Routes to turbulence in Taylor-Couette flow.

Fluid flows between rotating concentric cylinders exhibit two distinct routes to turbulence. In flows dominated by inner-cylinder rotation, a sequence of linear instabilities leads to temporally chaotic dynamics as the rotation speed is increased. The resulting flow patterns occupy the whole system and sequentially lose spatial symmetry and coherence in the transition process.

Quantification of lysosphingomyelin and lysosphingomyelin-509 for the screening of acid sphingomyelinase deficiency.

Background: Acid sphingomyelinase deficiency (ASMD) is a lysosomal disorder caused by deficiency of acid sphingomyelinase (ASM) leading to the accumulation of sphingomyelin (SM) in a variety of cell types. Lysosphingomyelin (LysoSM) is the de-acetylated form of SM and it has been shown as a biomarker for ASMD in tissues, plasma, and dried blood spots (DBS) and lysosphingomyelin-509 (LysoSM509) is the carboxylated analogue of LysoSM. High levels of Lysosphingomyelin 509 (LysoSM509) have also been shown in ASMD patients.

Non-cryopreserved peripheral blood stem cells as a safe and effective alternative for autologous transplantation in multiple myeloma.

Background: Autologous stem cell transplantation is the standard procedure for multiple myeloma and the grafts are usually cryopreserved. Previous studies reported advantages in the use of fresh peripheral blood stem cells (PBSC) autotransplantation compared to cryopreservation of the grafts. This study compared the transplant-related outcomes of two graft preservation methods: fresh storage (4°C/72 h) and cryopreservation (-80°C).

Experience of the NPC Brazil Network with a Comprehensive Program for the Screening and Diagnosis of Niemann-Pick Disease Type C.

Niemann-Pick disease type C (NPC) is a lysosomal disorder caused by impaired cholesterol metabolism. Levels of lysosphingomyelin 509 (LysoSM509) have been shown elevated in dried blood spots (DBS) of NPC and acid sphingomyelinase deficiency patients. In this study, we report our experience using a two-tier approach (1st tier is the quantification of lysoSM509 by ultra-performance liquid chromatography tandem mass spectrometry followed by the 2nd tier with next-generation sequencing of the and genes).

Measurement of sulfatides in the amniotic fluid supernatant: A useful tool in the prenatal diagnosis of metachromatic leukodystrophy.

Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal disorder caused by deficiency of arylsulfatase A (ARSA), leading to an accumulation of sulfatides. Sulfatides have been quantified in urine, dried blood spots (DBS), and tissues of patients with MLD. Newborn screening (NBS) for MLD has already been proposed based on a two-tier approach with the quantification of sulfatides in DBS followed by the quantification of ARSA by liquid chromatography-tandem mass spectrometry (LC-MS/MS).

COVID-19 impact on the diagnosis of Inborn Errors of Metabolism: Data from a reference center in Brazil.

The COVID-19 pandemic led to the reorganization of health care in several countries, including Brazil. Inborn Errors of Metabolism (IEM) are a group of rare and difficult to diagnose genetic diseases caused by pathogenic variants in genes that code for enzymes, cofactors, or structural proteins affecting different metabolic pathways. The aim of this study was to evaluate how COVID-19 affected the diagnosis of patients with IEM during the first year of the pandemic in Brazil comparing two distinct periods: from March 1st, 2019 to February 29th, 2020 (TIME A) and from March 1st, 2020 to February 28th, 2021 (TIME B), by the analysis of the number of tests and diagnoses performed in a Reference Center in South of Brazil.

Sanfilippo syndrome type B: Analysis of patients diagnosed by the MPS Brazil Network.

Mucopolysaccharidosis type IIIB is a rare autosomal recessive disorder characterized by deficiency of the enzyme N-acetyl-alpha-d-glucosaminidase (NAGLU), caused by biallelic pathogenic variants in the NAGLU gene, which leads to storage of heparan sulfate and a series of clinical consequences which hallmark is neurodegeneration. In this study clinical, epidemiological, and biochemical data were obtained from MPS IIIB patients diagnosed from 2004-2019 by the MPS Brazil Network ("Rede MPS Brasil"), which was created with the goal to provide an easily accessible and comprehensive investigation of all MPS types. One hundred and ten MPS IIIB patients were diagnosed during this period.

Genotype-phenotype studies in a large cohort of Brazilian patients with Hunter syndrome.

