A modified mouse model of Friedreich's ataxia with conditional allele homozygosity delays onset of cardiomyopathy.

Friedreich's ataxia (FA) is an autosomal recessive disorder caused by a deficiency in frataxin (FXN), a mitochondrial protein that plays a critical role in the synthesis of iron-sulfur clusters (Fe-S), vital inorganic cofactors necessary for numerous cellular processes. FA is characterized by progressive ataxia and hypertrophic cardiomyopathy, with cardiac dysfunction as the most common cause of mortality in patients. Commonly used cardiac-specific mouse models of FA use the muscle creatine kinase (MCK) promoter to express Cre recombinase in cardiomyocytes and striated muscle cells in mice with one conditional allele and one floxed-out/null allele.

The clinical picture of ERCC6L2 disease: from bone marrow failure to acute leukemia.

Biallelic germ line excision repair cross-complementing 6 like 2 (ERCC6L2) variants strongly predispose to bone marrow failure (BMF) and myeloid malignancies, characterized by somatic TP53-mutated clones and erythroid predominance. We present a series of 52 subjects (35 families) with ERCC6L2 biallelic germ line variants collected retrospectively from 11 centers globally, with a follow-up of 1165 person-years. At initial investigations, 32 individuals were diagnosed with BMF and 15 with a hematological malignancy (HM).

Syndromes predisposing to leukemia are a major cause of inherited cytopenias in children.

Prolonged cytopenias are a non-specific sign with a wide differential diagnosis. Among inherited disorders, cytopenias predisposing to leukemia require a timely and accurate diagnosis to ensure appropriate medical management, including adequate monitoring and stem cell transplantation prior to the development of leukemia. We aimed to define the types and prevalences of the genetic causes leading to persistent cytopenias in children.

overexpression of frataxin causes toxicity mediated by iron-sulfur cluster deficiency.

Friedreich's ataxia is a rare disorder resulting from deficiency of frataxin, a mitochondrial protein implicated in the synthesis of iron-sulfur clusters. Preclinical studies in mice have shown that gene therapy is a promising approach to treat individuals with Friedreich's ataxia. However, a recent report provided evidence that AAVrh10-mediated overexpression of frataxin could lead to cardiotoxicity associated with mitochondrial dysfunction.

Laboratory Indices in Patients with Positive and Borderline Flow Cytometry Eosin-5-Maleimide-Screening Test Results for Hereditary Spherocytosis.

Objective: To evaluate laboratory indices in patients with hereditary spherocytosis, with positive and borderline flow cytometry eosin-5-melamide (EMA)-bound red blood cells screening test.

Study Design: We compared laboratory indices of 151 samples obtained from 139 different individual patients with negative, borderline, or positive EMA-test results. We also compared the clinical data of the patients in each EMA test results group.

Utility of the Pediatric Bleeding Questionnaire in Predicting Posttonsillectomy Bleeding.

Objective: Posttonsillectomy bleeding is a dreadful complication that may be life-threatening. Preoperative coagulation tests have not been shown to be effective in predicting this complication. The Pediatric Bleeding Questionnaire (PBQ) is a validated and sensitive tool in diagnosing children with abnormal hemostatic functions, and the objective of our study was to assess its utility as a preoperative screening tool for predicting posttonsillectomy bleeding.

Assessing the involvement of the placental microbiome and virome in preeclampsia using non coding RNA sequencing.

Objectives: Preeclampsia is a dangerous pregnancy complication. The source of preeclampsia is unknown, though the placenta is believed to have a central role in its pathogenesis. An association between maternal infection and preeclampsia has been demonstrated, yet the involvement of the placental microbiome in the etiology of preeclampsia has not been determined.

Emicizumab prophylaxis: Prospective longitudinal real-world follow-up and monitoring.

Introduction: Real-world data on prophylaxis of severe haemophilia A (HA) patients treated by emicizumab are scarce.

Aim: To study the efficacy and safety of longitudinal emicizumab prophylaxis and assess laboratory monitoring correlations in a large patient cohort.

Methods: HA patients with and without FVIII inhibitors, initiating emicizumab prophylaxis, were prospectively enrolled.

Improved transplant outcomes with myeloablative conditioning for hemophagocytic lymphohistiocytosis in HLA-matched and mismatched donors: a national multicenter retrospective study.

We report the results of national retrospective study of 45 children with hemophagocytic lymphohistiocytosis (HLH) who underwent allogeneic hematopoietic stem-cell transplantation (HSCT) in Israel between the years 2000-2018. Donors were either HLA-matched (n = 26), partially mismatched (n = 7), haploidentical (n = 8), or cord-blood (n = 4). Myeloablative conditioning (MAC) was used in 20 procedures, and reduced-intensity conditioning (RIC) in 25.

Minor Clinical Impact of COVID-19 Pandemic on Patients With Primary Immunodeficiency in Israel.

In the last few months the world has witnessed a global pandemic due to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19). Obviously, this pandemic affected individuals differently, with a significant impact on populations considered to be at high-risk. One such population, was assumed to be patients with primary genetic defect involving components or pathways of the immune system.

CDR3 and V genes show distinct reconstitution patterns in T cell repertoire post-allogeneic bone marrow transplantation.

