Comparative assessment of immunogenicity of recombinant insulin Aspart from BioGenomics and its originator NovoRapid® in adult patients with type 2 diabetes mellitus.

OBJECTIVES: To assess and compare the immunogenicity of recombinant Insulin Aspart [manufactured by BioGenomics Limited (BGL-ASP)] with its originator NovoRapid® (manufactured by Novo Nordisk) in adult patients with type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: BGL-IA-CTP301 study was a randomized, open label, parallel group, multicenter phase-III clinical study to compare the efficacy and safety of recombinant Insulin Aspart 100 U/mL [manufactured by BioGenomics Limited (BGL-ASP)] with its reference medicinal product (RMP); NovoRapid® [manufactured by Novo Nordisk], in adult patients with Type 2 diabetes mellitus (T2DM). The primary objective of the study was to compare the immunogenicity of BGL-ASP and RMP; NovoRapid® in patient serum samples collected from phase-III clinical study. Immunogenicity was studied as the incidence of patients positive for anti-insulin Aspart (AIA) antibodies, developed against BGL-ASP/RMP at baseline, end of 12 week and end of 24 week of the treatment period. The changes in incidence of patients positive for AIA antibodies post-baseline were also studied to assess and compare the treatment-emergent antibody response (TEAR) between the treatment groups (BGL-ASP and RMP). Statistical evaluation was done by Fisher's exact test to compare the overall incidence of patients positive for AIA antibodies and the TEAR positives observed post-baseline in both the treated groups. An in-vitro neutralizing antibody assay (Nab assay) was also performed to study the effect of AIA antibodies in neutralizing the biological activity/metabolic function of the insulin. The neutralizing potential of AIA was studied by its effect on %glucose uptake. We also evaluated the association between AIA antibody levels and its impact on biological activity by studying the correlation between them. RESULTS: Analysis of immunogenicity data suggested that the percentage of patients positive for AIA antibodies until week 24 was similar and comparable in both the treatment groups, BGL-ASP and RMP; NovoRapid®. The changes in incidence of patients positive for AIA post-baseline in terms of TEAR positives were also similar and comparable between the treatment groups. The results of the Nab assay with confirmed positive AIA samples from BGL-ASP- and RMP-treated groups did not have any negative impact on %glucose uptake by the cells in Nab assay, confirming the absence of neutralizing antibodies in both the treatment groups. The correlation studies also showed absence of association between AIA antibody levels and percentage glucose uptake in both BGL-ASP and RMP-NovoRapid® treatment groups. CONCLUSIONS: The immunogenicity assessment based on the overall incidence of patients positive for AIA, changes in incidence of patients positive for AIA post-baseline, TEAR rates and absence of neutralizing antibodies, were found to be apparently similar and comparable in both the treatment groups (BGL-ASP and RMP). We conclude from our studies that the immunogenicity of BGL-ASP is similar and comparable to RMP and the observed immunogenicity in terms of anti-insulin Aspart antibody levels had no impact on the biological activity of insulin.

Primary diffuse leptomeningeal primitive neuroectodermal tumor presenting as chronic meningitis.

Primary diffuse leptomeningeal primitive neuroectodermal tumor is a rare meningeal neoplasm which can masquerade as chronic meningitis. While the clinical presentation and radiological features may provide a clue to this condition, meningeal biopsy is essential to clinch the diagnosis. A high index of suspicion and a low threshold for re-evaluating cases of neuroinfection that do not respond to empirical therapy are essential in this scenario. We present the case of a nine year old boy who was initiated on antituberculous treatment for chronic meningitis with hydrocephalus. Meningeal biopsy revealed a primary diffuse leptomeningeal primitive neuroectodermal tumor.

Real-World Practice Patterns and Predictors of Continuous versus Intermittent Androgen Deprivation Therapy Use for Prostate Cancer in Older Men.

