Evaluation of Oxidative Stress and Antioxidant Status in Patients with Cardiovascular Disease in Rural Populations of the Nilgiris, South India

Objective. The objective of this work was to study the risk factors of ischaemic heart disease (IHD) in rural populations of the Nilgiris, south India, with stress on the various social habits and oxidant stress. Methods. A total of 72 patients with cardiovascular disease (CVD) and 12 healthy volunteers were screened. Forty-seven patients with CVD (intervention group) and 10 healthy volunteers (control group) were randomly selected for the study. Written informed consent was obtained from all the participants, and their demographic details were collected. A 6 mL blood sample was collected from each of the participants, and the serum was separated in the samples. The levels of enzymic (superoxide dismutase, catalase) and nonenzymic antioxidants (ascorbic acid) in the plasma were determined biochemically. The level of thiobarbituric acid species (TBARS), which is a predictor of lipid peroxidation, was measured. Results. The participants of the study were stratified as according to demographic and social variables. The values of all the antioxidants and TBARS were statistically compared. Significantly reduced antioxidant levels and increased TBARS levels were found in the intervention group compared with the control group. The results suggest that the lowered antioxidant level may be a result of the oxidant stress of the disease. Statistically significant differences were not found in the antioxidant and TBARS levels when comparing smokers versus nonsmokers, alcoholics versus nonalcoholics, and vegetarians versus nonvegetarians. Conclusion. The major causes of CVD amongst the rural populations of the Nilgiris, south India, are preventable causes such as smoking and high fat intake, all of which cause oxidative stress, as seen in our study through various serum markers

Intrusion Detection Systems Based on Artificial Intelligence Techniques in Wireless Sensor Networks

[EN] Intrusion detection system (IDS) is regarded as the second line of defense against network anomalies and threats. IDS plays an important role in network security. There are many techniques which are used to design IDSs for specific scenario and applications. Artificial intelligence techniques are widely used for threats detection. This paper presents a critical study on genetic algorithm, artificial immune, and artificial neural network (ANN) based IDSs techniques used in wireless sensor network (WSN)The authors extend their appreciation to the Distinguished Scientist Fellowship Program(DSFP) at King Saud University for funding this research.Alrajeh, NA.; Lloret, J. (2013). Intrusion Detection Systems Based on Artificial Intelligence Techniques in Wireless Sensor Networks. International Journal of Distributed Sensor Networks. 2013(351047):1-6. https://doi.org/10.1155/2013/351047S16201335104

Niche-Based Screening in Multiple Myeloma Identifies a Kinesin-5 Inhibitor with Improved Selectivity over Hematopoietic Progenitors

SummaryNovel therapeutic approaches are urgently required for multiple myeloma (MM). We used a phenotypic screening approach using co-cultures of MM cells with bone marrow stromal cells to identify compounds that overcome stromal resistance. One such compound, BRD9876, displayed selectivity over normal hematopoietic progenitors and was discovered to be an unusual ATP non-competitive kinesin-5 (Eg5) inhibitor. A novel mutation caused resistance, suggesting a binding site distinct from known Eg5 inhibitors, and BRD9876 inhibited only microtubule-bound Eg5. Eg5 phosphorylation, which increases microtubule binding, uniquely enhanced BRD9876 activity. MM cells have greater phosphorylated Eg5 than hematopoietic cells, consistent with increased vulnerability specifically to BRD9876’s mode of action. Thus, differences in Eg5-microtubule binding between malignant and normal blood cells may be exploited to treat multiple myeloma. Additional steps are required for further therapeutic development, but our results indicate that unbiased chemical biology approaches can identify therapeutic strategies unanticipated by prior knowledge of protein targets

Niche-Based Screening in Multiple Myeloma Identifies a Kinesin-5 Inhibitor with Improved Selectivity over Hematopoietic Progenitors

Novel therapeutic approaches are urgently required for multiple myeloma (MM). We used a phenotypic screening approach using co-cultures of MM cells with bone marrow stromal cells to identify compounds that overcome stromal resistance. One such compound, BRD9876, displayed selectivity over normal hematopoietic progenitors and was discovered to be an unusual ATP non-competitive kinesin-5 (Eg5) inhibitor. A novel mutation caused resistance, suggesting a binding site distinct from known Eg5 inhibitors, and BRD9876 inhibited only microtubule-bound Eg5. Eg5 phosphorylation, which increases microtubule binding, uniquely enhanced BRD9876 activity. MM cells have greater phosphorylated Eg5 than hematopoietic cells, consistent with increased vulnerability specifically to BRD9876’s mode of action. Thus, differences in Eg5-microtubule binding between malignant and normal blood cells may be exploited to treat multiple myeloma. Additional steps are required for further therapeutic development, but our results indicate that unbiased chemical biology approaches can identify therapeutic strategies unanticipated by prior knowledge of protein targets

