Prognostic Stratification of GBMs Using Combinatorial Assessment of IDH1 Mutation, MGMT Promoter Methylation, and TERT Mutation Status: Experience from a Tertiary Care Center in India

AbstractThis study aims to establish the best and simplified panel of molecular markers for prognostic stratification of glioblastomas (GBMs). One hundred fourteen cases of GBMs were studied for IDH1, TP53, and TERT mutation by Sanger sequencing; EGFR and PDGFRA amplification by fluorescence in situ hybridization; NF1expression by quantitative real time polymerase chain reaction (qRT-PCR); and MGMT promoter methylation by methylation-specific PCR. IDH1 mutant cases had significantly longer progression-free survival (PFS) and overall survival (OS) as compared to IDH1 wild-type cases. Combinatorial assessment of MGMT and TERT emerged as independent prognostic markers, especially in the IDH1 wild-type GBMs. Thus, within the IDH1 wild-type group, cases with only MGMT methylation (group 1) had the best outcome (median PFS: 83.3 weeks; OS: not reached), whereas GBMs with only TERT mutation (group 3) had the worst outcome (PFS: 19.7 weeks; OS: 32.8 weeks). Cases with both or none of these alterations (group 2) had intermediate prognosis (PFS: 47.6 weeks; OS: 89.2 weeks). Majority of the IDH1 mutant GBMs belonged to group 1 (75%), whereas only 18.7% and 6.2% showed group 2 and 3 signatures, respectively. Interestingly, none of the other genetic alterations were significantly associated with survival in IDH1 mutant or wild-type GBMs.Based on above findings, we recommend assessment of three markers, viz., IDH1, MGMT, and TERT, for GBM prognostication in routine practice. We show for the first time that IDH1 wild-type GBMs which constitute majority of the GBMs can be effectively stratified into three distinct prognostic subgroups based on MGMT and TERT status, irrespective of other genetic alterations

Comparison of the Success of Two Techniques for the Endotracheal Intubation with C-MAC Video Laryngoscope Miller Blade in Children: A Prospective Randomized Study

Background. Ease of endotracheal intubation with C-MAC video laryngoscope (VLS) with Miller blades 0 and 1 has not been evaluated in children. Methods. Sixty children weighing 3-15 kg with normal airway were randomly divided into two groups. Intubation was done with C-MAC VLS Miller blade using either nonstyletted endotracheal tube (ETT) (group WS) or styletted ETT (group S). The time for intubation and total procedure, intubation attempts, failed intubation, blade repositioning or external laryngeal maneuver, and complications were recorded. Results. The median (minimum/maximum) time for intubation in group WS and group S was 19.5 (9/48) seconds and 13.0 (18/55) seconds, respectively ( = 0.03). The median (minimum/maximum) time for procedure in group WS was 30.5 (18/72) seconds and in group S was 24.5 (14/67) seconds, respectively ( = 0.02). Intubation in first attempt was done in 28 children in group WS and in 30 children in group S. Repositioning was required in 14 children in group WS and in 7 children in group S ( = 0.06). There were no failure to intubate, desaturation, and bradycardia in both groups. Conclusion. Styletted ETT significantly reduces time for intubation and time for procedure in comparison to nonstyletted ETT

Comparison of the Success of Two Techniques for the Endotracheal Intubation with C-MAC Video Laryngoscope Miller Blade in Children: A Prospective Randomized Study

Background. Ease of endotracheal intubation with C-MAC video laryngoscope (VLS) with Miller blades 0 and 1 has not been evaluated in children. Methods. Sixty children weighing 3–15 kg with normal airway were randomly divided into two groups. Intubation was done with C-MAC VLS Miller blade using either nonstyletted endotracheal tube (ETT) (group WS) or styletted ETT (group S). The time for intubation and total procedure, intubation attempts, failed intubation, blade repositioning or external laryngeal maneuver, and complications were recorded. Results. The median (minimum/maximum) time for intubation in group WS and group S was 19.5 (9/48) seconds and 13.0 (18/55) seconds, respectively (p=0.03). The median (minimum/maximum) time for procedure in group WS was 30.5 (18/72) seconds and in group S was 24.5 (14/67) seconds, respectively (p=0.02). Intubation in first attempt was done in 28 children in group WS and in 30 children in group S. Repositioning was required in 14 children in group WS and in 7 children in group S (p=0.06). There were no failure to intubate, desaturation, and bradycardia in both groups. Conclusion. Styletted ETT significantly reduces time for intubation and time for procedure in comparison to nonstyletted ETT

