Identification of potential flavonoid compounds as antibacterial therapeutics against Klebsiella pneumoniae infection using structure-based virtual screening and molecular dynamics simulation.

Klebsiella pneumoniae, which is among the top three pathogens on WHO's priority list, is one of the gram-negative bacteria that doctors and researchers around the world have fought for decades. Capsular polysaccharide (CPS) protein is extensively recognized as an important K. pneumoniae virulence factor. Thus, CPS has become the most characterized target for the discovery of novel drug candidates. The ineffectiveness of currently existing antibiotics urges the search for potent antimicrobial compounds. Flavonoids are a group of plant metabolites that have antibacterial potential and can enhance the present medications to elicit improved results against diverse diseases without adverse reactions. Henceforth, the present study aims to illustrate the inhibitory potential of flavonoids with varying pharmacological properties, targeting the CPS protein of K. pneumoniae by in silico approaches. The flavonoid compounds (n = 169) were retrieved from the PubChem database and screened using the structure-based virtual screening approach. Compounds with the highest binding score were estimated through their pharmacokinetic effects by ADMET descriptors. Finally, four potential inhibitors with PubChem CID: (4301534, 5213, 5481948, and 637080) were selected after molecular docking and drug-likeness analysis. All four lead compounds were employed for the MDS analysis of a 100 ns time period. Various studies were undertaken to assess the stability of the protein-ligand complexes. The binding free energy was computed using MM-PBSA, and the outcomes indicated that the molecules are having stable interactions with the binding site of the target protein. The results revealed that all four compounds can be employed as potential therapeutics against K. pneumoniae.

Planning and financing of RMNCH+A under National Health Mission: A case study of the Gurugram District of Haryana State.

BACKGROUND: The Health Planning Process under National Health Mission (NHM) is participatory in nature and the State Programme Implementation Plan (PIP) is an aggregation of District PIPs which is examined and approved by the National Programme Coordination Committee (NPCC), Ministry of Health and Family Welfare, Government of India. Many times there are delays in releasing of Record of Proceedings (ROPs)/approvals. This affects utilisation of NHM funds at district level and below and desired outcomes are not achieved. The present study aims to analyse the process of fund flow, disbursement and utilisation of funds on various components under Reproductive Maternal New born Child and Adolescent Health (RMNCH+A) in the district Gurugram. METHODOLOGY: The study was conducted in the District Gurugram of Haryana State, India. One Community Health Centres (CHCs), two Primary Health Centres (PHCs) and four Sub Health Centres were randomly selected. Primary and secondary data were collected in the study. Medical Officer (I/C), Accounts Staff and Health Workers were interviewed using separate schedules regarding process of disbursement, delays in release and utilisation of funds. Separate checklists were prepared to collect data on availability and utilisation of funds at District, CHC and PHC levels under different components of programme. FINDINGS: Study found that PIP is prepared with inputs from Block level but community participation at (PHC) and below was not present. There was a delay in reaching funds to district due to delayed release of ROPs. Almost 30%-40% of the budget could not be utilised due to delay in receiving of budget. Utilisation of funds was less in some programme activities due to vacant positions project staff. Only 38% and 31% of the funds were utilised under the child health and family planning budget head for the district of Gurugram in the year 2016-17. Accounts staffs were overburdened which affected monitoring of funds utilisation. Budget release from State to District and below was through e-Banking. Auxiliary Nurse Midwives (ANMs) at Sub centre used to get Untied Funds at the end of third quarter. The Government introduced new 18 broad budget heads in NHM Budget for improving utilisation of budget. CONCLUSION: Delayed release of ROPs and erroneous estimation of budget under the programme, very rigid and large number of budget heads poses challenges of understanding and analysing expenditure and affects utilisation of funds under the NHM. Moreover, vacant positions in the programme, unrealistic planning, weak community participation in planning of expenditure and unexplained budget cut in ROPs were main challenges faced by the District.

