A rapid aerodynamic prediction method for unconventional transonic aircraft configurations

This paper presents some results comparing the use of the Full Potential equations, coupled with the turbulent integral boundary layer equations for aircraft transonic cruise analysis. Use of such a method in the conceptual design stage is shown to be capable of yielding accurate enough data in a few minutes on a single processor, where Navier - Stokes simulations on 100+ processors take several days

Inflammatory mediators as biomarkers in brain disorders.

Neurodegenerative diseases such as Alzheimer, Parkinson, amyotrophic lateral sclerosis, and Huntington are incurable and debilitating conditions that result in progressive death of the neurons. The definite diagnosis of a neurodegenerative disorder is disadvantaged by the difficulty in obtaining biopsies and thereby to validate the clinical diagnosis with pathological results. Biomarkers are valuable indicators for detecting different phases of a disease such as prevention, early onset, treatment, progression, and monitoring the effect of pharmacological responses to a therapeutic intervention. Inflammation occurs in neurodegenerative diseases, and identification and validation of molecules involved in this process could be a strategy for finding new biomarkers. The ideal inflammatory biomarker needs to be easily measurable, must be reproducible, not subject to wide variation in the population, and unaffected by external factors. Our review summarizes the most important inflammation biomarkers currently available, whose specificity could be utilized for identifying and monitoring distinctive phases of different neurodegenerative diseases

GRAMMATICA APPLICATA: APPRENDIMENTO, PATOLOGIE, INSEGNAMENTO

Recension

NAFLD and Atherosclerosis Are Prevented by a Natural Dietary Supplement Containing Curcumin, Silymarin, Guggul, Chlorogenic Acid and Inulin in Mice Fed a High-Fat Diet

Non-alcoholic fatty liver disease (NAFLD) confers an increased risk of cardiovascular diseases. NAFDL is associated with atherogenic dyslipidemia, inflammation and renin-angiotensin system (RAS) imbalance, which in turn lead to atherosclerotic lesions. In the present study, the impact of a natural dietary supplement (NDS) containing Curcuma longa, silymarin, guggul, chlorogenic acid and inulin on NAFLD and atherosclerosis was evaluated, and the mechanism of action was examined. C57BL/6 mice were fed an HFD for 16 weeks; half of the mice were simultaneously treated with a daily oral administration (os) of the NDS. NAFLD and atherogenic lesions in aorta and carotid artery (histological analysis), hepatic expression of genes involved in the NAFLD (PCR array), hepatic angiotensinogen (AGT) and AT1R mRNA expression (real-time PCR) and plasma angiotensin (ANG)-II levels (ELISA) were evaluated. In the NDS group, steatosis, aortic lesions or carotid artery thickening was not observed. PCR array showed upregulation of some genes involved in lipid metabolism and anti-inflammatory activity (Cpt2, Ifng) and downregulation of some genes involved in pro-inflammatory response and in free fatty acid up-take (Fabp5, Socs3). Hepatic AGT, AT1R mRNA and ANG II plasma levels were significantly lower with respect to the untreated-group. Furthermore, NDS inhibited the dyslipidemia observed in the untreated animals. Altogether, these results suggest that NDS prevents NAFLD and atherogenesis by modulating the expression of different genes involved in NAFLD and avoiding RAS imbalance

Outcome following a short period of adalimumab dose escalation as rescue therapy in psoriatic patients

Background: Advances in biologic treatments have led to a new therapeutic frontier for moderate-to-severe psoriasis. Nevertheless, the efficacy of anti-TNFα decreases with time, requiring adjustments to maintain valuable Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) responses. Objectives: To evaluate the efficacy and safety of adalimumab dose escalation (40 mg, subcutaneous, once a week for 24 weeks) in psoriatic adult patients with secondary loss of response (PASI ≥50 to ≤75 or PASI≥75 and DLQI ≥5). Materials and Methods: A multicentre, observational study involving different Italian third-level referral centres for psoriasis enrolled a total of 64 adult patients with moderate-to-severe psoriasis who were treated with adalimumab and experienced a secondary loss of response. Primary end-points were PASI< 75 or PASI ≥50 to ≤ 75 with DLQI ≤ 5, and the secondary end-point was the ability to maintain a therapeutic response, resuming adalimumab every other week. Results: At Week 16 and Week 24, 29/64 (45.3%) and 35/64 (54.6%) responded based on PASI, and mean DLQI was 4.9 and 4.09, respectively. At Week 36 and Week 48, 45.3% and 28.1% patients achieved the second end-point, respectively. No adverse events were recorded except for one patient with recurrent tonsillitis. Conclusion: Adalimumab escalation could be considered in cases with loss of response before switching to alternative biologic therapy

