Differential Gene Expression Profiles Involved in the Inflammations Due to COVID-19 and Inflammatory Bowel Diseases and the Investigation of Predictive Biomarkers.

Gastrointestinal manifestations in COVID-19 were attributed to 74-86% of the hospitalised patients due to severe or prolonged pathogenesis. Though it is a respiratory disease, the impact it elicits on the gastrointestinal tract and brain are intense. Inflammatory bowel disease including Crohn's disease and ulcerative colitis are idiopathic inflammatory disorders of the gastrointestinal tract. The intrinsic mechanisms involved in gut inflammations due to a respiratory viral disease can be deciphered when the gene expression profiles of COVID-19 and IBD are compared. The current study utilises an integrated bioinformatics approach to unravel them. The publicly available gene expression profiles of colon transcriptomes infected with COVID-19, Crohn's disease and Ulcerative colitis were retrieved, integrated and analysed for the identification of differentially expressed genes. The inter-relational analysis along with gene annotation and pathway enrichment detailed the functional and metabolic pathways of the genes during normal and diseased conditions. The protein-protein interactions deduced from the STRING database and the identified hub genes predicted potential biomarker candidates for COVID-19, Crohn's disease and ulcerative colitis. The inflammatory response pathways were upregulated and enrichment of chemokine signalling, altered lipid metabolism, coagulation and complement cascades were seen in all three conditions along with impaired transport mechanisms. CXCL11, MMP10, and CFB are predicted to be overexpressed biomarkers, whilst GUCA2A, SLC13A2, CEACAM, and IGSF9 as downregulated novel biomarker candidates for colon inflammations. The three miRNAs hsa-miR-16-5p, hsa-miR-21-5p, and hsa-miR-27b-5p exhibited significant interactions with the upregulated hub genes and four long non-coding RNAs NEAT1, KCNQ1OT1, and LINC00852 capable of regulating miRNA were also predicted. This study offers significant information on the underlying molecular mechanisms of inflammatory bowel disease with identification of potential biomarkers.

Response to insecticides and underlying mechanisms of resistance in the field populations of Aedes aegypti Linnaeus (Diptera: Culicidae) in Puducherry, India.

Background & objectives: Mosquito-borne diseases are major threats to human health worldwide. Successful control of vector mosquitoes requires periodic updates on their response to the insecticides that are in use. Different classes of neurotoxic insecticides have been used in vector control programs. Ae. aegypti and Ae. albopictus are the primary vectors of dengue and have developed resistance to organophosphates and synthetic pyrethroids that are used in vector control programs. Monitoring insecticide pressure and studying the underlying mechanisms of resistance in the field populations of Aedes aegypti are important to formulate resistant management strategies for their control programs. Methods: Aedes aegypti were collected from study sites Lawspet and Abishegapakkam and F1 progeny was subject to biochemical assays to determine the enzyme activity. Insecticide susceptibility tests were conducted to determine vector susceptibility/resistance to malathion and deltamethrin. Adult dried mosquitoes were subjected to multiplex PCR to detect point mutation in the VGSC gene. Results: Insecticide susceptibility test results revealed that Aedes aegypti is resistant to malathion and incipient resistance to deltamethrin has emerged. It was observed that ß-esterase and monoxygense activity were significantly higher in Lawspet sample than the laboratory strain, whereas it was comparatively lower in Abishegapakkam sample than laboratory strain. Multiplex PCR assays showed no kdr mutation in all Ae. aegypti strains. Interpretation & conclusion: Monitoring insecticide resistance in Ae. aegypti would help the local health authorities to implement a rationalized approach for insecticide use in vector control.

Meta-analysis of the microbial biomarkers in the gut-lung crosstalk in COVID-19, community-acquired pneumonia and Clostridium difficile infections.

