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Abstract Introduction Despite new anti-seizure medications (ASMs) being introduced into clinical practice, about one-third of people with epilepsy do not reach seizure control. Cenobamate is a novel tetrazole-derived carbamate compound with a dual mechanism of action. In randomized controlled trials, adjunctive cenobamate reduced the frequency of focal seizures in people with uncontrolled epilepsy. Studies performed in real-world settings are useful to complement this evidence and better characterize the drug profile. Methods The Italian BLESS (“Cenobamate in Adults With Focal-Onset Seizures”) study is an observational cohort study aimed to evaluate the effectiveness, tolerability, and safety of adjunctive cenobamate in adults with uncontrolled focal epilepsy in the context of real-world clinical practice. The study is ongoing and conducted at 50 centers in Italy. This first interim analysis includes participants enrolled until June 2023 and with 12-week outcome data available. Results Forty participants with a median age of 36.5 (interquartile range [IQR] 26.0–47.5) years were included. The median monthly seizure frequency at baseline was 6.0 (IQR 2.5–17.3) seizures and 31 (77.5%) participants had failed four or more ASMs before cenobamate. At 12 weeks from starting cenobamate, the median reduction in monthly seizure frequency was 52.8% (IQR 27.1–80.3%); 22 (55.0%) participants had a ≥ 50% reduction in baseline seizure frequency and six (15.0%) reached seizure freedom. The median number of concomitant ASMs decreased from 3 (IQR 2–3) at baseline to 2 (IQR 2–3) at 12 weeks and the proportion of patients treated with > 2 concomitant ASMs decreased from 52.5% to 40.0%. Seven (17.5%) patients reported a total of 12 adverse events, 11 of which were considered adverse drug reactions to cenobamate. Conclusion In adults with uncontrolled focal seizures, the treatment with adjunctive cenobamate was well tolerated and was associated with improved seizure control and a reduction of the burden of concomitant ASMs. Trial Registration Number NCT05859854 (ClinicalTrials.gov Identifier).

Abstract This paper proposes a novel solution to the problem of robust ripple‐free hybrid robust regulator ensuring the elimination of intersample ripples. The paper considers a structurally stable regulation approach in the hybrid framework. A regulator is designed using this technique under periodic sampling and is applied to the nonlinear model of a quadrotor. The control of unmanned autonomous vehicles has become a research topic that is important by itself, particularly in the case of multi‐rotor systems due to their versatility in various applications. Tracking a reference signal for such vehicles can be challenging, particularly when the frequency of communication is limited, or the control station is located far away. The proposed controller is hence tested for this challenging application.

Abstract Mild mesial temporal lobe epilepsy (MTLE) patients may remain untreated for a considerable time after disease onset or achieve seizure control with a single anti‐seizures medication (ASM). Thus, they represent an optimal population to investigate whether ASMs might have influence on brain structure. We consecutively enrolled 56 mild MTLE patients (22/56 untreated, 34/56 on‐monotherapy) and 58 healthy controls, matched for age and gender. All subjects underwent 3T‐brain MRI, using FreeSurfer for automated morphometry. Differences in gray matter were assessed using one‐way Analysis of Covariance (ANCOVA), adjusting for age, disease duration and intracranial volume. No significant change was observed between treated and untreated patients. We observed a significant reduction in cortical thickness of left inferior parietal, inferior temporal, middle temporal gyri, and right inferior parietal gyrus, temporal pole in monotherapy patients compared to healthy controls, as well as an increase in left isthmus of cingulate gyrus in untreated MTLE subjects compared to controls. Surface and subcortical volumes analysis revealed no differences among groups. Our study demonstrated no substantial morphological abnormalities between untreated mild MTLE patients and those undergoing monotherapy. Although exploratory, these results may reassure about safety of commonly used drugs and their marginal role in influencing neuroimaging results. Plain Language Summary This study investigated the following question: can medications against epileptic seizures have an effect on brain structure in mild mesial temporal lobe? Preliminary results from our analyses suggest not, as we did not find any difference in brain gray matter between untreated patients and those treated with a single anti‐seizures medication. On the other hand, epilepsy patients presented cortical thinning compared to healthy controls in several regions of the temporal and parietal lobes, in line with previous studies investigating the disease.

