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The prelimbic division (PrL) of the medial prefrontal cortex (mPFC) is a cerebral division that is putatively implicated in the chronic pain and depression. We investigated the activity of PrL cortex neurons in Wistar rats that underwent chronic constriction injury (CCI) of sciatic nerve and were further subjected to the forced swimming (FS) test and mechanical allodynia (by von Frey test). The effect of blockade of synapses with cobalt chloride (CoCl2), and the treatment of the PrL cortex with cannabidiol (CBD), the CB1 receptor antagonist AM251 and the 5-HT1A receptor antagonist WAY-100635 were also investigated. Our results showed that CoCl2 decreased the time spent immobile during the FS test but did not alter mechanical allodynia. CBD (at 15, 30 and 60 nmol) in the PrL cortex also decreased the frequency and duration of immobility; however, only the dose of 30 nmol of CBD attenuated mechanical allodynia in rats with chronic NP. AM251 and WAY-100635 in the PrL cortex attenuated the antidepressive and analgesic effect caused by CBD but did not alter the immobility and the mechanical allodynia when administered alone. These data show that the PrL cortex is part of the neural substrate underlying the comorbidity between NP and depression. Also, the previous blockade of CB1 cannabinoid receptors and 5-HT1A serotonergic receptors in the PrL cortex attenuated the antidepressive and analgesics effect of the CBD. They also suggest that CBD could be a potential medicine for the treatment of depressive and pain symptoms in patients with chronic NP/depression comorbidity.

OBJECTIVE We aimed to investigate the impact of applying the 2019 European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) classification criteria for systemic lupus erythematosus (SLE) in a previously described cohort of women with undifferentiated connective tissue disease (UCTD). METHODS This study included 133 women with UCTD. At the time of inclusion into the study, none of the patients met any classification criteria for other defined systemic connective tissue disease. RESULTS When applying the 2019 EULAR/ACR classification criteria to the cohort, 22 patients (17%) fulfilled the classification criteria for SLE. Patients classified as having SLE had significantly higher frequencies of mucocutaneous manifestations (23% versus 5%; P = 0.007), arthritis (59% versus 17%; P < 0.001), isolated urine abnormalities (18% versus 1%; P < 0.001), and highly specific antibodies (50% versus 15%; P < 0.001) compared to the other patients with UCTD. At follow-up, these patients were statistically significantly more likely to also meet the 1997 ACR revised SLE criteria and the Systemic Lupus International Collaborating Clinics (SLICC) criteria (18.2% versus 1.8%; P < 0.001) compared to the other UCTD patients. Patients who were diagnosed as having SLE according to the ACR 1997 update of the SLE revised criteria and the SLICC criteria during the follow-up scored higher on outcome measures when classified as having SLE according to the new 2019 EULAR/ACR classification criteria when compared to the other patients with UCTD (mean ± SD score 8.3 ± 3.7 versus 4.5 ± 4; P < 0.05). CONCLUSION When applying the 2019 EULAR/ACR criteria for SLE in a cohort of patients with UCTD, we observed that in up to 17% of cases the original classification could be challenged. New implementation will help to identify earlier patients at higher risk of developing more severe CTD manifestations.

Complex agroforestry systems (AFS) based on the diversity of natural ecosystems have been strategic for the restoration of the degraded areas allying biodiversity conservation with food production that allows minimizing restoration costs. We supposed that AFS may provide diversification of production and earnings for farmers over time depending on the system design, species utilized, and management. The financial analysis conducted in a biodiverse, multistratified, and successional AFS, with 20 species mostly from the Rainforest, associated with annual species pointed out that the restoration costs were minimized. The financial analysis was based on technical and economic coefficients obtained for two years and simulated for 20 years. The established AFS (EAFS), however, demonstrated low financial performance in the first 10 years of the project with IRR of -3.9% and 5.6% and B/C ratio of 0.8 and 1.1 for 10 and 20 years, respectively, with payback in 14 years. Based on the results obtained, simulation of a system (SAFS) was carried out from changes in the arrangement, species selection, and management. The SAFS presented IRR of 20.7% e 13.5%, B/C ratio of 1.6 and 1.8 for 10 and 20 years, respectively, with payback in 2 years. It has been shown that financial analysis might help to promote agroforestry restoration and the environmental compliance of rural properties through the financial prognosis of the system that allows the generation of products with a positive financial balance over the time required for the ecological restoration process.

The Covid-19 emergency in prisons is a public health warming due to overcrowding, poor structural conditions,and life promiscuities.Worldwide a lot of prisoners were Sars-CoV-2 positive and in Italy several outbreaks occurred in many prisons.This paper examines, using a clinical audit, a Covid-19 outbreak occurred in an Italian prison during the spring2021.The study showed that the best measures to mitigate the outbreak negative consequences both in prisoners andin the staff are the preventive actions, the hygiene and disinfection of the common detention areas; the reductionof overcrowding; the stop of the working activities during the quarantine period.Only an improvement of living conditions inside the prisons may reduce the risk of infection among inmates.

The aim of this retrospective study was to evaluate mid-term implant and prosthesis survival in patients with edentulous atrophic maxillae submitted to zygomatic implant-supported fixed rehabilitation and to identify possible related risk factors. Data were collected from records of patients with edentulous atrophic maxillae, in good general health and who were rehabilitated by means of acrylic resin full-arch screw-retained prosthesis supported by at least one zygomatic implant, between the years of 2006–2017. Implant and prosthesis survival rates were calculated. The association between implant and prosthesis loss and quantitative and qualitative variables of interest was verified with t tests and Fisher’s exact tests, respectively. For the significant variables in the latter, odds ratio and 95% confidence intervals were additionally calculated. The sample comprised 66 patients in whom 171 zygomatic implants were placed to support maxillary screw-retained full-arch prostheses. Implant and prosthesis survival rates of 94.15% and 92.4%, respectively, were observed in a mean of 3.6 years of follow-up (up to 11.7 years). Implant loss was 4.33 more likely to occur when adverse events were recorded after the procedure of implant placement (P = 0.026) and 10.31 more likely to occur in implants that had their prosthesis repaired during follow-up visits (P = 0.004). Prosthesis loss was 22.00 times more likely to occur when implants were previously lost (P

Objetivo: caracterizar os idosos atendidos em um Serviço de Urgência e Emergência Psiquiátrica quanto ao perfil sociodemográfico, diagnóstico psiquiátrico, prescrição de medicamentos e conduta médica e avaliar suas associações com o sexo. Método: estudo transversal, quantitativo, em que os dados foram obtidos a partir dos prontuários de pacientes atendidos no referido serviço, entre julho/2015 e junho/2016. A variável independente foi o sexo e as dependentes foram: idade; procedência; informante; tratamento psiquiátrico anterior; diagnóstico; medicamentos prescritos e conduta. Resultados: nos 152 prontuários analisados, observam-se idade prevalente entre 60 a 69 anos, maioria de mulheres, procedência do município local e comparecimento com acompanhante. Os diagnósticos prevalentes são a esquizofrenia e os transtornos mentais e comportamentais decorrentes do uso de substâncias psicoativas. As medicações prescritas com maior frequência são da classe dos antipsicóticos e anti-histamínicos, seguidas dos ansiolíticos/sedativos. O critério de Beers considera a prescrição de medicamentos do grupo dos benzodiazepínicos, antipsicóticos e anti-histamínicos inapropriada para idosos. A principal conduta foi a alta, sem encaminhamento a outro serviço. Conclusão: embora haja incentivo do Ministério da Saúde, com a criação de novas políticas de saúde mental, muitos profissionais mantêm o modelo de atendimento baseado na queixa e conduta, dificultando a reabilitação psicossocial dos pacientes.

