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Background: Seasonal allergic rhinoconjunctivitis (SAR) is a worldwide health problem, especially in Westernized countries. Previous studies of the “Panallergens in Pediatrics” (PAN-PED) cohort found that molecular spreading (ie, the progressive increase in serum specific IgE antibody levels) of the IgE response to the grass pollen, Phleum pratense, molecules is directly associated with polysensitization to pollen in general.The research question is aimed at verifying whether this association can also be detected for non-pollen allergens, specifically Dermatophagoides pteronyssinnus (D.pt), to better understand the relationship between a perennial allergen (D.pt) and a seasonal allergen (Phleum pratense).To this end, our first objective was to analyze the biobank of the PAN-PED cohort serum by measuring the IgE levels to D.pt and its major recombinant molecules (Der p1, Der p2, Der p23); subsequently we investigated their correlation towards Phleum pratense IgE response, studying also the relationship between the molecular spreading of these 2 different allergens. Methods: Among 1120 patients positive to Phleum pratense, 638 were also sensitized to D.pt. Patients underwent skin prick tests (SPT) for inhalant extracts, and their serum was tested for total IgE (tIgE), and sIgE to pollen and perennial allergens. Considering the molecular allergen detection through the component resolved diagnosis (CRD), out of 638 patients, 146 were further investigated by performing IgE tests of the 3 major D.pt. molecules: Der p1, Der p2, and Der p23. Results: We found that a broader molecular response to Phleum pratense molecules, assessed by CRD, was associated with higher tIgE levels, polysensitization to pollens, and higher IgE levels to pollens, but also to lower IgE levels to D.pt and lower degree of sensitization to rDer p1, r Der p2, and rDer p23. In a multivariate linear model, the number of Phleum pratense molecules recognized by IgE was still inversely associated with the IgE level to D.pt extract. Conclusions: The main finding of this study was the detection of an inverse association, never described in the literature, between the molecular spreading of the IgE response to Phleum pratense and the IgE response to D.pt. This led us to speculate on the etiopathogenetic hypothesis according to which, among the majority of pollen allergic patients, a strong and molecularly diversified IgE response may be limited to pollen allergens and may be preventing or contrasting the development of an equally strong and diversified IgE sensitization to D.pt molecules. The biological mechanisms underlying this phenomenon deserve to be investigated.

Abstract Cerrado is the second largest biome in Brazil, and it is responsible for providing us several ecosystem services, including the functions of storing Carbon and biodiversity conservation. In this study, we developed a modeling approach to predict the Aboveground biomass (AGB) in Cerrado vegetation using Artificial Neural Networks (ANNs), vegetation indices retrieved from RapidEye satellite imagery, and field data acquired within the Federal District territory, Brazil. Correlation testing was performed to identify potential vegetation index candidates to be used as input in the AGB modeling. Several ANNs were trained to predict the AGB in the study area using vegetation indices and field data. The optimum ANN was selected according to criteria of mean error of the estimate, correlation coefficient, and graphical analysis. The best performing ANN showed a predictive power of 90% and RMSE less than 17%. The validation tests showed no significant difference between the observed and ANN-predicted values. We estimated an average AGB of 16.55± 8.6 Mg.ha-1 in shrublands in the study area. Our study results indicate that vegetation indices and ANNs combined could accurately estimate the AGB in the Cerrado vegetation in the study area, showing to be a promising methodological approach to be broadly applied throughout the Cerrado biome.

Abstract Background BRCA1:c.5017_5019del (p.His1673del) is a founder variant relatively frequent in Northern Italy. Despite previous suggestion of pathogenicity, variant classification in public databases is still conflicting, needing additional evidence. Methods Maximum likelihood penetrance of breast/ovarian and other cancer types was estimated using full pedigree data from 53 informative Italian families. The effect of the variant on BRCA1‐ABRAXAS1 interaction was assessed using a GFP‐fragment reassembly‐based PPI assay. Results were combined with additional data from multiple sources to classify the variant according to ACMG/AMP classification rules specified for BRCA1/2. Results Variant‐carriers displayed increased risk for ovarian cancer (HR = 33.0, 95% CI = 7.0–155.0; cumulative risk at age 70 = 27.6%, 95% CI = 12.6–40.0%) but not for breast cancer (HR = 0.7, 95% CI = 0.2–2.2). An increased risk of uterine cancer (HR = 8.0, 95% CI = 1.03–61.6) emerged, warranting further evaluation. Likelihood‐ratio in favor of pathogenicity was 98898642.82 under assumption of standard BRCA1 breast and ovarian penetrance, and 104240832.84 after excluding breast cancer diagnoses (based on penetrance results). Functional analysis demonstrated that the variant abrogates the BRCA1‐ABRAXAS1 binding, supporting the PS3 code assignment within the ACMG/AMP rule‐based model. Collectively, these findings allowed to classify the variant as pathogenic. Conclusion Pathogenicity of BRCA1:c.5017_5019del(p.His1673del) has been confirmed; however, breast cancer risk in Italian families is not increased, unlike in families from other countries and in carriers of most BRCA1 pathogenic variants. The knowledge of atypical risk profiles for this and other variants will pave the way for personalized management based on specific genotype.

