1,193 research outputs found
La ricerca della paternit\ue0 deve essere ammessa. La civilistica postunitaria e le riforme del diritto di famiglia. Questioni di diritto transitorio
La norma del codice civile italiano del 1865 che prevede il divieto di indagini sulla paternit\ue0 naturale costituisce una profonda innovazione, sia rispetto alla prassi giudiziaria medievale e moderna, sia rispetto alla legislazione preunitaria di primo Ottocento.
La circostanza determina un vasto dibattito dottrinale, con una forte corrente di civilisti impegnati nel chiedere una riforma del codice, ma produce anche una rilevante casistica giurisprudenziale, in relazione soprattutto alla risoluzione di questioni di diritto transitorio. Complessa in specie la situazione dei territori gi\ue0 appartenuti al Lombardo-Veneto e sottoposti in precedenza alla molto diversa disciplina dell\u2019 A. B. G. B. austriac
Impact of child obesity on adipose tissue physiology: assessment of adipocytokines and inflammatory cytokines as biomarkers of obesity
Obesity could be interpreted as a low grade inflammatory state. The role of cytokines for innate and acquired immune response and adipocytokines in pathogenesis of obesity is not completely understood. The aim of the study was to evaluate anthropometric parameters, adipocytokines and inflammatory cytokine levels as biomarkers of childhood obesity. This investigation was designed as a longitudinal observational study. Forty-seven obese children (19 males and 28 females) were enrolled by Pediatric Clinic of the Foundation IRCCS Policlinico San Matteo, Pavia, Italy. For each patients a blood sample, used for other biochemical evaluations, was collected. Cytokines and adipocytokines plasmatic levels were determined using an ELISA method. Plasma leptin levels are in correlation with age (r=0.5; P<0.001) and BMI-z score (r=0.36; P<0.001), particularly in girls; plasma resistin levels are in inverse correlation with age, particularly in boys (r=-0.67; P<0.001) and in correlation with BMI-z score (r=0.52; P=0.002). Plasma leptin and resistin levels show a good correlation with antrophometric parameters of child obesity (sex and BMI z score). This study suggests that leptin and resistin can be considered as biomarker of childhood obesity and its comorbility. We observed a statistically significant correlation between plasma leptin and resistin levels and antrophometric parameters of child obesity (sex and BMI z score). This study suggests that adipocytokines, such as leptin and resistin, can be considered as biomarkers of childhood obesity
Audience effect on domestic dogs’ behavioural displays and facial expressions
In the present study we investigated the infuence of positive and negative arousal situations and
the presence of an audience on dogs’ behavioural displays and facial expressions. We exposed dogs
to positive anticipation, non-social frustration and social frustration evoking test sessions and
measured pre and post-test salivary cortisol concentrations. Cortisol concentration did not increase
during the tests and there was no diference in pre or post-test concentrations in the diferent test
conditions, excluding a diferent level of arousal. Displacement behaviours of “looking away” and
“snifng the environment” occurred more in the frustration-evoking situations compared to the
positive anticipation and were correlated with cortisol concentrations. “Ears forward” occurred
more in the positive anticipation condition compared to the frustration-evoking conditions, was
positively infuenced by the presence of an audience, and negatively correlated to the pre-test cortisol
concentrations, suggesting it may be a good indicator of dogs’ level of attention. “Ears fattener”,
“blink”, “nose lick”, “tail wagging” and “whining” were associated with the presence of an audience
but were not correlated to cortisol concentrations, suggesting a communicative component of
these visual displays. These fndings are a frst step to systematically test which subtle cues could be
considered communicative signals in domestic dogs
Exome sequencing in schizophrenic patients with high levels of homozygosity identifies novel and extremely rare mutations in the GABA/glutamatergic pathways