Anxiety and depression are symptoms associated with ethanol withdrawal that lead individuals to relapse. In the kynurenine pathway, the enzyme indoleamine 2,3 dioxygenase (IDO) is responsible for the conversion of tryptophan to kynurenine, and dysregulation of this pathway has been associated with psychiatric disorders, such as anxiety and depression. The present study evaluated the early and late behavioral and biochemical effects of ethanol withdrawal in rats. Male Wistar rats were submitted to increasing concentrations of ethanol in drinking water during 21 days. In experiment 1, both control and withdrawal groups were submitted to a battery of behavioral tests 3, 5, 10, 19, and 21 days following ethanol removal. In experiment 2, animals were euthanized 3 days (short-term) or 21 days (long-term) after withdrawal, and the brains were dissected altogether, following kynurenine concentration analysis in prefrontal cortex, hippocampus, and striatum. Short-term ethanol withdrawal decreased the exploration of the open arms in the elevated plus-maze. In the forced swimming test, long-term ethanol-withdrawn rats displayed higher immobility time than control animals. Ethanol withdrawal altered neither locomotion nor motor coordination of rats. In experiment 2, kynurenine concentrations were increased in the prefrontal cortex after a long-term period of withdrawal. In conclusion, short-term ethanol withdrawal produced anxiety-like behaviors, while long-term withdrawal favored depressive-like behaviors. Long-term ethanol withdrawal elevated kynurenine levels, specifically in the prefrontal cortex, suggesting that the depressive-like responses observed after long-term withdrawal might be related to the increased IDO activity.

High-grade gliomas, including anaplastic oligodendroglioma, represent the most common malignant neoplasms of the central nervous system in the adult. The standard treatment of anaplastic oligodendroglioma consists of maximum surgical resection, radiotherapy and subsequent chemotherapy. Despite multimodal treatment, theoretically, all cases can relapse. Immune checkpoint inhibitors (ICIs) as pembrolizumab demonstrated promising results in many types of tumors, particularly in the presence of mismatch repair deficiency (MMRd). However, no ICI benefit was demonstrated in high-grade glioma prospective studies, although no biomarker was analyzed. Here, we describe an interesting case of recurrent anaplastic oligodendroglioma with MMRd, reporting a prolonged disease stability during pembrolizumab treatment.

Medulloblastoma is an embryonal neuroepithelial tumor that affects mainly childhood and more rarely adults. Medulloblastoma occurring as multiple nodules at diagnosis is a rare and tricky presentation. Here, we describe the case of a previously healthy 47-year-old woman with multiple posterior fossa cerebellar tumors. Histological, immunohistochemical, and molecular analyses were performed to best characterize the two excised lesions. The histopathological analysis revealed different variants of medulloblastoma in the excised nodules, one being extensive nodularity, rare in adults, and the other desmoplastic/nodular with areas of anaplasia. Immunostains and molecular analysis classified both nodules as SHH medulloblastoma. Adult medulloblastoma is extremely rare. Important differences exist between adult medulloblastoma and medulloblastoma arising in children and infants. Such differences are in location, distribution of histological variants and of molecular subgroups, survival rates, and therapeutic options. An extensive morphological and molecular characterization of such rare tumors is necessary to choice the best-tailored therapy.

This article explores the Nordic denial of colonial involvement and complicity and the way it operates in welfare work with refugees in Denmark. Deploying a postcolonial welfare analytics that puts...

Background Paraplegia after lumbar spinal surgery has been previously described. It was generally provoked by a missed thoracic compression because of degenerative processes, arachnoid cyst, and spinal cord tumor such as meningioma. We describe here a case of a patient with neurofibromatosis type 2 (NF-2) with multiple spinal meningiomas that developed postoperative paraplegia because of decompensation of spinal cord compression below and far from the operated level. Case Description A 54-year-old woman with NF-2 was followed-up for multiple spinal meningiomas (C7-T1, T6-7, T9-10 levels). Surgery for the symptomatic and larger lesion (C7-T1) was scheduled. Postoperatively, the patient was found to have paraplegia with sensor anesthesia below the level of the T6 vertebra. An urgent spinal magnetic resonance imaging (MRI) scan was performed revealing the absence of complication at the operated level (C7-T1) but the appearance of a marked intramedullary hyperintensity at the T6-7 level. An urgent T6-7 laminectomy and removal of the meningioma was performed. The postoperative phase was marked by a poor recuperation. Spinal MRI scan at 3 months clearly showed a severely injured spinal cord at the T6-7 level consistent with the neurologic status of the patient. Conclusions We report here the first case of acute neurologic deterioration after decompensation of a spinal cord compression below the operated level in spinal intradural surgery. Neurosurgeons must be aware of this possible complication when treating patients with multiple spinal meningiomas.

Background: Exposure to stressful aversive situations induces physiological and behavioral changes. Serotonin has been suggested to mediate such changes, as well as adaptation to stressful events. Serotoninergic projections arising from the median raphe nucleus to the dorsal hippocampus have been suggested to promote adaptation to chronic aversive stimuli. Such pathway may involve serotonin type 1a receptor-mediated neurotransmission. However, the serotonin 7 receptor can also be found in the median raphe nucleus and may be involved in mechanisms underlying response to stress. Aims: In this work we sought to investigate if activation of serotonin type 7 receptors would attenuate stress-induced deficits in different animal models of depression. Methods: Male Wistar rats with a guide-cannula aimed to the median raphe nucleus were submitted to restraint or forced swim stress and were tested in an elevated plus maze or forced swim test, respectively, 24 h later. SB 258741 (serotonin type 7 receptor antagonist) and/or LP 44 (serotonin type 7 receptor agonist) were administered intra-median raphe nucleus immediately before or after exposure to stress or before test. Control groups received intra-median raphe nucleus treatment 24 h or immediately before test in the elevated plus maze or forced swim test. Results: LP 44 attenuated restraint-induced exploratory deficits independently of the moment it was administered. Similar results were observed in the forced swim test, with the exception on post-stress condition. These effects on adaptation to stress induced by serotonin type 7 receptor activation were prevented by previous treatment with SB 258741. Conclusions: Our data support the idea that activation of median raphe nucleus serotonin 7 receptor is important to the development of adaptation to stress.

Secreting pituitary adenomas are tumors for which few treatment options are available, including surgical treatment and management of hormonal imbalance due to altered pituitary secretion. In case of inoperable relapse, radiotherapy or chemotherapeutic treatment can be considered; the effectiveness of these treatments, however, remains limited. In the immunotherapy era, it is necessary to select patients who can benefit from immunotherapeutic treatment. Mismatch repair deficiency is strongly associated with responsiveness to anti-PD-1 in other cancers and can be detected using immunohistochemistry for MLH1, MSH2, MHS6, and PMS2. In this case report, we report a case of rapid disease progression to pembrolizumab in a patient with a MMRd pituitary adrenocorticotropic hormone (ACTH)-secreting adenoma. For the best of our knowledge, we described for the first time, a poor efficacy of pembrolizumab in a patient with ACTH-secreting pituitary adenoma having mismatch repair deficiency probably caused by high levels of cortisol in this patient. Prospective study should be performed to assess the activity of immune checkpoint inhibitor alone or in association with temozolomide in this subsetting of pituitary adenomas.

Preterm newborns are considered at risk of acquired coagulopathy and are often prophylactically infused with fresh frozen plasma (FFP) even in the absence of bleeding. To assess the coagulation asset of preterm neonates and the biological plausibility of such infusions, we investigated at birth 87 very low birth weight (≤1500 g) preterm (gestational age35 weeks) newborns and 64 full-term newborns. Preterm neonates were also investigated at different time-points up to 30 days after birth. Plasma from preterm and full-term neonates were subjected to the measurement of prothrombin and activated partial thromboplastin time (PT, APTT), pro- and anticoagulant factors as well as to thrombin-generation procedures both with and without thrombomodulin. PT and APTT of preterm newborns were longer than those of full-term neonates [PT: 15.9 s (11.7-51.2)-vs-13.8 (11.0-25.4), p 0.001. APTT: 59.0 (37.8-97.5)-vs- 47.3 (28.1-71.9), p 0.001] and tended to shortening after 30 days from birth. Thrombin-generation defined as endogenous thrombin potential (ETP) was increased in preterm as compared to full-term neonates at birth [1322 nM·min (474-2384)-vs-1006 (697-1612), p 0.001] and did not change appreciably over time up to 30 days from birth. In conclusion, plasma from preterm neonates displays a procoagulant imbalance at birth as shown by increasing ETP, despite the prolongation of PT and APTT. The results define preterm newborns as having hyper- rather than hypo-coagulability and argue against the infusion of FFP when given prophylactically and/or based solely on prolongation of PT or APTT.