Objetivo: Descrever a mortalidade materna nas macrorregiões de saúde de Mato Grosso do Sul no período de 2011 a 2019. Métodos: Estudo descritivo e transversal de casos notificados de mortalidade materna no estado de Mato Grosso do Sul e suas macrorregiões de saúde, no período de 2011 a 2019. Foram extraídos por meio do acesso a fonte de dados do Sistema de Informações sobre Mortalidade. Os dados de faixa etária, escolaridade, cor, estado civil, local de ocorrência, causa e período gravídico-puerperal foram armazenados no software Microsoft Excel. A Razão de Mortalidade Materna foi calculada para cada macrorregião. Resultados: Foram identificados 237 óbitos maternos, com 46,0% na macrorregião de Campo Grande, 32,5% em Dourados, 11,4% em Três lagoas e 10,1% em Corumbá. Foram registrados 391.171 nascidos vivos no estado de Mato Grosso do Sul e o coeficiente de mortalidade materna nesse período foi de 60,6/100.000 nascidos vivos. Conclusão: Os números de mortalidade materna se mantem elevados e, o coeficiente de mortalidade materna classificado como muito alto. Apesar dos avanços para a melhoria na assistência obstétrica e a existência de políticas públicas em saúde, o número de mortes que poderiam ser evitadas com o uso de tecnologias simples no nível primário de atenção à saúde para identificação de complicações continua alarmante.

This paper draws attention to the environmental impact of passive smart windows, a novel high-performance glazing technologies that can change their solar transmittance to control the amount of solar gain, thus reducing cooling energy demand. Despite the large influence of building envelope technologies on overall embodied carbon in buildings, the environmental impact of passive smart windows has been inadequately addressed, with a dearth of numerical data on various impact categories beyond energy consumption and Global Warming Potential (GWP). While current literature focuses on the advantages of these technologies in terms of operational energy savings, other critical environmental considerations are currently missing. This paper aims to bridge the existing gap by introducing a novel framework for evaluating the broader environmental impact of passive smart windows through a multi-category LCA method. By analysing the life cycle of these technologies, including production, usage, and disposal, the research seeks to provide a holistic understanding of their contribution to sustainability. The framework is based on systematic literature review on current state-of-art approaches and Interviews with key stakeholders in the dynamic glazing value chain. Literature review and interview results are presented, and then the framework is demonstrated through a case study of a thermochromic technologies for an office building in the Netherlands. Preliminary results show the critical areas where improvements on the methods or on the performance of the technology are required for the achievement of holistically sustainable high-performing glazing.

The Cerrado has high plant and vertebrate diversity and is an important biome for conserving species and provisioning ecosystem services. Volume equations in this biome are scarce because of their size and physiognomic diversity. This study was conducted to develop specific volumetric models for the phytophysiognomies Gallery Forest, Dry Forest, Forest Savannah, and Savannah Woodland, a generic model and a model for Cerrado forest formation. Twelve 10 m × 10 m (100 m²) (National Forest Inventory) plots were used for each phytophysiognomy at different sites (regions) of the Federal District (FD) where trees had a diameter at breast height (DBH; 1.30 m) ≥5 cm in forest formations and a diameter at base height (Db; 0.30 m) ≥5 cm in savanna formations. Their diameters and heights were measured, they were cut and cubed, and the volume of each tree was obtained according to the Smalian methodology. Linear and nonlinear models were adjusted. Criteria for the selection of models were determined using correlation coefficients, the standard error of the estimates, and a graphical analysis of the residues. They were later validated by the chi-square test. The resultant models indicated that fit by specific phytophysiognomy was ideal; however, the generic and forest formation models exhibited similar performance to specific models and could be used in extensive areas of the Cerrado, where they represent a high potential for generalization. To further increase our understanding, similar research is recommended for the development of specific and generic models of the total volume in Cerrado areas.

Research related to Cerradão vegetation focuses more on the floristic-structural aspect, with rare studies on the quantification of volume and biomass stocks, and even fewer investigating the increments of these attributes. Using a systematic sampling method with subdivided strips and 400 m2 plots, the density found was 1135, 1165, and 1229 trees/ha in 2012, 2020, and 2023, respectively, in Lajeado State Park, Tocantins State, Brazil. Volume was estimated using the equation v=0.000085D2.122270H0.666217, and biomass was estimated using the equation AGB=0.0673ρD2H0.976. Vegetation dynamics were assessed using growth increment, recruitment, mortality, turnover rate, and time. The results indicated that dynamics have increased since the start of monitoring. Typical Cerrado species, in the strict sense, were replaced by those from forest environments. The total production in volume and biomass was 160.91 m3/ha and 118.10 Mg/ha, respectively, in 2023. The species of Emmotum nitens, Mezilaurus itauba, Ocotea canaliculata, and Sacoglottis guianensis showed the highest increment values in volume and biomass. For the community, the average values were 4.04 m3/ha/year and 3.54 Mg/ha/year. The community has not yet reached its carrying capacity and stores a significant amount of biomass. This is influenced by the transition of the study area from an exploited environment to a conservation unit (park) and by its location in a transitional area with the Amazon biome.

