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Objectives We aimed to assess the performance of radiomics and machine learning (ML) for classification of non-cystic benign and malignant breast lesions on ultrasound images, compare ML’s accuracy with that of a breast radiologist, and verify if the radiologist’s performance is improved by using ML. Methods Our retrospective study included patients from two institutions. A total of 135 lesions from Institution 1 were used to train and test the ML model with cross-validation. Radiomic features were extracted from manually annotated images and underwent a multistep feature selection process. Not reproducible, low variance, and highly intercorrelated features were removed from the dataset. Then, 66 lesions from Institution 2 were used as an external test set for ML and to assess the performance of a radiologist without and with the aid of ML, using McNemar’s test. Results After feature selection, 10 of the 520 features extracted were employed to train a random forest algorithm. Its accuracy in the training set was 82% (standard deviation, SD, ± 6%), with an AUC of 0.90 (SD ± 0.06), while the performance on the test set was 82% (95% confidence intervals (CI) = 70–90%) with an AUC of 0.82 (95% CI = 0.70–0.93). It resulted in being significantly better than the baseline reference (p = 0.0098), but not different from the radiologist (79.4%, p = 0.815). The radiologist’s performance improved when using ML (80.2%), but not significantly (p = 0.508). Conclusions A radiomic analysis combined with ML showed promising results to differentiate benign from malignant breast lesions on ultrasound images. Key Points • Machine learning showed good accuracy in discriminating benign from malignant breast lesions • The machine learning classifier’s performance was comparable to that of a breast radiologist • The radiologist’s accuracy improved with machine learning, but not significantly

Background: Acetaminophen and ibuprofen are the only antipyretics drugs approved in children, and are considered safe and well tolerated. However, data regarding the adverse drug reaction (ADR) profile of these drugs in children are scattered. Aim: The aim of our study is to evaluate the ADRs of acetaminophen and ibuprofen through an observational study over a period of 15 years (January 2005-April 2020). Reports of suspected ADRs to the active substances ‘acetaminophen’ and ‘ibuprofen’ are listed and accessible through the Italian spontaneous reporting database (RAM system) by AIFA (Pharmacovigilance of the Italian Drug Agency). Methods: Acetaminophen ADRs in paediatric populations were 15% of cases, with more frequent involvement of skin and soft tissue (54.36%) and gastrointestinal apparatus (44.09%); liver dysfunction accounts for 5.67%. Results: Ibuprofen paediatric ADRs were 26%: skin and soft tissues in 63.16% of cases, gastrointestinal tract in 47.75%, hematemesis and melena in 6.38%; kidney injury in 2.25% of cases. Conclusion: Children aged 2 to 11 are more frequently affected by ADRs than infants and adolescents. The risk of gastrointestinal and renal side effects is significantly higher with ibuprofen. Hepatobiliary side effects are more frequently linked to acetaminophen. Potentially fatal ADRs have been reported sporadically for both drugs.

This study evaluates the cognitive impairment impact on the caregiver's burden and quality of life.Patient-caregiver dyads admitted to dementia Diagnostic-Therapeutic Care Pathway underwent a psychological and neuropsychological assessment. Overall, 30 caregivers (age 58.97 ± 14.68) of patients with dementia and 28 caregivers (age 58.57 ± 12.22) of patients with MCI were recruited. Caregiver's burden is positively correlated to the number (r = .37, p = .003) and severity (r = .37, p = .003) of neuropsychiatric patient's symptoms and with the caregiver's distress (r = .36, p = .004). It is also negatively related to good quality of life perception (r = - .52, p =

Donations after circulatory death (DCD) are still challenging in Italy because of prolonged ischemia time (tWIT) due to the law and logistical issues. This cohort study was primarily aimed at assessing the association between successful transplantation and DCD types in the North Italy Transplant program. Adjusted risk ratios (RR) and 95% confidence intervals (CIs) for type III versus type II DCD were estimated using a Poisson regression model with a robust error variance. All consecutive DCD between 2008 and 2020 were included. Among 142 DCD, 102 were eligible for liver donation, and 96 were proposed: 68/69 (99%) and 28/33 (85%) type III and II DCD, respectively. Sixty-nine livers were recovered, 51/68 (75%) from type III and 18/28 (64%) from type II DCD, respectively (RR: 1.18; 95% CI: 0.87-1.60). After ex-vivo perfusion, 50/68 (74%) and 14/28 (50%) livers from type III and type II DCD were transplanted (RR: 1.49; 95% CI: 1.01-2.19). The estimate decreased after further controlling for tWIT (RR: 1.11; 95% CI: 0.55-2.24). Five patients (7.8%) experienced a PNF, 3/50 and 2/14 from type III and type II DCD, respectively. Type III DCD livers were more likely to be transplanted than type II. Warm ischemia time might explain this difference.

The peculiar combined, or binary involvement of epithelium and stroma makes basal cell carcinoma (BCC) a unique tumour. Nerve fibres have been shown to play an active role in different cancers. A prospective observational study was carried out on punch biopsies harvested within BCC surgical excision specimens. A total of 10 samples of histologically diagnosed BCC, derived from 10 different patients (five females, five males), was included in the study. Within the BCCs, seven different histological sub-types were identified: morphea-like, basosquamous, micronodular, mixed nodular-micronodular, adenoid, nodular and superficial multifocal. Nerve fibres were stained for indirect immunofluorescence targeting protein gene product 9.5. Three different morphological patterns of nerve fibre distribution within the BCCs were identified. Pattern 1 displayed a normal skin nerve pattern, in which the fibres were dislodged by the growing tumour masses. Pattern 2 featured a ball of curved, tangled nerve fibres close to the tumour masses, slightly resembling piloneural collar nerve fibres, wrapped around hair follicles in the normal anatomical setting. Pattern 3 showed nerve fibres crowding in the sub-epidermal layer with focal epidermal hyperinnervation. Such a pattern is reminiscent of the typical anatomical neuro-epithelial interaction in mechanosensory organs. Our study may disclose a hidden third player, of nerves. Thus, tissue involvement of BCCs may be better represented by the triad of epithelium, stroma and nerves, each component retaining some features associated with its developmental setting.

Background The average hemoglobin content of red cell concentrates (RCC) varies depending on the method of preparation. Surprisingly less data are available concerning the clinical impact of those differences. Study Design and Methods The effects of two types of RCC (RCC‐A, RCC‐B) on transfusion regime were compared in a non‐blinded, prospective, randomized, two‐period, and crossover clinical trial. RCC‐A was obtained by whole blood leukoreduction and subsequent plasma removal, RCC‐B removing plasma and buffy coat first, followed by leukoreduction. Eligible patients were adult, with transfusion‐dependent thalassemia (TDT). Results RCC‐A contained 63.9 (60.3–67.8) grams of hemoglobin per unit (median with 1st and 3rd quartile), RCC‐B 54.5 (51.0–58.2) g/unit. Fifty‐one patients completed the study. With RCC‐B, the average pre‐transfusion hemoglobin concentration was 9.3 ± 0.5 g/dl (mean ± SD), the average transfusion interval 14.2 (13.7–16.3) days, the number of RCC units transfused per year 39.3 (35.4–47.3), and the transfusion power index (a composite index) 258 ± 49. With RCC‐A, the average pre‐transfusion hemoglobin concentration was 9.6 ± 0.5 g/dl (+2.7%, effect size 0.792), the average transfusion interval 14.8 (14.0–18.5) days (+4.1%, effect size 0.800), the number of RCC units transfused per year 34.8 (32.1–42.5) (−11.4%, effect size −1.609), and the transfusion power index 272 ± 61 (+14.1%, effect size 0.997). All differences were statistically highly significant (p

Objectives The purpose of this study was to compare data obtained from the reticulocyte channel (RET channel) heated to 41 °C with those obtained from impedance channel (I-Channel) at room temperature in the samples with the mean corpuscular hemoglobin concentration (MCHC) < 370 g/L and in samples with the MCHC > 370 g/L, in the presence of cold agglutinins. Methods In this study, 60 blood samples (group 1) with the MCHC < 370 g/L (without cold agglutinins) and 78 blood samples (group 2) with the MCHC > 370 g/L (with cold agglutinins) were used to compare the two analytical channels of the XN-9000 analyzer in different preanalytical conditions. The parameters evaluated in both groups were the following: red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), mean cell volume (MCV), RBC-most frequent volume (R-MFV), mean hemoglobin concentration (MCH) and mean cellular hemoglobin concentration (MCHC). Results The results of this study showed an excellent correlation with both channels of the XN-9000 analyzer in samples with and without cold agglutinins, except for the MCHC. The bias between the values obtained in the I-channel and those obtained in the RET channel of both groups was insignificant and remained within the limits of acceptability, as reported by Ricos et al. for all considered parameters, except for MCHC. Conclusions The presence of cold agglutinins in blood samples can be detected by a spurious lowering of the RBC count and by a spurious increase in the MCHC. The RET channel represents a great opportunity to correct the RBC count in a rapid manner without preheating. However, neither methodology can completely solve the residual presence of cold agglutinins in all samples, despite the MCHC values being < 370 g/L.

