Promjene u broju eritrocita i trombocita pokazatelji su babezioze u pasa

In the present study we evaluated the haematological changes in samples of blood obtained from 30 dogs naturally infected with large Babesia, before and after therapy with imidocarb dipropionate. The results were compared with those obtained from 50 healthy dogs. The evaluation included red blood cell count (RBC), mean corpuscular volume (MCV), haematocrit (HTC), red distribution width (RDW), platelet counts (PLT), mean platelet volume (MPV) and plateletcrit (PCT). Analyses were performed with an automated blood cell counter (Abbott Cell-Dyn CD 3500). The most common disorders in affected dogs were thrombocytopenia with decreased PCT and increased MPV (suggested activation of platelets). Since RDW did not show any changes in babesiosis (suggested uniform population of RBC’s), decreased RBC, MCV and HCT were present in the majority of dogs with babesiosis, before and after therapy. Our results suggest that erythrocyte and platelet indices could provide clinical information about the underlying conditions of anaemia and thrombocytopenia.U istraživanju su vrednovane hematološke promjene u uzorcima krvi 30 pasa s babeziozom, prirodno zaraženih, prije i poslije terapije imidocarb-dipropionatom. Rezultati su uspoređeni s rezultatima dobivenim u 50 zdravih pasa. Istraženi su broj eritrocita, prosječni volumen eritrocita, hematokrit, distribucija eritrocita, broj trombocita, prosječni volumen trombocita i trombokrit. Mjerenja su izvedena upotrebom automatskog hematološkog analizatora (Abbott Cell-Dyn CD 3500). Najčešća promjena kod pasa s babeziozom bila je trombocitopenija sa sniženim trombokritom i povećanim prosječnim volumenom trombocita, koji upućuje na aktivaciju trombocita. Do promjena u raspodjeli eritrocita nije došlo kod babezioze (jednolična populacija eritrocita). Sniženi broj eritrocita, prosječni volumen eritrocita i hematokrit bili su prisutni u većine pasa oboljelih od babezioze, prije i poslije liječenja. Rezultati upućuju na to da promjene u broju eritrocita i trombocita mogu biti korisne u pružanju kliničkih informacija o mogućim uzrocima anemije i trombocitopenije

Promjene u broju eritrocita i trombocita pokazatelji su babezioze u pasa

In the present study we evaluated the haematological changes in samples of blood obtained from 30 dogs naturally infected with large Babesia, before and after therapy with imidocarb dipropionate. The results were compared with those obtained from 50 healthy dogs. The evaluation included red blood cell count (RBC), mean corpuscular volume (MCV), haematocrit (HTC), red distribution width (RDW), platelet counts (PLT), mean platelet volume (MPV) and plateletcrit (PCT). Analyses were performed with an automated blood cell counter (Abbott Cell-Dyn CD 3500). The most common disorders in affected dogs were thrombocytopenia with decreased PCT and increased MPV (suggested activation of platelets). Since RDW did not show any changes in babesiosis (suggested uniform population of RBC’s), decreased RBC, MCV and HCT were present in the majority of dogs with babesiosis, before and after therapy. Our results suggest that erythrocyte and platelet indices could provide clinical information about the underlying conditions of anaemia and thrombocytopenia.U istraživanju su vrednovane hematološke promjene u uzorcima krvi 30 pasa s babeziozom, prirodno zaraženih, prije i poslije terapije imidocarb-dipropionatom. Rezultati su uspoređeni s rezultatima dobivenim u 50 zdravih pasa. Istraženi su broj eritrocita, prosječni volumen eritrocita, hematokrit, distribucija eritrocita, broj trombocita, prosječni volumen trombocita i trombokrit. Mjerenja su izvedena upotrebom automatskog hematološkog analizatora (Abbott Cell-Dyn CD 3500). Najčešća promjena kod pasa s babeziozom bila je trombocitopenija sa sniženim trombokritom i povećanim prosječnim volumenom trombocita, koji upućuje na aktivaciju trombocita. Do promjena u raspodjeli eritrocita nije došlo kod babezioze (jednolična populacija eritrocita). Sniženi broj eritrocita, prosječni volumen eritrocita i hematokrit bili su prisutni u većine pasa oboljelih od babezioze, prije i poslije liječenja. Rezultati upućuju na to da promjene u broju eritrocita i trombocita mogu biti korisne u pružanju kliničkih informacija o mogućim uzrocima anemije i trombocitopenije

Abnormal hypermethylation at imprinting control regions in patients with S-adenosylhomocysteine hydrolase (AHCY) deficiency