How to improve educational behaviors for caregivers and patients having Central Venous Access Device (CVAD). a scoping review

Objective: Central venous access devices (CVADs) are essential to the modern management of patients with hematological malignancies and solid tumors. Educational programs play a crucial role in promoting appropriate patient actions to support patient safety during hospitalization and homecare. This review aimed to identify literature concerning educational interventions to promote patients’ actions to overcome CVAD-related problems and improve self-monitoring and self-management. Materials and Methods: Documentary evaluation of international databases, such as PubMed, CINAHL, Scopus and Cochrane. Searching for data on population, context and concept regarding CVAD self-management. The extracted data was subject to thematic analysis. The following scoping reviews were developed using the five-stage framework outlined by Arksey and O’Malley, and advanced by Levac and colleagues. Results: Of the 2802 articles identified, 19 research articles were selected in this review. Educational programs have been shown to improve CVAD self management, to decrease stress and anxiety related to their use, and to reduce the onset of complications. In addition, nurses have proven to be the professional reference figure for educational interventions. Conclusions: The results of the study lead to the conclusion that programs aimed at improving selfcare and reducing the onset of complications in patients living with chronic and debilitating diseases should be made available to a larger portion of individuals. Both generic and specific programs are needed, in the different contexts of home and hospital, for the short and long term, in order to ameliorate participants’ abilities. The results of this study should, therefore, encourage health professionals to plan, carry out, and evaluate the establishment of educational programs with patient participation

Machine Learning algorithm unveils glutamatergic alterations in the post-mortem schizophrenia brain

Schizophrenia is a disorder of synaptic plasticity and aberrant connectivity in which a major dysfunction in glutamate synapse has been suggested. However, a multi-level approach tackling diverse clusters of interacting molecules of the glutamate signaling in schizophrenia is still lacking. We investigated in the post-mortem dorsolateral prefrontal cortex (DLPFC) and hippocampus of schizophrenia patients and non-psychiatric controls, the levels of neuroactive d- and l-amino acids (l-glutamate, d-serine, glycine, l-aspartate, d-aspartate) by HPLC. Moreover, by quantitative RT-PCR and western blotting we analyzed, respectively, the mRNA and protein levels of pre- and post-synaptic key molecules involved in the glutamatergic synapse functioning, including glutamate receptors (NMDA, AMPA, metabotropic), their interacting scaffolding proteins (PSD-95, Homer1b/c), plasma membrane and vesicular glutamate transporters (EAAT1, EAAT2, VGluT1, VGluT2), enzymes involved either in glutamate-dependent GABA neurotransmitter synthesis (GAD65 and 67), or in post-synaptic NMDA receptor-mediated signaling (CAMKIIα) and the pre-synaptic marker Synapsin-1. Univariable analyses revealed that none of the investigated molecules was differently represented in the post-mortem DLPFC and hippocampus of schizophrenia patients, compared with controls. Nonetheless, multivariable hypothesis-driven analyses revealed that the presence of schizophrenia was significantly affected by variations in neuroactive amino acid levels and glutamate-related synaptic elements. Furthermore, a Machine Learning hypothesis-free unveiled other discriminative clusters of molecules, one in the DLPFC and another in the hippocampus. Overall, while confirming a key role of glutamatergic synapse in the molecular pathophysiology of schizophrenia, we reported molecular signatures encompassing elements of the glutamate synapse able to discriminate patients with schizophrenia and normal individuals

Machine Learning algorithm unveils glutamatergic alterations in the post-mortem schizophrenia brain

