Search

GM3 synthase deficiency (GM3SD) is caused by biallelic variants in the ST3GAL5 gene. Early clinical features of GM3SD include infantile onset of severe irritability and feeding difficulties, early intractable seizures, growth failure, hypotonia, sensorineural hearing impairment. We describe the generation and characterization the human induced pluripotent stem cell (hiPSC) line derived from fibroblasts of a 13-year-old girl with GM3 synthase deficiency resulted compound heterozygous for two new variants in the ST3GAL5 gene, c.1166A > G (p.His389Arg) and the c.1024G > A (p.Gly342Ser). The generated hiPSC line shows a normal karyotype, expresses pluripotency markers, and is able to differentiate into the three germ layers.

Congenital Disorders of Glycosylation (CDG) are rare inherited metabolic diseases caused by genetic defects in the glycosylation of proteins and lipids. In this study, we describe the generation and characterization of one human induced pluripotent stem cell (hiPSC) line from a 15-year-old male patient with CDG. The patient carried three variants, one (c.122G > A; p.Arg41Gln) inherited from his father and two (c.445 T > G; p.Leu149Arg and the novel c.980C > G; p.Thr327Arg) inherited from his mother in the ALG8 gene (OMIM #608103). The generated hiPSC line shows a normal karyotype, expresses pluripotency markers, and is able to differentiate into the three germ layers.

Abstract Background Charcot-Marie-Tooth disease (CMT) type 4B3 (CMT4B3) is a rare form of genetic neuropathy associated with variants in the MTMR5/SBF1 gene. MTMR5/SBF1 is a pseudophosphatase predicted to regulate endo-lysosomal trafficking in tandem with other MTMRs. Although almost ubiquitously expressed, pathogenic variants primarily impact on the peripheral nervous system, corroborating the involvement of MTMR5/SBF1 and its molecular partners in Schwann cells-mediated myelinization. Case presentation We report a case of severe CMT4B3 characterized by early-onset motor and axonal polyneuropathy in an Italian child in absence of any evidence of brain and spine MRI abnormalities or intellectual disability and with a biochemical profile suggestive of mitochondrial disease. Using an integrated approach combining both NGS gene panels and WES analysis, we identified two novel compound heterozygous missense variants in MTMR5/SBF1 gene, p.R763H (c.2291G > A) and p.G1064E (c.3194G > A). Studies in muscle identified partial defects of oxidative metabolism. Conclusion We describe the first case of an early onset severe polyneuropathy with motor and axonal involvement, due to recessive variants in the MTMR5/SBF1 gene, with no evidence of brain and spine MRI abnormalities, intellectual disability, no clinical and neurophysiological evidences of distal sensory impairment, and rapid neuromuscular deterioration. This report suggests that MTMR5/SBF1 should be considered in cases of infantile-onset CMT with secondary mitochondrial dysfunction.

Abstract Background Mutations in lysyl-tRNA synthetase (KARS1), an enzyme that charges tRNA with the amino acid lysine in both the cytoplasm and mitochondria, have been associated thus far with autosomal recessive Charcot–Marie–Tooth type CMTRIB, hearing loss type DFNB89, and mitochondrial encephalohepatopathy (MEH) featuring neurodevelopmental disorders with microcephaly, white matter changes, and cardiac and hepatic failure in less than 30 patients. Case presentation We report the clinical, biochemical and molecular findings of a 14-month-old girl with severe MEH compatible clinical features, profound sensorineural hearing loss, leopard spot retinopathy, pancytopenia, and advanced liver disease with portal hypertension leading to death at the age of 30 months. Conclusions Whole exome sequencing identified two rare variants in KARS1 gene. Our report expands the allelic and clinical features of tRNA synthase disorders. Moreover, with our report we confirm the usefulness of WES as first tier diagnostic method in infants with complex multisystem phenotypes.

This article re-examines the sources on the exile period that the Athenian family of the Alcmaeonids spent in Delphi after the murder of Hipparchus in 514 BC. The ancient tradition on this episode is contradictory (especially with regard to the construction of the new temple of Apollo and the “corruption” of the Pythia). Therefore, it can be rather difficult to tell Alcmaeonid propaganda apart from that of their Athenian adversaries. Another hypothesis, however, deserves to be assessed: rather than in Athens, the charge of corrupting the Pythia might itself have been elaborated within a Delphic environment.

