Search

Introdução: O diagnóstico de tuberculose (TB) na infância fundamenta-se na aplicação de escore clínico. Febre é o sintoma mais frequente tanto na forma de TB pulmonar quanto extrapulmonar (TBE). A disseminação da TB associa-se ao comprometimento imunológico por doenças subjacentes ou ausência de vacinação levando a formas graves de TB/TBE. Este caso se inicia como febre de origem indeterminada (FOI) levando 17 meses para diagnosticar TB em aparelho auditivo (TBA) em criança, sexo, feminino, de 10 anos. Objetivo: Apresentar manifestações clínicas, diagnóstico e evolução de um caso raro de TBA. Método: Relato de caso baseado em dados clínicos e laboratoriais de prontuário. Resultados: Queixa inicial otalgia em orelha esquerda (OE) e febre tratada como otite média aguda em abril/2022 com amoxicilina com melhora. Recidiva otalgia, odinofagia e febre acima de 38°C intermitentes por 4 meses.Em junho/2022 inicia tosse produtiva, radiografia de tórax normal, tratada como IVAS. É internada por FOI, apresentou derrame pericárdico suspeito de endocardite, realizada punção de Marfan, culturas negativas, biópsia inconclusiva, investigação reumatológica suspeita de lúpus eritematoso sistêmico ou síndrome genética. Recebeu pulso terapia com corticoide que resolveu a febre, iniciou 1mg/kg/dia de prednisona uso contínuo. Evolui com hematúria, hipertensão arterial, apatia e fácies cushingoide. Março/2023 piora a otalgia, zumbido, hipoacusia e secreção purulenta em OE. Novamente internada, na tomografia de mastoide apresentou pólipo em orelha média esquerda, com bióspia excesional em julho/23: processo inflamatório granulomatoso com reação gigantocelular de tipo Langhans, necrotizante, com granulomas confluentes, pesquisa histoquímica para BAAR positiva. Manteve tosse produtiva, baciloscopia no escarro positiva. Foi iniciado rifampicina (R), isoniazida (H), pirazinamida, etambutol na fase de ataque, segue em fase de manutenção com RH. Realizado desmame de corticoide e hipotensores com remissão total da febre, dos sintomas otológicos, urinários, vasculares e psíquicos em 90 dias. No quarto mês houve drenagem de secreção purulenta pela cicatriz da punção de Marfan, sem fístula, com resolução em 40 dias, derrame pericárdico residual em ecocardiograma preservada função cardiológica. Segue em tratamento, mantendo ferida operatória retroauricular OE em cicatrização por segunda intenção. Conclusão: TBA foi a principal manifestação de TB disseminada isso mostra a importância de insistir na busca por TB/TBE na presença de FOI no Brasil.

Introdução: Tuberculose ocular (TO) é uma forma rara de tuberculose extrapulmonar (TE), tem apresentação clínica variável, apresenta poucos dados na literatura e o diagnóstico é realizado de forma presumida. Neste estudo levantamos dados de casos do Programa de Controle de Tuberculose (TB) de São Bernardo do Campo, SP. Objetivo: Análise do perfil epidemiológico dos casos de TO de um serviço de referência terciária para TB. Método: Foram analisados retrospectivamente casos diagnosticados e tratados no período de 01/01/2018 a 31/12/2023, através da plataforma TBWEB e prontuário. O diagnóstico de TO foi realizado segundo 3 critérios, dois obrigatórios para o início do tratamento: a) apresentação clínica oftalmológica, b) teste tuberculínico maior de 10mm (ou IGRA reagente); e o terceiro critério avaliado após 6 meses: c) resposta terapêutica. Os dados foram comparados com dados de literatura publicada. Resultados: Avaliou-se 35 casos de TO, correspondendo a 2,1% do total os casos de TB (1652) e 11,1% dos casos de TE (314), dados de literatura relatam 2% de TO em relação à frequência de TE. A faixa etária adulta entre 18 e 60 anos abrangeu 97,1%(34) dos casos. Quanto ao sexo 71,4%(25) femininos e 28,6%(10) masculinos. A forma clínica predominante 31,4%(11) foi uveíte unilateral, 20%(7) uveíte bilateral, 17,1%(6) esclerite unilateral e 8,6%(3) coriorretinites, outras apresentações somaram 22,9%(8) dos casos. Dos sintomas: 49%(17) relataram perda parcial da visão, 23%(8) turvação visual, 23%(8) hiperemia e 11%(4) dor ocular. Quanto à exposição 62,8%(22) eram não expostos para TB, 28,6%(10) eram contato de TB confirmado, 8,6%(3) trataram TB pulmonar. Das comorbidades:14,3%(5) diabetes. Diagnóstico diferencial: 48%(17) excluíram outras doenças infecciosas (HIV, CMV, sífilis e toxoplasmose) e 17,1%(6) excluíram doenças reumatológicas. O tratamento em 100%(35) dos casos foi: rifampicina, isoniazida, pirazinamida e etambutol, via oral; variando entre: 6 meses 40%(14) dos casos, 7 meses 8,6%(3), 9 meses 25,7%(9) e 12 meses 17,1%(6). Desfecho: 40%(14) apresentaram recuperação total, 28,6%(10) apresentaram melhora parcial dos sintomas, 20%(7) não melhoraram, 2,9%(1) mudaram o diagnóstico, 2,9%(1) perderam segmento por transferência, 5,7%(2) não houve registro no prontuário. Conclusão: TO apresentou frequência 5,5 vezes maior em relação aos dados de literatura, talvez por ser um serviço de referência regional. A resolutividade (total + parcial) de 68,6%(24) sugere a necessidade de investimentos em diagnóstico diferencial.

