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Pharmacological inhibition of carbonic anhydrases with a positively charged pyridinium sulfonamide phenocopies the neuroprotective effects of Car9 genetic ablation in a murine setting of oxygen/glucose deprivation followed by re-oxygenation and is associated with improved neuronal function in ischemic rats
No full textCarbonic anhydrases constitute a family of metalloenzymes vital for maintaining acid-base balance and regulating pH in physio-pathological processes. These findings suggest carbonic anhydrases as potential therapeutic targets for treating pH-associated disorders, including cerebral ischemia, to mitigate hypoxia- and reoxygenation-induced neuronal damage. A focus on carbonic anhydrase IX showed that ischemic stress altered subcellular distributions of this enzyme in rodent neuronal populations. Given the enzyme's canonical membrane localization, we implemented pharmacological inhibition using a membrane-impermeant sulfonamide inhibitor in neuronal models of brain ischemia. The treatments exerted neuroprotective effects on neurons from Car9 knockout mice. Moreover, administration of the sulfonamide inhibitor to rats subjected to transient middle cerebral artery occlusion decreased infarct volumes and improved neurological deficits. Our results support the involvement of carbonic anhydrase IX in postischemic damage and pave the way for possible pharmacological interventions with selective inhibitors in the management of brain ischemia
Demographic dynamics and the labor market
No full textIl Paper si sofferma sulle implicazioni della transizione demografica e sulle sue ricadute sull’occupazione, analizzando gli strumenti che il management aziendale dispone per orientare le scelte organizzative del personale ed incidere sulla permanenza nel mercato del lavoro
Clinical presentation, diagnostics, and outcomes of infants with congenital and postnatal tuberculosis: a multicentre cohort study of the Paediatric Tuberculosis Network European Trials Group (ptbnet)
No full textBackground: According to estimates, globally more than 200,000 pregnant women develop tuberculosis (TB) annually. Despite this, data on perinatal TB remain scarce. This study aimed to describe perinatal TB, comprising congenital (cTB) and postnatal (pTB) TB, in a European setting. Methods: Retrospective cohort study via the Paediatric Tuberculosis Network European Trials Group (ptbnet) capturing and comparing cases of cTB and pTB diagnosed at 104 participating European healthcare institutions between 1995 and 2019. Findings: Forty-six cases reported by 20 centres were included in the final analysis (cTB, n = 27; pTB, n = 19). Median age at symptom onset was one week in cTB (IQR: 0–1 weeks), and 12 weeks in pTB patients (IQR: 5–18 weeks). Prematurity was more common in cTB than pTB patients [57.9% (11/19); 95% CI: 36.3–76.9% vs. 21.1% (4/19); 95% CI: 8.5–43.3%; p = 0.049], and the average birth weight was significantly lower [1680 g; IQR: 932–2805 g vs. 2890 g; IQR: 2461–3400 g; p = 0.0043]. Microbiological confirmation was achieved in most patients [85.2% (23/27); 95% CI: 67.5–94.1% vs. 78.9% (15/19); 95% CI: 56.7–91.5%; p = 0.70]. The sensitivity of interferon-gamma release assays was poor in both groups [25.0% (3/12) 95% CI: 8.9–53.2% vs. 35.7% (5/14) 95% CI: 16.3–61.2%; p = 0.68]; in contrast, the sensitivity of the tuberculin skin tests (at 5 mm cut-off) was significantly higher in pTB patients [16.7% (2/12) 95% CI: 4.7–44.8% vs. 66.7% (10/15); 95% CI: 41.7–84.8%; p = 0.0185]. Approximately half of the patients required intensive care support [51.9% (14/27) 95% CI: 34.0–69.3% vs. 47.4% (9/19); 95% CI: 27.3–68.3%; p > 0.99]. Four (4/46; 8.7%) patients died, and four (4/46; 8.7%) had severe long-term sequelae. Interpretation: There was substantial mortality and morbidity in this patient cohort, despite the high-resource setting. cTB was associated with premature birth and low birth weight. In contrast to microbiological tests, immunological tests perform poorly in perinatal TB, and should therefore not be used as rule-out tests. Funding: No study-specific funding
Italian glaucoma virtual clinics: Developing a consensus for remote patient management
