Disentangling the role of wild birds in avian metapneumovirus (aMPV) epidemiology: A systematic review and meta-analysis

Given the avian metapneumovirus (aMPV) disease burden in poultry worldwide and the evidence of a possible role played by wild birds in the virus epidemiology, the present study summarizes aMPV serological and molecular data on free-ranging avifauna available in the literature by conducting a systematic review and meta-analysis. A computerized literature research was performed on PubMed, Scopus, CAB Direct and Web of Science to identify relevant publications across the period 1990–2021, along with the screening of reference lists. A random-effect model was applied to calculate pooled prevalence estimates with 95% confidence intervals. The inconsistency index statistic (I2) was applied to assess between-study heterogeneity. Subgroup analyses for molecular studies only were performed according to geographical area of samplings, taxonomic order, genus and migration patterns of the birds surveyed. A total of 11 publications on molecular surveys and 6 on serological ones were retained for analysis. The pooled molecular prevalence was 6% (95% CI: 1–13%) and a high between-study heterogeneity was detected (I2 = 96%, p <.01). Moderator analyses showed statistically significant differences according to geographical area studied, taxonomic order and genus. Concerning serological prevalence, a pooled estimate of 14% (95% CI: 1–39%), along with a high between-study heterogeneity, was obtained (I2 = 98%, p <.01). Moderator analysis was not performed due to the scarcity of eligible serological studies included. Overall, molecular and serological evidence suggests that some wild bird taxa could play a role in aMPV epidemiology. Particularly, wild ducks, geese, gulls and pheasants, according to scientific contributions hereby considered, proved to be susceptible to aMPV, and due to host ecology, may act as a viral carrier or reservoir. Further surveys of wild birds are encouraged for a better comprehension of the poultry/wild bird interface in aMPV epidemiology and for better characterizing the virus host breadth

Infectious bursal disease virus in free-living wild birds: A systematic review and meta-analysis of its sero-viroprevalence on a global scale

Infectious bursal disease virus (IBDV) is an economically important pathogen for poultry, whereas knowledge of its occurrence in non-poultry hosts is limited. The objective of this systematic review and meta-analysis is to summarize the up-to-date knowledge about the sero-viroprevalence of IBDV in wild birds on a global scale. A computerized literature research was performed on PubMed, Scopus, CAB Direct and Web of Science to find relevant publications, along with the screening of reference lists. Journal articles, book chapters, scientific correspondences, conference proceedings and short communications on IBDV virological and/or serological surveys in free-living wild birds published between 1970 and 2021 were considered as eligible. Among 184 studies found, 36 original contributions met the pre-established criteria. A random-effect model was applied to calculate pooled seroprevalence estimates with 95% confidence intervals, whereas the paucity of virological studies (n = 6) only allowed a qualitative description of the data. The pooled seroprevalence was estimated to be 6% (95% CI: 3%–9%) and a high heterogeneity was detected (I2= 96%). Sub-group analyses were not performed due to the scarcity of available information about hypothetical moderators. With respect to virological studies, IBDV was detected in Anseriformes, Columbiformes, Galliformes, Passeriformes and Pelecaniformes and different strains related to poultry infection were isolated. Our estimates of serological data showed a moderate exposure of wild birds to IBDV. The susceptibility of different species to IBDV infection underlines their potential role in its epidemiology at least as carriers or spreaders. Indeed, the isolation of IBDV in healthy wild birds with a migratory attitude might contribute to a long-distance spread of the virus and to strain diversity. While a wild reservoir host could not be clearly identified, we believe our work provides useful insights for conducting future surveys which are needed to broaden our knowledge of IBDV occurrence in wild birds

Vaccine Interaction and Protection against Virulent Avian Metapneumovirus (aMPV) Challenge after Combined Administration of Newcastle Disease and aMPV Live Vaccines to Day-Old Turkeys

Newcastle disease virus (NDV) and avian metapneumovirus (aMPV) are among the most impactful pathogens affecting the turkey industry. Since turkeys are routinely immunized against both diseases, the hatchery administration of the combined respective live vaccines would offer remarkable practical advantages. However, the compatibility of NDV and aMPV vaccines has not yet been experimentally demonstrated in this species. To address this issue, an aMPV subtype B live vaccine was administered to day-old poults either alone or in combination with one of two different ND vaccines. The birds were then challenged with a virulent aMPV subtype B strain, clinical signs were recorded and aMPV and NDV vaccine replication and humoral immune response were assessed. All results supported the absence of any interference hampering protection against aMPV, with no significant differences in terms of clinical scoring. In addition, the mean aMPV vaccine viral titers and antibody titers measured in the dual vaccinated groups were comparable or even higher than in the group vaccinated solely against aMPV. Lastly, based on the NDV viral and antibody titers, the combined aMPV and NDV vaccination does not seem to interfere with protection against NDV, although further studies involving an actual ND challenge will be necessary to fully demonstrate this hypothesis

