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We aimed to investigate the role of interleukin-1 beta (IL-1β) in the mechanisms underlying mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE+HS). We assessed a cohort of 194 patients with MTLE+HS and 199 healthy controls. Patients were divided into those with positive and negative antecedent febrile seizures (FS). We used a multidimensional approach, including (i) genetic association with single nucleotide polymorphisms (SNPs) in the IL1B gene; (ii) quantification of the IL1B transcript in the hippocampal tissue of patients with refractory seizures; and (iii) quantification of the IL-1β protein in the plasma. We found a genetic association signal for two SNPs, rs2708928 and rs3730364*C in the IL1B gene, regardless of the presence of FS (adjusted p = 9.62e–11 and 5.14e–07, respectively). We found no difference between IL1B transcript levels when comparing sclerotic hippocampal tissue from patients with MTLE+HS, without FS, and hippocampi from autopsy controls (p > 0.05). Nevertheless, we found increased IL-1β in the plasma of patients with MTLE+HS with FS compared with controls (p = 0.0195). Our results support the hypothesis of a genetic association between MTLE+HS and the IL1B gene

Abstract Background Focal cortical dysplasias (FCDs) are malformations of cortical development that present cortical dyslamination and abnormal cell morphology and are frequently associated with refractory epilepsy. FCD type IIb presents dysmorphic neurons (DNs) and balloon cells (BCs), which are the hallmarks of this dysplasia. Moreover, hypertrophic neurons (HyNs) may be present in FCD types I, II and III. The objective of this study was to perform a detailed morphology and immunophenotype study of BCs, DNs, and HyNs in a cohort of FCD IIb patients. Methods Cortices resected as a treatment for refractory epilepsy from 18 cases of FCD type IIb were analysed using Bielschowsky method and haematoxylin and eosin as routine stains. Immunophenotype was performed using specific antibodies to detect epitopes differentially expressed by abnormal cells. Results All cases showed cortical dyslamination, BCs, DNs, and HyNs. No cell layer or column could be identified, except for cortical layer I. Lesions predominated in the frontal cortex (11 cases). DNs were large neurons and presented a clumped and or displaced Nissl substance towards the cell membrane, and a cytoplasm accumulation of neurofilament that displaced the nucleus to the cell periphery, as shown by Bielschowsky staining and immunohistochemistry. HyNs were as large as DNs, but without alterations of Nissl substance or dense neurofilament accumulation, with a central nucleus. BCs were identified as large, oval-shaped and pale eosinophilic cells, which lacked the Nissl substance, and presented an eccentric nucleus. BCs and DNs expressed epitopes of both undifferentiated and mature cells, detected using antibodies against nestin, vimentin, class III β-tubulin, pan-neuronal filaments, neurofilament proteins, β-tubulin and NeuN. Only BCs expressed GFAP. Conclusion FCDs present with disorganization of the cerebral cortex architecture, abnormal cell morphology, are frequently associated with refractory epilepsy, and their post-surgical prognosis depends on the type of FCD. The diagnosis of focal cortical dysplasia in a surgical specimen relies on the identification of the abnormal cells present in a dysplastic cortex specimen. The current report contributes to the identification of balloon cells, dysmorphic and hypertrophic neurons in the context of focal cortical dysplasia type IIb.

The aim was to determine if patients with writer' cramp (WC) have abnormalities in kinesthetic motor imagery of hand movements. We timed the execution and simulation of a "finger tap task" and a "writing task" in 9 patients with simple WC and 9 matched healthy controls. In the "finger tap task, patients tended to be slower than controls to execute without vision (p=0.190) and to simulate the movements (p=0.094). In the "writing task", patients were slower than controls to execute writing with vision (p=0.0001) and without vision of the movements (p=0.0001) and to mentally simulate it (p=0.04). Patients were slower to execute writing than to simulate it (p=0.021) In general, there were not significant correlations between times of execution and simulation of both tasks. In conclusion, patients with WC seem to have slowing in the processes of mental simulation of hand movements that is not specific for writing.O objetivo do estudo foi determinar se pacientes com cãibra do escrivão (CE) teriam anormalidades na imagem motora de movimentos manuais. Foi cronometrado o tempo gasto para a execução e simulação de uma tarefa de "batida dos dedos" e outra de "escrita" em 9 pacientes com CE simples e 9 controles pareados. Na tarefa de "batida dos dedos" os pacientes apresentaram tendência a serem mais lentos que os controles para executá-la com visão dos movimentos (p=0,190) e para simulá-la (p=0,094). Na tarefa de "escrita", os pacientes foram mais lentos que os controles para executá-la com visão (p=0.0001) e sem visão dos movimentos (p=0,0001) e também para simulá-la (p=0,04). Os pacientes foram mais lentos para escrever que para simular a escrita (p=0,021). Não encontramos correlação entre os tempos de execução e simulação das tarefas. Pacientes com CE apresentam alentecimento no processo de simulação mental de movimentos manuais.