Objective: The use of regorafenib in recurrent glioblastoma patients has been recently approved by the Italian Medicines Agency (AIFA) and added to the National Comprehensive Cancer Network (NCCN) 2020 guidelines as a preferred regimen. Given its complex effects at the molecular level, the most appropriate imaging tools to assess early response to treatment is still a matter of debate. Diffusion-weighted imaging and O-(2-18F-fluoroethyl)-L-tyrosine positron emission tomography ([18F]FET PET) are promising methodologies providing additional information to the currently used RANO criteria. The aim of this study was to evaluate the variations in diffusion-weighted imaging/apparent diffusion coefficient (ADC) and [18F]FET PET-derived parameters in patients who underwent PET/MR at both baseline and after starting regorafenib. Methods: We retrospectively reviewed 16 consecutive GBM patients who underwent [18F]FET PET/MR before and after two cycles of regorafenib. Patients were sorted into stable (SD) or progressive disease (PD) categories in accordance with RANO criteria. We were also able to analyze four SD patients who underwent a third PET/MR after another four cycles of regorafenib. [18F]FET uptake greater than 1.6 times the mean background activity was used to define an area to be superimposed on an ADC map at baseline and after treatment. Several metrics were then derived and compared. Log-rank test was applied for overall survival analysis. Results: Percentage difference in FET volumes correlates with the corresponding percentage difference in ADC (R = 0.54). Patients with a twofold increase in FET after regorafenib showed a significantly higher increase in ADC pathological volume than the remaining subjects (p = 0.0023). Kaplan–Meier analysis, performed to compare the performance in overall survival prediction, revealed that the percentage variations of FET- and ADC-derived metrics performed at least as well as RANO criteria (p = 0.02, p = 0.024 and p = 0.04 respectively) and in some cases even better. TBR Max and TBR mean are not able to accurately predict overall survival. Conclusion In recurrent glioblastoma patients treated with regorafenib, [18F]FET and ADC metrics, are able to predict overall survival and being obtained from completely different measures as compared to RANO, could serve as semi-quantitative independent biomarkers of response to treatment. Advances in knowledge Simultaneous evaluation of [18F]FET and ADC metrics using PET/MR allows an early and reliable identification of response to treatment and predict overall survival.

The concern about the offspring’s health is one of the reasons for a reduced family size of women with rheumatic diseases (RD). Increased risk of autoimmune diseases (AD) and neurodevelopmental disorders (ND) has been reported in children born to patients with RD. Within a nationwide survey about reproductive issues of women with RD, we aimed at exploring the long-term outcome of their children. By surveying 398 patients who received their diagnosis of RD during childbearing age (before the age of 45), information about the offspring were obtained from 230 women who declared to have had children. A total of 148 (64.3%) patients were affected by connective tissue diseases (CTD) and 82 (35.7%) by chronic arthritis. Data on 299 children (156 males, 52.1%; mean age at the time of interview 17.1 ± 9.7 years) were collected. Twelve children (4.0%), who were born to patients with CTD in 75% of the cases, were affected by AD (8 cases of celiac disease). Eleven children had a certified diagnosis of ND (3.6%; 6 cases of learning disabilities); 9 of them were born to mothers with CTD (5 after maternal diagnosis). No association was found between ND and prenatal exposure to either maternal autoantibodies or anti-rheumatic drugs. Absolute numbers of offspring affected by AD and ND were low in a multicentre cohort of Italian women with RD. This information can be helpful for the counselling about reproductive issues, as the health outcomes of the offspring might not be an issue which discourage women with RD from having children.

Objective Patients with Cushing’s syndrome (CS) are at high risk of venous thromboembolism related to a hypercoagulability due to procoagulant imbalance. However, whether these alterations are reversible after disease remission is still unclear. The endogenous thrombin potential (ETP) measured with and without the addition of thrombomodulin provides a global representation of coagulation and previous data confirmed hypercoagulable profile in patients with active hypercortisolism. Aim of this study was to assess the short- and long-term modification of ETP in patients with CS after disease remission. Design and methods Nineteen patients with CS for whom surgical remission was achieved, were prospectively evaluated for clinical characteristics, cortisol secretion profile and ETP at different time points: (i) before surgical intervention; (ii) after 6 months and (iii) 5 years from the time of persistent remission. Nineteen healthy subjects matched for age and gender were also evaluated as control group. Results Before surgery, patients showed higher ETP-ratio (with/without thrombomodulin) than controls (0.62 ± 0.09-vs-0.56 ± 0.09, p = 0.034). No significant correlation between ETP-ratio and cortisol secretion was found. 6 months after remission, ETP-ratio was still significantly increased compared to controls (0.64 ± 0.09-vs-0.56 ± 0.09, p = 0.01), but was similar to baseline (0.64 ± 0.09-vs-0.62 ± 0.09, p = 0.87). At 5 years, ETP-ratio showed a significant decrease (0.55 ± 0.14-vs-0.62 ± 0.09, p = 0.02) and was comparable to controls (0.55 ± 0.14-vs-0.56 ± 0.09, p = 0.7). Conclusions Plasma hypercoagulability detected in patients with active hypercortisolism persists at short-term evaluation and seems to be completely reversible after long-term remission of disease. These data, as part of a whole evaluation of thrombotic risk, can contribute to make appropriate therapeutic choice in these patients.

The thermal and convective evolution of terrestrial planets like Mars is governed by a number of initial conditions and parameters, which are poorly constrained. We use Mixture Density Networks (MDN) to invert various sets of synthetic present‐day observables and infer five parameters: reference viscosity, activation energy and activation volume of the diffusion creep rheology, an enrichment factor for radiogenic elements in the crust, and initial mantle temperature. The data set comes from 6,130 two‐dimensional simulations of the thermal evolution of Mars' interior. We quantify the possibility of constraining a parameter using the log‐likelihood value from the MDN. Reference viscosity can be constrained to within 32% of its entire range (1019 − 1022 Pa s), when all the observables are available: core‐mantle‐boundary heat flux, surface heat flux, radial contraction, melt produced, and duration of volcanism. Furthermore, crustal enrichment factor (1–50) can be constrained, at best, to within 15%, and the activation energy (105 − 5 × 105 J mol−1) to within 80%. Initial mantle temperature can be constrained to within 39% of its range (1,600–1,800 K). Using the full present‐day temperature profile or parts of it as an observable tightens the constraints further. The activation volume (4 × 10−6 − 10 × 10−6 m3 mol−1) cannot be constrained. We also tested different levels of uncertainty in the observables and found that constraints on different parameters loosen differently, with initial temperature being the most sensitive. Finally, we present how a joint probability model for all parameters can be obtained from the MDN., Plain Language Summary: The mantle of rocky planets like Mars behaves like a highly viscous fluid over geological time scales. Key parameters and initial conditions for the non‐linear partial differential equations governing mantle flow are poorly known. Machine Learning (ML) can help us avoid running several thousand computationally expensive fluid dynamic simulations each time to determine if an observable can constrain a parameter. Using an ML approach, we invert a set of synthetic observables such as present‐day surface heat flux, duration of volcanism and radial contraction to constrain important parameters controlling the long‐term evolution of the planet's interior, such as the reference mantle viscosity or the partitioning of radiogenic heat sources between mantle and crust. We demonstrate that by training a probabilistic ML algorithm on the data and applying it, we can quantify the constraints on parameters. This provides a high‐dimensional framework for analyzing inverse problems in geodynamics., Key Points: Mixture Density Networks provide a probabilistic framework for inverting observables to infer parameters of Mars' interior evolution Reference viscosity, crustal enrichment in heat‐producing elements and initial mantle temperature can be well constrained Activation energy of diffusion creep can be weakly constrained; constraining activation volume requires new observational signatures, Helmholtz Einstein International Berlin Research School in Data Science (HEIBRiDS), Berlin Institute for the Foundations of Learning and Data (BIFOLD), Deutsche Forschungsgemeinschaft (DFG) Research Unit FOR 2440

