A Rare Case of Brucellosis with Multivalvular Endocarditis and Complete Heart Block.

BACKGROUND: Brucellosis is a public health concern that affects multiple organs. However, cardiovascular problems arise infrequently, affecting fewer than 2% of cases, typically presenting as endocarditis. CASE PRESENTATION: A 50-year male was admitted with low-grade fever, night sweats, weight loss (13 kg), malaise, and generalized weakness for the past 6 months. On clinical examination, he was febrile with 39.0°C, an average heart rate of 54 bpm, and 100/40 mmHg blood pressure. On cardiovascular examination, S1 and S2 were soft with pan systolic murmur present in the mitral area, and the early diastolic murmur was present in the left third intercostal space. Electrocardiography was suggestive of third-degree heart block with AV dissociation. Transthoracic echocardiography showed mobile vegetations attached to multiple valves- an aortic valve (18.2x11.9mm) and a mitral valve (2.9x7.5mm) with perivalvular abscess. He was given oral doxycycline (100mg B.D.) and rifampicin (600mg/day); the patient responded, but the AV block did not resolve. CONCLUSION: This report has drawn attention to multivalvular involvement and cardiac rhythm abnormalities in Brucellosis (in this case, A.V. dissociation was present) because early diagnosis and treatment can cause a significant decrease in morbidity as well as mortality by appropriate treatment.

Exploring the cytotoxic potential of biflavones of Araucaria cunninghamii: Precise identification combined by LC-HRMS-metabolomics and database mining, targeted isolation, network pharmacology, in vitro cytotoxicity, and docking studies.

The leaves of Araucaria cunninghamii are known to be nonedible and toxic. Previous studies have identified biflavones in various Araucaria species. This study aimed to investigate the in vitro cytotoxicity of the isolated compounds from Araucaria cunninghamii after metabolomics and network pharmacological analysis. Methanol extract of Araucaria cunninghamii leaves was subjected to bioassay-guided fractionation. The active fraction was analyzed using LC-HRMS, through strategic database mining, by comparing the data to the Dictionary of Natural Products to identify 12 biflavones, along with abietic acid, beta-sitosterol, and phthalate. Eight compounds were screened for network pharmacology study, where in silico ADME analysis, prediction of gene targets, compound-gene-pathway network and hierarchical network analysis, protein-protein interaction, KEGG pathway, and Gene Ontology analyses were done, that showed PI3KR1, EGFR, GSK3B, and ABCB1 as the common targets for all the compounds that may act in the gastric cancer pathway. Simultaneously, four biflavones were isolated via chromatography and identified through NMR as dimeric apigenin with varying methoxy substitutions. Cytotoxicity study against the AGS cell line for gastric cancer showed that AC1 biflavone (IC50 90.58 µM) exhibits the highest cytotoxicity and monomeric apigenin (IC50 174.5 µM) the lowest. Besides, the biflavones were docked to the previously identified targets to analyze their binding affinities, and all the ligands were found to bind with energy ≤-7 Kcal/mol.

LCMS-DNP based dereplication of Araucaria cunninghamii Mudie gum-resin: identification of new cytotoxic labdane diterpene.

As a part of natural defense, plants initiate the secretion of gum containing numerous pharmacologically active essential metabolites. A fraction of such gum-resin from Araucaria cunninghamii Mudie, when screened against human cancer cell lines, was found to be active. Further, it was subjected to an LCMS-DNP (Dictionary of Natural Products) based dereplication study followed by a detailed phytochemical investigation to obtain pure metabolites. Also, the gum resin of A. cunninghamii was found to be a rich source of abietanes and labdanes. The LCMS-DNP-based dereplication study identified many known metabolites, which were isolated for the first time from this plant as well as a new labdane diterpenoid (9). The compounds were characterized via spectroscopic techniques, which were subsequently compared with the already existing literature data. The metabolites were screened against seven human cancer cell lines. The anticancer activity was further supported by molecular docking studies.

Identification of sulfonamide-based butyrylcholinesterase inhibitors using machine learning.