Respiratory infections are the leading causes of mortality and the current pandemic COVID-19 is one such trauma that imposed catastrophic devastation to the health and economy of the world. Unravelling the correlations and interplay of the human microbiota in the gut-lung axis would offer incredible solutions to the underlying mystery of the disease progression. The study compared the microbiota profiles of six samples namely healthy gut, healthy lung, COVID-19 infected gut, COVID-19 infected lungs, Clostridium difficile infected gut and community-acquired pneumonia infected lungs. The metagenome data sets were processed, normalized, classified and the rarefaction curves were plotted. The microbial biomarkers for COVID-19 infections were identified as the abundance of Candida and Escherichia in lungs with Ruminococcus in the gut. Candida and Staphylococcus could play a vital role as putative prognostic biomarkers of community-acquired pneumonia whereas abundance of Faecalibacterium and Clostridium is associated with the C. difficile infections in gut. A machine learning random forest classifier applied to the data sets efficiently classified the biomarkers. The study offers an extensive and incredible understanding of the existence of gut-lung axis during dysbiosis of two anatomically different organs.

Metabolic and molecular modelling of zebrafish gut biome to unravel antimicrobial peptides through metagenomics.

Recently efforts have been taken for unravelling mysteries between host-microbe interactions in gut microbiome studies of model organisms through metagenomics. Co-existence and the co-evolution of the microorganisms is the significant cause of the growing antimicrobial menace. There needs a novel approach to develop potential antimicrobials with capabilities to act directly on the resistant microbes with reduced side effects. One such is to tap them from the natural resources, preferably the gut of the most closely related animal model. In this study, we employed metagenomics approaches to identify the large taxonomic genomes of the zebra fish gut. About 256 antimicrobial peptides were identified using gene ontology predictions from Macrel and Pubseed servers. Upon the property predictions, the top 10 antimicrobial peptides were screened based on their action against many resistant bacterial species, including Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, E. coli, and Bacillus cereus. Metabolic modelling and flux balance analysis (FBA) were computed to conclude the antibiotic such as tetracycline, cephalosporins, puromycin, neomycin biosynthesis pathways were adopted by the microbiome as protection strategies. Molecular modelling strategies, including molecular docking and dynamics, were performed to estimate the antimicrobial peptides' binding against the target-putative nucleic acid binding lipoprotein and confirm stable binding. One specific antimicrobial peptide with the sequence "MPPYLHEIQPHTASNCQTELVIKL" showed promising results with 53% hydrophobic residues and a net charge +2.5, significant for the development of antimicrobial peptides. The said peptide also showed promising interactions with the target protein and expressed stable binding with docking energy of -429.34 kcal/mol and the average root mean square deviation of 1 A0. The study is a novel approach focusing on tapping out potential antimicrobial peptides to be developed against most resistant bacterial species.

Structural, functional, resistome and pathogenicity profiling of the Cooum river.

The microbial community's structure and functions determine the health, quality, and anthropogenic conditions of the river ecosystems. The presence of Bacteria such as Arcobacter spp, Escherichia spp, and Campylobacters spp, have been shown to reflect the poor water quality of rivers. Apprehension of the microbial community in polluted water bodies is significant because it affects human health and the environment. Culture-independent metagenomic and metatranscriptomic approaches employed in the current study of the Cooum river unraveled the taxonomic classification of diverse microbes, including archaea, bacteria, viruses, and phages. The presence of abundant Macellibacteroides fermentans, Arcobacter bivolvorium, Arcobacter butzleri, Methanothrix soenhngeii, and Bacteroides graminisolvens were noted. Viruses and phages like Caudovirales, Human mastadenovirus C, Siphoviridae, Escherichia phage, Erwinia phage, Synechoccus phage, and Vibrio phage were relatively predominant. Various metabolic pathways like methane, sulfur, and nitrogen metabolism adopted by the microbiome confer dangerous gases. Mechanisms such as secretory systems, signal transduction, Chemotaxis, quorum sensing, transportation of chemicals and ions were significantly enriched. The microbes expressed antimicrobial resistance mechanisms as identified from the genes encoding beta-lactamase enzymes and aminoglycoside phosphotransferase enzymes. Metal resistance mechanisms against copper, tellurium, chromium, and cadmium were plentiful. Presence of human pathogens interactions with Yersinia pestis, Campylobacter jejuni, Escherichia coli, Helicobacter pylori, and Francisella tularensis subsp. tularensis suggested the possibilities of transmission of pathogenesis to humans. The current study is the first to apprehend the detailed microbiome composition of one of the highly polluted rivers in South India. The study elaborated the microbiome's structure, functions, and metabolic potential at a specific site of the polluted river.