Objective To assess the effect of optimal management of pregnancy on a composite outcome of miscarriage and complicated birth among women with rheumatoid arthritis (RA). Methods Data were extracted from health care databases of the Lombardy Region, Italy (2004-2013) as a part of the Record-Linkage on Rheumatic Diseases Study. Analyses included women with RA identified through a copayment exemption code (International Classification of Diseases, Ninth Revision, Clinical Modification code 714.0) and controls from the general population, ages 18-50 years. Seven health care quality indicators (HCQI) were constructed and summarized in 3 pathway indicators: diagnostic, therapeutic, and prenatal follow-up. Complicated birth or miscarriage were used to identify the adverse pregnancy outcome (APO). The relationship between HCQI and APO was analyzed using logistic models, and the results were presented as odds ratios (ORs) and 95% confidence intervals (95% CIs). Results Data from the study cohort included the first pregnancy observed in 443 patients with RA compared with 6,097 women belonging to the general population. In the RA population, patients who followed the 3 pathway indicators had a reduced risk of overall APO, with an OR of 0.60 (95% CI 0.39-0.94), and reduced risk of miscarriage/perinatal death, with an OR of 0.40 (95% CI 0.24-0.69), compared to those who did not follow the pathway indicators. Compared with the general population, patients with RA who met all HCQI during pregnancy displayed a risk of APO with an OR of 0.92 (95% CI 0.61-1.38) and miscarriage/perinatal death with an OR of 0.77 (95% CI 0.47-1.29). Conclusion The adherence to an ideal clinical pathway of pregnancy management in women with RA restored the risk of APO to that expected for the general population.

Antiphospholipid antibodies (aPL) can induce fetal loss in experimental animal models. Human studies did find hypocomplementemia associated with pregnancy complications in patients with antiphospholipid syndrome (APS), but these results are not unanimously confirmed. To investigate if the detection of low C3/C4 could be considered a risk factor for adverse pregnancy outcomes (APO) in APS and aPL carriers’ pregnancies we performed a multicenter study including 503 pregnancies from 11 Italian and 1 Russian centers. Data in women with APS and asymptomatic carriers with persistently positive aPL and preconception complement levels were available for 260 pregnancies. In pregnancies with low preconception C3/C4, a significantly higher prevalence of pregnancy losses was observed (p = 0.008). A subgroup analysis focusing on triple aPL-positive patients found that preconception low C3 and/or C4 levels were associated with an increased rate of pregnancy loss (p = 0.05). Our findings confirm that decreased complement levels before pregnancy are associated with increased risk of APO. This has been seen only in women with triple aPL positivity, indeed single or double positivity does not show this trend. Complement levels are cheap and easy to be measured therefore they could represent a useful aid to identify patients at increased risk of pregnancy loss.

BACKGROUND Despite advances in surgical and first-line treatment, all glioblastoma pts relapse. The aim of this study is to evaluate the benefit of metronomic temozolomide (mTMZ) for recurrent glioblastoma. METHODS 120 pts treated at Veneto Institute of Oncology from September 2013 to March 2021 were retrospectively reviewed. Major inclusion criteria were: first-line therapy with Stupp protocol, relapse after first or subsequent line of therapy, treatment with mTMZ schedule (50mg/m2 continuously), hystologically confirmed diagnosis. RESULTS mFollow-up was 15.6ms, mAge 59ys (range 18-81), ECOG PS 0-2 in 107pts (89%) and 3 in 11 (9%). MGMT was methylated in 66 of 105 (62%) evaluable pts, IDH mutated in 9 of 106 (8%). mNumber of prior lines of treatment was 2 (range 1-7); 41% of pts received mTMZ beyond the third line. mTime between last standard TMZ (sTMZ) cycle and mTMZ administration was 6ms (range 1-50); 40% of pts started mTMZ after 3ms from sTMZ. All pts were evaluable for response: 3 (2%) and 48 (40%) showed PR and SD. mOS from the start of mTMZ was 5.4ms (95% CI 4.3-6.4), mPFS 2.6ms (95% CI 2.3-2.8). On univariate analysis, MGMTmet and MGMTunmet pts had a mOS of 5.6 and 4.4ms (p= 0.03); mOS for pts with ECOG PS > or ≤ 2 was 2.3 and 6.0ms (p< 0.001). On multivariate analysis, MGMTmet status (HR= 2.3, 95% CI, p= 0.004) and ECOG PS (HR= 0.5, 95% CI, p= 0.017) remained significant for PFS; ECOG PS (HR= 0.4, 95% CI, p= 0.001) was the only factor significantly associated with OS. The most common grade 3-4 hematologic toxicities were lymphopenia (10%) and thrombocytopenia (3%). Grade 3-4 nonhematologic toxicities were uncommon. CONCLUSIONS Rechallenge with mTMZ can be a well tolerated treatment option for recurrent glioblastoma, even in heavily pretreated pts. Pts with MGMTmet and good ECOG PS might report the major benefit.

International audience; Calibration, the estimation of model parameters based on fitting the model to experimental data, is among the first steps in many applications of process-based models and has an important impact on simulated values. We propose a novel method of developing guidelines for calibration of process-based models, based on development of recommendations for calibration of the phenology component of crop models. The approach was based on a multi-model study, where all teams were provided with the same data and asked to return simulations for the same conditions. All teams were asked to document in detail their calibration approach, including choices with respect to criteria for best parameters, choice of parameters to estimate and software. Based on an analysis of the advantages and disadvantages of the various choices, we propose calibration recommendations that cover a comprehensive list of decisions and that are based on actual practices.

Motor symptoms of Parkinson's disease (PD)-bradykinesia, akinesia, and tremor at rest-are consequences of the neurodegeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) and dopaminergic striatal deficit. Animal models have been widely used to simulate human pathology in the laboratory. Rodents are the most used animal models for PD due to their ease of handling and maintenance. Moreover, the anatomy and molecular, cellular, and pharmacological mechanisms of PD are similar in rodents and humans. The infusion of the neurotoxin, 6-hydroxydopamine (6-OHDA), into a medial forebrain bundle (MFB) of rats reproduces the severe destruction of dopaminergic neurons and simulates PD symptoms. This protocol demonstrates how to perform the unilateral microinjection of 6-OHDA in the MFB in a rat model of PD and shows the motor deficits induced by 6-OHDA and predicted dopaminergic lesions through the stepping test. The 6-OHDA causes significant impairment in the number of steps performed with the contralateral forelimb.

This paper investigates the suitability of the community cooperatives (CC) model for the implementation of renewable energy communities (REC), as prescribed by art. 22 of EU Directive 2018/2001, and temporarily transposed into the Italian law by art. 42-bis of the Law Decree n. 162/2019. The hypothesis explored analyses the potential synergies between RECs and CC, based on their similarities. In particular, the article takes into consideration: the actors involved in both the RECs and the CCs; the geographical scope in which they develop, and the purposes that these two legal forms intended to achieve. Through a literature review and the analysis of EU, national and regional legislations, the paper aims at (1) clarifying the main features of RECs and the CCs in Italy; (2) exploring the main differences between CCs and the other legal forms of cooperative (e.g., mutual cooperative, cooperative benefit, etc.) and assessing the extent to which CCs are more suitable to implement renewable energy communities. As a result of the literature and regulatory review, several similarities between CCs and RECs can be detected, particularly, in reference to the strategic valorization of the cooperation between citizens and the local public entities. These similarities allow the authors to provisionally conclude that, in Italy, CCs may be adopted as a tool to implement RECs.

L-DOPA-induced dyskinesias (LIDs) refer to motor complications that arise from prolonged L-DOPA administration to patients with Parkinson's disease (PD). The most common pattern observed in the clinic is the peak-dose dyskinesia which consists of clinical manifestations of choreiform, dystonic, and ballistic movements. The 6-hydroxydopamine (6-OHDA) rat model of PD mimics several characteristics of LIDs. After repeated L-DOPA administration, 6-OHDA-lesioned rats exhibit dyskinetic-like movements (e.g., abnormal involuntary movements, AIMs). This protocol demonstrates how to induce and analyze AIMs in 6-OHDA-lesioned rats with 90%-95% dopaminergic depletion in the nigrostriatal pathway. Repeated administration (3 weeks) of L-DOPA (5 mg/kg, combined with 12.5 mg/kg of benserazide) can induce the development of AIMs. The time course analysis reveals a significant increase in AIMs at 30-90 min (peak-dose dyskinesia). Rodent models of LIDs are an important preclinical tool to identify effective antidyskinetic interventions.