No full textPurpose: To establish expert consensus on guidelines for implementing glaucoma virtual clinics in Italy, focusing on patient suitability, essential clinical assessments and staffing requirements. Methods: A modified Delphi method was used to achieve consensus among selected Italian glaucoma specialists. The steering group developed a structured questionnaire with 66 items across key areas: Patient Categories, Clinical Assessments, Roles and Staffing and Guidelines for glaucoma virtual clinic implementation. A panel of experts reviewed and rated each item across multiple rounds to reach consensus. Results: Out of 19 invited glaucoma specialists, 16 and 11 participated in rounds 1 and 2, respectively. Consensus was achieved on 57.6% of the questions, identifying specific patient profiles suitable for glaucoma virtual clinics, essential diagnostic tests and required roles in a virtual setting. Experts agreed on the importance of standardized assessments and the necessity of support staff such as orthoptists and ophthalmic assistants in the glaucoma virtual clinic structure. Conclusion: This Delphi panel provides guidance for implementing glaucoma virtual clinics in Italy, establishing guidelines on patient selection, required assessments and staffing needs. Tailored glaucoma virtual clinics can enhance glaucoma care accessibility, streamline workflows and address the growing demand from healthcare systems
Information index augmented eRG to model vaccination behaviour: A case study of COVID-19 in the US
No full textRecent pandemics triggered the development of a number of mathematical models and computational tools apt at curbing the socio-economic impact of these and future pandemics. The need to acquire solid estimates from the data led to the introduction of effective approaches such as the epidemiological Renormalization Group (eRG). A recognized relevant factor impacting the evolution of pandemics is the feedback stemming from individuals’ choices. The latter can be taken into account via the information index which accommodates the information–induced perception regarding the status of the disease and the memory of past spread. Therefore, we show how to augment the eRG through the information index. We first develop the behavioural version of the eRG (BeRG) and then test it against the US vaccination campaign for COVID-19. We find that the BeRG improves the description of the pandemic dynamics of the US divisions for which the epidemic peak occurs after the start of the vaccination campaign. Additionally, we observe, via the BeRG model, a behavioural impact on the increase in the number of vaccinated individuals for all US divisions when compared to the original eRG model. The BeRG reasonably captures the COVID-19 vaccination behaviour which has not undergone stressful periods as the nearly linear growth of the vaccinated individuals suggests. Our results strengthen the relevance of taking into account the human behaviour component when modelling pandemic evolution. To inform public health policies, the model can be readily employed to investigate the socio-epidemiological dynamics, including vaccination campaigns, for other world regions
Sulcus‐deepening trochleoplasty grants satisfactory results with minimal patellofemoral arthritis at 23–30 years of follow‐up
No full textPurpose: The purpose of this study was to evaluate the radiographic and clinical outcomes of sulcus-deepening trochleoplasty at a minimum follow-up of 23 years. Methods: The authors evaluated a retrospective series of 10 patients (11 knees) who underwent trochleoplasty between 1993 and 2000. All patients were assessed at a minimum follow-up of 23 years by an independent clinician who noted any patellar redislocations and collected the International Knee Documentation Committee (IKDC), Kujala scores and range of motion. Radiographic examination was performed to assess patellofemoral arthritis using the Iwano classification. Results: A total of 11 knees, from five women and five men aged 25.6 ± 6.9 years (range, 15–47 years) underwent trochleoplasty during the inclusion period. All 11 knees underwent adjuvant procedures during trochleoplasty (100%): 10 had tibial tuberosity osteotomy (TTO) and vastus medialis plasty and 1 had only vastus medialis plasty (had prior TTO). At a follow-up of 24.4 ± 2.1 years (range, 23–30 years), two patients were lost to follow-up (18%). The Iwano classification was Grade 1 in three patients (33%), Grade 2 in four patients (44%) and Grade 4 in two patients (22%). The flexion range was 130 ± 8.7° and satisfaction was 9.2 ± 0.7, Kujala was 76.9 ± 8.5 and IKDC was 65.5 ± 13.8. Conclusion: At 23–30 years following sulcus-deepening trochleoplasty in this small series of 10 patients (11 knees), patients had satisfactory clinical scores, only 1 patient reported an episode of traumatic patellar dislocation, and two knees had patellofemoral arthritis of Iwano Grade >2 (22%). Level of Evidence: Level IV