Objective: To define the prevalence of variants in collagen VI genes through a next-generation sequencing (NGS) approach in undiagnosed patients with suspected neuromuscular disease and to propose a diagnostic flowchart to assess the real pathogenicity of those variants. Methods: In the past five years, we have collected clinical and molecular information on 512 patients with neuromuscular symptoms referred to our center. To pinpoint variants in COLVI genes and corroborate their real pathogenicity, we sketched a multistep flowchart, taking into consideration the bioinformatic weight of the gene variants, their correlation with clinical manifestations and possible effects on protein stability and expression. Results: In Step I, we identified variants in COLVI-related genes in 48 patients, of which three were homozygous variants (Group 1). Then, we sorted variants according to their CADD score, clinical data and complementary studies (such as muscle and skin biopsy, study of expression of COLVI on fibroblast or muscle and muscle magnetic resonance). We finally assessed how potentially pathogenic variants (two biallelic and 12 monoallelic) destabilize COL6A1-A2-A3 subunits. Overall, 15 out of 512 patients were prioritized according to this pipeline. In seven of them, we confirmed reduced or absent immunocytochemical expression of collagen VI in cultured skin fibroblasts or in muscle tissue. Conclusions: In a real-world diagnostic scenario applied to heterogeneous neuromuscular conditions, a multistep integration of clinical and molecular data allowed the identification of about 3% of those patients harboring pathogenetic collagen VI variants.

Mapping brain functions is crucial for neurosurgical planning in patients with drug-resistant seizures. However, presurgical language mapping using either functional or structural networks can be challenging, especially in children. In fact, most of the evidence on this topic derives from cross-sectional or retrospective studies in adults submitted to anterior temporal lobectomy. In this prospective study, we used fMRI and DTI to explore patterns of language representation, their predictors and impact on cognitive performances in 29 children and young adults (mean age at surgery: 14.6 ± 4.5 years) with focal lesional epilepsy. In 20 of them, we also assessed the influence of epilepsy surgery on language lateralization. All patients were consecutively enrolled at a single epilepsy surgery center between 2009 and 2015 and assessed with preoperative structural and functional 3T brain MRI during three language tasks: Word Generation (WG), Rhyme Generation (RG) and a comprehension task. We also acquired DTI data on arcuate fasciculus in 24 patients. We first assessed patterns of language representation (relationship of activations with the epileptogenic lesion and Laterality Index (LI)) and then hypothesized a causal model to test whether selected clinical variables would influence the patterns of language representation and the ensuing impact of the latter on cognitive performances. Twenty out of 29 patients also underwent postoperative language fMRI. We analyzed possible changes of fMRI and DTI LIs and their clinical predictors. Preoperatively, we found atypical language lateralization in four patients during WG task, in one patient during RG task and in seven patients during the comprehension task. Diffuse interictal EEG abnormalities predicted a more atypical language representation on fMRI (p = 0.012), which in turn correlated with lower attention (p = 0.036) and IQ/GDQ scores (p = 0.014). Postoperative language reorganization implied shifting towards atypical language representation. Abnormal postoperative EEG (p = 0.003) and surgical failures (p = 0.015) were associated with more atypical language lateralization, in turn correlating with worsened fluency. Neither preoperative asymmetry nor postoperative DTI LI changes in the arcuate fasciculus were observed. Focal lesional epilepsy associated with diffuse EEG abnormalities may favor atypical language lateralization and worse cognitive performances, which are potentially reversible after successful surgery.

Introduction: Cardiac rhabdomyomas represent a frequent manifestation of tuberous sclerosis. Tumor growth, mainly prenatally, can result in intrauterine fetal or neonatal deaths in almost 10% of patients. Case Report: We treated 3 consecutive infants aged less than 12 months with sirolimus, an oral mTOR inhibitor. All patients achieved significant reductions in cardiac rhabdomyomas. A complete response was documented in 2 patients, while a partial response with tumor debulking greater than 50% was seen in the other one. The median time to best cardiac response was 1.9 months in all patients, and 3.3 months in those with complete response. The side effects profile was acceptable. Conclusion: Sirolimus may have a significant role in promoting natural regression of cardiac rhabdomyomas. Prospective clinical trials are needed.

