Local Application of Sodium Salicylate Enhances Auditory Responses in the Rat’s Dorsal Cortex of the Inferior Colliculus

Sodium salicylate (SS) is a widely used medication with side effects on hearing. In order to understand these side effects, we recorded sound-driven local-field potentials in a neural structure, the dorsal cortex of the inferior colliculus (ICd). Using a microiontophoretic technique, we applied SS at sites of recording and studied how auditory responses were affected by the drug. Furthermore, we studied how the responses were affected by combined local application of SS and an agonists/antagonist of the type-A or type-B γ-aminobutyric acid receptor (GABAA or GABAB receptor). Results revealed that SS applied alone enhanced auditory responses in the ICd, indicating that the drug had local targets in the structure. Simultaneous application of the drug and a GABAergic receptor antagonist synergistically enhanced amplitudes of responses. The synergistic interaction between SS and a GABAA receptor antagonist had a relatively early start in reference to the onset of acoustic stimulation and the duration of this interaction was independent of sound intensity. The interaction between SS and a GABAB receptor antagonist had a relatively late start, and the duration of this interaction was dependent on sound intensity. Simultaneous application of the drug and a GABAergic receptor agonist produced an effect different from the sum of effects produced by the two drugs released individually. These differences between simultaneous and individual drug applications suggest that SS modified GABAergic inhibition in the ICd. Our results indicate that SS can affect sound-driven activity in the ICd by modulating local GABAergic inhibition

Analysis and Implementation of Malicious Node in AODV Routing Protocol

The Mobile Ad-hoc Network (MANET) is constructed based on wireless medium and it is of self organizing behaviour. MANET is easy to establish and having dynamic topology. The mobile Ad-hoc networks are vulnerable to various networks attacks because MANET operational environment is open and dynamic or live. MANET uses the Routing protocols for data transfer. Two different types of Routing protocols are available: Table Driven and On Demand Routing Protocols. Malicious node is the one type of mobile node but its work is completely different compared to normal Mobile nodes. Malicious nodes have capability to change or remove Routing Information. It also sends or advertises the fake Route Request to attract user’s data. Malicious node disturbs the Network to carry correct flow of operation. It is responsible for attacks on the existing normal mobile nodes and creates receiver collision, limited transmission power, false misbehaviour etc. Malicious or selfish node carries attacks on the networks so it directly effects to the routing Performance. The objective of this work is to check Network performance in malicious environment and provide prevention for the attack. Throughput and Delay are analysed for Denial of Service (DoS) attack and prevention scenarios. Keywords: MANET, AODV, Selfish Node, DoS Attack, Routing Protocol

The level and distribution of the GABABR1 and GABABR2 receptor subunits in the rat\u27s inferior colliculus

The type B γ-aminobutyric acid receptor (GABAB receptor) is an important neurotransmitter receptor in the midbrain auditory structure, the inferior colliculus (IC). A functional GABAB receptor is a heterodimer consisting of two subunits, GABABR1 and GABABR2. Western blotting and immunohistochemical experiments were conducted to examine the expression of the two subunits over the IC including its central nucleus, dorsal cortex, and external cortex (ICc, ICd, and ICx). Results revealed that the two subunits existed in both cell bodies and the neuropil throughout the IC. The two subunits had similar regional distributions over the IC. The combined level of cell body and neuropil labelling was higher in the ICd than the other two subdivisions. Labelling in the ICc and ICx was stronger in the dorsal than the ventral regions. In spite of regional differences, no defined boundaries were formed between different areas. For both subunits, the regional distribution of immunoreactivity in the neuropil was parallel to that of combined immunoreactivity in the neuropil and cell bodies. The density of labelled cell bodies tended to be higher but sizes of cell bodies tended to be smaller in the ICd than in the other subdivisions. No systematic regional changes were found in the level of cell body immunoreactivity, except that GABABR2-immunoreactive cell bodies in the ICd had slightly higher optic density than in other regions. Elongated cell bodies existed throughout the IC. Many labelled cell bodies along the outline of the IC were oriented in parallel to the outline. No strong tendency of orientation was found in labelled cell bodies in ICc. Regional distributions of the subunits in ICc correlated well with inputs to this subdivision. Our finding regarding the contrast in the level of neuropil immunoreactivity among different subdivisions is consistent with the fact that the GABAB receptor has different pre- and postsynaptic functions in different IC regions

Data-driven assessment, contextualisation and implementation of 134 variables in the risk for type 2 diabetes:an analysis of Lifelines, a prospective cohort study in the Netherlands