BACKGROUND: Several neurological complications occurred in SARS-CoV-2 disease (COVID-19), mainly related to inflammatory and vascular disorders. The involvement of the peripheral nervous system (PNS) has been mostly reported as Guillain-Barré Syndrome, while focal peripheral neuropathies have been rarely described. CASE REPORT: We report the cases of ten patients hospitalized in Rehabilitation Units after COVID-19, who presented severe focal motor involvement. Electrophysiological investigations revealed focal sensory-motor neuropathies, atypical for many aspects: bilaterality, location and contemporary involvement of different nervous districts. We speculate that their pathogenesis is possibly related to prolonged abnormal postures maintained during hospitalization in Intensive Care Unit, virus neurotropism and thrombotic vascular damage involving vasa nervorum. CLINICAL REHABILITATION IMPACT: Motor neuropathies could induce severe disability and their early recognition in post COVID-19 patients is of primary importance for a specific rehabilitation treatment.

Background Long-chain n-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may alter oxidative status and immune function after exercise. The aim of this pilot study was to determine the probable association between n-3 supplementation and physical exercise, observing the variations in markers of oxidative stress and inflammation. Methods Thirty-nine subjects of both sexes aged 17–30 years were divided into two groups: 1) (n = 21) trained Athletes; 2) (n = 18) Sedentary subjects. All subjects were given about 4 g/day of n-3 supplementation, rich in EPA and DHA, for 8 weeks. Blood, saliva and urine samples were collected pre- (T0) and post- (T1) supplementation. Hematological parameters (tryglicerides, total cholesterol, HDL, CPK, LDH, HGH, IGF-1), oxidative markers (MDA, 8-OHdG, PCc), antioxidant parameters (GPx, SOD, CAT, DPPH scavenger), exercise-induced stress markers (testosterone and cortisol) and an inflammatory marker (TNF-α) were measured. All tests were two-sided and a p-value of less than 0.05 was considered as statistically significant. Results The results showed that MDA and TNF-αmean values significantly decreased after supplementation in both Athletes and Sedentary subjects: variation was greater in Athletes than in Sedentary control subjects. Generally, our results suggested that supplementation with n-3 PUFAs created a synergic variation in the parameters from a baseline state (T0) to a treated state after supplementation (T1), in terms of size and modality, which was significantly different in Athletes compared to Sedentary subjects. Conclusion In conclusion, supplementation with about 4 g/day of n-3 PUFAs, rich in EPA and DHA, for 8 weeks, seemed to be effective in counteracting some parameters involved in oxidative stress and inflammation, induced by acute strenuous physical exercise.

Infants are at risk of vitamin K deficiency that may lead to vitamin K deficiency bleeding (VKDB). Although many vitamin K prophylactic regimens have been developed throughout the years, still cases of late form VKBD may occur. The introduction of combined prophylactic strategy with prolonged oral prophylaxes after the intramuscular dose at birth has showed a decrease of the late severe VKDB incidence. Nevertheless, there is still lack of consensus about the administration scheme after the first dose at birth. CONCLUSION: Late form VKBD is not eradicated, and the best prophylactic regimen in term and preterm infants is still an open debate.

Background Delayed umbilical cord clamping is associated with greater haemoglobin concentration and iron storage between 3 and 6 months of life and with less need of blood transfusion and lower incidence of neonatal hypotension compared to early umbilical cord clamping. Methods The aim was to test the hypothesis that delayed cord clamping is better than early cord clamping in term infants born by elective caesarean section. Group A was subjected to immediate cord clamping while in the Group B, the umbilical cord was clamped 1 min after birth. Primary aim was revealed the difference in pre-ductal saturation between two groups while secondary aim was investigating the difference in HR, Ht, bilirubin and glycaemia. Pre-ductal SpO2 and HR were recorded at 5 and 10 min after birth, T was analysed 10 min after birth, glycaemia was revealed at 120 min while Ht and bilirubin were collected at 72 h. Results 132 newborns were enrolled in the study and allocated in ratio 1:1 to group A or B. Delayed cord clamping did not improve SpO2, HR and T values compared to immediate cord clamping (p > 0,05). However, Group B showed greater haematocrit and bilirubin values at 72 h compared to Group A (56,71 ± 6663 vs 51,56 ± 6929; p p p > 0,05). Conclusions Group B did not reveal any differences in SpO2, HR, T and glycaemia compared to Group A. Group B showed greater values of haematocrit and bilirubin but without need of phototherapy. Trial registration Umbilical Cord Clamping: What Are the Benefits; NCT03878602. Registered 18 March 2019 retrospectively registered.

Objective CYP11A1 mutations cause P450 side-chain cleavage (scc) deficiency, a rare form of congenital adrenal hyperplasia with a wide clinical spectrum. We detail the phenotype and evolution in a male sibship identified by HaloPlex targeted capture array. Family study The youngest of three brothers from a non-consanguineous Scottish family presented with hyperpigmentation at 3.7 years. Investigation showed grossly impaired glucocorticoid function with ACTH elevation, moderately impaired mineralocorticoid function, and normal external genitalia. The older brothers were found to be pigmented also, with glucocorticoid impairment but normal electrolytes. Linkage studies in 2002 showed that all three brothers had inherited the same critical regions of the maternal X chromosome suggesting an X-linked disorder, but analysis of NR0B1 (DAX-1, adrenal hypoplasia) and ABCD1 (adrenoleukodystrophy) were negative. In 2016, next-generation sequencing revealed compound heterozygosity for the rs6161 variant in CYP11A1 (c.940G>A, p.Glu314Lys), together with a severely disruptive frameshift mutation (c.790_802del, K264Lfs*5). The brothers were stable on hydrocortisone and fludrocortisone replacement, testicular volumes (15–20 mL), and serum testosterone levels (24.7, 33.3, and 27.2 nmol/L) were normal, but FSH (41.2 µ/L) was elevated in the proband. The latter had undergone left orchidectomy for suspected malignancy at the age of 25 years and was attending a fertility clinic for oligospermia. Initial histology was reported as showing nodular Leydig cell hyperplasia. However, histological review using CD56 staining confirmed testicular adrenal rest cell tumour (TART). Conclusion This kinship with partial P450scc deficiency demonstrates the importance of precise diagnosis in primary adrenal insufficiency to ensure appropriate counselling and management, particularly of TART.