Identification of new psychoactive substances (NPS) in biological and non-biological samples represents a hard challenge for forensic toxicologists. Their great chemical variety and the speed with which new NPS are synthesised and spread make stringent the need of advanced tools for their detection based on multidisciplinary approaches. For this reason, in August 2016, the “Unit of Research and Innovation in Forensic Toxicology and Neuroscience of Addiction” (U.R.I.To.N.) was founded by the Forensic Toxicology Division of the University of Florence. In this Research Unit, various professionals (i.e. forensic toxicologists, chemists, physicians) collaborate to study all the aspects of drugs of abuse, especially NPS. Herein, we describe the multidisciplinary approach comprising liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS), gas chromatography hyphenated to mass spectrometry (GC–MS) and solution nuclear magnetic resonance analysis that allowed the identification of three NPS such as 1-(benzofuran-5-yl)-N-methylpropan-2-amine, 2-amino-1-(4-bromo-2,5-dimethoxyphenyl)ethan-1-one (bk-2C-B), and 3-(2-aminopropyl)indole (α-methyltryptamine) in seized materials.

Identifying possible new biological activities of psychoactive substances belonging to various chemical classes may lead to a better understanding of their mode of action and side effects. We report here that amines structurally related to amphetamine, a widely used psychoactive substance, such as amphetamine, methamphetamine, phentermine, mephentermine, and chlorphenteramine, potently activate several carbonic anhydrase (CA, EC 4.2.1.1) isoforms involved in important physiological functions. Of the 11 investigated human (h) isoforms, the widespread hCA I and II, the secreted hCA VI, as well as the cytosolic hCA XIII, and membrane-bound hCA IX and XIV were poorly activated by these amines, whereas the extracellular hCA IV, the mitochondrial enzymes hCA VA/VB, the cytosolic hCA VII, and the transmembrane isoform hCA XII were potently activated. Some of these enzymes are abundant in the brain, raising the possibility that some of the cognitive effects of such psychoactive substances might be related to their activation of these enzymes.

Hereditary spastic paraplegia (HSP) refers to a group of genetically heterogeneous neurodegenerative motor neuron disorders characterized by progressive age-dependent loss of corticospinal motor tract function, lower limb spasticity, and weakness. Recent clinical use of next generation sequencing (NGS) methodologies suggests that they facilitate the diagnostic approach to HSP, but the power of NGS as a first-tier diagnostic procedure is unclear. The larger-than-expected genetic heterogeneity—there are over 80 potential disease-associated genes—and frequent overlap with other clinical conditions affecting the motor system make a molecular diagnosis in HSP cumbersome and time consuming. In a single-center, cross-sectional study, spanning 4 years, 239 subjects with a clinical diagnosis of HSP underwent molecular screening of a large set of genes, using two different customized NGS panels. The latest version of our targeted sequencing panel (SpastiSure3.0) comprises 118 genes known to be associated with HSP. Using an in-house validated bioinformatics pipeline and several in silico tools to predict mutation pathogenicity, we obtained a positive diagnostic yield of 29% (70/239), whereas variants of unknown significance (VUS) were found in 86 patients (36%), and 83 cases remained unsolved. This study is among the largest screenings of consecutive HSP index cases enrolled in real-life clinical-diagnostic settings. Its results corroborate NGS as a modern, first-step procedure for molecular diagnosis of HSP. It also disclosed a significant number of new mutations in ultra-rare genes, expanding the clinical spectrum, and genetic landscape of HSP, at least in Italy.

The yawing of horizontal-axis wind turbines (HAWT) is a major topic in the comprehension of the dynamical behavior of these kinds of devices. It is important for the study of mechanical loads to which wind turbines are subjected and it is important for the optimization of wind farms because the yaw active control can steer the wakes between nearby wind turbines. On these grounds, this work is devoted to the numerical and experimental analysis of the yawing behavior of a HAWT. The experimental tests have been performed at the wind tunnel of the University of Perugia on a three-bladed small HAWT prototype, having two meters of rotor diameter. Two numerical set ups have been selected: a proprietary code based on the Blade Element Momentum theory (BEM) and the aeroelastic simulation software FAST, developed at the National Renewable Energy Laboratory (NREL) in Golden, CO, USA. The behavior of the test wind turbine up to ± 45 ∘ of yaw offset is studied. The performances (power coefficient C P ) and the mechanical behavior (thrust coefficient C T ) are studied and the predictions of the numerical models are compared against the wind tunnel measurements. The results for C T inspire a subsequent study: its behavior as a function of the azimuth angle is studied and the periodic component equal to the blade passing frequency 3P is observed. The fluctuation intensity decreases with the yaw angle because the distance between tower and blade increases. Consequently, the tower interference is studied through the comparison of measurements and simulations as regards the fore-aft vibration spectrum and the force on top of the tower.

