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In this study, it is aimed to determine effect of ultrasonication on some chemical and microbiological properties of sour cherry juice by response surface methodology, since ultrasound is known as an alternative method for thermal food processing. Sour cherry juice was sonicated at varying amplitude levels (50, 75, 100%); moderate temperatures (20, 30, 40 ℃); and treatment times of 2, 6, 10 min at a constant frequency of 20 kHz. Different ultrasonication amplitudes, temperatures, and times had no significant effect on pH,°Bx, and titratable acidity. A significant increase in total monomeric anthocyanins was observed as the amplitude level and temperature increased (p < 0.01). An increase in the total phenolics was also obtained as the temperature increased (p < 0.05). The effect of amplitude level on antioxidant capacity of sour cherry juice was also found significant (p < 0.05). Color parameters (L*, a*, b*, C, h) generally increased by increasing temperature, amplitude level, and treatment time. It was determined that Escherichia coli O157:H7 significantly affected by temperature and treatment time (p < 0.05). [ABSTRACT FROM AUTHOR]

The powder samples and methanol extract of 11 medicinal plants were subjected to analysis of proximate composition and measurement of antioxidant activity. Different parameters studied include phenolic contents, moisture, ash, crude fiber, fats and waxes. The assays employed were ferric reducing antioxidant power, trolox equivalent antioxidant capacity and scavenging effect on the 1,1-diphenyl-2-picrylhydrazyl free radical. Results obtained indicate that the antioxidant potential varied significantly from plant to plant. The total phenolic contents were determined spectrophotometrically using Folin-Ciocalteu reagent. Significant correlation is observed between ferric reducing antioxidant power and phenolic contents (R²= 0.96). These findings show that the polyphenolic constituents in the extracts are responsible for free radical scavenging capacity. [ABSTRACT FROM AUTHOR]

: Many non-responders to azathioprine or mercaptopurine (6-mercaptopurine) have high normal thiopurine methyltransferase activity and preferentially metabolize mercaptopurine to produce 6-methylmercaptopurine instead of the active 6-tioguanine (6-tioguanine) metabolites. : To describe the use of allopurinol in mercaptopurine/azathioprine non-responders to deliberately shunt metabolism of mercaptopurine towards 6-tioguanine. : Fifteen thiopurine non-responders whose metabolites demonstrated preferential metabolism towards 6-methylmercaptopurine are described. Subjects were commenced on allopurinol 100 mg po daily and mercaptopurine/azathioprine was reduced to 25–50% of the original dose. Patients were followed clinically and with serial 6-tioguanine and 6-methylmercaptopurine metabolite measurements. : After initiating allopurinol, 6-tioguanine levels increased from a mean of 185.73 ± 17.7 to 385.4 ± 41.5 pmol/8 × 108 red blood cells ( P < 0.001), while 6-methylmercaptopurine decreased from a mean of 10 380 ± 1245 to 1732 ± 502 pmol/8 × 108 RBCs ( P < 0.001). Allopurinol led to a decrease in white blood cell from a mean of 8.28 ± 0.95 to 6.1 ± 0.82 × 108/L ( P = 0.01). : The addition of allopurinol to thiopurine non-responders with preferential shunting to 6-methylmercaptopurine metabolites appears to be an effective means to shift metabolism towards 6-tioguanine. [ABSTRACT FROM AUTHOR]

