Microbiota That Affect Risk for Shigellosis in Children in Low-Income Countries

Pathogens in the gastrointestinal tract exist within a vast population of microbes. We examined associations between pathogens and composition of gut microbiota as they relate to Shigella spp./enteroinvasive Escherichia coli infection. We analyzed 3,035 stool specimens (1,735 nondiarrheal and 1,300 moderate-to-severe diarrheal) from the Global Enteric Multicenter Study for 9 enteropathogens. Diarrheal specimens had a higher number of enteropathogens (diarrheal mean 1.4, nondiarrheal mean 0.95; p<0.0001). Rotavirus showed a negative association with Shigella spp. in cases of diarrhea (odds ratio 0.31, 95% CI 0.17–0.55) and had a large combined effect on moderate-to-severe diarrhea (odds ratio 29, 95% CI 3.8–220). In 4 Lactobacillus taxa identified by 16S rRNA gene sequencing, the association between pathogen and disease was decreased, which is consistent with the possibility that Lactobacillus spp. are protective against Shigella spp.–induced diarrhea. Bacterial diversity of gut microbiota was associated with diarrhea status, not high levels of the Shigella spp. ipaH gene.     

Recrystallization techniques for the synthesis of ZnO nanorods: an in situ process for carbon doping and enhancing the dispersion concentration of ZnO nanorods

Zinc acetate is recrystallized as lumber-shaped tetragonal rods by a novel recrystallization technique. Subsequently, the recrystallized zinc acetate is converted into ZnO nanorods in a glass vial by the simplest and cheapest method without utilizing any expensive instrumentation. Carbon is doped in ZnO nanorods during the preparation ZnO nanorods without any extra steps, chemicals, or effort. The carbon-doped ZnO nanorods can be dispersed in a solvent at very high concentrations and are also stable for a very long time, which are comparatively higher than those of the other existing ZnO nanoparticles. The higher dispersion concentration and higher stability of ZnO nanoparticles are explained by a scheme that demonstrates the suspending mechanism of the ZnO nanoparticles at higher concentrations with higher stabilities in a solvent through the anchoring groups of carbon. No materials are used for surface modification; no surface coatings, ionic materials, or pH controlling materials are used to increase the dispersion concentration and stability. This is the first observation of the doped carbon playing a significant role in the dispersion of ZnO nanoparticles at higher concentrations by withholding them in the solvent. Therefore, doped carbon at the surface of ZnO nanoparticles prevents the self-aggregation of ZnO nanoparticles in the solution phase by interfacial barrier layers among ZnO nanorods and interfacial interactive layer between ZnO nanorod and solvent.

Dispersed ZnO hexagonal nanorods in ethanol solvent and its interfacial behavior in this liquid phase.     

Detection of genomic deletions of PKP2 in arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease that predominantly affects the right ventricle and is associated with ventricular arrhythmias that may lead to sudden cardiac death. Mutations within at least seven separate genes have been identified to cause ARVC, however a genetic culprit remains elusive in approximately 50% of cases. Although negative genetic testing may be secondary to pathogenic mutations within undiscovered genes, an alternative explanation may be the presence of large deletions or duplications involving known genes. These large copy number variants may not be detected with standard clinical genetic testing which is presently limited to direct DNA sequencing. We describe two cases of ARVC possessing large deletions involving plakophilin‐2 (PKP2) identified with microarray analysis and/or multiplex ligation‐dependent probe amplification (MLPA) that would have been classified as genotype negative with standard clinical genetic testing. A deletion of the entire coding region of PKP2 excluding exon 1 was identified in patient 1 and his son. In patient 2, MLPA analysis of PKP2 revealed deletion of the entire gene with subsequent microarray analysis demonstrating a de novo 7.9 Mb deletion of chromosome 12p12.1p11.1. These findings support screening for large copy number variants in clinically suspected ARVC cases without clear disease causing mutations following initial sequencing analysis.     

Age-dependent neurological phenotypes in a mouse model of PRRT2-related diseases

Paroxysmal kinesigenic dyskinesia is an episodic movement disorder caused by dominant mutations in the proline-rich transmembrane protein PRRT2, with onset in childhood and typically with improvement or resolution by middle age. Mutations in the same gene may also cause benign infantile seizures, which begin in the first year of life and typically remit by the age of 2 years. Many details of PRRT2 function at the synapse, and the effects of mutations on neuronal excitability in the pathophysiology of epilepsy and dyskinesia, have emerged through the work of several groups over the last decade. However, the age dependence of the phenotypes has not been explored in detail in transgenic models. Here, we report our findings in heterozygous and homozygous Prrt2 knockout mice that recapitulate the age dependence of dyskinesia seen in the human disease. We show that Prrt2 deletion reduces the levels of synaptic proteins in a dose-dependent manner that is most pronounced at postnatal day 5 (P5), attenuates at P60, and disappears by P180. In a test for foot slippage while crossing a balance beam, transient loss of coordination was most pronounced at P60 and less prominent at age extremes. Slower traverse time was noted in homozygous knockout mice only, consistent with the ataxia seen in rare individuals with biallelic loss of function mutations in Prrt2. We thus identify three age-dependent phenotypic windows in the mouse model, which recapitulate the pattern seen in humans with PRRT2-related diseases.

     

Treatment of variola major with cytosine arabinoside.

A controlled study of the efficacy of cytosine arabinoside in the treatment of patients with variola major was performed. Cytosine aravinoside was given intravenously at a dose approximating 3 mg/kg of body weight every 24 hr for up to seven days. All nine patients receiving cytosine arabinoside and four of the 11 patients receiving placebo died. In three of the patients receiving cytosine aravinoside, death occurred late in the illness at a time when the patient's lesions began to dry up, the patient's temperature became normal, and the patient's general condition appeared to improve. The virus could be isolated from the blood at day 7 from three of four patients treated with cytosine arabinoside as compared with zero of six control patients. Hematologic data showed a depression in the number of circulating granulocytes. It is possible that the drug lowered the resistance to infection either through direct suppression of granulocytes or through interference with other immune mechanisms. Cytosine arabinside administered in the doses used in this study is not effective in the treatment of variola major.