Treatment-resistant schizophrenia (TRS) represents a main clinical issue, associated with worse functional outcome and higher healthcare costs. Clozapine is the most effective antipsychotic for TRS, although 40% of resistant patients, defined as ultra-treatment resistant (UTR), are clozapine-refractory. Previous literature suggests that TRS is characterized by worse cognitive functioning and a more disrupted neurobiological substrate, but only few studies focused on UTR schizophrenia. Moreover, despite this evidence and the central role of cognition, to date no study has investigated long-term cognitive outcome in TRS. Based on these premises, this study aims to analyze cross-sectional and long-term cognitive functioning of patients with schizophrenia, stratified according to antipsychotic response: first-line responders (FLRs), clozapine responders (CRs) and UTRs. We analyzed cross-sectional and retrospective cognitive evaluations of 93 patients with schizophrenia (32 FLRs, 42 CRs, 19 UTRs) over a mean follow-up period of 9 years, also taking into account possible influencing factors such as clinical severity and antipsychotic load. Analyses showed that UTR is associated with overall impaired cognitive functioning and represents the main predictor of long-term cognitive decline. We observed no significant differences between FLR and CR patients, which showed moderate cognitive improvement over time. This is the first study to report an association of treatment resistance with longitudinal cognitive course in schizophrenia, indicating that UTR is correlated with cognitive decline over time. This decline may either be a consequence of the persistence of psychotic symptoms or depend on a distinct and more disrupted neurobiological substrate affecting both cognition and antipsychotic response.

Helicobacter pylori is the most frequent cause of chronic active gastritis (CAG), namely the first step for gastric cancer development. When infection is not detected at histology, another test is advised. EndoFaster is novel device that reveal the presence of H. pylori by determining ammonium concentration in the gastric juice during endoscopy. We evaluated whether this test may improve etiological diagnosis in CAG patients. In 595 consecutive patients who underwent upper endoscopy gastric juice was analysed with EndoFaster and standard biopsies were taken. CAG with typical bacteria was detected in 102 (17.1%) patients, and CAG without H. pylori was found in 36 (6.3%) cases. EndoFaster detected the infection in 22 (61.1%) of these patients. Neither ongoing proton pump inhibitor therapy nor previous eradication therapy affect the test accuracy. By using EndoFaster, another test to search for the infection in H. pylori-negative CAG patients may be avoided in more than 60% of cases, impacting on both patients discomfort and health resources use.

Clozapine is the only evidence-based drug indicated for Treatment Resistant Schizophrenia but it is largely underprescribed, partially due to its life-threatening adverse effects (AEs). However, clozapine treatment is burdened by other common AEs as constipation, hypersalivation, postural hypotension, tachycardia and metabolic abnormalities. Few studies have investigated sex-related differences in clozapine's tolerability, reporting women to experience more frequently weight gain, hyperglycemia and constipation, while men hypertension and dyslipidemia. Based on these premises, we investigated clinical, psychopathological and metabolic sex-related differences among 147 treatment-resistant patients treated with clozapine, with a specific focus on non-life-threatening AEs. We observed significant higher prevalence of tachycardia in men, and of orthostatic hypotension and constipation in women. Concerning metabolic alterations, we observed significant lower levels of HDL-cholesterol and higher prevalence of hypertriglyceridemia among men, whereas females showed higher prevalence of abdominal obesity. Consistently with previous studies, our data confirm the presence of sex-related differences in clozapine tolerability, with a main effect of sex especially for tachycardia, postural hypotension and constipation. Although non-life-threatening, these common AEs significantly affect patients' quality of life, undermine compliance and cause treatment discontinuation. A better understanding of this topic could contribute to tailor therapeutic approaches, thus improving tolerability, compliance and clinical stability.

BACKGROUND: Spleen stiffness (SS) has gained a lot of interest in the context of liver cirrhosis and portal hypertension stratification. However, there is a paucity of data on confounding factors that may alter SS values. METHODS: Between January 2018 and October 2019, we enrolled 120 healthy subjects and 117 patients with hepatitis C virus (HCV) infection who did not have significant liver fibrosis (i.e., F0–1). Abdominal ultrasound evaluation was performed on each individual to measure portal vein diameter, portal flow velocity, spleen bipolar diameter, and splenic area. We also performed liver and spleen elastography. RESULTS: HCV patients had higher SS (p 32 IU/L. Besides, the relationship between SS and ALT was described by cubic polynomial regression according to the following equation: 11.735 + 0.404 (ALT)(1) − 0.002 (ALT)(2) + 4.26 × 10(–6) (ALT)(3). CONCLUSIONS: Our results bring new light to the role of inflammation as a confounding factor for SS measurement. Therefore, particular attention should be paid to serum transaminase for a correct evaluation of spleen elastography.

The present work has two main objectives: the realization of a Virtual Training system about assembly operations in two immersive virtual environments and the comparison between the features offered. The first solution proposed is the use of commercial software IC.IDO, produced by ESI Group. It is designed for applications throughout all the PLM, offering support both in the design and production phases, as well as after-sales assistance. At the opposition, the second solution proposed is the use of the Open-source software Unity. This graphics engine has found significant success in gaming field in the recent years, as it allows more flexibility to the developer for the implementation of the features but requires greater competence in terms of programming. The following paragraphs firstly address the path outlined from the collection of customer’s requirements to the virtual prototypes’ release, following the Systems Engineering approach. Secondly, a benchmark between IC.IDO and Unity’s features is illustrated to point out their main differences, strengths and weaknesses.

Introduction: Cognitive deficits and metabolic disturbances are among the main determinants of functional impairment and reduced life expectancy in patients with schizophrenia, and they may share underlying biological mechanisms. Among these, interleukin-1β (IL-1β), a key mediator of inflammatory response, is of particular interest. IL-1β C-511T polymorphism has been associated with neuropsychiatric conditions and, in the general population, with cognitive and metabolic alterations. This study aims to evaluate the effects of the IL-1β C-511T polymorphism on both cognition and metabolic syndrome in a sample of patients affected by schizophrenia, with a focus on sex differences. Methods: 138 patients with schizophrenia were assessed for metabolic parameters and neurocognitive measures by means of the Brief Assessment of Cognition Scale. The effects of IL-1β C-511T polymorphism on cognition and metabolic syndrome were evaluated in the context of general linear models. Results: The analysis showed a significant interaction between IL-1β genotype and sex on 2 core cognitive domains. In detail, among CC homozygous, females outperformed males on processing speed, while among T carriers, males outperformed females on executive functions. A significant interaction also emerged between metabolic syndrome, sex, and IL-1β genotype for executive functions, with worse performance for T carrier females with metabolic syndrome. No significant direct effect was observed for metabolic syndrome on cognition. Conclusion: These findings support the hypothesis that IL-1β polymorphism could play a key role in mediating the complex and refined relationship between metabolic syndrome and cognitive performance.

The surface of nanowires is a source of interest mainly for electrical prospects. Thus, different surface chemical treatments were carried out to develop recipes to control the surface effect. In this work, we succeed in shifting and tuning the semiconductivity of a Si nanowire-based device from n- to p-type. This was accomplished by generating a hole transport layer at the surface by using an electrochemical reaction-based nonequilibrium position to enhance the impact of the surface charge transfer. This was completed by applying different annealing pulses at low temperature (below 400 °C) to reserve the hydrogen bonds at the surface. After each annealing pulse, the surface was characterized by XPS, Kelvin probe measurements, and conductivity measured by FET based on a single Si NW. The mechanism and conclusion were supported experimentally and theoretically. To this end, this strategy has been demonstrated as an essential tool which could pave a new road for regulating semiconductivity and for other low-dimensional nanomaterials., M.B. is thankful for the MAOF Grant from the Council for Higher Education in Israel for new faculty members. A.S. is appreciative of the institutional scholarships for Ph.D. students that they received from Ben-Gurion University of the Negev. W.W. is thankful for the fundamental research funds from the Central Universities (JC2002). L.Z. is thankful for the support of a postdoctoral fellowship from the Jacob Blaustein Center for Scientific Cooperation, the National Natural Science Foundation of China (61904134), and the National Natural Science Foundation of Shaanxi Province (2019JQ-291). The computing resources and the related technical support used for this work have been provided by CRESCO/ENEAGRID High Performance Computing infrastructure and its staff, along with additional support from S. Migliori and S. Giusepponi. E.N.E.A. acknowledges funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 824158 (EoCoE-II). J.A. acknowledges funding from Generalitat de Catalunya 2017 SGR 327 and the Spanish MINECO coordinated project ENE2017-85087-C3. ICN2 is supported by the Severo Ochoa program from Spanish MINECO (SEV-2017-0706) and is funded by the CERCA Programme/Generalitat de Catalunya.

