Microbiological characteristics of poultry meats - Results of inspections carried out in the province of Milano, Italy

Examinations were conducted in terms of microbiological quality/quantity (TMC, Coliforms, E. coli, S. aureus, Sulphate-reducing Clostridia, B. cereus, Salmonella spp. and Lysteria spp. and Campylobacter spp.) on 240 poultry meat samples (chicken, turkey and quail) acquired pursuant to the standards set by the Regional Plan of programming and coordination in the field of operations concerning official inspections of Lombardia animal origin and by a few private companies for self-inspection. The TMC was consistently low and in line with reports in the literature, as was the case with coliforms, E. coli, S. aureus, sulphatereducing Clostrides and B. cereus. In the case of Salmonella spp., only 5 samples tested positive: one for S. typhimurium and one for S. enteritidis (chicken); only one sample from turkey tested positive for S. blokley, and two out of five samples analysed from quail tested positive result for S. typhimurium. About 3% of the samples analyzed tested positive for Listeria monocitogenes, but they were within the legal limits. Research on Campylobacter thermophiles has involved only 50 samples, of which only 5 have tested positive. These results confirm the high quality of hygiene and cleanliness of poultry meat, in accordance with that reported in the national literature and with respect to EU norms

Genetic interaction screen for severe neurodevelopmental disorders reveals a functional link between Ube3a and Mef2 in Drosophila melanogaster

Neurodevelopmental disorders (NDDs) are clinically and genetically extremely heterogeneous with shared phenotypes often associated with genes from the same networks. Mutations in TCF4, MEF2C, UBE3A, ZEB2 or ATRX cause phenotypically overlapping, syndromic forms of NDDs with severe intellectual disability, epilepsy and microcephaly. To characterize potential functional links between these genes/proteins, we screened for genetic interactions in Drosophila melanogaster. We induced ubiquitous or tissue specific knockdown or overexpression of each single orthologous gene (Da, Mef2, Ube3a, Zfh1, XNP) and in pairwise combinations. Subsequently, we assessed parameters such as lethality, wing and eye morphology, neuromuscular junction morphology, bang sensitivity and climbing behaviour in comparison between single and pairwise dosage manipulations. We found most stringent evidence for genetic interaction between Ube3a and Mef2 as simultaneous dosage manipulation in different tissues including glia, wing and eye resulted in multiple phenotype modifications. We subsequently found evidence for physical interaction between UBE3A and MEF2C also in human cells. Systematic pairwise assessment of the Drosophila orthologues of five genes implicated in clinically overlapping, severe NDDs and subsequent confirmation in a human cell line revealed interactions between UBE3A/Ube3a and MEF2C/Mef2, thus contributing to the characterization of the underlying molecular commonalities

Quantitative MRI Harmonization to Maximize Clinical Impact: The RIN-Neuroimaging Network

Neuroimaging studies often lack reproducibility, one of the cardinal features of the scientific method. Multisite collaboration initiatives increase sample size and limit methodological flexibility, therefore providing the foundation for increased statistical power and generalizable results. However, multisite collaborative initiatives are inherently limited by hardware, software, and pulse and sequence design heterogeneities of both clinical and preclinical MRI scanners and the lack of benchmark for acquisition protocols, data analysis, and data sharing. We present the overarching vision that yielded to the constitution of RIN-Neuroimaging Network, a national consortium dedicated to identifying disease and subject-specific in-vivo neuroimaging biomarkers of diverse neurological and neuropsychiatric conditions. This ambitious goal needs efforts toward increasing the diagnostic and prognostic power of advanced MRI data. To this aim, 23 Italian Scientific Institutes of Hospitalization and Care (IRCCS), with technological and clinical specialization in the neurological and neuroimaging field, have gathered together. Each IRCCS is equipped with high- or ultra-high field MRI scanners (i.e., ≥3T) for clinical or preclinical research or has established expertise in MRI data analysis and infrastructure. The actions of this Network were defined across several work packages (WP). A clinical work package (WP1) defined the guidelines for a minimum standard clinical qualitative MRI assessment for the main neurological diseases. Two neuroimaging technical work packages (WP2 and WP3, for clinical and preclinical scanners) established Standard Operative Procedures for quality controls on phantoms as well as advanced harmonized quantitative MRI protocols for studying the brain of healthy human participants and wild type mice. Under FAIR principles, a web-based e-infrastructure to store and share data across sites was also implemented (WP4). Finally, the RIN translated all these efforts into a large-scale multimodal data collection in patients and animal models with dementia (i.e., case study). The RIN-Neuroimaging Network can maximize the impact of public investments in research and clinical practice acquiring data across institutes and pathologies with high-quality and highly-consistent acquisition protocols, optimizing the analysis pipeline and data sharing procedures

