Prevalence of hemoglobin variants in a diabetic population at high risk of hemoglobinopathies and optimization of HbA1c monitoring by incorporating HPLC in the laboratory workup

Background: In Tunisia, diabetes mellitus and hemoglobinopathies are major public health problems. Glycated hemoglobin (HbA1c) is  recommended for long-term monitoring of diabetes mellitus, but the presence of hemoglobin variants may interfere with HbA1c measurement. The aim was to determine the prevalence of hemoglobin variants in Tunisian diabetics and optimize the monitoring of diabetics using HbA1c.Methods: The study enrolled 9,792 Tunisian diabetic patients. HbA1c was measured by cation-exchange highpressure liquid chromatography (HPLC). All the chromatograms were analyzed for the presence of Hbvariants.Results: We identified 228 cases (2.33%) of Hb variants with D-10 HPLC (Bio-Rad): 191 with HbA/S trait, 27 with HbA/C trait, and 10 hemoglobin variants with the mention ‘Variant-Window’ on the chromatograms and subsequently identified as HbA/S on Variant I HPLC (Bio-Rad). Thus, the prevalence of HbS was 2.05%. We did not find any homozygous variant. All HbA1c results were reported to the treating physician.Conclusions: To evaluate glycated hemoglobin in populations with a high prevalence of hemoglobinopathies, we should use the HPLC method, which is easy, economical, and reliable. Based on an algorithm, hemoglobinvariants visualized on HPLC should be reported to the physician to improve the management of patients.Keywords: hemoglobinopathies; HbA1c; HPLC; diabetes mellitus; prevalence; Tunisi

Is there an optimal strategy for real-time continuous glucose monitoring in pediatrics? A 12-month French multi-center, prospective, controlled randomized trial (Start-In!)

AIM: To compare the efficacy of three strategies for real-time continuous glucose monitoring (RT-CGM) over 12 months in children and adolescents with type 1 diabetes. METHODS: A French multicenter trial (NCT00949221) with a randomized, controlled, prospective, open, and parallel-group design was conducted. After 3 months of RT-CGM, patients were allocated to one of three groups: return to self-monitoring of blood glucose, continuous CGM (80% of the time), or discontinuous CGM (40% of the time). The primary outcome was hemoglobin A1c (HbA1c) levels from 3 to 12 months. The secondary outcomes were acute metabolic events, hypoglycemia, satisfaction with CGM and cost. RESULTS: We included 151 subjects, aged 2 to 17 years, with a mean HbA1c level of 8.5% (SD0.7; 69 mmol/mol). The longitudinal change in HbA1c levels was similar in all three groups, at 3, 6, 9 and 12 months. The medical secondary endpoints did not differ between groups. The rate of severe hypoglycemia was significantly lower than that for the pretreatment year for the entire study population. Subjects reported consistent use and good tolerance of the device, regardless of age or insulin treatment. The use of full-time RT-CGM for 3 months costs the national medical insurance system €2629 per patient. CONCLUSION: None of the three long-term RT-CGM strategies evaluated in pediatric type 1 diabetes was superior to the others in terms of HbA1c levels. CGM-use for 3 months decreased rates of severe hypoglycemia. Our results confirm the feasibility of long-term RT-CGM-use and the need to improve educational support for patients and caregivers

Neurodevelopmental and Epilepsy Phenotypes in Individuals With Missense Variants in the Voltage-Sensing and Pore Domains of KCNH5

Background and Objectives KCNH5 encodes the voltage-gated potassium channel EAG2/Kv10.2. We aimed to delineate the neurodevelopmental and epilepsy phenotypic spectrum associated with de novo KCNH5 variants.Methods We screened 893 individuals with developmental and epileptic encephalopathies for KCNH5 variants using targeted or exome sequencing. Additional individuals with KCNH5 variants were identified through an international collaboration. Clinical history, EEG, and imaging data were analyzed; seizure types and epilepsy syndromes were classified. We included 3 previously published individuals including additional phenotypic details.Results We report a cohort of 17 patients, including 9 with a recurrent de novo missense variant p.Arg327His, 4 with a recurrent missense variant p.Arg333His, and 4 additional novel missense variants. All variants were located in or near the functionally critical voltage-sensing or pore domains, absent in the general population, and classified as pathogenic or likely pathogenic using the American College of Medical Genetics and Genomics criteria. All individuals presented with epilepsy with a median seizure onset at 6 months. They had a wide range of seizure types, including focal and generalized seizures. Cognitive outcomes ranged from normal intellect to profound impairment. Individuals with the recurrent p.Arg333His variant had a self-limited drug-responsive focal or generalized epilepsy and normal intellect, whereas the recurrent p.Arg327His variant was associated with infantile-onset DEE. Two individuals with variants in the pore domain were more severely affected, with a neonatal-onset movement disorder, early-infantile DEE, profound disability, and childhood death.Discussion We describe a cohort of 17 individuals with pathogenic or likely pathogenic missense variants in the voltage-sensing and pore domains of Kv10.2, including 14 previously unreported individuals. We present evidence for a putative emerging genotype-phenotype correlation with a spectrum of epilepsy and cognitive outcomes. Overall, we expand the role of EAG proteins in human disease and establish KCNH5 as implicated in a spectrum of neurodevelopmental disorders and epilepsy.</p

Conditions for Shear Band Formation in Tungsten Alloys

Local loading conditions associated with shear banding formation in laboratory tungsten alloy specimens are examined. The specimens consist of compression specimens of large length to diameter ratio made of 91W-6Ni-3Co swaged tungsten alloys tested with the Hopkinson pressure bar and symmetric Taylor techniques. Experimental and numerical results provide insights on the effect of the hydrostatic pressure on shear band formation in tungsten alloys.Les conditions locales de chargement liées aux observations expérimentales de bandes de cisaillement des alliages de tungstène sont examinées. Ces bandes ont été observées avec des échantillons de compression dynamique à grand rapport de longueur sur diamètre composés d'alliages corroyés de tungstène 91W-6Ni-3Co. Les échantillons ont été testés à l'aide des techniques aux barres d'Hopkinson et de Taylor symétrique. Les résultats expérimentaux et numériques révèlent le rôle de la pression hydrostatique sur la formation de bandes de cisaillement dans les alliages de tungstène

CORRELATION OF MICROSTRUCTURE AND TEMPERED MARTENSITE EMBRITTLEMENT IN 2 4340 STEELS

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