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BackgroundGrowth hormone deficiency (GHD) is the first and most common endocrine complication in pediatric brain tumor survivors (BTS). GHD can occur due to the presence of the tumor itself, surgery, or cranial radiotherapy (CRT).AimsThis study aimed to evaluate management and adherence to current guidelines of the Italian centers engaged in the diagnosis and follow-up of GHD patients with BTS.MethodsA multidisciplinary scientific board of pediatric endocrinologists, oncologists and radiologists with neuroimaging expertise discussed and reviewed the main issues relating to the management of GHD in pediatric BTS and developed a survey. The survey included questions relating to organizational aspects, risk factors, diagnosis, definition of stable disease, and treatment. The online survey was sent to an expanded panel of specialists dedicated to the care of pediatric BTS, distributed among the three specialty areas and throughout the country (23 Italian cities and 37 Centers).ResultsThe online questionnaire was completed by 86.5% (32 out of 37) of the Centers involved. Most had experience in treating these patients, reporting that they follow more than 50 BTS patients per year. Responses were analyzed descriptively and aggregated by physician specialty. Overall, the results of the survey showed some important controversies in real life adherence to the current guidelines, with discrepancies between endocrinologists and oncologists in the definition of risk factors, diagnostic work-up, decision-making processes and safety. Furthermore, there was no agreement on the neuroimaging definition of stable oncological disease and how to manage growth hormone therapy in patients with residual tumor and GHD.ConclusionsThe results of the first Italian national survey on the management of GHD in BTS highlighted the difference in management on some important issues. The time to start and stop rhGH treatment represent areas of major uncertainty. The definition of stable disease remains critical and represents a gap in knowledge that must be addressed within the international guidelines in order to increase height and to improve metabolic and quality of life outcomes in cancer survivors with GHD.

Disturbed nocturnal sleep contributes to the central sensitization of pain, thus predisposing to orofacial pain. Central disorders of hypersomnolence are characterized by excessive daytime sleepiness (EDS) not linked to impairment of nocturnal sleep or misaligned circadian rhythms. The main disorder of this group is narcolepsy type 1 (NT1), which seems to be related to alterations in pain perception mediation, supposedly caused by low orexin levels. The aim of this study was to evaluate the pain sensitivity and the prevalence of temporomandibular disorders (TMDs) in patients with NT1. After a 3-day hospital evaluation with laboratory polysomnography, 39 consecutive adult patients diagnosed with NT1 and 39 matched heathy controls were evaluated by means of Axis I and Axis II of the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) protocol. Furthermore, pain sensitivity was investigated by measuring the pressure pain thresholds (PPTs) on the head–neck muscles by means of a Fischer algometer. No significant differences were found between the PPTs of the two groups for all the muscles evaluated, nor in the prevalence of TMD diagnoses, but the NT1 group reported significantly higher values in the Patient Health Questionnaire (PHQ-9), corresponding to a depressive state. The present study presents an important investigation into NT1 patients, showing no alterations in pain perception and no differences in the prevalence of TMD diagnosis compared to the controls.

Rhabdomyosarcoma frequently affects the craniofacial region with a rapid growing pattern that usually results in swelling of the interested area. The present paper describes a peculiar occurrence of rhabdomyosarcoma in a 12-year-old boy and the importance of a careful evaluation of clinical history to choose the correct diagnostic strategy. The patient was evaluated in the orthodontics section of the Dental School of the University of Bologna by an orofacial pain specialist, with a compliance of excruciating pain around the right ear that occurred 4 months earlier after a sports trauma. The patient had been previously evaluated by a pediatrician and an ENT specialist who requested a computerized tomography that did not show pathological conditions in the head/neck district. The drug therapy for pain control was not effective. The clinical examination showed a severe limitation of mouth opening, periauricular paresthesia and mandibular hyperalgesia on the right side. The patient reported intermittent, very intense stabs of pain occurring every 5 min, with a continuous dull pain in the temporal area. A nuclear magnetic resonance was requested and showed the presence of a solid expansive lesion in the right pterygoid area that eroded the cranial base and the medial portion of the mandibular condyle. An incisional biopsy led to the diagnosis of embryonal rhabdomyosarcoma. This case report emphasizes the importance of not underestimating the presence of pain in young subjects, suggesting a proper approach to apparently simple clinical cases.