FZR1, which encodes the Cdh1 subunit of the anaphase-promoting complex, plays an important role in neurodevelopment by regulating the cell cycle and by its multiple post-mitotic functions in neurons. In this study, evaluation of 250 unrelated patients with developmental and epileptic encephalopathies and a connection on GeneMatcher led to the identification of three de novo missense variants in FZR1. Whole-exome sequencing in 39 patient-parent trios and subsequent targeted sequencing in an additional cohort of 211 patients was performed to identify novel genes involved in developmental and epileptic encephalopathy. Functional studies in Drosophila were performed using three different mutant alleles of the Drosophila homologue of FZR1 fzr. All three individuals carrying de novo variants in FZR1 had childhood-onset generalized epilepsy, intellectual disability, mild ataxia and normal head circumference. Two individuals were diagnosed with the developmental and epileptic encephalopathy subtype myoclonic atonic epilepsy. We provide genetic-association testing using two independent statistical tests to support FZR1 association with developmental and epileptic encephalopathies. Further, we provide functional evidence that the missense variants are loss-of-function alleles using Drosophila neurodevelopment assays. Using three fly mutant alleles of the Drosophila homologue fzr and overexpression studies, we show that patient variants can affect proper neurodevelopment. With the recent report of a patient with neonatal-onset with microcephaly who also carries a de novo FZR1 missense variant, our study consolidates the relationship between FZR1 and developmental and epileptic encephalopathy and expands the associated phenotype. We conclude that heterozygous loss-of-function of FZR1 leads to developmental and epileptic encephalopathies associated with a spectrum of neonatal to childhood-onset seizure types, developmental delay and mild ataxia. Microcephaly can be present but is not an essential feature of FZR1-encephalopathy. In summary, our approach of targeted sequencing using novel gene candidates and functional testing in Drosophila will help solve undiagnosed myoclonic atonic epilepsy or developmental and epileptic encephalopathy cases. [ABSTRACT FROM AUTHOR]

Objective The aim of this in vitro study was to evaluate the long-term effect of calcium hydroxide ( CH) on the microtensile fracture strength ( MTFS) of endodontically treated human teeth. Materials and Methods A total of 105 caries-free extracted human mandibular incisors were used. The teeth were divided into seven experimental groups of 15 teeth each. The root canals of all the teeth were rotary instrumented. The teeth in the control group were immediately obturated and tested for MTFS. The rest of the teeth were vertically compacted with CH and a sterile saline solution mixture and sealed with temporary filling. The teeth were stored in a moist environment for 30, 90, 180, 270, 360, and 540 days. On scheduled dates, the root canals were obturated and then the teeth were tested for MTFS with an Instron testing machine. The Kruscal- Wallis test and a post hoc Dunn's multiple comparison test was utilized. The statistical significance level was established at P < 0.05. Results The introduction of CH into the root canals seems to decrease the MTFS of teeth statistically significantly through the 180th, 270th, 360th, and 540th days, respectively, compared with the control group. The results clearly indicated that there are statistically significant differences between group 2 and group 7 ( P < 0.001) and between group 3 and group 7 ( P < 0.05). There were no statistically significant differences between the rest of the groups ( P > 0.05). Conclusions The results indicate that long-term CH treatments can significantly reduce the strength of the teeth, causing an increase in fracture risk. [ABSTRACT FROM AUTHOR]

Sheep and goats are sharing different helminth parasites including Haemonchus contortus. Control of these helminths is based mainly on the use of anthelmintics. However, in goats, the application of anthelmintics is often carried out mainly at dosages determined for sheep without knowing the real effects and metabolism features. One of the several anthelmintic classes used against these parasites is (pro) benzimidazoles which are still widely in use in small ruminants in many countries. The objective of this study was to determine (i) the correlation between plasma and tissue or gastrointestinal content dispositions of ricobendazole (RBZ) in goats and (ii) the in vivo exposure of ricobendazole by H. contortus. Ten goats were experimentally infected with 10,000 larvae of H. contortus. Four weeks of post‐infection, the animals received RBZ subcutaneously at 5 mg/kg body weight. Two goats were sacrificed per time at 1, 2, 4, 6 and 12 h after drug administration and, blood, bile, urine, liver, lung, muscle and kidney gastrointestinal tissues/fluids were collected. Adult H. contortus were collected from abomasum, and all samples were analysed by HPLC system. Ricobendazole (RBZ) and its sulphone metabolite were extensively excreted by urine and distributed to all tissues and digestive tract, mainly into the abomasum fluid. RBZ concentration in the lung and ABZSO2 in the kidney were relatively higher than those of other tissues, respectively. The parent drug and its metabolite were recovered in both male and female H. contortus. This study indicates that in goats the plasma concentration profiles of RBZ are strongly correlated with those achieved in different target tissues or fluids, which in turn, reflect the amount of drug taken up by parasites. [ABSTRACT FROM AUTHOR]