La formazione della coppia è un processo in continua evoluzione, negli ultimi anni le richieste d’aiuto per la psicoterapia di coppia sono sempre più in aumento. I motivi sembrano riguardare il presente, ma spesso sono legati ad un malessere radicato nel tempo. Attraverso la lente dello psicoterapeuta della Gestalt abbiamo analizzato prevalentemente gli studi della teoria dell’attaccamento riferiti al lavoro con le coppie attraverso un’integrazione di approcci, teorie e pratiche, in particolare la terapia di coppia focalizzata sulle emozioni. Secondo la teoria dell’attaccamento gli stili relazionali degli adulti con i propri partner sono paralleli alle relazioni bambino-caregiver, caratterizzandosi perciò per la ricerca di determinate caratteristiche nell’altra persona. Il lavoro psicoterapeutico con le coppie ha tra i propri obiettivi quello di modificare i modelli operativi interni di attaccamento dei pazienti. La terapia di coppia focalizzata sulle emozioni si basa sulla risposta emotiva e su quello che i partner sentono all’interno di una relazione supportante. Consente un’esperienza emotiva risanatrice, trasformando i cicli di interazione negativa presenti nella relazione e sperimentati con i caregiver primari. La psicoterapia della Gestalt ci aiuta a osservare come i partner della coppia realizzano o bloccano la loro intenzionalità di raggiungere e farsi raggiungere dall'altro. Lo scopo della ricerca è stato esaminare i correlati tra teoria dell’attaccamento, terapia focalizzata sulle emozioni e terapia della Gestalt, in vista di ulteriori studi che permettano un maggior approfondimento delle dinamiche di coppia in terapia.

ABSTRACT: The microbiota of a cheese play a critical role in influencing its sensory and physicochemical properties. In this study, traditional Apulian Caciocavallo cheeses coming from 4 different dairies in the same area and produced following standardized procedures were examined, as well as the different bulk milks and natural whey starter (NWS) cultures used. Moreover, considering the cheese wheels as the blocks of Caciocavallo cheeses as whole, these were characterized at different layers (i.e., core, under-rind, and rind) of the block using a multi-omics approach. In addition to physical-chemical characterization, culturomics, quantitative PCR, metagenomics, and metabolomics analysis were carried out after salting and throughout the ripening time (2 mo) to investigate major shifts in the succession of the microbiota and flavor development. Culture-dependent and 16S rRNA metataxonomics results clearly clustered samples based on microbiota biodiversity related to the production dairy plant as a result of the use of different NWS or the intrinsic conditions of each production site. At the beginning of the ripening, cheeses were dominated by Lactobacillus, and in 2 dairies (Art and SdC), Streptococcus genera were associated with the NWS. The analysis allowed us to show that although the diversity of identified genera did not change significantly between the rind, under-rind, and core fractions of the same samples, there was an evolution in the relative abundance and absolute quantification, modifying and differentiating profiles during ripening. The real-time PCR, also known as quantitative or qPCR, mainly differentiated the temporal adaptation of those species originating from bulk milks and those provided by NWS. The primary starters detected in NWS and cheeses contributed to the high relative concentration of 1-butanol, 2-butanol, 2-heptanol, 2-butanone, acetoin, delta-dodecalactone, hexanoic acid ethyl ester, octanoic acid ethyl ester, and volatile free fatty acids during ripening, whereas cheeses displaying low abundances of Streptococcus and Lactococcus (dairy Del) had a lower total concentration of acetoin compared with Art and SdC. However, the subdominant strains and nonstarter lactic acid bacteria present in cheeses are responsible for the production of secondary metabolites belonging to the chemical classes of ketones, alcohols, and organic acids, reaffirming the importance and relevance of autochthonous strains of each dairy plant although only considering a delimited production area.