Background Although many studies emphasize the importance of using oxygen saturation (SpO2) targets in the NICUs, there is a wide variability in used saturation ranges among centers. Primary aim was to draw a representative picture on how the management of oxygen monitoring is performed in the Italian NICUs. Second aim was to identify healthcare-professionals related factors associated with oxygen targeting in the preterm population. Methods Cross-sectional study with data collection via an electronic survey form. A questionnaire containing pre-piloted and open questions on monitoring and management of the SpO2 was administered to neonatologists across the network of the Italian Society of Neonatology. The questions focused on: the infrastructure, specific training, healthcare professionals and patients-related factors. The results of the survey were anonymously collected, summarized and analyzed. Results Out of 378 questionnaires, 93 were correctly filled. Thirty-six different SpO2 ranges were observed. Centers using written standard operating procedures on oxygen management and SpO2 monitoring maintained a correct average range of SpO2 90–95%, avoided hyperoxia and reconsidered saturation targets in relation to comorbidities. 39.8% of responders disabled alarms during neonatal care. One center used biomarkers for complete monitoring of neonatal oxygenation status. Conclusions There is considerable variation in SpO2 targets for preterm infants in the Italian NICUs. Standard operating procedures and specific training for health care personnel are the main factors playing a role for the correct maintenance of the recommended oxygen targets in preterms.

Thyroid diseases are characterized by a wide range of physical and mental symptoms that can affect biological function, emotional and social life of patients. However, their impact on work functioning is not yet fully understood. Therefore, this review aims to address the way in which thyroid diseases can affect occupational outcomes, i.e., the employment rate, sick leave, working capacity and work income of patients. A systematic review of Pubmed, Scopus and ISI Web of Knowledge databases has been performed. Although it is not possible to extrapolate precise data for benign pathologies, about a third of the survivors of thyroid cancer could be unemployed. Hyperthyroid and hypothyroid patients presented a greater risk of long-term sick leave than controls, depending on the severity of the disease. Hyperthyroidism impaired working ability in about a third of affected patients, particularly in cases complicated by orbitopathy with diplopia. A possible influence of thyroid diseases on various occupational outcomes emerged from our review, however further research seems necessary to understand the relationship between work problems, specific pathological characteristics over time and risk factors in the workplace. This may support a comprehensive, interdisciplinary management of thyroid disorders, with benefits for patients’ personal, social and professional life.

Cognitive deficits represent core features of schizophrenia, affecting quality of life and functioning. The excitatory amino acid transporter 2 (EAAT2) is responsible for the majority of glutamate reuptake and its activity is crucial for glutamatergic neurotransmission, prevention of excitotoxic damage and cerebral metabolism. Different studies reported that EAAT2 rs4354668 (−181 T/G) influences cognitive functions and brain structures in patients with schizophrenia. Specifically, the G allele, linked to lower EAAT2 expression, was associated with impaired prefrontal cognitive performance and reduced grey matter volumes. Cognitive remediation therapy (CRT) is one of the best available tool to treat cognitive deficits in schizophrenia, able to induce a neuroplastic modulation of cognitive functions. The present study aims to investigate the effects of rs4354668 on CRT outcome, also considering possible genotype interaction with antipsychotic (AP) treatment, since EAAT2 expression is negatively influenced by clozapine. We examined rs4354668 in 88 clinically stabilized patients with schizophrenia, treated with CRT and assessed at enrolment, at the end of CRT and after 3 months. We observed greater working memory improvements among patients carrying the T/T genotype, regardless of AP treatment. Moreover, we reported a significant interaction between pharmacological treatment and rs4354668 on executive functions, with greater improvements among T/T patients treated with APs other than clozapine. These observations suggest that impaired EAAT2 expression may attenuate CRT outcome. Moreover, our results indicate the possibility that rs4354668 could also differentially influence the response to CRT depending on the AP treatment.

In laparoscopic minimally invasive robotic surgery, a teleoperated robot is interposed between the patient and the surgeon. Despite the robot aid, the manipulation capabilities of surgical instruments are far from those of the human hand. In this letter, we want to make a step forward toward robotic solutions that can improve manipulation capabilities of the surgical instruments. A new concept of needle-driver tool is presented, which takes inspiration from the human hand model. The idea is to modify a standard laparoscopic tool by introducing an additional degree of freedom, which allows in-hand reorientation of the suturing needle. A 3D printed prototype has been built to validate the tool design. The improved manipulation capabilities have been assessed quantitatively by evaluating a weighted dexterity index along a single stitch trajectory. Moreover, a comparison between our tool and a standard needle driver has been done in terms of time required for the execution of a complete suturing sequence.

Objectives: Cognitive reserve (CR), defined as individual differences in the ability to cope with brain damage, seem to be associated to the several psychopathological features in psychiatric patients, such as the functional outcome. This study aims to identify different profiles of CR by combining intelligence quotient (IQ) and premorbid functioning, two measures independently associated to CR in previous works, as well as to explore CR effect on both Theory of Mind (ToM) baseline performance and improvement after socio-cognitive trainings. Methods: Sixty patients with chronic schizophrenia underwent a socio-cognitive rehabilitation. All patients were assessed for psychopathology, neurocognition, and ToM at baseline and post-treatment. CR profiles were explored with K-means cluster analysis, while differences between clusters in both baseline assessments and post-treatment ToM improvement, were analyzed by means of analysis of variance and repeated measures analysis of covariance. Results: The analysis revealed three CR profiles, respectively, characterized by low early premorbid functioning and mild intellectual impairment, average/high early premorbid functioning trend with moderate intellectual impairment and good early premorbid functioning associated to IQ within normal limits. Analyses showed a significant effect of CR on both baseline ToM performance and treatment outcome: patients with higher CR reached significantly better ToM scores. Conclusions: These results underline the clinical relevance of defining CR profiles of patients to customize trainings: subjects with a lower CR may benefit from more intensive programs. A deeper knowledge about CR may considerably increase our understanding of individual differences and thus potentiate treatment outcome. (JINS, 2018, 24, 563–571)

BACKGROUND Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition in children. Although ADHD is treatable, barriers remain to engagement in treatment, especially among socioeconomically disadvantaged and racial and ethnic minority families. Our goal was to examine the process by which families engage in ADHD treatment and to identify targets for an intervention to improve engagement in care. METHODS We conducted in-depth semistructured qualitative interviews with 41 parents of diverse youth aged 3 to 17 years old in treatment of ADHD at an urban safety net hospital. Parents were asked about their journey through diagnosis and treatment, community attitudes about ADHD, and other factors influencing treatment access and decision-making. Transcripts were analyzed by using thematic analysis. RESULTS Of children with ADHD, 69.2% were male, 57.7% were Black or African American, and 38.5% were of Hispanic, Latino, or Spanish origin. Parents were 92.7% female, were 75.6% English speaking, and had a median income of $20 000. Parents described 6 stages to the process of engaging in care for their child’s ADHD, which unfolded like a developmental process: (1) normalization and hesitation, (2) fear and stigmatization, (3) action and advocacy, (4) communication and navigation, (5) care and validation, and (6) preparation and transition. Barriers often occurred at points of stage mismatch between parents and providers and/or systems. Difficulty resolving an earlier stage interfered with the progression through subsequent stages. CONCLUSIONS The 6 stages framework could be used to develop new strategies to measure engagement and to design family-centered interventions to facilitate engagement in ADHD treatment.

Prematurity is a risk factor for the development of chronic adult diseases. Metabolomics can correlate the biochemical changes to a determined phenotype, obtaining real information about the state of health of a subject at that precise moment. Significative differences in the metabolomic profile of preterm newborns compared to those born at term have been already identified at birth. An observational case–control study was performed at the University Hospital of Siena. The aim was to evaluate and compare the metabolomic profiles of young adults born preterm to those born at term. Urinary samples were collected from 67 young adults (18–23 years old) born preterm (mean gestational age of 30 weeks, n = 49), and at term of pregnancy (mean gestational age of 38 weeks, n = 18). The urinary spectra of young adults born preterm was different from those born at term and resembled what was previously described at birth. The Random Forest algorithm gave the best classification (accuracy 82%) and indicated the following metabolites as responsible for the classification: citrate, CH2 creatinine, fumarate and hippurate. Urine spectra are promising tools for the early identification of neonates at risk of disease in adulthood and may provide insight into the pathogenesis and effects of fetal programming and infants’ outcomes.