Restoration of T cell repertoire diversity after allogeneic bone marrow transplantation (allo-BMT) is crucial for immune recovery. T cell diversity is produced by rearrangements of germline gene segments (V (D) and J) of the T cell receptor (TCR) α and β chains, and selection induced by binding of TCRs to MHC-peptide complexes. Multiple measures were proposed for this diversity.

A Study of the Efficacy and Safety of Subcutaneous Injections of Tocilizumab in Adults with Rheumatoid Arthritis.

Background: Tocilizumab is an interleukin 6 (IL-6) receptor antagonist used treat moderate to severe active rheumatoid arthritis (RA). Both intravenous (IV) and subcutaneous (SC) routes are approved for the treatment of adults with RA.

Objectives: To evaluate SC tocilizumab in a real-life clinical setting.

Patterns of salivary microbiota injury and oral mucositis in recipients of allogeneic hematopoietic stem cell transplantation.

Oral mucositis (OM) is a common debilitating dose-limiting toxicity of cancer treatment, including hematopoietic stem cell transplantation (HSCT). We hypothesized that the oral microbiome is disturbed during allogeneic HSCT, partially accounting for the variability in OM severity. Using 16S ribosomal RNA gene sequence analysis, metabolomic profiling, and computational methods, we characterized the behavior of the salivary microbiome and metabolome of 184 patients pre- and post-HSCT.

Spatial Equivalent Circuit Model for Simulation of On-Chip Thermoelectric Harvesters.

Interest in autonomous low-power energy sources has risen with the development and widespread use of devices with very low energy consumption. Interest in thermoelectric harvesters has increased against this background. Thermoelectric harvesters, especially harvesters on-chip, have peculiar properties related to the thermal route, thermal transients, and spatial temperature distribution within the chip.

Hybrid Internal Combustion Engine based Auxiliary Power Unit.

The brief presents some principles of the ON/OFF operational strategy applied to energy management of a hybrid internal combustion engine (ICE) based auxiliary power unit (APU). It is shown that significant reduction of fuel consumption (78% for the example system presented) and maintenance expenses (80% operation time decrease was attained by the system) may be achieved by such a strategy, shifting the system operation point towards corresponding optimal region. The side effect of aggravated amount of starting events is cured by employing an actively balanced supercapacitor (SC)-based emergency starter (SCS).

Cat Scratch Disease Presenting as Fever of Unknown Origin Is a Unique Clinical Syndrome.

Background: Fever of unknown origin (FUO) is a rare manifestation of cat scratch disease (CSD). Data regarding CSD-associated FUO (CSD-FUO), particularly in adults, are limited. We aimed to study disease manifestations and long-term clinical outcome.

Characterization and genotype-phenotype correlation of patients with Fanconi anemia in a multi-ethnic population.

Fanconi anemia (FA), an inherited bone marrow failure (BMF) syndrome, caused by mutations in DNA repair genes, is characterized by congenital anomalies, aplastic anemia, high risk of malignancies and extreme sensitivity to alkylating agents. We aimed to study the clinical presentation, molecular diagnosis and genotype-phenotype correlation among patients with FA from the Israeli inherited BMF registry. Overall, 111 patients of Arab (57%) and Jewish (43%) descent were followed for a median of 15 years (range: 0.

Deep microbial analysis of multiple placentas shows no evidence for a placental microbiome.

Objectives: To resolve the controversy regarding the presence of a microbiota in the placenta.

Design: Classical and molecular microbiological study.

Setting: All samples were collected during caesarean section.

Expert panel diagnosis demonstrated high reproducibility as reference standard in infectious diseases.

Objective: If a gold standard is lacking in a diagnostic test accuracy study, expert diagnosis is frequently used as reference standard. However, interobserver and intraobserver agreements are imperfect. The aim of this study was to quantify the reproducibility of a panel diagnosis for pediatric infectious diseases.

Leucocyte adhesion deficiency-A multicentre national experience.

Leucocyte adhesion deficiency (LAD) is a rare, innate autosomal recessive immunodeficiency with three subtypes. Twenty-nine patients with LADs were diagnosed and treated in Israeli Medical Centers and in the Palestinian Authority. We discuss the phenotypic, genotypic and biochemical features of LAD-I, LAD-II and LAD-III diagnosed during the neonatal period and early infancy in 18, 6 and 5 patients, respectively.

Targeted next generation sequencing for the diagnosis of patients with rare congenital anemias.

Background: Most patients with anemia are diagnosed through clinical phenotype and basic laboratory testing. Nonetheless, in cases of rare congenital anemias, some patients remain undiagnosed despite undergoing an exhaustive workup. Genetic testing is complicated by the large number of genes involved in rare anemias and the similarities in the clinical presentation of the different syndromes.

Anemia and bleeding in patients receiving anticoagulant therapy for venous thromboembolism.

In patients receiving anticoagulant therapy for venous thromboembolism (VTE), the important issue of anemia influence on the risk of bleeding has not been consistently studied. We used the large registry data RIETE (Registro Informatizado Enfermedad Tromboembólica) to compare the rate of major bleeding in patients receiving anticoagulant therapy for VTE according to the presence or absence of anemia at baseline. Patients with or without cancer were separately studied.