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Pentylenetetrazole (PTZ) is a common convulsant agent used in animal models to investigate the mechanisms of seizures. Although adult zebrafish have been recently used to study epileptic seizures, a thorough characterization of the PTZ-induced seizures in this animal model is missing. The goal of this study was to perform a detailed temporal behavior profile characterization of PTZ-induced seizure in adult zebrafish. The behavioral profile during 20 min of PTZ immersion (5, 7.5, 10, and 15 mM) was characterized by stages defined as scores: (0) short swim, (1) increased swimming activity and high frequency of opercular movement, (2) erratic movements, (3) circular movements, (4) clonic seizure-like behavior, (5) fall to the bottom of the tank and tonic seizure-like behavior, (6) death. Animals exposed to distinct PTZ concentrations presented different seizure profiles, intensities and latencies to reach all scores. Only animals immersed into 15 mM PTZ showed an increased time to return to the normal behavior (score 0), after exposure. Total mortality rate at 10 and 15 mM were 33% and 50%, respectively. Considering all behavioral parameters, 5, 7.5, 10, and 15 mM PTZ, induced seizures with low, intermediate, and high severity, respectively. Pretreatment with diazepam (DZP) significantly attenuated seizure severity. Finally, the brain PTZ levels in adult zebrafish immersed into the chemoconvulsant solution at 5 and 10 mM were comparable to those described for the rodent model, with a peak after a 20-min of exposure. The PTZ brain levels observed after 2.5-min PTZ exposure and after 60-min removal from exposure were similar. Altogether, our results showed a detailed temporal behavioral characterization of a PTZ epileptic seizure model in adult zebrafish. These behavioral analyses and the simple method for PTZ quantification could be considered as important tools for future investigations and translational research.

To compare the incidence of AM hospitalizations and complications across three periods: pre-pandemic, pandemic, and post-pandemic. Additionally, the study aims to evaluate associations with patient age, need for surgical intervention, antibiotic therapy, and isolated etiological agents. This retrospective cohort study reviewed pediatric charts from three 22-month periods: pre-pandemic (P1), pandemic (P2), and post-pandemic (P3). These periods were compared in terms of case numbers, presence and severity of AM complications, patient demographics (age and sex), and treatment approaches. A total of 9 AM cases were recorded in (P1), 5 in the (P2), and 25 in (P3). This represents a 25.5 % reduction in AM incidence during the pandemic compared to the pre-pandemic period, though this was not statistically significant (p = 0.8027). However, a significant 103.3 % increase in AM incidence was noted between the pre- and post-pandemic periods (p = 0.0322). No significant differences were found among periods regarding age, sex, complications, case severity, surgical intervention, antibiotic duration, or length of hospitalization. Although AM incidence slightly declined during the pandemic, the post-pandemic period showed a significant rise in the incidence of cases compared to pre-pandemic values.

ObjectivesWe aimed to provide a region-wide comprehensive account of the direct effects of COVID-19 on chronic disease patients, in terms of disease incidence, severity and mortality, over a 2-year pandemic period (2020–2021).DesignPopulation-based retrospective study.Setting/participantsAdult patients, affected by at least 1 of 32 prevalent chronic conditions, residing in the Emilia-Romagna Region in Italy, during the years 2020 (N=1 791 189, 47.7% of the overall adult regional population) and 2021 (N=1 801 071, 47.8%).ResultsCOVID-19 incidence among chronic disease patients was 4.1% (74 067 cases) in 2020 and 7.3% (126 556 cases) in 2021, varying across pathologies, with obesity and dementia showing the highest incidence. Hospitalisation rate for pneumonia or acute respiratory distress syndrome among SARS-CoV-2-positive patients was 15.4%. COVID-19-related excess mortality, that is, deaths from COVID-19 as either main or contributing (1.5% of the total) cause of death, was observed during the three pandemic waves, with observed/expected death ratios ranging from +38% (March 2020) to +11% (December 2021). Increased risks of both COVID-19-related hospitalisation and death were associated with male gender, elderly age and many pre-existing pathologies, including cardiovascular, cerebrovascular and respiratory diseases, neurological and psychiatric disorders, and metabolic dysfunctions. The higher the number of concomitant pathologies, the greater the risk of COVID-19-related adverse outcomes: the likelihood of hospitalisation and death more than doubled for people with more than two comorbidities, compared with those with one underlying condition.ConclusionsThis study presents a thorough and up-to-date quantification of the direct impact of COVID-19 on chronic disease patients. The results obtained are particularly relevant considering that people with pre-existing chronic conditions accounted for almost all cases of COVID-19-related hospitalisation (82.6%) and death (91.5%) in a vast region of Italy, among the hardest hit by the pandemic.