Aim: This study reports the designing of BChE inhibitors through machine learning (ML), followed by in silico and in vitro evaluations. Methodology: ML technique was used to predict the virtual hit, and its derivatives were synthesized and characterized. The compounds were evaluated by using various in vitro tests and in silico methods. Results: The gradient boosting classifier predicted N-phenyl-4-(phenylsulfonamido) benzamide as an active BChE inhibitor. The derivatives of the inhibitor, i.e., compounds 34, 37 and 54 were potent BChE inhibitors and displayed blood-brain barrier permeability with no significant AChE inhibition. Conclusion: The ML prediction was effective, and the synthesized compounds showed the BChE inhibitory activity, which was also supported by the in silico studies.

Virtual screening and molecular simulation study of natural products database for lead identification of novel coronavirus main protease inhibitors.

3CL like protease (3CLpro or Mpro) is one of the main proteases of 2019-nCoV. The 3CLpro is a nonstructural protein of SARS-CoV and has an essential role in viral replication and transcription, thus, could be a potential target for anti-SARS drug development. The present study employed ligand- and structure-based approaches to identify the potent inhibitors of 2019-nCoV protease. The e-pharmacophore developed from 3CLpro-1 yielded virtual hits, that were subjected through drug likeliness and PAINS filters to remove interfering compounds. Further comprehensive docking studies, free energy calculations and ADMET studies resulted in two virtual leads- MolPort-000-410-348 and MolPort-002-530-156. The compounds MolPort-000-410-348 and MolPort-002-530-156 displayed good docking score of -12.09 and -13.38 Kcal/mol and free binding energy of -63.34 ± 2.03 and -61.52 ± 2.24 Kcal/mol, respectively. The compounds also exhibited satisfactory predicted ADMET profile and were subjected to molecular dynamic (MD) studies. The MD simulation produced stable complexes of these ligands with 3CLpro protein and ligand RMSD in acceptable limits. Communicated by Ramaswamy H. Sarma.

Therapeutic Potential of Genus Pongamia and Derris: Phytochemical and Bioactivity.

Genus Pongamia and Derris belong to the Leguminosae family and are reported synonymously in literature. Although many compounds have been isolated from different plant parts but seed oil is known to produce non-edible medicinally important furanoflavonoids. The seed oil, commonly known as Karanj oil in Ayurvedic and Siddha traditional systems of medicine, is reported for the treatment of various skin infections and psoriasis. Several phytopharmacological investigations have proved the medicinal potential of furanoflavonoids in the skin and other disorders. Not only furanoflavonoids but several other important phenolic constituents such as chalcones, dibenzoylmethanes, aurones, isoflavones, flavanone dihydroflavonol, flavans, pterocarpans, rotenoids, coumarins, coumestans, stilbenoids and peltygynoids and their glycosides have been reported for different biological activities including antihyperglycemic, anti-inflammatory, anticancer, insecticidal, anti-alzheimer's, gastro protective, antifungal, antibacterial, etc. In the present review, the phytochemistry and pharmacological activities of the genera Pongamia and Derris have been summarized.

In-vitro antitumor activity of compounds from Glycyrrhiza glabra against C6 glioma cancer cells: identification of natural lead for further evaluation.

A HP20 resin-based unique method was adopted to get an active fraction of the hydroalcoholic extract of G. glabra roots. The fraction showed potent cytotoxicity against cancer cell line and was further subjected to detailed phytochemical investigation to obtain ten biomarkers. The isolated compounds were also tested for the cytotoxicity against the C6 glioma cell line in vitro using MTT assay. Among the isolated compounds, glycyrrhetic acid (1), glabrol (6), and glabridin (9) exhibited significant cytotoxicity. The compounds showed a dose-dependent decrease in cell viability. The active compounds were subjected to molecular docking study against topoisomerase I and topoisomerase II to support the mechanism of antitumor activity.

Novel coronavirus disease 2019 (COVID-19) pandemic: Considerations for the biomedical waste sector in India.