Bone mineral density in young adult women with congenital adrenal hyperplasia

Background: There is equipoise regarding the status of bone mineral density (BMD) in patients with congenital adrenal hyperplasia (CAH), where patients need to be on long-term low-dose steroids. Objective: We aimed to evaluate BMD at the hip, spine and forearm in women with CAH and compare it to healthy young adult women of the same age range. Subjects and Methods: Fifteen adult women with CAH with age ranging from 18 to 40 years (mean ± standard deviation = 27.5 ± 6.2 years) underwent dual-energy X-ray absorptiometry along with laboratory evaluation. BMD at lumbar spine, hip, forearm along with T-scores were measured. Serum total calcium, phosphate, alkaline phosphatase, 25 hydroxy Vitamin D, intact parathyroid hormone, total testosterone, and dehydroepiandrosterone were assayed. History of any fractures in the past was taken. Fifteen healthy women in the same age range were taken as controls for comparison. Results: The BMD at hip (0.85 ± 0.02 g/cm2) in CAH was significantly lower as compared with controls (0.92 ± 0.03 g/cm2, P = 0.029). BMD at lumbar spine was also reduced (0.96 ± 0.02 vs. 1.03 ± 0.03, P = 0.057). The BMD at forearm was not significantly different between CAH and controls. The mean Vitamin D was 9.8 ng/ml (deficient range). There was no history of fractures in CAH. Conclusion: Young adult CAH women had lower BMD at spine and hip than healthy young adult women of the same age range. The forearm BMD was not different from controls. No change in fracture frequency was present. Patients with CAH being treated with steroids are at increased risk of osteopenia, and their bone health needs to be monitored

An Experimental and Computational Study of the Loading and Release of Aspirin from Zeolite HY

The anti-inflammatory drug, aspirin, was loaded into three zeolite HY hosts with silica to alumina ratios (SiO₂/Al₂O₃) of 5, 30, and 60. The aspirin loading in the zeolite HY samples as measured by thermogravimetric analysis decreased from 106, to 78, to 69 mg aspirin/g zeolite with increasing SiO₂/Al₂O₃. The surface areas and pore volumes, measured using nitrogen adsorption–desorption experiments, indicated that the aspirin was loaded into the internal pore surface of these materials. The Fourier transform infrared and ²⁷Al and ¹³C magic angle spinning nuclear magnetic resonance spectra of the aspirin-loaded materials provided molecular level information about aspirin–zeolite interactions. Quantum calculations at both Hartree–Fock and density functional theory levels of theory were conducted in order to understand the nature of intermolecular interactions between the zeolite host and the aspirin. The release of the aspirin from HY was dependent on the hydrophobicity of the zeolite host with more hydrophobic zeolites (higher SiO₂/Al₂O₃) releasing the aspirin less readily

Aspirin Loading and Release from MCM-41 Functionalized with Aminopropyl Groups via Co-condensation or Postsynthesis Modification Methods

A comprehensive study of aspirin loading and release from MCM-41 and amine functionalized MCM-41 was conducted. Two different functionalization methods, co-condensation and postsynthesis modification, were utilized and compared. All of the MCM-41 samples were thoroughly characterized before and after aspirin loading by powder X-ray diffraction, nitrogen adsorption isotherms, and thermogravimetric analysis to determine the structure and physicochemical properties such as surface area, pore volume, and functional group loading. Molecular level details about the aspirin–MCM-41 interactions were revealed through FTIR and ¹³C solid-state NMR experiments. For the aminopropyl-functionalized MCM-41, the carboxylic acid group of aspirin associates with the amine group of the functionalized MCM-41. In all of the samples, an interaction between the aspirin phenyl group and the mesoporous silica host was hypothesized based on shifts in the phenyl group ¹³C NMR resonances. Molecular dynamics simulations supported the NMR observations in that the phenyl group of the aspirin was determined to be oriented parallel to the pore wall. The release data indicated that both the distribution and loading of the amine functional groups in MCM-41 influenced the release properties of aspirin