Sex-related differences in psychopharmacology present unique challenges in both clinical and research settings. Recognition of sex differences in psychopharmacological treatment has increased in recent years, but a significant research gap regarding variations between men and women still exists. Biological factors, including hormonal fluctuations, genetic factors, and brain structure differences, contribute significantly to differential drug responses. Moreover, social determinants can influence the differential burden of psychiatric disorders between the sexes and may impact treatment plans. Incorporating sex as a key variable in personalized treatment programs and plans holds the potential to optimize efficacy and minimize adverse effects in psychopharmacology. Sex-related challenges in psychopharmacology necessitate a nuanced approach to treatment. Further research is needed to fully understand these differences and to develop guidelines for personalized medication management. By addressing these challenges, clinicians can improve treatment outcomes and enhance the quality of life of patients with psychiatric disorders.

Branchiogenic fistulas are congenital alterations that affect the cervical compartments. Those of the fourth branchial cleft are rarest and can begin late with very serious complications. The suppurative thyroiditis can be a complication of these alterations. We describe a case of 3-year-old girl with high fever, left cervical swelling and increased inflammation indices. The neck ultrasound showed an abscess of the left thyroid lobe and a fluid mass with aerial content in laterocervical region. On MRI, the fluid mass extended from the left piriform sinus to the mediastinum. Fluoroscopy also highlighted a fistolose trait that extended from the left side wall of the esophagus, anteriorly towards the trachea. Treatment of these pathologies must be early and a late diagnosis can put patients' lives at risk.

Abstract Community-acquired pneumonia can lead to a serious complication called empyema, which refers to pus within the pleural space. While it poses a significant threat to morbidity, particularly in children, it is fortunately not associated with high mortality rates. However, determining the best course of management for children, including decisions regarding antibiotic selection, administration methods, and treatment duration, remains a topic of ongoing debate. This scoping review aims to map the existing literature on empyema in children, including types of studies, microbiology, therapies (both antimicrobial and surgical) and patient outcomes. We systematically searched PubMed and SCOPUS using the terms “pediatric” (encompassing children aged 0 to 18 years) and “pleural empyema” to identify all relevant studies published since 2000. This search adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA ScR) checklist. A total of 127 studies was included. Overall, 15 attempted to compare medical treatments (alone or in combination with pleural drainage or fibrinolysis) with more invasive surgical approaches, and six studies compared diverse surgical interventions. However, the diversity of study designs makes it difficult to derive firm conclusions on the optimal approach to pediatric empyema. The heterogeneity in inclusion criteria, pharmacological/surgical approaches and settings limit the ability to draw definitive conclusions. Overall, 78 out of 10,896 children (0.7%) included in the review died, with mortality being higher in Asia and Africa. Our scoping review highlights important gaps regarding several aspects of empyema in children, including specific serotypes of the most common bacteria involved in the etiology, the optimal pharmacological and surgical approach, and the potential benefits of newer antibiotics with optimal lung penetration. New trials, designed on a multi-country level a higher number of patients and more rigorous inclusion criteria and designs, should be urgently funded.

In 1950 on Mount Zlatý kůň (‘Golden Horse’) in modern-day Czech Republic a system of caves was discovered. During many years of research in this area, human and animal osteological remains have been excavated, among which the most interesting ones were nine fragments of a female skull, now dated to ca. 43,000 yrs BP which are one of the earliest known anatomically modern humans in Eurasia. The aim of this research was to use purely digital techniques to: (1) to reconstruct the skull based on the 3D data of preserved fragments, (2) to approximate the probable appearance of the female it belonged to, and (3) to analyze the calculated shape of the reconstructed mandible and volume of the neurocranium in the context of similarities and differences with other representatives of the genus Homo. Computer techniques used in this research constitute a new, original approach to the problem of 3D analyses and may be useful primarily in bioarchaeological sciences, where metric analyses of the most valuable bone artifacts are often severely limited due to the incompleteness of the material available for research. The digital techniques presented here may also contribute significantly to the field of surgery, with the possibility of being adapted for applications in cranial prosthetics and post-traumatic reconstructive surgery.

