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Glioblastoma (GBM) is the most common malignant primary brain cancer that, despite recent advances in the understanding of its pathogenesis, remains incurable. GBM contains a subpopulation of cells with stem cell-like properties called cancer stem cells (CSCs). Several studies have demonstrated that CSCs are resistant to conventional chemotherapy and radiation thus representing important targets for novel anti-cancer therapies. Proton sensing receptors expressed by CSCs could represent important factors involved in the adaptation of tumours to the extracellular environment. Accordingly, the expression of acid-sensing ion channels (ASICs), proton-gated sodium channels mainly expressed in the neurons of peripheral (PNS) and central nervous system (CNS), has been demonstrated in several tumours and linked to an increase in cell migration and proliferation. In this paper we report that the ASIC3 isoform, usually absent in the CNS and present in the PNS, is enriched in human GBM CSCs while poorly expressed in the healthy human brain. We propose here a novel therapeutic strategy based on the pharmacological activation of ASIC3, which induces a significant GBM CSCs damage while being non-toxic for neurons. This approach might offer a promising and appealing new translational pathway for the treatment of glioblastoma. [ABSTRACT FROM AUTHOR]

The purpose of this study is to investigate the diagnostic and prognostic role of cerebrospinal fluid (CSF) biomarkers in the diagnostic work-up of glucose transporter 1 (GLUT1) deficiency. Reported here is a systematic review according to PRISMA guidelines collecting clinical and biochemical data about all published patients who underwent CSF analysis. Clinical phenotypes were compared between groups defined by the levels of CSF glucose (≤ 2.2 mmol/L versus > 2.2 mmol/L), CSF/blood glucose ratio (≤ 0.45 versus > 0.45), and CSF lactate (≤ 1 mmol/L versus > 1 mmol/L). Five hundred sixty-two patients fulfilled the inclusion criteria with a mean age at the diagnosis of 8.6 ± 6.7 years. Patients with CSF glucose ≤ 2.2 mmol/L and CSF/blood glucose ratio ≤ 0.45 presented with an earlier onset of symptoms (16.4 ± 22.0 versus 54.4 ± 45.9 months, p < 0.01; 15.7 ± 23.8 versus 40.9 ± 38.0 months, p < 0.01) and received an earlier molecular genetic confirmation (92.1 ± 72.8 versus 157.1 ± 106.2 months, p < 0.01). CSF glucose ≤ 2.2 mmol/L was consistently associated with response to ketogenic diet (p = 0.018) and antiseizure medications (p = 0.025). CSF/blood glucose ratio ≤ 0.45 was significantly associated with absence seizures (p = 0.048), paroxysmal exercise‐induced dyskinesia (p = 0.046), and intellectual disability (p = 0.016) while CSF lactate > 1 mmol/L was associated with a response to antiseizure medications (p = 0.026) but not to ketogenic diet. Conclusions:This systematic review supported the diagnostic usefulness of lumbar puncture for the early identification of patients with GLUT1 deficiency responsive to treatments especially if they present with co-occurring epilepsy, movement, and neurodevelopmental disorders. What is Known: • Phenotypes of GLUT1 deficiency syndrome range between early epileptic and developmental encephalopathy to paroxysmal movement disorders and developmental impairment What is New: • CSF blood/glucose ratio may predict better than CSF glucose the diagnosis in children presenting with early onset absences • CSF blood/glucose ratio may predict better than CSF glucose the diagnosis in children presenting with paroxysmal exercise induced dyskinesia and intellectual disability. • CSF glucose may predict better than CSF blood/glucose and lactate the response to ketogenic diet and antiseizure medications. [ABSTRACT FROM AUTHOR]

Progressive ataxia and palatal tremor (PAPT) and anti-IgLON5 disease share possible clinical presentations. Furthermore, both have been associated to a tauopathy mainly affecting the brainstem. Nonetheless, anti-IgLON5 antibodies have never been tested in PAPT. We report on two PAPT cases without evidence of anti-IgLON5 antibodies in both CSF and serum. Despite common clinical and pathological characteristics, PAPT and IgLON5 disease are two distinct entities. [ABSTRACT FROM AUTHOR]

CDKL5 deficiency disorder (CDD) is a complex clinical condition resulting from non-functional or absent CDKL5 protein, a serine–threonine kinase pivotal for neural maturation and synaptogenesis. The disorder manifests primarily as developmental epileptic encephalopathy, with associated neurological phenotypes, such as hypotonia, movement disorders, visual impairment, and gastrointestinal issues. Its prevalence is estimated at 1 in 40,000–60,000 live births, and it is more prevalent in females due to the lethality of germline mutations in males during fetal development. This Italian multi-center observational study focused on 34 patients with CDKL5-related epileptic encephalopathy, aiming to enhance the understanding of the clinical and molecular aspects of CDD. The study, conducted across 14 pediatric neurology tertiary care centers in Italy, covered various aspects, including phenotypic presentations, seizure types, EEG patterns, treatments, neuroimaging findings, severity of psychomotor delay, and variant-phenotype correlations. The results highlighted the heterogeneity of seizure patterns, with hypermotor-tonic-spasms sequence seizures (HTSS) noted in 17.6% of patients. The study revealed a lack of clear genotype–phenotype correlation within the cohort. The presence of HTSS or HTSS-like at onset resulted a negative prognostic factor for the presence of daily seizures at long-term follow-up in CDD patients. Despite extensive polypharmacotherapy, including medications such as valproic acid, clobazam, cannabidiol, and others, sustained seizure freedom proved elusive, affirming the inherent drug-resistant nature of CDD. The findings underscored the need for further research to explore response rates to different treatments and the potential role of non-pharmacological interventions in managing this challenging disorder. [ABSTRACT FROM AUTHOR]

Background: Lupus nephritis (LN) is a very severe manifestation of lupus. There is no consensus on which treatment goals should be achieved to protect kidney function in children with LN. Methods: We retrospectively analyzed trends of commonly used laboratory biomarkers of 428 patients (≤ 18 years old) with biopsy-proven LN class ≥ III. We compared data of patients who developed stable kidney remission from 6 to 24 months with those who did not. Results: Twenty-five percent of patients maintained kidney stable remission while 75% did not. More patients with stable kidney remission showed normal hemoglobin and erythrocyte sedimentation rate from 6 to 24 months compared to the group without stable kidney remission. eGFR ≥ 90 ml/min/1.73m2 at onset predicted the development of stable kidney remission (93.8%) compared to 64.7% in those without stable remission (P < 0.00001). At diagnosis, 5.9% and 20.2% of the patients showed no proteinuria in the group with and without stable kidney remission, respectively (P = 0.0001). dsDNA antibodies decreased from onset of treatment mainly during the first 3 months in all groups, but more than 50% of all patients in both groups never normalized after 6 months. Complement C3 and C4 increased mainly in the first 3 months in all patients without any significant difference. Conclusions: Normal eGFR and the absence of proteinuria at onset were predictors of stable kidney remission. Significantly more children showed normal levels of Hb and erythrocyte sedimentation rate (ESR) from 6 to 24 months in the group with stable kidney remission. [ABSTRACT FROM AUTHOR]

