ACE Gene I/D Polymorphism and Acute Pulmonary Embolism in COVID19 Pneumonia: A Potential Predisposing Role

Most recent studies have stressed a high risk of thromboembolism in patients with SARS-CoV-2 infection, particularly in those with severe COVID-19 pneumonia. Counterbalance between angiotensin-converting-enzyme (ACE) and ACE2 activities in COVID-19 disease may be crucially involved in the thrombo-inflammatory process. Currently, no study has investigated ACE I/D polymorphism involvement in COVID-19 disease complicated by pulmonary embolism, hence the aim of the present pilot study. This is a retrospective, single-center observational case-control study, conducted at the Sub-Intensive Care Unit of A.O.R.N. Ospedali dei Colli, Cotugno Hospital, Naples (Italy). We included 68 subjects with severe/critical COVID-19 pneumonia. COVID-19 patients were divided according to occurrence of PE (PE+, n = 25) or absence of thromboembolic complications (PE−, n = 43). Assessment of ACE I/D polymorphisms showed a statistically significant difference between PE+ and PE− patients (p = 0.029). Particularly, prevalence of D/D homozygous polymorphism was significantly higher in PE+ COVID-19 patients than in PE− (72 vs. 46.5%; p = 0.048), while heterozygote I/D polymorphism was significantly lower expressed in PE+ patients than in PE− (16 vs. 48.8%; p = 0.009). Computed tomographic pulmonary angiography showed predominantly mono/bilateral sub-segmental embolisms. In conclusion, our findings let us hypothesize a genetic susceptibility to thromboembolism in COVID-19 disease. ACE D/D polymorphism might represent a genetic risk factor, although studies on larger populations are needed

Overview and future challenges of nearly zero energy buildings (nZEB) design in Southern Europe

In times of great transition of the European construction sector to energy efficient and nearly zero energy buildings (nZEB), a market observation containing qualitative and quantitative indications should help to fill out some of the current gaps concerning the EU 2020 carbon targets. Next to the economic challenges, there are equally important factors that hinder renovating the existing residential building stock and adding newly constructed high performance buildings. Under these circumstances this paper summarises the findings of a cross-comparative study of the societal and technical barriers of nZEB implementation in 7 Southern European countries. The study analyses the present situation and provides an overview on future prospects for nZEB in Southern Europe. The result presents an overview of challenges and provides recommendations based on available empirical evidence to further lower those barriers in the European construction sector. The paper finds that the most Southern European countries are poorly prepared for nZEB implementation and especially to the challenge opportunity of retrofitting existing buildings. Creating a common approach to further develop nZEB targets, concepts and definitions in synergy with the climatic, societal and technical state of progress in Southern Europe is essential. The paper provides recommendations for actions to shift the identified gaps into opportunities for future development of climate adaptive high performance buildings. (C) 2017 Elsevier B.V. All rights reserved.info:eu-repo/semantics/publishedVersio