Background High tumor levels of urokinase-type plasminogen activator (uPA)-plasminogen activator inhibitor-1 (PAI-1) heteromers independently predict poor survival in early breast cancer. The pathogenetic role of this protein complex, however, remains largely obscure. Material and Methods Neutrophil trafficking was analyzed in orthotopic (multi-channel flow cytometry) and heterotopic (ear; multi-channel in vivo microscopy) mouse models of 4T1 breast cancer, in a mouse peritonitis assay (multi-channel flow cytometry), as well as in the mouse cremaster muscle (multi-channel in vivo microscopy). Cytokine expression in tumors was determined by multiplex ELISA. Phenotypic and functional properties of primary mouse neutrophils, microvascular endothelial cells (cell line bEnd.3), macrophages (cell line RAW 264.7), and breast cancer cells (cell line 4T1) were characterized in different in vitro assays. uPA/PAI-1 expression and neutrophil infiltration in human breast cancer samples were assessed by RNA sequencing, immunhistochemistry, and ELISA. Results and Discussion Here, we demonstrate that uPA-PAI-1 heteromerization multiplies the potential of the single proteins to attract pro-tumorigenic neutrophils. To this end, tumor-released uPA-PAI-1 activates peritumoral macrophages (VLDL receptor- and ERK/MAPK-pathway). This promotes neutrophil trafficking to cancerous lesions (enhanced β2 integrin activation and clustering) and primes these immune cells towards a pro-tumorigenic phenotype (elevated neutrophil elastase expression), thus supporting tumor growth and metastasis. Blockade of uPA-PAI-1 heteromerization by a novel inhibitor effectively interfered with these events and prevented tumor progression. Conclusions Here, we identified an already therapeutically targetable interplay between hemostasis and innate immunity that drives advanced stages of breast cancer as well as characterized the underlying mechanisms of this process. As a personalized immunotherapeutic strategy, blockade of uPA-PAI-1 heteromerization might be particularly beneficial for patients with highly aggressive uPA-PAI-1high tumors. This study was supported by Deutsche Forschungsgemeinschaft (DFG), Sonderforschungsbereich (SFB) 914 Disclosure Information B. Uhl: None. L. Mittmann: None. J. Dominik: None. R. Hennel: None. B. Smiljanov: None. F. Haring: None. J. Schaubacher: None. C. Braun: None. L. Padovan: None. R. Pick: None. M. Canis: None. C. Schulz: None. M. Mack: None. E. Gutjahr: None. P. Sinn: None. J. Heil: None. K. Steiger: None. S.M. Kanse: None. W. Weichert: None. M. Sperandio: None. K. Lauber: None. F. Krombach: None. C. Reichel: None.

Background Although gliomas are strictly confined to the central nervous system, their negative influence over the immune system can extend to peripheral circulation. The immune suppression exerted by myeloid cells is capable of affecting both response to therapy and disease outcome. Here we analyzed the expansion of several myeloid parameters in the blood of low- and high-grade gliomas and assessed their relevance as biomarkers of disease and clinical outcome. Methods Peripheral blood was obtained from 134 low- and high-grade glioma patients before surgery and treatment. Myeloid cell subsets such as total CD14+, CD14+/p-STAT3+, CD14+/PD-L1+, CD15+ cells and 4 myeloid derived suppressor cell (MDSC) subsets, were evaluated by multiparametric flow cytometry. Arginase-1 (ARG1) quantity and activity was determined in the plasma. Principal component analysis was performed to define correlations between myeloid markers. Multivariable logistic regression model was used to obtain a diagnostic score to discriminate glioma patients from healthy controls, and between each glioma grade. A glioblastoma prognostic model was determined by multiple Cox regression using clinical and myeloid parameters. Results In the blood of glioma patients, changes in myeloid parameters associated with immune suppression were identified and allowed us to define a diagnostic score calculating the risk of being a glioma patient, that included CD15+ cells, MDSC1, MDSC3, p-STAT3 and ARG1 activity. Of note, the same parameters, together with age, can also be used to calculate the risk score in differentiating each glioma grade. Finally, a prognostic model for glioblastoma patients stemmed out from a Cox multiple analysis, highlighting the role of MDSC, p-STAT3 and ARG1 activity together with clinical parameters in predicting the patient outcome. Conclusions This work emphasizes the role of systemic immune suppression carried out by myeloid cells in gliomas. The identification of biomarkers associated with immune landscape, diagnosis and outcome of glioblastoma patients lays the ground for their clinical use for stratification and follow up.

Despite multimodal treatment with surgery and radiochemotherapy, the prognosis of glioblastoma remains poor, and practically all glioblastomas relapse. To date, no standard treatment exists for recurrent glioblastoma patients and traditional therapies have showed limited efficacy. Regorafenib is an oral multi-targeted tyrosine kinase inhibitor showing encouraging benefits in recurrent GBM patients enrolled in the REGOMA trial. We performed a large study to investigate clinical outcomes and the safety of regorafenib in a real-life population of recurrent glioblastoma patients. Patients receiving regorafenib outside clinical trials at the Veneto Institute of Oncology were retrospectively reviewed. The major inclusion criteria were: histologically confirmed diagnosis of glioblastoma, prior first line therapy according to “Stupp protocol”, Eastern Cooperative Oncology Group (ECOG) performance status score ≤1. According to the original schedule, patients received regorafenib 160 mg once daily for the first 3 weeks of each 4-week cycle. The primary endpoints of the study were overall survival and safety. A total of 54 consecutive patients were enrolled. The median age was 56, MGMT methylated status was found in 28 out of 53 available patients (52.8%), IDH mutation in 5 (9.3%) and 22 patients were receiving steroids at baseline. The median overall survival was 10.2 months (95% CI, 6.4–13.9), the OS-12 was 43%. Age, MGMT methylation status and steroid use at baseline were not statistically significant on a multivariate analysis for OS. Patients reporting a disease control as best response to regorafenib demonstrated a significant longer survival (24.8 months vs. 6.2 months for patients with progressive disease, p = 0.0001). Grade 3 drug-related adverse events occurred in 10 patients (18%), 1 patient (2%) reported a grade 4 adverse event (rash maculo-papular). No death was considered to be drug-related. This study reported the first large “real-life” experience of regorafenib in recurrent glioblastoma. Overall, our results are close to the ones reported in the previous phase 2 study, despite the fact that we had a longer survival. We showed the encouraging activity and tolerability of this treatment in recurrent glioblastoma patients when used as a second-line treatment.