Insecticide resistance status of three vectors of Japanese encephalitis in east central India.

Japanese encephalitis (JE) has been reported in different districts of Odisha state (east central India) since 1992. During 2016, a major outbreak of JE and acute encephalitis syndrome (AES) occurred in the Malkangiri district of Odisha, causing 103 deaths in children, of which 37 were caused by JE and 66 by AES. Information on insecticide resistance in JE vectors is important for the selection of appropriate insecticides for use in vector control. The present study was designed to determine the resistance status of three important vectors of JE, Culex vishnui, Culex tritaeniorhynchus and Culex bitaeniorhynchus (Diptera: Culicidae), against dichlorodiphenyltrichloroethane (DDT), malathion and deltamethrin in three districts of Odisha state affected by JE. Female adult mosquitoes were collected using mouth aspirators both indoors and outdoors in JE-affected villages and used in susceptibility bioassays following World Health Organization guidelines. Knock-downs were recorded every 10 min up to 1 h and mortality rates were recorded at 24 h post-exposure. Culex vishnui and Cx. tritaeniorhynchus showed resistance to DDT, malathion and deltamethrin, whereas Cx. bitaeniorhynchus was susceptible in all study districts. The information generated by this study will be highly useful in the planning and implementing of appropriate vector control operations for the prevention and control of JE in east central India.

Structural insights and binding of a natural ligand, succinic acid with serine and cysteine proteases.

In the age of growing infectious diseases, there is a great demand for new inhibitors which can exhibit minimum side effects. Owing to the importance of proteases in life cycle and invasion, they have been projected as attractive targets for structure based drug designing against microbes including viruses. Here we report the inhibitory activity of a well known natural compound succinic acid against both serine and cysteine proteases. The ligand is found co-crystallized with Bovine pancreatic trypsin in one of our crystallization trials and the diffraction data up to1.9 Å reveal its interactions with the catalytic triad residues Histidine 57 and Serine 195. Binding of the ligand with these proteases have been validated using caseinolysis inhibition. With trypsin, ITC analysis showed tight binding of the ligand, resulting in change in Gibb's free energy (ΔG) by -20.31 kJ/mol. To understand the existence of succinic acid at the active site, molecular docking was performed and it revealed binding of it with trypsin and papain at corresponding active sites. This dual inhibitory activity of natural ligand, succinic acid can be accounted for the recent reports on anti-viral property of plant extracts where dicarboxilic fatty acids are normally abundant.

A novel guaiane sesquiterpene derivative, guai-2-en-10α-ol, from Ulva fasciata Delile inhibits EGFR/PI3K/Akt signaling and induces cytotoxicity in triple-negative breast cancer cells.