Neuroendocrine neoplasms (NENs) are rare tumors with diverse clinical behaviors. Large databases like the Surveillance, Epidemiology, and End Results (SEER) program and national NEN registries have provided significant epidemiological knowledge, but they have limitations given the recent advancements in NEN diagnostics and treatments. For instance, newer imaging techniques and therapies have revolutionized NEN management, rendering older data less representative. Additionally, crucial parameters, like the Ki67 index, are missing from many databases. Acknowledging these gaps, the Italian Association for Neuroendocrine Tumors (Itanet) initiated a national multicenter prospective database in 2019, aiming to gather data on newly-diagnosed gastroenteropancreatic neuroendocrine (GEP) NENs. This observational study, coordinated by Itanet, includes patients from 37 Italian centers. The database, which is rigorously maintained and updated, focuses on diverse parameters including age, diagnostic techniques, tumor stage, treatments, and survival metrics. As of October 2023, data from 1,600 patients have been recorded, with an anticipation of reaching 3600 by the end of 2025. This study aims at understanding the epidemiology, clinical attributes, and treatment strategies for GEP-NENs in Italy, and to introduce the Itanet database project. Once comprehensive follow-up data will be acquired, the goal will be to discern predictors of treatment outcomes and disease prognosis. The Itanet database will offer an unparalleled, updated perspective on GEP-NENs, addressing the limitations of older databases and aiding in optimizing patient care. Study registration: This protocol was registered in clinicaltriasl.gov (NCT04282083). [ABSTRACT FROM AUTHOR]

Background: The nationally determined contribution (NDC) presented by Argentina within the framework of the Paris Agreement is aligned with the decisions made in the context of the United Nations Framework Convention on Climate Change (UNFCCC) on the reduction of emissions derived from deforestation and forest degradation, as well as forest carbon conservation (REDD+). In addition, climate change constitutes one of the greatest threats to forest biodiversity and ecosystem services. However, the soil organic carbon (SOC) stocks of native forests have not been incorporated into the Forest Reference Emission Levels calculations and for conservation planning under climate variability due to a lack of information. The objectives of this study were: (i) to model SOC stocks to 30 cm of native forests at a national scale using climatic, topographic and vegetation as predictor variables, and (ii) to relate SOC stocks with spatial–temporal remotely sensed indices to determine biodiversity conservation concerns due to threats from high inter-annual climate variability. Methods: We used 1040 forest soil samples (0–30 cm) to generate spatially explicit estimates of SOC native forests in Argentina at a spatial resolution of approximately 200 m. We selected 52 potential predictive environmental covariates, which represent key factors for the spatial distribution of SOC. All covariate maps were uploaded to the Google Earth Engine cloud-based computing platform for subsequent modelling. To determine the biodiversity threats from high inter-annual climate variability, we employed the spatial–temporal satellite-derived indices based on Enhanced Vegetation Index (EVI) and land surface temperature (LST) images from Landsat imagery. Results: SOC model (0–30 cm depth) prediction accounted for 69% of the variation of this soil property across the whole native forest coverage in Argentina. Total mean SOC stock reached 2.81 Pg C (2.71–2.84 Pg C with a probability of 90%) for a total area of 460,790 km2, where Chaco forests represented 58.4% of total SOC stored, followed by Andean Patagonian forests (16.7%) and Espinal forests (10.0%). SOC stock model was fitted as a function of regional climate, which greatly influenced forest ecosystems, including precipitation (annual mean precipitation and precipitation of warmest quarter) and temperature (day land surface temperature, seasonality, maximum temperature of warmest month, month of maximum temperature, night land surface temperature, and monthly minimum temperature). Biodiversity was influenced by the SOC levels and the forest regions. Conclusions: In the framework of the Kyoto Protocol and REDD+, information derived in the present work from the estimate of SOC in native forests can be incorporated into the annual National Inventory Report of Argentina to assist forest management proposals. It also gives insight into how native forests can be more resilient to reduce the impact of biodiversity loss. [ABSTRACT FROM AUTHOR]

The development of in vitro seed amplification assays (SAA) detecting misfolded alpha-synuclein (αSyn) in cerebrospinal fluid (CSF) and other tissues has provided a pathology-specific biomarker for Lewy body disease (LBD). However, αSyn SAA diagnostic performance in early pathological stages or low Lewy body (LB) pathology load has only been assessed in small cohorts. Moreover, the relationship between SAA kinetic parameters, the number of αSyn brain seeds and the LB pathology burden assessed by immunohistochemistry has never been systematically investigated. We tested 269 antemortem CSF samples and 138 serially diluted brain homogenates from patients with and without neuropathological evidence of LBD in different stages by the αSyn Real-Time Quaking-Induced Conversion (RT-QuIC) SAA. Moreover, we looked for LB pathology by αSyn immunohistochemistry in a consecutive series of 604 Creutzfeldt–Jakob disease (CJD)-affected brains. αSyn CSF RT-QuIC showed 100% sensitivity in detecting LBD in limbic and neocortical stages. The assay sensitivity was significantly lower in patients in early stages (37.5% in Braak 1 and 2, 73.3% in Braak 3) or with focal pathology (50% in amygdala-predominant). The average number of CSF RT-QuIC positive replicates significantly correlated with LBD stage. Brain homogenate RT-QuIC showed higher sensitivity than immunohistochemistry for the detection of misfolded αSyn. In the latter, the kinetic parameter lag phase (time to reach the positive threshold) strongly correlated with the αSyn seed concentration in serial dilution experiments. Finally, incidental LBD prevalence was 8% in the CJD cohort. The present results indicate that (a) CSF RT-QuIC has high specificity and sufficient sensitivity to detect all patients with LB pathology at Braak stages > 3 and most of those at stage 3; (b) brain deposition of misfolded αSyn precedes the formation of LB and Lewy neurites; (c) αSyn SAA provides “quantitative” information regarding the LB pathology burden, with the lag phase and the number of positive replicates being the most promising variables to be used in the clinical setting. [ABSTRACT FROM AUTHOR]

This article describes a case study of a 70-year-old woman who presented with acute onset blurred vision and subsequently developed symptoms of left hemispheric dysfunction, including aphasia, right gaze palsy, and right hemiplegia. The initial diagnostic work-up ruled out intracranial hemorrhage and large vessel occlusion. However, the patient's symptoms spontaneously improved and then worsened, leading to the discovery of an acute bilateral thalamic infarction. The authors suggest that the transient and side-changing nature of the symptoms may be due to a temporary disruption of thalamo-cortical networks rather than pure anatomical damage. Thalamic infarction should be considered as a differential diagnosis in cases of acute onset hemispheric dysfunction. [Extracted from the article]

Management of COVID-19 patients experiencing persisting respiratory failure despite corticosteroids remains challenging. Data on high-dose intravenous anakinra (HD-ANK) in this context are lacking. We aimed to investigate the impact of HD-ANK on mortality in COVID-19 patients progressing to non-invasive ventilation (NIV) while receiving corticosteroids. We retrospectively analyzed the impact of HD-ANK on 28-day mortality in individuals hospitalized with COVID-19 necessitating NIV after corticosteroid initiation. A total of 256 patients were identified: 146 received standard-of-care only (SOC), and 110 received HD-ANK+SOC. The groups were well-balanced at baseline. In-hospital mortality at 28 days did not differ between the two groups. HD-ANK is not beneficial in patients with severe COVID-19 deteriorating despite corticosteroids. [ABSTRACT FROM AUTHOR]