Mucopolysaccharidosis type II (MPS II) is an X-linked inherited disease caused by pathogenic variants in the IDS gene, leading to deficiency of the lysosomal enzyme iduronate-2-sulfatase and consequent widespread storage of glycosaminoglycans, leading to several clinical consequences, with progressive manifestations which most times includes cognitive decline. MPS II has wide allelic and clinical heterogeneity and a complex genotype-phenotype correlation. We evaluated data from 501 Brazilian patients diagnosed with MPS II from 1982 to 2020.

Updated birth prevalence and relative frequency of mucopolysaccharidoses across Brazilian regions.

The mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by 11 enzyme deficiencies, classified into seven types. Data on the birth prevalence of each MPS type are available for only a few countries, and the totality of cases may be underestimated. To determine the epidemiological profile of MPS in each Brazilian region, we analyzed data collected between 1982 and 2019 by a national reference laboratory and identified 1,652 patients.

Newborn screening for lysosomal disorders in Brazil: A pilot study using customized fluorimetric assays.

Lysosomal storage disorders (LSDs) are a group of genetic disorders characterized by deficiency of specific lysosomal enzymes. In general, patients are clinically normal at birth, and progressively develop severe signs and symptoms. Diagnosis is usually made several years after onset of manifestations, preventing patients to have the benefits of the early treatment.

Diagnosis of Mucopolysaccharidoses.

The mucopolysaccharidoses (MPSs) include 11 different conditions caused by specific enzyme deficiencies in the degradation pathway of glycosaminoglycans (GAGs). Although most MPS types present increased levels of GAGs in tissues, including blood and urine, diagnosis is challenging as specific enzyme assays are needed for the correct diagnosis. Enzyme assays are usually performed in blood, with some samples (as leukocytes) providing a final diagnosis, while others (such as dried blood spots) still being considered as screening methods.

Multiplex testing for the screening of lysosomal storage disease in urine: Sulfatides and glycosaminoglycan profiles in 40 cases of sulfatiduria.

Purpose: To describe an efficient and effective multiplex screening strategy for sulfatide degradation disorders and mucolipidosis type II/III (MLII/III) using 3 mL of urine.

Methods: Glycosaminoglycans were analyzed by liquid chromatography-tandem mass spectrometry. Matrix assisted laser desorption/ionization-time of flight tandem mass spectrometry was used to identify free oligosaccharides and identify 22 ceramide trihexosides and 23 sulfatides, which are integrated by 670 calculated ratios.

Transferrin isoelectric focusing for the investigation of congenital disorders of glycosylation: analysis of a ten-year experience in a Brazilian center.

Objectives: To characterize cases of suspected congenital disorders of glycosylation (CDG) investigated in a laboratory in southern Brazil using the transferrin isoelectric focusing TfIEF test from 2008 to 2017.

Method: Observational, cross-sectional, retrospective study. The laboratory records of 1,546 individuals (median age=36 months, 25-75 IQR=10-108; males=810) submitted to the TfIEF test during the period were reviewed.

Features of the Molecular Structure and Luminescence of Rare-Earth Metal Complexes with Perfluorinated (Benzothiazolyl)phenolate Ligands.

A set of Sc, Nd, Sm, Eu, Ho, Gd, Er, Yb complexes with perfluorinated 2-(benzothiazol-2-yl)phenolate ligands Ln(SON)(DME) were synthesized by the reactions of silylamides Ln[N(SiMe)] with phenol H(SON). The structure of the initial phenol, Sc, and Er complexes was established using X-ray analysis, which revealed that the obtained compounds are mononuclear, in contrast to the binuclear non-fluorinated analogues [Ln(SON)] synthesized earlier. All the obtained complexes, both in solid state and in tetrahydrofuran (THF) solutions, upon excitation by light with λ 395 or 405 nm show intense luminance of the ligands at 440-470 nm.

Information and Diagnosis Networks - tools to improve diagnosis and treatment for patients with rare genetic diseases.