BACKGROUND Regorafenib (REG), an oral multikinase inhibitor of angiogenic, stromal, and oncogenic receptor tyrosine kinases showed encouraging benefit in recurrent GBM patients enrolled in the randomized, phase 2 REGOMA trial. We investigated the clinical outcome and safety of REG in a real-life population of recurrent glioblastoma patients treated at Veneto Institute of Oncology as off-label use. MATERIAL AND METHODS Patients receiving REG at Veneto Institute of Oncology (Padua, Italy) were entered prospectively on a clinical database. Data were retrospectively analyzed. The primary endpoints of the study were overall survival (OS) and safety. The major inclusion criteria were: histologically confirmed diagnosis of GBM, disease progression as defined by RANO criteria after surgery followed by radiochemotherapy with temozolomide, ECOG PS ≤ 2; PTS with ≥ 2 prior lines of therapy were excluded. According to original schedule, patients received REG 160 mg once daily for the first 3 weeks of each 4-week cycle until disease progression, death, unacceptable toxicity, or consent withdrawal. Kaplan-Meier method was used to estimate the survival curves, RANO criteria for radiological assessment, CTCAE v5.0 for drug related adverse events. RESULTS From February 2018 to September 2020, 54 consecutive patients were treated with REG and enrolled in this study: median age was 56, ECOG PS 0–1 in 91% of patients, MGMTmet in 53%, second surgery at the time of relapse were performed in 30% of enrolled patient, 41% of patients underwent steroids at baseline. At the time of analysis, median follow-up was 11.1 ms, 30 PTS (56%) had died and 50 PTS (93%) had progressed. Median OS was 10.2 ms (95%CI, 6.4–13.9), 12m-OS was 43%; median PFS was 2.3ms (95%CI, 1.3–3.3) and 6m-PFS was 18%. All patients were evaluable for response: disease control rate (DCR) was 46.3%; stable disease was reported in 38.8% and partial response in 7.4%. Age, MGMT status and corticosteroid use at baseline were not statistically significant on multivariate analysis for OS. Grade 3 drug-related adverse events (AEs) occurred in 10 patients (18%) and the most frequent were hand-foot skin reaction, asthenia and increased lipase and transaminases; 1 PT (2%) reported a grade 4 AE (rash maculo-papular). AEs led to REG dose reductions in 37% of patients and, it was permanently discontinued in 5%. No death was considered to be drug-related. CONCLUSION We reported a large, mono-institutional “real world” experience of REG in recurrent glioblastoma patients. Overall, results are close to those reported in REGOMA trial although, we showed a longer OS. Toxicity was moderate and manageable. Encouraging clinical benefits of REG in recurrent GBM population were confirmed.

Simple Summary Diffuse low-grade gliomas (LGG) are relatively uncommon primary brain cancers. In recent years, the molecular, diagnostic, and therapeutic approaches have evolved. IDH (isocitrate dehydrogenase) mutations can affect the great majority of these tumors with distinct genetic and clinical characteristics, carrying a more favorable prognosis compared with wild-type IDH. In patients with LGG, the most common manifestation is seizure and new neuroradiological tools are available to improve the diagnostic and therapeutic pathways. Surgical intervention is performed with the goal of maximum safe resection; postoperative chemoradiotherapy showed benefits in selected patients. New treatments based on molecular profiling, new small molecule and immunotherapy approaches could improve survival and quality of life. In this review, in order to identify the optimal clinical management of patients with LGG, we discuss the relevant biological and clinical characteristics, new therapeutic approaches, and future research directions for these tumors. Abstract Diffuse low-grade gliomas (LGG) represent a heterogeneous group of primary brain tumors arising from supporting glial cells and usually affecting young adults. Advances in the knowledge of molecular profile of these tumors, including mutations in the isocitrate dehydrogenase genes, or 1p/19q codeletion, and in neuroradiological techniques have contributed to the diagnosis, prognostic stratification, and follow-up of these tumors. Optimal post-operative management of LGG is still controversial, though radiation therapy and chemotherapy remain the optimal treatments after surgical resection in selected patients. In this review, we report the most important and recent research on clinical and molecular features, new neuroradiological techniques, the different therapeutic modalities, and new opportunities for personalized targeted therapy and supportive care.

Objective To evaluate the bone repair associated with the use of biphasic ceramics based on hydroxyapatite and β-tricalcium phosphate (HA/TCP) in the procedures of maxillary sinus membrane elevation in human beings. Material and method Ten patients with a residual bone ridge in the posterior maxillary region between 3 mm and 5 mm in height were selected and indicated for procedures of bone grafting associated with maxillary sinus lift procedure. The maxillary sinuses were filled with HA/TCP, and after 8 months, the implants were implanted and a bone biopsy was collected with the aid of a trephine drill, which was then submitted to histological analysis for the evaluation of the composition of the grafted area. Result The histological description analysis of the biopsies revealed the presence of vital and immature bone tissue, juxtaposed to the biomaterial. Histomorphometric analysis showed that the biopsy composition was in average 28.8%, 27.4%, and 43.6% of bone tissue, biomaterial, and soft tissue, respectively. Conclusion The areas grafted with HA/TCP presented the adequate amount of bone formation that allowed the implantation of the implants. The success of the grafting procedure with this biomaterial was associated with its osteoconduction potential that allowed the formation of bone tissue in close contact with HA/TCP.

Background In August 2020, in the context of COVID-19 pandemics, an autochthonous dengue outbreak was identified for the first time in Italy. Methods Following the reporting of the index case of autochthonous dengue, epidemiological investigation, vector control and substances of human origin safety measures were immediately activated, according to the national arbovirus surveillance plan. Dengue cases were followed-up with weekly visits and laboratory tests until recovery and clearance of viral RNA from blood. Results The primary dengue case was identified in a young woman, who developed fever after returning from Indonesia to northern Italy, on 27 July 2020. She spent the mandatory quarantine for COVID-19 at home with relatives, six of whom developed dengue within two weeks. Epidemiological investigation identified further five autochthonous dengue cases among people who lived or stayed near the residence of the primary case. The last case of the outbreak developed fever on 29 September 2020. Dengue cases had a mild febrile illness, except one with persistent asthenia and myalgia. DENV-1 RNA was detected in blood and/or urine in all autochthonous cases, up to 35 days after fever onset. All cases developed IgM and IgG antibodies which cross-reacted with West Nile virus (WNV) and other flaviviruses. Sequencing of the full viral genome from blood samples showed over 99% nucleotide identity with DENV-1 strains isolated in China in 2014–2015; phylogenetic analysis classified the virus within Genotype I. Entomological site inspection identified a high density of Aedes albopictus mosquitoes, which conceivably sustained local DENV-1 transmission. Aedes koreicus mosquitoes were also collected in the site. Conclusions Areas in Europe with high density of Aedes mosquitoes should be considered at risk for dengue transmission. The presence of endemic flaviviruses, such as WNV, might pose problems in the laboratory diagnosis.

The Moisture Separator Re-heater (MSR) is a key component of Nuclear Power Plants (NPP) both in terms of performance and avoiding erosion and erosion/corrosion damage. Wet steam is usually dried in a MSR by inertial separation using separator elements. Depending on the design of a MSR, the technology of separator elements contributes significantly to its size and performance, hence is seen as a subject for in-depth investigation, improvement and innovation. Computational Fluid Dynamics (CFD) has been used to understand the working principles of moisture separating devices, in particular the OpenFOAM platform has been utilized for this scope. Eulerian/Lagrangian models, wall-droplet interaction and water film formation models have been adopted to determine the physical phenomena occurring during the moisture separation process. Additional sub-models have been implemented to make a more robust solver and to solve in a comprehensive way all the possible physical processes: in particular a two-layers turbulence model and a film breakup model have been implemented. An out-of-the-box thinking approach was adopted to devise a new proposed chevron vane. Aerodynamic principles were used to design an innovative concept of separator panel, which can entrap the moisture droplets and water rivulets through a subsequent formation of recirculating steam representing artificial slots (hidden pockets) within the separator channel. The control of the steam separation on precise regions of the separator panel wall, helps the drainage of the water film without the utilization of physical obstacles (pockets or drainage channels). To validate the results achieved from the numerical simulation and to characterize separation performance of a new kind of separator technology, a bespoke test rig has been designed, built and put into operation at typical MSR operating conditions [1]. Throttling calorimeter methodology has been adopted to measure, with very good accuracy, the residual moisture content after the separator. The design developed has shown excellent separation performance. Particularly, this solution will allow improved MSR performance and significantly reduced MSR size. This represents an innovative technology which is a major advance on current technology available within the industry. The novel design features have been patented by General Electric. The first operation of a MSR with this technology is eagerly awaited.

