Suppression of DGAT2 Expression Improves Hepatic Steatosis and Prevents Fat Induced Insulin Resistance

It is well known that metabolites resulting from the accumulation of fat in tissue results in fatty liver, obesity, and insulin resistance. Because triglyceride synthesis is essential for this process, inhibition of the final step of TG synthesis has been considered as a new therapeutic target for hepatosteatosis and insulin resistance. In this study, we investigated the metabolic impact of acyl CoA: diacylglycerol acyltransferase 1 (DGAT1) and 2 (DGAT2) suppression. We used antisense oligonucleotides (ASOs) to reduce the expression of these enzymes in liver and fat in Sprague Dawley rats fed a 27% safflower oil high fat diet (HFD) for 4 weeks. Rats were injected with one of the following: saline, control ASO, DGAT1 ASO or DGAT2 ASO subcutaneously twice a week for 4 weeks. DGAT1 and DGAT2 ASO treatment reduced DGAT1 and DGAT2 mRNA levels in liver by 95% and 57% respectively but only DGAT2 ASO treatment significantly reduced TG content when compared to the saline group. We determined the effects of ASO treatment on insulin action in vivo during a 135 min hyperinsulinemic(4mU/kg/min)-euglycemic clamp. Glucose turnover and uptake were assessed using [3-3H]glucose infusion and [1-14C]2-deoxyglucose injection during clamps. DGAT2 ASO treated rats were protected from HFD induced insulin resistance as demonstrated by an 80% increase in glucose infusion rate (24.0±0.9 vs. 13.4±1.1 mg/kg/min, p\u3c0.001). This was accounted for by significant suppression of hepatic glucose production (82±6 vs. 53±11% p\u3c0.05) and a 54% increase in insulin-stimulated whole body glucose uptake (25.3±1.1 vs. 16.3±0.7 mg/kg/min, p\u3c0.001) when compared to the control ASO group. Insulin-stimulated glucose uptake in skeletal muscle and suppression of plasma free fatty acid levels during the clamp were also significantly increased in DGAT2 ASO treated rats when compared to controls (2DG uptake: 329±31 vs. 263±28 nmol/g/min, p=0.03, suppression of FFA: 64±4 vs. 48±5%, p=0.015). Of note, the DGAT2 ASO group showed less weight gain than controls despite the same food consumption over the treatment period. The ratio of weight gain versus food consumption, efficiency of weight gain, was significantly lower in the DGAT2 group when compared to other groups, suggesting an increase in energy expenditure in the DGAT2 ASO group. In summary, this study demonstrates that the reduction of DGAT2 using an ASO protects against insulin resistance in liver and peripheral tissue

Efficacy of local anaesthetic cocktail infiltration in a total knee replacement: a prospective, randomized study

Background: The aim of this study is to assess the efficacy of local anaesthetic cocktail infiltration in pain management during a total knee arthroplasty.Methods: In this study we had 25 patients each in study and control group. The study group was infiltrated with the local anesthetic cocktail just before final implantation. Pain was documented by a visual analogue scale in a double blinded manner. Statistical significance was calculated using an unpaired “t” test.Results: In study group, pain levels were significantly lower as compared to control group for the first 48 hours after surgery with a ‘p’ value of 0.0224 (<0.05). The need of intravenous tramadol for breakthrough pain on the second day was significantly lower in study group as compared to control group with a ‘p’ value of 0.033(<0.05).Conclusions: This study shows that the local high volume anaesthetic infiltration is effective in reducing immediate postoperative pain and the need of IV opioids for the first 48 hours after surgery

AUTOMATIC PENALTY CHARGING FOR TRAFFIC REGULATION

The research, "Automatic Penalty Charging for Traffic Regulation", is an attempt to design a system which will automatically incur penalty to the car driver and owner for violation of traffic rules. There are 3 units to be designed. One will be a standalone system attached to the ignition mechanism of the car, the other will be a standalone system which will be attached to the traffic signal points and the third will be mainframe RTO unit. For car ignition the driver has to place his RFID driving license card near to the reader. The design aims to reduce bribery, corruption, pollution, congestion in a city

A scoping review of natural language processing of radiology reports in breast cancer

Various natural language processing (NLP) algorithms have been applied in the literature to analyze radiology reports pertaining to the diagnosis and subsequent care of cancer patients. Applications of this technology include cohort selection for clinical trials, population of large-scale data registries, and quality improvement in radiology workflows including mammography screening. This scoping review is the first to examine such applications in the specific context of breast cancer. Out of 210 identified articles initially, 44 met our inclusion criteria for this review. Extracted data elements included both clinical and technical details of studies that developed or evaluated NLP algorithms applied to free-text radiology reports of breast cancer. Our review illustrates an emphasis on applications in diagnostic and screening processes over treatment or therapeutic applications and describes growth in deep learning and transfer learning approaches in recent years, although rule-based approaches continue to be useful. Furthermore, we observe increased efforts in code and software sharing but not with data sharing

Physician Accuracy in Interpreting Potential ST‐Segment Elevation Myocardial Infarction Electrocardiograms