Immunologic resilience and COVID-19 survival advantage.

BACKGROUND: The risk of severe coronavirus disease 2019 (COVID-19) varies significantly among persons of similar age and is higher in males. Age-independent, sex-biased differences in susceptibility to severe COVID-19 may be ascribable to deficits in a sexually dimorphic protective attribute that we termed immunologic resilience (IR). OBJECTIVE: We sought to examine whether deficits in IR that antedate or are induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection independently predict COVID-19 mortality. METHODS: IR levels were quantified with 2 novel metrics: immune health grades (IHG-I [best] to IHG-IV) to gauge CD8+ and CD4+ T-cell count equilibrium, and blood gene expression signatures. IR metrics were examined in a prospective COVID-19 cohort (n = 522); primary outcome was 30-day mortality. Associations of IR metrics with outcomes in non-COVID-19 cohorts (n = 13,461) provided the framework for linking pre-COVID-19 IR status to IR during COVID-19, as well as to COVID-19 outcomes. RESULTS: IHG-I, tracking high-grade equilibrium between CD8+ and CD4+ T-cell counts, was the most common grade (73%) among healthy adults, particularly in females. SARS-CoV-2 infection was associated with underrepresentation of IHG-I (21%) versus overrepresentation (77%) of IHG-II or IHG-IV, especially in males versus females (P < .01). Presentation with IHG-I was associated with 88% lower mortality, after controlling for age and sex; reduced risk of hospitalization and respiratory failure; lower plasma IL-6 levels; rapid clearance of nasopharyngeal SARS-CoV-2 burden; and gene expression signatures correlating with survival that signify immunocompetence and controlled inflammation. In non-COVID-19 cohorts, IR-preserving metrics were associated with resistance to progressive influenza or HIV infection, as well as lower 9-year mortality in the Framingham Heart Study, especially in females. CONCLUSIONS: Preservation of immunocompetence with controlled inflammation during antigenic challenges is a hallmark of IR and associates with longevity and AIDS resistance. Independent of age, a male-biased proclivity to degrade IR before and/or during SARS-CoV-2 infection predisposes to severe COVID-19.

A nurse-led paediatric oncology fast-track clinic proves a successful ambulatory intervention for patients.

AIM: To assess the impact of a pilot nurse-led paediatric oncology fast-track clinic (OFTC) for complications and side effects following chemotherapy within a paediatric tertiary hospital. METHODS: Prospective clinical data from the first 100 patients seen in the OFTC were compared with retrospective data of oncology patient presentations to the emergency department (ED) (over a 1-year period, n = 196) who would have been eligible for review in the OFTC. Parent and patient satisfaction of clinical care were also assessed via surveys pre- and post-OFTC implementation. RESULTS: Analysis which achieved statistical difference was a reduction in the number of blood tubes taken in OFTC (average 1.9 for those discharged from clinic, 2.9 for those admitted from clinic) in comparison to those seen in the ED (average 3.2) (p = 0.0027). The average number of interventions per patient seen in the ED were 2.1 (standard deviation 1.64) compared with 1.7 (standard deviation 1.55) interventions per patient seen in the OFTC, and who were not admitted following review. This result approached statistical significance with p = 0.0963. Other results which did not meet statistical significance included a reduction in treatment times, hospital admissions and medical oncology reviews. CONCLUSION: Our pilot study implementing an OFTC for the triage and assessment of chemotherapy-related complications has proven successful from an operational and consumer perspective. The clinic improved care by ensuring expedited review, more streamlined interventions, and less overall hospital admissions. The improvements in efficiency were also mirrored by increased parent and patient satisfaction.

Cost of treatment and consequences for chronic hepatitis B and C virus infection at a tertiary care hospital in Delhi.