Food systems have the potential to support human health, respecting the environmental sustainability principles. Food sustainability, enclosed in the concept of environmental sustainability, involves different aspects, including the recycling of food waste derived from the agri-food production chain, the use of biotechnologies ensuring the sustainability of the recovery processes of bioactive compounds from food waste and, last but not least, the awareness of having to consume and waste less food. Food loss and waste is generated during the whole supply chain, from production to household utilization. The utilization of agricultural wastes as an abundant, renewable and low-cost source for the production of high value-added products is currently explored. The bioactive compounds present in these sources have been proved to possess a wide range of biological activities; therefore, research is needed into the application of environmentally friendly traditional and advanced techniques with low production costs in the extraction, isolation and purification of phytochemical compounds from agricultural wastes in high yields and at maximal quality. Authors of this manuscript propose and discuss an innovative and sustainable extraction system of polyphenols from vegetable waste, based on an enzymatic pre-treatment coupled with a solid-liquid extraction by using a particular extractor (Naviglio Estrattore®). This extraction system, organic solvent free, allowed to extract relevant amount of polyphenols (flavonoids in particular) from several vegetable waste products.

Summary Congenital isolated ACTH deficiency (IAD) is a rare condition characterised by low plasma ACTH and serum cortisol with normal production of other pituitary hormones. TBX19 (also known as TPIT) is a T-box pituitary restricted transcription factor important for POMC gene transcription and terminal differentiation of POMC-expressing cells. TBX19 gene mutations have been shown to cause neonatal-onset congenital IAD. We report a neonate of Romanian origin, who presented at 15 h of life with respiratory arrest and hypoglycaemia which recurred over the following 2 weeks. Biochemical investigations revealed IAD, with undetectable serum cortisol (cortisol < 1 μg/dL; normal range (NR): 7.8–26.2) and plasma ACTH levels within the normal range (22.1 pg/mL; NR: 4.7–48.8). He responded to hydrocortisone treatment. Patient DNA was analysed by a HaloPlex next-generation sequencing array targeting genes for adrenal insufficiency. A novel homozygous synonymous mutation p.Thr96= (Chr1:168260482; c.288G>A; rs376493164; allele frequency 1 × 10−5, no homozygous) was found in exon 2 of the TBX19 gene. The effect of this was assessed by an in vitro splicing assay, which revealed aberrant splicing of exon 2 giving rise to a mutant mRNA transcript whereas the WT vector spliced exon 2 normally. This was identified as the likely cause of IAD in the patient. The predicted protein product would be non-functional in keeping with the complete loss of cortisol production and early presentation in the patient. Learning points Synonymous variants (a nucleotide change that does not alter protein sequence) usually thought to be benign may still have detrimental effects on RNA and protein function causing disease. Hence, they should not be ignored, especially if very rare in public databases. In vitro splicing assays can be employed to characterise the consequence of intronic and exonic nucleotide gene changes that may alter splicing. Establishing a diagnosis due to a TBX19 mutation is important as it defines a condition of isolated ACTH deficiency not associated with additional pituitary deficiencies.

Purpose: In patients with >1 non–small cell lung carcinoma (NSCLC), the distinction between separate primary lung carcinomas (SPLCs) and intrapulmonary metastases (IPMs) is a common diagnostic dilemma with critical staging implications. Here, we compared the performance of comprehensive next-generation sequencing (NGS) with standard histopathologic approaches for distinguishing NSCLC clonal relationships in clinical practice. Experimental Design: We queried 4,119 NSCLCs analyzed by 341–468 gene MSK-IMPACT NGS assay for patients with >1 surgically resected tumor profiled by NGS. Tumor relatedness predicted by prospective histopathologic assessment was contrasted with comparative genomic profiling by subsequent NGS. Results: Sixty patients with NGS performed on >1 NSCLCs were identified, yielding 76 tumor pairs. NGS classified tumor pairs into 51 definite SPLCs (median, 14; up to 72 unique somatic mutations per pair), and 25 IPMs (24 definite, one high probability; median, 5; up to 16 shared somatic mutations per pair). Prospective histologic prediction was discordant with NGS in 17 cases (22%), particularly in the prediction of IPMs (44% discordant). Retrospective review highlighted several histologic challenges, including morphologic progression in some IPMs. We subsampled MSK-IMPACT data to model the performance of less comprehensive assays, and identified several clinicopathologic differences between NGS-defined tumor pairs, including increased risk of subsequent recurrence for IPMs. Conclusions: Comprehensive NGS allows unambiguous delineation of clonal relationship among NSCLCs. In comparison, standard histopathologic approach is adequate in most cases, but has notable limitations in the recognition of IPMs. Our results support the adoption of broad panel NGS to supplement histology for robust discrimination of NSCLC clonal relationships in clinical practice.

Primary adrenal insufficiency (PAI) is a potentially life‐threatening condition that requires urgent diagnosis and treatment. Whilst the most common causes are congenital adrenal hyperplasia (CAH) in childhood and autoimmune adrenal insufficiency in adolescence and adulthood, more than 30 other physical and genetics cause of PAI have been reported. Reaching a specific diagnosis can have implications for management and for monitoring associated features, as well as for counselling families about recurrence risk in siblings and relatives. Here, we describe some recent insights into the genetics of adrenal insufficiency and associated molecular mechanisms. We discuss (a) the role of the nuclear receptors DAX‐1 (NR0B1) and steroidogenic factor‐1 (SF‐1, NR5A1) in human adrenal and reproductive dysfunction; (b) multisystem growth restriction syndromes due to gain‐of‐function in the growth repressors CDKN1C (IMAGE syndrome) and SAMD9 (MIRAGE syndrome), or loss of POLE1; (c) nonclassic forms of STAR and P450scc/CYP11A1 insufficiency that present with a delayed‐onset adrenal phenotype and represent a surprisingly prevalent cause of undiagnosed PAI; and (d) a new sphingolipidosis causing PAI due to defects in sphingosine‐1‐phosphate lyase‐1 (SGPL1). Reaching a specific diagnosis can have life‐long implications for management. In some situations, milder or nonclassic forms of these conditions can first present in adulthood and may have been labelled, “Addison's disease.”

BACKGROUND The management of high-risk human papillomavirus (HR-HPV)-related oropharyngeal head and neck squamous cell carcinomas (HNSCCs) are distinct from HNSCC linked to smoking and alcohol use. HR-HPV-positive HNSCC frequently presents as a cervical lymph node metastasis. Because fine-needle aspiration (FNA) is often the initial diagnostic procedure, evaluating HR-HPV status in cytology specimens is important. The overexpression of p16 is a surrogate for HR-HPV; however, the evaluation of p16 in FNAs remains controversial. METHODS From September 2015 to December 2016, cytopathologists performed 25 FNAs of neck lymph nodes that were suspicious for HR-HPV-positive HNSCC. Initial passes produced smears for on-site evaluation and CytoLyt material. Additional passes were formalin-fixed. A CytoLyt cell block (CCB) and a formalin-fixed cell block (FFCB) were prepared, and p16 immunocytochemistry was performed. RESULTS In 24 of 25 cases, the FFCB had diffuse (≥70% of cells), strong nuclear/cytoplasmic p16 staining. In all 24 of these cases, HR-HPV was detected by in situ hybridization. The corresponding CCB had weak-to-moderate p16 staining in

Air conditioning (AC) systems have been increasingly adopted as the main cooling strategy in Brazilian buildings, and this may affect people's response to hot indoor spaces. A field study was conducted in naturally-ventilated classrooms located in the northeast region of Brazil with the purpose of evaluating the subjective responses of the students as a function of different thermal backgrounds in relation to the use of AC. Indoor microclimatic variables were measured and a questionnaire was applied to the students, in which the thermal perception, air movement perception and cooling strategy preference were recorded. The thermal background of the participants in relation to AC was classified as follows: recent prior exposure (exposure to AC 1 h before the field survey), long-term exposure (routine experience of AC), and hours of AC exposure daily (in cases where long-term exposure was declared). Long-term exposure to AC influenced the thermal perception of the students and significant differences between exposed and unexposed students were observed for a temperature of 28–30 °C (standard effective temperature - SET). The influence of recent prior exposure to AC was negligible compared to that of long-term exposure. Among the students with experience of long-term exposure to indoor AC, those who declared exposure to 12 or more hours daily responded with the warmest thermal sensation (TS) values and the highest percentage of preference for AC as a cooling strategy. Hot discomfort was a key factor in the influence of long-term exposure on human thermal perception.