Abstract In this work, we investigated the oncogenic role of Streptococcus gallolyticus subsp. gallolyticus (SGG), a gut bacterium associated with colorectal cancer (CRC). We showed that SGG UCN34 accelerates colon tumor development in a chemically induced CRC murine model. Full proteome and phosphoproteome analysis of murine colons chronically colonized by SGG UCN34 revealed that 164 proteins and 725 phosphorylation sites were differentially regulated. Ingenuity Pathway Analysis (IPA) indicates a pro-tumoral shift specifically induced by SGG UCN34, as ~ 90% of proteins and phosphoproteins identified were associated with digestive cancer. Comprehensive analysis of the altered phosphoproteins using ROMA software revealed up-regulation of several cancer hallmark pathways such as MAPK, mTOR and integrin/ILK/actin, affecting epithelial and stromal colonic cells. Importantly, an independent analysis of protein arrays of human colon tumors colonized with SGG showed up-regulation of PI3K/Akt/mTOR and MAPK pathways, providing clinical relevance to our findings. To test SGG’s capacity to induce pre-cancerous transformation of the murine colonic epithelium, we grew ex vivo organoids which revealed unusual structures with compact morphology. Taken together, our results demonstrate the oncogenic role of SGG UCN34 in a murine model of CRC associated with activation of multiple cancer-related signaling pathways.

Wildfires have short- and long-term impacts on the geoenvironment, including the changes to biogeochemical and mechanical properties of soils, landfill stability, surface- and groundwater, air pollution, and vegetation. Climate change has increased the extent and severity of wildfires across the world. Simultaneously, anthropogenic activities—through the expansion of urban areas into wildlands, abandonment of rural practices, and accidental or intentional fire-inception activities—are also responsible for a majority of fires. This paper provides an overall review and critical appraisal of existing knowledge about processes induced by wildfires and their impact on the geoenvironment. Burning of vegetation leads to loss of root reinforcement and changes in soil hydromechanical properties. Also, depending on the fire temperature, soil can be rendered hydrophobic or hydrophilic and compromise soil nutrition levels, hinder revegetation, and, in turn, increase post-fire erosion and the debris flow susceptibility of hillslopes. In addition to direct hazards, wildfires pollute air and soil with smoke and fire suppression agents releasing toxic, persistent, and relatively mobile contaminants into the geoenvironment. Nevertheless, the mitigation of wildfires’ geoenvironmental impacts does not fit within the scope of this paper. In the end, and in no exhaustive way, some of the areas requiring future research are highlighted.

Abstract Background The development of e-health technologies for teleconsultation and exchange of knowledge is one of the core purposes of European Reference Networks (ERNs), including the ERN EURO-NMD for rare neuromuscular diseases. Within ERNs, the Clinical Patient Management System (CPMS) is a web-based platform that seeks to boost active collaboration within and across the network, implementing data sharing. Through CPMS, it is possible to both discuss patient cases and to make patients’ data available for registries and databases in a secure way. In this view, CPMS may be considered a sort of a temporary storage for patients’ data and an effective tool for data sharing; it facilitates specialists’ consultation since rare diseases (RDs) require multidisciplinary skills, specific, and outstanding clinical experience. Following European Union (EU) recommendation, and to promote the use of CPMS platform among EURO-NMD members, a twelve-month pilot project was set up to train the 15 Italian Health Care Providers (HCPs). In this paper, we report the structure, methods, and results of the teaching course, showing that tailored, ERN-oriented, training can significantly enhance the profitable use of the CPMS. Results Throughout the training course, 45 professionals learned how to use the many features of the CPMS, eventually opening 98 panels of discussion—amounting to 82% of the total panels included in the EURO-NMD. Since clinical, genetic, diagnostic, and therapeutic data of patients can be securely stored within the platform, we also highlight the importance of this platform as an effective tool to discuss and share clinical cases, in order to ease both case solving and data storing. Conclusions In this paper, we discuss how similar course could help implementing the use of the platform, highlighting strengths and weaknesses of e-health for ERNs. The expected result is the creation of a “map” of neuromuscular patients across Europe that might be improved by a wider use of CPMS.

ABSTRACTQuickly understanding the genomic changes that lead to pathogen emergence is necessary to launch mitigation efforts and reduce harm. In this study, we tracked in real time a 2022 bacterial plant disease outbreak in U.S. geraniums (Pelargonium × hortorum) caused by Xhp2022, a novel lineage of Xanthomonas hortorum. Genomes from 31 Xhp2022 isolates from seven states showed limited chromosomal variation and all contained a single plasmid (p93). Time tree and single nucleotide polymorphism whole-genome analysis estimated that Xhp2022 emerged within the last decade. The phylogenomic analysis determined that p93 resulted from the cointegration of three plasmids (p31, p45, and p66) found sporadically across isolates from previous outbreaks. Although p93 had a 49 kb nucleotide reduction, it retained putative fitness genes, which became predominant in the 2022 outbreak. Overall, we demonstrated, through rapid whole-genome sequencing and analysis, a recent, traceable event of genome reduction for niche adaptation typically observed over millennia in obligate and fastidious pathogens.IMPORTANCEThe geranium industry, valued at $4 million annually, faces an ongoing Xanthomonas hortorum pv. pelargonii (Xhp) pathogen outbreak. To track and describe the outbreak, we compared the genome structure across historical and globally distributed isolates. Our research revealed Xhp population has not had chromosome rearrangements since 1974 and has three distinct plasmids. In 2012, we found all three plasmids in individual Xhp isolates. However, in 2022, the three plasmids co-integrated into one plasmid named p93. p93 retained putative fitness genes but lost extraneous genomic material. Our findings show that the 2022 strain group of the bacterial plant pathogen Xanthomonas hortorum underwent a plasmid reduction. We also observed several Xanthomonas species from different years, hosts, and continents have similar plasmids to p93, possibly due to shared agricultural settings. We noticed parallels between genome efficiency and reduction that we see across millennia with obligate parasites with increased niche specificity.