Novel Therapeutic Strategies for secondary prevention of Temporal Lobe Epilepsy

L’epilessia del lobo temporale mesiale è una delle forme più frequenti di epilessia, spesso gravata da comorbidità che hanno un impatto significativo sulla qualità della vita. Ad oggi la terapia farmacologica è solo sintomatica e circa un terzo dei pazienti è farmaco-resistente. Questo tipo di epilessia ha frequentemente, alla base, un evento precipitante seguito da un periodo definito "epilettogenesi”, nel quale si verificano molteplici fenomeni fisiopatologici come perdita di neuroni, plasticità neuronale e neurogenesi aberrante, modificazioni delle cellule gliali, alterazione della barriera emato-encefalica, neuroinfiammazione. Tutti questi fenomeni portano, a distanza anche di anni, allo sviluppo della malattia. Durante il mio dottorato di ricerca ho indagato possibili nuove strategie terapeutiche, che potessero modulare l'epilettogenesi e prevenire lo sviluppo di epilessia: Valutazione dell’ipotesi che il 7,8 diidrossiflavone (7,8- DHF), un agente antiossidante e agonista del recettore TrkB per BDNF, possa esercitare un ruolo anti-epilettogeno. Per raggiungere questo obiettivo, è stato utilizzato il modello litio-pilocarpina nel ratto. L'effetto del 7,8- DHF è stato valutato sia sull'esordio della malattia (in termini di frequenza e gravità delle crisi epilettiche) sia sulle co-morbidità (attraverso l'utilizzo di test comportamentali per la locomozione, l'ansia e la memoria spaziale). Inoltre, è stata eseguita un'analisi ex vivo per comprendere i meccanismi alla base degli effetti del 7,8- DHF. Abbiamo scoperto che il 7,8- DHF a basso (5 mg/kg), ma non ad alto (10 mg/kg) dosaggio, può esercitare forti effetti anti-epilettogeni nel modello litio-pilocarpina, e che questi effetti sono correlati a pattern specifici di fosforilazione di TrkB e di attivazione delle vie di segnalazione TrkB-dipendenti. Studio dell'effetto del Peptide di rigenerazione neuronale 2945 (NRP2945) nel modello di pilocarpina di mTLE, utilizzando due diversi paradigmi di somministrazione di NRP2945: (i) a seguito di stato epilettico indotto da pilocarpina, per valutare la sua capacità di prevenire lo sviluppo di epilessia (vale a dire un possibile effetto anti-epilettogeno) e (ii) nella fase cronica dell'epilessia, per valutarne l'effetto sulle crisi spontanee. Abbiamo scoperto che NRP2945 esercita un forte effetto anti-epilettogeno, riducendo la frequenza delle convulsioni spontanee, esercitando un significativo effetto neuroprotettivo e attenuando i comportamenti ansiosi e il deterioramento cognitivo. Questi effetti sembrano dipendere dalla modulazione del processo di epilettogenesi e non dalla soppressione delle crisi, perché NRP2945 non ha ridotto la frequenza o la durata delle crisi spontanee quando somministrato ad animali già epilettici.Mesial temporal lobe epilepsy is one of the most frequent forms of epilepsy, often burdened by comorbidities that have a significant impact on the quality of life. To date, drug therapy is only symptomatic and one third of the patients are drug resistant. This type of epilepsy often originates from a precipitating event followed by a period defined "epileptogenesis", in which multiple pathophysiological phenomena occur, including loss of neurons, neuronal plasticity and aberrant neurogenesis, modifications of glial cells, alteration of the BBB and neuroinflammation. These phenomena may lead, sometimes years later, to the development of the disease. During my PhD I investigated possible new therapeutic strategies for the of epileptogenesis: • Evaluation of the hypothesis that 7,8 dihydroxyflavone (7,8- DHF), an antioxidant agent and an agonist of the BDNF receptor TrkB, may exert an anti-epileptogenic role. To pursue this goal, the rat lithium pilocarpine model was used. The effect of 7,8- DHF was evaluated both at the onset of the disease (in terms of frequency and severity of seizures) and on epilepsy comorbidities (through the use of behavioural tests for locomotion, anxiety and memory). In addition, an ex vivo analysis was performed to understand the mechanisms underlying the effects of 7,8- DHF. We found that 7,8- DHF at low (5 mg/kg), but not at high (10 mg/kg) dosage, can exert strong anti-epileptic effects in the lithium-pilocarpine model, and that these different effects are related to differences in TrkB phosphorylation patterns and activation of TrkB-dependent signalling pathways. • Study of the effect of the Neuronal Regeneration Peptide 2945 (NRP2945) in the pilocarpine model of mTLE, using two different NRP2945 administration paradigms: (i) following pilocarpine-induced status epilepticus, to evaluate its ability to prevent epilepsy development (i.e., a presumed anti-epileptogenic effect) and (ii) in the chronic phase of epilepsy, to evaluate its effect on spontaneous seizures. We found that NRP2945 exerts a strong anti-epileptogenic effect, reducing the frequency of spontaneous seizures, exerting a significant neuroprotective effect, and attenuating anxious behaviours and cognitive impairment. These effects appear to depend on the modulation of the epileptogenesis process and not on seizure suppression, because NRP2945 did not reduce the frequency or duration of spontaneous seizures when administered to already epileptic animals

Sampling Cerebrospinal Fluid and Blood from Lateral Tail Vein in Rats during EEG Recordings