A transversely isotropic structural model for wood, based on a polytope strength criterion, is proposed and deployed in the analysis of solid wood columna-capreoli A-trusses reproducing the geometry and connection details of those currently erected in the Aula Magna of the Monastery San Lorenzo ad Septimum in Aversa. The predictivity of the polytope strength criterion is assessed verifying its capability of identifying the closest crisis mode against experimental evidence from a simple flexural test, with minimal wood sacrifice. The model is employed in parametric optimization analyses to infer a design provision for the columna-capreoli connection which appears to be in reasonable agreement with the rule of the art empirically inferable from the observation of many samples of open-node King Post A-trusses belonging to the architectural heritage in Campania of historical and artistic value. A final discussion examines a perspective of extending these optimization analyses to the sustainability of the built environment.

IntroductionThe current Infectious Disease Society of America and American Thoracic Society (IDSA/ATS) guidelines recommend linezolid or vancomycin as an empiric treatment for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in hospitalized patients with specific risk factors,. A nasal PCR-assay for MRSA, with its high negative predictive value, can guide a rapid antibiotic de-escalation avoiding unnecessary anti-MRSA treatment. The indiscriminate use of these drugs has contributed to the emergence of resistant S. aureus strains leading to adverse effects without any survival benefit, increasing hospital stays and associated costs. Aim of the study is the use of this diagnostic tool to reduce empirical anti-MRSA treatment duration in pneumonia, shortening antimicrobial therapy days while measuring in-hospital mortality, length of stay and adverse drug event incidence.MethodsIt is a prospective, randomized single-center controlled trial planned to be conducted in the Azienda Consorziale Policlinico di Bari. The research project will have a duration of 12 months following the approval of the Ethical Committee of the University of Bari. The minimum sample size is 38 patients per group, for a total of 76 subjects, calculated assuming a standard deviation of 10, a power of 90%, a type I error of 5% and a 10% drop-out rate. We will enroll eligible patients ensuring their evidence-based management according to guidelines, we will perform a nasal swab for MRSA in patients in the experimental group and discontinue the empirical anti-MRSA therapy if the nasal swab result is negative. For both arms, follow-up visits will be on day 2, 5, 7, 14, and 28 relatives to the enrollment visit (day 0). Data will be collected on the clinical course of pneumonia and laboratory tests.DiscussionOur study will provide evidence on the duration (in days) of the antibiotic intake as a primary outcome of the study. Secondary outcome measures include in-hospital mortality, the length of stay and days of mechanical ventilation (in VAP), and the incidence of adverse events related to the administration of the therapy.Clinical trial registrationhttps://classic.clinicaltrials.gov/ct2/show/NCT06238297, identifier NCT06238297.

Abstract Background Mental health (MH) is extremely relevant when referring to people living with a chronic disease, such as people living with HIV (PLWH). In fact – although life expectancy and quality have increased since the advent of antiretroviral therapy (ART) – PLWH carry a high incidence of mental disorders, and this burden has been exacerbated during the COVID-19 pandemic. In this scenario, UNAIDS has set new objectives for 2025, such as the linkage of at least 90% of PLWH to people-centered, context-specific MH services. Aim of this study was to determine the prevalence of MD in PLWH followed at the Clinic of Infectious Diseases of the University of Bari, Italy. Methods From January 10th to September 10th, 2022, all PLWH patients accessing our outpatient clinic were offered the following standardized tools: HAM-A for anxiety, BDI-II for depression, PC-PTSD-5 for post-traumatic stress disorder, CAGE-AID for alcohol-drug abuse. Factors associated with testing positive to the four MD were explored with a multivariable logistic regression model. Results 578 out of 1110 HIV-patients agreed to receive MH screening, with 141 (24.4%) people resulting positive to at least one MH disorder. HAM-A was positive in 15.8% (n = 91), BDI-II in 18% (n = 104), PC-PTSD-5 in 5% (n = 29) and CAGE in 6.1% (n = 35). The multivariable logistic regression showed a higher probability of being diagnosed with anxiety, depression and post-traumatic stress disorder for PLWH who reported severe stigma, social isolation, psychological deterioration during the COVID-19 pandemic and for those receiving a dolutegravir (DTG)-based regimen. Moreover, history of drug use (OR 1.13; [95% CE 1.06–4.35]), family stigma (2.42 [1.65–3.94]) and social isolation (2.72 [1.55;4.84]) were found to be associated to higher risk for substance use disorder. Conclusions In this study, stigma was a strong predictor for being diagnosed of a MH disorder among PLWH. Also, the possible role of dolutegravir as a risk factor for the onset of MH disorders should be considered in clinical practice, and MH of patients receiving DTG-containing regimens should be constantly monitored.