Background: Dupilumab has been shown to be a safe and effective drug for the treatment of atopic dermatitis (AD) in children from 6 months to 11 years in randomized clinical trials. Aim: The aim of this real-life study was to determine the effectiveness in disease control and safety of dupilumab at W52 in moderate-to-severe AD children aged 6-11 years. Methods: All data were collected from 36 Italian dermatological or paediatric referral centres. Dupilumab was administered at label dosage with an induction dose of 300 mg on day 1 (D1), followed by 300 mg on D15 and 300 mg every 4 weeks (Q4W). Treatment effect was determined as overall disease severity, using EASI, P-NRS, S-NRS and c-DLQI at baseline, W16, W24, and W52. Ninety-six AD children diagnosed with moderate-to-severe AD and treated with dupilumab were enrolled. Results: Ninety-one (94.8%) patients completed the 52-week treatment period and were included in the study. A significant improvement in EASI score, P-NRS, S-NRS and c-DLQI was observed from baseline to weeks 16, 24 and 52. Conclusions: Our real-life data seem to confirm dupilumab effectiveness and safety in paediatric patients. Moreover, our experience highlighted that patients achieving clinical improvement at W16 preserved this condition over time.

Cytomegalovirus (CMV) is a highly prevalent pathogen that remains dormant in majority of the cases. Severe CMV infection is generally limited to immunocompromised hosts. While occasional cases of CMV hepatitis are observed in healthy immunocompetent hosts, it is very rare to find this associated with focal liver lesions mimicking malignancy. Cases of non-immunosuppressed CMV reactivation, CMV-associated liver lesions, and CMV-associated portal vein thrombosis have all been reported individually, we present a single case of CMV with all of these rare manifestations.

Abstract The monitoring and prediction of the groundwater level (GWL) significantly influence the landslide kinematics. Based on the long-term fluctuation characteristics of the GWL and the time lag of triggering factors, a dynamic prediction model of the GWL based on the Maximum information coefficient (MIC) algorithm and the long-term short-term memory (LSTM) model was proposed. The Sifangbei landslide in the Three Gorges Reservoir area (TGRA) in China, wherein eight GWL monitoring sensors were installed in different locations, was taken as a case study. The monitoring data represented that the fluctuation of the GWL has a specific time lag concerning the accumulated rainfall (AR) and the reservoir water level (RWL). In addition, there were spatial differences in the fluctuation of the GWL, which was controlled by the elevation and the micro landform. From January 19, 2015, to March 6, 2017, the measured data were used to set up the predicted models. The MIC algorithm was adopted to calculate the lag time of the GWL, the RWL, and the AR. The LSTM model is a time series prediction algorithm that can transmit historical information. The Gray wolf optimization (GWO) algorithm was used to seek the most suitable hyperparameter of the LSTM model under the specific prediction conditions. The single-factor GWO-LSTM model without considering triggering factors and the support vector machine regression (SVR) model were considered to compare the prediction results. The results indicate that the MIC-GWO-LSTM model reached the highest accuracy and improved the prediction accuracy by considering the factor selection process with the learner training process. The proposed MIC-GWO-LSTM model combines the advantages of each algorithm and effectively constructs the response relationship between the GWL fluctuation and triggering factors; it also provides a new exploration for the GWL prediction, monitoring, and early warning system in the TGRA.

Abstract This paper proposes a three-phase method that combines multi-source (i.e. topographic, thematic, monitoring) input data in a GIS environment to rank—at small (1:250,000) scale—administrative units (e.g. municipalities) based on their exposure to slow-moving landslide risk within a selected area (e.g. a region) and, accordingly, detect those primarily requiring mitigation measures. The method is applied in the Calabria region (southern Italy) where several municipalities are widely affected by slow-moving landslides that systematically cause damage to buildings and infrastructure networks resulting in significant economic losses. The results obtained are validated based on the information gathered from previous studies carried out at large (municipal) scale. The work undertaken represents a first, fundamental step of a wider circular approach that can profitably facilitate the decision makers in addressing the issue of the slow-moving landslide risk mitigation in a sustainable way.

Summary: Predicting the pathogenicity of acceptor splice-site variants outside the essential AG is challenging, due to high sequence diversity of the extended splice-site region. Critical analysis of 24,445 intronic extended acceptor splice-site variants reported in ClinVar and the Leiden Open Variation Database (LOVD) demonstrates 41.9% of pathogenic variants create an AG dinucleotide between the predicted branchpoint and acceptor (AG-creating variants in the AG exclusion zone), 28.4% result in loss of a pyrimidine at the −3 position, and 15.1% result in loss of one or more pyrimidines in the polypyrimidine tract. Pathogenicity of AG-creating variants was highly influenced by their position. We define a high-risk zone for pathogenicity: > 6 nucleotides downstream of the predicted branchpoint and >5 nucleotides upstream from the acceptor, where 93.1% of pathogenic AG-creating variants arise and where naturally occurring AG dinucleotides are concordantly depleted (5.8% of natural AGs). SpliceAI effectively predicts pathogenicity of AG-creating variants, achieving 95% sensitivity and 69% specificity. We highlight clinical examples showing contrasting mechanisms for mis-splicing arising from AG variants: (1) cryptic acceptor created; (2) splicing silencer created: an introduced AG silences the acceptor, resulting in exon skipping, intron retention, and/or use of an alternative existing cryptic acceptor; and (3) splicing silencer disrupted: loss of a deep intronic AG activates inclusion of a pseudo-exon. In conclusion, we establish AG-creating variants as a common class of pathogenic extended acceptor variant and outline factors conferring critical risk for mis-splicing for AG-creating variants in the AG exclusion zone, between the branchpoint and acceptor.

