The role of children in the spread of COVID-19: Using household data from Bnei Brak, Israel, to estimate the relative susceptibility and infectivity of children.

One of the significant unanswered questions about COVID-19 epidemiology relates to the role of children in transmission. This study uses data on infections within households in order to estimate the susceptibility and infectivity of children compared to those of adults. The data were collected from households in the city of Bnei Brak, Israel, in which all household members were tested for COVID-19 using PCR (637 households, average household size of 5.3). In addition, serological tests were performed on a subset of the individuals in the study. Inspection of the PCR data shows that children are less likely to be tested positive compared to adults (25% of children positive over all households, 44% of adults positive over all households, excluding index cases), and the chance of being positive increases with age. Analysis of joint PCR/serological data shows that there is under-detection of infections in the PCR testing, which is more substantial in children. However, the differences in detection rates are not sufficient to account for the differences in PCR positive rates in the two age groups. To estimate relative transmission parameters, we employ a discrete stochastic model of the spread of infection within a household, allowing for susceptibility and infectivity parameters to differ among children and adults. The model is fitted to the household data using a simulated maximum likelihood approach. To adjust parameter estimates for under-detection of infections in the PCR results, we employ a multiple imputation procedure using estimates of under-detection in children and adults, based on the available serological data. We estimate that the susceptibility of children (under 20 years old) is 43% (95% CI: [31%, 55%]) of the susceptibility of adults. The infectivity of children was estimated to be 63% (95% CI: [37%, 88%]) relative to that of adults.

Genotype-phenotype correlations analysis of mutations in the phenylalanine hydroxylase (PAH) gene.

The aims of our research were to define the genotype-phenotype correlations of mutations in the phenylalanine hydroxylase (PAH) gene that cause phenylketonuria (PKU) among the Israeli population. The mutation spectrum of the PAH gene in PKU patients in Israel is described, along with a discussion on genotype-phenotype correlations. By using polymerase chain reaction/denaturing high-performance liquid chromatography (PCR/dHPLC) and DNA sequencing, we screened all exons of the PAH gene in 180 unrelated patients with four different PKU phenotypes [classic PKU, moderate PKU, mild PKU, and mild hyperphenylalaninemia (MHP)]. In 63.2% of patient genotypes, the metabolic phenotype could be predicted, though evidence is also found for both phenotypic inconsistencies among subjects with more than one type of mutation in the PAH gene. Data analysis revealed that about 25% of patients could participate in the future in (6R)-L: -erythro-5, 6, 7, 8-tetrahydrobiopterin (BH4) treatment trials according to their mutation genotypes. This study enables us to construct a national database in Israel that will serve as a valuable tool for genetic counseling and a prognostic evaluation of future cases of PKU.

Clinical and molecular findings in a family with the carbonic anhydrase II deficiency syndrome.

Carbonic anhydrase II (CA2) deficiency syndrome is an autosomal recessive disorder leading to osteopetrosis, renal tubular acidosis, and cerebral calcifications. Affected members of an Arab family with the CA2 deficiency syndrome carried the "Egyptian mutation" in CA2, i.e., c.191 del A, H64fsX90. One affected member, homozygote for the mutation, developed primary pulmonary hypertension. Primary pulmonary hypertension was never described before in patients with this unique syndrome. The likelihood of both occurring randomly in a single individual is very low. We therefore speculate that there might be a possibility of an etiologic link between these entities.

Flow conditions modulate homocysteine induced changes in the expression of endothelial cell genes associated with cell-cell interaction and cytoskeletal rearrangement.

In the present study we analyzed changes in the pattern of gene expression in endothelial cells (HUVEC) exposed to elevated homocysteine levels under flow conditions. RNA samples of untreated and homocysteine treated EC were analyzed using a human cDNA array containing 588 cDNAs relevant to the cardiovascular system. Exposure to homocysteine under flow resulted in altered expression of 8 genes, the alterations of 3 of which were further confirmed by RT-PCR analysis: upregulation of MCP-1 and of profilin-I, and downregulation of alpha-catenin. The increased expression of profilin-I and the decreased expression of alpha-catenin were also confirmed at the protein level by Western blot analysis. Furthermore, immunostaining for alpha-catenin demonstrated complete loss of the protein from intercellular junctions following exposure to homocysteine under flow. All these changes were not observed in cells exposed to homocysteine under static conditions. We show that under flow conditions, homocysteine modulates the expression of genes/proteins involved in actin cytoskeleton reorganization, as well as in the formation and/or maintenance of cell-cell junction, thus contributing to the morphological changes (e.g. cell retraction) reflecting endothelial cell injury.