Identification of a Contiguous 6-Residue Determinant in the MHV Receptor That Controls the Level of Virion Binding to Cells

AbstractMurine carcinoembryonic antigens serve as receptors for the binding and entry of the enveloped coronavirus mouse hepatitis virus (MHV) into cells. Numerous receptor isoforms are now known, and each has extensive differences in its amino terminal immunoglobulin-like domain (NTD) to which MHV binds via its protruding spike proteins. Some of these receptor alterations may affect the ability to bind viral spikes. To identify individual residues controlling virus binding differences, we have used plasmid and vaccinia virus vectors to express two forms of MHV receptor differing only in their NTD. The two receptors, designated biliary glycoproteins (Bgp) 1aand 1bNTD, varied by 29 residues in the 107 amino acid NTD. When expressed from cDNAs in receptor-negative HeLa cells, these two Bgp molecules were displayed on cell surfaces to equivalent levels, as both were equally modified by a membrane-impermeant biotinylation reagent. Infectious center assays revealed that the 1aisoform was 10 to 100 times more effective than 1bNTDin its ability to confer sensitivity to MHV (strain A59) infection. Bgp1awas also more effective than Bgp1bNTDin comparative virus adsorption assays, binding 6 times more MHV (strain A59) and 2.5 times more MHV (strain JHMX). Bgp1awas similarly more effective in promoting the capacity of viral spikes to mediate intercellular membrane fusion as judged by quantitation of syncytia following cocultivation of spike and receptor-bearing cells. To identify residues influencing these differences, we inserted varying numbers of 1bresidues into the Bgp1abackground via restriction fragment exchange and site-directed mutagenesis. Analysis of the resulting chimeric receptors showed that residues 38 to 43 of the NTD were key determinants of the binding and fusion differences between the two receptors. These residues map to an exposed loop (C-C′ loop) in a structural model of the closely related human carcinoembryonic antigen

Role Of Social Media As Time Variant In Health Monitoring System

Early monitoring of health information is corresponding to post-factum examines and empowers a scope of applications, for example, estimating social hazard factors and activating health efforts. We detail two issues: health progress location and health change pectation. We initially propose the Temporal Ailment Topic Aspect Model (TM– ATAM), another inactive model devoted to taking care of the primary issue by catching advances that include health related points. TM– ATAM is a non-evident expansion to ATAM that was intended to remove health related themes. It learns health related subject advances by limiting the expectation mistake on theme disseminations between back to back posts at various time and geographic granularities. To tackle the second issue, we create T– ATAM, a Temporal Ailment Topic Aspect Model where time is treated as an arbitrary variable locally inside ATAM

A study on the clinical manifestations and the incidence of benign and malignant tumors in a solitary thyroid nodule

Tumors are either benign or malignant. The thyroid nodule, which is usually a clinical manifestation of most of the thyroid disorders, is one among them which has been the subject of controversies with divergent opinions and views. Clinical presentation of thyroid nodules varies widely ranging from solitary nodules to benign and malignant tumors. Thyroid nodules accounts up to 8% of the adult population having palpable nodules. However studies on its incidence in the population residing near seacoast are limited. Hence, the present study is carried in an aim to evaluate the clinico-pathological correlation of solitary thyroid nodule and the incidence of malignancy in the population residing at sea coast. The study is conducted in the Narayana Medical College & Hospital (NMCH), which is situated within 10-15 km radius of the seacoast in Nellore district of Andhra Pradesh, India. In this study, 73 subjects were selected who presented with thyroid swelling which was clinically confirmed as solitary thyroid nodule. Out of 73 cases, 12 cases (16.5%) were found to have malignant lesions with remaining 61 cases (83.5%) being benign lesions. The incidence of malignancy among solitary thyroid nodule subjects is up to 16.5% in the population residing near seacoast. Thus the present study warrants people to consult surgeons for early diagnosis and adequate treatment without being passive as most of these swellings are asymptomatic for long duration

Acute Endovascular Reperfusion Therapy in Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

[email protected] Randomized controlled trials (RCTs) of endovascular therapy for acute ischemic stroke have had inconsistent results. We evaluated the efficacy and safety of endovascular therapy in published RCTs. Methods We performed a systematic review of RCTs of endovascular therapy with thrombolytic or mechanical reperfusion compared with interventions without endovascular therapy. Primary outcome was the frequency of good functional outcome (modified Rankin scale (mRS) of 0-2 at 90 days) and secondary outcomes were mortality at 90 days and symptomatic intracranial hemorrhage (sICH). Random-effects meta-analysis was performed and the Cochrane risk of bias assessment was used to evaluate quality of evidence. Results Ten studies involving 1,612 subjects were included. Endovascular therapy was not significantly associated with good functional outcome (Relative Risk [RR] =1.17; 95% CI, 0.97 to 1.42; p=0.10 and Absolute Risk Difference [ARD] =7%; 95%CI -0.1% to 14%; p=0.05); heterogeneity was moderate among studies (I2=30%). Mortality was unchanged with endovascular therapy (RR=0.92; 95 % CI, 0.75 to 1.13; p=0.45) and there was no difference in sICH (RR=1.20; 95 % CI, 0.79 to 1.82; p=0.39). The quality of evidence was low for all outcomes and the recommendation is weak for the use of endovascular therapy as per GRADE methodology. Conclusions Intra-arterial therapy did not show significant increase in good outcomes and no changes in either mortality or sICH in patients with acute ischemic stroke. We need further RCTs with better design and quality to evaluate the true efficacy of endovascular therapy.Revisión por pare