Differential diagnosis of neurodegenerative dementias with the explainable MRI based machine learning algorithm MUQUBIA

Biomarker-based differential diagnosis of the most common forms of dementia is becoming increasingly important. Machine learning (ML) may be able to address this challenge. The aim of this study was to develop and interpret a ML algorithm capable of differentiating Alzheimer's dementia, frontotemporal dementia, dementia with Lewy bodies and cognitively normal control subjects based on sociodemographic, clinical, and magnetic resonance imaging (MRI) variables. 506 subjects from 5 databases were included. MRI images were processed with FreeSurfer, LPA, and TRACULA to obtain brain volumes and thicknesses, white matter lesions and diffusion metrics. MRI metrics were used in conjunction with clinical and demographic data to perform differential diagnosis based on a Support Vector Machine model called MUQUBIA (Multimodal Quantification of Brain whIte matter biomArkers). Age, gender, Clinical Dementia Rating (CDR) Dementia Staging Instrument, and 19 imaging features formed the best set of discriminative features. The predictive model performed with an overall Area Under the Curve of 98%, high overall precision (88%), recall (88%), and F1 scores (88%) in the test group, and good Label Ranking Average Precision score (0.95) in a subset of neuropathologically assessed patients. The results of MUQUBIA were explained by the SHapley Additive exPlanations (SHAP) method. The MUQUBIA algorithm successfully classified various dementias with good performance using cost-effective clinical and MRI information, and with independent validation, has the potential to assist physicians in their clinical diagnosis

Colchicine for prevention of postpericardiotomy syndrome and postoperative atrial fibrillation : the COPPS-2 randomized clinical trial

IMPORTANCE: Postpericardiotomy syndrome, postoperative atrial fibrillation (AF), and postoperative effusions may be responsible for increased morbidity and health care costs after cardiac surgery. Postoperative use of colchicine prevented these complications in a single trial. OBJECTIVE: To determine the efficacy and safety of perioperative use of oral colchicine in reducing postpericardiotomy syndrome, postoperative AF, and postoperative pericardial or pleural effusions. DESIGN, SETTING, AND PARTICIPANTS: Investigator-initiated, double-blind, placebo-controlled, randomized clinical trial among 360 consecutive candidates for cardiac surgery enrolled in 11 Italian centers between March 2012 and March 2014. At enrollment, mean age of the trial participants was 67.5 years (SD, 10.6 years), 69% were men, and 36% had planned valvular surgery. Main exclusion criteria were absence of sinus rhythm at enrollment, cardiac transplantation, and contraindications to colchicine. INTERVENTIONS: Patients were randomized to receive placebo (n=180) or colchicine (0.5 mg twice daily in patients 6570 kg or 0.5 mg once daily in patients <70 kg; n=180) starting between 48 and 72 hours before surgery and continued for 1 month after surgery. MAIN OUTCOMES AND MEASURES: Occurrence of postpericardiotomy syndrome within 3 months; main secondary study end points were postoperative AF and pericardial or pleural effusion. RESULTS: The primary end point of postpericardiotomy syndrome occurred in 35 patients (19.4%) assigned to colchicine and in 53 (29.4%) assigned to placebo (absolute difference, 10.0%; 95% CI, 1.1%-18.7%; number needed to treat\u2009=\u200910). There were no significant differences between the colchicine and placebo groups for the secondary end points of postoperative AF (colchicine, 61 patients [33.9%]; placebo, 75 patients [41.7%]; absolute difference, 7.8%; 95% CI, -2.2% to 17.6%) or postoperative pericardial/pleural effusion (colchicine, 103 patients [57.2%]; placebo, 106 patients [58.9%]; absolute difference, 1.7%; 95% CI, -8.5% to 11.7%), although there was a reduction in postoperative AF in the prespecified on-treatment analysis (placebo, 61/148 patients [41.2%]; colchicine, 38/141 patients [27.0%]; absolute difference, 14.2%; 95% CI, 3.3%-24.7%). Adverse events occurred in 21 patients (11.7%) in the placebo group vs 36 (20.0%) in the colchicine group (absolute difference, 8.3%; 95% CI; 0.76%-15.9%; number needed to harm\u2009=\u200912), but discontinuation rates were similar. No serious adverse events were observed. CONCLUSIONS AND RELEVANCE: Among patients undergoing cardiac surgery, perioperative use of colchicine compared with placebo reduced the incidence of postpericardiotomy syndrome but not of postoperative AF or postoperative pericardial/pleural effusion. The increased risk of gastrointestinal adverse effects reduced the potential benefits of colchicine in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT0155218