Patient living with chronic viral hepatitis in India faces the high cost of treatment and impoverishment. The present study is aimed to assess the cost of treatment and economic consequences among chronically infected viral hepatitis patients at a tertiary care hospital in Delhi. The descriptive cross-sectional study was undertaken during October 2016-January 2017. Three hundred and eighty-nine participants were interviewed through a schedule for variables and assessing both direct and indirect costs. Costs of hospital expenditure were extracted from records available with patients or databases of the hospital. The average outpatient expenditure and the inpatient costs were calculated. Direct nonmedical costs were also included. The analysis revealed the total cost of treatment ranged from Rs. 16,600/-to Rs. 1,709,000/-with a median of Rs. 193,500 per year. The cost of treatment increased with the severity of the disease. The cost of treatment led to impoverishment in 52.8% of families and imposed a substantial economic burden and consequences on the patients.

Susceptibility to neurofibrillary tangles: role of the PTPRD locus and limited pleiotropy with other neuropathologies.

Tauopathies, including Alzheimer's disease (AD) and other neurodegenerative conditions, are defined by a pathological hallmark: neurofibrillary tangles (NFTs). NFT accumulation is thought to be closely linked to cognitive decline in AD. Here, we perform a genome-wide association study for NFT pathologic burden and report the association of the PTPRD locus (rs560380, P=3.8 × 10-8) in 909 prospective autopsies. The association is replicated in an independent data set of 369 autopsies. The association of PTPRD with NFT is not dependent on the accumulation of amyloid pathology. In contrast, we found that the ZCWPW1 AD susceptibility variant influences NFT accumulation and that this effect is mediated by an accumulation of amyloid ß plaques. We also performed complementary analyses to identify common pathways that influence multiple neuropathologies that coexist with NFT and found suggestive evidence that certain loci may influence multiple different neuropathological traits, including tau, amyloid ß plaques, vascular injury and Lewy bodies. Overall, these analyses offer an evaluation of genetic susceptibility to NFT, a common end point for multiple different pathologic processes.

Ang II induce kidney damage by recruiting inflammatory cells and up regulates PPAR gamma and Renin 1 gene: effect of ß carotene on chronic renal damage.

Antioxidants are widely used for prevention of diseases associated with oxidative stress and ischemic disorder. We investigated the hypothesis of antioxidants (α-tocopherol and ß-carotene) can suppress the renal disorder in apo E-/-mice. Renal damage induced by chronic infusion of Angiotensin II (Ang II) into 4 month old male apo E-/-mice. After that the mice were treated with diet enriched α tocopherol and ß carotene (800 mg/kg) for 150 days. Ang II treated kidney showed polycystic appearance with accumulation of clear fluid and constriction of renal artery and renal vein was noticed. Vacuolar/cystic degeneration as well as inflammatory reactions was noticed in the tubules/glomerulus of Ang II treated mice. ß carotene treated mice showed enormous numbers of regenerated tubules in the kidney and over expression of ICAM proteins in the regenerated tubules. CD 45.2, MAC 3 proteins were over expressed in the inflammatory cells infiltrated into the tubular region of Ang II treated kidney. Gene expression studies revealed up regulation of Renin 1 (Ren 1) and PPARγ genes in the kidney of Ang II treated animals, but the ß carotene treatment controlled the expression of these genes in the regenerated kidneys. ß carotene may have protective effective on chronic renal disorder. It may repress the inflammatory genes (Ren 1, PPARγ) to achieve the protective effect on Ang II induced renal damage.

Designing a Next-Generation Multiepitope-Based Vaccine against Staphylococcus aureus Using Reverse Vaccinology Approaches.