Inbreeding is a known risk factor for recessive Mendelian diseases and previous studies have suggested that it could also play a role in complex disorders, such as psychiatric diseases. Recent inbreeding results in the presence of long runs of homozygosity (ROHs) along the genome, which are also defined as autozygosity regions. Genetic variants in these regions have two alleles that are identical by descent, thus increasing the odds of bearing rare recessive deleterious mutations due to a homozygous state. A recent study showed a suggestive enrichment of long ROHs in schizophrenic patients, suggesting that recent inbreeding could play a role in the disease. To better understand the impact of autozygosity on schizophrenia risk, we selected, from a cohort of 180 Italian patients, seven subjects with extremely high numbers of large ROHs that were likely due to recent inbreeding and characterized the mutational landscape within their ROHs using Whole Exome Sequencing and, gene set enrichment analysis. We identified a significant overlap (17%; empirical p-value = 0.0171) between genes inside ROHs affected by low frequency functional homozygous variants (107 genes) and the group of most promising candidate genes mutated in schizophrenia. Moreover, in four patients, we identified novel and extremely rare damaging mutations in the genes involved in neurodevelopment (MEGF8) and in GABA/glutamatergic synaptic transmission (GAD1, FMN1, ANO2). These results provide insights into the contribution of rare recessive mutations and inbreeding as risk factors for schizophrenia. ROHs that are likely due to recent inbreeding harbor a combination of predisposing low-frequency variants and extremely rare variants that have a high impact on pivotal biological pathways implicated in the disease. In addition, this study confirms that focusing on patients with high levels of homozygosity could be a useful prioritization strategy for discovering new high-impact mutations in genetically complex disorders
Novel bicistronic lentiviral vectors correct β-Hexosaminidase deficiency in neural and hematopoietic stem cells and progeny: implications for in vivo and ex vivo gene therapy of GM2 gangliosidosis.
Abstract The favorable outcome of in vivo and ex vivo gene therapy approaches in several Lysosomal Storage Diseases suggests that these treatment strategies might equally benefit GM2 gangliosidosis. Tay-Sachs and Sandhoff disease (the main forms of GM2 gangliosidosis) result from mutations in either the HEXA or HEXB genes encoding, respectively, the α- or β-subunits of the lysosomal β-Hexosaminidase enzyme. In physiological conditions, α- and β-subunits combine to generate β-Hexosaminidase A (HexA, αβ) and β-Hexosaminidase B (HexB, ββ). A major impairment to establishing in vivo or ex vivo gene therapy for GM2 gangliosidosis is the need to synthesize the α- and β-subunits at high levels and with the correct stoichiometric ratio, and to safely deliver the therapeutic products to all affected tissues/organs. Here, we report the generation and in vitro validation of novel bicistronic lentiviral vectors (LVs) encoding for both the murine and human codon optimized Hexa and Hexb genes. We show that these LVs drive the safe and coordinate expression of the α- and β-subunits, leading to supranormal levels of β-Hexosaminidase activity with prevalent formation of a functional HexA in SD murine neurons and glia, murine bone marrow-derived hematopoietic stem/progenitor cells (HSPCs), and human SD fibroblasts. The restoration/overexpression of β-Hexosaminidase leads to the reduction of intracellular GM2 ganglioside storage in transduced and in cross-corrected SD murine neural progeny, indicating that the transgenic enzyme is secreted and functional. Importantly, bicistronic LVs safely and efficiently transduce human neurons/glia and CD34+ HSPCs, which are target and effector cells, respectively, in prospective in vivo and ex vivo GT approaches. We anticipate that these bicistronic LVs may overcome the current requirement of two vectors co-delivering the α- or β-subunits genes. Careful assessment of the safety and therapeutic potential of these bicistronic LVs in the SD murine model will pave the way to the clinical development of LV-based gene therapy for GM2 gangliosidosis
Villa Ceriani e il suo parco, nuove idee per il riuso conservativo
Nel corso della primavera 2021 Villa Ceriani e il
parco sono stati oggetto delle analisi e dei progetti di conservazione
e riuso del corso e laboratori di restauro del Politecnico
di Milano, Polo territoriale di Lecco. L’efficace e fattiva collaborazione
con il Comune e soprattutto con la direttrice del Museo
archeologico di Erba ha permesso di mettere a fuoco le necessitĂ
e le aspettative delle amministrazioni pubbliche e dei cittadini
riguardo una delle piĂą prestigiose e ben conservate ville del territorio
comunale. I laboratori di restauro hanno permesso agli
studenti di approfondire la conoscenza del sito e dei manufatti
grazie al metodo rigoroso della conservazione.
I risultati sono stati molti e riguardano diversi aspetti. Innanzitutto,
gli studenti hanno affrontato la complessità che l’intervento
sul costruito storico implica negli aspetti applicativi.
