Association between Intraoperative Bactibilia and Postoperative Septic Complications in Biliary Tract Surgery

Background: The present study intended to clarify the role of biliary bacteria in the development of postoperative septic complications in patients undergoing biliary operations and need for antibiotic prophylaxis.Patient and methods: A total of 121 patients with various biliary tract diseases underwent various surgical interventions. The relation between contaminated ductal bile and postoperative septic complications was analyzed prospectively.Results: 42/121 patients were bile culture positive (B+) while 79/121 patients were bile culture negative (B-).14 patients in B (+) group developed septic complications compared to only 3 patients in B (-) group (P = 0.0001). In B (+) group, bacteria found in ductal bile were also detected in infected sites of 85% of patients with septic complications. In B (+) group postoperative antibiotic modification significantly (p=0.001) reduced infectious complications.Conclusion: Infected bile plays a critical role in development of post operative septic complications. Hence patients with risk factors for bactibilia should receive prophylactic antibiotics covering endogenous gram negative organisms which should be modified in postoperative phase according to the results of sensitivity. However this issue requires further investigations by studies conducted on similar lines

Pharmacoinformatics-based identification of transmembrane protease serine-2 inhibitors from Morus Alba as SARS-CoV-2 cell entry inhibitors

Transmembrane protease serine-2 (TMPRSS2) is a cell-surface protein expressed by epithelial cells of specific tissues including those in the aerodigestive tract. It helps the entry of novel coronavirus (n-CoV) or Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the host cell. Successful inhibition of the TMPRSS2 can be one of the crucial strategies to stop the SARS-CoV-2 infection. In the present study, a set of bioactive molecules from Morus alba Linn. were screened against the TMPRSS2 through two widely used molecular docking engines such as Autodock vina and Glide. Molecules having a higher binding affinity toward the TMPRSS2 compared to Camostat and Ambroxol were considered for in-silico pharmacokinetic analyses. Based on acceptable pharmacokinetic parameters and drug-likeness, finally, five molecules were found to be important for the TMPRSS2 inhibition. A number of bonding interactions in terms of hydrogen bond and hydrophobic interactions were observed between the proposed molecules and ligand-interacting amino acids of the TMPRSS2. The dynamic behavior and stability of best-docked complex between TRMPRSS2 and proposed molecules were assessed through molecular dynamics (MD) simulation. Several parameters from MD simulation have suggested the stability between the protein and ligands. Binding free energy of each molecule calculated through MM-GBSA approach from the MD simulation trajectory suggested strong affection toward the TMPRSS2. Hence, proposed molecules might be crucial chemical components for the TMPRSS2 inhibition

Observation of second-harmonic generation induced by pure spin currents

Extensive efforts are currently being devoted to developing a new electronic technology, called spintronics, where the spin of electrons is explored to carry information. [1,2] Several techniques have been developed to generate pure spin currents in many materials and structures. [3-10] However, there is still no method available that can be used to directly detect pure spin currents, which carry no net charge current and no net magnetization. Currently, studies of pure spin currents rely on measuring the induced spin accumulation with optical techniques [5, 11-13] or spin-valve configurations. [14-17] However, the spin accumulation does not directly reflect the spatial distribution or temporal dynamics of the pure spin current, and therefore cannot monitor the pure spin current in a real-time and real-space fashion. This imposes severe constraints on research in this field. Here we demonstrate a second-order nonlinear optical effect of the pure spin current. We show that such a nonlinear optical effect, which has never been explored before, can be used for the non-invasive, non-destructive, and real-time imaging of pure spin currents. Since this detection scheme does not rely on optical resonances, it can be generally applied in a wide range of materials with different electronic bandstructures. Furthermore, the control of nonlinear optical properties of materials with pure spin currents may have potential applications in photonics integrated with spintronics.Comment: 19 pages, 3 figures, supplementary discussion adde

Cooling of Dark-Matter Admixed Neutron Stars with density-dependent Equation of State

We propose a dark-matter (DM) admixed density-dependent equation of state where the fermionic DM interacts with the nucleons via Higgs portal. Presence of DM can hardly influence the particle distribution inside neutron star (NS) but can significantly affect the structure as well as equation of state (EOS) of NS. Introduction of DM inside NS softens the equation of state. We explored the effect of variation of DM mass and DM Fermi momentum on the NS EOS. Moreover, DM-Higgs coupling is constrained using dark matter direct detection experiments. Then, we studied cooling of normal NSs using APR and DD2 EOSs and DM admixed NSs using dark-matter modified DD2 with varying DM mass and Fermi momentum. We have done our analysis by considering different NS masses. Also DM mass and DM Fermi momentum are varied for fixed NS mass and DM-Higgs coupling. We calculated the variations of luminosity and temperature of NS with time for all EOSs considered in our work and then compared our calculations with the observed astronomical cooling data of pulsars namely Cas A, RX J0822-43, 1E 1207-52, RX J0002+62, XMMU J17328, PSR B1706-44, Vela, PSR B2334+61, PSR B0656+14, Geminga, PSR B1055-52 and RX J0720.4-3125. It is found that APR EOS agrees well with the pulsar data for lighter and medium mass NSs but cooling is very fast for heavier NS. For DM admixed DD2 EOS, it is found that for all considered NS masses, all chosen DM masses and Fermi momenta agree well with the observational data of PSR B0656+14, Geminga, Vela, PSR B1706-44 and PSR B2334+61. Cooling becomes faster as compared to normal NSs in case of increasing DM mass and Fermi momenta. It is infered from the calculations that if low mass super cold NSs are observed in future that may support the fact that heavier WIMP can be present inside neutron stars.Comment: 24 Pages, 15 Figures and 2 Tables. Version accepted in The European Physical Journal