Staphylococcus aureus is a human bacterial pathogen that can cause a wide range of symptoms. As virulent and multi-drug-resistant strains of S. aureus have evolved, invasive S. aureus infections in hospitals and the community have become one of the leading causes of mortality and morbidity. The development of novel techniques is therefore necessary to overcome this bacterial infection. Vaccines are an appropriate alternative in this context to control infections. In this study, the collagen-binding protein (CnBP) from S. aureus was chosen as the target antigen, and a series of computational methods were used to find epitopes that may be used in vaccine development in a systematic way. The epitopes were passed through a filtering pipeline that included antigenicity, toxicity, allergenicity, and cytokine inducibility testing, with the objective of identifying epitopes capable of eliciting both T and B cell-mediated immune responses. To improve vaccine immunogenicity, the final epitopes and phenol-soluble modulin α4 adjuvant were fused together using appropriate linkers; as a consequence, a multiepitope vaccine was developed. The chosen T cell epitope ensemble is expected to cover 99.14% of the global human population. Furthermore, docking and dynamics simulations were used to examine the vaccine's interaction with the Toll-like receptor 2 (TLR2), revealing great affinity, consistency, and stability between the two. Overall, the data indicate that the vaccine candidate may be extremely successful, and it will need to be evaluated in experimental systems to confirm its efficiency.

In silico screening of phytochemical compounds and FDA drugs as potential inhibitors for NSP16/10 5' methyl transferase activity.

The recent global pandemic associated with the highly contagious novel coronavirus (SARS-CoV-2) has led to an unpredictable loss of life and economy worldwide, and the discovery of antiviral drugs is an urgent necessity. For the discovery of new drug leads and for the treatment of various diseases, natural products and purified photochemical from medicinal plants are used. The RNA cap was methylated by two S-adenosyl-L-methionine (SAM)-dependent methyltransferases of SARS coronavirus (SARS-CoV-2), catalyzed by NSP16 2'-O-Mtase. Natural substrate SAM, 128 Phytocompounds retrieved from the Phytocompounds database, and 11 standard FDA-approved HIV drugs reclaimed from the PubChem database are subjected to docking analysis. The docking study was done using AutoDock Vina. Further, admetSAR and DruLiTO servers are used to analyze the drug-likeness properties. The NSP16/10 structure and natural substrate SAM, Phytocompounds Withanolide (WTL), and HIV standard drug Dolutegravir (DLT) as hit compounds were identified by molecular dynamics using the Gromacs GPU-enabled package. To examine the effectiveness of the identified drugs versus COVID-19, further in vitro and in vivo studies are required. Communicated by Ramaswamy H. Sarma.

Acute Kidney Injury in a Tertiary Care Center of South India.

Background and Objective: Data regarding the epidemiology and outcomes of acute kidney injury (AKI) from our part of the world are limited. The irking consequences of AKI, both on the patient and the health care system, are being increasingly recognized. We aimed to study the epidemiology and short-term outcomes of AKI and to analyze the factors associated with adverse renal outcomes. Materials and Methods: We retrospectively studied AKI patients stratified according to the Kidney Disease: Improving Global Outcomes (KDIGO) stage, regarding clinicodemographic data, renal replacement therapy (RRT), and 90-day outcomes. Those with preexisting CKD Stage 4 (defined by estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2) and above, prior renal transplant (s), or acute glomerulonephritis were excluded. The primary outcome was a composite of de novo CKD (eGFR <60 mL/min/1.73 m2) or CKD progression (decline in eGFR category to any higher stage) in patients with baseline CKD at 90 days. The secondary outcome was a composite of de novo CKD, CKD progression, or death at 90 days. Results: Of the 358 patients, 52.5% had Stage 3 AKI. Eighty-eight patients (24.6%) had baseline CKD. Sepsis (51.4%) was the predominant etiology followed by nephrotoxins (42.5%). Renal replacement therapy (RRT) was required in 94 (26.3%) patients with hemodialysis being the most common modality. After excluding lost to follow-up, 66 patients (20.3%) had the primary outcome, and 195 patients (60%) had the secondary outcome. The 90-day mortality was observed in 39.7% of patients. AKI stage (P = 0.002), baseline CKD (P = 0.000) and RRT need (P = 0.005) were significantly associated with the primary outcome, while age >60 (P = 0.018), SOFA (Sequential Organ Failure Assessment) ≥9 (P = 0.000), hypoalbuminemia (P = 0.024), baseline CKD (P = 0.000) and RRT need (P = 0.001) were associated with the secondary outcome. Conclusion: Sepsis was the dominant precipitant of AKI and a major proportion had preventable etiology. AKI severity, baseline CKD status, and RRT need were found to predict the development or progression of CKD.