Schizophrenia is a disorder of synaptic plasticity and aberrant connectivity in which a major dysfunction in glutamate synapse has been suggested. However, a multi-level approach tackling diverse clusters of interacting molecules of the glutamate signaling in schizophrenia is still lacking. We investigated in the post-mortem dorsolateral prefrontal cortex (DLPFC) and hippocampus of schizophrenia patients and non-psychiatric controls, the levels of neuroactive d- and l-amino acids (l-glutamate, d-serine, glycine, l-aspartate, d-aspartate) by HPLC. Moreover, by quantitative RT-PCR and western blotting we analyzed, respectively, the mRNA and protein levels of pre- and post-synaptic key molecules involved in the glutamatergic synapse functioning, including glutamate receptors (NMDA, AMPA, metabotropic), their interacting scaffolding proteins (PSD-95, Homer1b/c), plasma membrane and vesicular glutamate transporters (EAAT1, EAAT2, VGluT1, VGluT2), enzymes involved either in glutamate-dependent GABA neurotransmitter synthesis (GAD65 and 67), or in post-synaptic NMDA receptor-mediated signaling (CAMKIIα) and the pre-synaptic marker Synapsin-1. Univariable analyses revealed that none of the investigated molecules was differently represented in the post-mortem DLPFC and hippocampus of schizophrenia patients, compared with controls. Nonetheless, multivariable hypothesis-driven analyses revealed that the presence of schizophrenia was significantly affected by variations in neuroactive amino acid levels and glutamate-related synaptic elements. Furthermore, a Machine Learning hypothesis-free unveiled other discriminative clusters of molecules, one in the DLPFC and another in the hippocampus. Overall, while confirming a key role of glutamatergic synapse in the molecular pathophysiology of schizophrenia, we reported molecular signatures encompassing elements of the glutamate synapse able to discriminate patients with schizophrenia and normal individuals

Abnormal RasGRP1 Expression in the Post-Mortem Brain and Blood Serum of Schizophrenia Patients

Schizophrenia (SCZ) is a polygenic severe mental illness. Genome-wide association studies (GWAS) have detected genomic variants associated with this psychiatric disorder and pathway analyses have indicated immune system and dopamine signaling as core components of risk in dorsolateral-prefrontal cortex (DLPFC) and hippocampus, but the mechanistic links remain unknown. The RasGRP1 gene, encoding for a guanine nucleotide exchange factor, is implicated in dopamine signaling and immune response. RasGRP1 has been identified as a candidate risk gene for SCZ and autoimmune disease, therefore representing a possible point of convergence between mechanisms involving the nervous and the immune system. Here, we investigated RasGRP1 mRNA and protein expression in post-mortem DLPFC and hippocampus of SCZ patients and healthy controls, along with RasGRP1 protein content in the serum of an independent cohort of SCZ patients and control subjects. Differences in RasGRP1 expression between SCZ patients and controls were detected both in DLPFC and peripheral blood of samples analyzed. Our results indicate RasGRP1 may mediate risk for SCZ by involving DLPFC and peripheral blood, thus encouraging further studies to explore its possible role as a biomarker of the disease and/or a target for new medication

Abnormal RasGRP1 Expression in the Post-Mortem Brain and Blood Serum of Schizophrenia Patients

Schizophrenia (SCZ) is a polygenic severe mental illness. Genome-wide association studies (GWAS) have detected genomic variants associated with this psychiatric disorder and pathway analyses have indicated immune system and dopamine signaling as core components of risk in dorsolateral-prefrontal cortex (DLPFC) and hippocampus, but the mechanistic links remain unknown. The RasGRP1 gene, encoding for a guanine nucleotide exchange factor, is implicated in dopamine signaling and immune response. RasGRP1 has been identified as a candidate risk gene for SCZ and autoimmune disease, therefore representing a possible point of convergence between mechanisms involving the nervous and the immune system. Here, we investigated RasGRP1 mRNA and protein expression in post-mortem DLPFC and hippocampus of SCZ patients and healthy controls, along with RasGRP1 protein content in the serum of an independent cohort of SCZ patients and control subjects. Differences in RasGRP1 expression between SCZ patients and controls were detected both in DLPFC and peripheral blood of samples analyzed. Our results indicate RasGRP1 may mediate risk for SCZ by involving DLPFC and peripheral blood, thus encouraging further studies to explore its possible role as a biomarker of the disease and/or a target for new medication