This study determined whether hippocampal kainate (KA) receptor mRNA levels were increased or decreased in temporal lobe epilepsy patients compared with nonseizure autopsies. Hippocampal sclerosis (HS;n= 17), nonsclerosis (non-HS;n= 11), and autopsy hippocampi (n= 9) were studied for KA1–2 and GluR5–7 mRNA levels using semiquantitativein situhybridization techniques, along with neuron densities. Compared with autopsy hippocampi, HS and non-HS cases showed decreased GluR5 and GluR6 hybridization densities per CA2 and/or CA3 pyramid. Furthermore, HS patients demonstrated increased KA2 and GluR5 hybridization densities per granule cell compared with autopsy hippocampi. These findings indicate that chronic temporal lobe seizures were associated with differential changes in hippocampal KA1–2 and GluR5–7 hybridization densities that vary by subfield and pathology group. In temporal lobe epilepsy patients, these results support the hypothesis that pyramidal cell GluR5 and GluR6 mRNA levels are decreased as a consequence of seizures, and in HS patients granule cell KA2 and GluR5 mRNA levels are increased in association with aberrant fascia dentata mossy fiber sprouting and/or hippocampal neuronal loss.

Cerebral cavernous malformations (CCMs) are well-defined, mostly singular lesions present in 0.4-0.9% of the population. Epileptic seizures are the most frequent symptom in patients with CCMs and have a great impact on social function and quality of life. However, patients with CCM-related epilepsy (CRE) who undergo surgical resection achieve postoperative seizure freedom in only about 75% of cases. This is frequently because insufficient efforts are made to adequately define and resect the epileptogenic zone. The Surgical Task Force of the Commission on Therapeutics of the International League Against Epilepsy (ILAE) and invited experts reviewed the pertinent literature on CRE. Definitions of definitive and probable CRE are suggested, and recommendations regarding the diagnostic evaluation and etiology-specific management of patients with CRE are made. Prospective trials are needed to determine when and how surgery should be done and to define the relations of the hemosiderin rim to the epileptogenic zone.

Abstract Background Since the 1990s, healthcare systems in many Western countries, including Italy, have undergone significant reforms, transforming organizational models and structures to meet the growing demand for healthcare services efficiently. This transformation has introduced new managerial roles for doctors-managers, particularly at the midlevel, creating “doctor-manager” positions that involve both clinical and managerial responsibilities. However, doctor-managers often struggle to balance these dual roles due to a lack of formal managerial training and the inherent conflict between clinical and economic objectives. This study aims to define new evaluation dimensions that can enhance the existing scale and develop a new tool to assess the necessary components of the managerial attitude dimension required by doctor-managers in the current Italian healthcare system. Methods This study updated Cicchetti’s 2005 scale to reflect the changes that have occurred in healthcare organizations over the past 20 years, focusing on the evolving roles and challenges of middle healthcare managers. A scoping review was conducted to explore the existing literature, resulting in the identification and analysis of 24 key articles. Thematic analysis, facilitated by NVivo software, identified 171 items related to managerial attitude. These items were further refined, resulting in a 61-item Health Middle Manager Competencies Scale. The scale was evaluated by a Delphi panel through an e-survey, and Cronbach’s alpha was used to assess reliability. Results The final Competencies Scale for Middle Managers of Health consists of 61 items, validated by the Delphi panel of experts. The panel reached consensus on the relevance and significance of each item, confirming the scale’s reliability with an acceptable Cronbach alpha. The new scale captures various dimensions of the competencies essential for middle managers in healthcare settings. Conclusion The study provides insights into the dimensions of doctor managerial attitude and contributes to the update of Cicchetti’s Scale to develop a new tool that assesses all the necessary components now required within the managerial attitude dimension.

