Clinical and cost-effectiveness of nurse-delivered sleep restriction therapy for insomnia in primary care (HABIT): a pragmatic, superiority, open-label, randomised controlled trial.

BACKGROUND: Insomnia is prevalent and distressing but access to the first-line treatment, cognitive behavioural therapy (CBT), is extremely limited. We aimed to assess the clinical and cost-effectiveness of sleep restriction therapy, a key component of CBT, which has the potential to be widely implemented. METHODS: We did a pragmatic, superiority, open-label, randomised controlled trial of sleep restriction therapy versus sleep hygiene. Adults with insomnia disorder were recruited from 35 general practices across England and randomly assigned (1:1) using a web-based randomisation programme to either four sessions of nurse-delivered sleep restriction therapy plus a sleep hygiene booklet or a sleep hygiene booklet only. There was no restriction on usual care for either group. Outcomes were assessed at 3 months, 6 months, and 12 months. The primary endpoint was self-reported insomnia severity at 6 months measured with the insomnia severity index (ISI). The primary analysis included participants according to their allocated group and who contributed at least one outcome measurement. Cost-effectiveness was evaluated from the UK National Health Service and personal social services perspective and expressed in terms of incremental cost per quality-adjusted life year (QALY) gained. The trial was prospectively registered (ISRCTN42499563). FINDINGS: Between Aug 29, 2018, and March 23, 2020 we randomly assigned 642 participants to sleep restriction therapy (n=321) or sleep hygiene (n=321). Mean age was 55·4 years (range 19-88), with 489 (76·2%) participants being female and 153 (23·8%) being male. 580 (90·3%) participants provided data for at least one outcome measurement. At 6 months, mean ISI score was 10·9 (SD 5·5) for sleep restriction therapy and 13·9 (5·2) for sleep hygiene (adjusted mean difference -3·05, 95% CI -3·83 to -2·28; p<0·0001; Cohen's d -0·74), indicating that participants in the sleep restriction therapy group reported lower insomnia severity than the sleep hygiene group. The incremental cost per QALY gained was £2076, giving a 95·3% probability that treatment was cost-effective at a cost-effectiveness threshold of £20 000. Eight participants in each group had serious adverse events, none of which were judged to be related to intervention. INTERPRETATION: Brief nurse-delivered sleep restriction therapy in primary care reduces insomnia symptoms, is likely to be cost-effective, and has the potential to be widely implemented as a first-line treatment for insomnia disorder. FUNDING: The National Institute for Health and Care Research Health Technology Assessment Programme.

Role of cytokines in development of pre-eclampsia associated with periodontal disease - Cohort Study.

AIM: The present study was designed to find any association of cytokines in women with periodontal disease and development of pre-eclampsia in North Indian population. MATERIALS AND METHODS: A total of 504 consecutively registered primigravida with a single live pregnancy were recruited at 14-18 weeks of gestation from antenatal clinic of Maulana Azad Medical College & associated Lok Nayak Hospital and Maulana Azad Institute of Dental Sciences, New Delhi. One periodontist performed oral health examination of all patients at inclusion into study. Blood samples were collected to measure the level of cytokines IL-4, IL-10, TNF-α and IFN-γ. RESULTS: The profile of blood levels of cytokines from women with periodontal disease was observed. The log serum levels of TNF-α & IL-4 at 16-18 weeks of gestation were significantly higher in women with periodontal disease (4.13 ± 2.06; 0.47 ± 1.56 pg/ml respectively) than in women with healthy gums (2.16 ± 1.51; 0.02 ± 1.84 pg/ml respectively, p < 0.001). Periodontal disease is associated with log serum TNF-α levels at cut-off ≥14.43 pg/ml at sensitivity 71.2% and specificity 62% (OR = 4.04; 95%CI = 2.77-5.87). Woman with periodontal disease who later developed pre-eclampsia had lower levels of TNF-α (3.72 ± 1.33 pg/ml) than those with periodontal disease who did not develop pre-eclampsia (4.20 ± 2.15 pg/ml, p ≥ 0.05). CONCLUSION: Reduced TNF-α level secretion in the early second trimester in women with periodontal disease appears to be associated with the development of pre-eclampsia.

Nurse-delivered sleep restriction therapy in primary care for adults with insomnia disorder: a mixed-methods process evaluation.

