Romania’s Role in the Process of Emergency Assistance for the Ukrainian Refugees in Times of Crisis

The magnitude of the influx of Ukrainian refugees, generated by the intensification of Russia’s aggression in Ukraine in 2022, caught the European Union and especially the Eastern European member states by surprise. The main objective of this article is to provide a comprehensive analysis of the emergency response provided by Romania, including the governmental measures adopted by Romanian authorities in collaboration with UNHCR and IOM, supported by civil society through volunteering. This study focuses specifically on examining and observing the evolution of Romania’s mechanisms of emergency response and assistance, as well as the legislative changes that occurred as a result of the significant influx of Ukrainian refugees on Romanian territory in the first four months following the escalation of the war (February – May 2022). To achieve this objective, official documents provided by the Romanian Government, the Strategic Coordination Group – Humanitarian Assistance, and reports provided by UNHCR and IOM will be analysed, with the primary method being content analysis. The case of Romania is a relevant study because prior to 2022, unlike other EU Eastern member states, it was not on the transit route of refugees and till today is not a full member of the Schengen area, thus through the analysis of the Romanian response, it can be determined whether Romania represents an example of best practices in emergency assistance regarding refugee management

Dried figs as sources of essential microelements

The paper aims to determine the concentration of some microelements essential in cardiovascular sistem health from dried figs and evaluate their mineral intake. The concentrations of Fe, Mn, Zn and Cu were determined from samples of dried figs from the local trade, imported from different countries in the Mediterranean areas. The results obtained, by flame atomic absorption spectrometry (FAAS) method, show that these fruits contain important quantities of essential microelements, depending on fig providers: 22.1 - 32.5 mg/kg Fe, 4.14 - 12.73 mg/kg Mn, 4.53 - 10.20 mg/kg Zn and 3.95 - 9.16 mg/kg Cu. The analytical results obtained allowed the evaluation of the mineral intake of these fruits for men and women aged between 19 - 50 years. Thus, a consumption of 40 g of dried figs covers a large part of the need for microelements, as follows: 13.99% Fe, 13.39% Mn, 2.83% Zn and 28.07% Cu - for men and 6.22% Fe, 17.11% Mn, 3.89% Zn and 28.07% Cu - for men. These results show that the dried figs analyzed could be considered as sources with some essential microelements, especially in terms of Cu, Mn and Fe

Sanfilippo syndrome : the tale of a challenging diagnosis

Sanfilippo syndrome or mucopolysaccharidosis III (MPS III), includes a group of four autosomal recessive lysosomal storage disorders caused by deficient activity of enzymes involved in the catabolism of heparan sulfate. The four types of MPS III are recognized in accordance with the deficient enzyme, resulting in the accumulation of heparan sulfate with particularly deleterious effects in the central nervous system. The incidence of MPS III remains to be established in Latin American countries. We describe the journey of a patient with MPS IIIB whom, even in the presence of speech delay and deterioration, behavioral problems and motor incoordination, showed unaltered urinary glycosaminoglycans (GAGs) levels. An investigation for MPS was undertaken and enzyme analysis indicated a deficiency of alpha-N-acetylglucosaminidase, leading to the diagnosis of MPS IIIB. With the correct diagnosis, the patient’s symptoms could be properly managed, and the parents received appropriate genetic counseling. The present case report reinforces the need of investigating MPS III in patients with language delay and/or regression, neurological impairment and behavioral alterations, even when urinary GAGs are within normal range. A definitive diagnosis ends the diagnostic journey and enables the medical team and family to provide a better care for the child

A Comprehensive Assessment of Qualitative and Quantitative Prodromal Parkinsonian Features in Carriers of Gaucher Disease-Identifying Those at the Greatest Risk