Abstract Background While extensive research exists on muscle injuries among adult football players, a notable gap persists in studies concerning younger footballers. The aim of the current study is to provide epidemiological data on the characteristics of time-loss muscle injuries in young football players participating in the Italian Under-19 male elite Championship (“Primavera 1”). Results Conducted as a multicentre, prospective, observational cohort study, this research gathered injury data from the 2022-23 season across 14 of the 18 Clubs in the first Italian Under-19 championship. The cohort comprised 391 players with a mean age (± standard deviation) of 18.0 ± 0.4 years. A total of 479 injuries were reported, resulting in 14,231 days of activity lost. Of these, muscle injuries were 209 (44%), accounting for 4,519 (32%) days lost. Overall muscle injuries incidence was 1.82/1000 hours, with a mean injury burden of 39.4 days lost/1000 hours. Almost all muscle injuries (206 out of 209: 98.5%) occurred in hamstrings, quadriceps, adductors, calf and iliopsoas. Hamstrings injuries were the most burdensome (18.8 days lost/1000 hours) accounting for nearly half of all days lost due to muscle injuries. Incidence and burden of adductors injuries (0.25 injuries and 4.1 days lost/1000 hours, respectively) were found to be comparable to calf injuries (0.24 injuries and 4.7 days lost/1000 hours, respectively). Iliopsoas injuries accounted for a noteworthy portion of the total, with an injury incidence of 0.16/1000 hours and a burden of 3.3 days lost/1000 hours. Injuries with myo-tendinous or myo-aponeurotic involvement demonstrated delayed return-to-football compared to those without such involvement (35.6 vs. 18.5 days, p

PURPOSEThis study aimed to develop a multivariable, weighted overall survival (OS) risk score (SRS) for nonmetastatic (M0) invasive breast cancer (M0-BC, SRSM0-BC).MATERIALS AND METHODSThis study included a training (1,890 patients) and a validation cohort (850 patients) from the Reggio Emilia Cancer Registry (RE-CR). Ten traditional prognostic variables were evaluated.RESULTSIn the training set, all the variables but the human epidermal growth factor receptor were significantly associated with OS at univariable analysis. A multivariable model identified an increased death risk for estrogen receptor (hazard ratio [HR], 2.0 [95% CI, 1.1 to 3.1]; P = .021), tumor stages T2-T3 (HR, 2.4 [95% CI, 1.3 to 4.7]; P = .009) and T4 (HR, 5.1 [95% CI, 2.0 to 13.0]; P < .001), and age >74 years (HR, 5.7 [95% CI, 4.0 to 8.2]; P < .001). By assigning scores according to HRs, four risk categories were generated (P for trend

The present communication examines the phenomenon of curfew in relation to the COVID-19 pandemic with special attention being laid on the management of the epidemic by Italian health authorities. A literature review and a historical–medical analysis were performed. A historical–medical excursus on the word curfew is offered and a comparison between military and health scenarios is given. Finally, this article stresses how words connected with wartime events should be contextualized when adopted in unmilitary scenarios such as pandemic emergencies and related public health responses.

Summary: Background: Severe and prolonged mpox courses have been described during the 2022–2023 outbreak. Identifying predictors of severe evolution is crucial for improving management and therapeutic strategies. We explored the predictors of mpox severity and tested the association between mpox severity and viral load in biological fluids. We also analysed the predictors of disease duration and kinetics of inflammatory markers and described the viral presence and duration of shedding in biological fluids. Methods: This multicentre historical cohort study included adults diagnosed with laboratory-confirmed mpox diagnosis between May 2022 and September 2023 at 15 Italian centres. Patients were followed up from the day of diagnosis until clinical recovery. Biological fluids (blood, urine, saliva, and oropharyngeal and rectal swabs) were collected from each subgroup during the course of the disease and after healing. The primary outcomes were disease severity (presence of mucosal involvement, extended rash, or need for hospitalisation) and its association with the cycle threshold value (Ct-value, surrogate of viral load) in biological fluids, using standard linear and linear mixed-effect logistic regression models. Among the secondary outcomes, predictors of disease duration were assessed using a linear regression model. Findings: A total of 541 patients were enrolled, including four (0.74%) women, with a median age of 38 years (IQR 33–44). Among the 235 people living with HIV (PLWH) (43.44%), 22 (4.07%) had a CD4 count lower than 350 cells/μL. Severe mpox was reported in 215 patients (39.74%). No patient died. Multivariable analysis showed that, severe mpox was more likely among Caucasians (OR 1.82; 95% CI 1.14–2.90, p = 0.012) and patients who had an onset of fever (1.95; 1.27–2.99, p = 0.002), lymphadenopathy (2.30; 1.52–3.48, p