Abstract Objectives We describe the Residras registry, dedicated to Dravet syndrome (DS) and to other phenotypes related to SCN1A mutations, as a paradigm of registry for rare and complex epilepsies. Our primary objectives are to present the tools and framework of the integrative platform, the main characteristics emerging from the patient cohort included in the registry, with emphasis on demographic, clinical outcome, and mortality. Methods Standardized data of enrolled pediatric and adult patients were collected in 24 Italian expert centers and regularly updated at least on a yearly basis. Patients were prospectively enrolled, at registry starting, but historical retrospective data were also included. Results At present, 281 individuals with DS and a confirmed SCN1A mutation are included. Most patients have data available on epilepsy (n = 263) and their overall neurological condition (n = 255), based on at least one follow‐up update. Median age at first clinical assessment was 2 years (IQR 0–9) while at last follow‐up was 11 years (IQR 5–18.5). During the 7‐year activity of the registry, five patients died resulting in a mortality rate of 1.84 per 1000‐person‐years. When analyzing clinical changes over the first 5‐year follow‐up, we observed a significant difference in cognitive function (P

Introduction Wheezing is common in preschool children and its clinical assessment often challenging for caretakers. This study aims to evaluate the impact of a novel digital wheeze detector (WheezeScan™) on disease control in a home care setting. Methods A multicentre randomised open-label controlled trial was conducted in Berlin, Istanbul and London. Participants aged 4–84 months with a doctor's diagnosis of recurrent wheezing in the past 12 months were included. While the control group followed usual care, the intervention group received the WheezeScan™ for at-home use for 120 days. Parents completed questionnaires regarding their child's respiratory symptoms, disease-related and parental quality of life, and caretaker self-efficacy at baseline (T0), 90 days (T1) and 4 months (T2). Results A total of 167 children, with a mean±sd age of 3.2±1.6 years, were enrolled in the study (intervention group n=87; control group n=80). There was no statistically significant difference in wheeze control assessed by TRACK (mean difference 3.8, 95% CI −2.3–9.9; p=0.2) at T1 between treatment groups (primary outcome). Children's and parental quality of life and parental self-efficacy were comparable between both groups at T1. The evaluation of device usability and perception showed that parents found it useful. Conclusion In the current study population, the wheeze detector did not show significant impact on the home management of preschool wheezing. Hence, further research is needed to better understand how the perception and usage behaviour may influence the clinical impact of a digital support.

The presence of carbapenem-resistant bacteria and carbapenem resistance genes (CRGs) in livestock is increasing. To evaluate the presence of carbapenemase-producing Enterobacteriaceae (CPE) and the main CRGs along swine food chains of the Marche Region (Central Italy), samples of faeces, feed, and animal-food derived products were collected from seven small/medium, medium, and large-scale pig farms. A total of 191 samples were analysed using a culture-dependent method, with the aim of isolating CPE. Isolates were analysed for their resistance to carbapenems using a modified Hodge test and the microdilution method for the minimum inhibitory concentration (MIC) determination. Moreover, the extraction of microbial DNA from each sample was performed to directly detect selected CRGs via qPCR. Among the 164 presumptive resistant isolates, only one strain from a liver sample, identified as Aeromonas veronii, had an ertapenem MIC of 256 μg/mL and carried a carbapenemase- (cphA) and a β-lactamase- (blaOXA-12) encoding genes. A low incidence of CRGs was found; only nine and four faecal samples tested positive for blaNDM-1 and blaOXA-48, respectively. Overall, the importance of monitoring CPE and CRGs in livestock and their food chains should be stressed to control all potential non-human CPE and CRGs reservoirs and to determine safety levels for human health.

Europe has recently seen a massive multi-ethnic influx of migrants, marred by high social costs of inter-ethnic confrontation. This has prompted scholars to develop training schemes to improve the social skills needed to cope with this situation. Decades of studies have acknowledged empathy as a crucial variable in the development of positive interpersonal and intergroup relations. In this study, we tested a training program for enhancing empathy towards ethnically diverse people in 170 six- to nine-year-old children. The materials were drawn from other best-known training schemes and active techniques were used. Multicultural empathy was assessed with a self-report measure. Test, retest and follow-up (at 6 months) comparisons demonstrated the training's efficacy, with improvement in multicultural empathy persisting six months later. The results suggest that it can be a useful tool to encourage the development of ethnocultural empathy starting from the first years of elementary school. The practical implications for school education are discussed.

Background: The SARS-CoV-2 pandemic has significantly affected the pediatric population. Long-term sequelae (Long COVID-19) may particularly involve the central nervous system, with possible effects on psychological well-being and quality of life (QoL), aspects that were already influenced by the restrictive measures and general social impact of the pandemic. Methods: We conducted a cross-sectional survey that aims at investigating the neuropsychological effects and the QoL impairment of SARS-CoV-2 on a cohort of children and adolescents in the Abruzzo region (Italy). A questionnaire was submitted to caregivers with the help of the PEDIATOTEM platform. A control group of healthy subjects was also included to distinguish between the effects of infection from the general influence of the pandemic. Results: A total of 569 subjects responded: 396 COVID-19 patients (99 of whom had Long COVID-19) and 111 controls. After the pandemic, when compared with the COVID-19 group, the controls reported significantly increased appetite, sleeping habits, and time spent remotely with friends and a reduction in physical activity and time spent in person with friends. A significant higher rate of controls asked for psychological/medical support for emotional problems. On the other hand, the Long COVID-19 group showed more fatigue and emotional instability with respect to non-Long-COVID-19 subjects. No differences in QoL results (EuroQOL) were found between the COVID-19 patients and controls, while the Long-COVID-19 subgroup showed significantly higher rates of pain/discomfort and mood instability, as confirmed by the analysis of variation of responses from the pre-COVID-19 to the post-COVID-19 period. Conclusions: Among COVID-19 patients, neuropsychological and QoL impairment was more evident in the Long COVID-19 subgroup, although emotional and relational issues were also reported by uninfected patients, with a growing request for specialist support as a possible consequence of social restriction.