PURPOSE: Phase-III randomized control trial evidence suggests intermittent androgen deprivation therapy (IADT) is not significantly inferior to continuous androgen deprivation therapy (ADT) for patients with prostate cancer (PC). However, clinical practice and guidelines differ in their recommendations. We evaluate real-world utilization and practice patterns of IADT. MATERIALS AND METHODS: Ontario men ≥65 years of age with PC who initiated ADT for ≥3 months were identified (1997-2017). Lapses in ADT ≥6 months (initial gap) and ≥3 months (subsequent gaps) were used to classify IADT. Neoadjuvant/adjuvant therapy was excluded. Disease stage adjustment was completed for patients with likely metastatic disease based on de novo presentation with ADT. Patient and physician predictors of IADT were analyzed using multivariable logistic regression. RESULTS: We identified 8,544 patients with 1,715 having previously received local therapy. Among all patients, 16.4% received IADT. This ranged from 11.4%-24.8% across health-planning regions and increased to 26.6% in those with previous local therapy. Mean followup was 8.3 years. Patients with prior local therapy (OR 1.85, 95% CI 1.59-2.17, p <0.001) and those in the highest income quintile (OR 1.32, 95% CI 1.08-1.60, p=0.005) had increased odds of receiving IADT. Radiation oncologists were more likely to use IADT than urologists (OR 1.99, 95% CI 1.59-2.50, p <0.001), as were physicians with more experience (≥10 years in practice: OR 1.44, 95% CI 1.11-1.88, p=0.007). In specialty-stratified analyses, case volume was significantly associated with IADT for radiation oncologists (highest quartile: OR 1.73, 95% CI 1.14-2.62, p=0.009). CONCLUSIONS: IADT remains underutilized for patients with PC who ≥65 years of age with only 1 in 4 to 1 in 6 eligible patients receiving this form of care. Clinical, sociodemographic and physician characteristics play an important role in treatment selection.

Time Evolution and Spatial Hierarchy of Crack Patterns.

Cracks generated due to desiccation of wet colloidal systems are ubiquitous, examples being nanomaterial films, painted walls, cemented floors, mud fields, river beds, and even giant rocks. In all such cases, crack patterns are often appreciably similar but for the length and time scales, which can be widely differing. In this work, we have examined the crack formation more closely to see if there exists some generality with regard to the length scale of parameters and the formation time. Specifically, using a commonly used colloidal dispersion and optimized conditions to form polygonal network patterns rather than isolated cracks (films of subcritical thickness), we have studied the time evolution of the pattern parameters, the area occupied by the cracks, their lengths, and the widths. As is well known, initially, a network of cracks forms, which we term as the primary generation, followed by interconnecting cracks inside the polygonal regions (secondary) and, later, cracks spreading in local regions (tertiary). We find that the area and the width increase nearly linearly with time with the change in the slope corresponding to the change in the generation. When normalized with respect to the final values, the trends obtained for different film thicknesses overlap, the only exception being the pattern containing unconnected cracks. Thus, the time evolution of cracks is shown to be predictable based on width filtering. Including the angle between cracks as further input into the recursive model, the possibility of identifying the hierarchy of crack segments is also shown. The approach may be useful in determining the age, authenticity, and details of old paintings, understanding the stress profile of geological rocks, and analyzing various natural and manmade hierarchical structures.

Adverse event profile for immunotherapy agents compared with chemotherapy in solid organ tumors: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Immunotherapy agents are an innovative oncological treatment modality and as a result their use has expanded widely. Understanding the treatment-related adverse events (AEs) of these drugs compared with traditional chemotherapy is crucial for clinical practice. DESIGN: A systematic review of studies indexed in Medline (PubMed), Embase, Web of Science, and the Cochrane Databases from January 2000 to 14 February 2019 was conducted. Randomized clinical trials comparing immunotherapy [cytotoxic T-lymphocyte protein-4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed death-ligand 1 (PD-L1)] with standard-of-care chemotherapy in the treatment of advanced solid-organ neoplasms were included if AEs were reported as an outcome. Primary outcome was AEs ≥ grade 3 in severity. Secondary outcomes were proportion of overall AEs, treatment discontinuation due to AEs, deaths due to AEs, and specific AEs [fatigue, diarrhea, acute kidney injury (AKI), colitis, pneumonitis, and hypothyroidism]. Paule-Mandel pooling and a random effects model were used to produce odds ratios (ORs) for measures of effects. RESULTS: Among 10 598 abstracts screened, we included 22 studies involving 12 727 patients. In the immunotherapy group, 16.5% of patients developed an AE ≥ grade 3 in severity, compared with 41.09% in the chemotherapy arm [OR = 0.26, 95% confidence interval (CI) 0.19-0.35, I2 = 92%]. Patients receiving immunotherapy also had lower odds of developing an AE overall (OR = 0.35, 95% CI 0.28-0.44; I2 = 77%), terminating therapy due to an AE (OR = 0.55, 95% CI 0.39-0.78, I2 = 80%), or dying from a treatment-related AE (OR = 0.67, 95% CI 0.46-0.98, I2 = 0%). When treated with chemotherapy versus immunotherapy, patients more frequently experienced fatigue (25.10% versus 15.83%), diarrhea (14.97% versus 11.13%), and AKI (1.79% versus 1.31%). However, colitis (1.02% versus 0.26%), pneumonitis (3.36% versus 0.36%), and hypothyroidism (6.82% versus 0.37%) were more common in those treated with immunotherapy. CONCLUSIONS: Treatment of advanced solid-organ malignancies with immunotherapy compared with traditional chemotherapy is associated with a lower risk of AEs.