Because the composition of body fluids reflects many physiological and pathological dynamics, biological liquid samples are commonly obtained in many experimental contexts to measure molecules of interest, such as hormones, growth factors, proteins, or small non-coding RNAs. A specific example is the sampling of biological liquids in the research of biomarkers for epilepsy. In these studies, it is desirable to compare the levels of molecules in cerebrospinal fluid (CSF) and in plasma, by withdrawing CSF and plasma in parallel and considering the time distance of the sampling from and to seizures. The combined CSF and plasma sampling, coupled with video-EEG monitoring in epileptic animals, is a promising approach for the validation of putative diagnostic and prognostic biomarkers. Here, a procedure of combined CSF withdrawal from cisterna magna and blood sampling from the lateral tail vein in epileptic rats that are continuously video-EEG monitored is described. This procedure offers significant advantages over other commonly used techniques. It permits rapid sampling with minimal pain or invasiveness, and reduced time of anesthesia. Additionally, it can be used to obtain CSF and plasma samples in both tethered and telemetry EEG recorded rats, and it may be used repeatedly across multiple days of experiment. By minimizing the stress due to sampling by shortening isoflurane anesthesia, measures are expected to reflect more accurately the true levels of investigated molecules in biofluids. Depending on the availability of an appropriate analytical assay, this technique may be used to measure the levels of multiple, different molecules while performing EEG recording at the same time

Early synthesis and correlation of serum anti-thyroid antibodies with clinical parameters in multiple sclerosis

A high frequency of anti-thyroid antibodies has been demonstrated in multiple sclerosis (MS), but there is a lack of data on the possible association of thyroid autoimmunity with disease activity. To assess whether anti-thyroid antibodies are synthesized early in MS or are induced over the course of the disease and whether or not they are correlated with clinical findings, we assayed serum anti-peroxidase and anti-thyroglobulin antibodies in 129 relapsing-remitting MS patients at the time of diagnosis and prior to any immunosuppressive or immunomodulatory treatment. Anti-peroxidase antibodies were detected in 28/129 (21.7%) MS patients, compared to 12/130 (9.2%) neurological controls (P=0.006) and 8/152 (5.3%) normal healthy subjects (P<0.0001). High titres of anti-thyroglobulin antibodies were detected in 11/129 (8.5%) MS patients compared to 6/130 (4.6%) patients with other neurological diseases (P=0.22) and 5/152 (3.3%) normal healthy subjects (P=0.07). Anti-peroxidase antibodies were associated with initial relapse in 14 of 28 (50%) of the patients compared to 18/101 (18%) without antibodies (P=0.001). Similarly, anti-thyroglobulin antibodies were associated with first relapse in 8/11 (73%) of the patients compared to 11/118 (9.3%) of those without (P<0.0001). However, there was no correlation between anti-thyroid antibody titres and disease duration or CSF IgG index values. By contrast, a significant inverse correlation was found between anti-thyroglobulin antibody titres and EDSS score (r(s)=-0. 75; P=0.008). Our findings demonstrate that anti-peroxidase and anti-thyroglobulin antibodies are synthesized early in relapsing-remitting MS and are associated with early clinical disease activity. Furthermore, high titres of anti-thyroglobulin antibodies are associated with low disability scores, suggesting a possible protective role of these antibodies that deserves further investigation

High frequency of psoriasis in relatives is associated with early onset in an Italian multiple sclerosis cohort

Objectives - An exploratory study has been carried out to assess the association of autoimmune diseases in multiple sclerosis (MS) families with clinical features and disability of MS patients. Material and methods - Age at onset, symptoms and signs at onset, and disability were assessed in 177 patients with definite MS and 178 age- and sex-matched control patients with autoimmune diseases (78 with endocrine and 100 with rheumatological diseases) and correlated with the most frequent autoimmune diseases recorded in the families. Results - Psoriasis was found in 30 relatives of 177 (16.9%) MS patients, thyroid disorders in 17 (9.6%) and allergies in 17 (9.6%). In the control group, psoriasis was found in 22 relatives of 178 (12%) patients, thyroid diseases in 19 (10.7%) and allergies in seven (3.9%). Of the 30 relatives with psoriasis in the MS group, 16 (53.3%) were fathers (P < 0.0001). There was a significant association of high frequency of family psoriasis with early age of MS onset (P = 0.025) but not with onset of symptoms or severe disability. Conclusion - In this Italian MS cohort, a subgroup of patients with a first- or second-degree relative with psoriasis had early onset of MS