Designing a novel multi-epitope vaccine to evoke a robust immune response against pathogenic multidrug-resistant Enterococcus faecium bacterium.

Enterococcus faecium is an emerging ESKAPE bacterium that is capable of causing severe public health complications in humans. There are currently no licensed treatments or vaccinations to combat the deadly pathogen. We aimed to design a potent and novel prophylactic chimeric vaccine against E. faecium through an immunoinformatics approach The antigenic Penicillin-binding protein 5 (PBP 5) protein was selected to identify B and T cell epitopes, followed by conservancy analysis, population coverage, physiochemical assessment, secondary and tertiary structural analysis. Using various immunoinformatics methods and tools, two linear B-cell epitopes, five CTL epitopes, and two HTL epitopes were finally selected for vaccine development. The constructed vaccine was determined to be highly immunogenic, cytokine-producing, antigenic, non-toxic, non-allergenic, and stable, as well as potentially effective against E. faecium. In addition, disulfide engineering, codon adaptation, and in silico cloning, were used to improve stability and expression efficiency in the host E. coli. Molecular docking and molecular dynamics simulations indicated that the structure of the vaccine is stable and has a high affinity for the TLR4 receptor. The immune simulation results revealed that both B and T cells had an increased response to the vaccination component. Conclusively, the in-depth in silico analysis suggests, the proposed vaccine to elicit a robust immune response against E. faecium infection and hence a promising target for further experimental trials.

Efficacy and Outcomes of CYP3A5 Genotype-Based Tacrolimus Dosing Compared to Conventional Body Weight-based Dosing in Living Donor Kidney Transplant Recipients.

Introduction: Clinical use of tacrolimus has been challenging due to its narrow therapeutic index and highly variable pharmacokinetics. In this study, we compared patients who received body weight-based tacrolimus dosing pre-transplant (transplanted from 2016 to 2018) with those who received CYP3A5 genotype-based dosing (2018 to 2020). Methods: Eighty-two renal transplant recipients were non-randomly assigned to genotype-adapted or bodyweight-based tacrolimus dosing groups. The primary end point was to study the proportion of subjects who achieved the target tacrolimus C0 on post-op day 4. Secondary end points included clinical outcomes and safety. Results: The proportion of subjects who achieved the target tacrolimus C0 on postoperative days 4 and 10 were significantly higher in the adapted group, 53.6% and 47.5%, compared to 24.3% and 17% in controls, respectively (P = 0.01). Adapted group subjects achieved their first target tacrolimus C0 significantly earlier (4 days) compared to 25 days in controls (P = 0.01). The total number of tacrolimus dose modifications required in the first postop month were lower in the adapted group; 47 compared to 68 in the controls (P = 0.05). The proportion of subjects with sub-therapeutic tacrolimus exposure on postoperative day 4 was significantly higher in the controls, 56% versus 10% in the adapted group (P < 0.001). There were no significant differences between the groups in the rate of biopsy proven acute rejections, adverse events, and graft function at the end of 3 months follow up. Conclusion: Genotype-based tacrolimus dosing leads to more subjects achieving the target tacrolimus C0 earlier. However, there may be a higher risk of tacrolimus nephrotoxicity.

Unraveling the tripartite interaction of volatile compounds of Streptomyces rochei with grain mold pathogens infecting sorghum.