Background: Children with lupus have a higher chance of nephritis and worse kidney outcome than adult patients. Methods: We retrospectively analyzed clinical presentation, treatment and 24-month kidney outcome in a cohort of 382 patients (≤ 18 years old) with lupus nephritis (LN) class ≥ III diagnosed and treated in the last 10 years in 23 international centers. Results: The mean age at onset was 11 years 9 months and 72.8% were females. Fifty-seven percent and 34% achieved complete and partial remission at 24-month follow-up, respectively. Patients with LN class III achieved complete remission more often than those with classes IV or V (mixed and pure). Only 89 of 351 patients maintained stable complete kidney remission from the 6th to 24th months of follow-up. eGFR ≥ 90 ml/min/1.73 m2 at diagnosis and biopsy class III were predictive of stable kidney remission. The youngest and the oldest age quartiles (2y—9y, 5m) (14y, 2m—18y,2m) showed lower rates of stable remission (17% and 20.7%, respectively) compared to the two other age groups (29.9% and 33.7%), while there was no difference in gender. No difference in achieving stable remission was found between children who received mycophenolate or cyclophosphamide as induction treatment. Conclusion: Our data show that the rate of complete remission in patients with LN is still not high enough. Severe kidney involvement at diagnosis was the most important risk factor for not achieving stable remission while different induction treatments did not impact outcome. Randomized treatment trials involving children and adolescents with LN are needed to improve outcome for these children. [ABSTRACT FROM AUTHOR]

INFN-CHNet is the cultural heritage network of the Italian National Institute of Nuclear Physics (INFN) and is constituted by units from Italy and from outside Europe, one of them at Universidad Nacional de San Martín (UNSAM) in Buenos Aires, Argentina. As a result of the initiative carried out during 2015 by the Accademia dei Lincei for the year of the Italian culture in Latin America, an INFN-CHNet laboratory was set at CEPyA-UNSAM with the collaboration of INFN and the Restoration Workshop Centro Tarea. Noteworthy, this laboratory is conceived as a multidisciplinary research facility with complementary skills, both scientific and humanistic. In this context, the first instrument jointly set up, optimised, and applied to Cultural Heritage was an X-ray fluorescence scanner. In this manuscript, we describe the instrument and its main features together with a set of representative yet novel applications in the field of cultural heritage, namely, the experimental study of hidden rock art through laboratory replicas that imitates the problems found in the archaeological sites (hematite drawings hidden below carbon deposition); the study and chemical characterisation of archaeological decorated pottery; and finally, the application of the XRF scanner to ancient photography, for quick and accurate identification of materials and techniques employed. Beyond these specific results, the primary output of this initiative has been the conception of a future network of scientific laboratories in South America, coordinated by CEPyA at UNSAM. [ABSTRACT FROM AUTHOR]

The Gran Chaco (Argentina, Paraguay, Bolivia and Brazil) has turned into a global deforestation hotspot as a consequence of the agricultural expansion. These land use changes can lead to large socio-ecological conflicts. To reduce adverse effects, common regional planning is needed, which requires diagnostic and prospective information on the territorial dynamics. In this context, we analyzed possible land use change threats over time according to four scenarios of agricultural expansion under different degrees of market opening and state regulation (inertial scenario, high transformation scenario, low transformation scenario, and rigorous law enforcement). Additionally, we identified areas of high susceptibility to deforestation by combining the spatial information from each scenario. We found that the magnitude of the land use changes in the Gran Chaco varies across scenarios, with common spatial patterns of change in the areas adjacent to paddocks previously deforested. This work contributed to a better understanding of the land use change patterns and to envisioning the potential consequences of alternative future land use change scenarios in the Gran Chaco. Particularly, deforestation was analyzed to measure the gap between scenarios and the internationally assumed zero-deforestation objectives. We also identified the areas of greater susceptibility to deforestation where protection efforts should be prioritized when designing future land-use policies and forest governance systems. We demonstrated how scenario generation and simulation models can provide deep insights into the spatiotemporal patterns of deforestation hotspot regions for more sustainable land use planning. [ABSTRACT FROM AUTHOR]

Introduction: Total pancreatectomy (TP) is most commonly performed to avoid postoperative pancreatic fistula (POPF) in patients with high-risk pancreas or to achieve tumor-free resection margins. As part of TP, a simultaneous splenectomy is usually performed primarily for the reason of oncologic radicality. However, the benefit of a simultaneous splenectomy remains unclear. Likewise, the technical feasibility as well as the safety of spleen and vessel preserving total pancreatectomy in pancreatic malignancies has hardly been evaluated. Thus, the aims of the study were to evaluate the feasibility as well as the results of spleen and vessel preserving total pancreatectomy (SVPTP). Material and methods: Patient characteristics, technical feasibility, perioperative data, morbidity, and mortality as well as histopathological results after SVPTP, mainly for pancreatic malignancies, from patient cohorts of two European high-volume-centers for pancreatic surgery were retrospectively analyzed. Mortality was set as the primary outcome and morbidity (complications according to Clavien-Dindo) as the secondary outcome. Results: A SVPTP was performed in 92 patients, predominantly with pancreatic adenocarcinoma (78.3%). In all cases, the splenic vessels could be preserved. In 59 patients, the decision to total pancreatectomy was made intraoperatively. Among these, the most common reason for total pancreatectomy was risk of POPF (78%). The 30-day mortality was 2.2%. Major complications (≥ IIIb according to Clavien-Dindo) occurred in 18.5% within 30 postoperative days. There were no complications directly related to the spleen and vascular preservation procedure. A tumor-negative resection margin was achieved in 71.8%. Conclusion: We could demonstrate the technical feasibility and safety of SVPTP even in patients mainly with pancreatic malignancies. In addition to potential immunologic and oncologic advantages, we believe a major benefit of this procedure is preservation of gastric venous outflow. We consider SVPTP to be indicated in patients at high risk for POPF, in patients with multilocular IPMN, and in cases for extended intrapancreatic cancers. [ABSTRACT FROM AUTHOR]

A few patients presenting with autoimmune encephalitis following COVID-19 vaccinations were reported, including a case diagnosed with anti-LGI1 encephalitis [[2]-[4]]. Even though this epidemiological data should be considered cautiously, the presence of a strict temporal relationship between disease onset and vaccination lets us hypothesize that anti-LGI1 encephalitis may represent a rare complication of COVID-19 vaccination. [Extracted from the article]

Background: There is an increasing demand for biological agents for integrated pest management programs, requiring a constant supply of insects in terms of quantity and quality. In this context, the development of insect-rearing methods and quality control parameters are essential in order to provide best-quality and economic viability products. The medfly Ceratitis capitata (Wiedemann) (Diptera: Tephritidae) is one of the most economically important species of fruit flies in several fruit-producing areas of Brazil, being massively reared in many countries for Sterile Insect Technique (SIT) programs. To achieve mass production scale, suitable larval diets are necessary for medfly rearing at laboratory conditions. Therefore, the objectives of this study were to determine the best artificial larval diet and the respective larval density for C. capitata on diets based on corn flour (CF), sugarcane bagasse (SB), and lyophilized carrot powder (CP), considering biological parameters of quality control and economic viability. Results: Based on the obtained results and although all diets produced quality pupae according to FAO/IAEA/USDA standards, the SB artificial diet promoted better results in the number of larvae, larval weight, number of pupae, and pupal weight, in comparison with CF and CP diets, as well as being the most economically viable. The optimal larval densities on CF, SB, and CP diets were, respectively, 0.5, 2.0, and 1.0 mL of eggs/kg of diet. Conclusions: The diet that was most suitable for insect yield and economic viability was the SB diet, followed by the CF and CP diets, in this order. [ABSTRACT FROM AUTHOR]