Background: With adoption of telemedicine, physicians are increasingly asked to diagnose ST‐segment elevation myocardial infarctions (STEMIs) based on electrocardiograms (ECGs) with minimal associated clinical information. We sought to determine physicians' diagnostic agreement and accuracy when interpreting potential STEMI ECGs. Methods and Results: A cross‐sectional survey was performed consisting of 36 deidentified ECGs that had previously resulted in putative STEMI diagnoses. Emergency physicians, cardiologists, and interventional cardiologists participated in the survey. For each ECG, physicians were asked, “based on the ECG above, is there a blocked coronary artery present causing a STEMI?” The reference standard for ascertaining the STEMI diagnosis was subsequent emergent coronary arteriography. Responses were analyzed with generalized estimating equations to account for nested and repeated measures. One hundred twenty‐four physicians interpreted a total of 4392 ECGs. Among all physicians, interreader agreement (kappa) for ECG interpretation was 0.33, reflecting poor agreement. The sensitivity to identify “true” STEMIs was 65% (95% CI: 63 to 67) and the specificity was 79% (95% CI: 77 to 81). There was a 6% increase in the odds of accurate ECG interpretation for every 5 years of experience since medical school graduation (OR 1.06, 95% CI: 1.02 to 1.10, P=0.01). After adjusting for experience, there was no significant difference in the odds of accurate interpretation by specialty—Emergency Medicine (reference), General Cardiology (AOR 0.97, 95% CI: 0.79 to 1.2, P=0.80), or Interventional Cardiology physicians (AOR 1.24, 95% CI: 0.93 to 1.7, P=0.15). Conclusions: There is significant physician disagreement in interpreting ECGs with features concerning for STEMI. Such ECGs lack the necessary sensitivity and specificity to act as a suitable “stand‐alone” diagnostic test

Redox signaling by glutathione peroxidase 2 links vascular modulation to metabolic plasticity of breast cancer

In search of redox mechanisms in breast cancer, we uncovered a striking role for glutathione peroxidase 2 (GPx2) in oncogenic signaling and patient survival. GPx2 loss stimulates malignant progression due to reactive oxygen species/hypoxia inducible factor-α (HIF1α)/VEGFA (vascular endothelial growth factor A) signaling, causing poor perfusion and hypoxia, which were reversed by GPx2 reexpression or HIF1α inhibition. Ingenuity Pathway Analysis revealed a link between GPx2 loss, tumor angiogenesis, metabolic modulation, and HIF1α signaling. Single-cell RNA analysis and bioenergetic profiling revealed that GPx2 loss stimulated the Warburg effect in most tumor cell subpopulations, except for one cluster, which was capable of oxidative phosphorylation and glycolysis, as confirmed by coexpression of phosphorylated-AMPK and GLUT1. These findings underscore a unique role for redox signaling by GPx2 dysregulation in breast cancer, underlying tumor heterogeneity, leading to metabolic plasticity and malignant progression

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Au nanoparticle assembly on CNTS using flash induced solid-state dewetting

Carbon Nanotubes (CNTs) are used extensively in various applications where substrate are required to be possessing higher surface area, porosity and electrical and thermal conductivity. Such properties can be enhanced to target a particular gas and biochemical for efficient detection when CNT matrix is functionalized with Nanoparticles (NPs). Conventional functionalization involves harsh oxidation repeated washing, filtration and sonication, which induce defects. The defects lead to hindered mobility of carriers, unwanted doping and also fragmentation of the CNTs in some cases. In this document we demonstrate functionalization of CNT with Au nanoparticles on a macro scale under dry and ambient condition using Xenon flash induced solid-state dewetting. A sputtered thin film was transformed into nanoparticles which were confirmed to be in a state of thermodynamic equilibrium. We worked on 3nm, 6nm, 9nm, 15nm, 30nm initial thickness of thin films. Xenon flash parameters of energy, number of pulse, Duration of pulse, duration of gap between consecutive pulses were optimized to achieve complete dewetting of Au thin films. 3nm deposition was in the form of irregular nano-islands which were transformed into stable nanoparticles with a single shot of 10J/cm2 of 2ms duration. 6nm and 9nm deposition was in form of continues film which was also dewetted into stable nanoparticles with a single pulse but with an increased energy density of 20J/cm2 and 35 J/cm2 respectively. In case of 15nm and 30nm deposition the thin film couldn\u27t be dewetted with a maximum energy density of 50 J/cm2, it was observed that 3 and 4 pulses of 2ms pulse duration and 2ms gap duration with an energy density of 50J/cm 2 were required to completely dewet the thicker films. However irregularity was induced in the sizes of the NPs due to Ostwald ripening phenomenon which causes smaller particle within a critical diffusion length to combine and form a larger particle during or after dewetting process. For comparison purpose the Au thin films were also dewetted by a conventional process involving annealing of samples until the thin film was fully transformed into NPs and the size of NPs seized to grow. Scanning electron microscope (SEM) was used to characterize the samples. Thermodynamic stability of the particles was confirmed with statistical analyses of size distribution after every additional pulse