VALUTATION OF OFFICIAL MOUSE BIOASSAY FOR THE DETECTION OF LIPOPHILIC MARINE TOXINS

The official biotoxicological (MBA) method for the determination of lipophilic marine toxins shows important gaps with regard to reproducibility, specificity and quality of the data provided and serious ethical contraindications. The Commission Regulation (EU) No 15/2011 establishes the date of December 31, 2014 as the deadline for replacement of the mouse test with a LC-MS/MS method by the laboratories of the member states responsible for the monitoring of marine biotoxins. In order to facilitate the interpretation of the MBA during this transition period, we further evaluated the specificity and selectivity of this assay in comparison with a LC-MS/MS method in detecting lipophilic marine toxins on mussels of the middle Adriatic Sea. Data show a high percentage of false-positive results on MBA due to interference by yessotoxins. It was also possible to evaluate the toxic profile of the samples analyzed

Non-pharmacological treatments for pediatric refractory epilepsies

Introduction: Antiseizure medications (ASMs) are the primary treatment option for epilepsies of wide etiologies, however, about 10–20% of children do not gain sustained seizure control and in this case, it is worth investigating ‘alternative’ therapeutic approaches aside from ASMs. Nowadays, non-pharmacological strategies for epilepsy treatment encompass dietary interventions, neurostimulation-based techniques, and biobehavioral approaches. Areas covered: A search on PubMed database was conducted. Experimental and clinical studies, as well as meta-analysis and structured reviews on the latest non-pharmacological treatments for drug-resistant epilepsy (DRE) in children, were included. Special attention is given to the efficacy and tolerability outcomes, trying to infer the role novel approaches may have in the future. Expert opinion: The large heterogeneity of primary clinical outcomes and the unavoidable subjective response of each patient to treatments prevents Researchers from the identification of a single, reliable, approach to treat DRE. The understanding of fine pathophysiologic processes is giving the way to the use of alternative therapies, such as the well-known ketogenic diet, in a ‘personalized’ view of treatment. The goal is to apply the non-pharmacological treatment most suitable for the patients sake

The Unfolded Protein Response in a Murine Model of Alzheimer’s Disease: Looking for Predictors

Alzheimer's disease (AD) represents the most frequent type of dementia worldwide, and aging is the most important risk factor for the sporadic form of the pathology. The endoplasmic reticulum (ER), the main cellular actor involved in proteostasis, appears significantly compromised in AD due to the accumulation of the beta-amyloid (A beta) protein and the phosphorylated Tau protein. Increasing protein misfolding activates a specific cellular response known as Unfolded Protein Response (UPR), which orchestrates the recovery of ER function. The aim of the present study was to investigate the role of UPR in a murine model of AD induced by intracerebroventricular (i.c.v.) injection of A beta 1-42 oligomers at 3 or 18 months. The oligomer injection in aged animals induced memory impairment, oxidative stress, and the depletion of glutathione reserve. Furthermore, the RNA sequencing and the bioinformatic analysis performed showed the enrichment of several pathways involved in neurodegeneration and protein regulations. The analysis highlighted the significant dysregulation of the protein kinase RNA-like ER kinase (PERK), inositol-requiring protein 1 alpha (IRE1 alpha) and activating transcription factor 6 (ATF-6). In turn, ER stress affected the PI3K/Akt/Gsk3 beta and MAPK/ERK pathways, highlighting Mapkapk5 as a potential marker, whose regulation could lead to the definition of new pharmacological and neuroprotective strategies to counteract AD

Diagnostic and therapeutic aspects of hemiplegic migraine

Hemiplegic migraine (HM) is a clinically and genetically heterogeneous condition with attacks of headache and motor weakness which may be associated with impaired consciousness, cerebellar ataxia and intellectual disability. Motor symptoms usually last <72 hours and are associated with visual or sensory manifestations, speech impairment or brainstem aura. HM can occur as a sporadic HM or familiar HM with an autosomal dominant mode of inheritance. Mutations in CACNA1A, ATP1A2 and SCN1A encoding proteins involved in ion transport are implicated. The pathophysiology of HM is close to the process of typical migraine with aura, but appearing with a lower threshold and more severity. We reviewed epidemiology, clinical presentation, diagnostic assessment, differential diagnosis and treatment of HM to offer the best evidence of this rare condition. The differential diagnosis of HM is broad, including other types of migraine and any condition that can cause transitory neurological signs and symptoms. Neuroimaging, cerebrospinal fluid analysis and electroencephalography are useful, but the diagnosis is clinical with a genetic confirmation. The management relies on the control of triggering factors and even hospitalisation in case of long-lasting auras. As HM is a rare condition, there are no randomised controlled trials, but the evidence for the treatment comes from small studies

The Challenges of Diagnosis and Treatment of Arrhythmogenic Cardiomyopathy: Are We there yet?