The Internet is a preferred source of health information. This study evaluated the quality, reliability and content of online audio-visual information on the mandibular advancement device (MAD) for the treatment of obstructive sleep apnea (OSA). “Mandibular advancement device” was searched on four online platforms. A total of 63 videos (51% from healthcare professionals, 22% from commercial companies, 21% from laypeople, and 6% from hospitals/universities) were evaluated using metrics, the video information and quality index (VIQI), modified-DISCERN, and the Journal of American Medical Association (JAMA) benchmark criteria and contents. VIQI had significantly lower scores for videos uploaded by laypeople (mean 7.92, 95%CI 5.90–9.95) versus healthcare professionals (12.38, 95%CI 11.28–13.47) and commercial companies (11.21, 95%CI 9.61–12.81). The m-DISCERN scores were significantly lower for laypeople (1.15, 95%CI 0.93–1.40) versus healthcare professionals (2.13, 95%CI 1.73–2.52) and hospitals/universities (3.00, 95%CI 1.70–4.30), as well as for commercial companies (1.43, 95%CI 1.13-1.73) versus hospitals/universities. Contents were significantly less complete for laypeople (1.54, 95%CI 0.60–2.48) versus healthcare professionals (3.25, 95%CI 2.66–3.84). The results of the present study suggest that the quality and completeness of online audio-visual information with respect to the use of MAD for the treatment of OSA are generally poor, and the currently available videos, especially those uploaded by laypeople, may determine misinformation and/or unrealistic treatment expectations.

The early stages of orthodontic treatment are frequently associated with pain that can vary in intensity and duration, representing one of the main reasons for treatment discontinuation. Whilst the use of drugs is recognised as being effective to control orthodontic pain, there are no reliable data indicating the best first archwire for efficacy and minimum discomfort. A prospective controlled cohort study was conducted to compare the intensity and the characteristics of orthodontic pain during the first 15 days of treatment with 2 archwires. Fifty subjects were enrolled and divided into two groups: one received 0.012 inch stainless steel (SS) as the first archwire; the other, a 0.014 inch super-elastic nickel–titanium (Ni-Ti) archwire. Patients compiled a visual analogue scale to measure pain intensity over 15 days, a questionnaire for pain characteristics, the Somatosensory Amplification Scale and the State-Trait Anxiety Inventory to control the psychosocial component of pain. Dental casts were digitally analysed to evaluate the initial arch length discrepancy. In the first 3 days of treatment, the mean VAS values of the SS group were significantly lower than those of the Ni-Ti group (p < 0.05). No significant differences emerged between the groups concerning pain characteristics. The 0.012 inch SS archwire could be used at the beginning of orthodontic treatment to minimise pain perception and improve compliance.

The widespread implementation of artificial intelligence technologies provides an appealing alternative to traditional search engines for online patient healthcare education. This study assessed ChatGPT-3.5's capabilities as a source of obstructive sleep apnea (OSA) information, using Google Search as a comparison. Ten frequently searched questions related to OSA were entered into Google Search and ChatGPT-3.5. The responses were assessed by two independent researchers using the Global Quality Score (GQS), Patient Education Materials Assessment Tool (PEMAT), DISCERN instrument, CLEAR tool, and readability scores (Flesch Reading Ease and Flesch–Kincaid Grade Level). ChatGPT-3.5 significantly outperformed Google Search in terms of GQS (5.00 vs. 2.50, p < 0.0001), DISCERN reliability (35.00 vs. 29.50, p = 0.001), and quality (11.50 vs. 7.00, p = 0.02). The CLEAR tool scores indicated that ChatGPT-3.5 provided excellent content (25.00 vs. 15.50, p < 0.001). PEMAT scores showed higher understandability (60–91% vs. 44–80%) and actionability for ChatGPT-3.5 (0–40% vs. 0%). Readability analysis revealed that Google Search responses were easier to read (FRE: 56.05 vs. 22.00; FKGL: 9.00 vs. 14.00, p < 0.0001). ChatGPT-3.5 delivers higher quality and more comprehensive OSA information compared to Google Search, although its responses are less readable. This suggests that while ChatGPT-3.5 can be a valuable tool for patient education, efforts to improve readability are necessary to ensure accessibility and utility for all patients. Healthcare providers should be aware of the strengths and weaknesses of various healthcare information resources and emphasize the importance of critically evaluating online health information, advising patients on its reliability and relevance. [ABSTRACT FROM AUTHOR]