BACKGROUND: Sleep restriction therapy (SRT) is a behavioural therapy for insomnia. AIM: To conduct a process evaluation of a randomised controlled trial comparing SRT delivered by primary care nurses plus a sleep hygiene booklet with the sleep hygiene booklet only for adults with insomnia disorder. DESIGN AND SETTING: A mixed-methods process evaluation in a general practice setting. METHOD: Semi-structured interviews were conducted in a purposive sample of patients receiving SRT, the practice nurses who delivered the therapy, and also GPs or practice managers at the participating practices. Qualitative data were explored using framework analysis, and integrated with nurse comments and quantitative data, including baseline Insomnia Severity Index score and serial sleep efficiency outcomes to investigate the relationships between these. RESULTS: In total, 16 patients, 13 nurses, six practice managers, and one GP were interviewed. Patients had no previous experience of behavioural therapy, needed flexible appointment times, and preferred face-to-face consultations; nurses felt prepared to deliver SRT, accommodating patient concerns, tailoring therapy, and negotiating sleep timings despite treatment complexity and delays between training and intervention delivery. How the intervention produced change was explored, including patient and nurse interactions and patient responses to SRT. Difficulties maintaining SRT, negative attitudes towards treatment, and low self-efficacy were highlighted. Contextual factors, including freeing GP time, time constraints, and conflicting priorities for nurses, with suggestions for alternative delivery options, were raised. Participants who found SRT a positive process showed improvements in sleep efficiency, whereas those who struggled did not. CONCLUSION: SRT was successfully delivered by practice nurses and was generally well received by patients, despite some difficulties delivering and applying the intervention in practice.

IL-10, TNF-α & IFN-γ: potential early biomarkers for preeclampsia.

The present study was designed to evaluate levels of IL4, IL10, TNF-α & IFN-γ at early second trimester and 24h from delivery to assess potential correlation of cytokine variation with preeclampsia. A total of 176 consecutive healthy, normotensive primigravidas with uncomplicated singleton pregnancies were recruited at 14-18weeks of gestation. Serum cytokine levels were estimated at recruitment and 24h from delivery. In present study, 14(7.95%) women developed preeclampsia. Levels of IL-10, TNF-α and IFN-γ (Mean±SE) at recruitment were statistically significantly lower in preeclamptic group (39.21±9.46pg/mL, 73.57±13.37pg/mL and 0.70±0.20pg/mL, respectively) than non-preeclamptic group (86.02±4.55pg/mL, 601.37±63.54pg/mL and 1.67±0.08pg/mL, respectively) (p<0.05). In preeclamptic group, IL-4 and TNF-α levels (Mean±SE) were significantly higher 24h from delivery (5.35±0.95pg/mL and 381.21±43.28pg/mL, respectively) than at recruitment (2.39±0.71pg/mL and 73.57±13.37pg/mL) (p=0.019 and 0.0001, respectively) while IL-10 and IFN-γ levels decreased after delivery but the change was not statistically significant. Therefore, the levels of IL-10, TNF-α and IFN-γ between 14 and 18weeks of gestation may act as potential early biomarkers in the diagnosis of preeclampsia.

Association of maternal periodontal health with adverse pregnancy outcome.

AIM: The present study aims to determine the association of periodontal disease (identified early in pregnancy) and adverse pregnancy outcomes in a North Indian population. MATERIAL AND METHODS: A total of 340 primigravida women, aged 20-35 years with single live pregnancy were recruited at 14-20 weeks period of gestation from the antenatal clinic. These women had undergone periodontal examination at time of recruitment. The pregnancy outcomes were recorded. RESULTS: Out of 340 primigravida women, 147 (43.23%) women had gingivitis and 61 (17.94%) women had periodontitis. Periodontitis was found to be significantly associated with pre-eclampsia, intrauterine growth restriction, preterm delivery, and low birthweight with odds ratios (95% confidence interval) of 7.48 (2.72-22.42), 3.35 (1.20-9.55), 2.72 (1.30-5.68) and 3.03 (1.53-5.97), respectively. CONCLUSIONS: The study shows a significant association between periodontitis (but not with gingivitis) and adverse pregnancy outcomes. Maternal periodontitis is associated with an increased risk of pre-eclampsia, intrauterine growth restriction, preterm delivery and low birthweight infants.

Hepatitis B virus BCP, Precore/core, X gene mutations/genotypes and the risk of hepatocellular carcinoma in India.