Diritto e procedura penale. Diritto canonico
No full textL’intervento ha riguardato la ricostruzione del primo reclutamento universitario presso l’Università di Napoli nelle materie del Diritto e procedura penale e del diritto canonico (1861-1886
Chemometric validation of an enzymatic method to detect glucose and fructose in wines
No full textFermentable sugars influence the alcohol content of the wine, as well as the wine's mouthfeel attributes (such as astringency, viscosity, and density) and overall texture, reduce the perception of astringency (by interacting with polyphenols), help retain aromatic compounds in the wine, and enhance its colloidal stability. Measuring fermentable sugars is essential for oenologists to decide the best harvest time and manage fermentation. Traditional titrimetric methods, like the Lane–Eynon method recognized by AOAC, require skilled personnel, lengthy analysis, careful monitoring, and hazardous reagents. The International Organisation of Vine and Wine recommends using simpler spectroscopic methods for measuring sugar levels in wines, though accuracy depends on analyst expertise. This research aimed to validate an automated enzymatic system for quantifying glucose and fructose in wine samples. Such technology can reduce costs by minimizing the need for specialized staff and increasing daily analysis throughput, while also lowering operator error and improving environmental sustainability through better solvent use. The validation process was performed on various wine types (dry red, dry white, moderately sweet, and sweet) by comparing results from the OIV-MA-AS311-02 method by a trained operator (reference method) to those from the automated system. Despite notable average discrepancies, the automated method was found suitable for its purpose, as the differences were less than the measurement uncertainty at similar concentrations, and its repeatability exceeded that of the reference method
Characterisation of milk ejection dynamics in dairy buffaloes based on Lactocorder ® measurements
No full textCurrent milking protocols for dairy buffaloes are often adapted from cattle, despite physiological and behavioural differences between the species. This study aimed to characterise milk ejection dynamics in Italian Mediterranean buffaloes and provide indications for species-specific milking protocols. Data was collected from 798 lactating buffaloes across four commercial farms between March and September 2024, for a total of 2768 individual milking records. Milk ejection traits were measured using a Lactocorder® device, recording peak milk flow rate (HMF), maximum milk yield per minute (HMG), total milking time (tMGG), milk yield during the first three minutes, and overmilking, defined as the time from milk flow <0.20 kg/min to cluster detachment. Traits were analysed using a generalised mixed model including farm, days in milk (DIM), parity, milk yield class, and month as fixed effects. On average, 21% of milk was released in the first minute, 46% by the second, and 66% by the third. Farms differed significantly in tMGG and overmilking (p < 0.05), which in turn were positively correlated (r = +0.43). HMF and HMG peaked in early lactation and declined over time (p < 0.05), whereas DIM did not affect tMGG or overmilking. Parity influenced most traits: second-parity buffaloes had the highest HMF and HMG (1.82 and 1.66 kg/min), while tMGG was longest in ≥5-parity buffaloes (7.83 min) and shortest in primiparous animals (7.00 min). These results indicate that extended milking may be unnecessary, increasing overmilking risk, and that multiparous buffaloes require closer monitoring and farm-specific detachment settings to improve efficiency, udder health, and welfare