206 research outputs found

    The Apps for Justice Project: Employing Design Thinking to Narrow the Access to Justice Gap

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    The building materials’ and components’ database for an evidences-based design approach

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    The design process has always to meet, since the preliminary approaching step, every specific requirement which is foreseen for the building to realize. In a certain way, this operation represents an every time different prototype which varies according to the design demands for the considered room and the carried function, but also according to the used building materials: such an approach is already difficult by itself, but if we consider that at present the availability of technical information about building materials, components and systems is often incomplete or lost among many documents or even absent, it is evident that the designer’s activity becomes very uneven. That is the reason why, the definition of a database for building materials in which indicating each informative attribute to be considered becomes fundamental in order to: - provide a correct, univocal, clear and complete information for every building stakeholder; - help manufacturers to individualize the real needed information to join to their products, so to allow an easier comparison among products themselves and, as a consequence, to push towards a better quality of the entire building process (improving production, design, but also management). The paper deals with an analysis of the necessary information for designers and for maintenance planners, providing different levels of deepening according to the intended use. A particular attention will be paid on the so called “evidences-based design” which gives the opportunity to point out and to consider the most meaningful design matters, making an aware choice of building materials, components and systems. The International Service Life Data Base developed by CSTB with Politecnico di Milano will be reported as a tool for service life prediction, and buildings’ management

    Medial prefrontal cortex neuronal activation and synaptic alterations after stress-induced reinstatement of palatable food seeking: a study using c-fos-GFP transgenic female rats

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    Relapse to maladaptive eating habits during dieting is often provoked by stress and there is evidence for a role of ovarian hormones in stress responses and feeding. We studied the role of these hormones in stress-induced reinstatement of food seeking and medial prefrontal cortex (mPFC) neuronal activation in c-fos-GFP transgenic female rats, which express GFP in strongly activated neurons. Food-restricted ovariectomized or sham-operated c-fos-GFP rats were trained to lever-press for palatable food pellets. Subsequently, lever-pressing was extinguished and reinstatement of food seeking and mPFC neuronal activation was assessed after injections of the pharmacological stressor yohimbine (0.5-2 mg/kg) or pellet priming (1-4 noncontingent pellets). Estrous cycle effects on reinstatement were also assessed in wild-type rats. Yohimbine- and pellet-priming-induced reinstatement was associated with Fos and GFP induction in mPFC; both reinstatement and neuronal activation were minimally affected by ovarian hormones in both c-fos-GFP and wild-type rats. c-fos-GFP transgenic rats were then used to assess glutamatergic synaptic alterations within activated GFP-positive and nonactivated GFP-negative mPFC neurons following yohimbine-induced reinstatement of food seeking. This reinstatement was associated with reduced AMPA receptor/NMDA receptor current ratios and increased paired-pulse facilitation in activated GFP-positive but not GFP-negative neurons. While ovarian hormones do not appear to play a role in stress-induced relapse of food seeking in our rat model, this reinstatement was associated with unique synaptic alterations in strongly activated mPFC neurons. Our paper introduces the c-fos-GFP transgenic rat as a new tool to study unique synaptic changes in activated neurons during behavio

    Median-to-ulnar nerve communication in carpal tunnel syndrome: An electrophysiological study

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    The median-to-ulnar communicating branch (MUC) is an asymptomatic variant of the upper limb innervation that can lead to interpretation errors in routine nerve conduction studies. The diagnosis of carpal tunnel syndrome (CTS) or ulnar nerve lesions can be complicated by the presence of MUC. In this study, we describe electrophysiological features of MUC in CTS patients presenting to our clinic. We enrolled MUB cases from consecutive CTS patients referred to our laboratory between the years 2014 and 2019. MUC was present in 53 limbs (36 patients) from the studied population. MUC was bilateral in 53% of patients. MUC type II was the most common subtype (74%), followed by types III and I; more coexisting MUC types were found in the majority of tested limbs. A positive correlation was demonstrated between the severity of CTS and the presence of positive onset, faster CV, or a double component of the compound muscle action potentials. We emphasize the importance of suspecting the presence of MUC in CTS in the presence of a positive onset or a double component in routine motor conduction studies

    Nitrosylcobalamin Potentiates the Anti-Neoplastic Effects of Chemotherapeutic Agents via Suppression of Survival Signaling

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    Nitrosylcobalamin (NO-Cbl) is a chemotherapeutic pro-drug derived from vitamin B12 that preferentially delivers nitric oxide (NO) to tumor cells, based upon increased receptor expression. NO-Cbl induces Apo2L/TRAIL-mediated apoptosis and inhibits survival signaling in a variety of malignant cell lines. Chemotherapeutic agents often simultaneously induce an apoptotic signal and activation of NF-kappaB, which has the undesired effect of promoting cell survival. The specific aims of this study were to 1) measure the anti-tumor effects of NO-Cbl alone and in combination with conventional chemotherapeutic agents, and to 2) examine the mechanism of action of NO-Cbl as a single agent and in combination therapy.Using anti-proliferative assays, electrophoretic mobility shift assay (EMSA), immunoblot analysis and kinase assays, we demonstrate an increase in the effectiveness of chemotherapeutic agents in combination with NO-Cbl as a result of suppressed NF-kappaB activation.Eighteen chemotherapeutic agents were tested in combination with NO-Cbl, in thirteen malignant cell lines, resulting in a synergistic anti-proliferative effect in 78% of the combinations tested. NO-Cbl pre-treatment resulted in decreased NF-kappaB DNA binding activity, inhibition of IkappaB kinase (IKK) enzymatic activity, decreased AKT activation, increased caspase-8 and PARP cleavage, and decreased cellular XIAP protein levels.The use of NO-Cbl to inhibit survival signaling may enhance drug efficacy by preventing concomitant activation of NF-kappaB or AKT

    Inherited neuromuscular disorders: Which role for serum biomarkers?