Objetivo: compreender a percepção pessoal e variáveis relacionadas à saúde de trabalhadores do varejo. Método: trata-se de um estudo qualitativo realizado com trabalhadores varejistas da região central do município de Campo Grande – Mato Grosso do Sul. Aplicou-se um questionário com questões sociodemográficas e semiestruturadas baseadas no Questionário de Qualidade de Vida no Trabalho abreviado. A análise dos dados comparou os resultados com a literatura nacional e internacional. Resultados: os participantes apresentaram necessidades de saúde relacionadas à atenção à saúde, saúde mental, satisfação, conforto e segurança, evidenciando diferentes necessidades nos contextos de lojas isoladas e empresas. Considerações finais: foi possível observar que são necessárias intervenções intersetoriais direcionadas às necessidades de cada grupo. É fundamental a continuidade de estudos que abordem um maior número de participantes e de regiões. ABSTRACT Objective: Tounder stand the personal perception and health-related variables of retail workers. Method: This is a qualitative study carried out with retail workers in the central region of the municipality of Campo Grande - Mato Grosso do Sul. A questionnaire with sociodemographic and semi-structured questions based on the abbreviated Quality of Work Life Questionnaire was applied. Data analysis compared the results with national and international literature. Results: The participants presented health needs related to health care, mental health, satisfaction, comfort and safety, evidencing different needs in the contexts of isolated stores and companies. Final considerations: It was possible to observe that intersectoral interventions directed to the needs of each group are necessary. It is essential to continue studies that address a greater number of participants and regions.

This paper discusses the transcultural investigations conducted by Jerzy Grotowski on traditional AfroDiasporic chants. Based on some notes on the collaboration with the Haitian artist Maud Robart, it argues that these investigations were not aimed at the expropriation of traditional performative knowledge, the emptying of its meanings or the aestheticization of its forms. In its political dimension, as it seeks to delineate, it was a work that had the potential to relativize the usual modes of perception of the individual, especially the modern and western one, towards what could be called a ‘decolonization of the self’.

Este artigo trata das investigações transculturais de Jerzy Grotowski sobre os cantos tradicionais afrodiaspóricos. A partir de alguns apontamentos sobre a colaboração realizada com a artista haitiana Maud Robart, busca-se explicitar que tais investigações não estavam direcionadas à expropriação dos conhecimentos performativos tradicionais, ao esvaziamento de seus sentidos e à estetização de suas formas. Em sua dimensão política, conforme se busca evidenciar, tratava-se de um trabalho que tinha a potência de relativizar os modos de percepção habituais do indivíduo, principalmente daquele moderno e ocidental, na direção do que poderia ser chamada de uma ‘descolonização do si mesmo’.

Abstract Introduction Fenfluramine (FFA) is an amphetamine derivative that promotes the release and blocks the neuronal reuptake of serotonin. Initially introduced as an appetite suppressant, FFA also showed antiseizure properties. This systematic review aimed to assess the efficacy and safety of FFA for the treatment of seizures in patients with epilepsy. Methods We systematically searched (in week 3 of June 2022) MEDLINE, the Cochrane Central Register of Controlled Trials, and the US National Institutes of Health Clinical Trials Registry. Randomized, double- or single-blinded, placebo-controlled studies of FFA in patients with epilepsy and uncontrolled seizures were identified. Efficacy outcomes included the proportions of patients with ≥ 50% and 100% reductions in baseline seizure frequency during the treatment period. Tolerability outcomes included the proportions of patients who withdrew from treatment for any reason and suffered adverse events (AEs). The risk of bias in the included studies was assessed according to the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions. The risk ratio (RR) along with the 95% confidence interval (CI) were estimated for each outcome. Results Three trials were identified and a total of 469 Dravet syndrome (DS) and Lennox–Gastaut syndrome (LGS) subjects were randomized. All three trials were judged to be at low risk of biases. In patients with DS, the RRs for ≥ 50% and 100% reductions in convulsive seizure frequency for the FFA group compared to placebo were 5.61 (95% CI 2.73–11.54) and 4.71 (95% CI 0.57–39.30), respectively. In patients with LGS, the corresponding RRs for ≥ 50% and 100% reductions in drop seizure frequency were 2.58 (95% CI 1.33–5.02) and 0.50 (95% CI 0.031–7.81), respectively. The drug was withdrawn for any reason in 10.1% and 5.8% of patients receiving FFA and placebo, respectively (RR 1.79, 95% CI 0.89–3.59). Treatment discontinuation due to AEs occurred in 5.4% and 1.2% of FFA- and placebo-treated patients, respectively (RR 3.63, 95% CI 0.93–14.16). Decreased appetite, diarrhoea, fatigue, and weight loss were AEs associated with FFA treatment. Conclusion Fenfluramine reduces the frequency of seizures in patients with DS and LGS. Decreased appetite, diarrhoea, fatigue, and weight loss are non-cardiovascular AEs associated with FFA.