A novel guaiane sesquiterpene derivative, guai-2-en-10α-ol, from Ulva fasciata Delile exhibits antimicrobial property. U. fasciata extract was reported to exhibit cytotoxicity against cancer. In the present study, we have studied the anticancer potential of the compound, guai-2-en-10α-ol, from U. fasciata. The compound showed selective cytotoxicity toward triple-negative breast cancer (TNBC) cell line (MDA MB-231) in a dose-dependent manner. In treated cells, the apoptotic hallmarks such as formation of apoptotic bodies, cell shrinkage, and nuclear condensation were observed. Many small molecules affect the function of cellular signaling pathways. As EGFR/PI3K/Akt pathway proteins are frequently altered in TNBC, we have studied the gene expression of key proteins of this pathway. The semiquantitative PCR results demonstrated the down-regulated expression of PDPK1 (positive regulator) and Akt (key activator) as well as up-regulated expression of PTEN (negative regulator), which suggested the interaction of guai-2-en-10α-ol with upstream protein. Further investigation showed the down-regulation of both PI3K and EGFR. As EGFR is the most upstream protein of the pathway, its protein level expression was investigated. Western blotting analysis confirmed the down-regulation of p-EGFR expression and activation of apoptosis upon compound treatment. Cell cycle analysis also evidenced the G1 phase arrest, which can be due to the inhibition of cell survival pathway. Computational studies showed the interaction of guai-2-en-10α-ol with Asp855 residue of EGFR kinase domain in active conformation. All these results demonstrate the anticancer potential of guai-2-en-10α-ol through EGFR/PI3K/Akt pathway.

Field performance of malaria rapid diagnostic test for the detection of Plasmodium falciparum infection in Odisha State, India.

BACKGROUND & OBJECTIVES: Rapid diagnostic tests (RDTs) have become an essential surveillance tool in the malaria control programme in India. The current study aimed to assess the performance of ParaHIT-f, a rapid test in diagnosis of Plasmodium falciparum infection through detecting its specific antigen, histidine rich protein 2 (PfHRP-2), in Odisha State, India. METHODS: The study was undertaken in eight falciparum malaria endemic southern districts of Odisha State. Febrile patients included through active case detection, were diagnosed by Accredited Social Health Activists (ASHAs) for P. falciparum infection using the RDT, ParaHIT-f. The performance of ParaHIT-f was evaluated using microscopy as the gold standard. RESULTS: A total of 1030 febrile patients were screened by both microscopy and the RDT for P. falciparum infection. The sensitivity of ParaHIT-f was 63.6% (95% CI: 56.0-70.6) and specificity was 98.9% (95% CI: 97.9-99.5), with positive and negative predictive values (PPV and NPV) of 92.6% (95% CI: 86.0-96.3) and 93.0% (95% CI: 91.0-94.5), respectively. When related to parasitaemia, the RDT sensitivity was 47.8% at the low parasitaemia of 4 to 40 parasites/µl of blood. INTERPRETATION & CONCLUSIONS: The results showed that the performance of the RDT, ParaHIT-f, was not as sensitive as microscopy in detecting true falciparum infections; a high specificity presented a low frequency of false-positive RDT results. t0 he sensitivity of ParaHIT-f was around 60 per cent. It is, therefore, essential to improve the efficiency (sensitivity) of the kit so that the true falciparum infections will not be missed especially in areas where P. falciparum has been the predominant species causing cerebral malaria.

Triple insecticide resistance in Anopheles culicifacies: A practical impediment for malaria control in Odisha State, India.

BACKGROUND & OBJECTIVES: In Odisha State, the control of malaria vectors has become dependent on synthetic pyrethroids, which are used for treatment of all approved long-lasting insecticidal nets (LLINs). The vast use of just one class of insecticide has led to the problem of resistance to insecticides in malaria vectors. One of the major malaria vectors in Odisha State is Anopheles culicifacies Giles. The aim of this study was to determine the resistance status of An. culicifacies to deltamethrin, a synthetic pyrethroid and other common insecticides used by the National Vector Borne Diseases Control Programme (NVBDCP) for indoor residual spraying in Odisha State. METHODS: Mosquitoes were collected during April 2014 - June 2014 from 15 randomly selected villages in five p0 lasmodium falciparum endemic southern districts of Odisha State. The blood-fed wild caught females were exposed to the diagnostic dosage of DDT (4.0%), malathion (5.0%) and deltamethrin (0.05%) for one hour. Mortality was recorded at 24 h after the exposure. RESULTS: Results indicated that An. culicifacies was resistant to all the three insecticides used in the malaria control programme in the five districts of Odisha State. INTERPRETATION & CONCLUSIONS: Resistance management strategy by appropriate rotation of different groups of insecticides including carbamates and incorporating a synergist with synthetic pyrethroids for treating mosquito nets should be considered for the control of malaria vectors in the area, especially where An. culicifacies is predominant. Periodical monitoring of susceptibility/resistance status of An. culicifacies to different insecticides is warranted.