A chemistry module has been implemented in Geant4‐DNA since Geant4 version 10.1 to simulate the radiolysis of water after irradiation. It has been used in a number of applications, including the calculation of G‐values and early DNA damage, allowing the comparison with experimental data. Since the first version, numerous modifications have been made to the module to improve the computational efficiency and extend the simulation to homogeneous kinetics in bulk solution. With these new developments, new applications have been proposed and released as Geant4 examples, showing how to use chemical processes and models. This work reviews the models implemented and application developments for modeling water radiolysis in Geant4‐DNA as reported in the ESA BioRad III Project. [ABSTRACT FROM AUTHOR]

Alternative means of control are becoming increasingly relevant to the improvement of safety and the reduction of postharvest losses and waste of fruit and vegetables, especially in view of the application of the EU Greed Deal. A previous study from our research group that focused on the electrolysis process of water and was conducted using NaCl and NaHCO3 as electrolytes proved to efficiently reduce pathogen inoculum in packinghouse washing water. In the present study, we examined the effect of the electrolyzed salt solutions (eNaCl and eNaHCO3) produced in the same experimental conditions previously reported to be used as postharvest treatments during handling and commercialization, and/or at the consumer's site. We tested the electrolyzed solutions, obtained in the presence or absence of the salts, against five relevant fungal pathogens in terms of conidia viability, and on various hosts in terms of rot incidence/severity. Chemical parameters of electrolyzed and non-electrolyzed solutions were also assessed. Although a different susceptibility to treatments was observed among pathogens, electrolyzed sodium chloride (eNaCl) was the most efficient treatment for preventing spore germination, as well as for minimizing fruit rot. However, a consistent control of fungal viability and consequent rot was also achieved using electrolyzed tap water (eW). The eNaHCO3, although less efficient on fungal viability, provided a significant effect against fruit rot. The investigated electrolyzed solutions seem promising for reducing the waste of fresh fruit and vegetables. [ABSTRACT FROM AUTHOR]

Many are skeptical of the appeal of authoritarian political systems. We argue that global audiences will embrace authoritarian models when they believe that autocracies can meet governance challenges better than democracies. We collect comprehensive data on the external messaging of the Chinese and American governments. We then conduct a randomized experiment in 19 countries across six continents exposing global citizens to real messages from the Chinese and American governments’ external media arms. We find that exposure to a representative set of Chinese messages strengthens perceptions that the Chinese Communist Party delivers growth, stability, and competent leadership. It also moves the average respondent from slightly preferring the American model to slightly preferring the Chinese model. In head‐to‐head matchups, messages from the US government are less persuasive. Our findings show how autocracies build global support by selling growth and competence, with important implications for democratic resilience. [ABSTRACT FROM AUTHOR]

Nel 1926, un gruppo di sette amici formatosi tra i banchi del Regio Istituto Tecnico Superiore di Milano – composto da Ubaldo Castagnoli, Luigi Figini, Gino Pollini, Guido Frette, Sebastiano Larco, Carlo Enrico Rava e Giuseppe Terragni – decide di unirsi e fondare il Gruppo 7. I sette giovani, tra il 1926 e il 1927, pubblicarono sulla rivista Rassegna Italiana alcuni articoli che vengono ancora oggi considerati uno dei momenti fondativi per la nuova architettura italiana. Ubaldo Castagnoli lasciò quasi subito il gruppo, venendo sostituito da Adalberto Libera e, per questa ragione, il suo nome scompare dai manuali di storia dell’architettura. La carriera di questo professionista si sviluppò all’interno di una delle più importanti aziende del Paese, la STIPEL, Società telefonica interregionale piemontese e lombarda (che nel 1964 fu inglobata nella SIP), con il ruolo di Direttore Centrale a disposizione della Direzione Generale per gli affari immobiliari. Ebbe inoltre un lungo rapporto professionale con Luigi Einaudi, prima e durante gli anni della Presidenza della Repubblica. Il lavoro di seguito presentato si propone di proseguire la ricerca recentemente inaugurata su questa figura ancora non adeguatamente indagata, allo scopo di approfondire gli esiti del dibattito culturale di quegli anni sulla sua vasta attività professionale, alla luce delle metodiche e tecniche delle discipline della rappresentazione.