In late December 2019, the world woke to a truth of a pandemic of Coronavirus Disease (COVID-19), inspired by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which has a place with a gathering of beta-coronavirus. As of July 21 India is still fighting to survive against the SARS-CoV-2 as called coronavirus disease. The contaminations, first constrained in the Kerala state, have inevitably spread to every single other area. The possibility to cause dangerous respiratory disappointment and quick transmission puts COVID-19 in the rundown of the Public Health Emergency of International Concern (PHEIC). There is a flow overall break out of the novel coronavirus Covid-19, which started from Wuhan in China and has now spread to more than 212 countries including 14,753,034 cases, as of 12:20 AM on July 21, 2020. Governments are feeling the squeeze to prevent the outbreak from spiralling into a worldwide wellbeing crisis. At this stage, readiness, straightforwardness, and sharing of data are vital to hazard evaluations and starting explosion control exercises. Since the episode of serious intense respiratory disorder (SARS) 18 years back, an enormous number of SARS-related coronaviruses (SARSr-CoVs) have been found in their regular repository have, bats. During this epidemic condition, expulsion of biomedical waste created from crisis facilities treating COVID-19 patients in like manner demands unprecedented thought as they can be potential bearers of the disease SARS-CoV-2. This article discusses the potential consequences of the COVID-19 pandemic on biomedical waste administrations, concentrating on basic focuses where option working methodology or extra moderation measures might be fitting.

Nutrient budgets and effluent characteristics in giant freshwater prawn (Macrobrachium rosenbergii) culture ponds.

It is important to understand nutrient budgets of aquaculture practices for efficiency of input resources and to utilize all output nutrient sources. The aim of the present study was to develop a nutrient budget for giant freshwater prawn (Macrobrachium rosenbergii) culture ponds. The study was conducted in farmer's ponds (0.25-0.5 ha) of Odisha, India, and the results showed that feed accounted 97% total nitrogen (N), 98.7% total phosphorus (P) and 90% total organic carbon (OC), respectively. The harvested prawn accounted for recovery of 37% N, 10% P and 15% OC, respectively. The N, P and OC accumulated in sediment were 52%, 76%, and 65%, respectively. Nutrient loads in the effluents were 2.22 ± 0.66 kg inorganic N, 0.40 ± 0.15 kg P, and 21.01 ± 6.4 kg OC per ton of prawn production. The present study implicated that high nutrient values observed in both water and sediment provide important opportunities for nutrient reuse through pond sediment applications to croplands as an organic manure, as well as pond water irrigation to crops as a "liquid fertilizer".

Carbon, nitrogen, and phosphorus budget in scampi (Macrobrachium rosenbergii) culture ponds.

Experiments were conducted for the study of nutrient budget in ten farmer's ponds (0.2-0.5 ha) in Orissa, India with a mean water depth of 1.0-1.2 m. Scampi (Macrobrachium rosenbergii) were stocked in these ponds at stocking density of 3.75-5.0/m(2). The average initial body weight of scampi was 0.02 mg. The culture period was for 4 months. Feed was the main input. Total feed applied to these ponds ranged from 945 to 2261 kg pond/cycle (crop). The feed conversion ratio varied 1.65 to 1.78. In addition to feed, rice straw, urea, and single super phosphate were applied to these ponds in small amounts for plankton production. At harvest time, the average weight of scampi varied from 60-90 g. The budget showed that feed was the major input of nitrogen (N), phosphorus (P), and carbon in these ponds. The inorganic fertilizer (urea and single super phosphate), organic fertilizer (rice straw and yeast extract), and inlet water, either from the initial fills or from rainwater, were the source of all other N, P, and organic carbon (OC) to these ponds. Total N applied to these ponds through all these inputs ranged from 44.45 to 103.98 kg N per crop, 12.23 to 28.79 kg P per crop, and from 381.54 to 905.22 kg OC per crop, respectively. Among all the inputs, feed alone accounted for 95.34 % N, 97.98 % P, and 94.27 % OC, respectively. Recovery of 16.34 to 38.66 kg N (average 29.27 kg), 1.28 to 3.02 kg P (average 2.29 kg), and 63.21 to 149.51 kg OC (average 113.20 kg), respectively, by the scampi harvest were observed in these ponds. Thus, harvest of scampi accounted for recovery of 35.18 to 39.01 (average 36.85%) of added N, 10.09 to 10.97 (average 10.44%) of added P, and 7.57 to 17.12 (average 16.34%) of added OC, respectively.