Introduction: Cord blood gas analysis reflects placental respiratory and metabolic function and is commonly used to assess fetal status at birth. Our aim was to identify the differences in blood gas parameters between the umbilical artery (UA) and umbilical vein (UV) in term and preterm infants. Methods: This was a prospective pilot study. Umbilical cord artery and UV samples were consecutively collected from 225 term and 57 preterm infants at the University Hospital of Padua and at the neonatal unit of Ruesch Hospital in Naples, Italy. Blood gas-analysis and glucose measurement were performed in all samples. Term infants were divided into adequate for gestational age (AGA) and small for gestational age (SGA) according to birth weight percentile. Data were analyzed using Pearson Product-Moment Correlation, independent-samples t-test, and paired-samples t-test. A p-value

This paper introduces a renewed gateway to ENEAGRID distributed computing resources named Fast Access to Remote Objects 2.0 (FARO 2.0). FARO 2.0 is a tool for application and desktop virtualization with a focus towards user experience (UX), providing trained as well as untrained users with a collection of centralized services that can be seamlessly used on their client through a remote desktop protocol. FARO 2.0 is a JavaFX application whose graphical user interface (GUI) and whose main logics have been implemented through the well-known Web technologies (HTML5, CSS3, Javascript) for easier maintainability and customizability, taking full advantage of the WebView component. The FARO 2.0 framework has been deployed both as a general purpose GUI for remote user access to ENEAGRID resources and as a specialized application or workflow-oriented GUI. They are applied in a set of applicative domains, ranging from materials science to technologies for energy and industry, environmental modeling, and nuclear fusion. Some examples and results are also presented.

BackgroundPersistent systemic inflammation leads to multidistrectual body dysfunctions. Attenuation of inflammation may improve patients’ functional and life prognoses. We hypothesized that essential amino acids (EAAs) given to elderly patients in rehabilitation after acute diseases may be associated with a reduced inflammatory state. Therefore, this retrospective study investigated whether the supplementation of EAAs – modulators of immune competence – was associated with a reduced inflammation rate in elderly patients.MethodsThe medical records of 282 patients admitted to the rehabilitation (rehab) institute after acute index events (surgery or medical diseases) (age: 81.18 ± 8.58 years; females: 67.9%) were analyzed.Results46 patients (16.3% of the entire population) had received EAA supplements (S), whereas the remaining 236 patients had not (N-S). Systemic inflammation (I) (serum C-reactive protein (CRP) > 0.5 mg/dL) was present in 67.4% of the I-S group and 57.2% of the I-N-S group. During rehab, the I-S group (but not the I-N-S group) showed a reduction in CRP levels ( p = 0.03) and an increase in circulating lymphocytes ( p = 0.035), immune cells of the adaptive immune system. C-reactive protein levels remained virtually unchanged in non-inflamed patients who received supplements but increased in non-inflamed patients who did not receive supplements ( p = 0.05). Stratified for developed infections, CRP levels reduced in S patients ( p = 0.008) but did not in N-S patients.ConclusionEAA supplementation was associated with reduced inflammation in both inflamed and infected patients. In addition, EAA supplementation was associated with increased circulating lymphocytes in inflamed patients.

Pancreatic Carcinoma (PC) cells have the ability to induce patient immunosuppression and to escape immunosurveillance. Low circulating lymphocytes are associated with an advanced stage of PC and reduced survival. Blood lymphocytes expressed as a percentage of Total White Blood Cells (L% TWBC) could predict chemotolerance (n° of tolerated cycles), survival time and Body Weight (BW) more effectively than lymphocytes expressed as an absolute value (LAB &gt, 1500 n°/mm3) or lymphocytes &gt, 22%, which is the lowest limit of normal values in our laboratory. Forty-one patients with advanced PC, treated with chemotherapy, were selected for this observational retrospective study. Patients were evaluated at baseline (pre-chemotherapy), and at 6, 12 and 18 months, respectively, after diagnosis of PC. The study found L ≥ 29.7% to be a better predictor of survival (COX model, using age, sex, BW, serum creatinine, bilirubin and lymphocytes as covariates), chemotolerance (r = +0.50, p = 0.001) and BW (r = +0.35, p = 0.027) than LAB &gt, 1500 or L &gt, 22%. BW did not significantly correlate with chemotolerance or survival. The preliminary results of this study suggest that L ≥ 29.7% is more effective than LAB &gt, 22% at predicting chemotolerance, survival time and nutritional status. A possible impact of nutritional status on chemotherapy and survival seems to be lymphocyte-mediated given the association between BW and L%. This study may serve as the basis for future research to explore whether nutritional interventions can improve lymphopenia, and if so, how this may be possible.

BACKGROUND The use of simulation-based medical education is strongly recommended to insure neonatal resuscitation skills for health caregivers. High fidelity simulation was executed to allow the evaluation of technical and non-technical skills. Salivary cortisol level was considered reliable biomarkers of adrenocortical activity and useful tool to learning assessment and stress response. METHODS Our primary aim was to test changes in salivary cortisol levels before and after the simulation for neonatal resuscitation between high and low fidelity setting. Secondary aim was to evaluate salivary cortisol level in the participants, leader and not leader. Fifty-two health care providers were divided in ratio 1:1 into low-fidelity (LF group) and high-fidelity scenario (HF group) of neonatal resuscitation. In each group the participants assumed the role of team leader or not team leader. Salivary samples were collected from all participants 5 minutes before and after each simulation scenario by using oral swab. Analysis of difference was analysed by Kruskal Wallis test. RESULTS Salivary cortisol levels were significantly higher in HF group (n=26) than LF group (n=26) before the performance (5,407 mmol/l vs 3,090 mmol/l; p=0.018). In the HF group, salivary cortisol levels were significantly lower after simulation than before (p=0.007), moreover not team leader showed higher salivary cortisol levels before of the simulation than after (p=0.003). Team leaders showed higher salivary cortisol levels than not team leader after high-fidelity scenario (p=0.039). CONCLUSIONS High-fidelity simulation scenario had a great impact on stress level, furthermore leaders showed higher salivary cortisol levels than not team leaders.

BACKGROUND: The landscape of guided bronchoscopy for the sampling of pulmonary parenchymal lesions is evolving rapidly. Shape-sensing robotic-assisted bronchoscopy (ssRAB) recently was introduced as means to allow successful sampling of traditionally challenging lesions. RESEARCH QUESTION: What are the feasibility, diagnostic yield, determinants of diagnostic sampling, and safety of ssRAB in patients with pulmonary lesions? STUDY DESIGN AND METHODS: Data from 131 consecutive ssRAB procedures performed at a US-based cancer center between October 2019 and July 2020 were captured prospectively and analyzed retrospectively. Definitions of diagnostic procedures were based on prior standards. Associations of procedure- and lesion-related factors with diagnostic yield were examined by univariate and multivariate generalized linear mixed models. RESULTS: A total of 159 pulmonary lesions were targeted during 131 ssRAB procedures. The median lesion size was 1.8 cm, 59.1% of lesions were in the upper lobe, and 66.7% of lesions were beyond a sixth-generation airway. The navigational success rate was 98.7%. The overall diagnostic yield was 81.7%. Lesion size of ≥ 1.8 cm and central location were associated significantly with a diagnostic procedure in the univariate analysis. In the multivariate model, lesions of ≥ 1.8 cm were more likely to be diagnostic compared with lesions < 1.8 cm, after adjusting for lung centrality (OR, 12.22; 95% CI, 1.66-90.10). The sensitivity and negative predictive value of ssRAB for primary thoracic malignancies were 79.8% and 72.4%, respectively. The overall complication rate was 3.0%, and the pneumothorax rate was 1.5%. INTERPRETATION: This study was the first to provide comprehensive evidence regarding the usefulness and diagnostic yield of ssRAB in the sampling of pulmonary parenchymal lesions. ssRAB may represent a significant advancement in the ability to access and sample successfully traditionally challenging pulmonary lesions via the bronchoscopic approach, while maintaining a superb safety profile. Lesion size seems to remain the major predictor of a diagnostic procedure.