ObjectivesWe aimed to provide a region-wide comprehensive account of the indirect effects of COVID-19 on patients with chronic disease, in terms of non-COVID-19 mortality, and access to both inpatient and outpatient health services over a 2-year pandemic period.DesignPopulation-based retrospective study.SettingAdult patients, affected by at least 1 of 32 prevalent chronic conditions, residing in the Emilia-Romagna Region in Italy, during the years 2020 (N=1 791 189, 47.7% of the overall adult regional population) and 2021 (N=1 801 071, 47.8%).ResultsOverall, non-COVID-19 mortality among patients with chronic disease during the pandemic (2.7%) did not differ substantially from the expected mortality (2.5%), based on a 3 years prepandemic period (2017–2019) and adjusting for the demographic and clinical characteristics of the population under study. Indeed, while the first pandemic wave was characterised by a significant non-COVID-19 excess mortality (March: +35%), the subsequent phases did not show such disruptive variations in non-COVID-19 deaths, which remained around or even below the excess mortality threshold. End-of-life care of patients with chronic disease, especially for non-COVID-19 cases, significantly shifted from hospitalisations (−19%), to homecare (ADI: +7%; w/o ADI: +9%). Overall, healthcare of patients without COVID-19 chronic disease decreased, with similar negative trends in hospitalisations (−15.5%), major procedures (−19.6%) and ER accesses (−23.7%). Homecare was the least affected by the pandemic, with an overall reduction of −9.8%. COVID-19 outbreak also impacted on different types of outpatient care. Rehabilitation therapies, specialist visits, diagnostic and lab tests were considerably reduced during the first pandemic wave and consequent lockdown, with access rates of patients without COVID-19 chronic disease below −60%.ConclusionsThis work thoroughly describes how a large and well-defined population of patients without COVID-19 chronic disease has been affected by the changes and reorganisation in the healthcare system during 2 years of the pandemic, highlighting health priorities and challenges in chronic disease management under conditions of limited resources.

Camu-camu (Myrciaria dubia) is known for its antioxidant properties, although little is known about its developmental safety effects, particularly on adult neural function under basal redox and oxidative stress conditions. Therefore, this study sought to address this gap by conducting three complementary protocols using Drosophila melanogaster to investigate these effects. The initial assays revealed that second-stage larvae consumed diets supplemented with various concentrations of camu-camu uniformly, establishing a 50% lethal concentration at 4.799 mg/mL. Hence, non-lethal (0.1, 0.5, and 1 mg/mL) and sub-lethal (5 and 10 mg/mL) concentrations were then chosen to evaluate the effects of camu-camu on preimaginal development and adult neural function. Our observations showed that camu-camu impacts the expression of antioxidant enzymes, reactive species, and lipoperoxidation. Notably, sub-lethal concentrations decreased preimaginal viability and locomotor activity, negatively influenced geotaxis and acetylcholinesterase activity, and increased reactive species, catalase, and glutathione S-transferase activity in flies. Additionally, the protective effects of camu-camu against oxidative stress induced by iron (20 mM) were assessed. Flies supplemented with 0.5 mg/mL of camu-camu during the larval period showed improved neural viability and function, and this supplementation was found to protect against oxidative stress. These findings are instrumental in evaluating the safety and efficacy of commercial supplements based on camu-camu, offering significant insights for future research and application.

The aim of our study was to investigate fiber type distribution and contractile characteristics of Latissimus Dorsi muscle (LDM). Samples were collected from 18 young healthy subjects (9 males and 9 females) through percutaneous fine needle muscle biopsy. The results showed a predominance of fast myosin heavy chain isoforms (MyHC) with 42% of MyHC 2A and 25% of MyHC 2X, while MyHC 1 represented only 33%. The unbalance toward fast isoforms was even greater in males (71%) than in females (64%). Fiber type distribution partially reflected MyHC isoform distribution with 28% type 1/slow fibers and 5% hybrid 1/2A fibers, while fast fibers were divided into 30% type 2A, 31% type A/X, 4% type X, and 2% type 1/2X. Type 1/slow fibers were not only less abundant but also smaller in cross-sectional area than fast fibers. During maximal isometric contraction, type 1/slow fibers developed force and tension significantly lower than the two major groups of fast fibers. In conclusion, the predominance of fast fibers and their greater size and strength compared to slow fibers reveal that LDM is a muscle specialized mainly in phasic and powerful activity. Importantly, such specialization is more pronounced in males than in females.