Poor follow-up rates at a self-pay northern Indian tertiary AIDS clinic

<p>Abstract</p> <p>Background</p> <p>In many developing countries, out-of-pocket payment remains a primary mechanism by which patients infected with HIV access treatment. In India, this has been changing as the National AIDS Control Organization (NACO) has been rolling out free antiretroviral therapy throughout the country since 2004. The vast majority of patients, however, remain without access to free medicines.</p> <p>Methods</p> <p>A retrospective chart review was performed on data obtained from a registry of ninety-three (93) patients attending a self-pay clinic at the All India Institute of Medical Sciences in Delhi, India. Multivariable Cox proportional hazard and logistic regression models were explored to assess the relationship between lost-to-follow-up status and the predictor variables: age, sex, household income, baseline CD4 count, and distance from clinic.</p> <p>Results</p> <p>Lost-to-follow-up rates were very high; 68% (63/93) were lost-to-follow-up till the time of chart review, including 59% (55/93) who were lost within one year. In both regression models, younger age, low baseline CD4 counts, and low income level were significantly associated with increased risk of lost-to-follow-up. Additionally, there was a significant interaction between income and CD4 counts. The patients with both low CD4 counts and low income level were more likely to be lost-to-follow-up than would be predicted by each covariable alone.</p> <p>Conclusion</p> <p>In this small cohort of AIDS patients attending a self-pay antiretroviral clinic at a large tertiary care center in Delhi, India, follow-up rates were quite poor. Poorer patients tended to present to clinic with more depressed CD4 counts and were less likely to be retained in care. These findings indicate that greater strides must be taken to improve the recruitment and retention of poor patients. The expansion of free antiretrovirals is one step among many necessary to achieve this objective.</p

Partial Inhibition of Estrogen-Induced Mammary Carcinogenesis in Rats by Tamoxifen: Balance between Oxidant Stress and Estrogen Responsiveness

Epidemiological and experimental evidences strongly support the role of estrogens in breast tumor development. Both estrogen receptor (ER)-dependent and ER-independent mechanisms are implicated in estrogen-induced breast carcinogenesis. Tamoxifen, a selective estrogen receptor modulator is widely used as chemoprotectant in human breast cancer. It binds to ERs and interferes with normal binding of estrogen to ERs. In the present study, we examined the effect of long-term tamoxifen treatment in the prevention of estrogen-induced breast cancer. Female ACI rats were treated with 17β-estradiol (E2), tamoxifen or with a combination of E2 and tamoxifen for eight months. Tissue levels of oxidative stress markers 8-iso-Prostane F2α (8-isoPGF2α), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, and oxidative DNA damage marker 8-hydroxydeoxyguanosine (8-OHdG) were quantified in the mammary tissues of all the treatment groups and compared with age-matched controls. Levels of tamoxifen metabolizing enzymes cytochrome P450s as well as estrogen responsive genes were also quantified. At necropsy, breast tumors were detected in 44% of rats co-treated with tamoxifen+E2. No tumors were detected in the sham or tamoxifen only treatment groups whereas in the E2 only treatment group, the tumor incidence was 82%. Co-treatment with tamoxifen decreased GPx and catalase levels; did not completely inhibit E2-mediated oxidative DNA damage and estrogen-responsive genes monoamine oxygenase B1 (MaoB1) and cell death inducing DFF45 like effector C (Cidec) but differentially affected the levels of tamoxifen metabolizing enzymes. In summary, our studies suggest that although tamoxifen treatment inhibits estrogen-induced breast tumor development and increases the latency of tumor development, it does not completely abrogate breast tumor development in a rat model of estrogen-induced breast cancer. The inability of tamoxifen to completely inhibit E2-induced breast carcinogenesis may be because of increased estrogen-mediated oxidant burden

Interplay between estrogen receptor and AKT in estradiol-induced alternative splicing.