Effects of preeclampsia and eclampsia on maternal metabolic and biochemical outcomes in later life: a systematic review and meta-analysis

Objective: To evaluate the association between preeclampsia (PE) and eclampsia (E) on subsequent metabolic and biochemical outcomes. Methods: Systematic review and meta-analysis of observational studies. We searched five engines until November 2018 for studies evaluating the effects of PE/E on metabolic and biochemical outcomes after delivery. PE was defined as presence of hypertension and proteinuria at >20 weeks of pregnancy; controls did not have PE/E. Primary outcomes were blood pressure (BP), body mass index (BMI), metabolic syndrome (MetS), blood lipids and glucose levels. Random effects models were used for meta-analyses, and effects reported as risk difference (RD) or mean difference (MD) and their 95% confidence interval (CI). Subgroup analyses by time of follow up, publication year, and confounder adjustment were performed. Results: We evaluated 41 cohorts including 3300 PE/E and 13,967 normotensive controls. Women were followed up from 3 months after delivery up to 32 years postpartum. In comparison to controls, PE/E significantly increased systolic BP (MD = 8.3 mmHg, 95%CI 6.8 to 9.7), diastolic BP (MD = 6.8 mmHg, 95%CI 5.6 to 8.0), BMI (MD = 2.0 kg/m2; 95%CI 1.6 to 2.4), waist (MD = 4.3 cm, 95%CI 3.1 to 5.5), waist-to-hip ratio (MD = 0.02, 95%CI 0.01 to 0.03), weight (MD = 5.1 kg, 95%CI 2.2 to 7.9), total cholesterol (MD = 4.6 mg/dL, CI 1.5 to 7.7), LDL (MD = 4.6 mg/dL; 95%CI 0.2 to 8.9), triglycerides (MD = 7.7 mg/dL, 95%CI 3.6 to 11.7), glucose (MD = 2.6 mg/dL, 95%CI 1.2 to 4.0), insulin (MD = 19.1 pmol/L, 95%CI 11.9 to 26.2), HOMA-IR index (MD = 0.7, 95%CI 0.2 to 1.2), C reactive protein (MD = 0.05 mg/dL, 95%CI 0.01 to 0.09), and the risks of hypertension (RD = 0.24, 95%CI 0.15 to 0.33) and MetS (RD = 0.11, 95%CI 0.08 to 0.15). Also, PE/E reduced HDL levels (MD = –2.15 mg/dL, 95%CI –3.46 to −0.85). Heterogeneity of effects was high for most outcomes. Risk of bias was moderate across studies. Subgroup analyses showed similar effects as main analyses. Conclusion: Women who had PE/E have worse metabolic and biochemical profile than those without PE/E in an intermediate to long term follow up period. ©Revisión por pare

Insulin resistance and endometrial cancer risk: A systematic review and meta-analysis

Abstract Aim: It has been suggested that chronic hyperinsulinemia from insulin resistance is involved in the etiology of endometrial cancer (EC). We performed a systematic review and meta-analysis to assess whether insulin resistance is associated with the risk of EC. Methods: We searched PubMed-Medline, Embase, Scopus, and Web of Science for articles published from database inception through 30th September 2014. We included all observational studies evaluating components defining insulin resistance in women with and without EC. Quality of the included studies was assessed by NewcastleeOttawa scale. Randomeffects models and inverse variance method were used to meta-analyze the association between insulin resistance components and EC. Results: Twenty-five studies satisfied our inclusion criteria. Fasting insulin levels (13 studies, n Z 4088) were higher in women with EC (mean difference [MD] 33.94 pmol/L, 95% confi- dence interval [CI] 15.04e52.85, p Z 0.0004). No differences were seen in postmenopausal versus pre- and postmenopausal subgroup analysis. Similarly, non-fasting/fasting C-peptide levels (five studies, n Z 1938) were also higher in women with EC (MD 0.14 nmol/L, 95% CI 0.08e0.21, p < 0.00001). Homeostatic model assessment - insulin resistance (HOMA-IR) values (six studies, n Z 1859) in EC patients were significantly higher than in women without EC (MD 1.13, 95% CI 0.20e2.06, p Z 0.02). There was moderate-to-high heterogeneity among the included studies. Conclusion: Currently available epidemiologic evidence is suggestive of significantly higher risk of EC in women with high fasting insulin, non-fasting/fasting C-peptide and HOMAIR values.Revisión por pare

A systematic review of the relative efficacy and toxicity of treatment regimens for HIV-associated cerebral toxoplasmosis: is trimephoprim-sulfamethaxozole a real option?