Current scholarship suggests attention should be focused on differences in specific job-related conditions to understand help-seeking behavior among police officers. This project examines how officers' feelings of department satisfaction and on-the-job emotions may be associated with trust in members of the community they police. Specifically, officers were asked to report trust levels both in a general sense and in the context of a potential officer-involved shooting (OIS) incident. Print and electronic surveys were completed by 169 police officers across 9 agencies located in 5 New Jersey counties between September 2019 and March 2020. Survey questions covered frequency of on-the-job emotions, satisfaction with department administration, and knowledge of local culture. Bivariate comparisons show officers' levels of both general and post-OIS community trust significantly differ based on reported frequency of emotion, assessment of job satisfaction and department administration, and wider cultural context. Furthermore, multivariate analyses indicate significant factors associated with trust levels include frequency of both positive (fulfillment) and negative (frustration) emotions, satisfaction with training, and attitudes towards the importance of understanding local culture. Findings suggest the complexity of police–community relationships should be more fully explored in relation to supporting aspects of job-related mental wellness in police officers. [ABSTRACT FROM AUTHOR]

Aim: Migration can lead to an increase in stress rates and can impact mental health, especially in certain migrant groups. Nonetheless, mental health needs and the importance of public health are not well captured in most studies using national samples. This study aimed to show the correlation between mental disorders, socio-demographic and cultural aspects among migrants. Subject and methods: One hundred nineteen migrants, applying for assessment to the Mental Health Operational Unit of the National Institute for Health, Migration and Poverty (NIHMP) in Rome, were recruited. Results: Migrants frequently reported mood disorders (mainly women). Men reported PTSD, somatization and adjustment disorders. Conclusions: Over time, diverse factors may produce a decline in an initially healthy migrant status. The research unveils a new focus on the psychopathology of migrants accessing the NIHMP, with important implications for migrants' mental health treatment and prevention. [ABSTRACT FROM AUTHOR]

Charcot-Marie-Tooth disease type 1A (CMT1A), caused by duplication of the peripheral myelin protein 22 (PMP22) gene, and CMT1B, caused by mutations in myelin protein zero (MPZ) gene, are the two most common forms of demyelinating CMT (CMT1), and no treatments are available for either. Prior studies of the MpzSer63del mouse model of CMT1B have demonstrated that protein misfolding, endoplasmic reticulum (ER) retention and activation of the unfolded protein response (UPR) contributed to the neuropathy. Heterozygous patients with an arginine to cysteine mutation in MPZ (MPZR98C) develop a severe infantile form of CMT1B which is modelled by MpzR98C/ + mice that also show ER stress and an activated UPR. C3-PMP22 mice are considered to effectively model CMT1A. Altered proteostasis, ER stress and activation of the UPR have been demonstrated in mice carrying Pmp22 mutations. To determine whether enabling the ER stress/UPR and readjusting protein homeostasis would effectively treat these models of CMT1B and CMT1A, we administered Sephin1/IFB-088/icerguestat, a UPR modulator which showed efficacy in the MpzS63del model of CMT1B, to heterozygous MpzR98C and C3-PMP22 mice. Mice were analysed by behavioural, neurophysiological, morphological and biochemical measures. Both MpzR98C/ + and C3-PMP22 mice improved in motor function and neurophysiology. Myelination, as demonstrated by g-ratios and myelin thickness, improved in CMT1B and CMT1A mice and markers of UPR activation returned towards wild-type values. Taken together, our results demonstrate the capability of IFB-088 to treat a second mouse model of CMT1B and a mouse model of CMT1A, the most common form of CMT. Given the recent benefits of IFB-088 treatment in amyotrophic lateral sclerosis and multiple sclerosis animal models, these data demonstrate its potential in managing UPR and ER stress for multiple mutations in CMT1 as well as in other neurodegenerative diseases. (Left panel) the accumulation of overexpressed PMP22 or misfolded mutant P0 in the Schwann cell endoplasmic reticulum (ER) leads to overwhelming of the degradative capacity, activation of ER-stress mechanisms, and myelination impairment. (Right panel) by prolonging eIF2α phosphorylation, IFB-088 reduces the amount of newly synthesized proteins entering the ER, allowing the protein quality control systems to better cope with the unfolded/misfolded protein and allowing myelination to progress. [ABSTRACT FROM AUTHOR]

Objectives: This work aimed to report the demographic and clinical characteristics of two new cases with non-paraneoplastic anti-Hu-associated gut motility impairment, and perform a thorough revision covering anti-Hu-associated paraneoplastic (PGID) and non-paraneoplastic (nPGID) gastrointestinal dysmotility. Background: Several case series have clearly established a relationship between certain type of cancers, the development of circulating anti-Hu antibodies, and the concomitant usually severe gastrointestinal dysmotility; in contrast, a few studies focused on anti-Hu-associated nPGID. Methods: We searched for studies regarding anti-Hu-associated gastrointestinal manifestations and extracted data concerning clinical characteristics of patients, including specific demographic, oncological, neurological, gastrointestinal, histological, and treatment response features. Results: Forty-nine articles with a total of 59 cases of anti-Hu-associated gastrointestinal dysmotility were analyzed. The patients' age at symptom onset significantly differed between PGID and nPGID (median 61 vs 31 years, p < 0.001). Most cancers (95%) in PGID were detected within 24 months from the beginning of gastrointestinal symptoms. The impairment of gastrointestinal motility was generalized (i.e., involving the whole gut) in 59.3% of patients, with no significant differences between PGID vs nPGID group. nPGID patients showed a better response to immunomodulatory/immunosuppressive treatment and a longer life expectancy. Conclusions: Anti-Hu-associated gastrointestinal dysmotility covers a wide clinical spectrum. Patients with otherwise unexplained gastrointestinal dysmotility, especially when associated with other neurological symptoms, should be tested for anti-Hu antibodies regardless age of onset and disease duration. Compared to PGID, nPGID occurs in younger patients with a long duration of disease. [ABSTRACT FROM AUTHOR]

This review provides an updated analysis of the main aspects involving the diagnosis and the management of children with acute ischemic stroke. Acute ischemic stroke is an emergency of rare occurrence in children (rate of incidence of 1/3500 live birth in newborns and 1–2/100,000 per year during childhood with peaks of incidence during the perinatal period, under the age of 5 and in adolescence). The management of ischemic stroke in the paediatric age is often challenging because of pleomorphic age-dependent risk factors and aetiologies, high frequency of subtle or atypical clinical presentation, and lacking evidence-based data about acute recanalization therapies. Each pediatric tertiary centre should activate adequate institutional protocols for the optimization of diagnostic work-up and treatments. Conclusion: The implementation of institutional standard operating procedures, summarizing the steps for the selection of candidate for neuroimaging among the ones presenting with acute neurological symptoms, may contribute to shorten the times for thrombolysis and/or endovascular treatments and to improve the long-term outcome. What is Known: •Acute ischemic stroke has a higher incidence in newborns than in older children (1/3500 live birth versus 1–2/100,000 per year). •Randomized clinical trial assessing safety and efficacy of thrombolysis and/or endovascular treatment were never performed in children What is New: •Recent studies evidenced a low risk (2.1% of the cases) of intracranial haemorrhages in children treated with thrombolysis. •A faster access to neuroimaging and hyper-acute therapies was associated with the implementation of institutional protocols for the emergency management of pediatric stroke. [ABSTRACT FROM AUTHOR]