Usage pattern, physical integrity & insecticidal efficacy of long-lasting insecticidal nets in Odisha State, India.

BACKGROUND & OBJECTIVES: One of the major strategies being pursued for malaria control by the National Vector Borne Disease Control Programme is the distribution of long lasting insecticidal nets (LLINs) in endemic areas since 2009. Information on durability of insecticidal efficacy and physical integrity of LLINs and community usage at different time intervals of their use is essential to plan net replacements to maintain universal coverage for an effective and sustainable malaria control strategy. Therefore, a study was undertaken to assess these parameters in two malaria endemic districts of the Odisha State. METHODS: A total of 309 households were selected in 15 villages of two community health centres (CHCs) (Borigumma and Laxmipur) from Koraput district and one (Khairput) from Malkangiri district. Data on net usage were collected during March to July 2014 using semi-structured questionnaires. PermaNet 2.0 were sampled from all households, replaced with new ones, and bioassays were carried out to determine the insecticidal efficacy of LLINs after four and half, four and two years of field use following the standard procedure of World Health Organization. RESULTS: LLIN use rate varied from 57.9 to 90.2 per cent in the study CHCs. The annual washing rate per net in Borigumma, Khairput and Laxmipur was 6.6, 3.2 and 4.8, respectively. The LLINs used two years in the field caused 100 per cent mortality and four to four and half years caused below 80 per cent mortality, except one net. INTERPRETATION & CONCLUSIONS: Nearly 20 per cent of the people were out of net coverage and hence the Programme to ensure 100 per cent coverage. The community should adequately be educated so as to increase the net use rate and avoid incorrect washing practices.

Comparison of efficacy of five types of long-lasting insecticidal nets against Anopheles fluviatilis, the primary malaria vector in east-central India.

Five types of long-lasting insecticidal nets (LNs), namely, Olyset, Netprotect, PermaNet, DuraNet, and Interceptor, were tested after 20 washes for efficacy in terms of mortality, deterrence effect, blood-feeding inhibition, and induced exophily of the malaria vector Anopheles fluviatilis in experimental huts in Malkangiri district of Odisha State, India. Efficacy of the three synthetic pyrethroids (SPs) used in the LNs was also analyzed. Use of LNs reduced the entry of An. fluviatilis into the huts by 73.3-83.2%, and the five LNs were comparable in terms of deterrence. The exit rate of An. fluviatilis from the huts with untreated net was 56.3%, and relative to this, Olyset followed by DuraNet induced significantly a higher exophily. In contrast, the exit rate was significantly lower with Interceptor. Among the three SPs, permethrin induced significantly greater exophily relative to the untreated control, and as a result of this, permethrin-treated Olyset produced a lower mortality. Blood-feeding rate of An. fluviatilis was significantly lower with all the five LNs than the control. Similarly, all the three SPs significantly inhibited blood feeding compared with the control. Interceptor and DuraNet, both alphacypermethrin-treated LNs, caused relatively a higher mortality of An. fluviatilis than the other LNs. The five brands of LNs and three SPs tested in the current study were equally effective in terms of deterrence and blood-feeding inhibition; only exiting and killing effect differed among them. Permethrin-treated LNs induced greater exophily, while, overall, alphacypermethrin-treated LNs killed more An. fluviatilis that entered the huts. Advantage of deterrence, excito-repellent, and killing effects of LNs and appropriate selection of SP for net treatment are discussed in this paper.

