The effect of Asthapada Panchaloha Shalaka Agnikarma in the pain management of Gridhrasi w.s.r. to Sciatica

Gridhrasi is a disease explained by Brihatrayees in the context of Vatavyadhi Adhyaya. The earliest reference about the details of Gridhrasi is available from Sushruta Samhita (1500 BC). Gridhrasi is included in Vatajna Natmaja Vyadhi and also considered as Mahagada by Acharya Charaka. In all Ayurvedic literature, there is no direct reference regarding Nidana, but it is included in Vataja Nanatmaja Vyadhi, general Vata Prakopaka Hetus are to be considered. On the basis of symptoms, Gridhrasi can be correlated with the disease Sciatica in the modern parlance, which occurs because of spinal nerve irritation and characterized by its distinct nature of pain in distribution of sciatic nerve and often it is associated with lumbago. The Gridhrasi is commonly seen in society as a major problem which incapacitates patient to perform his daily routine activities because of severe pain from Kati Pradesha to Padanguli. In modern medicine in reference to sciatica treatment, there is no definite curative treatment other than symptomatic management. Objectives of the study was to evaluate the effect of Asthapada Panchaloha Shalaka Agnikarma in the pain management of Gridhrasi w.s.r. to Sciatica and to compare the effect of Bindu Panchaloha Shalaka Agnikarma in the pain management of Gridhrasi. In present study 40 patients with confirmed clinical diagnosis of Gridhrasi/Sciatica were selected randomly and divided into two groups of each 20 patients. Group A patients were treated with Asthapada Panchaloha Shalaka Agnikarma and Group B patients were treated with Bindu Panchaloha Shalaka Agnikarma. After the treatment it was observed that there was statistically significant results in the main signs and symptoms i.e. pain in lumbar region, numbness, SLR test. The study shows that the treatment is statistically significant in Group A when compared to Group B. Group A overall result is 87.29% and Group B overall result is 84.64%

Peri conceptional association of the triad of hyperhomocsteinemia, hypothyroidism and impaired carbohydrate metabolism with recurrent pregnancy loss

Background: Recurrent pregnancy loss is a cause of great concern to the affected couple as well as the treating physician. We evaluated the periconceptional association of the triad of hyperhomocystienemia, hypothyroidism, and impaired carbohydrate metabolism with RPL and to identify the potential risk factors for RPL which are probably nutritional.Methods: Seven hundred ninety-six consecutive pregnancies with two or more abortions referring to our Infertility clinic were selected to be studied in a descriptive, prospective observational study in 2012-2014. All the pregnant women were subjected to routine blood tests/ examination/ imaging as per hospital protocols. All underwent TSH, FT4, GTT 75 gm (fasting and 2 h postprandial) as per routine antenatal workup. Additionally, fasting plasma homocysteine, antinuclear antibody, anti phospholipid antibody, anti- thyroid peroxidase antibody tests were performed for patients with RPL. All the patients were studied for the triad of hypothyroidism, hyperhomocysteinemia and impaired carbohydrate metabolism.Results: The incidence of RPL was found to be 5.65 %. Majority of women (51.1%) were in the age group 30-34 years. Majority of the women (55.6%) had 2 previous abortions. Majority of women (57.7%) had conceived normally. Majority of women (46.7%) had BMI<25. PCOS was reported in 28.9% women. HHcy, hypothyroidism and impaired carbohydrate metabolism was found in 78%, 73% and 73% women, respectively. The presence of two factors was reported in 60 to 65% women. 56% women reported the presence of the triad. About 7% of the patients underwent repeat abortion in second trimester of which 66.6% had the association of triad.Conclusions: Investigating these three factors in patients with RPL would help in early recognition, monitoring, and aggressive surveillance, which will help prevent obstetric complications. Simple nutritional correction may allow for better maternal and fetal programming and appropriate risk modulation

Identification of Co-Existing Mutations and Gene Expression Trends Associated With K13-Mediated Artemisinin Resistance in Plasmodium falciparum

Plasmodium falciparum infects millions and kills thousands of people annually the world over. With the emergence of artemisinin and/or multidrug resistant strains of the pathogen, it has become even more challenging to control and eliminate the disease. Multiomics studies of the parasite have started to provide a glimpse into the confounding genetics and mechanisms of artemisinin resistance and identified mutations in Kelch13 (K13) as a molecular marker of resistance. Over the years, thousands of genomes and transcriptomes of artemisinin-resistant/sensitive isolates have been documented, supplementing the search for new genes/pathways to target artemisinin-resistant isolates. This meta-analysis seeks to recap the genetic landscape and the transcriptional deregulation that demarcate artemisinin resistance in the field. To explore the genetic territory of artemisinin resistance, we use genomic single-nucleotide polymorphism (SNP) datasets from 2,517 isolates from 15 countries from the MalariaGEN Network (The Pf3K project, pilot data release 4, 2015) to dissect the prevalence, geographical distribution, and co-existing patterns of genetic markers associated with/enabling artemisinin resistance. We have identified several mutations which co-exist with the established markers of artemisinin resistance. Interestingly, K13-resistant parasites harbor α-ß hydrolase and putative HECT domain–containing protein genes with the maximum number of SNPs. We have also explored the multiple, publicly available transcriptomic datasets to identify genes from key biological pathways whose consistent deregulation may be contributing to the biology of resistant parasites. Surprisingly, glycolytic and pentose phosphate pathways were consistently downregulated in artemisinin-resistant parasites. Thus, this meta-analysis highlights the genetic and transcriptomic features of resistant parasites to propel further exploratory studies in the community to tackle artemisinin resistance.</p