Abstract Objective Perampanel (PER) is indicated as adjunctive antiseizure medication (ASM) in adolescents and adults with epilepsy. Data from clinical trials show good efficacy and tolerability, while limited information is available on the routine clinical use of PER, especially when used as only add‐on treatment. Methods We performed an observational, retrospective, multicenter study on people with focal or generalized epilepsy aged >12 years, consecutively recruited from 52 Italian epilepsy centers. All patients received PER as the only add‐on treatment to a background ASM according to standard clinical practice. Retention rate, seizure frequency, and adverse events were recorded at 3, 6, and 12 months after PER introduction. Subanalyses by early or late use of PER and by concomitant ASM were also conducted. Results Five hundred and three patients were included (age 36.5 ± 19.9 years). Eighty‐one percent had focal epilepsy. Overall, the retention rate was very high in the whole group (89% at 12 months) according with efficacy measures. No major differences were observed in the subanalyses, although patients who used PER as early add‐on, as compared with late add‐on, more often reached early seizure freedom at 3‐month follow‐up (66% vs 53%, P = .05). Treatment‐emergent adverse events occurred in 25%, far less commonly than in PER randomized trials. Significance This study confirms the good efficacy and safety of PER for focal or generalized epilepsy in real‐life conditions. We provide robust data about its effectiveness as only add‐on treatment even in patients with a long‐standing history of epilepsy and previously treated with many ASMs.

The ecological influence of functional traits on species persistence as well as on their role over the organization of forest communities in the Brazilian Cerrado biome have not been fully understood yet. In this study, we assessed the effects of six functional groups, characterized by three seed dispersal syndromes (i.e., anemochory, autochory, and zoochory) and three wood density classes (i.e., hardwood, lightwood, and softwood), on tree spatial distribution patterns, habitat occupancy, and ecosystem services (biomass hyper dominance and abundance) provided by a forest community located in the “Parque do Lajeado”, state of Tocantins, Brazil. The similarity among study sites was characterized by applying the tree dominant height approach and the environmental and soil variables as input. The floristic similarity was assessed by applying the Bray-Curtis index. The zoochoric species showed more aggregated spatial pattern at local scale, which indicates that it is more sensitive to environmental gradients than other dispersal syndromes. Meanwhile, hardwood density species were more established in the community, being more persistent to environmental filters. We observed that a small number of species contributed with about 50% of the abundance and biomass of the community, whose functional traits (wood density and dispersal syndrome) indirectly affect the relationship among the community species richness and their ecosystem functions. We observed that the functional traits related to seed dispersal and wood density functional groups resulted in different spatial distribution patterns of those tree species. Therefore, functional traits and environmental factors combined have substantially affected the structure and composition of forest communities at local scale.

A stepwise increase in the utilization of ketogenic dietary therapies for drug-resistant epilepsy has been observed in Italy in the last decade, although it is still considered often underused in many centers when compared to other countries. The Dietary Therapy Study Group of the Italian League against Epilepsy proposes practical recommendations to improve shared knowledge and facilitate the application of ketogenic dietary therapies, optimizing its efficacy and tolerability. The experts involved (11 child neuropsychiatrists, two adult neurologists, one psychologist, one pharmacologist, one pediatric endocrinologist, one representative of patients' associations, and three dietitians and clinical nutritionists) responded to a survey on current clinical practice issues and were asked to discuss controversial topics related to supplementation, long-term maintenance, transition, and a multidisciplinary approach to ketogenic dietary therapies. Practical indications for patient selection, diet initiation, management, side effects prevention, and follow-up are provided.

BackgroundNasal provocation testing (NPT) is a reference methodology to identify the culprit allergen in patients with allergic rhinitis. Selecting the right allergen for NPT is particularly difficult in poly-sensitized patients with seasonal allergic rhinitis (SAR). Predictors of NPT outcomes may facilitate the proper use of this test or even substitute it.ObjectiveTo identify predictors of grass pollen NPT outcome from an array of clinical data, e-diary outcomes, and allergy test results in poly-sensitized pediatric patients with SAR.MethodsPoly-sensitized, SAR patients with grass pollen allergy, participating in the @IT.2020 pilot project in Rome and Pordenone (Italy), participated in a baseline (T0) visit with questionnaires, skin prick testing (SPT), and blood sampling to measure total (ImmunoCAP, TFS, Sweden) and specific IgE antibodies to grass pollen extracts and their major allergenic molecules (ESEP, Euroimmun Labordiagnostika, Germany). During the pollen season, patients filled the AllergyMonitor® e-diary app measuring their symptoms, medication intake, and allergy-related well-being via the Visual Analogue Scale (VAS). After the pollen season (T1), patients answered clinical questionnaires and underwent a nasal provocation test (NPT) with grass pollen extract.ResultsWe recruited 72 patients (age 14.3 ± 2.8 years, 46 males) sensitized to grass and/or other pollens, including olive (63; 87.5%) and pellitory (49; 68.1%). Patients positive to grass pollen NPT (61; 84.7%), compared to the negative ones, had worse VAS values in the e-diary, larger SPT wheal reactions, and higher IgE levels, as well as specific activity to timothy and Bermuda grass extracts, rPhl p 5 and nCyn d 1. A positive NPT to grass pollen was predicted by an index combining the specific activity of IgE towards Phl p 5 and Cyn d 1 (AUC: 0.82; p

