Tuberin levels during cellular differentiation in brain development.

Tuberin is a member of a large protein complex, Tuberous Sclerosis Complex (TSC), and acts as a sensor for nutrient status regulating protein synthesis and cell cycle progression. Mutations in the Tuberin gene, TSC2, permits the formation of tumors that can lead to developmental defects in many organ systems, including the central nervous system. Tuberin is expressed in the brain throughout development and levels of Tuberin have been found to decrease during neuronal differentiation in cell lines in vitro. Our current work investigates the levels of Tuberin at two stages of embryonic development in vivo, and we study the mRNA and protein levels during a time course using immortalized cell lines in vitro. Our results show that total Tuberin levels are tightly regulated through developmental stages in the embryonic brain. At a cell biology level, we show that Tuberin levels are higher when cells are cultured as neurospheres, and knockdown of Tuberin results in a reduction in the number of neurospheres. This functional data supports the hypothesis that Tuberin is an important regulator of stemness and the reduction of Tuberin levels might support functional differentiation in the central nervous system. Understanding how Tuberin expression is regulated throughout neural development is essential to fully comprehend the role of this protein in several developmental and neural pathologies.

Barium-Promoted Yttria-Zirconia-Supported Ni Catalyst for Hydrogen Production via the Dry Reforming of Methane: Role of Barium in the Phase Stabilization of Cubic ZrO2.

Developing cost-effective nonprecious active metal-based catalysts for syngas (H2/CO) production via the dry reforming of methane (DRM) for industrial applications has remained a challenge. Herein, we utilized a facile and scalable mechanochemical method to develop Ba-promoted (1-5 wt %) zirconia and yttria-zirconia-supported Ni-based DRM catalysts. BET surface area and porosity measurements, infrared, ultraviolet-visible, and Raman spectroscopy, transmission electron microscopy, and temperature-programmed cyclic (reduction-oxidation-reduction) experiments were performed to characterize and elucidate the catalytic performance of the synthesized materials. Among different catalysts tested, the inferior catalytic performance of 5Ni/Zr was attributed to the unstable monoclinic ZrO2 support and weakly interacting NiO species whereas the 5Ni/YZr system performed better because of the stable cubic ZrO2 phase and stronger metal-support interaction. It is established that the addition of Ba to the catalysts improves the oxygen-endowing capacity and stabilization of the cubic ZrO2 and BaZrO3 phases. Among the Ba-promoted catalysts, owing to the optimal active metal particle size and excess ionic CO3 2- species, the 5Ni4Ba/YZr catalyst demonstrated a high, stable H2 yield (i.e., 79% with a 0.94 H2/CO ratio) for up to 7 h of time on stream. The 5Ni4Ba/YZr catalyst had the highest H2 formation rate, 1.14 mol g-1 h-1 and lowest apparent activation energy, 20.07 kJ/mol, among all zirconia-supported Ni catalyst systems.

Survival after palliative radiation therapy for cancer: The METSSS model.

BACKGROUND: We propose a predictive model that identifies patients at greatest risk of death after palliative radiotherapy, and subsequently, can help medical professionals choose treatments that better align with patient choice and prognosis. METHODS: The National Cancer Database was queried for recipients of palliative radiotherapy during first course of treatment. Cox regression models and adjusted hazard ratios with 95% confidence intervals were used to evaluate survival predictors. The mortality risk index was calculated using predictors from the estimated Cox regression model, with higher values indicating higher mortality risk. Based on tertile cutpoints, patients were divided into low, medium, and high risk groups. RESULTS: A total of 68,505 patients were included from 2010-2014, median age 65.7 years. Several risk factors were found to predict survival: (1) location of metastases (liver, bone, lung, and brain); (2) age; (3) tumor primary (prostate, breast, lung, other); (4) gender; (5) Charlson-Deyo comorbidity score; and (6) radiotherapy site. The median survival times were 11.66 months, 5.09 months, and 3.28 months in the low (n=22,621), medium (n=22,638), and high risk groups (n=22,611), respectively. A nomogram was created and validated to predict survival, available online, https://tinyurl.com/METSSSmodel. Harrel's C-index was 0.71 and receiver operator characteristic area under the curve was 0.76 at 4 years. CONCLUSION: We created a predictive nomogram for survival of patients receiving palliative radiotherapy during their first course of treatment (named METSSS), based on Metastases location, Elderly (age), Tumor primary, Sex, Sickness/comorbidity, and Site of radiotherapy.

Sex-specific associations of asthma acquisition with changes in DNA methylation during adolescence.