Food for pollinators: quantifying the nectar and pollen resources of urban flower meadows

Planted meadows are increasingly used to improve the biodiversity and aesthetic amenity value of urban areas. Although many ‘pollinator-friendly’ seed mixes are available, the floral resources these provide to flower-visiting insects, and how these change through time, are largely unknown. Such data are necessary to compare the resources provided by alternative meadow seed mixes to each other and to other flowering habitats. We used quantitative surveys of over 2 million flowers to estimate the nectar and pollen resources offered by two exemplar commercial seed mixes (one annual, one perennial) and associated weeds grown as 300m2 meadows across four UK cities, sampled at six time points between May and September 2013. Nectar sugar and pollen rewards per flower varied widely across 65 species surveyed, with native British weed species (including dandelion, Taraxacum agg.) contributing the top five nectar producers and two of the top ten pollen producers. Seed mix species yielding the highest rewards per flower included Leontodon hispidus, Centaurea cyanus and C. nigra for nectar, and Papaver rhoeas, Eschscholzia californica and Malva moschata for pollen. Perennial meadows produced up to 20x more nectar and up to 6x more pollen than annual meadows, which in turn produced far more than amenity grassland controls. Perennial meadows produced resources earlier in the year than annual meadows, but both seed mixes delivered very low resource levels early in the year and these were provided almost entirely by native weeds. Pollen volume per flower is well predicted statistically by floral morphology, and nectar sugar mass and pollen volume per unit area are correlated with flower counts, raising the possibility that resource levels can be estimated for species or habitats where they cannot be measured directly. Our approach does not incorporate resource quality information (for example, pollen protein or essential amino acid content), but can easily do so when suitable data exist. Our approach should inform the design of new seed mixes to ensure continuity in floral resource availability throughout the year, and to identify suitable species to fill resource gaps in established mixes

The care response to the health needs of people with intellectual disabilities: a proposal to apply the DAMA (Disabled Advanced Medical Assistance) model