Delivering climate risk information to farmers at scale: the Intelligent agricultural Systems Advisory Tool (ISAT)

One of the strategies for helping smallholder farmers cope with climate variability and change is the provision of climate services that better decision making around the planning and management of agricultural systems. However, providing such services with location specific timely and actionable information to millions of farmers operating across diverse conditions requires innovative solutions. ICRISAT and its partners have developed and piloted one such system called “Intelligent agricultural Systems Advisory Tool – ISAT” capable of generating and disseminating data driven location specific advisories that assist farmers in anticipating and responding to the emerging conditions through the season. Using a decision tree approach, a structured and systematic approach to decision making was devised that considers the insights obtained from the analysis of historical climatic conditions, climate and weather forecasts and prevailing environmental conditions. Microsoft India developed a platform to access real time data from various ‘public’ sources, perform the data analytics, implement the decision tree and generate and disseminate messages to farmers and associated actors. The ISAT generated advisories are designed to support both pre-season planning and in-season management. During the 2017 monsoon, ISAT was piloted with 417 farmers across four different locations. The messaging system worked extremely well in picking appropriate location specific message from the database and delivering the same to the mobiles of the registered farmers. Mid and end season surveys revealed that more than 80% of the farmers from all villages were satisfied with the frequency, relevance and understandability of the messages delivered. About 58% of the farmers rated the messages are reliable by being correct more than 75% of the times and helped them in managing their farms better by conducting farm operations timely with reduced risk. Compared to farmers in the control villages, groundnut yields of farmers in 5 treatment villages are higher by ~ 16% but this results varied between -7.7 to 56.2%. This study has demonstrated the opportunities available to harness the untapped power of digital technologies to provide actionable advisories timely to smallholder farmers using appropriate data analytics and information dissemination systems

Delivering climate risk information to farmers at scale: the Intelligent agricultural Systems Advisory Tool (ISAT)

One of the strategies for helping smallholder farmers cope with climate variability and change is the provision of climate services that better decision making around the planning and management of agricultural systems. However, providing such services with location specific timely and actionable information to millions of farmers operating across diverse conditions requires innovative solutions. ICRISAT and its partners have developed and piloted one such system called “Intelligent agricultural Systems Advisory Tool – ISAT” capable of generating and disseminating data driven location specific advisories that assist farmers in anticipating and responding to the emerging conditions through the season. Using a decision tree approach, a structured and systematic approach to decision making was devised that considers the insights obtained from the analysis of historical climatic conditions, climate and weather forecasts and prevailing environmental conditions. Microsoft India developed a platform to access real time data from various ‘public’ sources, perform the data analytics, implement the decision tree and generate and disseminate messages to farmers and associated actors. The ISAT generated advisories are designed to support both pre-season planning and in-season management. During the 2017 monsoon, ISAT was piloted with 417 farmers across four different locations. The messaging system worked extremely well in picking appropriate location specific message from the database and delivering the same to the mobiles of the registered farmers. Mid and end season surveys revealed that more than 80% of the farmers from all villages were satisfied with the frequency, relevance and understandability of the messages delivered. About 58% of the farmers rated the messages are reliable by being correct more than 75% of the times and helped them in managing their farms better by conducting farm operations timely with reduced risk. Compared to farmers in the control villages, groundnut yields of farmers in 5 treatment villages are higher by ~ 16% but this results varied between -7.7 to 56.2%. This study has demonstrated the opportunities available to harness the untapped power of digital technologies to provide actionable advisories timely to smallholder farmers using appropriate data analytics and information dissemination systems

Effect of Lowering the pH of Sodium Hypochlorite on Control of Pseudomonas aeruginosa in Maintenance of Pharmaceutical Water System

Drinking water or potable water is a common source for generation of purified water or demineralized water which is used for processing of medicinal products such as tablets, capsules, syrups, and nasal sprays. Before allowing for purification, it is manufacturer’s responsibility to ensure the microbial load control in the source water to get good quality product water and to avoid biofilm formation in waterlines. The current research involves the study of an effectiveness of sodium hypochlorite (NaOCl) at various concentrations of water pH on microbial control by following pour plate technique. The aim of this study was to examine the effect of lowering the pH on the recovery of Pseudomonas aeruginosa. Three groups were tested by challenging known population of P. aeruginosa by varying the pH of 5.0, 7.0 and 9.0. No significant difference was observed at pH 5.0 and 7.0 and the recovery increased when the pH increased at 9.0. Effective microbial control was obtained at neutral pH. The increase of pH resulted decrease of effectiveness of NaOCl