Sorghum is a major grain crop used in traditional meals and health drinks, and as an efficient fuel. However, its productivity, value, germination, and usability are affected by grain mold, which is a severe problem in sorghum production systems, which reduces the yield of harvested grains for consumer use. The organic approach to the management of the disease is essential and will increase consumer demand. Bioactive molecules like mVOC (volatile organic compound) identification are used to unravel the molecules responsible for antifungal activity. The Streptomyces rochei strain (ASH) has been reported to be a potential antagonist to many pathogens, with high levels of VOCs. The present study aimed to study the inhibitory effect of S. rochei on sorghum grain mold pathogens using a dual culture technique and via the production of microbial volatile organic compounds (mVOCs). mVOCs inhibited the mycelial growth of Fusarium moniliforme by 63.75 and Curvularia lunata by 68.52%. mVOCs suppressed mycelial growth and inhibited the production of spores by altering the structure of mycelia in tripartite plate assay. About 45 mVOCs were profiled when Streptomyces rochei interacted with these two pathogens. In the present study, several compounds were upregulated or downregulated by S. rochei, including 2-methyl-1-butanol, methanoazulene, and cedrene. S. rochei emitted novel terpenoid compounds with peak areas, such as myrcene (1.14%), cymene (6.41%), and ç-terpinene (7.32%) upon interaction with F. moniliforme and C. lunata. The peak area of some of the compounds, including furan 2-methyl (0.70%), benzene (1.84%), 1-butanol, 2-methyl-(8.25%), and myrcene (1.12)%, was increased during tripartite interaction with F. moniliforme and C. lunata, which resulted in furan 2-methyl (6.60%), benzene (4.43%), butanol, 2-methyl (18.67%), and myrcene (1.14%). These metabolites were implicated in the sesquiterpenoid and alkane biosynthetic pathways and the oxalic acid degradation pathway. The present study shows how S. rochei exhibits hyperparasitism, competition, and antibiosis via mVOCs. In addition to their antimicrobial functions, these metabolites could also enhance plant growth.

Acute myeloid leukemia patients with variant or unusual translocations involving chromosomes 8 and 21 - A comprehensive cytogenetic profiling of three cases with review of literature.

Background: t(8;21)(q22;q22) is the most frequent recurrent translocation in acute myeloid leukemia (AML) resulting in an in-frame fusion of RUNX1/RUNX1T1 that regulates various genes involved in the signaling pathways. This leukemogenic alteration is usually associated with a favorable clinical outcome. Variants of t(8;21) can be formed involving a third or fourth chromosome in ~3-4% of t(8;21)-AML. Due to the rarity of variant t(8;21), its clinicopathological features and prognostic significance are still unclear. Here we present three AML cases with cryptic rearrangements of chromosomes 8 and 21 without standard RUNX1/RUNX1T1. Materials and Methods: Conventional karyotyping and fluorescence in situ hybridization and/or spectral karyotyping of the pretreatment bone marrow aspirate of de novo AML patients were performed to delineate chromosomal abnormalities. Results: We identified three cases with novel variants of t(8;21); der(13)t(8;21;13), isodicentric derivative 8 with chromosome 21[,+idicder(8)(q11.1)t(8;21)(q22;q11.1)] and der(21)t(8;12;21)(q22;q?;q22). Conclusion: AML with t(8;21)(q22;q22);RUNX1-RUNX1T1 forms a distinct WHO subcategory and hence the identification of variants or unusual translocations associated with t(8;21) deserves more attention. Contribution to the variant/ unusual t(8;21) database will further refine the risk stratification and may help to significantly advance the current treatment regimen.

Light Weight Deep Learning Algorithm for Voice Call Quality of Services (Qos) in Cellular Communication.

In this paper, a deep learning algorithm was proposed to ensure the voice call quality of the cellular communication networks. This proposed model was consecutively monitoring the voice data packets and ensuring the proper message between the transmitter and receiver. The phone sends its unique identification code to the station. The telephone and station maintain a constant radio connection and exchange packets from time to time. The phone can communicate with the station via analog protocol (NMT-450) or digital (DAMPS, GSM). Cellular networks may have base stations of different standards, which allow you to improve network performance and improve its coverage. Cellular networks are different operators connected to each other, as well as a fixed telephone network that allows subscribers of one operator to another to make calls from mobile phones to landlines and from landlines to mobiles. The simulation is conducted in Matlab against different performance metrics, that is, related to the quality of service metric. The results of the simulation show that the proposed method has a higher QoS rate than the existing method over an average of 97.35%.