With 30 antennas and a maximum baseline length of 25 km, the Giant Metrewave Radio Telescope (GMRT) is the premier low-frequency radio interferometer today. We have carried out a study of possible expansions of the GMRT, via adding new antennas and installing focal plane arrays (FPAs), to improve its point-source sensitivity, surface brightness sensitivity, angular resolution, field of view, and UV coverage. We have carried out array configuration studies, aimed at minimizing the number of new GMRT antennas required to obtain a well-behaved synthesized beam over a wide range of angular resolutions for full-synthesis observations. This was done via two approaches, tomographic projection and random sampling, to identify the optimal locations for the new GMRT antennas. We report results for the optimal locations of the antennas of an expanded array (the 'EGMRT'), consisting of the existing 30 GMRT antennas, 30 new antennas at short distances, ≲2.5 km from the GMRT array centre, and 26 additional antennas at relatively long distances, ≈5–25 km from the array centre. The collecting area and the field of view of the proposed EGMRT array would be larger by factors of, respectively, ≈3 and ≈30, than those of the GMRT. Indeed, the EGMRT continuum sensitivity and survey speed with 550–850 MHz FPAs installed on the 45 antennas within a distance of ≈2.5 km of the array centre would be far better than those of any existing interferometer, and comparable to the sensitivity and survey speed of Phase-1 of the Square Kilometre Array. [ABSTRACT FROM AUTHOR]

Background Sanger sequencing, still the standard technique for genetic testing in most diagnostic laboratories and until recently widely used in research, is gradually being complemented by next-generation sequencing ( NGS). No single mutation detection technique is however perfect in identifying all mutations. Therefore, we wondered to what extent inconsistencies between Sanger sequencing and NGS affect the molecular diagnosis of patients. Since mutations in SCN1A, the major gene implicated in epilepsy, are found in the majority of Dravet syndrome ( DS) patients, we focused on missed SCN1A mutations. Methods We sent out a survey to 16 genetic centers performing SCN1A testing. Results We collected data on 28 mutations initially missed using Sanger sequencing. All patients were falsely reported as SCN1A mutation-negative, both due to technical limitations and human errors. Conclusion We illustrate the pitfalls of Sanger sequencing and most importantly provide evidence that SCN1A mutations are an even more frequent cause of DS than already anticipated. [ABSTRACT FROM AUTHOR]

Dravet syndrome is a severe epilepsy syndrome characterized by infantile onset of therapy-resistant, fever-sensitive seizures followed by cognitive decline. Mutations in SCN1A explain about 75% of cases with Dravet syndrome; 90% of these mutations arise de novo. We studied a cohort of nine Dravet-syndrome-affected individuals without an SCN1A mutation (these included some atypical cases with onset at up to 2 years of age) by using whole-exome sequencing in proband-parent trios. In two individuals, we identified a de novo loss-of-function mutation in CHD2 (encoding chromodomain helicase DNA binding protein 2). A third CHD2 mutation was identified in an epileptic proband of a second (stage 2) cohort. All three individuals with a CHD2 mutation had intellectual disability and fever-sensitive generalized seizures, as well as prominent myoclonic seizures starting in the second year of life or later. To explore the functional relevance of CHD2 haploinsufficiency in an in vivo model system, we knocked down chd2 in zebrafish by using targeted morpholino antisense oligomers. chd2-knockdown larvae exhibited altered locomotor activity, and the epileptic nature of this seizure-like behavior was confirmed by field-potential recordings that revealed epileptiform discharges similar to seizures in affected persons. Both altered locomotor activity and epileptiform discharges were absent in appropriate control larvae. Our study provides evidence that de novo loss-of-function mutations in CHD2 are a cause of epileptic encephalopathy with generalized seizures. [Copyright &y& Elsevier]