Camu-camu (Myrciaria dubia) is known for its antioxidant properties, although little is known about its developmental safety effects, particularly on adult neural function under basal redox and oxidative stress conditions. Therefore, this study sought to address this gap by conducting three complementary protocols using Drosophila melanogaster to investigate these effects. The initial assays revealed that second-stage larvae consumed diets supplemented with various concentrations of camu-camu uniformly, establishing a 50% lethal concentration at 4.799 mg/mL. Hence, non-lethal (0.1, 0.5, and 1 mg/mL) and sub-lethal (5 and 10 mg/mL) concentrations were then chosen to evaluate the effects of camu-camu on preimaginal development and adult neural function. Our observations showed that camu-camu impacts the expression of antioxidant enzymes, reactive species, and lipoperoxidation. Notably, sub-lethal concentrations decreased preimaginal viability and locomotor activity, negatively influenced geotaxis and acetylcholinesterase activity, and increased reactive species, catalase, and glutathione S-transferase activity in flies. Additionally, the protective effects of camu-camu against oxidative stress induced by iron (20 mM) were assessed. Flies supplemented with 0.5 mg/mL of camu-camu during the larval period showed improved neural viability and function, and this supplementation was found to protect against oxidative stress. These findings are instrumental in evaluating the safety and efficacy of commercial supplements based on camu-camu, offering significant insights for future research and application.

This retrospective analysis of the prospective IGOMIPS registry reports on 1191 minimally invasive pancreatic resections (MIPR) performed in Italy between 2019 and 2022, including 668 distal pancreatectomies (DP) (55.7%), 435 pancreatoduodenectomies (PD) (36.3%), 44 total pancreatectomies (3.7%), 36 tumor enucleations (3.0%), and 8 central pancreatectomies (0.7%). Spleen-preserving DP was performed in 109 patients (16.3%). Overall incidence of severe complications (Clavien–Dindo ≥ 3) was 17.6% with a 90-day mortality of 1.9%. This registry analysis provided some important information. First, robotic assistance was preferred for all MIPR but DP with splenectomy. Second, robotic assistance reduced conversion to open surgery and blood loss in comparison to laparoscopy. Robotic PD was also associated with lower incidence of severe postoperative complications and a trend toward lower mortality. Fourth, the annual cut-off of ≥ 20 MIPR and ≥ 20 MIPD improved selected outcome measures. Fifth, most MIPR were performed by a single surgeon. Sixth, only two-thirds of the centers performed spleen-preserving DP. Seventh, DP with splenectomy was associated with higher conversion rate when compared to spleen-preserving DP. Eighth, the use of pancreatojejunostomy was the prevalent reconstruction in PD. Ninth, final histology was similar for MIPR performed at high- and low-volume centers, but neoadjuvant chemotherapy was used more frequently at high-volume centers. Finally, this registry analysis raises important concerns about the reliability of R1 assessment underscoring the importance of standardized pathology of pancreatic specimens. In conclusion, MIPR can be safely implemented on a national scale. Further analyses are required to understand nuances of implementation of MIPR in Italy.

The response to resistance training and protein supplementation in the latissimus dorsi muscle (LDM) has never been investigated. We investigated the effects of resistance training (RT) and protein supplementation on muscle mass, strength, and fiber characteristics of the LDM. Eighteen healthy young subjects were randomly assigned to a progressive eight-week RT program with a normal protein diet (NP) or high protein diet (HP) (NP 0.85 vs. HP 1.8 g of protein·kg−1·day−1). One repetition maximum tests, magnetic resonance imaging for cross-sectional muscle area (CSA), body composition, and single muscle fibers mechanical and phenotype characteristics were measured. RT induced a significant gain in strength (+17%, p < 0.0001), whole muscle CSA (p = 0.024), and single muscle fibers CSA (p < 0.05) of LDM in all subjects. Fiber isometric force increased in proportion to CSA (+22%, p < 0.005) and thus no change in specific tension occurred. A significant transition from 2X to 2A myosin expression was induced by training. The protein supplementation showed no significant effects on all measured outcomes except for a smaller reduction of 2X myosin expression. Our results suggest that in LDM protein supplementation does not further enhance RT-induced muscle fiber hypertrophy nor influence mechanic muscle fiber characteristics but partially counteracts the fast-to-slow fiber shift.