Background and purposeKetogenic diet (KD) is an emerging treatment option for super-refractory status epilepticus (SRSE). We evaluated the effectiveness of KD in patients presenting SRSE including NORSE (and its subcategory FIRES).MethodsA retrospective review of the medical records was performed at the Necker Enfants Malades Hospital. All children with SRSE in whom KD was started during the last 10 years were included. A systematic search was carried out for all study designs, including at least one patient of any age with SRSE in whom KD was started. The primary outcome was the responder rate and Kaplan–Meier survival curves were generated for the time-to-KD response. As secondary outcomes, Cox proportional hazard models were created to assess the impact of NORSE-related factors on KD efficacy.ResultsSixteen children received KD for treatment of SRSE, and three had NORSE presentation (one infectious etiology, two FIRES). In medical literature, 1,613 records were initially identified, and 75 were selected for review. We selected 276 patients receiving KD during SRSE. The most common etiology of SRSE was acute symptomatic (21.3%), among these patients, 67.7% presented with NORSE of immune and infectious etiologies. Other etiologies were remote symptomatic (6.8%), progressive symptomatic (6.1%), and SE in defined electroclinical syndromes (14.8%), including two patients with genetic etiology and NORSE presentation. The etiology was unknown in 50.7% of the patients presenting with cryptogenic NORSE, of which 102 presented with FIRES. Overall, most patients with NORSE benefit from KD (p < 0.004), but they needed a longer time to achieve RSE resolution after starting KD compared with other non-NORSE SRSE (p = 0.001). The response to KD in the NORSE group with identified etiology compared to the cryptogenic NORSE was significantly higher (p = 0.01), and the time to achieve SE resolution after starting KD was shorter (p = 0.04).ConclusionsThe search for underlying etiology should help to a better-targeted therapy. KD can have good efficacy in NORSE; however, the time to achieve SE resolution seems to be longer in cryptogenic cases. These findings highlight the therapeutic role of KD in NORSE, even though this favorable response needs to be better confirmed in prospective controlled studies.

Scleroglucan (Sclg) and Guar Gum (GG) are both capable to give gels in the presence of borax and this study is focused on how a mixed system of the two polysaccharides can be affected by the addition of borax. The anisotropic swelling behavior of tablets obtained by compression of the freeze-dried new gel system is also investigated and compared to that of Sclg and GG alone. Rheological characterization evidences a synergistic effect in terms of critical time, mesh size, as well as crosslinking density. Also creep recovery experiments, carried out in the presence of borax, show a synergistic effect: when the polymers are mixed, a quite low compliance was estimated in comparison to that of Sclg and GG. On the other side, the flexible chains of GG induce the self-healing properties of the mixed gel system, since the rigid triple helix of Sclg does not show such peculiar characteristics. The deep insight of the physico-chemical properties of the new hydrogel system can play a fundamental role for the optimization of its practical application (e.g., in drug delivery, cosmetic products, human tissue repair, wound dressing and food staff).

Nanocarriers have been extensively developed in the biomedical field to enhance the treatment of various diseases. However, to effectively deliver therapeutic agents to desired target tissues and enhance their pharmacological activity, these nanocarriers must overcome biological barriers, such as mucus gel, skin, cornea, and blood-brain barriers. Polysaccharides possess qualities such as excellent biocompatibility, biodegradability, unique biological properties, and good accessibility, making them ideal materials for constructing drug delivery carriers. Nanogels, as a novel drug delivery platform, consist of three-dimensional polymer networks at the nanoscale, offering a promising strategy for encapsulating different pharmaceutical agents, prolonging retention time, and enhancing penetration. These attractive properties offer great potential for the utilization of polysaccharide-based nanogels as drug delivery systems to overcome biological barriers. Hence, this review discusses the properties of various barriers and the associated constraints, followed by summarizing the most recent development of polysaccharide-based nanogels in drug delivery to overcome biological barriers. It is expected to provide inspiration and motivation for better design and development of polysaccharide-based drug delivery systems to enhance bioavailability and efficacy while minimizing side effects.

The novel amphiphilic polyacrylate grafted with cholesterol moieties, PAAbCH, previously synthesized, was deeply characterized and investigated in the lab and on a pre-industrial scale. Solid-state NMR analysis confirmed the polymer structure, and several water-based pharmaceutical and cosmetic products were developed. In particular, stable oil/water emulsions with vegetable oils, squalene, and ceramides were prepared, as well as hydrophilic medicated films loaded with diclofenac, providing a prolonged drug release. PAAbCH also formed polyelectrolyte hydrogel complexes with chitosan, both at the macro- and nano-scale. The results demonstrate that this polymer has promising potential as an innovative excipient, acting as a solubility enhancer, viscosity enhancer, and emulsifying agent with an easy scale-up transfer process.