Long-term effect of panretinal photocoagulation on optic nerve head parameters in diabetic retinopathy using Heidelberg retinal tomography III

PURPOSE: The aim of this study was to evaluate the effect of panretinal photocoagulation (PRP) in diabetic retinopathy patients using Heidelberg retinal tomography III (HRT). SUBJECTS AND METHODS: A total of 90 eyes of 90 consecutive newly diagnosed patients with diabetic retinopathy (nonproliferative diabetic retinopathy, NPDR, Group I and proliferative, PDR, Group II) were recruited for the study. The eyes with PDR were subjected to PRP. The effect of PRP was measured on optic nerve head (ONH) parameters using HRT. RESULTS: Follow-up up to 4 years in both groups indicated that in Group II proliferative diabetic retinopathy (PDR) participants undergoing PRP, the ONH parameters showed a significant difference in cup area (P = 0.023), cup volume (P = 0.001), mean cup depth (P = 0.015), maximum cup depth (P < 0.001), mean retinal nerve fiber layer (RNFL) thickness (P < 0.001) at 1 year of follow-up, and remained significant in all at 4 years of follow-up, whereas there was no significant difference in any of the optic disc parameters in the participants of Group I belonging to NPDR group as compared to PDR group after 4 years. CONCLUSION: PRP affected the ONH morphology in the PDR group and the effect of this change should be interpreted with caution. This may require setting a new baseline for RNFL measurements using the HRT when documenting RNFL loss or glaucoma progression in patients who have undergone PRP

Nutrient intake of adolescents in rural area of Himachal Pradesh

Background: The nutrient requirements during adolescence are higher than at any other stage of life. Inadequate nutrient intake leads to poor growth, delayed sexual maturation, slow linear growth, anaemia and osteomalacia. Aim &Objective: To assess the nutrient intake of adolescents in 13-15 years belonging to rural area of Shimla district, Himachal Pradesh. Material & Methods: A school based cross-sectional study was conducted during 2014 - 2015 in rural area of Shimla district. Thirty clusters were identified using population proportionate to size sampling method.  A total of 170 adolescents in the age group of 13-15 years studying in government schools were enrolled. Dietary assessment was done using 24h dietary recall method. Results: The percentage deficit in boys for calorie, iron, zinc and calcium intake was found 37.9%, 53.7%, 35.5% and 22.4% respectively as compared to Recommended Dietary Allowances (RDA). The girls had percentage deficit for calorie, iron, zinc and calcium intake as 47.7%, 61.5%, 53.6%, and 43.6 % respectively as compared to RDA. Conclusion: The findings of present study indicate that the nutrient intake of adolescents aged 13-15 years was inadequate

Chemical Insight into the Adsorption of Chromium(III) on Iron Oxide/Mesoporous Silica Nanocomposites

Magnetic iron oxide/mesoporous silica nanocomposites consisting of iron oxide nanoparticles embedded within mesoporous silica (MCM-41) and modified with aminopropyl functional groups were prepared for application to Cr­(III) adsorption followed by magnetic recovery of the nanocomposite materials from aqueous solution. The composite materials were extensively characterized using physicochemical techniques, such as powder X-ray diffraction, thermogravimetric and elemental analysis, nitrogen adsorption, and zeta potential measurements. For aqueous Cr­(III) at pH 5.4, the iron oxide/mesoporous silica nanocomposite exhibited a superior equilibrium adsorption capacity of 0.71 mmol/g, relative to 0.17 mmol/g for unmodified mesoporous silica. The aminopropyl-functionalized iron oxide/mesoporous silica nanocomposites displayed an equilibrium adsorption capacity of 2.08 mmol/g, the highest adsorption capacity for Cr­(III) of all the materials evaluated in this study. Energy-dispersive spectroscopy (EDS) with transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) experiments provided insight into the chemical nature of the adsorbed chromium species