Background: Pyrimethamine and sulfadiazine (P-S) combination is effective and considered the mainstay therapy for cerebral toxoplasmosis (CT). Alternative treatment regimens are available, but their relative efficacy and tolerability are not well known. Particularly, trimephoprim-sulfamethaxozole (TMP-SMX) shows potential advantages (i.e., tolerability, posology, parenteral formulation, cost, and accessibility) but its use is infrequent when P-S is available. Methods: We searched PubMed and 4 other databases to identify randomized controlled trials (RCTs) and cohort studies comparing different regimens for the treatment of HIV-associated CT. Two independent reviewers searched and identified studies and extracted data. Risk ratios (RRs) were pooled across studies using random-effects models. Results: Nine studies were included (5 RCTs, 3 retrospective cohorts, 1 prospective cohort). Treatment with P-S has the same or better clinical efficacy than P-C or TMP-SMX in terms of partial or complete response clinical response (P-C vs P-S: RR 0.87, 95%CI 0.70-1.08; TMP-SMX vs P-S: RR 0.97, 95%CI 0.78-1.21) and radiological response (P-C vs P-S: RR 0.92, 95%CI 0.82-1.03). Safety profile in terms of skin rash (P-C vs P-S: RR 0.81, 95%CI 0.56-1.17; TMP-SMX vs P-S: RR 0.17, 95%CI 0.02-1.29), liver impairment (P-C vs P-S: RR 0.48, 95%CI 0.24-0.97) and drug discontinuation due to adverse events (P-C vs P-S: RR 0.32, 95%CI 0.07-1.47) were worse with P-S regimen. Conclusion: The available evidence fails to identify any one superior regimen for the treatment of CT. However, P-S regimen has worse safety profile than P-C or TMP-SMX. Although current evidence does not allow a definitive recommendation, use of TMP-SMX for treatment of HIV-associated CT is consistent with the available data. More large studies comparing alternative therapies are needed.IDWeek, Evento que se llevó a cabo del 7 -11 de Octubre de 2015, en la ciudad de San Diego, CA, EE.UU. Evento Sesión HIV: Other Opportunistic Infections in HIV. Saturday, October 10, 2015. Room: Poster Hal

Less Engagement in Pleasure Activities is associated with poorer quality of life for Veterans with Comorbid Post-Deployment Conditions

Objective: The presence of multiple comorbid conditions is common after combat deployment and complicates treatment. A potential treatment approach is to target shared mechanisms across conditions that maintain poorer health-related quality of life (HRQOL). One such mechanism may be decrements in pleasurable activities. Impairment in pleasurable activities frequently occurs after deployment and may be associated with poorer HRQOL. Method: In this brief report, we surveyed 126 Veterans who had previously sought an assessment at a Veterans Affairs post-deployment health clinic and assessed pleasurable activities, HRQOL, and post-deployment health symptoms. Results: Forty-three percent of Veterans met our criteria for all three post-deployment conditions (PTSD, depression and chronic wide-spread physical symptoms). Greater engagement in pleasurable activities was associated with better HRQOL for all Veterans regardless of type or level of post-deployment health symptoms. Conclusion: Future research should study if interventions that encourage Veterans with post-deployment health conditions to engage in pleasurable activities are effective rehabilitation strategies

Hunig's base catalyzed synthesis of new 1-(2,3-dihydro-1H-inden-1-yl)-3-aryl urea/ thiourea derivatives as potent antioxidants and 2HCK enzyme growth inhibitors

A series of 1-(2,3-dihydro-1H-indan-1-yl)-3-aryl urea/thiourea derivatives (4a-j) have been synthesized from the reaction of 2,3-dihydro-1H-inden-1-amine (2) with various aryl isocyanates/isothiocyanates (3a-j) by using N,N-DIPEA base (Hunig's base) catalyst in THF at reflux conditions. All of them are structurally confirmed by spectral (IR, 1H & 13C NMR and MASS) and elemental analysis and screened for their in-vitro antioxidant activity against DPPH and NO free radicals and found that compounds 4b, 4i, 4h & 4g are potential antioxidants. The obtained in vitro results were compared with the molecular docking, ADMET, QSAR and bioactivity study results performed for them and identified that the recorded in silico binding affinities were observed in good correlation with the in vitro antioxidant results. The Molecular docking analysis had unveiled the strong hydrogen bonding interactions of synthesized ligands with ARG 160 residue of protein tyrosine kinase (2HCK) enzyme and plays an effective role in its inhibition. Toxicology studies have assessed the potential risks of 4a-j and inferred that all of them were in the limits of potential drugs. The conformational analysis of 4a-j inferred that the urea/thiourea spacer linking 2,3-dihydro-1H-inden-1-amino and substituted aryl units has facilitated all these molecules to effectively bind with ARG 160 amino acid residue present on the α-helix of the protein tyrosine kinase (2HCK) enzyme specifically on chain A of hemopoetic cell kinase. Collectively this study has established a relationship between the antioxidant potentiality and ligands binding with ARG 160 amino acid residue of chain A of 2HCK enzyme to inhibit its growth as well as proliferation of reactive oxygen species in vivo