Bipolar disorder (BD) is a psychiatric condition causing acute dysfunctional mood states and emotion regulation. Specific neuropsychological features are often present also among patients in euthymic phase, who do not show clear psychotic symptoms, and for whom the characterization from functional magnetic resonance imaging (fMRI) is very limited. This study aims at identifying the neural and behavioral correlates of the default mode network (DMN) using the fractional amplitude of low frequency fluctuations (fALFF). Eighteen euthymic BD patients (10 females; age = 54.50 ± 11.38 years) and sixteen healthy controls (HC) (8 females; age = 51.16 ± 11.44 years) underwent a 1.5T fMRI scan at rest. The DMN was extracted through independent component analysis. Then, DMN time series was used to compute the fALFF, which was correlated with clinical scales. From the between-group comparison, no significant differences emerged in correspondence to regions belonging to the DMN. For fALFF analysis, we reported significant increase of low-frequency fluctuations for lower frequencies, and decreases for higher frequencies compared to HC. Correlations with clinical scales showed that an increase in higher frequency spectral content was associated with lower levels of mania and higher levels of anxious symptoms, while an increase in lower frequencies was linked to lower depressive symptoms. Starting from our findings on the DMN in euthymic BD patients, we suggest that the fALFF derived from network time series represents a viable approach to investigate the behavioral correlates of resting state networks, and the pathophysiological mechanisms of different psychiatric conditions.

Introduction: Brazil has experienced a rapid demographic transition process, bringing with it new challenges to public health, among them, alcohol dependence among the elderly. Objective: to analyze the literary evidence on prevention and intervention actions for the elderly dependent on alcohol in Primary Health Care (PHC). Method: Integrative Literature Review carried out in 2020 in the LILACS, BDEnf, CUMED, IBECS, MedLine, SciELO, SCOPUS and Web of Science databases, based on the following descriptors: “Elderly”, “Alcohol”, “Alcoholism”, “Disorders Related to Alcohol Use” and “Primary Health Care”. Inclusion criteria were: original articles available online in full, in English, Portuguese and Spanish, and exclusion articles for bibliographic review, theses, dissertations and expert opinion. A total of 1159 articles were identified, after exclusion due to duplication, application of exclusion criteria and qualitative analysis, six articles remained. Results: From the analysis of the data obtained, three categories were structured: Need for screening for alcohol consumption in elderly patients in PHC, Efficiency of Brief Intervention for in elderly patients in PHC and Barriers for implementing screening for alcohol consumption. alcohol and Brief Intervention. Conclusions: the application of strategies to cope with alcohol consumption to elderly patients in Primary Health Care has proven cost benefit, but they are not widely implemented, with more barriers than facilitators for their implementation. In this context, it is necessary to carry out studies aimed at evaluating the effectiveness of screening for alcohol consumption and Brief Intervention in the elderly due to the scarcity of studies nationwide.

(1) Background: vaccination of healthcare workers (HCWs) against seasonal influenza is considered the most effective way to protect HCWs, ensure patient’s safety and to maintain essential health care services during influenza epidemics. With the present study we aimed to evaluate the efficacy of incremental bundles of measures implemented during the last three flu campaigns and to assess the attitudes towards influenza vaccination and a potential vaccine against COVID-19 among HCWs, in a large university hospital in Pisa, Italy. (2) Methods: We described measures implemented during 2018/2019, 2019/2020 and 2020/2021 and assessed their impact on flu vaccine coverage (VC) among employees and residents in Pisa university hospital. We considered sex, profession and ward to investigate differences in uptake. In addition, in 2020 a survey was developed and distributed to all employees to evaluate flu and COVID-19 vaccines attitudes. (3) Results: during the 2018/19 and 2019/20 flu campaigns the overall VC rate among HCWs was, respectively, 10.2% and 11.9%. In 2020/21 the overall VC rate jumped to 39.3% (+ 230.6%). Results from the survey indicated a more positive attitude towards flu vaccine as compared to COVID-19 vaccines among the 10.6% of the staff members who responded to the survey. In addition, 70.97% of HCWs totally agreed that being vaccinated against influenza would be more important than the previous years because of COVID-19 emergency. (4) Conclusions: a significant increase in VC was observed in 2020/21, especially among those sub-groups with consistently lower uptake in previous years. The COVID-19 pandemic positively influenced flu vaccination uptake during the 2020/21 season.

This study evaluated the anatomical factors that influence the virtual planning of zygomatic implants by using cone-beam computerized tomography (CBCT) scans. CBCT scans of 268 edentulous patients were transferred to specialized implant planning software for the following measurements: maxillo-sinus concavity size (small, medium, and large), zygoma width, implant insertion angle, implant length, and implant apical anchorage. Concavity sizes found were as follows: 34.95% small, 52.30% medium, and 7.35% large. The mean insertion angle was 43.2 degrees, and the average implant apical anchorage was 9.1 mm. The most frequent implant length was 40 mm. Significant differences were found when the different types of concavities in relation to the installation angle, the distance of the apical portion of the implant in contact with the zygomatic bone, and the lateral-lateral thickness of the zygomatic bone were compared (P < .001). Medium-sized maxillary sinus concavity presented greater apical anchorage of the implant (9.7 mm) and was the most frequent type (52.30%). The zygomatic bone is a viable site for zygomatic fixtures, and the use of specialized implant planning software is an important tool to achieve predictable outcomes for zygomatic implants and allows good visualization of the relation between implants and anatomical structures.

This paper presents an octacore DCO, implemented in a 28 nm CMOS technology, able to achieve an outstanding phase noise performance: −126 dBc/Hz at 1 MHz offset from the 10.7 GHz carrier with 173 mW power consumption. The design is scalable, as the network coupling the oscillator cores can be reconfigured allowing to switch off some cores to save power without incurring in any additional phase noise penalty other than the one expected from the reduction of the number of the active cores. The DCO achieves a 27% tuning range with 6 MHz frequency resolution.

Agriculture and land use practices must be significantly improved to satisfy the needs of future generations without placing further pressure on global ecosystems. Agroforestry systems (AFS) have been quoted as one of the best options to mitigate environmental impacts and at the same time, improve smallholders’ livelihoods in agricultural areas. However, studies investigating the environmental aspects and yield of agroforestry systems in rural settlements, established by governmental initiatives, are still uncommon in the literature. Therefore, the goal of this paper was to assess the contribution of five biodiverse AFS, located in the Cerrado biome, to global warming mitigation and the provision of ecosystem services to smallholder farmers. Additionally, the importance of agroforestry projects to family farms in Brazil was discussed. Relying on data from forestry inventory and in-depth interviews with farmers, the crop yield (including fruit) was estimated; and the life cycle assessment method was used to determine the Global Warming Potential (GWP), accounting for all emissions to establish and manage the AFS up until the date of analysis. The results show the significant capacity of AFS sequester carbon, represented by the negative values of GWP, ranging from (−263) to (−496) t CO2 equivalents per hectare. Each farmer adopted different tree and crop species at the AFS establishment what influenced yields and GWP. The high number of fruit trees contributed positively to the AFS outputs, allowing farmers to consume and sell a large variety of products. Furthermore, the households also benefit from microclimate and aesthetic benefits provided by the AFSs. Future agroforestry projects in rural settlements can contribute significantly to improve household livelihoods, as well as environmental protection. However, efforts should be taken to provide farmers with sound knowledge, financial support, and access to markets to thrive.

There are currently no FDA-approved medications to reduce cocaine relapse. The majority of preclinical studies aimed at identifying the neurobiology underlying relapse involve the self-administration of cocaine alone, whereas many, if not a majority, of cocaine users engage in polysubstance use. Here we developed a rat model of sequential cocaine and alcohol self-administration to test the hypothesis that this combination produces distinct neuroadaptations relative to those produced by cocaine alone. Male rats underwent intravenous cocaine self-administration (2 h/day) followed by 6 h access to unsweetened alcohol (20% v/v) for 12 days. After extinction training, we assessed surface expression of the glutamate transporter GLT-1 and glutamate efflux in the nucleus accumbens (NA) core during the reinstatement of cocaine-seeking. We also tested the ability of ceftriaxone to attenuate the reinstatement of cocaine-seeking and assessed reinstatement-induced Fos expression in several regions critical for reinstatement. Alcohol consumption did not alter cocaine intake, nor did access to cocaine alter alcohol consumption. However, we noted significant changes in glutamate homeostasis in the NA core of cocaine + alcohol rats relative to rats consuming cocaine alone, such as increased surface GLT-1 expression and a lack of increase in glutamate efflux during reinstatement of cocaine-seeking. A history of cocaine + alcohol also altered patterns of reinstatement-induced Fos expression. These changes likely account for the inability of ceftriaxone to attenuate cocaine relapse in cocaine + alcohol rats, while it does so in rats consuming only cocaine. As such glutamate neuroadaptations are targeted by medications to reduce cocaine relapse, preclinical models should consider polysubstance use.