Background: we sought to review the evolution in the diagnosis and treatment of Arrhythmogenic Cardiomyopathy (ACM), a clinically multifaceted entity beyond the observation of ventricular arrhythmias, and the outcome of therapies aiming at sudden death prevention in a single center experience. Methods: retrospective analysis of the data of consecutive patients with an implanted cardioverter-defibrillator (ICD) and a confirmed diagnosis of ACM according to the proposed Padua Criteria, who were referred to our center from January 1992 to October 2021. Results: we enrolled 72 patients (66% males, mean age at implant 46 ± 16 years), 63.9% implanted for primary prevention. At the time of ICD implant, 29 (40.3%) patients had a right ventricular involvement, 24 (33.3%) had a dominant LV involvement and 19 (26.4%) had a biventricular involvement. After a median follow-up of 6,1 years [IQR: 2.5–9.9], 34 patients (47.2%) had 919 sustained episodes of ventricular arrhythmias (VA). 27 patients (37.5%) had 314 episodes of life-threatening arrhythmias (LT-VA), defined as sustained ventricular tachycardia ≥200 beats/min. Considering only the patients with an ICD capable of delivering ATP, 80.4% of VA and 65% of LT-VA were successfully terminated with ATP. 16 (22.2%) patients had an inappropriate ICD activation, mostly caused by atrial fibrillation, while in 9 patients (12.5%) there was a complication needing reintervention (in 3 cases there was a loss of ventricular sensing dictating lead revision). During the follow-up 11 (15.3%) patients died, most of them due to heart failure, and 8 (11.1%) underwent heart transplantation. Conclusions: ACM is increasingly diagnosed owing to heightened suspicion at ECG examination and to improved imaging technology and availability, though the diagnostic workflow is particularly challenging in the earliest disease stages. ICD therapy is the cornerstone of sudden death prevention, albeit its efficacy is not based on controlled studies, and VT ablation/medical therapy are complementary to this strategy. The high burden of ATP-terminated VA makes shock-only devices debatable. The progressive nature of ACM leads to severe biventricular enlargement and refractory heart failure, which pose significant treatment issues when a predominant RV dysfunction occurs owing to the reduced possibility for mechanical circulatory assistance

Pentacene thin films on ferromagnetic oxide: Growth mechanism and spintronic devices

[EN] Cation-exchange membranes made exclusively from ceramic materials have been synthesized by means of the impregnation of microporous ceramic supports with zirconium phosphate. Changes in the pore size distribution and total pore volume of the supports were provoked by the addition of starch as pore former in the fabrication procedure. This allowed the production of supports with increased effective electrical conductivities and with larger pores available for the zirconium phosphate deposition. An improved functionality for the exchange of cations was given to the ceramic membranes by means of their impregnation with the active particles of zirconium phosphate. The ion-exchange properties of the membranes were increased with further impregnation cycles and the resulting current–voltage curves showed a similar shape to that typical of commercial polymeric ion-exchange membranes. The production of ionexchange membranes with increased chemical and radiation stability will broaden their applicability for the treatment of specific industrial waste waters, which are very aggressive for the current commercial ion-exchange membranes.The authors acknowledge the technical help from Federico Bona at CNR-ISMN in Bologna and the extensive use of the scanning probe microscopes at "Centro Interfacolta Misure" of the University of Parma. Financial support from the FP7 Projects NMP-2010-SMALL-4-263104 (HINTS), NMP3-SL-2010-246073 (GRENADA), and NMP3-LA-2010-246102 (IFOX) is acknowledged.Graziosi, P.; Riminucci, A.; Prezioso, M.; Newby, C.; Brunel, D.; Bergenti, I.; Pullini, D.... (2014). Pentacene thin films on ferromagnetic oxide: Growth mechanism and spintronic devices. Applied Physics Letters. 105(2):1-5. https://doi.org/10.1063/1.4890328S15105

GLP-1 Mediates Regulation of Colonic ACE2 Expression by the Bile Acid Receptor GPBAR1 in Inflammation

Background & Aims: ACE2, a carboxypeptidase that generates Ang-(1-7) from Ang II, is highly expressed in the lung, small intestine and colon. GPBAR1, is a G protein bile acid receptor that promotes the release of the insulinotropic factor glucagon-like peptide (GLP)-1 and attenuates intestinal inflammation. Methods: We investigated the expression of ACE2, GLP-1 and GPBAR1 in two cohorts of Crohn’s disease (CD) patients and three mouse models of colitis and Gpbar1−/− mice. Activation of GPBAR1 in these models and in vitro was achieved by BAR501, a selective GPBAR1 agonist. Results: In IBD patients, ACE2 mRNA expression was regulated in a site-specific manner in response to inflammation. While expression of ileal ACE2 mRNA was reduced, the colon expression was induced. Colon expression of ACE2 mRNA in IBD correlated with expression of TNF-α and GPBAR1. A positive correlation occurred between GCG and GPBAR1 in human samples and animal models of colitis. In these models, ACE2 mRNA expression was further upregulated by GPABR1 agonism and reversed by exendin-3, a GLP-1 receptor antagonist. In in vitro studies, liraglutide, a GLP-1 analogue, increased the expression of ACE2 in colon epithelial cells/macrophages co-cultures. Conclusions: ACE2 mRNA expression in the colon of IBD patients and rodent models of colitis is regulated in a TNF-α-and GLP-1-dependent manner. We have identified a GPBAR1/GLP-1 mechanism as a positive modulator of ACE2