Conceptual influence of the Baylis-Hillman reaction on recent trends in organic synthesis.

This mini review describes our endeavors for the last 28 years in understanding and developing the Baylis-Hillman reaction as an useful and powerful tool in synthetic chemistry. We have also mentioned briefly how we initiated the research program in this area.

Nutrients budget and effluents characteristics in polyculture of scampi (Macrobrachium rosenbergii) and Indian major carps ponds using organic inputs.

Experiments were conducted for the study of nutrient budget in farmers' ponds (0.4-0.6 ha) in Orissa, India, at stocking densities of 0.30-0.38/m(2) for scampi (Macrobrachium rosenbergii) and 0.60-0.70/m(2) for Indian major carps (Catla catla, Labeo rohita and Cirrhinus mrigala). The average initial body weights of scampi and the major carps were 0.02 and 8-10 g, respectively. The culture period was 272-292 days. Feed was the main input. The FCR (feed conversion ratio) varied from 1.78 to 1.83. Feed and cow dung were applied to these ponds as organic inputs. At harvest time, the average weight of scampi and carps varied from 73 to 92 g and from 718 to 820 g, respectively. Among all the inputs, feed alone accounted for 97.60% total nitrogen (N), 97.90% total phosphorus (P) and 94.72% total organic carbon (OC), respectively. The harvest of scampi and carps accounted for recovery of 52.45% N, 19.43% P and 18.12% OC, respectively. N, P and OC accumulated in sediment were 38.31, 71.40 and 69.50%, respectively. The median nutrient loads in the fish pond effluents were equivalent to 0.58 kg of inorganic N, 0.135 kg of P and 8.83 kg of total OC per ton of Indian major carps and scampi production.

Intramolecular cycloaddition in 6,6-spiroepoxycyclohexa-2,4-dienone: simple aromatics to (+/-)-platencin.

A formal total synthesis of platencin from a simple aromatic precursor is described. Transformation of the aromatic compound into reactive spiroepoxycyclohexa-2,4-dienone and intramolecular cycloaddition are the key features of our methodology. 2-Hydroxymethyl-6-(3-hydroxy-hex-5-enyl)-phenol was oxidized with NaIO(4) to give a dimer that, upon a retro-Diels-Alder reaction, generated the spiroepoxycyclohexa-2,4-dienone that underwent intramolecular Diels-Alder reaction to give a tricyclic adduct having a core structure of platencin and appropriately disposed functional groups in a single step. Reduction of the double bond present in the ethano-bridge, manipulation of the oxirane ring and introduction of a double bond in the six-membered ring furnished a tricyclic intermediate which has already been converted into platencin.

Diels-Alder cycloaddition and ring-closing metathesis: a versatile, stereoselective, and general route to embellished bridged bicyclic systems, carbocyclic framework of secoatisanes, and homologues.

A general and stereoselective methodology for the synthesis of bridged bicyclic octenones having various types of alkenyl chains and a tricyclic framework of secoatisanes and higher analogues is reported. In situ generation and cycloaddition of 2-allyl-6,6-spiroepoxycyclohexadienones with ethyl acrylate gave bicyclo[2.2.2]octanes having an allyl group at the bridgehead and other chemically distinguishable functionality in a regio- and stereoselective fashion. Selective manipulation of adducts led to the introduction of other olefinic chain of variable lengths at the carbon adjacent to the bridge head. Ring-closing metathesis in bicyclooctanes having olefin tethers provided an efficient route to tricyclic systems having bicyclo[2.2.2]octane framework having spiro-fused six-, seven-, and eight-membered rings.