Novel Antidiabetic Agents and Their Effects on Lipid Profile: A Single Shot for Several Cardiovascular Targets

Type-2 diabetes mellitus (DM) represents one of the most important risk factors for cardiovascular diseases (CVD). Hyperglycemia and glycemic variability are not the only determinant of the increased cardiovascular (CV) risk in diabetic patients, as a frequent metabolic disorder associated with DM is dyslipidemia, characterized by hypertriglyceridemia, decreased high-density lipoprotein (HDL) cholesterol levels and a shift towards small dense low-density lipoprotein (LDL) cholesterol. This pathological alteration, also called diabetic dyslipidemia, represents a relevant factor which could promotes atherosclerosis and subsequently an increased CV morbidity and mortality. Recently, the introduction of novel antidiabetic agents, such as sodium glucose transporter-2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP4i) and glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs), has been associated with a significant improvement in CV outcomes. Beyond their known action on glycemia, their positive effects on the CV system also seems to be related to an ameliorated lipidic profile. In this context, this narrative review summarizes the current knowledge regarding these novel anti-diabetic drugs and their effects on diabetic dyslipidemia, which could explain the provided global benefit to the cardiovascular system

Monitoring the freezing point of buffalo milk

The aim of this study was to evaluate the basic freezing point of buffalo milk. Bulk milk samples were collected from buffalo and cattle farms in Caserta area from 2008 to 2014. The analysis involved a total of 1886 buffalo milk samples and 1711 bovine milk samples. These were also tested for fat, protein and lactose contents by means of infrared spectrometry. The freezing point was determined by means of a thermistor cryoscope. Data underwent statistical analysis. Our research showed an average freezing point of -0.528°C for buffalo milk and - 0.522°C for bovine milk. Given the lack of data on the freezing point of buffalo milk, our study provides the first indication of a basic freezing point of the milk of this species in Italy

Anti-epileptogenic effect of NRP2945 in the pilocarpine model of temporal lobe epilepsy

Innovative therapeutic strategies are highly needed to tackle the major medical needs of epilepsy, like prevention of epilepsy development in at-risk individuals, treatment of severe and drug-resistant forms, control of comorbidities. The Neural Regeneration Peptide NRP2945 (a peptidomimetic analogue of the human CAPS-2 protein) has been recently found to exert many potentially anti-epileptic effects, for example increased neuronal survival and differentiation. In the present study, we tested the effects of NRP2945 on the development of epilepsy (epileptogenesis) and on chronic, spontaneous seizures, by using the pilocarpine model of temporal lobe epilepsy. We found that NRP2945 exerts a robust anti-epileptogenic effect, reducing the frequency of spontaneous seizures, exerting a significant neuroprotective effect and attenuating anxiety-like behaviors and cognitive impairment. These effects appear to depend on modulation of the epileptogenesis process and not on seizure suppression, because NRP2945 did not reduce frequency or duration of spontaneous seizures when administered to already epileptic animals. These findings may form the basis for a preventive therapy for individuals at-risk of developing epilepsy

The Dichotomous Role of Inflammation in the CNS: A Mitochondrial Point of View

Innate immune response is one of our primary defenses against pathogens infection, although, if dysregulated, it represents the leading cause of chronic tissue inflammation. This dualism is even more present in the central nervous system, where neuroinflammation is both important for the activation of reparatory mechanisms and, at the same time, leads to the release of detrimental factors that induce neurons loss. Key players in modulating the neuroinflammatory response are mitochondria. Indeed, they are responsible for a variety of cell mechanisms that control tissue homeostasis, such as autophagy, apoptosis, energy production, and also inflammation. Accordingly, it is widely recognized that mitochondria exert a pivotal role in the development of neurodegenerative diseases, such as multiple sclerosis, Parkinson&rsquo;s and Alzheimer&rsquo;s diseases, as well as in acute brain damage, such in ischemic stroke and epileptic seizures. In this review, we will describe the role of mitochondria molecular signaling in regulating neuroinflammation in central nervous system (CNS) diseases, by focusing on pattern recognition receptors (PRRs) signaling, reactive oxygen species (ROS) production, and mitophagy, giving a hint on the possible therapeutic approaches targeting mitochondrial pathways involved in inflammation