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    Inherited neuromuscular disorders (INMD) are a heterogeneous group of rare diseases that involve muscles, motor neurons, peripheral nerves or the neuromuscular junction. Several different lab abnormalities have been linked to INMD: sometimes they are typical of the disorder, but they usually appear to be less specific. Sometimes serum biomarkers can point out abnormalities in presymtomatic or otherwise asymptomatic patients (e.g., carriers). More often a biomarker of INMD is evaluated by multiple clinicians other than expert in NMD before the diagnosis, because of the multisystemic involvement in INMD. The authors performed a literature search on biomarkers in inherited neuromuscular disorders to provide a practical approach to the diagnosis and the correct management of INMD. A considerable number of biomarkers have been reported that support the diagnosis of INMD, but the role of an expert clinician is crucial. Hence, the complete knowledge of such abnormalities can accelerate the diagnostic workup supporting the referral to specialists in neuromuscular disorders

    Comorbidity in myasthenia gravis: multicentric, hospital-based, and controlled study of 178 Italian patients

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    Background Myasthenia gravis (MG) is an autoimmune disorder with fluctuating weakness that causes significant disability and morbidity. Comorbidities may influence the course of MG, particularly in specific subgroups. The aim of this study is to investigate the frequency of comorbidities in MG patients compared to healthy controls (HC) and to evaluate their distribution according to age at disease onset, sex, and disease severity. Methods MG patients attending the University Hospital "Paolo Giaccone" in Palermo and "SS Annunziata" Hospital in Chieti were enrolled; HC were enrolled from the general population. Non-parametric statistics and logistic regression were used to assess the association of specific comorbidities according to age at disease onset, sex, disease subtypes, and severity of the disease. Results A total of 356 subjects were included in the study: 178 MG patients (46% F; median age 60 years [51-71]) and 178 sex- and age-matched HC (46% F, median age 59 years [50-66]). Overall, 86% of MG patients and 76% of HC suffered from comorbidities, and MG patients had a higher number of comorbidities compared to HC. Patients with late-onset suffered from more comorbidities than those with early-onset MG. Hypertension was more common in male patients with MG, while thymic hyperplasia, osteoporosis, and autoimmune diseases were more common in females. Respiratory disorders and thymoma were more common in patients with more severe disease (p < 0.05 for all comparisons). Conclusion MG patients, particularly those with late onset, showed a higher prevalence of comorbidities than HC. Assessment of comorbidities in MG is an essential issue to identify the appropriate treatment and achieve the best management

    Ventajas y riesgos del uso de pastas dentales con nanotecnologĂ­as

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    El presente artículo de actualización analiza las ventajas y riesgos del uso de nanopartículas en pastas dentales. La nanotecnología puede mejorar sus propiedades ayudando al proceso de remineralización del diente, controlar el crecimiento bacteriano o proporcionar minerales para mejorar el control del pH. Con este fin se han agregado: nanohidroxiapatita, nanocalcio, fosfato de calcio, trimetafosfato de sodio, nanopartículas de plata, quitosán, entre otras. Por otro lado, se han descripto algunos efectos nocivos de estas nanotecnologías, lo que nos motiva a intensificar su estudio. Conclusiones: La nano-odontología ha otorgado nuevas herramientas para la atención preventiva de la salud. La toxicidad oral para los nanodentífricos es baja, pero algunos pueden llegar al intestino, y a través de él a la circulación sanguínea y causar disturbios sistémicos. Es necesario profundizar las investigaciones en estos materiales, a fin de mejorar sus efectos beneficiosos, e identificar y eliminar sus riesgo

    Know Your Current Ih: Interaction with a Shunting Current Explains the Puzzling Effects of Its Pharmacological or Pathological Modulations

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    The non-specific, hyperpolarization activated, Ih current is particularly involved in epilepsy and it exhibits an excitatory or inhibitory action on synaptic integration in an apparently inconsistent way. It has been suggested that most of the inconsistencies could be reconciled invoking an indirect interaction with the M-type K+ current, another current involved in epilepsy. However, here we show that the original experiments, and the simplified model used to explain and support them, cannot explain in a conclusive way the puzzling Ih actions observed in different experimental preparations. Using a realistic model, we show instead how and why a shunting current, such as that carried by TASK-like channels, and dependent on Ih channel is able to explain virtually all experimental findings on Ih up- or down-regulation by modulators or pathological conditions. The model results suggest several experimentally testable predictions to characterize in more details this elusive and peculiar interaction, which may be of fundamental importance in the development of new treatments for all those pathological and cognitive dysfunctions caused, mediated, or affected by Ih
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