenesis of C. difficile infection.

Urban green areas provide multiple ecosystem services in cities, mitigating environmental risks and providing a healthier environment for humans. Even if urban ecology has become popular in the last decade, the soil environment with its microbiota, which sustains many other biodiversity layers, remains overlooked. Here, a comprehensive database of scientific papers published in the last 30 years investigating different aspects of soil microbial diversity was built and systematically reviewed. The aim was to identify the taxa, experimental methods and geographical areas that have been investigated, and to highlight gaps in knowledge and research prospects. Our results show that current knowledge on urban soil microbiota remains incomplete, mainly due to the lack of publications on functional aspects, and is biased, in terms of investigated taxa, with most studies focused on Prokaryotes, and geographic representativeness, with the interest focused on a few large cities in the Northern hemisphere. By coupling bibliometrics with statistical modelling we found that soil microbial traits such as biomass and respiration and omics techniques attract the interest of the scientific community while multi-taxa and time-course studies appeal more to the general public.

Enteric glial cells (EGCs) are components of the intestinal epithelial barrier essential for regulating the enteric nervous system. Clostridium difficile is the most common cause of antibiotic-associated colitis, toxin B (TcdB) being the major virulence factor, due to its ability to breach the intestinal epithelial barrier and to act on other cell types. Here we investigated TcdB effects on EGCs and the activated molecular mechanisms. Already at 2 hours, TcdB triggered ROS formation originating from NADPH-oxidase, as demonstrated by their reduction in the presence of the NADPH-oxidase inhibitor ML171. Although EGCs mitochondria support almost completely the cellular ATP need, TcdB exerted weak effects on EGCs in terms of ATP and mitochondrial functionality, mitochondrial ROS production occurring as a late event. ROS activated the JNK signalling and overexpression of the proapoptotic Bim not followed by cytochrome c or AIF release to activate the downstream apoptotic cascade. EGCs underwent DNA fragmentation through activation of the ROS/JNK/caspase-3 axis, evidenced by the ability of ML171, N-acetylcysteine, and the JNK inhibitor SP600125 to inhibit caspase-3 or to contrast apoptosis. Therefore, TcdB aggressiveness towards EGCs is mainly restricted to the cytosolic compartment, which represents a peculiar feature, since TcdB primarily influences mitochondria in other cellular types.

Most symptomatic SARS-CoV-2 infections produce mild to moderate symptoms. Although most patients are managed in the outpatient setting, little is known about the effect of general practitioners' (GP) management strategies on the outcomes of COVID-19 outpatients in Italy. Describe the management of Italian GPs of SARS-CoV-2 infected adult patients and explore whether GP active care and monitoring are associated with reducing hospitalisation and death. Retrospective observational study of SARS-CoV-2 infected adult outpatients managed by GPs in Modena (Italy) from March 2020 to April 2021. Information on management and monitoring strategies, patients' socio-demographic characteristics, comorbidities, and outcomes (hospitalisation and death due to COVID-19) were retrieved through an electronic medical record review and analysed descriptively and through multiple logistic regression. Out of the 5340 patients from 46 GPs included in the study, 3014 (56%) received remote monitoring, and 840 (16%) had at least one home visit. More than 85% of severe or critical patients were actively monitored (73% daily) and 52% were visited at home. Changes over time in patients' therapeutic management were observed in concordance with the guidelines' release. Active daily remote monitoring and home visits were strongly associated with reduced hospitalisation rate (OR 0.52, 95% CI 0.33-0.80 and OR 0.50, 95% CI 0.33-0.78 respectively). GPs effectively managed an increasing number of outpatients during the first waves of the pandemic. Active monitoring and home visits were associated with reduced hospitalisation in COVID-19 outpatients.

The article describes an experimental method tested in Lecce (Italy) which introduces a city vision as a Living Lab, where the general public has an active role in the process towards Smart City paradigm. The methodology moves from considering a Smart City not just a technology environment, but also an organic system where public institutions, organizations, enterprises and citizens collaborate with each other to co-design and co-create integrated services supported by technological innovation. The framework developed regards the implementation of an Idea Management System (IMS) to support citizens participation in the context of the candidacy of Lecce as European Capital of Culture 2019. The application, which is now focused on ideas sharing and voting, will be further developed to cover the whole idea management process. \"Lecce 2019 - Idea Management System\" will then be used as a tool to support Smart City planning. The aim is to implement open innovation and knowledge sharing practices, extending these to neighboring municipalities in Salento. [PUBLICATION ABSTRACT]