Ilena Pochiero,1 Fabrizio Calisti,1 Alessandro Comandini,1 Alessandra Del Vecchio,1 Isabella Costamagna,1 Maria Teresa Rosignoli,1 Agnese Cattaneo,1 Sasikiran Nunna,2 Ilaria Peduto,3 Franca Heiman,3 Hsiu-Ching Chang,2 Chi-Chang Chen,2 Christoph Correll4– 6 1Angelini Regulatory, Research & Development, Angelini Pharma S.p.A., Rome, Italy; 2IQVIA, Plymouth Meeting, PA, USA; 3IQVIA Solutions Italy S.r.l., RWS, Milan, Italy; 4Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany; 5Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA; 6Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USACorrespondence: Ilena PochieroAngelini Pharma S.p.A., Viale Amelia 70, Rome, ItalyEmail ilena.pochiero@angelinipharma.comPurpose: The primary objectives were to describe weight changes following initiation of lurasidone versus other antipsychotics and estimate the risk of clinically relevant (≥ 7%) weight changes.Patients and Methods: This retrospective, longitudinal comparative cohort study was based on electronic medical records (EMRs) of United States (US) adult patients with schizophrenia who were prescribed lurasidone or other antipsychotics as monotherapy between 1 April 2013 and 30 June 2019.Results: Overall, the study included 15,323 patients with a diagnosis of schizophrenia; 6.1% of patients received lurasidone, 60.4% received antipsychotics associated with a medium-high risk of weight gain (clozapine, olanzapine, quetiapine, risperidone, paliperidone) and 33.5% received antipsychotics with a low risk of weight gain (aripiprazole, first-generation antipsychotics, ziprasidone). Lurasidone was associated with the smallest proportion of patients experiencing clinically relevant weight gain and the greatest proportion of patients with clinically relevant weight loss. The risk of clinically relevant weight gain was numerically higher with all antipsychotics versus lurasidone and was statistically significant for olanzapine (hazard ratio [HR]=1.541; 95% confidence interval [CI]=1.121; 2.119; p=0.0078) versus lurasidone. The likelihood of ≥ 7% weight loss was significantly greater with lurasidone versus all antipsychotics (p< 0.05), except ziprasidone.Conclusion: This real-world study suggests that lurasidone has a lower risk of clinically relevant weight gain and a higher likelihood of clinically relevant weight loss than other commonly used antipsychotics.Keywords: retrospective studies, weight gain, real world clinical trials

Abstract Background Several studies have been focusing on the potential role of atmospheric pollutants in the diffusion and impact on health of Covid-19. This study’s objective was to estimate the association between ≤10 μm diameter particulate matter (PM10) exposure and the likelihood of experiencing pneumonia due to Covid-19 using individual-level data in Italy. Methods Information on Covid-19 patients was retrieved from the Italian IQVIA® Longitudinal Patient Database (LPD), a computerized network of general practitioners (GPs) including anonymous data on patients’ consultations and treatments. All patients with a Covid-19 diagnosis during March 18th, 2020 – June 30th, 2020 were included in the study. The date of first Covid-19 registration was the starting point of the 3-month follow-up (Index Date). Patients were classified based on Covid-19-related pneumonia registrations on the Index date and/or during follow-up presence/absence. Each patient was assigned individual exposure by calculating average PM10 during the 30-day period preceding the Index Date, and according to GP’s office province. A multiple generalized linear mixed model, mixed-effects logistic regression, was used to assess the association between PM10 exposure tertiles and the likelihood of experiencing pneumonia. Results Among 6483 Covid-19 patients included, 1079 (16.6%) had a diagnosis of pneumonia. Pneumonia patients were older, more frequently men, more health-impaired, and had a higher individual-level exposure to PM10 during the month preceding Covid-19 diagnosis. The mixed-effects model showed that patients whose PM10 exposure level fell in the second tertile had a 30% higher likelihood of having pneumonia than that of first tertile patients, and the risk for those who were in the third tertile was almost doubled. Conclusion The consistent findings toward a positive association between PM10 levels and the likelihood of experiencing pneumonia due to Covid-19 make the implementation of new strategies to reduce air pollution more and more urgent.

Giorgio Lorenzo Colombo,1 Franca Heiman,2 Ilaria Peduto2 1CEFAT - Department of Drug Sciences, University of Pavia, Pavia, Italy; 2Real World Solutions, IQVIA Solutions Italy S.r.l., Milan, ItalyCorrespondence: Ilaria PedutoIQVIA Solutions Italy S.r.l., Via Fabio Filzi 29, Milan, 20124, ItalyEmail ilaria.peduto@iqvia.comPurpose: Understand the demographics and clinical features of patients with osteoarthritis (OA), quantify healthcare resource utilization by OA patients, and estimate the annual direct medical costs per OA patient from a National Health Service (NHS) perspective in Italy.Patients and Methods: Retrospective observational cohort analysis using data from electronic medical records captured by the Italian IQVIA Longitudinal Patient Database (LPD). Only direct medical costs reimbursed by the NHS were considered. Patients were included if they received at least one diagnosis of OA during the period from January 1 to December 31, 2018. Each patient was observed for 3 years: a 24-month baseline period preceding the index date, and a 12-month follow-up period starting at the index date.Results: A total of 71,467 patients met inclusion criteria: 43.98% had not been prescribed NSAIDs/opioids, 40.76% had been prescribed NSAIDs, and 15.26% an opioid. Mean age was 71.36 years, and 68.2% of the patients were women. At least one comorbidity was present in 91.34% of the patients; 38.05% were newly diagnosed with OA. During 1-year of follow-up, 173,884 prescriptions with an associated diagnosis of OA were found: 47.36% had been prescribed an NSAID, 9.11% diclofenac, 8.30% codeine+paracetamol, and 7.32% ketoprofen. Nearly 15% of the patients had at least 1 request for a specialist visit and 23.82% had at least 1 request for exams. Orthopedic visits accounted for 60% of all specialist visits. Yearly mean costs per patient were € 622, for approximately € 2.5 billion per year in direct costs, considering 3.9 million patients with OA in Italy. Protheses were a major driver in annual costs: € 143.45 in patients without a prosthesis and € 10,090.91 in those with a joint prosthesis.Conclusion: This real-world analysis of direct costs of care of patients with OA in Italy confirms the substantial economic burden. Direct costs dramatically increased when joint replacement was needed.Keywords: osteoarthritis, costs, real-world, Italy