Transparent and Flexible Supercapacitors with Networked Electrodes.

Transparent and flexible energy storage devices have received immense attention due to their suitability for innovative electronics and displays. However, it remains a great challenge to fabricate devices with high storage capacity and high degree of transmittance. This study describes a simple process for fabrication of supercapacitors with ≈75% of visible transparency and areal capacitance of ≈3 mF cm-2 with high stability tested over 5000 cycles of charging and discharging. The electrodes consist of Au wire networks obtained by a simple crackle template method which are coated with MnO2 nanostructures by electrodeposition process. Importantly, the membrane separator itself is employed as substrate to bring in the desired transparency and light weight while additionally exploiting its porous nature in enhancing the interaction of electrolyte with the active material from both sides of the substrate, thereby enhancing the storage capacity. The method opens up new ways for fabricating transparent devices.

Study of sleep microstructure in patients of migraine without aura.

PURPOSE: Although the relationship between sleep and migraine has been widely reported, studies on sleep microstructure are few. The aim was to study and compare microstructural polysomnographic characteristics in patients of "migraine without aura" (MOA) with controls. METHODS: Twenty-five patients of MOA and 25 age- and gender-matched healthy controls were subjected to overnight polysomnography. Microstructural sleep analysis, including arousal and cyclic alternating pattern (CAP) analysis was performed. Arousals and CAP parameters were compared between the two groups using the Mann-Whitney U test (p ≤ 0.05). RESULTS: The overall arousal index (p = 0.528) and that during non-rapid eye movement (NREM) sleep (p = 0.503) were comparable between the two groups. However, the arousal index was lower in migraineurs during rapid eye movement (REM) sleep (p = 0.001). The overall CAP rate (p = 0.020) as well as the number of CAP cycles and sequences (p = 0.032) was lower among migraineurs. The total phase A duration (p < 0.0001) was increased, and conversely, phase B duration (p = 0.001) was decreased in migraineurs. The phase A1 duration (p = 0.036) was higher in migraineurs. Finally, phase A1 (p = 0.357) index was comparable, and conversely, A2 (p < 0.0001) and A3 (p = 0.020) indices were decreased in migraineurs. CONCLUSIONS: This study showed a decreased REM arousability as well as a decreased overall CAP rate and CAP cycling in patients with migraine as compared to controls. This indicates that there is probably an alteration of the arousal mechanisms in patients with migraine that may facilitate the occurrence of headache paroxysms during sleep.

Complications following surgery with or without radiotherapy or radiotherapy alone for prostate cancer.