Context Although primary adrenal insufficiency (PAI) in children and young people is often due to congenital adrenal hyperplasia (CAH) or autoimmunity, other genetic causes occur. The relative prevalence of these conditions is poorly understood. Objective We investigated genetic causes of PAI in children and young people over a 25 year period. Design, Setting and Participants Unpublished and published data were reviewed for 155 young people in the United Kingdom who underwent genetic analysis for PAI of unknown etiology in three major research centers between 1993 and 2018. We pre-excluded those with CAH, autoimmune, or metabolic causes. We obtained additional data from NR0B1 (DAX-1) clinical testing centers. Intervention and Outcome Measurements Genetic analysis involved a candidate gene approach (1993 onward) or next generation sequencing (NGS; targeted panels, exomes) (2013-2018). Results A genetic diagnosis was reached in 103/155 (66.5%) individuals. In 5 children the adrenal insufficiency resolved and no genetic cause was found. Pathogenic variants occurred in 11 genes: MC2R (adrenocorticotropin receptor; 30/155, 19.4%), NR0B1 (DAX-1; 7.7%), CYP11A1 (7.7%), AAAS (7.1%), NNT (6.5%), MRAP (4.5%), TXNRD2 (4.5%), STAR (3.9%), SAMD9 (3.2%), CDKN1C (1.3%), and NR5A1/steroidogenic factor-1 (SF-1; 0.6%). Additionally, 51 boys had NR0B1 variants identified through clinical testing. Although age at presentation, treatment, ancestral background, and birthweight can provide diagnostic clues, genetic testing was often needed to define the cause. Conclusions PAI in children and young people often has a genetic basis. Establishing the specific etiology can influence management of this lifelong condition. NGS approaches improve the diagnostic yield when many potential candidate genes are involved.

Marine and coastal ecosystems are among the most productive environments in the world and their stocks of natural capital offer a bundle of vital ecosystem services. Anthropogenic pressure seriously threatens health and long-term sustainability of marine environments. For these reasons, integrated approaches capable of combining ecological and socio-economic aspects are needed to achieve nature conservation and sustainability targets. In this study, the value of natural capital of the Egadi Islands Marine Protected Area (EI-MPA) was assessed through a biophysical and trophodynamic environmental accounting model. The emergy value of both autotrophic and heterotrophic natural capital stocks was calculated for the main habitats of the EI-MPA. Eventually, the emergy value of natural capital was converted into monetary units to better communicate its importance to local managers and policy-makers. The total value of natural capital in the EI-MPA resulted in 1.12·10 21 sej, equivalent to about 1.17 billion of euros. In addition, using Marxan software, the results of the environmental accounting were integrated with spatial data on main human uses. This integration took into account the trade-offs between conservation measures and human exploitation by means of two different scenarios, with and without considering human uses in the EI-MPA. The comparison between the scenarios highlighted the importance of taking into account human activities in marine spatial planning (MSP), allowing the identification of key areas for natural capital conservation. In conclusion, this study showed the importance of integrating environmental accounting with conservation planning to support effective strategies for ecological protection and sustainable management of human activities. The results of this study represent a first benchmark useful to explore alternative nature conservation strategies in the EI-MPA, and, more in general, in Mediterranean MPAs.

BackgroundEarly-onset neonatal sepsis (EOS) is a serious and potentially life-threatening disease in newborns. C reactive protein (CRP) is the most used laboratory biomarker for the detection of EOS. Little is known about normal reference values of CRP during the perinatal period as several factors are able to influence it.ObjectivesTo identify an appropriate range of CRP values in healthy term newborns during the first 48 hours of life.DesignCRP determination was performed in 859 term newborns at 12, 24 and 48 hours of life. Mode of delivery, maternal vaginal culture results, intrapartum antimicrobial prophylaxis (IAP) and other perinatal variables were recorded.ResultsCRP mean values were significantly higher at 48 hours (4.10 mg/L) than at both 24 (2.30 mg/L) and 12 hours of life (0.80 mg/L). CRP levels were affected by a number of perinatal proinflammatory variables. In particular, CRP mean values were significantly higher in babies born by vaginal delivery (3.80 mg/L) and emergency caesarean section (3.60 mg/L) than in babies born by elective caesarean section (2.10 mg/L). Completed course of IAP led to lower CRP mean values (2.90 mg/L) than IAP not completed (3.80 mg/L) or not performed (4.70 mg/L).ConclusionsPostnatal age and mode of delivery significantly influence CRP values. Reliable reference values are crucial in order to obtain an adequate diagnostic accuracy.

Background:Work-related stress is a relevant phenomenon in terms of health and safety at work, as occupational distress has a negative impact on individual and organisational well-being. It is a complex and multifactorial phenomenon, whose evaluation must be carried out through a specific and adequate methodology.Objective:This work aims to identify versatile tools that can quickly provide reliable measures of work distress. It analyzes the proposal elaborated by the “Comitato Unico di Garanzia per le Pari Opportunità, la Valorizzazione del Benessere di chi lavora e contro le Discriminazioni” of Rome,i.e. the tool “Valutazione è prevenzione, Sicurezza è partecipazione”.Methods:A study was carried out on a sample of 474 employees of the Neapolitan Judicial Offices, who were given a standardized questionnaire to investigate the stress, associated with the proposal of the Comitato Unico di Garanzia.Results:From the elaboration of the results, it emerges that the conditions of working wellbeing are linked to two main factors related to the perception of workers both of physical-environmental and organisational-relational aspects. In particular, it emerged that the new assessment tool, consisting of a small number of items, contributes to the detection of work stress, so it is necessary to deepen through future research the contribution that this tool can offer to the survey on work-related stress.Conclusion:Having highlighted two factors that significantly saturate the presence of a working discomfort, through an agile tool, allows us to plan a new research path, which can approach the complexity of the phenomenon through the methods of deep learning.

Computer-assisted cognitive remediation (CACR) is a computer-based rehabilitation treatment aimed at improving cognition and at developing strategies that can be applied to various functional areas. Different protocols are currently used with great variability over the intensity and duration of treatments. In this study, we evaluated the effects of a brief and intensive CACR training (i.e., 15 sessions for 3 weeks) on cognitive domains, as well as the durability of cognitive gains and their generalization to functional areas, 3 months after CACR training. Thirty-eight patients with schizophrenia were recruited and assessed for psychopathology, cognitive performance, and functioning before the rehabilitative intervention. Patients were reassessed for cognition after CACR rehabilitation. Moreover, a subsample of 13 patients was evaluated for cognition and functioning 3 months after CACR completion. Results show significant improvements in multiple cognitive domains after CACR. Furthermore, 3 months after CACR completion, significant improvements were also detected in executive functions and daily functioning. This study suggests that a brief and intense CACR training is effective on cognitive and functional domains and that it could be feasible and affordable for health care services, thus offering patients the best options for fulfilling recovery goals.