Abstract Remdesivir (RDV) was the first Food and Drug Administration (FDA)-approved medication for COVID-19, with discordant data on efficacy in reducing mortality risk and disease progression. In the context of a dynamic and rapidly changing pandemic landscape, the utilization of real-world evidence is of utmost importance. The objective of this study is to evaluate the impact of RDV on patients who have been admitted to two university referral hospitals in Italy due to COVID-19. All patients older than 18 years and hospitalized at two different universities (Bari and Palermo) were enrolled in this study. To minimize the effect of potential confounders, we used propensity score matching with one case (Remdesivir) and one control that never experienced this kind of intervention during hospitalization. Mortality was the primary outcome of our investigation, and it was recorded using death certificates and/or medical records. Severe COVID-19 was defined as admission to the intensive care unit or a qSOFAscore ≥ 2 or CURB65scores ≥ 3. After using propensity score matching, 365 patients taking Remdesivir and 365 controls were included. No significant differences emerged between the two groups in terms of mean age and percentage of females, while patients taking Remdesivir were less frequently active smokers (p

Abstract Background Obesity represents an epidemic of rising numbers worldwide year after year. In the Orthopedic field, obesity is one of the major causes leading to osteoarthritis needing Total Joint Arthroplasty (TJA). Still, contextually, it represents one of the most significant risk factors for joint replacement complications and failures. So, bariatric Surgery (BS) is becoming a valuable option for weight control and mitigating obesity-related risk factors. This review of the literature and meta-analysis aims to evaluate periprosthetic joint infections (PJI) and surgical site infections (SSI) rates in patients who underwent TKA after BS compared to obese patients without BS. Methods Systematic review was performed according to Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines up to October 2023. We included longitudinal studies comparing obese patients who underwent total knee arthroplasty after bariatric surgery (study group) and obese patients who underwent TKA (control group). The surgical site infection and Periprosthetic joint infection rate were compared among groups using a meta-analytical approach. Results The online database and references investigation identified one hundred and twenty-five studies. PJI rate differed significantly among groups, (z = -21.8928, p

Abstract Despite progress in the prevention and diagnosis of cancer, current technologies for tumor detection present several limitations including invasiveness, toxicity, inaccuracy, lengthy testing duration and high cost. Therefore, innovative diagnostic techniques that integrate knowledge from biology, oncology, medicinal and analytical chemistry are now quickly emerging in the attempt to address these issues. Following this approach, here we developed a paper-based electrochemical device for detecting cancer-derived Small Extracellular Vesicles (S-EVs) in fluids. S-EVs were obtained from cancer cell lines known to express, at a different level, the αvβ6 integrin receptor, a well-established hallmark of numerous epithelial cancer types. The resulting biosensor turned out to recognize αvβ6-containing S-EVs down to a limit of 0.7*103 S-EVs/mL with a linear range up to 105 S-EVs /mL, and a relative standard deviation of 11%, thus it may represent a novel opportunity for αvβ6 expressing cancers detection.

BackgroundThe study’s main objectives were to evaluate the distribution of levels of procrastination and its relationship with sleep quality, smoking status, alcohol consumption, and skipping breakfast, as a proxy measure of an unhealthy dietary pattern, among Italian university students.MethodsA cross-sectional study was conducted at the “Magna Græcia” University of Catanzaro in the Southern part of Italy, using stratified random sampling techniques. Eligible students were sent an anonymous online survey aimed at assessing sociodemographic characteristics, procrastination levels using the Pure Procrastination Scale, sleep quality using Pittsburgh Sleep Quality Index, smoking status, alcohol consumption using WHO’s Alcohol Use Disorders Identification Tool, and breakfast habits.ResultsThe study included 518 participants with a mean age of 23 year. More than half of the sample was enrolled in medicine or life science majors and the procrastination mean score was 15 (±5.9 SD). Being procrastinators was significantly more frequently among students who were poor sleepers, hazardous alcohol consumers and breakfast skippers. When analyzing the clustering of risky behaviors, it was found that as the number of risky behaviors increased, the procrastination score exhibited an exponential increase.ConclusionThe study findings showed that university students who engage in procrastination tend to adopt risky health behaviors. The data gathered could be useful to derive targeted interventions aimed at groups more exposed to harmful health behaviors and to encourage institutional policies to promote healthy lifestyles within universities. Universities can act as hubs for cultivating a culture of well-being and promoting a healthy environment.