Slow-moving landslides are widespread natural hazards that can affect social and economic activities, causing damage to structures and infrastructures. This paper aims at proposing a procedure to analyze road damage induced by slow-moving landslides based on the joint use of landslide susceptibility maps, a road-damage database developed using Google Street View images and ground-displacement measurements derived from the interferometric processing of satellite SAR images. The procedure is applied to the municipalities of Vaglio Basilicata and Trivigno in the Basilicata region (southern Italy) following a matrix-based approach. First, a susceptibility analysis is carried out at the municipal scale, using data from landslide inventories and thematic information available over the entire municipalities. Then, the susceptibility index, the class of movement and the level of damage are calculated for the territorial units corresponding to the road corridors under investigation. Finally, the road networks are divided into stretches, each one characterized by a specific level of risk (or attention required) following the aggregation of the information provided by the performed analyses. The results highlight the importance of integrating all of these different approaches and data for obtaining quantitative information on the spatial and temporal behavior of slow-moving landslides affecting road networks.

ObjectiveBulimia nervosa (BN) and binge eating disorder (BED) are eating disorders (EDs) characterized by recurrent binge eating (BE) episodes. Overlap exists between ED diagnostic groups, with BE episodes presenting one clinical feature that occurs transdiagnostically. Neuroimaging of the responses of those with BN and BED to disorder-specific stimuli, such as food, is not extensively investigated. Furthermore, to our knowledge, there have been no previous published studies examining the neural response of individuals currently experiencing binge eating, to low energy foods. Our objective was to examine the neural responses to both low energy and high energy food images in three emotive categories (disgust; fear; and happy) in BN and BED participants.MethodsNineteen females with BN (n = 14) or BED (n = 5), comprising the binge eating group (BEG; N = 19), and 19 age-matched healthy control (HC)’s completed thorough clinical assessment prior to functional MRI (fMRI). Neural response to low energy and high energy foods and non-food images was compared between groups using whole-brain exploratory analyses, from which six regions of interest (ROI) were then selected: frontal, occipital, temporal, and parietal lobes; insula and cingulate.ResultsIn response to low energy food images, the BEG demonstrated differential neural responses to all three low energy foods categories (disgust; fear; and happy) compared to HCs. Correlational analyses found a significant association between frequency of binge episodes and diminished temporal lobe and greater occipital lobe response. In response to high energy food images, compared to HC’s, the BEG demonstrated significantly decreased neural activity in response to all high energy food images. The HC’s had significantly greater neural activity in the limbic system, occipital lobe, temporal lobe, frontal lobe, and limbic system in response to high energy food images.ConclusionResults in the low energy food condition indicate that binge frequency may be related to increased aberrant neural responding. Furthermore, differences were found between groups in all ROI’s except the insula. The neural response seen in the BEG to disgust food images may indicate disengagement with this particular stimuli. In the high energy food condition, results demonstrate that neural activity in BN and BED patients may decrease in response to high energy foods, suggesting disengagement with foods that may be more consistent with those consumed during a binge eating episode.

Transition zones between bridges and embankments are the most maintenance-prone locations in the road network of The Netherlands due to the very compressible soft soil layers that are widespread in the subsoil of the country. This aspect causes (differential) settlements at the ground surface, damage and maintenance costs for the road owner, and delays to road users. This paper provides the proof-of-concept of an innovative multi-source data-driven method based on the assimilation of both conventional settlement plate and satellite DInSAR data in numerical geotechnical modelling with the aim of supporting informed maintenance decisions.

Buildings in subsiding areas may suffer from settlements causing damages of different severity levels with high impact in terms of yearly economic losses. In these contexts, a systematic damage assessment jointly with continuous monitoring of relevant parameters (e.g. settlements exhibited by points located on the roof) can be extremely useful to control the building behaviour and develop forecasting models. In this regard, the paper presents the results of an integrated analysis carried out on a subsidence-affected urban area in the Netherlands where the availability of multi-temporal building damage surveys and a long DInSAR monitoring dataset allowed both retrieving quantitative empirical relationships between the cause (magnitude of the selected intensity parameter, IP) and the effect (recorded damage severity level, DL) and generating empirical fragility and vulnerability curves. The results pointed out the importance of considering the exact dating of the onset of building damage and the corresponding magnitude of the considered IP in the generation of quantitative forecasting models.

ABSTRACT Xylella fastidiosa (Xf) is a globally distributed plant-pathogenic bacterium. The primary control strategy for Xf diseases is eradicating infected plants; therefore, timely and accurate detection is necessary to prevent crop losses and further pathogen dispersal. Conventional Xf diagnostics primarily relies on quantitative PCR (qPCR) assays. However, these methods do not consider new or emerging variants due to pathogen genetic recombination and sensitivity limitations. We developed and tested a metagenomics pipeline using in-house short-read sequencing as a complementary approach for affordable, fast, and highly accurate Xf detection. We used metagenomics to identify Xf to the strain level in single- and mixed-infected plant samples at concentrations as low as 1 pg of bacterial DNA per gram of tissue. We also tested naturally infected samples from various plant species originating from Europe and the United States. We identified Xf subspecies in samples previously considered inconclusive with real-time PCR (quantification cycle [Cq], >35). Overall, we showed the versatility of the pipeline by using different plant hosts and DNA extraction methods. Our pipeline provides taxonomic and functional information for Xf diagnostics without extensive knowledge of the disease. This pipeline demonstrates that metagenomics can be used for early detection of Xf and incorporated as a tool to inform disease management strategies. IMPORTANCE Destructive Xylella fastidiosa (Xf) outbreaks in Europe highlight this pathogen’s capacity to expand its host range and geographical distribution. The current disease diagnostic approaches are limited by a multiple-step process, biases to known sequences, and detection limits. We developed a low-cost, user-friendly metagenomic sequencing tool for Xf detection. In less than 3 days, we were able to identify Xf subspecies and strains in field-collected samples. Overall, our pipeline is a diagnostics tool that could be easily extended to other plant-pathogen interactions and implemented for emerging plant threat surveillance.