Background: Histological findings of kidney involvement have been rarely reported in pediatric patients with SARS-CoV-2 infection. Here, we describe clinical, laboratory, and histological findings of two pediatric cases with almost exclusive kidney involvement by SARS-CoV-2. Results: A 10-year-old girl with IgA vasculitis nephritis underwent kidney biopsy, showing diffuse and segmental mesangial-proliferative glomerulonephritis, and steroid therapy was initiated. After the worsening of the clinical picture, including an atypical skin rash, she was diagnosed with SARS-CoV-2. The re-evaluation of initial biopsy showed cytoplasmatic blebs and virus-like particles in tubular cells at electron microscopy. Despite SARS-CoV-2 clearance and the intensification of immunosuppression, no improvement was observed. A second kidney biopsy showed a crescentic glomerulonephritis with sclerosis, while virus-like particles were no longer evident. The second patient was a 12-year-old girl with a 3-week history of weakness and weight loss. Rhinitis was reported the month before. No medications were being taken. Blood and urine analysis revealed elevated serum creatinine, hypouricemia, low molecular weight proteinuria, and glycosuria. A high SARS-CoV-2-IgG titre was detected. Kidney biopsy showed acute tubular-interstitial nephritis. Steroid therapy was started with a complete resolution of kidney involvement. Conclusion: We can speculate that in both cases SARS-CoV-2 played a major role as inflammatory trigger of the kidney damage. Therefore, we suggest investigating the potential kidney damage by SARS-CoV-2 in children. Moreover, SARS-CoV-2 can be included among infectious agents responsible for pediatric acute tubular interstitial nephritis. [ABSTRACT FROM AUTHOR]

Inherited disorders of neurotransmitter metabolism are rare neurodevelopmental diseases presenting with movement disorders and global developmental delay. This study presents the results of the first standardized deep phenotyping approach and describes the clinical and biochemical presentation at disease onset as well as diagnostic approaches of 275 patients from the registry of the International Working Group on Neurotransmitter related Disorders. The results reveal an increased rate of prematurity, a high risk for being small for gestational age and for congenital microcephaly in some disorders. Age at diagnosis and the diagnostic delay are influenced by the diagnostic methods applied and by disease-specific symptoms. The timepoint of investigation was also a significant factor: delay to diagnosis has decreased in recent years, possibly due to novel diagnostic approaches or raised awareness. Although each disorder has a specific biochemical pattern, we observed confounding exceptions to the rule. The data provide comprehensive insights into the phenotypic spectrum of neurotransmitter disorders. [ABSTRACT FROM AUTHOR]

The lack of robust mental health programs throughout the USA has resulted in police frequently being responsible for responding to calls about people with mental illness who are in crisis. Working with people with mental illness as offenders or as individuals needing emergency assistance is a regular part of the job for many in law enforcement, yet specialized training is not a regular part of most academy or in-service training curricula. Crisis Intervention Team (CIT) programs consist of a 40-h training for police and mental health personnel. The programs teach officers about mental illness, its causes and symptoms, and focuses on de-escalation tactics and use of available community resources as alternatives to criminal justice outcomes for calls. The current study explores officers' feelings of preparedness to work with community members with mental illness and their levels of endorsement of mental health stigma. Researchers surveyed police from nine different local departments in southern New Jersey. Half of the surveyed officers completed CIT training, allowing for comparisons between officers who were trained and those who were not. Results indicate that the CIT-trained officers were more likely to endorse different types of mental health stigma than non-trained officers, but those who were CIT-trained reported feeling better prepared for calls involving people with mental illness. [ABSTRACT FROM AUTHOR]

Local adaptation of animals to the environment can abruptly become a burden when faced with rapid climatic changes such as those foreseen for the Italian peninsula over the next 70 years. Our study investigates the genetic structure of the Italian goat populations and links it with the environment and how genetics might evolve over the next 50 years. We used one of the largest national datasets including > 1000 goats from 33 populations across the Italian peninsula collected by the Italian Goat Consortium and genotyped with over 50 k markers. Our results showed that Italian goats can be discriminated in three groups reflective of the Italian geography and its geo-political situation preceding the country unification around two centuries ago. We leveraged the remarkable genetic and geographical diversity of the Italian goat populations and performed landscape genomics analysis to disentangle the relationship between genotype and environment, finding 64 SNPs intercepting genomic regions linked to growth, circadian rhythm, fertility, and inflammatory response. Lastly, we calculated the hypothetical future genotypic frequencies of the most relevant SNPs identified through landscape genomics to evaluate their long-term effect on the genetic structure of the Italian goat populations. Our results provide an insight into the past and the future of the Italian local goat populations, helping the institutions in defining new conservation strategy plans that could preserve their diversity and their link to local realities challenged by climate change. [ABSTRACT FROM AUTHOR]

We report the electrical detection of captured gases through measurement of the quantum tunneling characteristics of gas-mediated molecular junctions formed across nanogaps. The gas-sensing nanogap device consists of a pair of vertically stacked gold electrodes separated by an insulating 6 nm spacer (~1.5 nm of sputtered α-Si and ~4.5 nm ALD SiO2), which is notched ~10 nm into the stack between the gold electrodes. The exposed gold surface is functionalized with a self-assembled monolayer (SAM) of conjugated thiol linker molecules. When the device is exposed to a target gas (1,5-diaminopentane), the SAM layer electrostatically captures the target gas molecules, forming a molecular bridge across the nanogap. The gas capture lowers the barrier potential for electron tunneling across the notched edge region, from ~5 eV to ~0.9 eV and establishes additional conducting paths for charge transport between the gold electrodes, leading to a substantial decrease in junction resistance. We demonstrated an output resistance change of >108 times upon exposure to 80 ppm diamine target gas as well as ultralow standby power consumption of <15 pW, confirming electron tunneling through molecular bridges for ultralow-power gas sensing. [ABSTRACT FROM AUTHOR]

Telepsychiatry, the use of televideo in psychiatric assessment and treatment, is utilized throughout Canada. Major depressive disorder (MDD) is common, with significant burdens of suffering and cost. This systematic review explores the literature on the use of televideo to diagnose and treat MDD, particularly acceptability and patient satisfaction, efficacy, and cost-effectiveness. A literature search was conducted for years 1946 to 2019. Study eligibility criteria included: MDD as the condition of interest, use of televideo technology, randomized controlled trials (RCTs), Adult (18 years or older) population, any clinical setting, and any healthcare professional providing care. The study must have included at least one of the following measures, satisfaction, efficacy, and cost-effectiveness. Fourteen studies were included. Satisfaction is equivalent to or significantly higher than face-to-face intervention. Both televideo and control groups found relief from depressive symptoms, with differences either statistically insignificant or in favour of televideo. Despite increased cost upfront for televideo due to the technology required, televideo would eventually be more cost-effective due to reducing travel expenses. Limitations include that there is little RCT data, and what exists often uses a collaborative treatment model. Many studies consisted solely of U.S. Veterans, and have limited generalizability. Further research needed to directly compare psychiatrist assessment over televideo versus in-person, and determine if particular patient subgroups benefit more from televideo or in-person intervention. Systematic review registration number: CRD42016048224. [ABSTRACT FROM AUTHOR]