Background: This study aims to assess the activity of solutions containing povidone-iodine (PI) and hydrogen peroxide (H2O2) alone or combined on the biofilm of microbial species in the contest of periprosthetic joint infection (PJI). Methods: Different antiseptic solutions were tested on 2-day-old biofilms of Gram-positive and Gram-negative bacteria and fungi at 1 and 3 minutes of exposure. The efficacy of these solutions was evaluated by measuring the biofilm metabolic activity by methoxynitrosulfophenyl-tetrazolium carboxanilide (XTT) reduction assay. The anti-biofilm effect of 5% PI and 0.3% PI + 0.5% H2O2 was tested on a 5-day-old biofilm using colony-forming unit counts and an XTT reduction assay. Results: PI and H2O2 solutions showed concentration-dependent anti-biofilm activity except for E. faecalis. PI at 5% was the most active solution against the 2-day-old biofilm of all test microorganisms. The 0.3% PI + 0.5% H₂O₂ solution had a significant effect only at 3 minutes. The 5% PI and 0.3% PI + 0.5% H₂O₂ effect was evaluated on 5-day-old biofilms. PI at 5% produced a significant reduction in metabolic activity at both 1 and 3 minutes; 0.3% PI + 0.5% H₂O₂ caused a significant activity against all Gram-positive strains after 3 minutes, with a greater metabolic activity reduction than 5% PI. Conclusions: In the case of PJI caused by Gram-positive bacteria, 0.3% PI + 0.5% H₂O₂ could be used for wound irrigation for 3 minutes of exposure. In the case of PJI with a different etiological agent or PJI with an unknown etiology, it is advisable to use 5% PI for 1 minute of exposure.

Abstract Objectives This study's primary purpose was to demonstrate the correlation of preoperative right ventricular free‐wall longitudinal strain (RVFWLS) and pre‐/postsurgical variation in strain (delta strain) with the clinical and echocardiographic diagnosis of right ventricular dysfunction. Its secondary purpose was to determine the correlation of RVFWLS and delta strain with length of stay (LOS) in the intensive care unit (ICU), ventilation days, trend of natriuretic peptide test. (NT‐proBNP) and lactate in the first 48 h, incidence of acute renal failure, and 28‐day mortality. Design Prospective observational study. Setting Cardio‐thoracic and Vascular Anaesthesia Department and ICU of the University Hospital Integrated Trust of Verona. Participants Patients scheduled for mitral surgery. Interventions None. Measurements and Main Results All clinical and transoesophageal echocardiographic (TEE) parameters were collected at baseline, before surgery (T1) and at admission in the ICU postsurgery (T2). During the postoperative period, the clinical and echocardiographic diagnoses of right, left, or biventricular dysfunction were evaluated. TEE parameters were evaluated by a cardiologist offline. The patients were divided into two subgroups according to the development of any type of ventricular dysfunction. No statistically significant differences emerged between the two groups. According to a logistic regression model, a T1‐RVFWLS value of −15% appeared to predict biventricular dysfunction (sensitivity: 100%; specificity: 91.3%). No correlation between T1‐ or T2‐RVFWLS and creatinine, hours of ventilation or ICU LOS was found. Conclusions Our study introduces a new parameter that could be used in perioperative evaluations to identify patients at risk of postoperative biventricular dysfunction.