BACKGROUND: Alternative splicing is critical for generating complex proteomes in response to extracellular signals. Nuclear receptors including estrogen receptor alpha (ERα) and their ligands promote alternative splicing. The endogenous targets of ERα:estradiol (E2)-mediated alternative splicing and the influence of extracellular kinases that phosphorylate ERα on E2-induced splicing are unknown. METHODS: MCF-7 and its anti-estrogen derivatives were used for the majority of the assays. CD44 mini gene was used to measure the effect of E2 and AKT on alternative splicing. ExonHit array analysis was performed to identify E2 and AKT-regulated endogenous alternatively spliced apoptosis-related genes. Quantitative reverse transcription polymerase chain reaction was performed to verify alternative splicing. ERα binding to alternatively spliced genes was verified by chromatin immunoprecipitation assay. Bromodeoxyuridine incorporation-ELISA and Annexin V labeling assays were done to measure cell proliferation and apoptosis, respectively. RESULTS: We identified the targets of E2-induced alternative splicing and deconstructed some of the mechanisms surrounding E2-induced splicing by combining splice array with ERα cistrome and gene expression array. E2-induced alternatively spliced genes fall into at least two subgroups: coupled to E2-regulated transcription and ERα binding to the gene without an effect on rate of transcription. Further, AKT, which phosphorylates both ERα and splicing factors, influenced ERα:E2 dependent splicing in a gene-specific manner. Genes that are alternatively spliced include FAS/CD95, FGFR2, and AXIN-1. E2 increased the expression of FGFR2 C1 isoform but reduced C3 isoform at mRNA level. E2-induced alternative splicing of FAS and FGFR2 in MCF-7 cells correlated with resistance to FAS activation-induced apoptosis and response to keratinocyte growth factor (KGF), respectively. Resistance of MCF-7 breast cancer cells to the anti-estrogen tamoxifen was associated with ERα-dependent overexpression of FGFR2, whereas resistance to fulvestrant was associated with ERα-dependent isoform switching, which correlated with altered response to KGF. CONCLUSION: E2 may partly alter cellular proteome through alternative splicing uncoupled to its effects on transcription initiation and aberration in E2-induced alternative splicing events may influence response to anti-estrogens.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Effect of the probiotic Lactobacilli reuteri (Prodentis) in the management of periodontal disease: a preliminary randomized clinical trial

Objectives: The aim of this study was to evaluate the effects of Lactobacilli reuteri (Prodentis) alone and in combination with scaling and root planing (SRP) in a double blind, randomized, placebo-controlled clinical trial of volunteers with chronic periodontitis. Methods: Thirty, otherwise systemically healthy, chronic periodontitis patients (19 males and 11 females, aged between 34 and 50 years) were included. The study period was 42 days. &#x2018;Split-mouth&#x2019; design was used for the SRP, which was performed on day 0; two quadrants (either right or left) were treated with SRP whereas the remaining two quadrants were left untreated. The participants received a toothbrush, toothpaste, and brushing instructions. L. reuteri Prodentis lozenges (1&#x00D7;108 CFU DSM17938&#x200A;+&#x200A;1&#x00D7;108 CFU ATCC PTA 5289) or the corresponding placebo lozenges were taken twice daily from day 21 to day 42. Statistical analysis was done for comparisons of clinical parameters (Plaque Index (PI), Gingival Index (GI), Gingival Bleeding Index (GBI), probing pocket depth (PPD), clinical attachment level (CAL)) and microbiological levels of the pathogens Aggregibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), and Prevotella intermedia (Pi). All p-values less than 0.05 were considered significant. Assessments were made on day 0 before SRP treatment, on day 21 before administration of the lozenges, and on day 42. Results: At day 42, the PI, GI, and GBI were significantly reduced by all treatment modalities. When ranked, the amount of PI, GI and GBI reduction by the different treatments was SRP&#x200A;+&#x200A;Prodentis&#x200A;&#x003E;&#x200A;Prodentis&#x200A;&#x003E;&#x200A;SRP&#x200A;+&#x200A;placebo&#x200A;&#x003E;&#x200A;placebo; all differences were statistically significant. For PPD and CAL, the best result was obtained with the SRP&#x200A;+&#x200A;Prodentis treatment. PPD was reduced from 5.08&#x00B1;0.75 to 3.78&#x00B1;0.61&#x2009;mm (p&#60;0.001) and CAL from 3.93&#x00B1;0.93 to 2.85&#x00B1;0.74&#x2009;mm (p&#60;0.001). Prodentis, either alone or following SRP, reduced Aa, Pi, and Pg by 1 log10 unit (p&#60;0.01). The SRP&#x200A;+&#x200A;placebo combination did not significantly affect the levels of the pathogens. Conclusion: The present randomized controlled trial confirms the plaque inhibition, anti-inflammatory, and antimicrobial effects of L. reuteri Prodentis. L. reuteri Prodentis probiotic can be recommended during non-surgical therapy and the maintenance phase of periodontal treatment. Considering the beneficial effects of probiotics, this therapy could serve as a useful adjunct or alternative to periodontal treatment when SRP might be contraindicated. Further studies are required in this direction