BACKGROUND: Men undergoing treatment of clinically localised prostate cancer may experience a number of treatment-related complications, which affect their quality of life. METHODS: On the basis of population-based retrospective cohort of men undergoing surgery, with or without subsequent radiotherapy, or radiotherapy alone for prostate cancer in Ontario, Canada, we measured the incidence of treatment-related complications using administrative and billing data. RESULTS: Of 36 984 patients, 15 870 (42.9%) underwent surgery alone, 4519 (12.2%) underwent surgery followed by radiotherapy, and 16 595 (44.9%) underwent radiotherapy alone. For all end points except urologic procedures, the 5-year cumulative incidence rates were lowest in the surgery only group and highest in the radiotherapy only group. Intermediary rates were seen in the surgery followed by radiotherapy group, except for urologic procedures where rates were the highest in this group. Although age and comorbidity were important predictors, radiotherapy as the primary treatment modality was associated with higher rates for all complications (adjusted hazard ratios 1.6-4.7, P=0.002 to <0.0001). CONCLUSIONS: In patients treated for prostate cancer, radiation after surgery increases the rate of complications compared with surgery alone, though these rates remain lower than patients treated with radiation alone. This information may inform patient and physician decision making in the treatment of prostate cancer.

Pre-treatment neutrophil-to-lymphocyte ratio as predictor of adverse outcomes in patients undergoing radical cystectomy for urothelial carcinoma of the bladder.

BACKGROUND: An elevated neutrophil-to-lymphocyte ratio (NLR) is associated with poor outcome in various tumours. Its prognostic utility in patients with urothelial carcinoma of the bladder (UCB) undergoing radical cystectomy (RC) is yet to be fully elucidated. METHODS: A cohort of patients undergoing RC for UCB in a tertiary referral centre between 1992 and 2012 was analysed. Neutrophil-to-lymphocyte ratio was computed using complete blood counts performed pre-RC, or before neo-adjuvant chemotherapy where applicable. Time-dependent receiver operating characteristic curves were used to determine the optimal cutoff point for predicting recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). The predictive ability of NLR was assessed using Kaplan-Meier analyses and multivariable Cox proportional hazards models. The likelihood-ratio test was used to determine whether multivariable models were improved by including NLR. RESULTS: The cohort included 424 patients followed for a median of 58.4 months. An NLR of 3 was determined as the optimal cutoff value. Patients with an NLR⩾3.0 had significantly worse survival outcomes (5y-RFS: 53% vs 64%, log-rank P=0.013; 5y-CSS: 57% vs 75%, log-rank P<0.001; 5y-OS: 43% vs 64%, log-rank P<0.001). After adjusting for disease-specific predictors, an NLR ⩾3.0 was significantly associated with worse RFS (HR=1.49; 95% CI=1.12-2.0, P=0.007), CSS (HR=1.88; 95% CI=1.39-2.54, P<0.001) and OS (average HR=1.67; 95% CI=1.17-2.39, P=0.005). The likelihood-ratio test confirmed that prognostic models were improved by including NLR. CONCLUSIONS: Neutrophil-to-lymphocyte ratio is an inexpensive prognostic biomarker for patients undergoing RC for UCB. It offers pre-treatment prognostic value in addition to established prognosticators and may be helpful in guiding treatment decisions.

Evaluation of normal abdominal aortic diameters in the Indian population using computed tomography.

OBJECTIVES: The aim of this study was to establish normal diameters for the suprarenal and infrarenal abdominal aorta measured at T12 and L3 vertebral levels in the Indian population and to study the variation in aortic diameters with age, sex, height, weight, body mass index (BMI), and body surface area (BSA). MATERIALS AND METHODS: One hundred and forty-two patients who underwent helical contrast-enhanced computed tomography (CT) scans of the abdomen for non-cardiovascular reasons were recruited.. The mean internal diameters of the suprarenal and infrarenal abdominal aorta (maximum anteroposterior and transverse diameter) were measured at T12 and L3 vertebral levels and tabulated according to various age groups for both men and women. Pearson correlation coefficient was used to evaluate the correlation between aortic diameters, height, weight, BSA, and BMI. RESULTS: The mean diameters of the suprarenal and infrarenal abdominal aorta measured at T12 and L3 vertebral levels, in men were 19.0 ± 2.3 and 13.8 ± 1.9 mm and in women 17.1 ± 2.3 and 12.0 ± 1.6 mm, respectively. The aortic diameter progressively increased in caliber with increasing age of the patients and was smaller in women than men. A significant positive correlation was found in men between the suprarenal and infrarenal aortic diameters and weight, BSA, and BMI. In women, this correlation was significant in the infrarenal aorta but not in the suprarenal aorta. CONCLUSION: We obtained a set of normal values for the abdominal aorta in the Indian population. The aortic diameters correlated with age, gender, and body size of the patients as seen with previously published data in the Western population. A brief comparison of data between Indian and Western population showed that the values obtained were less than published elsewhere and hence, this should be considered while formulating intervention protocols.