Effect of dietary ß carotene on cerebral aneurysm and subarachnoid haemorrhage in the brain apo E-/- mice.

Atherosclerosis will lead to stenosis/occlusion in the lumen of various arteries of living body. This can lead various conditions including myocardial infarction, cerebral infarction/aneurysm and peripheral artery disease. Ang II is believed to be an important regulatory peptide involved in maintaining cardiovascular homeostasis and pathogenesis of various cardiovascular diseases. Matrix metalloproteinase's (MMPs), adhesion molecules and plasminogen systems are involved in the inflammatory reaction of various blood vessels as well as pathogenesis of cerebro vasuclar disease in apo E(-/-) mice during angiotensin II injection. The present study analyses the role of ang II in development of cerebral aneurysm and also evaluated the mRNA levels of MMPs, adhesion molecules, plasminogen systems and peroxisome proliferators-associated receptors in the brain of apo E(-/-) mouse during the progression of cerebral aneurysm and ischemic conditions. Also, this study evaluates the role of dietary ß carotene on cerebrovascular disease. Serum total cholesterol (TC), Low density lipoprotein (LDL) and triglyceride (TG) levels were significantly increased in angiotensin II treated animals and further ß carotene supplementation reduces TC but does not affect the triglyceride and LDL levels. Circulating levels of macrophages were significantly increased in angiotensin treated animals and further beta carotene supplementation significantly reduced the circulating macrophages. Cerebro meningeous aneurysm, subarachnoid haemorrhage, multiple foci of infarction, necrosis and infiltration of inflammatory cells were observed in the cerebral hemispheres of ang II treated animals, however, infarction size were reduced and no aneurysm, inflammatory foci was observed in ß carotene treated animals. Real time analysis showed down regulation of mRNA levels of MMP 2, uPA, PAI, PPAR-A, MCSF1 and up regulation of tPA and MCP-1 in the brain during the progression of cerebral aneurysm and ß carotene supplementation to bring to normal expression levels of all the candidate genes for cerebrovascular diseases. Based on above results, Ang II may induced cerebral aneurysm, ischemia/infarction on brain through RAS system by down regulating the mRNA levels of MMP 2, uPA, PAI, PPAR-A, MCSF1 and up regulating tPA and MCP-1 and ß carotene attenuates the disease condition and bring down to normal expression levels of above genes.

A comparison of the pitfall trap, Winkler extractor and Berlese funnel for sampling ground-dwelling arthropods in tropical montane cloud forests.

Little is known about the ground-dwelling arthropod diversity in tropical montane cloud forests (TMCF). Due to unique habitat conditions in TMCFs with continuously wet substrates and a waterlogged forest floor along with the innate biases of the pitfall trap, Berlese funnel and Winkler extractor are certain to make it difficult to choose the most appropriate method to sample the ground-dwelling arthropods in TMCFs. Among the three methods, the Winkler extractor was the most efficient method for quantitative data and pitfall trapping for qualitative data for most groups. Inclusion of floatation method as a complementary method along with the Winkler extractor would enable a comprehensive quantitative survey of ground-dwelling arthropods. Pitfall trapping is essential for both quantitative and qualitative sampling of Diplopoda, Opiliones, Orthoptera, and Diptera. The Winkler extractor was the best quantitative method for Psocoptera, Araneae, Isopoda, and Formicidae; and the Berlese funnel was best for Collembola and Chilopoda. For larval forms of different insect orders and the Acari, all the three methods were equally effective.

Biosynthesis and Characterization of a Novel Fibrinolytic Alkaline Serine Protease from Newly Isolated Bacillus flexus BF12 for Biomedical Applications.

