Improvement for the quality of the agro-food products – condition for the Romanian agriculture integration in the European Union

Romanian agro-food products’ competitivity depends, as a priority, on their quality. There are some factors that conduct to a decrease in productivity for agricultural production in Romania and in its quality, the main are: financial difficulties in input supply, small dimension of the farms and lack of the technologies, management and marketing for the main part of the farms. In order to improve agro-food products’ quality, it is necessary to harmonize Romanian quality standards to those of the European Union and to support the quality of the traded agro-food products. One of the agro-food branches of the economy which may become competitive on the European Union market is wine, with the condition of quality improving. In this paper we present some measures for wine quality improving. We intend to present some ways of improving the wine quality.Wine; Quality; Agro-food products; Competitiveness.

De novo and bi-allelic pathogenic variants in NARS1 cause neurodevelopmental delay due to toxic gain-of-function and partial loss-of-function effects

Aminoacyl-tRNA synthetases (ARSs) are ubiquitous, ancient enzymes that charge amino acids to cognate tRNA molecules, the essential first step of protein translation. Here, we describe 32 individuals from 21 families, presenting with microcephaly, neurodevelopmental delay, seizures, peripheral neuropathy, and ataxia, with de novo heterozygous and bi-allelic mutations in asparaginyl-tRNA synthetase (NARS1). We demonstrate a reduction in NARS1 mRNA expression as well as in NARS1 enzyme levels and activity in both individual fibroblasts and induced neural progenitor cells (iNPCs). Molecular modeling of the recessive c.1633C\u3eT (p.Arg545Cys) variant shows weaker spatial positioning and tRNA selectivity. We conclude that de novo and bi-allelic mutations in NARS1 are a significant cause of neurodevelopmental disease, where the mechanism for de novo variants could be toxic gain-of-function and for recessive variants, partial loss-of-function

Stroke care indicators in the Republic of Moldova – the RES-Q registry

Introducere. Până la aderarea Moldovei in anul 2016 la platforma internațională RES-Q (Registry of Stroke Care Quality) - Registrul Calității Îngrijirii Accidentului Vascular Cerebral (AVC), nu au existat date privind indicatorii de calitate intraspitalicești ai ictusului. Scopul acestei lucrări a fost de a evalua calitatea asistenței medicale acordată pacienților cu AVC în Moldova în baza datelor registrului RES-Q. Material și metode. Au fost analizate datele tuturor pacienților cu ictus ischemic și hemoragic acut din registrul RES-Q din 15 spitale din Moldova. Datele au fost colectate timp de o lună pe an pe parcurs a 3 ani (2017-2019). Analiza datelor între spitale s-a realizat din considerentul accesului acestora la computer tomografia cerebrală. Adițional, datele din Moldova au fost comparate cu cele din trei țări ale proiectului ESO-EAST (European Stroke Organization Enhancing and Accelerating Stroke Treatment): România, Lituania și Georgia. Rezultate. Studiul a inclus un număr total de 1660 pacienți, cu vârsta medie de 68 ani (49% - bărbați). Moldova a înregistrat rezultate mai slabe la numărul de CT efectuate (81% [95% CI 79-84%]), la evaluarea disfagiei (29% [95% CI 27-32%]), efectuarea trombolizei intravenoase (3% [95% CI 2-4%]), administrarea de anticoagulante (44% [95% CI 39-49%]) și statine (42% [95% CI 39-45%]) la externare, la mortalitatea intraspitalicească prin AVC (17% [95% CI 15- 19%]). În interiorul Moldovei calitatea asistenței prin AVC s-a comparat reieșind din accesul la CT. Concluzii. Studiul nostru a identificat lacune serioase ale performanțelor asistenței intraspitalicești în ictus, cum ar fi lipsa scanărilor prin CT în multe spitale publice, absența unei rețele naționale centralizate în domeniul AVC, acces extrem de scăzut la tratamentul prin tromboliză și implementarea nesatisfăcătoare a tratamentului de profilaxie secundară a ictusului.Introduction. There were no data on in-hospital stroke care indicators until Moldova’s accession to the international Registry of Stroke Care Quality (RES-Q) platform in 2016. The aim of this paper was to assess the acute stroke care quality in Moldova based on the data of the RES-Q registry. Material and methods. We analyzed the data of all patients with acute ischemic and hemorrhagic stroke of the RES-Q from 15 Moldovan hospitals. Data were collected for one month each year, during a 3-year period (2017-2019). Data analysis was performed between hospitals according to their access to a brain CT facility for Moldovan participating hospitals. Additionally, Moldovan data were compared with other three ESO-EAST (European Stroke Organization Enhancing and Accelerating Stroke Treatment) project countries: Romania, Lithuania, and Georgia. Results. A total of 1660 patients were recruited in the study, mean age of 68 years (49% men). Moldova registered poorer results in number of brain CT performed (81% [95% CI 79-84%]), dysphagia screening (29% [95% CI 27-32%]), IV thrombolysis performed (3% [95% CI 2-4%]), administration of anticoagulants (44% [95% CI 39-49%]) and statins (42% [95% CI 39-45%]) at discharge, in-hospital stroke mortality (17% [95% CI 15- 19%]). Within Moldova the stroke care quality was driven by the access to CT scan. Conclusions. Our study highlighted some serious gaps of in-hospital stroke care performance in Moldova, such as the lack of CT scans in many public hospitals, the absence of a national stroke center network, extremely low accessibility of IV thrombolysis and unsatisfactory implementation of secondary stroke prevention treatment