Made available in DSpace on 2019-10-06T15:54:42Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-01-01 Edentulous patients with an atrophic maxilla associated with lip-palate fissures have unpredictable results after undergoing grafting procedures. In situations where the atrophic maxilla does not adequately allow reconstruction, the use of zygomatic implants has been indicated, and probably these implants can be indicated for the rehabilitation of patients with lip-palate fissures. This case report describes the oral rehabilitation treatment of a patient with a lip-palate cleft treated with zygomatic implants and implant-supported fixed prosthesis with two years of follow-up. A 65-year-old female patient had a lip-palate cleft and previously underwent surgery to close the cleft. The patient had a severely atrophic maxilla and had difficulty adapting to a removable total prosthesis. Due to the small amount of bone remaining and extensive fibrous tissue in the palate region, a rehabilitation with conventional implants associated with zygomatic implants was chosen. Two zygomatic implants and a conventional implant were placed on the right side, and a zygomatic implant and conventional implant were placed on the left side; these implants were later activated by a protocol-Type prosthesis. The zygomatic implants provided an adequate aesthetic and functional outcome of the prosthesis in a patient with cleft palate. Department of Periodontology/Implantology Dental School Federal University of Uberlandia-UFU Department of Diagnosis and Surgery Univ. Est. Paul.-UNESP Instituto Latino Americano de Ensino e Pesquisa Odontológico-ILAPEO Univ. Sagrado Coração Department of Diagnosis and Surgery Univ. Est. Paul.-UNESP

The paper deals with marina operator liability insurance (hereinafter: MOLI) in the context of Croatian and Slovenian insurance law and business practice. The authors analyse, discuss and compare the salient features of MOLI contracts, their standard terms and conditions, scope of coverage and exclusions in Croatian and Slovenian law. The paper describes the relevant business practice in the two Adriatic countries. The analysis is based on the comparative study of the relevant national legislation and private regulation, as well as on the data and documentation gathered by field research, consisting of written questionnaires and live interviews with the representatives of insurance companies and marina operators. Our thesis is that the legal framework in the two observed jurisdictions, as well as the insurers’ private regulation in Croatia and Slovenia are very similar. The aim is to establish the common features of MOLI contracts and of the related practices of marina operators and their insurers in the respective countries and explain the background that has led to the formation of a MOLI product specific for the eastern Adriatic marina industry. Suggestions are given for the improvement of the relevant business practices and administrative requirements regarding the minimum insurance standards imposed on marina operators by the concessioning process.

As a result of stroke, impairments such as hemiparesis, gait deficits, impaired motor function and physical deconditioning can occur. In which, gait is one of the most important functional limitations and this way the evaluation becomes important to determine the functional profile and consequently to develop an appropriate treatment. The objective of this study was to evaluate and correlate functional capacity with the level of motor and functional impairment in chronic hemiparetic. This is a cross-sectional study using the Six-Minute Walking Test (6MWT) to assess functional capacity and the Fugl Meyer Protocol (FM) to assess the level of motor and functional impairment. Twelve hemiparetic subjects were included. Statistical analysis revealed no significant correlation between the 6MWT and FM. We conclude that the present study revealed a non-correlation between functional capacity and motor impairment in chronic hemiparetic.

Energy efficiency in buildings is a key issue in the current energy transition. In order to reduce building energy consumption, users’ behaviour and the perception of indoor environmental comfort must be taken into account; these aspects are inextricably linked to energy demand, consumption and related costs. In this paper, we present the methodological framework, technological solutions and outcomes of the ComfortSense project. ComfortSense aimed at decoupling energy demand from indoor comfort. We focused on Heating, Ventilating and Air Conditioning (HVAC) systems in buildings, on users’ behaviour and on comfort perception by treating buildings as socio-technical systems. Our approach - which was multidisciplinary and included the contribution of sociologists, physicists and computer scientists - was based on Internet of Things technologies, on a Living Lab design and testing process and on a Crowdsensing approach. Physical parameters (objective variables), such as temperature, CO2 concentration and relative humidity, were measured by a Wireless Sensor Network and by wearable devices, while the users’ perception of comfort (subjective variables) were recorded as real-time feedback through a Mobile App in three pilot buildings of the University of Turin, engaging about a thousand buildings’ users (professors, researchers, students and employees). Objective and subjective variables were correlated through an ad-hoc Direct Virtual Sensor. Thanks to the Direct Virtual Sensor forecasting we demonstrated that, adopting an adaptive indoor comfort management, users’ comfort can be remarkably improved while reducing the energy consumption of HVAC systems.

Obesity is a risk factor for cardiovascular diseases. The latter being dependent (at least in part) on plasma procoagulant imbalance (i.e., hypercoagulability). Information on hypercoagulability associated with obesity is scanty and mainly based on global traditional coagulation tests or on the measurement of individual components of coagulation (i.e., pro- and anticoagulants). Plasma from 33 obese subjects was investigated soon before endoscopic balloon placement and after removal (6 months later) by thrombin-generation procedures that are thought to represent much better than any other in vitro test the coagulation process occurring in vivo. We found that obese subjects possess a state of hypercoagulability as demonstrated by the modification of the main parameters of thrombin-generation. In particular, the median value (min–max) of the endogenous thrombin potential (ETP) of obese subjects at baseline was higher than that of controls [1968 (1335–2533) vs. 1710 (1010–2119), p

The aim of this research letter was to report the results of a pilot study designed to compare the real and virtual position of implants placed using computer-guided flapless implant surgery for single restorations in the premaxilla. A total of 8 patients (2 men and 6 women) with a mean age of 40 years old (range: 32–73 years) had a total of 11 implants inserted using a tooth-supported stereolithographic guide. After implant placement, the positions (coronal, central, and apical) and angulation of the implants installed in relation to those planned were determined via the superposition of pre- and postoperative 3-dimensional models using Dental Slice software (Bioparts, Brasília, Brazil). The mean angular deviation was 2.54° ± 0.71°. The deviations found for the coronal, central, and apical positions were 1.3 ± 0.77 mm, 1.49 ± 0.58 mm, and 2.13 ± 1.32 mm, respectively.

Background: Depatuxizumab Mafodotin (Depatux-M, ABT-414) is an antibody-drug conjugate consisting of a specific antibody against activated EGFR and a cytotoxic agent with antimicrotubule activity. The INTELLANCE 2/EORTC 1410 phase 2 trial produced interesting results for the combination regimen of Depatux-M and temozolomide in EGFR-amplified glioblastoma patients at first recurrence. For the first time worldwide, our work investigated the clinical outcome and safety of this combination in a real-life population. Materials and Methods: Patients were enrolled from seven AINO (Italian Association of Neuro-Oncology) Institutions. The major inclusion criteria were: histologically confirmed diagnosis of glioblastoma, EGFR-amplified, one or more prior systemic therapies and ECOG PS ≤ 2. According to the original schedule, patients received Depatux-M 1.25 mg/kg every 2 weeks combined with temozolomide. The primary endpoints of the study were overall survival and safety. Results: A total of 36 patients were enrolled. The median age was 57 years, ECOG PS was 0–1 in 28 patients (88%), MGMT methylated status was found in 22 (64%), 15 patients (42%) received the combined treatment as second-line therapy. The median OS was 8.04 months (95% CI, 5.3–10.7), the 12 month-OS was 37%. On univariate and multivariate analyses, the MGMT methylation status was the only factor resulting significantly associated with survival. Grade 3 ocular toxicity occurred in 11% of patients, no grade 4 ocular toxicity was reported. No death was considered to be drug-related. Conclusions: The study reported the first “real world” experience of Depatux-M plus temozolomide in recurrent glioblastoma patients. Encouraging clinical benefits were demonstrated, even though most patients were treated beyond second-line therapy. Overall, the results are close to those reported in the previous phase 2 trial. Toxicity was moderate and manageable.