Aims/hypothesis We aimed to assess and contextualise 134 potential risk variables for the development of type 2 diabetes and to determine their applicability in risk prediction. Methods A total of 96,534 people without baseline diabetes (372,007 person-years) from the Dutch Lifelines cohort were included. We used a risk variable-wide association study (RV-WAS) design to independently screen and replicate risk variables for 5-year incidence of type 2 diabetes. For identified variables, we contextualised HRs, calculated correlations and assessed their robustness and unique contribution in different clinical contexts using bootstrapped and cross-validated lasso regression models. We evaluated the change in risk, or 'HR trajectory', when sequentially assigning variables to a model. Results We identified 63 risk variables, with novel associations for quality-of-life indicators and non-cardiovascular medications (i.e., proton-pump inhibitors, anti-asthmatics). For continuous variables, the increase of 1 SD of HbA(1c), i.e., 3.39 mmol/mol (0.31%), was equivalent in risk to an increase of 0.53 mmol/l of glucose, 19.8 cm of waist circumference, 8.34 kg/m(2) of BMI, 0.67 mmol/l of HDL-cholesterol, and 0.14 mmol/l of uric acid. Other variables required an increase of >3 SD, which is not physiologically realistic or a rare occurrence in the population. Though moderately correlated, the inclusion of four variables satiated prediction models. Invasive variables, except for glucose and HbA(1c), contributed little compared with non-invasive variables. Glucose, HbA(1c) and family history of diabetes explained a unique part of disease risk. Adding risk variables to a satiated model can impact the HRs of variables already in the model. Conclusions Many variables show weak or inconsistent associations with the development of type 2 diabetes, and only a handful can reliably explain disease risk. Newly discovered risk variables will yield little over established factors, and existing prediction models can be simplified. A systematic, data-driven approach to identify risk variables for the prediction of type 2 diabetes is necessary for the practice of precision medicine

Sarcina ventriculi: A Rare Case of Life-Threatening Perforated Gastric Ulcer and Review of Literature

Sarcina ventriculi is a gram-positive anaerobic bacterium reported rarely in patients with a history of gastrointestinal surgery and delayed gastric emptying. Sarcina has been implicated in the development of gastric ulcers, emphysematous gastritis, and gastric perforation. So far, less than 30 cases of Sarcina isolated from gastric specimens have been reported, including 3 cases associated with life-threatening illness:emphysematous gastritis and gastric perforation. Herein, we report a case of a 58-yearold woman with history of gastric surgery who presented for evaluation of persistent gastric pain and incurable ulcer. She underwent total gastrectomy, and the resected stomach demonstrated a perforated ulcer with the presence of Sarcina microorganisms.We also report a second case of a 56-year-old woman with history of NSAID use who presented with gastric outlet obstruction. The gastric biopsy identified concurrent Helicobacter pylori and Sarcina. Given Sarcina's association with emphysematous gastritis and gastric perforation, its identification on gastric biopsies should be clearly stated in pathology reports and, depending on the clinical scenario, prompt clinicians to add adjunctive antimicrobials to anti-ulcer therapeutic regimens

Compendium of Single Event Effects Test Results for Commercial Off-The-Shelf and Standard Electronics for Low Earth Orbit and Deep Space Applications

We present the results of Single Event Effects (SEE) testing with high energy protons and with low and high energy heavy ions for electrical components considered for Low Earth Orbit (LEO) and for deep space applications

A green bio-organic catalyst (taurine) promoted one-pot synthesis of (R/S)-2-thioxo-3,4-dihydropyrimidine(TDHPM)-5-carboxanilides: chiral investigations using circular dichroism and validation by computational approaches

Owing to the massive importance of dihydropyrimidine (DHPMs) scaffolds in the pharmaceutical industry and other areas, we developed an effective and sustainable one-pot reaction protocol for the synthesis of (R/S)-2-thioxo-DHPM-5-carboxanilides via the Biginelli-type cyclo-condensation reaction of aryl aldehydes, thiourea and various acetoacetanilide derivatives in ethanol at 100 °C. In this protocol, taurine was used as a green and reusable bio-organic catalyst. Twenty-three novel derivatives of (R/S)-TDHPM-5-carboxanilides and their structures were confirmed by various spectroscopy techniques. The aforementioned compounds were synthesized via the formation of one asymmetric centre, one new C–C bond, and two new C–N bonds in the final product. All the newly synthesized compounds were obtained in their racemic form with up to 99% yield. In addition, the separation of the racemic mixture of all the newly synthesized compounds was carried out by chiral HPLC (Prep LC), which provided up to 99.99% purity. The absolute configuration of all the enantiomerically pure isomers was determined using a circular dichroism study and validated by a computational approach. With up to 99% yield of 4d, this one-pot synthetic approach can also be useful for large-scale industrial production. One of the separated isomers (4R)-(+)-4S developed as a single crystal, and it was found that this crystal structure was orthorhombic