HLA-DRB1*1501 influences long-term disability progression and tissue damage on MRI in relapse-onset multiple sclerosis

BACKGROUND: Whether genetic factors influence the long-term course of multiple sclerosis (MS) is unresolved. OBJECTIVE: To determine the influence of HLA-DRB1*1501 on long-term disease course in a homogeneous cohort of clinically isolated syndrome (CIS) patients. METHODS: One hundred seven patients underwent clinical and MRI assessment at the time of CIS and after 1, 3, 5 and 15 years. HLA-DRB1*1501 status was determined using Sanger sequencing and tagging of the rs3135388 polymorphism. Linear/Poisson mixed-effects models were used to investigate rates of change in EDSS and MRI measures based on HLA-DRB1*1501 status. RESULTS: HLA-DRB1*1501 -positive (n = 52) patients showed a faster rate of disability worsening compared with the HLA-DRB1*1501 -negative (n = 55) patients (annualised change in EDSS 0.14/year vs. 0.08/year, p < 0.025), and a greater annualised change in T2 lesion volume (adjusted difference 0.45 mL/year, p < 0.025), a higher number of gadolinium-enhancing lesions, and a faster rate of brain (adjusted difference -0.12%/year, p < 0.05) and spinal cord atrophy (adjusted difference -0.22 mm2/year, p < 0.05). INTERPRETATION: These findings provide evidence that the HLA-DRB1*1501 allele plays a role in MS severity, as measured by long-term disability worsening and a greater extent of inflammatory disease activity and tissue loss. HLA-DRB1*1501 may provide useful information when considering prognosis and treatment decisions in early relapse-onset MS

LETM1 couples mitochondrial DNA metabolism and nutrient preference

The diverse clinical phenotypes of Wolf\u2013Hirschhorn syndrome (WHS) are the result of haploinsufficiency of several genes, one of which, LETM1, encodes a protein of the mitochondrial inner membrane of uncertain function. Here, we show that LETM1 is associated with mitochondrial ribosomes, is required for mitochondrial DNA distribution and expression, and regulates the activity of an ancillary metabolic enzyme, pyruvate dehydrogenase. LETM1 deficiency in WHS alters mitochondrial morphology and DNA organization, as does substituting ketone bodies for glucose in control cells. While this change in nutrient availability leads to the death of fibroblasts with normal amounts of LETM1, WHS-derived fibroblasts survive on ketone bodies, which can be attributed to their reduced dependence on glucose oxidation. Thus, remodeling of mitochondrial nucleoprotein complexes results from the inability of mitochondria to use specific substrates for energy production and is indicative of mitochondrial dysfunction. However, the dysfunction could be mitigated by a modified diet\u2014for WHS, one high in lipids and low in carbohydrates

Genetic and phenotypic characterization of complex hereditary spastic paraplegia

The hereditary spastic paraplegias are a heterogeneous group of degenerative disorders that are clinically classified as either pure with predominant lower limb spasticity, or complex where spastic paraplegia is complicated with additional neurological features, and are inherited in autosomal dominant, autosomal recessive or X-linked patterns. Genetic defects have been identified in over 40 different genes, with more than 70 loci in total. Complex recessive spastic paraplegias have in the past been frequently associated with mutations in SPG11 (spatacsin), ZFYVE26/SPG15, SPG7 (paraplegin) and a handful of other rare genes, but many cases remain genetically undefined. The overlap with other neurodegenerative disorders has been implied in a small number of reports, but not in larger disease series. This deficiency has been largely due to the lack of suitable high throughput techniques to investigate the genetic basis of disease, but the recent availability of next generation sequencing can facilitate the identification of disease- causing mutations even in extremely heterogeneous disorders. We investigated a series of 97 index cases with complex spastic paraplegia referred to a tertiary referral neurology centre in London for diagnosis or management. The mean age of onset was 16 years (range 3 to 39). The SPG11 gene was first analysed, revealing homozygous or compound heterozygous mutations in 30/97 (30.9%) of probands, the largest SPG11 series reported to date, and by far the most common cause of complex spastic paraplegia in the UK, with severe and progressive clinical features and other neurological manifestations, linked with magnetic resonance imaging defects. Given the high frequency of SPG11 mutations, we studied the autophagic response to starvation in eight affected SPG11 cases and control fibroblast cell lines, but in our restricted study we did not observe correlations between disease status and autophagic or lysosomal markers. In the remaining cases, next generation sequencing was carried out revealing variants in a number of other known complex spastic paraplegia genes, including five in SPG7 (5/97), four in FA2H (also known as SPG35) (4/97) and two in ZFYVE26/SPG15. Variants were identified in genes usually associated with pure spastic paraplegia and also in the Parkinson’s disease-associated gene ATP13A2, neuronal ceroid lipofuscinosis gene TPP1 and the hereditary motor and sensory neuropathy DNMT1 gene, highlighting the genetic heterogeneity of spastic paraplegia. No plausible genetic cause was identified in 51% of probands, likely indicating the existence of as yet unidentified genes

Clinical, pathological and functional characterization of riboflavin-responsive neuropathy.