S-adenosylhomocysteine hydrolase (AHCY) deficiency is a rare autosomal recessive disorder in methionine metabolism caused by mutations in the AHCY gene. Main characteristics are psychomotor delay including delayed myelination and myopathy (hypotonia, absent tendon reflexes etc.) from birth, mostly associated with hypermethioninaemia, elevated serum creatine kinase levels and increased genome wide DNA methylation. The prime function of AHCY is to hydrolyse and efficiently remove S-adenosylhomocysteine, the by-product of transmethylation reactions and one of the most potent methyltransferase inhibitors. In this study, we set out to more specifically characterize DNA methylation changes in blood samples from patients with AHCY deficiency. Global DNA methylation was increased in two of three analysed patients. In addition, we analysed the DNA methylation levels at differentially methylated regions (DMRs) of six imprinted genes (MEST, SNRPN, LIT1, H19, GTL2 and PEG3) as well as Alu and LINE1 repetitive elements in seven patients. Three patients showed a hypermethylation in up to five imprinted gene DMRs. Abnormal methylation in Alu and LINE1 repetitive elements was not observed. We conclude that DNA hypermethylation seems to be a frequent but not a constant feature associated with AHCY deficiency that affects different genomic regions to different degrees. Thus AHCY deficiency may represent an ideal model disease for studying the molecular origins and biological consequences of DNA hypermethylation due to impaired cellular methylation status

Universally Composable Accumulators

Accumulators, first introduced by Benaloh and de Mare (Eurocrypt 1993), are compact representations of arbitrarily large sets and can be used to prove claims of membership or non-membership about the underlying set. They are almost exclusively used as building blocks in real-world complex systems, including anonymous credentials, group signatures and, more recently, anonymous cryptocurrencies. Having rigorous security analysis for such systems is crucial for their adoption and safe use in the real world, but it can turn out to be extremely challenging given their complexity. In this work, we provide the first universally composable (UC) treatment of cryptographic accumulators. There are many different types of accumulators: some support additions, some support deletions and some support both; and, orthogonally, some support proofs of membership, some support proofs of non-membership, and some support both. Additionally, some accumulators support public verifiability of set operations, and some do not. Our UC definition covers all of these types of accumulators concisely in a single functionality, and captures the two basic security properties of accumulators: correctness and soundness. We then prove the equivalence of our UC definition to standard accumulator definitions. This implies that existing popular accumulator schemes, such as the RSA accumulator, already meet our UC definition, and that the security proofs of existing systems that leverage such accumulators can be significantly simplified. Finally, we use our UC definition to get simple proofs of security. We build an accumulator in a modular way out of two weaker accumulators (in the style of Baldimtsi et. al (Euro S&P 2017), and we give a simple proof of its UC security. We also show how to simplify the proofs of security of complex systems such as anonymous credentials. Specifically, we show how to extend an anonymous credential system to support revocation by utilizing our results on UC accumulators

Consensus recommendations for the diagnosis, treatment and follow-up of inherited methylation disorders

Inherited methylation disorders are a group of rarely reported, probably largely underdiagnosed disorders affecting transmethylation processes in the metabolic pathway between methionine and homocysteine. These are methionine adenosyltransferase I/III, glycine N-methyltransferase, S-adenosylhomocysteine hydrolase and adenosine kinase deficiencies. This paper provides the first consensus recommendations for the diagnosis and management of methylation disorders. Following search of the literature and evaluation according to the SIGN-methodology of all reported patients with methylation defects, graded recommendations are provided in a structured way comprising diagnosis (clinical presentation, biochemical abnormalities, differential diagnosis, newborn screening, prenatal diagnosis), therapy and follow-up. Methylation disorders predominantly affect the liver, central nervous system and muscles, but clinical presentation can vary considerably between and within disorders. Although isolated hypermethioninemia is the biochemical hallmark of this group of disorders, it is not always present, especially in early infancy. Plasma S-adenosylmethionine and S-adenosylhomocysteine are key metabolites for the biochemical clarification of isolated hypermethioninemia. Mild hyperhomocysteinemia can be present in all methylation disorders. Methylation disorders do not qualify as primary targets of newborn screening. A low-methionine diet can be beneficial in patients with methionine adenosyltransferase I/III deficiency if plasma methionine concentrations exceed 800 μmol/L. There is some evidence that this diet may also be beneficial in patients with S-adenosylhomocysteine hydrolase and adenosine kinase deficiencies. S-adenosylmethionine supplementation may be useful in patients with methionine adenosyltransferase I/III deficiency. Recommendations given in this article are based on general principles and in practice should be adjusted individually according to patient's age, severity of the disease, clinical and laboratory findings

Novel cerebrospinal fluid biomarkers of glucose transporter type 1 deficiency syndrome: Implications beyond the brain's energy deficit