A comparison of patient-reported outcomes in patients undergoing abdominal wall repair with either synthetic or biosynthetic mesh: a pilot study.

PURPOSE: Repair of midline ventral incisional hernias (VIHR) requires mesh reinforcement. Mesh types can be categorised into synthetic, biosynthetic, or biological. There is a lack of evidence to support one type of mesh over another. The aim of this pilot study was to compare mesh sensation in patients having undergone elective open repair with synthetic or biosynthetic mesh. METHODS: Four years of prospectively collected data were retrospectively reviewed on 40 patients who had undergone VIHR, using either biosynthetic or synthetic mesh placed in the retromuscular plane. The decision on type of mesh used was governed by patient characteristics. Patients were invited to complete the Carolinas Comfort Scale (CCS) questionnaire, the higher the score indicating a poorer quality of life. The maximum length of follow-up was 36 months. RESULTS: Twenty patients received permanent synthetic and 20 biosynthetic mesh. There was no clinical evidence of hernia recurrence in either group in the short to medium term. Overall, 97% (39/40) patients reported an average of either no or mild symptoms (mean CCS score 17.9 of 115). Patients with a biosynthetic repair had a significant lower CCS at ≥ 18 months (p < 0.05). CONCLUSION: After VIHR, patients have low CCS scores, indicating good quality of life outcomes, in the short to medium term irrespective of the mesh used. However, biosynthetic mesh had lower CCS scores in the medium term. This may help surgeons and patients make better informed decisions about which mesh to use in their individual circumstances.

Delphi consensus statement for understanding and managing the subcostal hernia: subcostal hernias collaborative report (scholar study).

INTRODUCTION: Subcostal hernias are categorized as L1 based on the European Hernia Society (EHS) classification and frequently involve M1, M2, and L2 sites. These are common after hepatopancreatic and biliary surgeries. The literature on subcostal hernias mostly comprises of retrospective reviews of small heterogenous cohorts, unsurprisingly leading to no consensus or guidelines. Given the limited literature and lack of consensus or guidelines for dealing with these hernias, we planned for a Delphi consensus to aid in decision making to repair subcostal hernias. METHODS: We adopted a modified Delphi technique to establish consensus regarding the definition, characteristics, and surgical aspects of managing subcostal hernias (SCH). It was a four-phase Delphi study reflecting the widely accepted model, consisting of: 1. Creating a query. 2. Building an expert panel. 3. Executing the Delphi rounds. 4. Analysing, presenting, and reporting the Delphi results. More than 70% of agreement was defined as a consensus statement. RESULTS: The 22 experts who agreed to participate in this Delphi process for Subcostal Hernias (SCH) comprised 7 UK surgeons, 6 mainland European surgeons, 4 Indians, 3 from the USA, and 2 from Southeast Asia. This Delphi study on subcostal hernias achieved consensus on the following areas-use of mesh in elective cases; the retromuscular position with strong discouragement for onlay mesh; use of macroporous medium-weight polypropylene mesh; use of the subcostal incision over midline incision if there is no previous midline incision; TAR over ACST; defect closure where MAS is used; transverse suturing over vertical suturing for closure of circular defects; and use of peritoneal flap when necessary. CONCLUSION: This Delphi consensus defines subcostal hernias and gives insight into the consensus for incision, dissection plane, mesh placement, mesh type, and mesh fixation for these hernias.

Solution-processed soldering of carbon nanotubes for flexible electronics.

We report a simple lithography-free, solution-based method of soldering of carbon nanotubes with Ohmic contacts, by taking specific examples of multi-walled carbon nanotubes (MWNTs). This is achieved by self-assembling a monolayer of soldering precursor, Pd(2+) anchored to 1,10 decanedithiol, onto which MWNTs could be aligned across the gap electrodes via solvent evaporation. The nanosoldering was realized by thermal/electrical activation or by both in sequence. Electrical activation and the following step of washing ensure selective retention of MWNTs spanning across the gap electrodes. The soldered joints were robust enough to sustain strain caused during the bending of flexible substrates as well as during ultrasonication. The estimated temperature generated at the MWNT-Au interface using an electro-thermal model is ∼150 °C, suggesting Joule heating as the primary mechanism of electrical activation. Further, the specific contact resistance is estimated from the transmission line model.