Objective We aimed at identifying baseline predictive factors for emergency department (ED) readmission, with hospitalisation/death, in patients with COVID-19 previously discharged from the ED. We also developed a disease progression velocity index.Design and setting Retrospective cohort study of prospectively collected data. The charts of consecutive patients with COVID-19 discharged from the Reggio Emilia (Italy) ED (2 March 2 to 31 March 2020) were retrospectively examined. Clinical, laboratory and CT findings at first ED admission were tested as predictive factors using multivariable logistic models. We divided CT extension by days from symptom onset to build a synthetic velocity index.Participants 450 patients discharged from the ED with diagnosis of COVID-19.Main outcome measure ED readmission within 14 days, followed by hospitalisation/death.Results Of the discharged patients, 84 (18.7%) were readmitted to the ED, 61 (13.6%) were hospitalised and 10 (2.2%) died. Age (OR=1.05; 95% CI 1.03 to 1.08), Charlson Comorbidity Index 3 versus 0 (OR=11.61; 95% CI 1.76 to 76.58), days from symptom onset (OR for 1-day increase=0.81; 95% CI 0.73 to 0.90) and CT extension (OR for 1% increase=1.03; 95% CI 1.01 to 1.06) were associated in a multivariable model for readmission with hospitalisation/death. A 2-day lag velocity index was a strong predictor (OR for unit increase=1.21, 95% CI 1.08 to 1.36); the model including this index resulted in less information loss.Conclusions A velocity index combining CT extension and days from symptom onset predicts disease progression in patients with COVID-19. For example, a 20% CT extension 3 days after symptom onset has the same risk as does 50% after 10 days.

Abstract Background The objective of our study was to evaluate the association between perinatal asphyxia and hypoxic-ischemic encephalopathy (HIE) with the presence of ante and intrapartum risk factors and/or abnormal fetal heart rate (FHR) findings, in order to improve maternal and neonatal management. Methods We did a prospective observational cohort study from a network of four hospitals (one Hub center with neonatal intensive care unit and three level I Spoke centers) between 2014 and 2016. Neonates of gestational age ≥ 35 weeks, birthweight ≥1800 g, without lethal malformations were included if diagnosed with perinatal asphyxia, defined as pH ≤7.0 or Base Excess (BE) ≤ − 12 mMol/L in Umbical Artery (UA) or within 1 h, 10 min Apgar 10 min. FHR monitoring was classified in three categories according to the American College of Obstetricians and Gynecologists (ACOG). Pregnancies were divided into four classes: 1) low risk; 2) antepartum risk; 3) intrapartum risk; 4) and both ante and intrapartum risk. In the first six hours of life asphyxiated neonates were evaluated using the Thomson score (TS): if TS ≥ 5 neonates were transferred to Hub for further assessment; if TS ≥ 7 hypothermia was indicated. Results Perinatal asphyxia occurred in 21.5‰ cases (321/14,896) and HIE in 1.1‰ (16/14,896). The total study population was composed of 281 asphyxiated neonates: 68/5152 (1.3%) born at Hub and 213/9744 (2.2%) at Spokes (p

Abstract Background Inflammation contributes to the pathophysiology of major depressive disorder (MDD), and anti-inflammatory strategies might therefore have therapeutic potential. This trial aimed to determine whether adjunctive aspirin or rosuvastatin, compared with placebo, reduced depressive symptoms in young people (15–25 years). Methods YoDA-A, Youth Depression Alleviation with Anti-inflammatory Agents, was a 12-week triple-blind, randomised, controlled trial. Participants were young people (aged 15–25 years) with moderate to severe MDD (MADRS mean at baseline 32.5 ± 6.0; N = 130; age 20.2 ± 2.6; 60% female), recruited between June 2013 and June 2017 across six sites in Victoria, Australia. In addition to treatment as usual, participants were randomised to receive aspirin (n = 40), rosuvastatin (n = 48), or placebo (n = 42), with assessments at baseline and weeks 4, 8, 12, and 26. The primary outcome was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to week 12. Results At the a priori primary endpoint of MADRS differential change from baseline at week 12, there was no significant difference between aspirin and placebo (1.9, 95% CI (− 2.8, 6.6), p = 0.433), or rosuvastatin and placebo (− 4.2, 95% CI (− 9.1, 0.6), p = 0.089). For rosuvastatin, secondary outcomes on self-rated depression and global impression, quality of life, functioning, and mania were not significantly different from placebo. Aspirin was inferior to placebo on the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) at week 12. Statins were superior to aspirin on the MADRS, the Clinical Global Impressions Severity Scale (CGI-S), and the Negative Problem Orientation Questionnaire scale (NPOQ) at week 12. Conclusions The addition of either aspirin or rosuvastatin did not to confer any beneficial effect over and above routine treatment for depression in young people. Exploratory comparisons of secondary outcomes provide limited support for a potential therapeutic role for adjunctive rosuvastatin, but not for aspirin, in youth depression. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12613000112763. Registered on 30/01/2013.