Carriers of GBA1 gene variants have a significant risk of developing Parkinson's disease (PD). A cohort study of GBA carriers between 40-75 years of age was initiated to study the presence of prodromal PD features. Participants underwent non-invasive tests to assess different domains of PD. Ninety-eight unrelated GBA carriers were enrolled (43 males) at a median age (range) of 51 (40-74) years; 71 carried the N370S variant (c.1226A > G) and 25 had a positive family history of PD. The Montreal Cognitive Assessment (MoCA) was the most frequently abnormal (23.7%, 95% CI 15.7-33.4%), followed by the ultrasound hyperechogenicity (22%, 95% CI 14-32%), Unified Parkinson's Disease Rating Scale part III (UPDRS-III) (17.2%, 95% CI 10.2-26.4%), smell assessment (12.4%, 95% CI 6.6-20.6%) and abnormalities in sleep questionnaires (11%, 95% CI 5.7-19.4%). Significant correlations were found between tests from different domains. To define the risk for PD, we assessed the bottom 10th percentile of each prodromal test, defining this level as "abnormal". Then we calculated the percentage of "abnormal" tests for each subject; the median (range) was 4.55 (0-43.5%). Twenty-two subjects had more than 15% "abnormal" tests. The limitations of the study included ascertainment bias of individuals with GBA-related PD in relatives, some incomplete data due to technical issues, and a lack of well-characterized normal value ranges in some tests. We plan to enroll additional participants and conduct longitudinal follow-up assessments to build a model for identifying individuals at risk for PD and investigate interventions aiming to delay the onset or perhaps to prevent full-blown PD

At a glance:the largest Niemann-Pick type C1 cohort with 602 patients diagnosed over 15 years

Niemann-Pick type C1 disease (NPC1 [OMIM 257220]) is a rare and severe autosomal recessive disorder, characterized by a multitude of neurovisceral clinical manifestations and a fatal outcome with no effective treatment to date. Aiming to gain insights into the genetic aspects of the disease, clinical, genetic, and biomarker PPCS data from 602 patients referred from 47 countries and diagnosed with NPC1 in our laboratory were analyzed. Patients’ clinical data were dissected using Human Phenotype Ontology (HPO) terms, and genotype–phenotype analysis was performed. The median age at diagnosis was 10.6 years (range 0–64.5 years), with 287 unique pathogenic/likely pathogenic (P/LP) variants identified, expanding NPC1 allelic heterogeneity. Importantly, 73 P/LP variants were previously unpublished. The most frequent variants detected were: c.3019C &gt; G, p.(P1007A), c.3104C &gt; T, p.(A1035V), and c.2861C &gt; T, p.(S954L). Loss of function (LoF) variants were significantly associated with earlier age at diagnosis, highly increased biomarker levels, and a visceral phenotype (abnormal abdomen and liver morphology). On the other hand, the variants p.(P1007A) and p.(S954L) were significantly associated with later age at diagnosis (p &lt; 0.001) and mildly elevated biomarker levels (p ≤ 0.002), consistent with the juvenile/adult form of NPC1. In addition, p.(I1061T), p.(S954L), and p.(A1035V) were associated with abnormality of eye movements (vertical supranuclear gaze palsy, p ≤ 0.05). We describe the largest and most heterogenous cohort of NPC1 patients published to date. Our results suggest that besides its utility in variant classification, the biomarker PPCS might serve to indicate disease severity/progression. In addition, we establish new genotype–phenotype relationships for “frequent” NPC1 variants.</p

Structural characterization of ß-amyloid oligomer-aggregates by ion mobility mass spectrometry and electron spin resonance spectroscopy

