Dietary UKMR-1 Roselle supplementation prevents nicotine-induced cardiac injury by inhibiting myocardial oxidative stress

UKMR-1, a local variant of mutant Roselle strain (Hibiscus sabdariffa) is enriched with free radical scavenging polyphenols such as anthocyanin, vitamin C and hydroxycitric acid. However, pharmacological actions of UKMR-1 are not fully known. This study was conducted to determine whether supplementation of aqueous UKMR-1 calyx extract was able to protect against nicotine-induced cardiac injury in rats. In this experimental study, healthy male albino rats were randomly allotted into three groups (n=7 per group): control, nicotine and UKMR-1+Nicotine groups. Nicotine (0.6 mg/kg, i.p.) was administered to both nicotine and UKMR-1+Nicotine groups for 28 consecutive days. UKMR-1+Nicotine group also received 100 mg/kg UKMR-1 extract orally via gavage 30 min prior to nicotine injection, daily. UKMR-1+Nicotine group had significantly (p<0.05) higher lactate dehydrogenase (LDH) activity, as well as lower malondialdehyde content in heart tissue homogenate than nicotine group, suggesting its cardio protective activity by inhibition of lipid peroxidation. UKMR-1 also lowered (p<0.05) the blood pressure in nicotine-administered rats. In addition, UKMR-1 significantly (p<0.05) restored activities of cytosolic superoxide dismutase, glutathione peroxidase and glutathione-S-transferase as well as redox balance ratio (GSH:GSSG). In conclusion, UKMR-1 was able to protect against myocardial injury in rat model of nicotine administration possibly by inhibiting oxidative stress

An Intelligent Optimized Route-Discovery Model for IoT-Based VANETs

Abstract: Please refer to full text to view abstrac

Predictors of mortality among hospitalized COVID-19 patients and risk score formulation for prioritizing tertiary care—An experience from South India

BACKGROUND: We retrospectively data-mined the case records of Reverse Transcription Polymerase Chain Reaction (RT-PCR) confirmed COVID-19 patients hospitalized to a tertiary care centre to derive mortality predictors and formulate a risk score, for prioritizing admission. METHODS AND FINDINGS: Data on clinical manifestations, comorbidities, vital signs, and basic lab investigations collected as part of routine medical management at admission to a COVID-19 tertiary care centre in Chengalpattu, South India between May and November 2020 were retrospectively analysed to ascertain predictors of mortality in the univariate analysis using their relative difference in distribution among ‘survivors’ and ‘non-survivors’. The regression coefficients of those factors remaining significant in the multivariable logistic regression were utilised for risk score formulation and validated in 1000 bootstrap datasets. Among 746 COVID-19 patients hospitalised [487 “survivors” and 259 “non-survivors” (deaths)], there was a slight male predilection [62.5%, (466/746)], with a higher mortality rate observed among 40–70 years age group [59.1%, (441/746)] and highest among diabetic patients with elevated urea levels [65.4% (68/104)]. The adjusted odds ratios of factors [OR (95% CI)] significant in the multivariable logistic regression were SaO(2)3; 3.01 (1.61–5.83), Age ≥50 years;2.52 (1.45–4.43), Pulse Rate ≥100/min: 2.02 (1.19–3.47) and coexisting Diabetes Mellitus; 1.73 (1.02–2.95) with hypertension and gender not retaining their significance. The individual risk scores for SaO(2)3–11, Age ≥50 years-9, Pulse Rate ≥100/min-7 and coexisting diabetes mellitus-6, acronymed collectively as ‘OUR-ARDs score’ showed that the sum of scores ≥ 25 predicted mortality with a sensitivity-90%, specificity-64% and AUC of 0.85. CONCLUSIONS: The ‘OUR ARDs’ risk score, derived from easily assessable factors predicting mortality, offered a tangible solution for prioritizing admission to COVID-19 tertiary care centre, that enhanced patient care but without unduly straining the health system

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Analysis techniques for nanometer digital integrated circuits

As technology has scaled into nanometer regime, manufacturing variations have emerged as a major limiter of performance (timing) in VLSI circuits. Issues related to timing are addressed in the first part of the dissertation. Statistical Static Timing Analysis (SSTA) has been proposed to perform full-chip analysis of timing under uncertainty such as manufacturing variations. In this dissertation, we propose an efficient sparse-matrix framework for a path-based SSTA. In addition to an efficient framework for doing timing analysis, to improve the accuracy of the timing analysis one needs to address the accuracy of: waveform modeling, and gate delay modeling. We propose a technique based on Singular Value Decomposition (SVD) that accurately models the waveform in a timing analyzer. To improve the gate delay modeling, we propose a closed form expression based on the centroid of power dissipation. This new metric is inspired by our key observation that the Sakurai-Newton (SN) delay metric can be viewed as the centroid of current. In addition to accurately analyzing the timing of a chip, improving timing is another major concern. One way to improve timing is to scale down the threshold voltage (Vth). But scaling down increases the subthreshold leakage current exponentially. Sleep transistors have been proposed to reduce leakage current while maintaining performance. We propose a path-based algorithm to size the sleep transistor to reduce leakage while maintaining the required performance. In the second part of dissertation we address power grid and thermal issues that arise due to the scaling of integrated circuits. In the case of power grid simulation, we propose fast and efficient techniques to analyze the power grid with accurate modeling of the transistor network. The transistor is modeled as a switch in series with an RC and the switch itself is modeled behaviorally. This model allows more accurate prediction of voltage drop compared to the current source model. In the case of thermal simulation, we address the issue of ignoring the nonlinearity of thermal conductivity in silicon. We found that ignoring the nonlinearity of thermal conductivity may lead to a temperature profile that is off by 10° C.Electrical and Computer Engineerin

Sleep Transistor Sizing Using Timing Criticality and Temporal Currents

Power gating is a circuit technique that enables high performance and low power operation. One of the challenges in power gating is sizing the sleep transistor which is used to gate the power supply. This paper presents a new methodology based on timing criticality and temporal currents to size the sleep transistor. The timing criticality information and temporal current estimation are obtained using static timing analyzer. The results obtained indicate that our proposed technique results in area reduction of sleep transistors by 80 % and 49 % compared to module based design and cluster based design respectively

Resveratrol Supplementation Protects against Nicotine-Induced Kidney Injury

Prolonged exposure to nicotine accelerates onset and progression of renal diseases in habitual cigarette smokers. Exposure to nicotine, either via active or passive smoking is strongly shown to enhance renal oxidative stress and augment kidney failure in various animal models. In this study, we investigated the effects of resveratrol supplementation on nicotine-induced kidney injury and oxidative stress in a rat model. Male Sprague-Dawley rats were given nicotine (0.6 mg/kg, i.p.) alone or in combination with either resveratrol (8 mg/kg, i.p.), or angiotensin II type I receptor blocker, irbesartan (10 mg/kg, p.o.) for 28 days. Upon completion of treatment, kidneys were investigated for changes in structure, kidney injury markers and oxidative stress. Administration of nicotine alone for 28 days resulted in significant renal impairment as shown by marked increase in plasma creatinine, blood urea nitrogen (BUN) and oxidative stress. Co-administration with resveratrol however successfully attenuated these changes, with a concomitant increase in renal antioxidants such as glutathione similar to the conventionally used angiotensin II receptor blocker, irbesartan. These data altogether suggest that targeting renal oxidative stress with resveratrol could alleviate nicotine-induced renal injury. Antioxidants may be clinically important for management of renal function in habitual smokers