The study aims to characterize mutations of the HBV genome involving BCP, Precore/core and X regions and also defines HBV genotypes in patients of hepatocellular carcinoma (HCC). The study involved 150 HBV-related HCC cases and 136 HBV-related chronic liver disease patients without HCC as controls. HBV DNA was subjected to mutational analysis using SSCP technique, genotyping by RFLP, and direct nucleotide sequencing. HBV DNA was found in 58.7% (88/150) of the HCC cases and 74.3% (101/136) of controls. HBV mutants were observed in 44.3% of HCC cases and 43.2% of controls. HBV/D was prevalent amongst the patients and controls, followed by HBV/A. The prevalence of the TT1504 mutation in the X gene, the V1753 and T1762/A1764 mutations in the BCP region, and G1914 mutation in the core gene were significantly higher in the HCC group than in the non-HCC group. Multivariate analyses showed that the TT1504, V1753, A1762T/G1764A, and the G1914 mutations and the patient's age, sex, and HBeAg status increased the risk of HCC development significantly. Also, patients with HCC had lower levels of serum albumin, viral load, and platelet counts but higher values of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, and Alpha feto-protein than those of controls (P < 0.001 for all comparisons). HBV/D was the predominant genotype associated with HCC cases seen in India. The presence of different types of HBV mutations, age, sex, HBeAg status, and viral load was found to increase significantly the risk of HCC development in India.

Molecular analysis of swine hepatitis E virus from north India.

BACKGROUND & OBJECTIVES: Hepatitis E is the main cause of enterically transmitted non-A, non-B hepatitis in developing countries. In the developed countries such as the USA, Japan and Taiwan, the viruses infecting humans and swine share the same genotype with a high sequence similarity. Genotype 1 circulates in humans whereas genotype 4 in pigs in India. The present study was designed to investigate the presence of anti-HEV antibodies and HEV-RNA in swine population from north India, to investigate the genotype prevalent in it, and to compare it with other swine and human HEV strains from India. METHODS: A total of 67 serum samples were collected from pigs of age period (1-6 months) from Indian Veterinary Research Institute (IVRI), Izatnagar, Bareily and subjected to anti-HEV IgG and HEV RNA detection. A phylogenetic tree was constructed using the neighbor-joining method and evaluated using the interior branch test method with MEGA 4 software. RESULTS: Anti-HEV IgG and HEV RNA was found in 38.8 and 4.5 per cent of swine samples studied respectively. The above samples were observed to be of genotype 4e. The three new sequences had nucleotide similarity with other swine sequences in genotype 4 ranging from 80-98 per cent. INTERPRETATION & CONCLUSIONS: The three sequences observed in the present study showed nucleotide similarity with other swine sequences from southern and western India. The present study suggests that genotype 4 'e' is prevalent in the north India.

Primary care treatment of insomnia: study protocol for a pragmatic, multicentre, randomised controlled trial comparing nurse-delivered sleep restriction therapy to sleep hygiene (the HABIT trial).

INTRODUCTION: Insomnia is a prevalent sleep disorder that negatively affects quality of life. Multicomponent cognitive-behavioural therapy (CBT) is the recommended treatment but access remains limited, particularly in primary care. Sleep restriction therapy (SRT) is one of the principal active components of CBT and could be delivered by generalist staff in primary care. The aim of this randomised controlled trial is to establish whether nurse-delivered SRT for insomnia disorder is clinically and cost-effective compared with sleep hygiene advice. METHODS AND ANALYSIS: In the HABIT (Health-professional Administered Brief Insomnia Therapy) trial, 588 participants meeting criteria for insomnia disorder will be recruited from primary care in England and randomised (1:1) to either nurse-delivered SRT (plus sleep hygiene booklet) or sleep hygiene booklet on its own. SRT will be delivered over 4 weekly sessions; total therapy time is approximately 1 hour. Outcomes will be collected at baseline, 3, 6 and 12 months post-randomisation. The primary outcome is self-reported insomnia severity using the Insomnia Severity Index at 6 months. Secondary outcomes include health-related and sleep-related quality of life, depressive symptoms, use of prescribed sleep medication, diary and actigraphy-recorded sleep parameters, and work productivity. Analyses will be intention-to-treat. Moderation and mediation analyses will be conducted and a cost-utility analysis and process evaluation will be performed. ETHICS AND DISSEMINATION: Ethical approval was granted by the Yorkshire and the Humber - Bradford Leeds Research Ethics Committee (reference: 18/YH/0153). We will publish our primary findings in high-impact, peer-reviewed journals. There will be further outputs in relation to process evaluation and secondary analyses focussed on moderation and mediation. Trial results could make the case for the introduction of nurse-delivered sleep therapy in primary care, increasing access to evidence-based treatment for people with insomnia disorder. TRIAL REGISTRATION NUMBER: ISRCTN42499563.