BackgroundThe eco-climatic crisis has been defined by the World Health Organization as the “single biggest health threat facing humanity,” influencing both the emergence of zoonoses and the spread of vector-borne and water-borne diseases. The aim of this survey was to explore knowledge, eco-anxiety and attitudes toward the ecological and climate crisis among young Italian doctors and medical students.MethodsA cross-sectional, multicenter survey was conducted from November 2022 to June 2023, by administering an anonymous questionnaire to Italian doctors and students of medicine. Endpoint of the study was a Knowledge, Attitudes and Practices (KAP) score on ecological and climate crisis (0–20 points). Association between variables and KAP score was assessed by Kruskal-Wallis’ or Spearman’s test, as appropriate, and significant variables were included into ordinal regression model and reported as adjusted odds ratio (aOR) with their 95% confidence intervals (CI).ResultsBoth KAP and eco-anxiety scores showed acceptable levels of consistency with Cronbach’s alpha. A total of 605 medical doctors and students living in 19 Italian regions were included in the study. Median age [Q1-Q3] was 27.6 [24.1–31.3] and females were 352 (58.2%). Despite showing good attitudes toward climate action, knowledge gap were found, with 42.5% (n = 257) of the respondents not knowing the temperature limits set by the Paris Agreements and 45.5% (n = 275) believing that climate change is caused by sunspots. Fears suggestive for eco-anxiety were common. At multivariable ordinal regression, high levels of eco-anxiety (aOR 1.29, p = 0.001) and low trust in government action (aOR 1.96, p = 0.003) were associated with a higher KAP score. Only one Italian medical school offered an educational module on climate change.ConclusionYoung Italian doctors and medical students are concerned about the climate crisis but show poor knowledge of these topics. The Italian academic system should urgently respond to this need.

IntroductionMesial temporal lobe epilepsy (MTLE) is one of the most prevalent forms of focal epilepsy in surgical series, particularly among adults. Over the decades, different surgical strategies have been developed to address drug-resistant epilepsy while safeguarding neurological and cognitive functions. Among these strategies, anterior temporal lobectomy (ATL), involving the removal of the temporal pole and mesial temporal structures, has emerged as a widely employed technique. Numerous modifications have been proposed to mitigate the risks associated with aphasia, cognitive issues, and visual field defects.MethodsOur approach is elucidated through intraoperative and cadaveric dissections, complemented by neuroradiological and cadaveric measurements of key anatomical landmarks. A retrospective analysis of patients with drug-resistant MTLE who were treated using our ATL technique at IRCCS Neuromed (Pozzilli) is presented.ResultsA total of 385 patients were treated with our ATL subpial technique anatomically focused on the anterior Sylvian point (ASyP). The mean FU was 9.9 ± 5.4 years (range 1–24). In total, 84%of patients were free of seizures during the last follow-up, with no permanent neurological deficits. Transient defects were as follows: aphasia in 3% of patients, visual field defects in 2% of patients, hemiparesis in 2% of patients, and cognitive/memory impairments in 0.8% of patients. In cadaveric dissections, the ASyP was found at a mean distance from the temporal pole of 3.4 ± 0.2 cm (range 3–3.8) at the right side and 3.5 ± 0.2 cm (3.2–3.9) at the left side. In neuroimaging, the ASyP resulted anterior to the temporal horn tip in all cases at a mean distance of 3.2 ± 0.3 mm (range 2.7–3.6) at the right side and 3.5 ± 0.4 mm (range 2.8–3.8) at the left side.DiscussionTo the best of our knowledge, this study first introduces the ASyP as a reliable and reproducible cortical landmark to perform the ATL to overcome the patients’ variabilities, the risk of Meyer’s loop injury, and the bias of intraoperative measurements. Our findings demonstrate that ASyP can be a safe cortical landmark that is useful in MTLE surgery because it is constantly present and is anterior to risky temporal regions such as temporal horn and language networks.