Stereospecific requirement of cholesterol in the function of the serotonin1A receptor

The serotonin1A receptor is an important member of the G protein-coupled receptor (GPCR) family. It is involved in the generation and modulation of a variety of cognitive and behavioral functions and serves as a drug target. Previous work from our laboratory has established the sensitivity of the function of the serotonin1A receptor to membrane cholesterol. Solubilization of the hippocampal serotonin1A receptor utilizing the zwitterionic detergent CHAPS is accompanied by loss of cholesterol and results in reduction in specific ligand binding. Replenishment of cholesterol to solubilized membranes restores specific ligand binding to the receptor. We utilized this strategy of sterol replenishment of solubilized membranes to explore the stereospecific stringency of cholesterol for receptor function. We used two stereoisomers of cholesterol, ent-cholesterol (enantiomer of cholesterol) and epi-cholesterol (a diastereomer of cholesterol), for this purpose. Importantly, we show here that while ent-cholesterol could replace cholesterol in supporting receptor function, epi-cholesterol could not. These results imply that the requirement of membrane cholesterol for the serotonin1A receptor function is diastereospecific, yet not enantiospecific. Our results extend and help define specificity of the interaction of membrane cholesterol with the serotonin1A receptor, and represent the first report utilizing ent-cholesterol to examine stereospecificity of GPCR-cholesterol interaction. © 2013 Elsevier B.V.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

New insights of superoxide dismutase inhibition of pyrogallol autoxidation

Autoxidation of pyrogallol in alkaline medium is characterized by increases in oxygen consumption, absorbance at 440 nm, and absorbance at 600 nm. The primary products are H2O2 by reduction of O-2 and pyrogallol-ortho-quinone by oxidation of pyrogallol. About 20 % of the consumed oxygen was used for ring opening leading to the bicyclic product, purpurogallin-quinone (PPQ). The absorbance peak at 440 nm representing the quinone end-products increased throughout at a constant rate. Prolonged incubation of pyrogallol in alkali yielded a product with ESR signal. In contrast the absorbance peak at 600 nm increased to a maximum and then declined after oxygen consumption ceased. This represents quinhydrone charge-transfer complexes as similar peak instantly appeared on mixing pyrogallol with benzoquinones, and these were ESR-silent. Superoxide dismutase inhibition of pyrogallol autoxidation spared the substrates, pyrogallol, and oxygen, indicating that an early step is the target. The SOD concentration-dependent extent of decrease in the autoxidation rate remained the same regardless of higher control rates at pyrogallol concentrations above 0.2 mM. This gave the clue that SOD is catalyzing a reaction that annuls the forward electron transfer step that produces superoxide and pyrogallol-semiquinone, both oxygen radicals. By dismutating these oxygen radicals, an action it is known for, SOD can reverse autoxidation, echoing the reported proposal of superoxide:semiquinone oxidoreductase activity for SOD. The following insights emerged out of these studies. The end-product of pyrogallol autoxidation is PPQ, and not purpurogallin. The quinone products instantly form quinhydrone complexes. These decompose into undefined humic acid-like complexes as late products after cessation of oxygen consumption. SOD catalyzes reversal of autoxidation manifesting as its inhibition. SOD saves catechols from autoxidation and extends their bioavailability

Genomic analysis of Indian isolates of Plasmodium falciparum: Implications for drug resistance and virulence factors

The emergence of drug resistance to frontline treatments such as Artemisinin-based combination therapy (ACT) is a major obstacle to the control and eradication of malaria. This problem is compounded by the inherent genetic variability of the parasites, as many established markers of resistance do not accurately predict the drug-resistant status. There have been reports of declining effectiveness of ACT in the West Bengal and Northeast regions of India, which have traditionally been areas of drug resistance emergence in the country. Monitoring the genetic makeup of a population can help to identify the potential for drug resistance markers associated with it and evaluate the effectiveness of interventions aimed at reducing the spread of malaria. In this study, we performed whole genome sequencing of 53 isolates of Plasmodium falciparum from West Bengal and compared their genetic makeup to isolates from Southeast Asia (SEA) and Africa. We found that the Indian isolates had a distinct genetic makeup compared to those from SEA and Africa, and were more similar to African isolates, with a high prevalence of mutations associated with antigenic variation genes. The Indian isolates also showed a high prevalence of markers of chloroquine resistance (mutations in Pfcrt) and multidrug resistance (mutations in Pfmdr1), but no known mutations associated with artemisinin resistance in the PfKelch13 gene. Interestingly, we observed a novel L152V mutation in PfKelch13 gene and other novel mutations in genes involved in ubiquitination and vesicular transport that have been reported to support artemisinin resistance in the early stages of ACT resistance in the absence of PfKelch13 polymorphisms. Thus, our study highlights the importance of region-specific genomic surveillance for artemisinin resistance and the need for continued monitoring of resistance to artemisinin and its partner drugs