Association of GLUT2 and TAS1R2 genotypes with risk for dental caries.

To determine whether common polymorphisms in the sweet taste receptor (TAS1R2) and glucose transporter (GLUT2) genes are associated with dental caries, 80 healthy Caucasian individuals aged 21-32 years were genotyped and grouped based on the TAS1R2 (Ile191Val) and GLUT2 (Thr110Ile) polymorphisms. Clinical and radiographic examinations were conducted by a single examiner who was blinded to the genotypes. To assess caries prevalence, three different caries scores were determined: DMFT (decayed, missing, and filled teeth), DMFT + X-ray and ICDAS (International Caries Detection and Assessment System). Associations between genotypes and caries prevalence were analyzed using Student's t test. Based on the genotypes for each of the GLUT2 and TAS1R2 genes, individuals were stratified into four groups for comparison of caries scores. A higher DMFT score (mean ± SE; 4.3 ± 0.4 vs. 6.1 ± 1.2, p = 0.04) was observed among carriers of the Ile allele for GLUT2 (risk group). Carriers of the Val allele for TAS1R2 (resistant group) demonstrated lower caries scores: DMFT (4.1 ± 0.5 vs. 5.8 ± 0.9, p = 0.05), DMFT + X-ray (4.9 ± 0.6 vs. 7.5 ± 0.9, p = 0.01), and ICDAS (19.5 ± 2.2 vs. 26.14 ± 2.82, p = 0.03). Based on genotype stratification, caries scores were significantly lower in the double resistant group as compared to the double risk groups: DMFT (9.1 ± 0.08 vs. 4.2 ± 0.01, p < 0.01), DMFT + X-ray (10.5 ± 0.07 vs. 5.2 ± 0.01, p < 0.01) and ICDAS (32.9 ± 0.2 vs. 19.9 ± 0.01, p = 0.01). In conclusion, GLUT2 and TAS1R2 genotypes individually and in combination are associated with caries risk. Considering the combination of risk/resistance genotypes might further our understanding of genetic predispositions to dental caries and improve the accuracy of caries prediction models.

Indole-3-acetic acid biosynthetic pathway and aromatic amino acid aminotransferase activities in Pantoea dispersa strain GPK.

This investigation deals with the production of IAA by a bacterial isolate Pantoea dispersa strain GPK (PDG) identified by 16S rRNA gene sequence analysis. HPLC and Mass spectral analysis of metabolites from bacterial spent medium revealed that, IAA production by PDG is Trp-dependent and follows indole-3-pyruvic acid (IPyA) pathway. Substrate specificity study of aromatic amino acid aminotransferase (AAT) showed high activities, only when tryptophan (Trp) and α-ketoglutarate (α-kg) were used as substrates. AAT is highly specific for Trp and α-kg as amino group donor and acceptor, respectively. The effect of exogenous IAA on bacterial growth was established. Low concentration of exogenous IAA induced the growth, whereas high concentration decreased the growth of bacterium. PDG treatment significantly increased the root length, shoot length and dry mass of the chickpea and pigeon pea plants.

Shielding Effect of Ryanodine Receptor Modulator in Rat Model of Autism.