reservedIntroduzione: Il seguente studio di tesi si propone di analizzare una possibile applicazione del modello DAMA (Disabled Advanced Medical Assistance) in un’Organizzazione Sanitaria per garantire un migliore accesso alle prestazioni sanitarie delle persone con disabilità intellettive. Inizialmente è stata svolta una revisione della letteratura per esaminare i bisogni di salute delle persone con disabilità intellettiva. Successivamente, attraverso l’analisi dei percorsi diagnostico-terapeutici a livello internazionale e italiano è stato approfondito il modello DAMA. Infine, viene presentato il contesto organizzativo dell’Azienda ULSS 2 Marca Trevigiana, in relazione alla risposta assistenziale fornita alle persone con disabilità intellettiva. Materiali e metodi: Viene descritta la metodologia di ricerca, avvenuta in primo luogo consultando la documentazione aziendale e il sito web dell’Azienda ULSS 2. Viene in seguito svolta un’intervista alla Coordinatrice del Centro per l’Autismo e somministrato un questionario ai caregiver delle persone con disabilità intellettiva che frequentano i Centri Diurni per Disabili a gestione diretta dell’Azienda trevigiana, distretto di Treviso, al fine di far emergere i bisogni di salute percepiti. Dai dati raccolti dall’analisi contestuale, dall’intervista e dal questionario sono emersi dei bisogni che hanno permesso la strutturazione del progetto. Proposta operativa: Viene presentata una proposta per l’applicazione del modello DAMA e viene illustrato il processo di decision making che ha orientato la scelta degli interventi prioritari. Il progetto si concentra sulla formazione del personale sanitario riguardo ai percorsi di presa in carico diagnostico-terapeutica delle persone con disabilità intellettiva grave all’interno di strutture sanitarie. Inoltre, prevede l’implementazione sperimentale del “Passaporto per la persona disabile in ospedale”. Nel contesto del progetto, vengono delineate le modalità di applicazione e definiti i possibili risultati attesi. Discussione: Viene sviluppata una lettura critica del progetto, concentrandosi sulle proposte e valutando sia i punti di forza che i limiti di queste. Si identificano possibili sviluppi futuri. L’outcome auspicato è quello di migliorare la presa in carico delle persone con disabilità nel contesto diagnostico-terapeutico. Conclusioni: Questo studio enfatizza l’importanza di creare percorsi diagnostico-terapeutici su misura per le persone con disabilità intellettiva grave, al fine di garantire il loro diritto alla salute. Anche se l’intervento rimane attualmente una proposta, ci si augura che possa essere attuato e rappresenti un passo in avanti verso il miglioramento della qualità di vita delle persone con disabilità.Introduction: The following thesis study aims to analyze a potential application of the DAMA model (Disabled Advanced Medical Assistance) within a Healthcare Organization to ensure better access to healthcare services for individuals with intellectual disabilities. Initially, a literature review was conducted to examine the healthcare needs of individuals with intellectual disabilities. Subsequently, through the analysis of diagnostic-therapeutic pathways at both international and Italian levels, the DAMA model was explored. Finally, the organizational context of the ULSS 2 Marca Trevigiana is presented in relation to the healthcare response provided to individuals with intellectual disabilities. Materials and methods: The research methodology is described, which firstly took place by consulting the company documentation and the website of Azienda ULSS 2. An interview was then carried out with the Coordinator of the Autism Centre and a questionnaire was administered to the caregivers of people with intellectual disabilities attending the Day Centres for the Disabled under direct management of the Azienda trevigiana, Treviso district, in order to bring out the perceived health needs. From the data collected from the contextual analysis, the interview and the questionnaire, needs emerged which allowed the structuring of the project. Operational proposal: A proposal for the application of the DAMA model is presented and the decision-making process that guided the choice of priority interventions is illustrated. The project focuses on the training of healthcare personnel on the diagnostic-therapeutic care pathways for people with severe intellectual disabilities in healthcare facilities. Furthermore, it envisages the experimental implementation of the 'Passport for the disabled person in hospital'. In the context of the project, implementation methods are outlined and possible expected results are defined. Discussion: A critical analysis of the project is developed, with a focus on its proposals and an evaluation of both their strengths and limitations. Possible future developments are identified. The desired outcome is to improve the care of individuals with disabilities within the diagnostic-therapeutic context. Conclusions: This study emphasises the importance of creating tailored diagnostic-therapeutic pathways for people with severe intellectual disability in order to guarantee their right to health. Although the intervention currently remains a proposal, it is hoped that it can be implemented and represents a step towards improving the quality of life of people with disabilities

Loss of PHF6 leads to aberrant development of human neuron-like cells

Pathogenic variants in PHD finger protein 6 (PHF6) cause Borjeson-Forssman-Lehmann syndrome (BFLS), a rare X-linked neurodevelopmental disorder, which manifests variably in both males and females. To investigate the mechanisms behind overlapping but distinct clinical aspects between genders, we assessed the consequences of individual variants with structural modelling and molecular techniques. We found evidence that de novo variants occurring in females are more severe and result in loss of PHF6, while inherited variants identified in males might be hypomorph or have weaker effects on protein stability. This might contribute to the different phenotypes in male versus female individuals with BFLS. Furthermore, we used CRISPR/Cas9 to induce knockout of PHF6 in SK-N-BE (2) cells which were then differentiated to neuron-like cells in order to model nervous system related consequences of PHF6 loss. Transcriptome analysis revealed a broad deregulation of genes involved in chromatin and transcriptional regulation as well as in axon and neuron development. Subsequently, we could demonstrate that PHF6 is indeed required for proper neuron proliferation, neurite outgrowth and migration. Impairment of these processes might therefore contribute to the neurodevelopmental and cognitive dysfunction in BFLS