Environmental management through sluice gated bed-dam: a revived strategy for the control of Anopheles fluviatilis breeding in streams.

BACKGROUND & OBJECTIVES: Integrated vector management (IVM) emphasizes sustainable eco-friendly methods and minimal use of chemicals. In this context, the present study highlights the environmental control of breeding of Anopheles fluviatilis, the primary malaria vector, through water management in a natural stream in Koraput district, Odisha, India. METHODS: The District Rural Development Agency (DRDA), Koraput, constructed two bed-dams across streams, one in Barigaon and the other in Pipalapodar village. The bed-dam in the former village was fitted with two sluice gates whereas the bed dam constructed in the latter village was without the sluice gate. the sluice gates were opened once in a week on a fixed day to flush out the water from the dam. Anopheles immatures were sampled systematically in the streams using a dipper for density measurement and species composition. RESULTS: There was a reduction of 84.9 per cent in the proportion of positive dips for anopheles larvae/pupae and a reduction of 98.4 per cent in immature density (number/dip) of An. fluviatilis in the experimental downstream compared to the control following opening of the sluice gates. INTERPRETATION & CONCLUSIONS: Our findins showed that opening of sluice gates of the bed-dam regularly once in a week resulted in the control of vector breeding in the downstream due to the flushing effect of the water released with a high flow from the bed-dam that stagnated water in the upstream. The outcome of the study encourages upscaling this measure to other areas, wherever feasible.

Estimation of vectorial capacity of Anopheles minimus Theobald & An. fluviatilis James (Diptera: Culicidae) in a malaria endemic area of Odisha State, India.

BACKGROUND & OBJECTIVES: Anopheles minimus and An. fluviatilis were incriminated as the major malaria vectors in Keonjhar district of Odisha State recently. This study was carried out to elucidate the potential role of these two vector species in transmission of malaria during different seasons, and vectorial capacity of these species was also estimated. METHODS: Three hilly and forested villages of Keonjhar district were randomly selected. Vectorial capacity (C) was calculated using the Macdonald's formula as modified by Garret-Jones. The human landing density of the vector species was obtained from all night human landing collections (bait protected by bed-net). Man feeding habit was estimated by multiplying the human blood index with feeding frequency, which was obtained on daily basis from the duration of gonotrophic cycle. The probability of survival through the extrinsic incubation cycle was calculated from the probability of survival through one day and duration of sporogonic cycle. RESULTS: The estimated vectorial capacity of An. minimus varied between 0.014 and 1.09 for Plasmodium falciparum (Pf) and between 0.1 and 1.46 for P. vivax (Pv). The C of An. minimus for both Pf and Pv was higher during rainy season than the other two seasons. The estimated C of An. fluviatilis varied between 0.04 and 1.28 for Pf and between 0.20 and 1.54 for Pv. INTERPRETATION & CONCLUSIONS: Based on the estimated values of vectorial capacity of the two vector species, the area could be stratified and such stratification would reflect the difference in the intensity of transmission between different strata and accordingly the appropriate control strategy could be adopted for each stratum.

Effect of house spraying with lambdacyhalothrin 10 per cent capsule suspension (CS) formulation in comparison with 10 per cent wettable powder (WP) against malaria vector in Malkangiri district, Odisha, India.

