Salazarcallesen0379
The utility of O
-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation status as a prognostic marker in patients with glioblastoma (GBM) has been established. However, the number of CpG sites that must be methylated to cause transcriptional silencing remains unclear, and no significant consensus exists on the optimal method of assessing MGMT methylation. We developed a new high-performance liquid chromatography (HPLC) method that enables accurate analysis of DNA methylation levels using long PCR products. In the present study, we analyzed the MGMT methylation status of 28 isocitrate dehydrogenase-wild-type GBMs treated with temozolomide using ion-exchange HPLC and set the optimal cutoff values.
We designed three primers for separate regions (regions 1-3) that had 21 to 38 CpGs for PCR and validated the MGMT promoter methylation status using frozen samples. There was a strong correlation between HPLC and bisulfite sequencing results (R = 0.794). The optimal cutoff values for MGMT methylation in HPLC were determined to allow differentiation of patient prognosis by receiver operating characteristic curve analysis. The cutoff values were 34.15% for region 1, 8.84% for region 2, and 36.72% for region 3. Kaplan-Meyer curve analysis estimated that the most differentiated prognosis was enabled in the setting of 8.84% methylation of MGMT in region 2. Progression-free survival and overall survival were significantly longer for patients in this setting of region 2 methylation (p = 0.00365 and p = 0.00258, respectively).
The combination of our HPLC method and the original primer setting provides a new standard method for determination of MGMT methylation status in patients with GBM and is useful for refining MGMT-based drug selection.
The combination of our HPLC method and the original primer setting provides a new standard method for determination of MGMT methylation status in patients with GBM and is useful for refining MGMT-based drug selection.
Coronavirus disease 2019 (COVID-19) is a new viral disease that has caused a pandemic in the world. Due to the lack of vaccines and definitive treatment, preventive behaviors are the only way to overcome the disease. Therefore, the present study aimed to determine the preventive behaviors from the disease based on constructs of the health belief model.
In the present cross-sectional study during March 11-16, 2020, 750 individuals in Golestan Province of Iran were included in the study using the convenience sampling and they completed the questionnaires through cyberspace. Factor scores were calculated using the confirmatory factor analysis. The effects of different factors were separately investigated using the univariate analyses, including students sample t-test, ANOVA, and simple linear regression. Finally, the effective factors were examined by the multiple regression analysis at a significant level of 0.05 and through Mplus 7 and SPSS 16.
The participants' mean age was 33.9 ± 9.45years; and 57.1% o perceived self-efficacy, fatalistic beliefs, perceived interests, and living in city had the greatest preventive behaviors from COVID-19 respectively. Preventive interventions were necessary among males and villagers.Advances in CRISPR technology have immensely improved our ability to manipulate nucleic acids, and the recent discovery of the RNA-targeting endonuclease Cas13 adds even further functionality. Here, we show that Cas13 works efficiently in Drosophila, both ex vivo and in vivo. We test 44 different Cas13 variants to identify enzymes with the best overall performance and show that Cas13 could target endogenous Drosophila transcripts in vivo with high efficiency and specificity. We also develop Cas13 applications to edit mRNAs and target mitochondrial transcripts. Our vector collection represents a versatile tool collection to manipulate gene expression at the post-transcriptional level.
Triazine coccidiostats are widely used in chickens and turkeys for coccidiosis control. Ethanamizuril is a novel triazine compound that exhibits anticoccidial activity in poultry. This study was designed to evaluate the subchronic toxicity of ethanamizuril in beagle dogs at doses of 12, 60 or 300 mg/kg/day in diet for 90 days.
Ethanamizuril was well tolerated at low and middle dosages in beagle dogs, and no drug-related toxical effects were observaed in terms of survival, clinical observations, organs weight and damage in these dose groups. However, in high dose administration group, food consumption and histologic changes in kidneys were noticed in both sexes of beagle dog, although the renal lesions were finally resolved at the end of 4 weeks exposure of ethanamizuril.
No-observed-adverse-effect level (NOAEL) was considered for ethanamizuril at dose of 60 mg/kg/day in Beagle dog. This result added toxicity effects of ethanamizuril to the safety database, which might guide safely using of ethanamizuril as a novel coccidiostat.
No-observed-adverse-effect level (NOAEL) was considered for ethanamizuril at dose of 60 mg/kg/day in Beagle dog. This result added toxicity effects of ethanamizuril to the safety database, which might guide safely using of ethanamizuril as a novel coccidiostat.
The diagnosis of rare diseases poses a particular challenge to clinicians. This study analyzes whether patients' pain drawings (PDs) help in the differentiation of two pain-associated rare diseases, Ehlers-Danlos Syndrome (EDS) and Guillain-Barré Syndrome (GBS).
The study was designed as a prospective, observational, single-center study. The sample comprised 60 patients with EDS (3 male, 52 female, 5 without gender information; 39.2 ± 11.4years) and 32 patients with GBS (10 male, 20 female, 2 without gender information; 50.5 ± 13.7years). Patients marked areas afflicted by pain on asketch of a human body with anterior, posterior, and lateral views. PDs were electronically scanned and processed. Each PD was classified based on the Ružička similarity to the EDS and the GBS averaged image (pain profile) in a leave-one-out cross validation approach. BI3231 A receiver operating characteristic (ROC) curve was plotted.
60-80% of EDS patients marked the vertebral column with the neck and the tailbone and the knee joints as pain areas, 40-50% the shoulder-region, the elbows and the thumb saddle joint.