Formation and accumulation of fibrillar plaques and aggregates of ß-amyloid peptide (Aß) in brain have been recognized as characteristics of Alzheimer s disease (AD). Oligomeric aggregates of Aß are considered critical intermediates leading to progressive neurodegeneration; however, molecular details of the oligomerization and aggregation pathway and the structures of Aß-oligomers are hitherto unclear. Using an in vitro fibril formation procedure of Aß(1 40), ß-amyloid aggregates were prepared and insoluble aggregates separated from soluble products by centrifugation. In this study, ion mobility mass spectrometry (IM-MS) was applied in combination with electron paramagnetic resonance spectroscopy (EPR) to the identification of the components of Aß-oligomers, and to their structural and topographical characterization. The formation of Aß-oligomers and aggregates was monitored by gel electrophoresis, and Aß-oligomer bands were identified by in-gel tryptic digestion and matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) to consist predominantly of Aß(1 40) peptide. First, ion mobility-MS studies of soluble Aß-aggregates prepared by incubation for 5 days were performed on a quadrupole time-of-flight mass spectrometer and revealed (1) the presence of at least two different conformational states, and (2), the formation of Met-35 oxidized products. For estimation of the size of Aß-aggregates using EPR spectroscopy, a modified Aß(1 40) peptide containing an additional N-terminal cysteine residue was prepared, and a 3-(2-iodoacetamido)-2,2,5,5-tetramethyl-1-pyrrolidinyloxy radical spin label derivative (IPSL) was coupled by S-alkylation. The EPR spectra of the spin-labeled Cys-Aß(1 40) oligomers were matched with spectra simulations using a multi-component simulation strategy, resulting in complete agreement with the gel electrophoresis results

Metabolic biomarker testing facilitates genetic diagnosis of Niemann-Pick disease by enabling classification of novel SMPD1 variants

Background: NiemannPick (NP) disease is a genetically heterogeneous metabolic disorder caused by bi-allelic variants in NPC1, NPC2, or SMPD1, with initial symptoms and age at onset varying widely. The interpretation of variants in NP disease genes is challenging when these alterations have never been observed before, and when parental samples are not available. Case Presentation: We clinically, genetically, and biochemically characterized an infant with a complex presentation and a negative family history. Clinical and paraclinical observations were consistent with NP disease. Genetic screening identified two previously unreported SMPD1 missense variants, which were initially classified as variants of unknown significance. Based on strongly increased plasma levels of lysosphingomyelin-509, both variants could be re-classified as likely pathogenic, thus establishing a diagnosis of NP disease type A/B. Conclusion: A combination of genetics with biochemical approaches facilitates conclusive diagnosis of metabolic disorders including NP disease. Blood-based biomarkers are particularly promising in this respect. [JBCGenetics 2019; 2(2.000): 147-150

Fifteen years of enzyme replacement therapy for mucopolysaccharidosis type VI (Maroteaux–Lamy syndrome) : a case report

Background: Mucopolysaccharidosis VI, or Maroteaux–Lamy disease, is an autosomal recessive disease characterized by defciency of the enzyme arylsulfatase B in the lysosomal catabolism of glycosaminoglycans. Due to reduced (or even null) enzyme activity, glycosaminoglycans (mainly dermatan sulfate) accumulates, leading to a multisystemic disease. Mucopolysaccharidosis VI induces reduced growth, coarse face, audiovisual defcits, osteoarticular deformities, and cardiorespiratory issues, hampering the quality of life of the patient. Enzyme replacement therapy with galsulfase (Naglazyme, BioMarin Pharmaceuticals Inc., USA) is the specifc treatment for this condition. Although studies have shown that enzyme replacement therapy slows the progression of the disease, the efects of long-term enzyme replacement therapy remain poorly understood. Case presentation: A 29-year-old, Caucasian, male patient diagnosed with mucopolysaccharidosis VI was treated with enzyme replacement therapy for over 15 years. Enzyme replacement therapy was initiated when patient was 13 years old. The patient evolved multiplex dysostosis, carpal tunnel syndrome, thickened mitral valve, and hearing and visual loss. Conclusions: Although enzyme replacement therapy did not prevent the main signs of mucopolysaccharidosis VI, it slowed their progression. Additionally, enzyme replacement therapy was associated with a longer survival compared with the untreated afected sibling. Taken together, the results indicate that enzyme replacement therapy positively modifed the course of the disease

Klinische Diagnostik von Lysosomalen Speicherkrankheiten

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