Inborn errors of neurotransmitter metabolism are ultrarare disorders affecting neurotransmitter biosynthesis, breakdown or transport or their essential cofactors. Neurotransmitter dysfunctions could also result from the impairment of neuronal receptors, intracellular signaling, vesicle release or other synaptic abnormalities. Epilepsy is the main clinical hallmark in some of these diseases (e.g. disorders of GABA metabolism, glycine encephalopathy) while it is infrequent in others (e.g. all the disorders of monoamine metabolism in exception for dihydropteridine reductase deficiency). This review analyzes the epileptogenic mechanisms, the epilepsy phenotypes and the principle for the clinical management of epilepsy in primary and secondary inherited disorders of neurotransmitter metabolism (disorders of GABA, serine and glycine metabolism, disorders of neurotransmitter receptors and secondary neurotransmitter diseases). [ABSTRACT FROM AUTHOR]

Sickness syndrome is an adaptive response that can be distinguished by specific signs and symptoms, such as fever and generalized hyperalgesia. Endothelin-1 (ET-1) is produced by inflammatory stimuli, including lipopolysaccharide, and involved in the pathogenesis of inflammation and pain by acting through ETA and ETB receptors. ET-1 also induces fever by acting on the central nervous system. The present study investigated the role of ET-1 in sickness syndrome responses, including hyperalgesia, anhedonia, and hypolocomotion. Intracerebroventricular ET-1 administration induced mechanical and thermal hyperalgesia in rats, which was ameliorated by the ETA receptor antagonist BQ123 and exacerbated by the ETB receptor antagonist BQ788. A cyclooxygenase blocker did not alter hyperalgesia that was induced by ET-1. Lipopolysaccharide administration induced hyperalgesia, and both BQ123 and BQ788 abolished this mechanical hyperalgesia, but the thermal response was only partially blocked. The blockade of ETA receptors in the hypothalamus also abolished lipopolysaccharide-induced mechanical hyperalgesia, and the ETB receptor antagonist did not influence this response. Lipopolysaccharide also induced anhedonia, reflected by lower sucrose preference, and reduced locomotor activity. Both antagonists restored locomotor activity, but only BQ788 reversed the reduction of sucrose preference. These results indicate that ET-1 and both ETA and ETB receptors are involved in various responses that are related to sickness syndrome, including hyperalgesia, anhedonia, and hypolocomotion, that is induced by LPS. Hypothalamic ETA but not ETB receptors are involved in mechanical hyperalgesia that is observed during lipopolysaccharide-induced sickness syndrome. [ABSTRACT FROM AUTHOR]

Amyotrophic Lateral Sclerosis (ALS) is a fatal disease characterized by the degeneration of upper and lower motor neurons (MNs). We find a significant reduction of the retromer complex subunit VPS35 in iPSCs-derived MNs from ALS patients, in MNs from ALS post mortem explants and in MNs from SOD1G93A mice. Being the retromer involved in trafficking of hydrolases, a pathological hallmark in ALS, we design, synthesize and characterize an array of retromer stabilizers based on bis-guanylhydrazones connected by a 1,3-phenyl ring linker. We select compound 2a as a potent and bioavailable interactor of VPS35-VPS29. Indeed, while increasing retromer stability in ALS mice, compound 2a attenuates locomotion impairment and increases MNs survival. Moreover, compound 2a increases VPS35 in iPSCs-derived MNs and shows brain bioavailability. Our results clearly suggest the retromer as a valuable druggable target in ALS. ALS is a neurodegenerative disease characterized by loss of motor neurons. Here, the authors showed that reduced levels of the VSP35 subunit in the retromer complex is a conserved ALS feature and identified a new lead compound increasing retromer stability ameliorating the disease phenotype. [ABSTRACT FROM AUTHOR]

Genetic factors contribute to the risk of thrombotic diseases. Recent genome wide association studies have identified genetic loci including SLC44A2 which may regulate thrombosis. Here we show that Slc44a2 controls platelet activation and thrombosis by regulating mitochondrial energetics. We find that Slc44a2 null mice (Slc44a2(KO)) have increased bleeding times and delayed thrombosis compared to wild-type (Slc44a2(WT)) controls. Platelets from Slc44a2(KO) mice have impaired activation in response to thrombin. We discover that Slc44a2 mediates choline transport into mitochondria, where choline metabolism leads to an increase in mitochondrial oxygen consumption and ATP production. Platelets lacking Slc44a2 contain less ATP at rest, release less ATP when activated, and have an activation defect that can be rescued by exogenous ADP. Taken together, our data suggest that mitochondria require choline for maximum function, demonstrate the importance of mitochondrial metabolism to platelet activation, and reveal a mechanism by which Slc44a2 influences thrombosis. Genetic association studies have identified loci including the choline transporter SLC44A2 as a potential regulator of thrombosis. Here the authors report that loss of SLC44A2 impairs platelet activation and thrombosis in mice via a reduction of mitochondrial ATP production. [ABSTRACT FROM AUTHOR]

Although length of stay (LoS) after childbirth has been diminishing in several high-income countries in recent decades, the evidence on the impact of early discharge (ED) on healthy mothers and term newborns after vaginal deliveries (VD) is still inconclusive and little is known on the characteristics of those discharged early. We conducted a population-based study in Friuli Venezia Giulia (FVG) during 2005–2015, to investigate the mean LoS and the percentage of LoS longer than our proposed ED benchmarks following VD: 2 days after spontaneous vaginal deliveries (SVD) and 3 days post instrumental vaginal deliveries (IVD). We employed a multivariable logistic as well as a linear regression model, adjusting for a considerable number of factors pertaining to health-care setting and timeframe, maternal health factors, newborn clinical factors, obstetric history factors, socio-demographic background and present obstetric conditions. Results were expressed as odds ratios (OR) and regression coefficients (RC) with 95% confidence interval (95%CI). The adjusted mean LoS was calculated by level of pregnancy risk (high vs. low). Due to a very high number of multiple tests performed we employed the procedure proposed by Benjamini-Hochberg (BH) as a further selection criterion to calculate the BH p-value for the respective estimates. During 2005–2015, the average LoS in FVG was 2.9 and 3.3 days after SVD and IVD respectively, and the pooled regional proportion of LoS > ED was 64.4% for SVD and 32.0% for IVD. The variation of LoS across calendar years was marginal for both vaginal delivery modes (VDM). The adjusted mean LoS was higher in IVD than SVD, and although a decline of LoS > ED and mean LoS over time was observed for both VDM, there was little variation of the adjusted mean LoS by nationality of the woman and by level of pregnancy risk (high vs. low). By contrast, the adjusted figures for hospitals with shortest (centres A and G) and longest (centre B) mean LoS were 2.3 and 3.4 days respectively, among "low risk" pregnancies. The corresponding figures for "high risk" pregnancies were 2.5 days for centre A/G and 3.6 days for centre B. Therefore, the shift from "low" to "high" risk pregnancies in all three latter centres (A, B and G) increased the mean adjusted LoS just by 0.2 days. By contrast, the discrepancy between maternity centres with highest and lowest adjusted mean LoS post SVD (hospital B vs. A/G) was 1.1 days both among "low risk" (1.1 = 3.4–2.3 days) and "high risk" (1.1 = 3.6–2.5) pregnanices. Similar patterns were obseved also for IVD. Our adjusted regression models confirmed that maternity centres were the main explanatory factor for LoS after childbirth in both VDM. Therefore, health and clinical factors were less influential than practice patterns in determining LoS after VD. Hospitalization and discharge policies following childbirth in FVG should follow standardized guidelines, to be enforced at hospital level. Any prolonged LoS post VD (LoS > ED) should be reviewed and audited if need be. Primary care services within the catchment areas of the maternity centres of FVG should be improved to implement the follow up of puerperae undergoing ED after VD. [ABSTRACT FROM AUTHOR]