BACKGROUND: Cardiovascular Diseases (CVDs) such as stroke, high blood pressure, peripheral vascular disease, ischemic heart disease and acute myocardial infarction are some of the leading causes of death. To treat CVDs, commercially available thrombolytic agents are widely used. However, these thrombolytic agents have various side effects. Alternatively, fibrinolytic enzymes from bacterial sources are highly safe and have direct blood clot lytic activity. METHODS: A fibrinolytic enzyme producing bacterial strain, Bacillus flexus BF12, was isolated from a solar saltpan in Kanyakumari District, Tamilnadu, India. Enzyme production was improved by optimizing physical factors and nutritional factors. RESULTS: A novel fibrinolytic enzyme was isolated from a strain of the studied B. flexus BF12. Enzyme production was enhanced significantly by optimizing process parameters. The critical physical factors (pH and salinity) and influencing nutritional factors (carbon, nitrogen and ions) were optimized by one variable at a time approach, followed by the statistical method. The strain BF12 was highly active at alkaline pH (>7.0) and between 4 and 6% NaCl concentration. The nutrients such as fructose (carbon source), beef extract (nitrogen source) and CaCl2 significantly influenced enzyme production. Central composite design and response surface methodology improved 3.2-fold enzyme yield than unoptimized culture medium. Fibrinolytic protease was purified by ammonium sulphate precipitation, dialysis and gel filtration chromatography. DISCUSSION: The molecular weight of an enzyme was found to be 23 kDa. It was active at a broad temperature (40-60 °C) and pH (7.0-9.0) ranges. Enzyme activity was enhanced by Ca2+ and Co2+ ions. The purified protease retained 100% enzyme activity in the presence of ethanol and acetone. Acetonitrile, butanol, DMSO, methanol and chloroform showed enzyme activity of 63%, 92.5%, 94.7%, 92.3% and 90.4%, respectively. The purified enzyme degraded 100% of human blood clot. CONCLUSION: The Bacillus flexus BF12 fibrinolytic enzyme shows promising potentials in nutraceutical and food fortification applications. The application of fibrinolytic enzymes could prevent CVDs.

A Rare Genetic Mutation in a Stone Former.

A 30-year-old woman with history of passage of stones since childhood presented with oliguria and pedal edema for 10 days. She had hypertension with a creatinine of 4.1 mg/dL. Evaluation showed presence of bilateral multiple renal calculi with features of chronicity of kidney disease. Metabolic work-up for nephrolithiasis turned out to be negative and eventually renal biopsy revealed features of chronic interstitial nephritis with greenish brown refractile crystals in the tubular lumen and interstitium. The possibility of dihydroxy adenine crystalline nephropathy was considered. Spectrophotometry of RBC lysates revealed decreased activity of Adenine phosphoribosyl-transferase enzyme. Gene amplification by PCR and sequential analysis identified a missense mutation in exon 3 region of APRT gene in the patient and her family members. This case report highlights the need to contemplate the diagnosis of DHA crystalline nephropathy in young patients with nephrolithiasis and the identification of a rare genetic mutation, which is being reported for the first time in India.

Association of IgA Nephropathy with Squamous Cell Carcinoma of the Tongue: - Case Report and Review of Literature.

A 32-year-old habitual tobacco chewer was diagnosed with squamous cell carcinoma of the tongue. He was initiated on chemo-radiation therapy. After completing 23 cycles of radiation and four cycles of cisplatin-based chemotherapy, he presented with acute nephritic syndrome. Renal biopsy showed IgA nephropathy and acute tubular injury. With supportive care, renal function stabilised with a reduction in proteinuria. We wish to highlight the poorly understood association between mucosal malignancies and IgA nephropathy. It is also interesting to note the peculiar temporal profile of glomerular involvement in our patient, where the onset of the glomerulonephritis was after the initiation of chemo-radiotherapy. This is unlike what has been described earlier.