BACKGROUND: Underlying biological mechanisms involved in sex differences in asthma status changes from pre- to post-adolescence are unclear. DNA methylation (DNAm) has been shown to be associated with the risk of asthma. OBJECTIVE: We hypothesized that asthma acquisition from pre- to post-adolescence was associated with changes in DNAm during this period at asthma-associated cytosine-phosphate-guanine (CpG) sites and such an association was sex-specific. METHODS: Subjects from the Isle of Wight birth cohort (IOWBC) with DNAm in blood at ages 10 and 18 years (n = 124 females, 151 males) were studied. Using a training-testing approach, epigenome-wide CpGs associated with asthma were identified. Logistic regression was used to examine sex-specific associations of DNAm changes with asthma acquisition between ages 10 and 18 at asthma-associated CpGs. The ALSPAC birth cohort was used for independent replication. To assess functional relevance of identified CpGs, association of DNAm with gene expression in blood was assessed. RESULTS: We identified 535 CpGs potentially associated with asthma. Significant interaction effects of DNAm changes and sex on asthma acquisition in adolescence were found at 13 of the 535 CpGs in IOWBC (P-values <1.0 × 10-3 ). In the replication cohort, consistent interaction effects were observed at 10 of the 13 CpGs. At 7 of these 10 CpGs, opposite DNAm changes across adolescence were observed between sexes in both cohorts. In both cohorts, cg20891917, located on IFRD1 linked to asthma, shows strong sex-specific effects on asthma transition (P-values <.01 in both cohorts). CONCLUSION AND CLINICAL RELEVANCE: Gender reversal in asthma acquisition is associated with opposite changes in DNAm (males vs females) from pre- to post-adolescence at asthma-associated CpGs. These CpGs are potential biomarkers of sex-specific asthma acquisition in adolescence.

Pharmacokinetics of gadobenate dimeglumine in children 2 to 5 years of age undergoing MRI of the central nervous system.

PURPOSE: To determine the pharmacokinetic profile of gadobenate dimeglumine in children aged between 2 and 5 years. MATERIALS AND METHODS: Fifteen children scheduled to undergo contrast-enhanced MRI for suspected disease of the central nervous system received a single intravenous injection of 0.1 mmol/kg gadobenate dimeglumine. Children were stratified into three age groups: 2 to <3 years, 3 to <4 years, and 4 to 5 (i.e., <6 years). Serial blood and urine samples collected at prespecified time-points before and after contrast administration were analyzed for gadolinium concentrations. Pharmacokinetic parameters were calculated using noncompartmental and compartmental techniques. RESULTS: Mean values of 65.7 µg/mL for highest blood gadolinium concentration, 0.2 L/h/kg for blood clearance, 0.32 L/kg for steady-state volume of distribution, and 1.2 h for terminal elimination half-life were determined across all age groups combined. On average, more than 80% of the dose was eliminated in the urine during the first 24 h after administration. All pharmacokinetic parameters were similar between age groups and no effects of gender were noted. No adverse events considered related to gadobenate dimeglumine administration were reported. CONCLUSION: In terms of pharmacokinetic profile no dosage adjustment from the approved adult gadobenate dimeglumine dose of 0.1 mmol/kg bodyweight is necessary in children aged between 2 and 5 years.

Preparation and formulation of transferosomes containing an antifungal agent for transdermal delivery: Application of Plackett-Burman design to identify significant factors influencing vesicle size.

Transferosomes containing an anti-fungal agent were prepared by Rotary Flask Evaporation -Sonication method. Eight batches were prepared in triplicate and vesicle size of each batch was determined. Plackett-Burman Design was employed to identify significant formulation and process parameters affecting vesicle size. The amount of lipid and surfactant, volume of ethanol and hydration medium as well as hydration time significantly affect the vesicle size.

A clinical study of Devadarvyadi-Vati on Grahani Dosha in children.

Childhood period is considered as the period of rapid growth and development, as it is the crucial stage of establishing future. Gastro-intestinal disorders show high prevalence in pediatric practice. These conditions generally produce chronic illness. Grahanidosha is a disease related with Agnidushti. This condition is seen more in childhood period due to faulty dietary habit and changing lifestyle. The present paper deals with study on etiopathogenesis of Grahanidosha and evaluates the efficacy of Deavadarvyadi-Vati. The etiological factors and symptoms were observed carefully to make clear etiopathogenesis. Total 32 patients (3-12 years) were registered and randomly divided into two groups. In Group A Devadarvyadi-Vati (treated group) and in Group B Bhunimbadi-Vati (control group) given for 4 weeks with Koshna Jala. In Group A (Devadarvyadi-Vati), marked improvement was observed in 21.43% of the patients, moderate improvement was observed in 57.14% of patients and mild improvement was observed in 21.43% of patients.