Abstract Introduction Around 75% of (re)emerging infections are of zoonotic origins. The risk of zoonotic transmission in Mozambique is high because approximately 81% of the country’s labor force is involved with agriculture, which represents a vulnerability for more frequent human-animal interaction and risk of spillover events. A One Health Zoonotic Disease Prioritization (OHZDP) workshop was conducted in Mozambique to facilitate coordination and collaboration within and across sectors to prevent, detect, and respond to zoonotic disease threats. Based on the success of this integrated workshop, the stakeholders developed actions whose results have a great impact on animal welfare, environment and improving public health. Methods In 2018, representatives from Mozambique’s human, animal, and environmental sectors from government, universities, research institutions and partners used US CDC’s OHZDP Process to prioritize endemic and emerging zoonotic diseases of greatest national concern and develop recommendations and key interventions needed to advance One Health in Mozambique. After the OHZDP workshop, the Mozambique One Health Secretariat used a theory of change methodology to identify activities for implementation from the recommendations of the OHZDP workshop. Since the OHZDP workshop, the Secretariat has monitored progress of activities annually. Results Mozambique’s priority zoonotic diseases are rabies, zoonotic tuberculosis, salmonellosis, zoonotic avian influenza, trypanosomiasis, brucellosis, and Crimean-Congo hemorrhagic fever. One Health recommendations and interventions to address the priority zoonotic diseases focused on One Health collaboration, communication, and coordination; laboratory; surveillance; preparedness and response; prevention; workforce development; and research. After the OHZDP workshop, Mozambique established One Health coordination mechanisms, developed training courses for surveillance, laboratory diagnosis, outbreak investigation, and preparedness and response for the priority zoonotic diseases, conducted joint research, and developed plans. Conclusion Prioritization of zoonotic diseases is critical as it facilitated the key One Health players in Mozambique to optimize resources, gain a greater understanding of zoonotic diseases, and implement policies and activities that promote multisectoral, interdisciplinary, and transdisciplinary collaboration across human, animal, and environmental sectors to prevent, detect, and respond to public health threats. The success of these activities implemented by the local Government and One Health partners were built from the implementation and momentum from the Mozambique’s OHZDP workshop.

Since the COVID-19 pandemic was first reported in 2019, it has rapidly spread around the world. Many countries implemented several measures to try to control the virus spreading. The healthcare system and consequently the general quality of life population in the cities have all been significantly impacted by the Coronavirus pandemic. The different waves of contagious were responsible for the increase in the number of cases that, unfortunately, many times lead to death. In this paper, we aim to characterize the dynamics of the six waves of cases and deaths caused by COVID-19 in Rio de Janeiro city using techniques such as the Poincaré plot, approximate entropy, second-order difference plot, and central tendency measures. Our results reveal that by examining the structure and patterns of the time series, using a set of non-linear techniques we can gain a better understanding of the role of multiple waves of COVID-19, also, we can identify underlying dynamics of disease spreading and extract meaningful information about the dynamical behavior of epidemiological time series. Such findings can help to closely approximate the dynamics of virus spread and obtain a correlation between the different stages of the disease, allowing us to identify and categorize the stages due to different virus variants that are reflected in the time series.

This work presents the computational modeling of reinforced concrete beams, strengthened to shear with carbon fiber-reinforced polymers (CFRP), using the finite element method (FEM) and the customized ANSYS software, version 19.2. It is important to emphasize that contact elements and bilinear cohesive zone models provided by ANSYS were used to model the concrete-reinforcement interface. These models were used to identify the modes of premature failure caused by the debonding of the reinforcement, which causes poor use of the CFRP's resistance properties. The structural elements used in this analysis were twelve simply supported reinforced concrete beams, without and with shear reinforcement using CFRP, which were experimentally tested by Khalifa (1999). From the analysis of the results, it was observed that the developed numerical models were able to accurately predict the behavior of the simulated beams, both in terms of load-displacement, as well as the load and rupture mode of the beams.

BackgroundEosinophilic esophagitis (EoE) is a chronic and progressive type 2 inflammatory disease affecting the esophagus. Its prevalence has increased in recent years due to increased awareness, evolving clinical guidelines, and heightened sensitivity among healthcare professionals managing the condition. The exact causes behind EoE’s development remain unknown, and its clinical presentation varies, often leading to significant diagnostic delays depending on the age at which symptoms manifest. Consequently, achieving long-term disease control through heightened awareness becomes imperative. EoE generates a significant clinical burden, resulting in substantial economic consequences for patients, healthcare systems, and society. This study aimed to assess the economic and social impacts on EoE patients within the Italian context.MethodsA cost-of-illness analysis was conducted from two perspectives: the National Health System (NHS) and the societal perspective. This analysis encompassed direct healthcare, indirect healthcare, and non-healthcare costs. Data were collected and assessed through a survey administered to a panel of expert clinicians and EoE-affected patients.ResultsManaging EoE incurs a significant burden on healthcare systems, amounting to €6,852.28 per patient per year. The primary cost component appears to be direct costs, comprising 60.73% of the total cost per patient for this condition, while indirect costs contribute to 29.68% of the overall management expenses.ConclusionThis analysis underscores a substantial financial burden on both the healthcare system and patients affected by eosinophilic esophagitis. It emphasizes the imperative need for a continuous and combined effort from clinicians, patients, and families to promptly recognize symptoms and adaptive behavior to mitigate diagnostic delays.