Background The association between maternal exposure to gaseous air pollutants and congenital heart defects (CHD) remains unclear. The concentration-response relationship and the time windows of susceptibility to gaseous pollutants may vary by pollutant species and CHD subtypes. Objective We aimed to examine the relationship between maternal exposures to four species of gaseous pollutants (NO2, O3, SO2, and CO) and atrial septal defect (ASD), which is a common subtype of CHD, and to determine the critical time windows of susceptibility for each gaseous pollutant. Methods Among 1,253,633 infants born between October 1, 2013 and December 31, 2016 in China, 1937 newborns were diagnosed with isolated ASD, a prevalence of 1.55‰. Maternal exposures to the gaseous pollutants were estimated by matching the geocoded maternal addresses with the gridded ambient concentrations. The adjusted odds ratios (aOR) between exposures and ASD were quantified by using mixed-effects logistic regression models. Results We found significantly positive associations between ASD and maternal exposures to NO2, O3, SO2, and CO during entire pregnancy, first-, second-, and third-trimester. However, no statistically significant association was found between maternal exposure to PM2.5, PM2.5-10 and ASD risk (P > 0.05). In the fully adjusted model with respect to average exposure over entire pregnancy, the adjusted odds ratios (aOR) for each 10 μg/m3 increment of NO2, O3, SO2 were 1.33 (95% CI: 1.22–1.45), 1.13 (95% CI: 1.10–1.16), 1.28 (95% CI: 1.20–1.35), respectively; the aOR for each 100 μg/m3 increment of CO was 1.10 (95% CI: 1.06–1.15). The observed concentration-response relationships varied by exposure periods and pollutants, with the strongest association for NO2 during the 1st-8th embryology weeks, for O3 during the third trimester, for SO2 during the second trimester, and for CO without obvious variation. Conclusions The findings suggest an increased risk of ASD in association with maternal exposures to four common gaseous pollutants. From the perspective of birth defects prevention and ASD risk mitigation, it is critical to reduce maternal exposure to gaseous pollutants especially during the most susceptible time windows.

Sudden infant death syndrome (SIDS) is defined as “the sudden death of an infant under 1 year of age which remains unexplained after thorough investigation including a complete autopsy, death scene investigation, and detailed clinical and pathological review”. A significant decrease of SIDS deaths occurred in the last decades in most countries after the beginning of national campaigns, mainly as a consequence of the implementation of risk reduction action mostly concentrating on the improvement of sleep conditions. Nevertheless, infant mortality from SIDS still remains unacceptably high. There is an urgent need to get insight into previously unexplored aspects of the brain system with a special focus on high-risk groups. SIDS pathogenesis is associated with a multifactorial condition that comprehends genetic, environmental and sociocultural factors. Effective prevention of SIDS requires multiple interventions from different fields. Developing brain susceptibility, intrinsic vulnerability and early identification of infants with high risk of SIDS represents a challenge. Progress in SIDS research appears to be fundamental to the ultimate aim of eradicating SIDS deaths. A complex model that combines different risk factor data from biomarkers and omic analysis may represent a tool to identify a SIDS risk profile in newborn settings. If high risk is detected, the infant may be referred for further investigations and follow ups. This review aims to illustrate the most recent discoveries from different fields, analyzing the neuroanatomical, genetic, metabolic, proteomic, environmental and sociocultural aspects related to SIDS.

Mechatronics and robotics appeared particularly effective in students’ education, allowing them to create non-traditional solutions in STEM disciplines, which have a direct impact and interaction with the world surrounding them. This paper presents the current state of the MiniCERNBot Educational Robotic platform for high-school and university students. The robot provides a comprehensive educative system with tutorials and tasks tuned for different ages on 3D design, mechanical assembly, control, programming, planning, and operation. The system is inspired to existing robotic systems and typical robotic interventions performed at CERN, and includes an education mock-up that follows the example of a previous real operation performed in CERN’s Antimatter Factory. The paper describes the learning paths where the MiniCERNBot platform can be used by students, at different ages and disciplines. In addition, it describes the software and hardware architecture, presenting results on modularity and network performance during education exercises. In summary, the objective of the study is improving the way STEM educational and dissemination activities at CERN Robotics Lab are performed, as well as their possible synergies with other education institutions, such as High-Schools and Universities, improving the learning collaborative process and inspiring students interested in technical studies. To this end, a new educational robotic platform has been designed, inspired on real scientific operations, which allows the students practice multidisciplinary STEM skills in a collaborative problem-solving way, while increasing their motivation and comprehension of the research activities.

Background/Aim H. pylori plays a major role in gastroduodenal diseases. Since its incidence is decreasing in developed countries, gastric biopsies were negative in several patients managed in clinical practice. We tested whether EndoFasterⓇ − a device allowing real-time H. pylori detection by gastric juice analysis – may optimize the need of biopsies. Methods In this prospective, multicentre study, the accuracy of EndoFasterⓇ for H. pylori detection was computed by using histology of gastric biopsies as a gold standard. Results Data of 525 consecutive patients were available, including 90 (17.1%) patients with infection. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy of EndoFasterⓇ were 87%, 84%, 53%, 97% and 85%, respectively. The overall accuracy of test was not affected neither by ongoing proton pump inhibitor therapy nor by previous eradication therapy. By using EndoFasterⓇ in our series, biopsy sampling could have been eventually avoided in a total of 279 patients, accounting for a reduction of 42.3%, accepting the risk of only 8 false negative cases. Conclusions The very high NPV of EndoFasterⓇ might allow to safely halve the need of taking gastric biopsies in unselected patients managed in clinical practice, avoiding an unavailing consume of health resources.

The Academy of Breastfeeding Medicine published a clinical protocol for Human Milk storage, recommending refrigeration at a temperature of 4 °C up to 4 d as the optimal conditions for the safety and bactericidal capacity of Human Milk. However, few studies were conducted to evaluate the change in milk composition during this type of refrigeration storage.To elucidate some uncertainties regarding the Human Milk composition and prolonged cold storage, we have investigated the effects of storage at 4 °C up to 96 h on an important category of oxidative stress markers: the Isoprostanes (F2-isoprostanes, F4-neuroprostanes and F3-isoprostanes).The experiment was repeated 3 times to ensure reproducibility of the results. We enrolled 3 donating healthy mothers for each time (total: 9 mothers). Milk was collected with standard extraction methods. Immediately after collection, each Human Milk sample from each mother was pooled and then divided into 5 aliquots. One aliquot (0 h) was immediately frozen at -80 °C until the analysis. The other aliquots (24 h, 48 h, 72 h, 96 h) were stored in a refrigerator at 4 °C respectively for 24, 48, 72 and 96 h, then immediately frozen at -80 °C until the analysis. Milk samples were then used to determine concentration of Isoprostanes in Liquid Chromatography - Mass Spectrometry and Liquid Chromatography - Tandem Mass Spectrometry.Isoprostanes were detectable in all Human Milk samples. There was no significant trend of the concentration of the tested analytes over time.This study provides evidence of the presence in human milk of all the tested isoprostanes: in particular, F2-isoprostanes, F4-neuroprostanes and F3-isoprostanes. Refrigeration and storage of fresh Human Milk in controlled conditions for 96 h did not significantly affect its bioactivity and nutritional quality related with these biomarkers.

The emergy accounting method has been widely applied to terrestrial and marine ecosystems although there is a lack of emergy studies focusing on phytoplankton primary production. Phytoplankton production is a pivotal process since it is intimately coupled with oceanic food webs, energy fluxes, carbon cycle, and Earth's climate. In this study, we proposed a new methodology to perform a biophysical assessment of the global phytoplankton primary production combining Machine Learning (ML) techniques and an emergy-based accounting model. Firstly, we produced global phytoplankton production estimates using an Artificial Neural Network (ANN) model. Secondly, we assessed the main energy inputs supporting the global phytoplankton production. Finally, we converted these inputs into emergy units and analysed the results from an ecological perspective. Among the energy flows, tides showed the highest maximum emergy contribution to global phytoplankton production highlighting the importance of thise flow in the complex dynamics of marine ecosystems. In addition, an emergy/production ratio was calculated showing different global patterns in terms of emergy convergence into the primary production process. We believe that the proposed emergy-based assessment of phytoplankton production could be extremely valuable to improve our understanding of this key biological process at global scale adopting a systems perspective. This model can also provide a useful benchmark for future assessments of marine ecosystem services at global scale.