Enhanced Recovery After Surgery (ERAS) protocols have changed perioperative care, aiming to optimize patient outcomes. This study assesses ERAS implementation effects on postoperative complications, length of hospital stay (LOS), and mortality in colorectal cancer (CRC) patients. A retrospective real-world analysis was conducted on CRC patients undergoing surgery within a Northern Italian Cancer Registry. Outcomes including complications, re-surgeries, 30-day readmission, mortality, and LOS were assessed in 2023, the year of ERAS protocol adoption, and compared with data from 2022. A total of 158 surgeries were performed, 77 cases in 2022 and 81 in 2023. In 2023, a lower incidence of postoperative complications was observed compared to that in 2022 (17.3% vs. 22.1%), despite treating a higher proportion of patients with unfavorable prognoses. However, rates of reoperations and readmissions within 30 days post-surgery increased in 2023. Mortality within 30 days remained consistent between the two groups. Patients diagnosed in 2023 experienced a statistically significant reduction in LOS compared to those in 2022 (mean: 5 vs. 8.1 days). ERAS protocols in CRC surgery yield reduced postoperative complications and shorter hospital stays, even in complex cases. Our study emphasizes ERAS’ role in enhancing surgical outcomes and recovery.

Analyzing the isotopic composition of cosmic rays (CRs) provides valuable insights into the galactic environment and helps refine existing propagation models. A particular interest is devoted to secondary-to-primary ratios of light isotopic components of CRs, the measurement of which can provide complementary information with respect to secondary-to-primary ratios like B/C. Given the complexity of the concurrent measurement of velocity and momentum required to differentiate isotopes of the same Z, a task typically accomplished using magnetic spectrometers, existing measurements of these ratios only effectively characterize the low-energy region (below 1 GeV/nucl). This study introduces a novel technique for isotopic distinction in CRs at high energies up to 100 GeV/nucl based on multiple scattering, which, combined with the proposed measurement of velocity, represent an interesting alternative to magnetic spectrometers. The performance of this technique was assessed through a dedicated simulation using the GEANT4 package, with specific emphasis on Z = 1 isotopes.

Abstract This paper investigates trabecular bone ontogenetic changes in two different Polish populations, one prehistoric and the other historical. The studied populations are from the Brześć Kujawski region in Kujawy (north-central Poland), one from the Neolithic Period (4500–4000 BC) and one from the Middle Ages (twelfth-sixteenth centuries AD), in total 62 vertebral specimens (32 males, 30 females). Eight morphometric parameters acquired from microCT scan images were analysed. Two-way ANOVA after Box-Cox transformation and multifactorial regression model were calculated. A significant decrease in percentage bone volume fraction (BV/TV; [%]) with age at death was observed in the studied sample; Tb.N (trabecular number) was also significantly decreased with age; trabecular separation (Tb.Sp) increased with advancing age; connectivity density (Conn.D) was negatively correlated with biological age and higher in the Neolithic population. These data are found to be compatible with data from the current biomedical literature, while no loss of horizontal trabeculae was recorded as would be expected based on modern osteoporosis.

Abstract A common feature of collapse models and an expected signature of the quantization of gravity at energies well below the Planck scale is the deviation from ordinary quantum-mechanical behavior. Here, we analyze the general consequences of such modifications from the point of view of quantum information theory and we anticipate applications to different quantum systems. We show that quantum systems undergo corrections to the quantum speed limit which, in turn, imply the modification of the Heisenberg limit for parameter estimation. Our results hold for a wide class of scenarios beyond ordinary quantum mechanics. For some nonlocal models inspired by quantum gravity, the bounds are found to oscillate in time, an effect that could be tested in future high-precision quantum experiments.

BackgroundPostoperative seroma is most frequent after mastectomy (ME) in combination with axillary lymph node dissection (ALND), and its reported incidence varies from 15.5% up to 90%. Seromas can be responsible for discomfort, infections and can lead to reconstruction failure. Therefore, many ways of seroma prevention have been studied, although from a recent overview it has become clear that no single method is reliably successful. Mechanical closure of the dead space, however, was consistently found to be significantly effective. The aim of our study is to evaluate if quilting of the axilla, in patients undergoing ME, immediate prosthetic breast reconstruction and ALND reduces the duration of drain maintenance, the incidence of seromas that require aspiration (clinically significant seromas, CSS) and reconstruction failure rate.Materials and methodsIn our study population we analyzed a total of 81 patients divided into two groups: 27 consecutive patients undergoing mastectomy, axillary lymph node dissection (ALND), breast reconstruction and quilting of the axilla. We subsequently randomly picked up a double number of patients (54) undergoing the same oncological and reconstructive procedures without undergoing axillary quilting, matched for clinical characteristics in order to analyze efficacy of the procedure while reducing any bias. Our observational retrospective data was collected from October 2016 to July 2020 in one single high-volume center. Our median follow-up time was of 40.6 months.ResultsIn the case group we observed a reduced time of drain maintenance: 16 vs. 20 days observed in the non-quilted group (p