Destructive Xylella fastidiosaXf

This paper focuses on the study of the Vögelsberg landslide located in the municipality of Wattens (Tyrol, Austria), which reactivated in 2016, causing damages to nearby buildings and infrastructures. Since the date of reactivation, a modern monitoring system has been implemented with the installation of in-situ geodetic automated tracking total stations (ATTS), an inclinometer and two piezometers. Here, we describe two distinctive methods, the Breaks for Additive Seasonal and Trend (BFAST) and the Vector Inclination Method (VIM) used to characterize the landslide from the kinematic and geometrical point of view. The main input data, used for both methods, derive from processing a stack of several Sentinel-1 differential interferograms with the Multiple Small Baseline Subset (MSBAS) 2D and 3D algorithms. BFAST allowed highlighting the seasonality of the phenomenon from the analysis of the time series as well as the trend and the breakpoints that identify the landslide reactivation phases. These latter were then correlated with the main triggering factors such as rain and snow melting. The application of the VIM through the exploitation of the MSBAS displacement vectors allowed the reconstruction of the depth of the landslide slip surface along both the longitudinal and transversal direction and, in turn, the evaluation of the volumes of material mobilized by the landslide. The results obtained further prove that procedures for the in-depth analysis of Multi-Temporal Interferometric Synthetic Aperture Radar (MT-InSAR) data can contribute to slow-moving landslide characterization, which represents a fundamental step for landslide hazard assessment within quantitative risk analyses.

Summary: Innate lymphoid cells (ILCs) have been shown to be significantly affected in the small intestine lamina propria and secondary lymphoid organs (SLOs) of conventional lymphopenic mice. How ILCs are regulated by adaptive immunity in SLOs remains unclear. In T cell-deficient mice, ILC2s are significantly increased in the mesenteric lymph nodes (MLNs) at the expense of CCR6+ ILC3s, which are nonetheless increased in the peripheral lymph nodes (PLNs). Here, we show that T cells regulate lymph node-resident ILCs in a tissue- and subset-specific way. First, reducing microbial colonization from birth restored CCR6+ ILC3s in the MLNs of T cell-deficient mice. In contrast, T cell reconstitution resulted in the contraction of both MLNs ILC2s and PLNs ILC3s, whereas antagonizing microbial colonization from birth had no impact on these populations. Finally, the accumulation of MLNs ILC2s was partly regulated by T cells through stroma-derived IL-33.

The paper investigates the changes in the physical, mechanical, and hydraulic properties of coarse-grained pyroclastic soils, considered under both wildfire-burned and laboratory heating conditions. The soil samples were collected on Mount “Le Porche” in the municipality of Siano (Campania Region, Southern Italy), hit by wildfires on 20 September 2019. The area is prone to fast-moving landslides, as testified by the disastrous events of 5–6 May 1998. The experimental results show that the analyzed surficial samples exhibited (i) grain size distribution variations due to the disaggregation of gravelly and sandy particles (mostly of pumice nature), (ii) chromatic changes ranging from black to reddish, (iii) changes in specific gravity in low-severity fire-burned soil samples different from those exposed to laboratory heating treatments; (iv) progressive reductions of shear strength, associated with a decrease in the cohesive contribution offered by the soil-root systems and, for more severe burns, even in the soil friction angle, and (v) changes in soil-water retention capacity. Although the analyses deserve further deepening, the appropriate knowledge on these issues could provide key inputs for geotechnical analyses dealing with landslide susceptibility on fire-affected slopes in unsaturated conditions.

This paper presents a mass movement inventory map at 1:5000 scale of the Verbicaro area (about 13 km2) located in the Calabria region (southern Italy). The Main Map results from the visual interpretation of aerial photographs, multi-temporal geomorphological field surveys, and field investigations of damage suffered by buildings. Some 53% of the study area is affected by a total of 252 landslides, comprising different types, state of activity, and size. The mapped landslides, mainly complex type, involve low-grade metamorphic rocks; among these, 15% are active and slow-move on pre-existing sliding surfaces. Moreover, out of 492 surveyed buildings, 347 are located on landslide-affected areas and experienced damages covering a broad range of severity levels. The Main Map can represent a useful tool for authorities in charge of land-use planning and urban management and can be used to pursue landslide risk analyses.

Abstract Background FPIES (Food Protein Induced Eneterolitis Syndrome) is a rare non IgE- mediated food allergy, usually affecting infants and children after first months of life. Clinical presentation is heterogeneous, usually characterised by repetitive vomiting and diarrhoea, lethargy, failure to thrive until to dehydration with hypotension and shock. The diagnosis is based on clinical criteria, after excludind other hypothetical conditions. Early recognition of FPIES is essential to set a correct dietatay management that is resolving for the patient. Case report We present the case of a 12 days old child who was admitted to the hospital for poor feeding, failure to thrive and severe metabolic acidosis. Conclusions The early onset of this case is peculiar and rember us to consider FPIES in differential diagnosis of newborn metabolica acidosis.