An Italian 13-year-old boy immunosuppressed due to kidney transplant presented in November 2018 with acute flaccid paralysis with anterior horn cell involvement resembling the clinical, radiological, and laboratory features of poliomyelitis. Enterovirus was molecularly identified in cerebral spinal fluid and stool samples and the sequence analysis of the VP1 gene of enterovirus genome revealed the presence of Echovirus 30 both in CSF and in stool samples. Echovirus 30 is an emerging neurotropic virus able to cause outbreaks of aseptic meningitis and meningoencephalitis all over the world, but acute flaccid paralysis is not a classical manifestation. A 6-month follow-up revealed a poor outcome with severe motor deficits and only slight improvement in disability. Clinicians must be aware of the possible role of Echovirus 30 in acute flaccid paralysis and active surveillance should consider the possible influence of immunosuppression on the symptoms caused by the widening spectrum of enterovirus infections. [ABSTRACT FROM AUTHOR]

Although there is no evidence that elevated rates of cesarean sections (CS) translate into reduced maternal/child perinatal morbidity or mortality, CS have been increasingly overused almost everywhere, both in high and low-income countries. The primary cesarean section (PCS) has become a major driver of the overall CS (OCS) rate, since it carries intrinsic risk of repeat CS (RCS) in future pregnancies. In our study we examined patterns of PCS, pl compared with planned TOLAC anned PCS (PPCS), vaginal birth after 1 previous CS (VBAC-1) and associated factors in Friuli Venezia Giulia (FVG), a region of North-Eastern Italy, collecting data from its 11 maternity centres (coded from A to K) during 2005–2015. By fitting three multiple logistic regression models (one for each delivery mode), we calculated the adjusted rates of PCS and PPCS among women without history of CS, whilst the calculation of the VBAC rate was restricted to women with just one previous CS (VBAC-1). Results, expressed as odds ratio (OR) with 95% confidence interval (95%CI), were controlled for the effect of hospital, calendar year as well as several factors related to the clinical and obstetric conditions of the mothers and the newborn, the obstetric history and socio-demographic background. In FVG during 2005–2015 there were 24,467 OCS (rate of 24.2%), 19,565 PCS (19.6%), 7,736 PPCS (7.7%) and 2,303 VBAC-1 (28.4%). We found high variability of delivery mode (DM) at hospital level, especially for PCS and PPCS. Breech presentation was the strongest determinant for PCS as well as PPCS. Leaving aside placenta previa/abuptio placenta/ante-partum hemorrhage, further significant factors, more importantly associated with PCS than PPCS were non-reassuring fetal status and obstructed labour, followed by (in order of statistical significance): multiple birth; eclampsia/pre-eclampsia; maternal age 40–44 years; placental weight 600-99 g; oligohydramios; pre-delivery LoS 3–5 days; maternal age 35–39 years; placenta weight 1,000–1,500 g; birthweight < 2,000 g; maternal age ≥ 45 years; pre-delivery LoS ≥ 6 days; mother's age 30–34 years; low birthweight (2,000–2,500 g); polyhydramnions; cord prolaspe; ≥6 US scas performed during pregnancy and pre-term gestations (33–36 weeks). Significant factors for PPCS were (in order of statistical significance): breech presentation; placenta previa/abruptio placenta/ante-partum haemorrhage; multiple birth; pre-delivery LoS ≥ 3 days; placental weight ≥ 600 g; maternal age 40–44 years; ≥6 US scans performed in pregnancy; maternal age ≥ 45 and 35–39 years; oligohydramnios; eclampsia/pre-eclampsia; mother's age 30–34 years; birthweight <2,000 g; polyhydramnios and pre-term gestation (33–36 weeks). VBAC-1 were more likely with gestation ≥ 41 weeks, placental weight <500 g and especially labour analgesia. During 2005–2015 the overall rate of PCS in FVG (19.6%) was substantially lower than the corresponding figure reported in 2010 for the entire Italy (29%) and still slightly under the most recent national PCS rate for 2017 (22.2%). The VBAC-1 rate on women with history of one previous CS in FVG was 28.4% (25.3% considering VBAC on all women with at least 1 previous CS), roughly three times the Italian national rate of 9% reported for 2017. The discrepancy between the OCS rate at country level (38.1%) and FVG's (24.2%) is therefore mainly attributable to RCS. Although there was a marginal decrease of PCS and PPCS crudes rates over time in the whole region, accompained by a progressive enhancement of the crude VBAC rate, we found remarkable variability of DM across hospitals. To further contain the number of unnecessary PCS and promote VBAC where appropriate, standardized obstetric protocols should be introduced and enforced at hospital level. Decision-making on PCS should be carefully scrutinized, introducing a diagnostic second opinion for all PCS, particularly for term singleton pregancies with cephalic presentation and in case of obstructed labour as well as non-reassuring fetal status, grey areas potentially affected by subjective clinical assessment. This process of change could be facilitated with education of staff/patients by opinion leaders and prenatal counseling for women and partners, although clinical audits, financial penalties and rewards to efficient maternity centres could also be considered. [ABSTRACT FROM AUTHOR]

Mutations in the gelsolin protein are responsible for a rare conformational disease known as AGel amyloidosis. Four of these mutations are hosted by the second domain of the protein (G2): D187N/Y, G167R and N184K. The impact of the latter has been so far evaluated only by studies on the isolated G2. Here we report the characterization of full-length gelsolin carrying the N184K mutation and compare the findings with those obtained on the wild type and the other variants. The crystallographic structure of the N184K variant in the Ca2+-free conformation shows remarkable similarities with the wild type protein. Only minimal local rearrangements can be observed and the mutant is as efficient as the wild type in severing filamentous actin. However, the thermal stability of the pathological variant is compromised in the Ca2+-free conditions. These data suggest that the N to K substitution causes a local disruption of the H-bond network in the core of the G2 domain. Such a subtle rearrangement of the connections does not lead to significant conformational changes but severely affects the stability of the protein. [ABSTRACT FROM AUTHOR]