Abstract Background Viral airway infections are a major reason for doctor’s visits at pre-school age, especially when associated with wheezing. While proper treatment requires adequate recognition of airway obstruction, caretakers are often struggling with this judgment, consequently leading to insufficient or late treatment and an unnecessary discomfort of the patient. Digital technologies may serve to support parental decision taking. The aim of the present pilot study is to acquire data on the feasibility of recruitment and observation procedures for a randomized controlled trial on the impact of a digital wheeze detector in a home management setting of pre-school wheezing. Methods This single-armed pilot study enrolled patients with a doctor’s diagnosis of wheezing aged 9 to 72 months. Participants were asked to use a digital wheeze detector (WheezeScan, Omron Healthcare, Japan) 2×/day for 30 days and record the child’s respiratory symptoms, detection of wheezing, and medication intake via an electronic diary (eDiary) app. Demographic and clinical data were collected at the recruitment visit. The asthma control test and the Parent Asthma Management Self-Efficacy Scale (PAMSES) were assessed both, at recruitment and follow-up. Results Twenty families were recruited and completed the monitoring. All but one completed the follow-up after 30 days. The recruitment procedures were feasible, and adherence to daily monitoring reached an average of 81%. The use of the wheeze detector was rated as uncomplicated. Parents detected wheezing without digital support in only 22/708 (3.1%) of the recorded events. By contrast, the wheeze detector indicated an airway obstruction in 140/708 (19.8%) of the recordings. Conclusion In parallel to feasible recruitment procedures, we observed good usability of the wheeze detection device and high adherence to eDiary recording. The positive outcomes show that the WheezeScan may empower parents by increasing their capacity for wheeze detection. This deserves to be investigated in a larger randomized controlled trial.

Abstract Digital health is an umbrella term which encompasses eHealth and benefits from areas such as advanced computer sciences. eHealth includes mHealth apps, which offer the potential to redesign aspects of healthcare delivery. The capacity of apps to collect large amounts of longitudinal, real‐time, real‐world data enables the progression of biomedical knowledge. Apps for rhinitis and rhinosinusitis were searched for in the Google Play and Apple App stores, via an automatic market research tool recently developed using JavaScript. Over 1500 apps for allergic rhinitis and rhinosinusitis were identified, some dealing with multimorbidity. However, only six apps for rhinitis (AirRater, AllergyMonitor, AllerSearch, Husteblume, MASK‐air and Pollen App) and one for rhinosinusitis (Galenus Health) have so far published results in the scientific literature. These apps were reviewed for their validation, discovery of novel allergy phenotypes, optimisation of identifying the pollen season, novel approaches in diagnosis and management (pharmacotherapy and allergen immunotherapy) as well as adherence to treatment. Published evidence demonstrates the potential of mobile health apps to advance in the characterisation, diagnosis and management of rhinitis and rhinosinusitis patients.

The endocrine and nervous systems reciprocally interact to manage physiological individual functions and homeostasis. The nervous system modulates hormone release through the hypothalamus, the main cerebrally specialized structure of the neuroendocrine system. The hypothalamus is involved in various metabolic processes, administering hormone and neuropeptide release at different levels. This complex activity is affected by the neurons of various cerebral areas, environmental factors, peripheral organs, and mediators through feedback mechanisms. Therefore, neuroendocrine pathways play a key role in metabolic homeostasis control, and their abnormalities are associated with the development of metabolic syndrome (MetS) in children. The impaired functioning of the genes, hormones, and neuropeptides of various neuroendocrine pathways involved in several metabolic processes is related to an increased risk of dyslipidaemia, visceral obesity, insulin resistance, type 2 diabetes mellitus, and hypertension. This review examines the neuroendocrine effects on the risk of MetS in children, identifying and underlying several conditions associated with neuroendocrine pathway disruption. Neuroendocrine systems should be considered in the complex pathophysiology of MetS, and, when genetic or epigenetic mutations in “hot” pathways occur, they could be studied for new potential target therapies in severe and drug-resistant paediatric forms of MetS.

BackgroundBRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs).MethodsWe characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database.ResultsAmong BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 × 10(-5)) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor-positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15-21.80] and progesterone receptor-positive (OR 5.04; 95 % CI 3.17-8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 × 10(-12)).ConclusionsOn the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.