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Developing Standard Treatment Workflows—way to universal healthcare in India

Primary healthcare caters to nearly 70% of the population in India and provides treatment for approximately 80–90% of common conditions. To achieve universal health coverage (UHC), the Indian healthcare system is gearing up by initiating several schemes such as National Health Protection Scheme, Ayushman Bharat, Nutrition Supplementation Schemes, and Inderdhanush Schemes. The healthcare delivery system is facing challenges such as irrational use of medicines, over- and under-diagnosis, high out-of-pocket expenditure, lack of targeted attention to preventive and promotive health services, and poor referral mechanisms. Healthcare providers are unable to keep pace with the volume of growing new scientific evidence and rising healthcare costs as the literature is not published at the same pace. In addition, there is a lack of common standard treatment guidelines, workflows, and reference manuals from the Government of India. Indian Council of Medical Research in collaboration with the National Health Authority, Govt. of India, and the WHO India country office has developed Standard Treatment Workflows (STWs) with the objective to be utilized at various levels of healthcare starting from primary to tertiary level care. A systematic approach was adopted to formulate the STWs. An advisory committee was constituted for planning and oversight of the process. Specialty experts' group for each specialty comprised of clinicians working at government and private medical colleges and hospitals. The expert groups prioritized the topics through extensive literature searches and meeting with different stakeholders. Then, the contents of each STW were finalized in the form of single-pager infographics. These STWs were further reviewed by an editorial committee before publication. Presently, 125 STWs pertaining to 23 specialties have been developed. It needs to be ensured that STWs are implemented effectively at all levels and ensure quality healthcare at an affordable cost as part of UHC

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

INFLUENCE OF PROCESS PARAMETERS ON THREE BODY ABRASIVE WEAR BEHAVIOUR OF FUNCTIONALLY GRADED ALUMINIUM ALLOY REINFORCED WITH ALUMINA

The aim of this research is to fabricate functionally graded aluminium composite reinforced with 15 wt% alumina using centrifugal casting technique with dimensions of Øout160 x Øin145 x 150 mm and to investigate its threebody abrasive wear behavior. Hardness tests and microstructural examinations were performed at distances of 2, 8 and 14 mm from outer diameter. Based on hardness test results, wear tests were carried out at a distance of 2 mm from outer diameter and a total of 16 experiments were conducted as per Taguchi’s Design of Experiments. The parameters varied were load applied on the specimen (29, 34, 41 and 53 N), sliding speed at the surface of the specimen (75, 100, 125 and 150 rpm) and time of operation (3, 5, 7 and 9 mins) and their influence on the wear rate was analyzed using Analysis of Variance and Signal-to-Noise ratio. The most dominating parameter was found out to be the load applied and subsequently a regression equation was generated. Finally, the worn surfaces were analyzed using Scanning Electron Microscope. The images obtained were used to explain the wear mechanisms and it was found out that increased load caused severe ploughing action on the surface. This indicates that the load applied on the component fabricated with this material is the major factor in determining is life

Vayuanukulani: Adaptive memory networks for air pollution forecasting

Air pollution is the leading environmental health hazard globally due to various sources which include factory emissions, car exhaust, and cooking stoves. As a precautionary measure, air pollution forecast serves as the basis for taking effective pollution control measures, and accurate air pollution forecasting has become an important task. In this paper, we forecast fine-grained ambient air quality information for 5 prominent locations in Delhi based on the historical and real-time ambient air quality and meteorological data reported by Central Pollution Control board. We present VayuAnukulani system, a novel end-to-end solution to predict air quality for next 24 hours by estimating the concentration and level of different air pollutants including nitrogen dioxide (NO2), particulate matter (PM2.5 and PM10) for Delhi. Extensive experiments on data sources obtained in Delhi demonstrate that the proposed adaptive attention based Bidirectional LSTM Network outperforms several baselines for classification and regression models. The accuracy of the proposed adaptive system is ~15-20% better than the same offline trained model. We compare the proposed methodology on several competing baselines, and show that the network outperforms conventional methods by ~7-18%.