BACKGROUND & OBJECTIVES: Selection of an insecticide and its appropriate formulation is a prerequisite of formulating any chemical control strategy against vectors. A hut scale field trial was carried out to study the effectiveness of house spraying with capsule suspension (CS) formulation of lambdacyhalothrin in comparison with its wettable powder (WP) formulation on mortality, density and behaviour of malaria vector in Malkangiri district, Odisha, India. METHODS: The two formulations were tested at 20 and 30 mg (a.i.)/m 2 for their effectiveness in terms of deterrence, excito-repellency, blood-feeding success, mortality and residual activity against Anopheles fluviatilis, the major malaria vector, in experimental huts in Malkangiri district, Odisha State, India. RESULTS: Both CS and WP formulations prevented the entry of An. fluviatilis in to the sprayed huts by >90 per cent for >6 months, the entire peak malaria transmission season in the area. The exit rate increased (90-99%) with different treatments and the feeding rate was reduced (91-97%). There was no significant difference between WP 30, CS 20 and CS 30 mg/m 2 in these respects. However, WP 20 mg/m 2 caused a lesser effect than the other three groups. The formulations or the dosages differed only in causing vector mortalities. Overall, the total mortality rate of An. fluviatilis was higher in the huts sprayed with CS 30 (58%) than the huts sprayed with CS 20 (48%), WP 20 (37%) and WP 30 mg/m 2 (47%). INTERPRETATION & CONCLUSIONS: Considering the duration of residual action and the effect on entry, exit, feeding and mortality of An. fluviatilis, the dosage 20 mg/m 2 of CS formulation of lambdacyhalothrin could be considered for further use.

Response of malaria vectors to conventional insecticides in the southern districts of Odisha State, India.

BACKGROUND & OBJECTIVES: Updating information on response (susceptible / resistant status) of vectors to the insecticides in use is essential to formulate and introduce appropriate resistance management strategy. Therefore, a study was undertaken in the 10 southern districts of Odisha State, which are endemic for Plasmodium falciparum malaria, to determine the insecticide susceptibility/ resistance status of Anopheles fluviatilis and An. culicifacies, the vectors of malaria. METHODS: Mosquitoes were collected during September 2010 - February 2012 from 60 randomly selected villages in the 10 districts and blood-fed females were exposed to the diagnostic dosage of DDT (4.0%), malathion (5.0%) and deltamethrin (0.05%) for one hour. Mortality was recorded at 24 h after the exposure. The test mortality was corrected to the control mortality. RESULTS: An. fluviatilis was susceptible to the three insecticides tested while, An. culicifacies was resistant to DDT and malathion in all the 10 districts except in two, where its response against malathion was under 'verification required' category. Against deltamethrin, An. culicifacies was susceptible in two districts; while in the other eight districts its response was under 'verification required' category. INTERPRETATION & CONCLUSIONS: Since An. fluviatilis the vector species primarily associated with transmission of malaria, was still susceptible to DDT, indoor residual spraying with DDT could be continued in the 10 districts. Also, in view of the large scale implementation of long lasting insecticidal nets and the signs of development of resistance in An. culicifacies to deltamethrin, response of the vectors to synthetic pyrethroids needs to be periodically monitored.

Interaction affinity of Delta and Epsilon class glutathione-s-transferases (GSTs) to bind with DDT for detoxification and conferring resistance in Anopheles gambiae, a malaria vector.

BACKGROUND & OBJECTIVES: The enzyme glutathione-s-transferases (GSTs) are associated with detoxification of DDT, as experimentally proved in Anopheles gambiae. Insect GSTs are classified into six classes and among them Delta and Epsilon class GSTs have been implicated in detoxification of organochlorine insecticides. Both Delta and Epsilon GSTs produce, in total, 24 transcripts that result in the production of corresponding enzyme proteins. However, the conventional assay estimates the level of total GSTs and relates to development of resistance to DDT. Hence, it would be more reliable to estimate the level of the specific class GSTs that shows higher affinity with DDT. This would also lead to design a specific molecular tool for resistance diagnosis. METHODS: Of the 24 GSTs, computational models for 23 GSTs, which are available in Swiss-Prot database, were retrieved and for the remaining one, D7-2, for which no model is available in the data bank, a structural model was developed using the sequence of An. dirus B with a PDB ID of 1R5A as the template. All the models were docked with DDT in the presence of reduced glutathione. RESULTS: The energy output showed that Delta, D6 has the highest interaction affinity with DDT. Hence, this particular GST (D6) is likely to get elevated on exposure of mosquitoes to DDT. INTERPRETATION & CONCLUSION: It would be, therefore, possible to design a specific molecular assay to determine the expression level of such high affinity transcript(s) and to use for resistance diagnosis reliably in the vector surveillance programme.