Abstract Background Seasonal influenza has a significant impact on public health, generating substantial direct healthcare costs, production losses and fiscal effects. Understanding these consequences is crucial to effective decision-making and the development of preventive strategies. This study aimed to evaluate the economic and the fiscal impact of implementing an incremental strategy for seasonal influenza prevention using the cell-based quadrivalent influenza vaccine (QIVc) among healthcare workers (HCWs) in Italy. Methods To estimate the economic impact of implementing this strategy, we performed a cost analysis that considered direct healthcare costs, productivity losses and fiscal impact. The analysis considered a 3-year time horizon. A deterministic sensitivity analysis was also conducted. Results Assuming a vaccination coverage rate of 30% among HCWs, the analysis considered a total of 203 018 vaccinated subjects. On analysing the overall differential impact (including direct costs, indirect costs and fiscal impact), implementing QIVc vaccination as a preventative measure against influenza among HCWs in Italy would yield societal resource savings of €23 638.78 in the first year, €47 277.56 in the second year, and €70 916.35 in the third year, resulting in total resource savings of €141 832.69. Conclusions The study demonstrated that implementing the incremental use of QIVc as part of a preventive strategy for seasonal influenza among HCWs in Italy could yield positive economic outcomes, especially in terms of indirect costs and fiscal impact. The resources saved could be utilized to fund further public health interventions. Policy-makers should consider these findings when making decisions regarding influenza prevention strategies targeting HCWs.

Robotic systems are increasingly being used in healthcare. These systems improve patient care both by freeing healthcare professionals from repetitive tasks and by assisting them with complex procedures. This analysis examines the development and implementation of the use of robotic systems in healthcare. It also examines the application of artificial intelligence (AI), which focuses on the autonomy of robotic systems, enabling them to perform tasks autonomously. It describes the main areas of use of robots in hospitals, gives examples of the main commercial or research robots, and analyzes the main practical and safety issues associated with the use of these systems. Using the main databases, including PubMed, IEEE Xplore, MDPI, ScienceDirect, ACM Digital Library, BioMed Central, Springer, and others, an extensive search for papers related to the topic was conducted. This resulted in 59 papers being identified as eligible for this review. The article concludes with a discussion of future research areas that will ensure the effective integration of autonomous robotic systems in healthcare.

Background: Eosinophilic esophagitis (EoE) is recognized as a chronic type 2 inflammatory disease characterized by the eosinophilic infiltration of the esophageal tissue, posing a significant disease burden and highlighting the necessity for novel management strategies to address unmet clinical needs. Objectives: To critically evaluate the existing literature on the epidemiology and management of EoE, identify evidence gaps, and assess the efficacy of current and emerging treatment modalities. Design: An extensive literature review was conducted, focusing on the epidemiological trends, diagnostic challenges, and therapeutic interventions for EoE. This was complemented by a survey among physicians and consultations with a scientific expert panel, including a patient’s association (ESEO Italia), to enrich the study findings. Data sources and methods: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, scrutinizing epidemiological studies and management research to compile comprehensive insights into the disease’s landscape. The physician survey and expert panel discussions aimed to bridge identified evidence gaps. Results: The review included 59 epidemiological and 51 management studies, uncovering variable incidence and prevalence rates of EoE globally, with an estimated diagnosed prevalence of 41 per 100,000 in Italy. Diagnostic challenges were identified, including nonspecific symptoms and the lack of definitive biomarkers, which complicate the use of endoscopy. Treatment options such as elimination diets, proton-pump inhibitors, and swallowed corticosteroids were found to have varying success rates, while Dupilumab, an emerging therapy targeting interleukin (IL)-4 and IL-13, shows promise. Conclusion: Despite advancements in understanding and managing EoE, significant unmet clinical needs remain, particularly in biomarker identification, therapy personalization, and cost-effectiveness evaluation. A comprehensive, multidimensional approach to patient management is required, emphasizing the importance of early symptom recognition, accurate diagnosis, and tailored treatment strategies. Dupilumab offers potential as a novel treatment, underscoring the need for future research to explore the economic and social dimensions of EoE care pathways.