Magnetic Resonance-guided high-intensity Focused Ultrasound (MRgFUS) of the thalamic ventral intermediate nucleus (Vim) for tremor has increasingly gained interest as a new non-invasive alternative to standard neurosurgery. Resting state functional connectivity (rs-FC) correlates of MRgFUS have not been extensively investigated yet. A region of interest (ROI)-to-ROI rs-FC MRI “connectomic” analysis focusing on brain regions relevant for tremor was conducted on 15 tremor-dominant patients with Parkinson's disease who underwent MRgFUS. We tested whether rs-FC between tremor-related areas was modulated by MRgFUS at 1 and 3 months post-operatively, and whether such changes correlated with individual clinical outcomes assessed by the MDS-UPDRS-III sub items for tremor. Significant increase in FC was detected within bilateral primary motor (M1) cortices, as well as between bilateral M1 and crossed primary somatosensory cortices, and also between pallidum and the dentate nucleus of the untreated hemisphere. Correlation between disease duration and FC increase at 3 months was found between the putamen of both cerebral hemispheres and the Lobe VI of both cerebellar hemispheres, as well as between the Lobe VI of untreated cerebellar hemisphere with bilateral supplementary motor area (SMA). Drop-points value of MDS-UPDRS at 3 months correlated with post-treatment decrease in FC, between the anterior cingulate cortex and bilateral SMA, as well as between the Lobe VI of treated cerebellar hemisphere and the interpositus nucleus of untreated cerebellum. Tremor improvement at 3 months, expressed as percentage of intra-subject MDS-UPDRS changes, correlated with FC decrease between bilateral occipital fusiform gyrus and crossed Lobe VI and Vermis VI. Good responders (≥50% of baseline tremor improvement) showed reduced FC between bilateral SMA, between the interpositus nucleus of untreated cerebellum and the Lobe VI of treated cerebellum, as well as between the untreated SMA and the contralateral putamen. Good responders were characterized at baseline by crossed hypoconnectivity between bilateral putamen and M1, as well as between the putamen of the treated hemisphere and the contralateral SMA. We conclude that MRgFUS can effectively modulate brain FC within the tremor network. Such changes are associated with clinical outcome. The shifting mode of integration among the constituents of this network is, therefore, susceptible to external redirection despite the chronic nature of PD.

The development of accurate physics models that enable track structure simulations of electrons in liquid water medium over a wide energy range, from the eV to the MeV scale, is a subject of continuous efforts due to its importance (among other things) in theoretical studies of radiation quality for application in radiotherapy and radiation protection. A few years ago, the Geant4-DNA very low-energy extension of the Geant4 Monte Carlo code had offered to users an improved set of physics models for discrete electron transport below 10 keV. In this work we present refinements to this model set and its extension to energies up to 1 MeV. Preliminary comparisons against the existing Geant4-DNA physics models with respect to total and differential ionization cross sections of electrons in liquid water are reported and discussed.

The accumulation of fragmented extracellular DNA reduces conspecific seed germination and plantlet growth in a concentration-dependent manner. This self-DNA inhibition was repeatedly reported, but the underlying mechanisms are not fully clarified. We investigated the species-specificity of self-DNA inhibition in cultivated vs. weed congeneric species (respectively, Setaria italica and S. pumila) and carried out a targeted real-time qPCR analysis under the hypothesis that self-DNA elicits molecular pathways that are responsive to abiotic stressors. The results of a cross-factorial experiment on root elongation of seedlings exposed to self-DNA, congeneric DNA, and heterospecific DNA from Brassica napus and Salmon salar confirmed a significantly higher inhibition by self-DNA as compared to non-self-treatments, with the latter showing a magnitude of the effect consistent with the phylogenetic distance between the DNA source and the target species. Targeted gene expression analysis highlighted an early activation of genes involved in ROS degradation and management (FSD2, ALDH22A1, CSD3, MPK17), as well as deactivation of scaffolding molecules acting as negative regulators of stress signaling pathways (WD40-155). While being the first exploration of early response to self-DNA inhibition at molecular level on C4 model plants, our study highlights the need for further investigation of the relationships between DNA exposure and stress signaling pathways by discussing potential applications for species-specific weed control in agriculture.