Bilateral macular hole formation secondary to sclopetaria caused by shockwaves transmitted by a posterior vector: case report

<p>Abstract</p> <p>Background</p> <p>Sclopetaria is a rare ophthalmic finding in trauma</p> <p>Case Presentation</p> <p>This is a report of a patient who developed macular holes from sclopetaria induced by indirect trauma. A 22-year-old male, suffered a gunshot wound that passed behind his eyes, resulting in bilateral macular hole formation</p> <p>Conclusion</p> <p>To our knowledge, this is the first reported case in which trauma posterior to the globes caused bilateral macular hole formation</p

Mendelian randomization study of adiposity-related traits and risk of breast, ovarian, prostate, lung and colorectal cancer

Background: Adiposity traits have been associated with risk of many cancers in observational studies, but whether these associations are causal is unclear. Mendelian randomization (MR) uses genetic predictors of risk factors as instrumental variables to eliminate reverse causation and reduce confounding bias. We performed MR analyses to assess the possible causal relationship of birthweight, childhood and adult body mass index (BMI), and waist-hip ratio (WHR) on the risks of breast, ovarian, prostate, colorectal and lung cancers. Methods: We tested the association between genetic risk scores and each trait using summary statistics from published genome-wide association studies (GWAS) and from 51 537 cancer cases and 61 600 controls in the Genetic Associations and Mechanisms in Oncology (GAME-ON) Consortium. Results: We found an inverse association between the genetic score for childhood BMI and risk of breast cancer [odds ratio (OR)=0.71 per standard deviation (s.d.) increase in childhood BMI; 95% confidence interval (CI): 0.60, 0.80; P=6.5×10-5). We also found the genetic score for adult BMI to be inversely associated with breast cancer risk (OR=0.66 per s.d. increase in BMI; 95% CI: 0.57, 0.77; P=2.5×10-7), and positively associated with ovarian cancer (OR=1.35; 95% CI: 1.05, 1.72; P=0.017), lung cancer (OR=1.27; 95% CI: 1.09, 1.49; P=2.9×10-3) and colorectal cancer (OR=1.39; 95% CI: 1.06, 1.82, P=0.016). The inverse association between genetically predicted adult BMI and breast cancer risk remained even after adjusting for directional pleiotropy via MR-Egger regression. Conclusions: Findings from this study provide additional understandings of the complex relationship between adiposity and cancer risks. Our results for breast and lung cancer are particularly interesting, given previous reports of effect heterogeneity by menopausal status and smoking status.</p

An Environment-Wide Association Study (EWAS) on Type 2 Diabetes Mellitus

Background: Type 2 Diabetes (T2D) and other chronic diseases are caused by a complex combination of many genetic and environmental factors. Few methods are available to comprehensively associate specific physical environmental factors with disease. We conducted a pilot Environmental-Wide Association Study (EWAS), in which epidemiological data are comprehensively and systematically interpreted in a manner analogous to a Genome Wide Association Study (GWAS). Methods and Findings: We performed multiple cross-sectional analyses associating 266 unique environmental factors with clinical status for T2D defined by fasting blood sugar (FBG) concentration $126 mg/dL. We utilized available Centers for Disease Control (CDC) National Health and Nutrition Examination Survey (NHANES) cohorts from years 1999 to 2006. Within cohort sample numbers ranged from 503 to 3,318. Logistic regression models were adjusted for age, sex, body mass index (BMI), ethnicity, and an estimate of socioeconomic status (SES). As in GWAS, multiple comparisons were controlled and significant findings were validated with other cohorts. We discovered significant associations for the pesticide-derivative heptachlor epoxide (adjusted OR in three combined cohorts of 1.7 for a 1 SD change in exposure amount; p,0.001), and the vitamin c-tocopherol (adjusted OR 1.5; p,0.001). Higher concentrations of polychlorinated biphenyls (PCBs) such as PCB170 (adjusted OR 2.2; p,0.001) were also found. Protective factors associated with T2D included b-carotenes (adjusted OR 0.6; p,0.001)