Conformational diseases, such as Alzheimer’s, Parkinson’s and Huntington’s diseases as well as ataxias and fronto-temporal disorders, are part of common class of neurological disorders characterised by the aggregation and progressive accumulation of mutant proteins which display aberrant conformation. In particular, Huntington’s disease (HD) is caused by mutations leading to an abnormal expansion in the polyglutamine (poly-Q) tract of the huntingtin protein (HTT), leading to the formation of inclusion bodies in neurons of affected patients. Furthermore, recent experimental evidence is challenging the conventional view of the disease by revealing the ability of mutant HTT to be transferred between cells by means of extracellular vesicles (EVs), allowing the mutant protein to seed oligomers involving both the mutant and wild type forms of the protein. There is still no successful strategy to treat HD. In addition, the current understanding of the biological processes leading to the oligomerization and aggregation of proteins bearing the poly-Q tract has been derived from studies conducted on isolated poly-Q monomers and oligomers, whose structural properties are still unclear and often inconsistent. Here we describe a standardised biochemical approach to analyse by isopycnic ultracentrifugation the oligomerization of the N-terminal fragment of mutant HTT. The dynamic range of our method allows one to detect large and heterogeneous HTT complexes. Hence, it could be harnessed for the identification of novel molecular determinants responsible for the aggregation and the prion-like spreading properties of HTT in the context of HD. Equally, it provides a tool to test novel small molecules or bioactive compounds designed to inhibit the aggregation of mutant HTT.

ABSTRACT: Background: Low back pain (LBP) is the most frequent indication to magnetic resonance imaging (MRI) examinations of the lumbosacral spine. The individual role of soft tissues, including muscles, on LBP is not fully understood and the contribution of each MRI-derived parameter of soft tissues status on the intensity of LBP has not been investigated in detail. Methods: The study design was observational retrospective, single center carried out at a University Hospital. Images were acquired using a using a 1.5 Tesla scanner. Patients completed a symptom questionnaire and rated their pain intensity using the Visual Analogue Scale (VAS). The VAS scores ​​were categorized as mild, moderate, and severe using cutoff values of 3.8 and 5.7, based on the literature. Biometric data, including weight and height, were also recorded to calculate the body mass index (BMI). The ratios between intramuscular fat infiltration and net muscle area were also calculated. Patient sample included 94 patients with LBP underwent MRI of the lumbosacral spine. Results: The stepwise analysis revealed that increasing psoas net area was associated with lower VAS levels (odds ratio [OR]: 0.94: 95% confidence interval [CI]: 0.90–0.98; p=.005), and an increase of one square centimeter of total psoas area resulted in a greater probability of reporting a mild (+1.21%; 95% CI: 0.37, 2.05%) or a moderate VAS (+0.40%; 95% CI: -0.02, 0.82%), Furthermore, a more severe VAS was associated with a higher BMI (OR: 1.13; 95% CI: 1.00–1.27). Conclusion: Our study demonstrates a relationship between LBP and MRI parameters of paravertebral and psoas muscles status. The psoas muscle is extremely important for spine stabilization and is linked to clinical symptoms of patients affected by LBP. These findings could contribute to future studies and improve treatment options in patients with LBP, possibly reducing the impact on disability, quality of life and socioeconomical burden.

Background: To tackle future health threats, the study aimed to assess healthcare workers’ (HCWs) adherence to infection prevention and control (IPC) measures and to evaluate whether knowledge and concerns related to COVID-19 could be its potential predictors. A secondary aim was to explore how and how much healthcare facilities support HCWs to implement IPC practices. Methods: This cross-sectional study was conducted between June and September 2021 in Southern Italy using a self-administered questionnaire. Socio-demographic and professional characteristics, COVID-19 preparedness and response plan in the facilities, knowledge about COVID-19’s transmission and non-pharmaceutical interventions (NPIs), concerns about the possibility of transmitting COVID-19 to family members and patients, adherence to IPC practices, and sources of information were investigated. Results: Among the 492 enrolled HCWs, the overall knowledge median score was 6 out of a maximum score of 8 and predictors of good knowledge were practicing in a facility that organized training courses about IPC measures and having more years in practice. HCWs were more concerned about the possibility of transmitting the infection to their family members (64.4%) than to negative patients (38.9%). A sizable proportion claimed to take off the face mask by touching only the straps or ties (76.3%) and to replace the face mask when it was wet (70.7%). Only 26.2% never/rarely touched the face mask while wearing it. Good adherence to preventative practices was more likely in HCWs other than physicians and practicing in a facility that organized training courses about IPC measures and in regional hospitals compared with those practicing in district hospitals. Conclusions: The study findings produce information about what worked well and where gaps were identified during COVID-19 pandemic, along with data useful for hospitals and health systems in general to better prepare and put in place appropriate interventions in case of similar future events.