Bogoliubov's description of Bose gases relies on the linear dynamics of noninteracting quasiparticles on top of a homogeneous condensate. Here, we theoretically explore the weakly nonlinear regime of a one-dimensional photon superfluid in which phononlike elementary excitations interact via their backreaction on the background flow. The generalized dispersion relation extracted from spatiotemporal intensity spectra reveals additional branches that correspond to bound Bogoliubov quasiparticles—phase-locked collective excitations originating from nonresonant harmonic generation and wave-mixing processes. These mechanisms are inherent to fluctuation dynamics and highlight nontrivial scattering channels other than resonant interactions that could be relevant in the emergence of dissipative and turbulent phenomena in superfluids.

Background Empyema (the presence of pus in the pleural space) is a severe complication of community-acquired pneumonia and significant cause of morbidity, but, fortunately, not mortality in children. Between 0.6 and 2% of pneumonias are complicated by empyema and the three main pathogens involved are Streptococcus pneumoniae, Staphylococcus aureus and group A Streptococcus 1,2,3,4. Optimal management in children, especially the choice of antibiotics, method of administration and duration of therapy, pleural dranage or surgery, are still a matter of debate and currently, lack of strong specific recommendations. This paper displays the study protocol for a scoping review that aims to summarize the available literature on the microbiological epidemiology, the medical and surgical treatment options, and the outcomes of pleural empyema in pediatric population. Methods Comprehensive research combining the terms pediatric (children aged 0 to 18 years) and pleural empyema will be performed on PubMed and SCOPUS to identify all eligible studies. At first, two reviewers will screen the abstract and then their full text to determine the articles that meet the inclusion criteria. This work will be carried out independently, everyone on a different Excel spreadsheet and each researcher will be blinded to the decision of the other researcher. When the process is completed, in case of discordance, any disagreement will be identified and resolved through discussion or with help of a third author. Dissemination The findings of this review will be published in a peer-reviewed journal.

Abstract Background The coronavirus 2019 (COVID-19) related containment measures led to the disruption of all virus distribution. Bronchiolitis-related hospitalizations shrank during 2020–2021, rebounding to pre-pandemic numbers the following year. This study aims to describe the trend in bronchiolitis-related hospitalization this year, focusing on severity and viral epidemiology. Methods We conducted a retrospective investigation collecting clinical records data from all infants hospitalized for bronchiolitis during winter (1st September-31th March) from September 2018 to March 2023 in six Italian hospitals. No trial registration was necessary according to authorization no.9/2014 of the Italian law. Results Nine hundred fifty-three infants were hospitalized for bronchiolitis this last winter, 563 in 2021–2022, 34 in 2020–2021, 395 in 2019–2020 and 483 in 2018–2019. The mean length of stay was significantly longer this year compared to all previous years (mean 7.2 ± 6 days in 2022–2023), compared to 5.7 ± 4 in 2021–2022, 5.3 ± 4 in 2020–2021, 6.4 ± 5 in 2019–2020 and 5.5 ± 4 in 2018–2019 (p

This paper deals with the nonlinear robust PWM control of a DC/AC differential boost inverter based on dynamic feedback linearization, active disturbance rejection, and sliding mode control techniques. The inverter topology consists of two synchronous boost converters linked through a load resistance. The model of each boost converter is put in Brunovski’s canonical form through dynamic feedback linearization, defining an auxiliary input depending on the control variable in an affine mode and a nonlinear disturbance containing endogenous and exogenous variables. Each disturbance is estimated by an extended state observer and compensated through a control law designed for tracking the desired trajectory, according to the active disturbance rejection control technique. Finally, a sliding mode component is designed and added to the previous control law to assure the robustness of the closed loop system against uncertainties due to electric parameters, supply voltage and load resistance deviations, and disturbance estimation errors. Experimental results validate the proposed control methodology.