We used next-generation metabolic screening to identify new biomarkers for improved diagnosis and pathophysiological understanding of glucose transporter type 1 deficiency syndrome (GLUT1DS), comparing metabolic cerebrospinal fluid (CSF) profiles from 12 patients to those of 116 controls. This confirmed decreased CSF glucose and lactate levels in patients with GLUT1DS and increased glutamine at group level. We identified three novel biomarkers significantly decreased in patients, namely gluconic + galactonic acid, xylose-α1-3-glucose, and xylose-α1-3-xylose-α1-3-glucose, of which the latter two have not previously been identified in body fluids. CSF concentrations of gluconic + galactonic acid may be reduced as these metabolites could serve as alternative substrates for the pentose phosphate pathway. Xylose-α1-3-glucose and xylose-α1-3-xylose-α1-3-glucose may originate from glycosylated proteins; their decreased levels are hypothetically the consequence of insufficient glucose, one of two substrates for O-glucosylation. Since many proteins are O-glucosylated, this deficiency may affect cellular processes and thus contribute to GLUT1DS pathophysiology. The novel CSF biomarkers have the potential to improve the biochemical diagnosis of GLUT1DS. Our findings imply that brain glucose deficiency in GLUT1DS may cause disruptions at the cellular level that go beyond energy metabolism, underlining the importance of developing treatment strategies that directly target cerebral glucose uptake

Examining the validity of the Athlete Engagement Questionnaire (AEQ) within a Portuguese sport setting

Sport psychology literature suggests that understanding engagement levels is pivotal to promote positive sporting experiences among athletes. The purpose of this study was to examine the psychometric properties of the Athlete Engagement Questionnaire among Portuguese sport athletes. Two distinct samples of Portuguese athletes from different competitive levels were collected, and the results of a confirmatory factor analysis demonstrated a good fit of the model to the data. A review of the psychometric properties indicated that all factors showed good composite reliability, convergent validity, and discriminant validity. In addition, a multi-groups analysis showed the invariance of the model in two independent samples providing evidence of cross validity. Implications of these results for scholars and coaches are discussed and guidelines for future studies are suggested

The genotypic and phenotypic spectrum of MTO1 deficiency.

BACKGROUND: Mitochondrial diseases, a group of multi-systemic disorders often characterized by tissue-specific phenotypes, are usually progressive and fatal disorders resulting from defects in oxidative phosphorylation. MTO1 (Mitochondrial tRNA Translation Optimization 1), an evolutionarily conserved protein expressed in high-energy demand tissues has been linked to human early-onset combined oxidative phosphorylation deficiency associated with hypertrophic cardiomyopathy, often referred to as combined oxidative phosphorylation deficiency-10 (COXPD10). MATERIAL AND METHODS: Thirty five cases of MTO1 deficiency were identified and reviewed through international collaboration. The cases of two female siblings, who presented at 1 and 2years of life with seizures, global developmental delay, hypotonia, elevated lactate and complex I and IV deficiency on muscle biopsy but without cardiomyopathy, are presented in detail. RESULTS: For the description of phenotypic features, the denominator varies as the literature was insufficient to allow for complete ascertainment of all data for the 35 cases. An extensive review of all known MTO1 deficiency cases revealed the most common features at presentation to be lactic acidosis (LA) (21/34; 62% cases) and hypertrophic cardiomyopathy (15/34; 44% cases). Eventually lactic acidosis and hypertrophic cardiomyopathy are described in 35/35 (100%) and 27/34 (79%) of patients with MTO1 deficiency, respectively; with global developmental delay/intellectual disability present in 28/29 (97%), feeding difficulties in 17/35 (49%), failure to thrive in 12/35 (34%), seizures in 12/35 (34%), optic atrophy in 11/21 (52%) and ataxia in 7/34 (21%). There are 19 different pathogenic MTO1 variants identified in these 35 cases: one splice-site, 3 frameshift and 15 missense variants. None have bi-allelic variants that completely inactivate MTO1; however, patients where one variant is truncating (i.e. frameshift) while the second one is a missense appear to have a more severe, even fatal, phenotype. These data suggest that complete loss of MTO1 is not viable. A ketogenic diet may have exerted a favourable effect on seizures in 2/5 patients. CONCLUSION: MTO1 deficiency is lethal in some but not all cases, and a genotype-phenotype relation is suggested. Aside from lactic acidosis and cardiomyopathy, developmental delay and other phenotypic features affecting multiple organ systems are often present in these patients, suggesting a broader spectrum than hitherto reported. The diagnosis should be suspected on clinical features and the presence of markers of mitochondrial dysfunction in body fluids, especially low residual complex I, III and IV activity in muscle. Molecular confirmation is required and targeted genomic testing may be the most efficient approach. Although subjective clinical improvement was observed in a small number of patients on therapies such as ketogenic diet and dichloroacetate, no evidence-based effective therapy exists