Introduction: A neurodevelopmental disorder, autism is typically identified with three primary behavioral consequences, such as social impairment, communication problems, and limited or stereotypical behavior. Because of its co-morbidity and lack of therapeutic options, autism is a global economic burden. A short chain of fatty acid, propionic acid is formed biologically by the gut microbiome. Propionic acid levels that are too high can cause leaky intestines, which can lead to autism-like symptoms. Methods: To induce autism, male Albino Wistar rats were given propionic acid (250 mg/kg/po on the 21st, 22nd, and 23rd postnatal days). Rats also received a ryanodine receptor antagonist (Ruthenium red: 3 mg/kg/po; postnatal 21st to 50th day) to see what influence it had on propionic acid-induced autism. Anxiety, social behavior, and repeated behaviors were all assessed, as well as oxidative stress, inflammatory indicators, neuro signaling proteins, and blood-brain barrier permeability. Results: Ruthenium red was found to counter the propionic acid-induced increases in anxiety, repetitive behavior prefrontal cortex levels of IL-6, TNF-α, TBARS, Evans blue leakage, and water content along with decreases in social behavior, IL-10, and GSH followed by hippocampus CREB and BDNF levels. Conclusion: Ryanodine receptor antagonists presented a neuroprotective effect in propionic acid-induced conditions like autism by modulatory effects on social and repetitive behavior, oxidative stress, neuroinflammation, and neuroprotein changes. Ryanodine receptors can be further explored in depth to manage autism as a condition. Highlights: Ruthenium red can reduce the propionic acid-induced anxiety of rats with autism.Ruthenium red can improve the propionic acid-induced changes in repetitive behavior of rats with autism.Ruthenium red can reduce the propionic acid-induced social behavior dysfunction in rats with autism. Plain Language Summary: Autism is a complex heterogeneous neurodevelopmental disorder mainly diagnosed with social behavior dysfunction, communication problems, and repetitive behavior. Due to high comorbidity and multiple unknown factors involvement, its exact etiology remains unclear, and so no successful treatment is available. Among the environmentally produced models of autism in rats, the most common is created by propionic acid (PPA). With short-chain type fatty acid, PPA is one of the mediators for the cycle of cell metabolism. This study attempted to study the effect of a ryano-dine receptor antagonist (Ruthenium red) on PPA-induced Anxiety, social behavior dysfunction, and repeated behaviors in rats with autism. The results showed the modulatory effects of Ruthenium red PPA-induced conditions including social and repetitive behavior, oxidative stress, neuroinflammation, and neuroprotein changes in rats with autism.

Resin Composite Versus Amalgam Restorations Placed in United States Dental Schools.

OBJECTIVES: To investigate the latest teaching policies for posterior resin composite placement versus amalgam and to determine the actual numbers of posterior resin composites versus amalgam restorations placed in American dental schools from 2008 to 2018. METHODS: Emails were sent to the deans of all 66 dental schools in the United States to collect data in the forms of: 1) Questionnaire on current teaching policies of posterior composite and amalgam restorations; and 2) Data entry form to collect the actual numbers of posterior composite and amalgam restorations placed in their clinics. Descriptive statistics were used to summarize ratios of posterior restorations. Inferential analysis (chi-square test and z-test) was employed to compare posterior restoration proportions over time and within each year. Level of significance was set at 0.05. RESULTS: For the teaching questionnaire, the response rate was 52% (n=34). Seventy-six per cent of the responding schools reported that they assign 50% or more of their preclinical restorative teaching time towards posterior resin composite placement, while 50% of the responding schools devoted 25% or less towards amalgam teaching. Data entry response rate was 26% (n=17). In 2008, amalgam and resin composite restorations were placed almost equally. However, resin composite restorations were placed significantly more frequently from 2009 onwards in all responding schools. The results revealed a significant ongoing increasing trend in placing posterior resin composites in all responding schools over time (p<0.05). CONCLUSIONS: Data analysis revealed a clear trend towards an increase in posterior resin composite restoration placement and a decrease in the number of amalgam restorations. However, the time assigned for posterior resin composite teaching is not aligned with quantity of restorations placed. Review and adjustment of the time allocated for teaching and training of each material are suggested.

Field effect transistors and photodetectors based on nanocrystalline graphene derived from electron beam induced carbonaceous patterns.

We describe a transfer-free method for the fabrication of nanocrystalline graphene (nc-graphene) on SiO(2) substrates directly from patterned carbonaceous deposits. The deposits were produced from the residual hydrocarbons present in the vacuum chamber without any external source by using an electron beam induced carbonaceous deposition (EBICD) process. Thermal treatment under vacuum conditions in the presence of Ni catalyst transformed the EBIC deposit into nc-graphene patterns, confirmed using Raman and TEM analysis. The nc-graphene patterns have been employed as an active p-type channel material in a field effect transistor (FET) which showed a hole mobility of ~90 cm(2) V(-1) s(-1). The nc-graphene also proved to be suitable material for IR detection.