Cesarean sections (CS) have become increasingly common in both developed and developing countries, raising legitimate concerns regarding their appropriateness. Since improvement of obstetric care at the hospital level needs quantitative evidence, using routinely collected health data we contrasted the performance of the 11 maternity centres (coded with an alphabetic letter A to L) of an Italian region, Friuli Venezia Giulia (FVG), during 2005–15, after removing the effect of several factors associated with different delivery modes (DM): spontaneous vaginal delivery (SVD), instrumental vaginal delivery (IVD), overall CS (OCS) and urgent/emergency CS (UCS). A multivariable logistic regression model was fitted for each individual DM, using a dichotomous outcome (1 = each DM; 0 = rest of hospital births) and comparing the stratum specific estimates of every term with their respective reference categories. Results were expressed as odds ratios (OR) with 95% confidence intervals (95%CI). The Benjamini-Hochberg (BH) false discovery rates (FDR) approach was applied to control alpha error due to the large number of statistical tests performed. In the entire FVG region during 2005–2015, SVD were 75,497 (69.1% out of all births), IVD were 7,281 (6.7%), OCS were 26,467 (24.2%) and UCS were 14,106 (12.9% of all births and 53.3% out of all CS). SVD were more likely (in descending order of statistical significance) with: higher number of previous livebirths; clerk/employed occupational status of the mother; gestational age <29 weeks; placentas weighing <500 g; stillbirth; premature rupture of membranes (PROM). IVD were predominantly more likely (in descending order of statistical significance) with: obstructed labour, non-reassuring fetal status, history of CS, labour analgesia, maternal age ≥35 and gestation >40 weeks. The principal factors associated with OCS were (in descending order of statistical significance): CS history, breech presentation, non-reassuring fetal status, obstructed labour, multiple birth, placental weight ≥ 600 g, eclampsia/pre-eclampsia, maternal age ≥ 35 and oligohydramnios. The most important risk factors for UCS were (in descending order of statistical significance): placenta previa/abruptio placenta/ antepartum hemorrage; non-reassuring fetal status, obstructed labour; breech presentation; PROM, eclampsia/pre-eclampsia; gestation 33–36 weeks; gestation 41+ weeks; oligohydramnios; birthweight <2,500 g, maternal age ≥ 35 and cord prolapse. After removing the effects of all other factors, we found great variability of DM rates across hospitals. Adjusting for all risk factors, all hospitals had a OCS risk higher than the referent (hospital G). Out of these 10 hospitals with increased adjusted risk of OCS, 9 (A, B, C, D, E, F, I, J, K) performed less SVD and 5 (A, C, D, I, J) less IVD. In the above 5 centres CS was therefore probably overused. The present study shows that routinely collected administrative data provide useful information for health planning and monitoring. Although the overall CS rate in FVG during 2005–15 was 24.2%, well below the corresponding average Italian national figure (38.1%), the variability of DM rates across FVG maternity centres could be targeted by policy interventions aimed at reducing the recourse to unnecessary CS. In some clinical conditions such as obstructed labor, non-reassuring fetal status, breech presentation, history of CS, higher maternal age and multiple birth, consideration may be given to more conservative DM. The overuse of CS in nulliparas and repeat CS (RCS) should be carefully monitored and subject to audit. [ABSTRACT FROM AUTHOR]

Opioids are essential for the treatment of pain, which is a serious symptom for children and adolescents affected by cancer. Intranasal opioids may be very useful for the treatment of breakthrough pain in children and adolescents with cancer, for their little invasiveness, ease of administration, rapid onset of action, and high bioavailability. Intranasal drug delivery may be influenced by anatomical and physiological factors (nasal mucosa absorption area, mucociliary clearance, enzymatic activity, anatomical anomalies, chronic or inflammatory alterations of nasal mucosa), drug-related factors (molecular weight, solubility), and delivery device. Fentanyl is a lipophilic opioid commonly proposed for intranasal use among pediatric patients, but no studies have been conducted yet about intranasal use of other available opioids for management of pediatric cancer pain. In this review, we analyze several elements which may influence absorption of intranasal opioids in children and adolescents, with a focus on pharmacokinetics and therapeutic aspects of each opioid currently available for intranasal use. [ABSTRACT FROM AUTHOR]

Is it possible to detect rock paintings coated by natural or anthropic concretions? In this work, a methodology to discover and characterize underlying paintings is proposed. This approach combines chemical studies by micro-Raman and SEM-EDS of micro-stratigraphic samples taken from the paintings and support rock. As a case of study, it is described the research performed in the archeological site of Oyola in the northwest of Argentina. Strong evidences of red, black, and white hidden paintings have been found. In addition, the method herein presented is thoroughly evaluated pointing out their possibilities and limitations as a tool for the understanding of the historical processes involving production and transformation of the rock art panels. To this end, the methodology was proofed to be a successful exploratory approach for painting detection, expanding its capabilities when complemented with non-invasive characterization techniques. [ABSTRACT FROM AUTHOR]

Over the time, instrument transportability has become more and more important, especially in Cultural Heritage, as often artworks cannot be moved from their site, either because of the size or due to problems with permission issues, or simply because moving them to a laboratory is physically impossible, as e.g. in the case of mural paintings. For this reason, the INFN-CHNet, the network for Cultural Heritage studies of the Italian National Institute of Nuclear Physics (INFN), has developed an XRF scanner for in situ analyses. The instrument is the result of a wide collaboration, where different units of the network have been developing the diverse parts, then merged in a single system. The XRF scanner has been designed to be a four-season and green instrument. The control/acquisition/analysis software has been fully developed by our group, using only open-source software. Other strong points of the system are easiness of use, high portability, good performances and ultra-low radiation dispersion, which allows us to use even when the public can be present. It can run both with mains or on batteries, in the latter case with a maximum runtime longer than 10 h. It has a very low cost, when compared to commercial systems with equivalent performances, and easily replaceable components, which makes it accessible for a much wider portion of the interested community. The system has been thought and designed as an open system, suitable for further development/improvements, that can result interesting for non-conventional XRF analysis. The CHNet XRF scanner has proved to be really very well suited for applications in the Cultural Heritage field, as testified by the many recent applications. This paper describes the present version of our instrument and reports on the tests performed to characterise its main features. [ABSTRACT FROM AUTHOR]

In recent years, the massive exploitation of agricultural land intended to meet growing food demand has led to a reduction in soil fertility through the depletion of nutrients and organic matter. To implement sustainable agriculture, it is necessary to reduce soil tillage and use residual biomasses that are easily available in the region as soil amendments. Furthermore, it is important to test these residual biomasses in order to exclude a possible increase of heavy metals in soils due to the incorporation of the aforementioned biomasses. The current study aimed to evaluate the effects on soil fertility and health following the application of organic fertilizers combined with different soil tillage practices and the agronomic response of Brassica carinata A. (Braun). The soil tillage treatments consisted of conventional (CT) and minimum tillage (MT), whereas the fertilization treatments were mineral fertilizer (Nmin), municipal solid waste compost (Ncomp), mixed compost and mineral fertilizer (Nmix), and sewage sludge (Nss). These treatments were compared with an unfertilized control (N0). The Ncomp and Nss treatments enhanced soil fertility, increasing the organic carbon and available phosphorus concentrations compared with N0 and Nmin, whereas no significant difference was showed between the soil tillage treatments in terms of soil fertility. In addition, Nss did not show any significant difference compared to Nmin in terms of crop biomass, whereas this parameter appeared higher in CT compared with MT. A principal component analysis showed that the concentrations of toxic elements applied by the organic amendments did not change the dynamic equilibrium of the soil-plant system. Over the short term, the replacement of CT and Nmin with MT and Nss can be achieved, thus guaranteeing the sustainable cultivation of Brassica, without significant changes in heavy metal concentration in soil. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]