Brown-Vialetto-Van Laere syndrome represents a phenotypic spectrum of motor, sensory, and cranial nerve neuropathy, often with ataxia, optic atrophy and respiratory problems leading to ventilator-dependence. Loss-of-function mutations in two riboflavin transporter genes, SLC52A2 and SLC52A3, have recently been linked to Brown-Vialetto-Van Laere syndrome. However, the genetic frequency, neuropathology and downstream consequences of riboflavin transporter mutations are unclear. By screening a large cohort of 132 patients with early-onset severe sensory, motor and cranial nerve neuropathy we confirmed the strong genetic link between riboflavin transporter mutations and Brown-Vialetto-Van Laere syndrome, identifying 22 pathogenic mutations in SLC52A2 and SLC52A3, 14 of which were novel. Brain and spinal cord neuropathological examination of two cases with SLC52A3 mutations showed classical symmetrical brainstem lesions resembling pathology seen in mitochondrial disease, including severe neuronal loss in the lower cranial nerve nuclei, anterior horns and corresponding nerves, atrophy of the spinothalamic and spinocerebellar tracts and posterior column-medial lemniscus pathways. Mitochondrial dysfunction has previously been implicated in an array of neurodegenerative disorders. Since riboflavin metabolites are critical components of the mitochondrial electron transport chain, we hypothesized that reduced riboflavin transport would result in impaired mitochondrial activity, and confirmed this using in vitro and in vivo models. Electron transport chain complex I and complex II activity were decreased in SLC52A2 patient fibroblasts, while global knockdown of the single Drosophila melanogaster riboflavin transporter homologue revealed reduced levels of riboflavin, downstream metabolites, and electron transport chain complex I activity. This in turn led to abnormal mitochondrial membrane potential, respiratory chain activity and morphology. Riboflavin transporter knockdown in Drosophila also resulted in severely impaired locomotor activity and reduced lifespan, mirroring patient pathology, and these phenotypes could be partially rescued using a novel esterified derivative of riboflavin. Our findings expand the genetic, clinical and neuropathological features of Brown-Vialetto-Van Laere syndrome, implicate mitochondrial dysfunction as a downstream consequence of riboflavin transporter gene defects, and validate riboflavin esters as a potential therapeutic strategy

Research and Science Today No.3

Research and Science Today Journal is a publication founded in 2011 and it is dedicated to the students of all levels (license, master and doctoral) of faculties in the country and abroad. We want to offer the participants the opportunity to present their scientific works in the following areas: Social Sciences, Economic Sciences, Legal Sciences, Humanities, Education Sciences, Engineering, Medicine and Sport. This journal provides students the opportunity to create and / or to improve their abilities to write scientific papers. So each appearance (two appearances per year at which we can add supplements) contains a number of papers written by students, masters and doctoral from the faculties from the country or / and abroad. The journal promotes original studies contributing to the progress of knowledge and it is motivated by the need to address issues of theory and practice in the areas mentioned above. The Journal is a training means of the factors involved in the conceptualization, development, implementation and evaluation , aiming the formation of creative personalities who could be able to adapt through the changing conditions of life. Journal wants to be a forum for debates disciplinaries and interdisciplinaries theoretical topics, to become a research support, to leverage this work at regional, national and international levels. We believe that this gathering will enjoy the support from both parts of the researchers and of the practitioners, and will provide appropriate training sources held professional through the current problems

Research and Science Today No.3

Research and Science Today Journal is a publication founded in 2011 and it is dedicated to the students of all levels (license, master and doctoral) of faculties in the country and abroad. We want to offer the participants the opportunity to present their scientific works in the following areas: Social Sciences, Economic Sciences, Legal Sciences, Humanities, Education Sciences, Engineering, Medicine and Sport. This journal provides students the opportunity to create and / or to improve their abilities to write scientific papers. So each appearance (two appearances per year at which we can add supplements) contains a number of papers written by students, masters and doctoral from the faculties from the country or / and abroad. The journal promotes original studies contributing to the progress of knowledge and it is motivated by the need to address issues of theory and practice in the areas mentioned above. The Journal is a training means of the factors involved in the conceptualization, development, implementation and evaluation , aiming the formation of creative personalities who could be able to adapt through the changing conditions of life. Journal wants to be a forum for debates disciplinaries and interdisciplinaries theoretical topics, to become a research support, to leverage this work at regional, national and international levels. We believe that this gathering will enjoy the support from both parts of the researchers and of the practitioners, and will provide appropriate training sources held professional through the current problems