Parry-Romberg syndrome (progressive hemifacial atrophy) with spasmodic dysphonia--a rare association.

Parry-Romberg syndrome is a rare clinical entity characterised by progressive hemifacial atrophy with appearance of 'saber'. Various neurological and otorhinolaryngological disorders are associated with this syndrome. The association of Parry -Romberg syndrome with Spasmodic dysphonia has rarely been reported. A 37 year old female presented with progressive atrophy of tissues of left side of face for 10 years and change in voice for 1 year. On examination, wasting and atrophy of tissues including tongue was noted on left side of the face. ENT examination revealed adductor spasmodic dysphonia. We report the rare association of Parry -Romberg syndrome with spasmodic dysphonia.

Crystal structure of methyl 1-methyl-3,5-diphenyl-7-tosyl-3,6,7,11b-tetra-hydro-pyrazolo-[4',3':5,6]pyrano[3,4-c]quinoline-5a(5H)-carboxyl-ate.

In the title compound, C35H31N3O5S, the piperidine ring adopts an envelope conformation, with the methine C atom as the flap, and the pyran ring adopts a sofa conformation. The mean planes of these two rings are almost normal to one another, making a dihedral angle of 85.96 (5)°. The two phenyl rings, one attached to the pyrazole ring and the other to the pyran ring, are inclined to one another by 65.41 (11)°. They are inclined to the mean planes of the rings to which they are attached by 12.59 (11) and 70.09 (9)°, respectively. There is an intra-molecular C-H⋯π inter-action involving the tosyl-ate methyl group and the phenyl ring attached to the pyrazole ring. In the crystal, mol-ecules are linked by C-H⋯π inter-actions, forming ribbons parallel to (10-2). The ribbons are linked by slipped parallel π-π inter-actions involving inversion-related pyrazole rings [inter-centroid distance = 3.672 (2) Å], forming slabs parallel to (001). A preliminary report of this structure has been published [Bakthadoss et al. (2014 ▶). Eur. J. Org. Chem. pp. 1505-1513].

An efficient cardio vascular disease prediction using multi-scale weighted feature fusion-based convolutional neural network with residual gated recurrent unit.

The cardiovascular disease (CVD) is the dangerous disease in the world. Most of the people around the world are affected by this dangerous CVD. In under-developed countries, the prediction of CVD remains the toughest job and it takes more time and cost. Diagnosing this illness is an intricate task that has to be performed precisely to save the life span of the human. In this research, an advanced deep model-based CVD prediction and risk analysis framework is proposed to minimize the death rate of humans all around the world. The data required for the prediction of CVD is collected from online data sources. Then, the input data is preprocessed using data cleaning, data scaling, and Nan and null value removal techniques. From the preprocessed data, three sets of features are extracted. The three sets of features include deep features, Principal Component Analysis (PCA), and Support Vector Machine (SVM)-based features. A Multi-scale Weighted Feature Fusion-based Deep Structure Network (MWFF-DSN) is developed to predict CVD. This structure is composed of a Multi-scale weighted Feature fusion-based Convolutional Neural Network (CNN) with a Residual Gated Recurrent Unit (GRU). The retrieved features are given as input to MWFF-DSN, and for optimizing weights, a Modernized Plum Tree Algorithm (MPTA) is developed. From the overall analysis, the developed model has attained an accuracy of 96% and it achieves a specificity of 95.95%. The developed model takes minimum time for the CVD and it gives highly accurate detection results.