Fulvio Nisi,1 Antonio Galzerano,1 Gaetano Cicchitto,2 Francesco Puma,3 Vito Aldo Peduto1 1Department of Anesthesiology, Intensive Care and Pain Therapy Centre, 2Department of Pneumology and Respiratory Medicine, 3Department of Thoracic Surgery, AO Santa Maria della Misericordia, Perugia, Italy Background: There are still no clear guidelines in the literature on per procedural bronchoscopic management for anesthesiologists, and few relevant datasets are available. To obtain rapid recovery from anesthesia, it is often necessary to keep patients in the recovery room for several hours until they become clinically stable. In this study, we tested the hypothesis that the laryngeal mask airway (LMA) enables better respiratory and hemodynamic recovery than the oxygen face mask (FM) in patients undergoing rigid bronchoscopy. Methods: Twenty-one patients undergoing elective bronchoscopy of the upper airway were randomized to ventilation assistance with FM or LMA after a rigid bronchoscopy procedure under general anesthesia. The primary endpoint was duration of post-surgical recovery and the secondary endpoints were postoperative hemodynamic and respiratory parameters. Assessment of the study endpoints was performed by an intensive care specialist blinded to the method of ventilation used. The statistical analysis was performed using the Fisher’s Exact test for nominal data and the Student's t-test for continuous data. Results: There was no statistically significant difference in post-procedural time between the two groups (P=0.972). The recovery parameters were significantly better in the LMA group than in the FM group, with significantly fewer desaturation, hypotensive, and bradycardic events (P

Coxiella burnetii infection (Q fever) is a widespread zoonosis with low endemicity in Switzerland, therefore no mandatory public report was required. A cluster of initially ten human cases of acute Q fever infections characterized by prolonged fever, asthenia and mild hepatitis occurred in 2012 in the terraced vineyard of Lavaux. Epidemiological investigations based on patients’ interviews and veterinary investigations included environmental sampling as well as Coxiella-specific serological assay and molecular examinations (real-time PCR in vaginal secretions) of suspected sheep. These investigations demonstrated that 43% of sheep carried the bacteria whereas 30% exhibited anti-Coxiella antibodies. Mitigation measures, including limiting human contacts with the flock, hygiene measures, flock vaccination and a public official alert, have permitted the detection of four additional human cases and the avoidance of a much larger outbreak. Since November 2012, mandatory reporting of Q fever to Swiss public health authorities has been reintroduced. A close follow up of human cases will be necessary to identify chronic Q fever.

Testing innovative procedures and techniques to update landslide inventory maps is a timely topic widely discussed in the scientific literature. In this regard remote sensing techniques – such as the Synthetic Aperture Radar Differential Interferometry (DInSAR) – can provide a valuable contribution to studies concerning slow-moving landslides in different geological contexts all over the world. In this paper, DInSAR data are firstly analysed via an innovative approach aimed at enhancing both the exploitation and the interpretation of remote sensing information; then, they are complemented with the results of an accurate analysis of survey-recorded damage to facilities due to slow-moving landslides. In particular, after being separately analysed to provide independent landslide movement indicators, the two datasets are combined in a DInSAR-Damage matrix which can be used to update the state of activity of slow-moving landslides. Moreover, together with the information provided by geomorphological maps, the two datasets are proven to be useful in detecting unmapped phenomena. The potentialities of the adopted procedure are tested in an area of southern Italy where slow-moving landslides are widespread and accurately mapped by using geomorphological criteria.

The disease-modifying effects of target of rapamycin complex 1 (TORC1) inhibitors during different stages of polycystic kidney disease (PKD) are not well defined. In this study, male Lewis Polycystic Kidney Disease (LPK) rats (a genetic ortholog of human NPHP9, phenotypically characterised by diffuse distal nephron cystic growth) and Lewis controls received either vehicle (V) or sirolimus (S, 0.2 mg/kg by intraperitoneal injection 5 days per week) during the early (postnatal weeks 3 to 10) or late stages of disease (weeks 10 to 20). In early-stage disease, sirolimus reduced kidney enlargement (by 63%), slowed the rate of increase in total kidney volume (TKV) in serial MRI by 78.2% (LPK+V: 132.3±59.7 vs. LPK+S: 28.8±12.0% per week) but only partly reduced the percentage renal cyst area (by 19%) and did not affect the decline in endogenous creatinine clearance (CrCl) in LPK rats. In late-stage disease, sirolimus reduced kidney enlargement (by 22%) and the rate of increase in TKV by 71.8% (LPK+V: 13.1±6.6 vs. LPK+S: 3.7±3.7% per week) but the percentage renal cyst area was unaltered, and the CrCl only marginally better. Sirolimus reduced renal TORC1 activation but not TORC2, NF-κB DNA binding activity, CCL2 or TNFα expression, and abnormalities in cilia ultrastructure, hypertension and cardiac disease were also not improved. Thus, the relative treatment efficacy of TORC1 inhibition on kidney enlargement was consistent at all disease stages, but the absolute effect was determined by the timing of drug initiation. Furthermore, cystic microarchitecture, renal function and cardiac disease remain abnormal with TORC1 inhibition, indicating that additional approaches to normalise cellular dedifferentiation, inflammation and hypertension are required to completely arrest the progression of PKDs.

Since its introduction in the Italian market, oxycodone/naloxone has been used in the treatment of pain in an exclusive use of non-ICU patients, mainly due to its oral formulation. In critically ill patients undergoing infusive analgesic-sedation in ICU the drug is strongly affected by the abolition of swallowing reflex. We describe the case of a patient with lower limbs compartment syndrome by direct trauma with a rapid switch on third day of hospitalization from analgesic sedation using propofol-remifentanil to oxycodone/naloxone and pregabalin.