BackgroundMobile health technologies enable allergists to monitor disease trends by collecting daily patient-reported outcomes of allergic rhinitis. To this end, patients with allergies are usually required to enter their symptoms and medication repetitively over long time periods, which may present a risk to data completeness and quality in the case of insufficient effort reporting. Completeness of patient’s recording is easily measured. In contrast, the intrinsic quality and accuracy of the data entered by the patients are more elusive. ObjectiveThe aim of this study was to explore the association of adherence to digital symptom recording with a predefined set of parameters of the patient-generated symptom and medication scores and to identify parameters that may serve as proxy measure of the quality and reliability of the information recorded by the patient. MethodsThe @IT.2020 project investigates the diagnostic synergy of mobile health and molecular allergology in patients with seasonal allergic rhinitis. In its pilot phase, 101 children with seasonal allergic rhinitis were recruited in Rome and instructed to record their symptoms, medication intake, and general conditions daily via a mobile app (AllergyMonitor) during the relevant pollen season. We measured adherence to daily recording as the percentage of days with data recording in the observation period. We examined the patient’s trajectories of 3 disease indices (Rhinoconjunctivitis Total Symptom Score [RTSS], Combined Symptom and Medication Score [CSMS], and Visual Analogue Scale [VAS]) as putative proxies of data quality with the following 4 parameters: (1) intravariation index, (2) percentage of zero values, (3) coefficient of variation, and (4) percentage of changes in trend. Lastly, we examined the relationship between adherence to recording and each of the 4 proxy measures. ResultsAdherence to recording ranged from 20% (11/56) to 100% (56/56), with 64.4% (65/101) and 35.6% (36/101) of the patients’ values above (highly adherent patients) or below (low adherent patients) the threshold of 80%, respectively. The percentage of zero values, the coefficient of variation, and the intravariation index did not significantly change with the adherence to recording. By contrast, the proportion of changes in trend was significantly higher among highly adherent patients, independently from the analyzed score (RTSS, CSMS, and VAS). ConclusionsThe percentage of changes in the trend of RTSS, CSMS, and VAS is a valuable candidate to validate the quality and accuracy of the data recorded by patients with allergic rhinitis during the pollen season. The performance of this parameter must be further investigated in real-life conditions before it can be recommended for routine use in apps and electronic diaries devoted to the management of patients with allergic rhinitis.

Opposite to other immunoglobulin (Ig) classes and subclasses, there is no consensus on the definition of normal levels of serum total IgE. However, longitudinal studies on birth cohorts produced growth charts of total IgE levels in helminth-free and never atopic children and defining the normal ranges of total serum IgE concentration at the individual, rather than population, level. Accordingly, very ‘low IgE producers’ (i.e., children whose tIgE level belong to the lowest percentiles) became atopic while keeping their total IgE levels in a range considered ‘normal’ if compared to the general age-matched population but ‘abnormally high’ if projected on the tIgE growth chart against the trajectory of that child’s own percentile levels. In ‘low IgE producers’, the IgE-specific activity, i.e., the ratio between allergen-specific and total IgE, is more important than the absolute specific IgE levels to confirm causality between allergen exposure and allergic symptoms. Patients with allergic rhinitis or peanut anaphylaxis but low or undetectable allergen-specific IgE levels must therefore be reconsidered considering their total IgE levels. Low IgE producers have been also associated with common variable immunodeficiency, lung diseases, and malignancies. A few epidemiological studies have shown a higher risk of malignancies in very low IgE producers, leading to a debated hypothesis proposing a novel, evolutionistic-relevant function for IgE antibodies for antitumor immune surveillance.

Most radiation schemes in weather and climate models use the “correlated k distribution” (CKD) method to treat gas absorption, which approximates a broadband spectral integration by N pseudo-monochromatic calculations. Larger N means more accuracy and a wider range of gas concentrations can be simulated but at greater computational cost. Unfortunately, the tools to perform this efficiency–accuracy trade-off (e.g. to generate separate CKD models for applications such as short-range weather forecasting to climate modelling) are unavailable to the vast majority of users of radiation schemes. This paper describes the experimental protocol for the Correlated K-Distribution Model Intercomparison Project (CKDMIP), whose purpose is to use benchmark line-by-line calculations: (1) to evaluate the accuracy of existing CKD models, (2) to explore how accuracy varies with N for CKD models submitted by CKDMIP participants, (3) to understand how different choices in the way that CKD models are generated affect their accuracy for the same N, and (4) to generate freely available datasets and software facilitating the development of new gas-optics tools. The datasets consist of the high-resolution longwave and shortwave absorption spectra of nine gases for a range of atmospheric conditions, realistic and idealized. Thirty-four concentration scenarios for the well-mixed greenhouse gases are proposed to test CKD models from palaeo- to future-climate conditions. We demonstrate the strengths of the protocol in this paper by using it to evaluate the widely used Rapid Radiative Transfer Model for General Circulation Models (RRTMG).

Este artigo aborda o estado da arte do sensoriamento remoto por radar e foi elaborado para fazer parte da edição especial de comemoração dos 50 anos desta revista. Neste estudo, é apresentada uma breve introdução sobre os fundamentos do sensoriamento remoto por radar, com destaque para os parâmetros mais importantes de imageamento e da superfície terrestre envolvidos no processo de obtenção de imagens de radar. Ênfase é dada para o comprimento de onda, polarização das ondas eletromagnéticas e geometria de obtenção de imagens (parâmetros de imageamento) e para a umidade de solos e da vegetação, rugosidade do terreno e estrutura da vegetação (parâmetros da superfície terrestre). Em seguida, são apresentados os principais sensores orbitais de radar de abertura sintética que estão atualmente em operação e os principais processamentos digitais de imagens de radar, destacando-se a conversão dos valores digitais para coeficientes de retroespalhamento, os filtros espaciais para redução do ruído speckle, as técnicas de decomposição de imagens e o processamento InSAR. Finalmente, é apresentada uma breve discussão sobre algumas aplicações potenciais, com especial atenção para o monitoramento de derrame de óleo em plataformas continentais, estimativa de biomassa aérea, monitoramento de desmatamento em coberturas florestais tropicais, detecção de áreas de plantio de arroz irrigado e estimativa de umidade de solos.