Brazil is a country of continental dimensions and most genetic services are concentrated in the Southeast and South, including the Medical Genetics Service of the Hospital de Clínicas de Porto Alegre (MGS/HCPA). As many areas on the country do not have adequate medical genetics support, networks were designed to extend the service of the MGS/HCPA reference center. This paper presents the information and diagnosis networks that have their headquarters at MGS/HCPA: SIAT (National Information System on Teratogenic Agents), SIEM (Information Service on Inborn Errors of Metabolism), Alô Genética (Hello Genetics - Medical Genetics Information Service for Primary Health Care Professionals); Rede MPS Brasil (MPS-Mucopolysaccharidosis Brazil Network); Rede EIM Brasil (IEM-Inborn Errors of Metabolism Brazil Network), Rede NPC Brasil (Niemann-Pick C - NPC Brazil Network), Rede DLD Brasil (LSD-Lysosomal Storage Disorders Brazil Network), Rede DXB (MSUD-Maple Syrup Urine Disease Network), RedeBRIM (Brazilian Network of Reference and Information in Microdeletion Syndromes Project), Rede Neurogenética (Neurogenetics Network), and Rede Brasileira de Câncer Hereditário (Brazilian Hereditary Cancer Network).

Lysosomal diseases: Overview on current diagnosis and treatment.

Lysosomal diseases (LDs), also known as lysosomal storage diseases (LSDs), are a heterogeneous group of conditions caused by defects in lysosomal function. LDs may result from deficiency of lysosomal hydrolases, membrane-associated transporters or other non-enzymatic proteins. Interest in the LD field is growing each year, as more conditions are, or will soon be treatable.

Population medical genetics: translating science to the community.

Rare genetic disorders are currently in the spotlight due to the elevated number of different conditions and significant total number of affected patients. The study of these disorders is extremely helpful for the elucidation of physiological processes related with complex disorders. Isolated populations are instrumental for the study of genetic disorders, considering their homogeneity and high proportion of affected patients in a small geographic area.

Turbulence and jet-driven zonal flows: Secondary circulation in rotating fluids due to asymmetric forcing.

We report on experiments and modeling on a rotating confined liquid that is forced by circumferential jets coaxial with the rotation axis, wherein system-scale secondary flows are observed to emerge. The jets are evenly divided in number between inlets and outlets and have zero net mass transport. For low forcing strengths the sign of this flow depends on the sign of a sloped end cap, which simulates a planetary β plane.

Molecular and biochemical biomarkers for diagnosis and therapy monitorization of Niemann-Pick type C patients.

Background: Niemann-Pick type C (NP-C), one of 50 inherited lysosomal storage disorders, is caused by NPC protein impairment that leads to unesterified cholesterol accumulation in late endosomal/lysosomal compartments. The clinical manifestations of NP-C include hepatosplenomegaly, neurological and psychiatric symptoms. Current diagnosis for NP-C is based on observation of the accumulated cholesterol in fibroblasts of affected individuals, using an invasive and time expensive test, called Filipin staining.

Relative frequency and estimated minimal frequency of Lysosomal Storage Diseases in Brazil: Report from a Reference Laboratory.

Lysosomal storage diseases (LSDs) comprise a heterogeneous group of more than 50 genetic conditions of inborn errors of metabolism (IEM) caused by a defect in lysosomal function. Although there are screening tests for some of these conditions, diagnosis usually depends on specific enzyme assays, which are only available in a few laboratories around the world. A pioneer facility for the diagnosis of IEM and LSDs was established in the South of Brazil in 1982 and has served as a reference service since then.

Elevation of glycosaminoglycans in the amniotic fluid of a fetus with mucopolysaccharidosis VII.

Objective: The aim of this study was to quantify glycosaminoglycans (GAGs) in amniotic fluid (AF) from an MPS VII fetus compared with age-matched fetuses obtained from normal pregnancies.

Method: Disaccharides were measured by liquid chromatography tandem mass spectrometry, compared to age-matched controls. Enzyme assay was performed in AF supernatant or cultured amniocytes.

Neurological outcomes after hematopoietic stem cell transplantation for cerebral X-linked adrenoleukodystrophy, late onset metachromatic leukodystrophy and Hurler syndrome.

Objective: To describe survival and neurological outcomes after HSCT for these disorders.

Methods: Seven CALD, 2 MLD and 2 MPS-IH patients underwent HSCT between 2007 and 2014. Neurological examinations, magnetic resonance imaging, molecular and biochemical studies were obtained at baseline and repeated when appropriated.

Oxidative and nitrative stress and pro-inflammatory cytokines in Mucopolysaccharidosis type II patients: effect of long-term enzyme replacement therapy and relation with glycosaminoglycan accumulation.

Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disease caused by a deficient activity of iduronate-2-sulfatase, leading to abnormal accumulation of glycosaminoglycans (GAG). The main treatment for MPS II is enzyme replacement therapy (ERT). Previous studies described potential benefits of six months of ERT against oxidative stress in patients.