OBJECTIVE: An assessment protocol was applied to quantify and describe muscular strength and motor abilities of 32 patients with Duchenne muscular dystrophy (DMD), aged between 5 and 12 years on steroid therapy. METHOD: Assessments were made monthly for the first six months and with intervals of two months thereafter until the 14-month end point. The tests employed included: the Medical Research Council (MRC) scale; the Hammersmith motor ability score; maximum weight lift; timed rise from floor and nine-meter walk. RESULTS: The results showed that loss of muscular strength and motor abilities were slowed in comparison to that observed in the natural evolution of the disease according to the literature. CONCLUSION: We conclude that a swift and objective assessment may be performed using the MRC scale for lower limbs and trunk, the Hammersmith motor ability score, timed nine-meter walk and weight lifts.OBJETIVO: Um protocolo de avaliação foi aplicado com o objetivo de quantificar e descrever evolutivamente a força muscular e as habilidades motoras de 32 pacientes com distrofia muscular de Duchenne (DMD), com idades variando de 5 a 12 anos, em corticoterapia. MÉTODO: As avaliações foram aplicadas mensalmente durante os primeiros seis meses e bimensais até completar um período de 14 meses. Os testes empregados foram: escala da "Medical Research Council" (MRC); Hammersmith "motor ability score"; levantamento da carga máxima de peso; cronometragem do tempo para levantar-se do chão e percorrer nove metros. RESULTADOS: Os resultados demonstraram que a perda da força muscular e das habilidades motoras foi mais lenta do que a observada na evolução natural da doença, como descrito na literatura internacional. CONCLUSÃO: Concluímos que uma rápida e objetiva avaliação pode ser executada utilizando a escala MRC para membros inferiores e tronco, Hammersmith motor ability score, cronometragem do tempo para percorrer 9 metros.e o levantamento de peso.

There has been a growing recognition of the importance of reward processing in PTSD, yet little is known of the underlying neural networks. This study tested the predictions that (1) individuals with PTSD would display reduced responses to happy facial expressions in ventral striatal reward networks, and (2) that this reduction would be associated with emotional numbing symptoms. 23 treatment-seeking patients with Posttraumatic Stress Disorder were recruited from the treatment clinic at the Centre for Traumatic Stress Studies, Westmead Hospital, and 20 trauma-exposed controls were recruited from a community sample. We examined functional magnetic resonance imaging responses during the presentation of happy and neutral facial expressions in a passive viewing task. PTSD participants rated happy facial expression as less intense than trauma-exposed controls. Relative to controls, PTSD participants revealed lower activation to happy (-neutral) faces in ventral striatum and and a trend for reduced activation in left amygdala. A significant negative correlation was found between emotional numbing symptoms in PTSD and right ventral striatal regions after controlling for depression, anxiety and PTSD severity. This study provides initial evidence that individuals with PTSD have lower reactivity to happy facial expressions, and that lower activation in ventral striatal-limbic reward networks may be associated with symptoms of emotional numbing.

Background. The behaviour of isobaric levobupivacaine in relation to gravity when used in obstetric spinal anesthesia is unclear. Methods. 46 women with ASA physical status 1 undergoing cesarean section were randomly allocated to 2 groups. Spinal anesthesia with 12.5 mg levobupivacaine was performed in the sitting position in all women. Those in the first group were placed in the supine position immediately after the injection, while those in the second group were asked to remain seated for 2 minutes before assuming the supine position. The sensory block level, the onset of sensory and motor blocks, the regression of the sensory block for 2 dermatomes of the sensory block, the first request for analgesics, and the regression of motor block were recorded. Results. No differences in onset times, sensory level, or Bromage score were observed between the two groups. The time of first analgesic request was earlier in the seated group (supine 131±42 min, seated 106±29 min, 𝑃=.02). Conclusion. Isobaric levobupivacaine in women at term produces a subarachnoid block the dermatomal level of which does not depend on gravitational forces.

This paper reports observations on the relationship between the yearly incidence of manifest esca (i.e. diseased plants which show foliar symptoms), hidden esca (that which remains asymptomatic throughout a growing season) and rainfall. Data from three vineyards (two in Tuscany and one in Emilia-Romagna, Italy) showed that rainfall in May–July or only in July was inversely related with hidden esca. For two vineyards, TB in Emilia-Romagna and CAR-3 in Tuscany, the spatial pattern of diseased vines in the first year of appearance of the foliar esca symptoms was also determined. The maps of the vines in these vineyards indicated that diseased plants mostly occurred alone. This suggests that the disease had its origin in infected rooted cuttings or was triggered by inoculum aerially dispersed from distant sources and/or occurring, at least in hypothesis, in the soil.

In mammals, liver size is related to animal body weight at the 2.5 to 3% proportion, a ratio mediated by the afflux of hepatotrophic factors. Formulas capable of modifying this ratio have been developed in previous studies on the rat, with enhancement of liver size brought about by intraperitoneal (portal) infusion of exogenous factors such as glucose, amino acids, insulin, glucagon, vitamins, electrolytes, and triiodothyronine. However, the efficacy of these formulations was accompanied by increased animal mortality (PARRA et al.19,20 ). The present study, which was carried out with small methodological modifications on a larger number of rats using daily intraperitoneal injections of a solution of exogenous hepatotrophic factors (40 ml/kg) for seven days, confirms the previous findings, with a 114.16 ± 7.90% enhancement of liver size beyond the expected value for the body weight of the animal. However, the problem of animal mortality was not fully resolved.

We studied the effects of protein-energy malnutrition on the liver morphology of rats as compared to animal emaciation and to reduction in size of the organs not irrigated by splanchnic blood such as kidneys and spleen. The animals were divided into two groups, one of them fed ad libitum rate (N=10) and the other (N=14) receiving water but no food for 7 days, and the changes in animal weight, liver, kidney and spleen mass were determined. DNA and the protein/DNA ratio, as well as hepatocyte size, were determined in liver tissue. The liver decreased in mass (27.14%) at a significantly higher proportion (p