Inoltre, la richiesta di continuo adattamento alle modalitĂ di
lavoro, (in classe, a distanza, per piccoli gruppi, raramente sul
posto, individualmente con momenti di discussione telematici,
ecc.) ha necessariamente sviluppato la capacitĂ di concentrazione
sull’obiettivo e di saper sfruttare, in modo flessibile, tutte
le risorse che venivano messe a disposizione o che occorreva
ricercare. Infine, le modalitĂ di comunicazione preferibilmente
on line hanno richiesto di svilupparne l’efficacia favorendo forme
espressive integrative (grafiche, fotografiche, di simulazione
via software) che hanno potenziato le capacitĂ trasversali alle
discipline curriculari del corso di Ingegneria edile - architettura
Nusinersen Induces Disease-Severity-Specific Neurometabolic Effects in Spinal Muscular Atrophy
Intrathecal delivery of Nusinersen-an antisense oligonucleotide that promotes survival motor neuron (SMN) protein induction-is an approved therapy for spinal muscular atrophy (SMA). Here, we employed nuclear magnetic resonance (NMR) spectroscopy to longitudinally characterize the unknown metabolic effects of Nusinersen in the cerebrospinal fluid (CSF) of SMA patients across disease severity. Modulation of amino acid metabolism is a common denominator of biochemical changes induced by Nusinersen, with distinct downstream metabolic effects according to disease severity. In severe SMA1 patients, Nusinersen stimulates energy-related glucose metabolism. In intermediate SMA2 patients, Nusinersen effects are also related to energy homeostasis but involve ketone body and fatty acid biosynthesis. In milder SMA3 patients, Nusinersen mainly modulates amino acid metabolism. Moreover, Nusinersen modifies the CSF metabolome of a more severe clinical group towards the profile of untreated SMA patients with milder disease. These findings reveal disease severity-specific neurometabolic signatures of Nusinersen treatment, suggesting a selective modulation of peripheral organ metabolism by this CNS-directed therapy in severe SMA patients
Identifying Trauma Patients in Need for Emergency Surgery in the Prehospital Setting: The Prehospital Prediction of In-Hospital Emergency Treatment (PROPHET) Study
Prehospital field triage often fails to accurately identify the need for emergent surgical or non-surgical procedures, resulting in inefficient resource utilization and increased costs. This study aimed to analyze prehospital factors associated with the need for emergent procedures (such as surgery or interventional angiography) within 6 h of hospital admission. Additionally, our goal was to develop a prehospital triage tool capable of estimating the likelihood of requiring an emergent procedure following hospital admission. We conducted a retrospective observational study, analyzing both prehospital and in-hospital data obtained from the Lombardy Trauma Registry. We conducted a multivariable logistic regression analysis to identify independent predictors of emergency procedures within the first 6 h from admission. Subsequently, we developed and internally validated a triage score composed of factors associated with the probability of requiring an emergency procedure. The study included a total of 3985 patients, among whom 295 (7.4%) required an emergent procedure within 6 h. Age, penetrating injury, downfall, cardiac arrest, poor neurological status, endotracheal intubation, systolic pressure, diastolic pressure, shock index, respiratory rate and tachycardia were identified as predictors of requiring an emergency procedure. A triage score generated from these predictors showed a good predictive power (AUC of the ROC curve: 0.81) to identify patients requiring an emergent surgical or non-surgical procedure within 6 h from hospital admission. The proposed triage score might contribute to predicting the need for immediate resource availability in trauma patients
Mindful approach to University education
A mindful approach to education and training could improve students' reflective capacities and have positive effects on clinical practice because it facilitates a helping relationship. The main aims of this study were to investigate whether participation in a mindful-based University training was associated with increases in mindfulness skills as measured by the 5-Facet M Questionnaire, and to present the Italian validation of the questionnaire. Sixty-seven students from the course Neuro and Psychomotor Therapy were enrolled. They filled in the self-administered 5-Facet M Questionnaire before and 1 month after a mindfulness-based training, focused on role-playing and followed by a feedback group discussion. The Italian version of the 5-Facet M Questionnaire had good psychometric properties. The pre- and post-training analysis showed a significant increase in the subscale 'Observing'. Findings suggest that role-playing and feedback group sessions are valid tools to improve students' mindfulness skills
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