Seroprevalence of subclinical HEV infection in pregnant women from north India: a hospital based study.

BACKGROUND & OBJECTIVE: Hepatitis E virus (HEV) is a major public health problem in the developing countries. HEV infection in pregnant women is more common and fatal in the third trimester. The mortality rate due to HEV-induced hepatitis is as high as 15-20 per cent. The present study was designed to determine the seroprevalence of subclinical HEV infection in pregnant primigravidae women. METHODS: A total of 300 asymptomatic healthy primigravidae (gestational age 16-24 wk) with no history of jaundice were included in the study. Prevalence of anti-HEV antibodies was determined by an enzyme linked immunosorbent assay (ELISA) kit. RESULTS: The overall prevalence of seropositive HEV IgG was 33.67 per cent among the pregnant women. The seropositivity of HEV IgG was significantly high in urban population (P<0.05), and related with the period of settlement (P<0.05) and source of water (P=0.05). Low socio-economic status of the pregnant women appeared to be the only risk factor (OR=1.96, CI=1.17-3.28) associated with HEV IgG antibody. INTERPRETATION & CONCLUSION: In the present study, exposure to HEV during pregnancy was higher in urban (slum areas) than rural population. Socio-economic status was a risk factor for anti-HEV IgG in pregnant women. Early preventive measures if taken, may decrease the maternal and perinatal mortality and morbidity of HEV infection.

Expression profile of MicroRNA: An Emerging Hallmark of Cancer.

MicroRNA (miRNAs), a class of small, endogenous non-coding RNA molecules of about 21-24 nucleotides in length, have unraveled a new modulatory network of RNAs that form an additional level of posttranscriptional gene regulation by targeting messenger RNAs (mRNAs). These miRNAs possess the ability to regulate gene expression by modulating the stability of mRNAs, controlling their translation rates, and consequently regulating protein synthesis. Substantial experimental evidence established the involvement of miRNAs in most biological processes like growth, differentiation, development, and metabolism in mammals including humans. An aberrant expression of miRNAs has been implicated in several pathologies, including cancer. The association of miRNAs with tumor growth, development, and metastasis depicts their potential as effective diagnostic and prognostic biomarkers. Furthermore, exploitation of the role of different miRNAs as oncogenes or tumor suppressors has aided in designing several miRNA-based therapeutic approaches for treating cancer patients whose clinical trials are underway. In this review, we aim to summarize the biogenesis of miRNAs and the dysregulations in these pathways that result in various pathologies and in some cases, resistance to drug treatment. We provide a detailed review of the miRNA expression signatures in different cancers along with their diagnostic and prognostic utility. Furthermore, we elaborate on the potential employment of miRNAs to enhance cancer cell apoptosis, regress tumor progression and even overcome miRNA-induced drug resistance.

Resveratrol reverses the adverse effects of bevacizumab on cultured ARPE-19 cells.

Age-related macular degeneration (AMD) and proliferative diabetic retinopathy (PDR) are one of the major causes of blindness caused by neo-vascular changes in the retina. Intravitreal anti-VEGF injections are widely used in the treatment of wet-AMD and PDR. A significant percentage of treated patients have complications of repeated injections. Resveratrol (RES) is a polyphenol phytoalexin with anti-oxidative, anti-inflammatory and anti-proliferative properties. Hence, we hypothesized that if RES is used in combination with bevacizumab (BEV, anti-VEGF), it could reverse the adverse effects that precipitate fibrotic changes, drusen formation, tractional retinal detachment and so on. Human retinal pigment epithelial cells were treated with various combinations of BEV and RES. There was partial reduction in secreted VEGF levels compared to untreated controls. Epithelial-mesenchymal transition was lower in BEV + RES treated cultures compared to BEV treated cultures. The proliferation status was similar in BEV + RES as well as BEV treated cultures both groups. Phagocytosis was enhanced in the presence of BEV + RES compared to BEV. Furthermore, we observed that notch signaling was involved in reversing the adverse effects of BEV. This study paves way for a combinatorial strategy to treat as well as prevent adverse effects of therapy in patients with wet AMD and PDR.

Virological course of hepatitis A virus as determined by real time RT-PCR: Correlation with biochemical, immunological and genotypic profiles.

AIM: To undertake analysis of hepatitis A viral load, alanine aminotransferase (ALT), and viral genotypes with duration of viremia, and to correlate these parameters with CD4(+)/ CD8(+) lymphocyte populations that control cell-mediated immunity. METHODS: Cell counts were carried out using fresh whole blood collected in EDTA vials using a fluorescence activated cell sorter. Hepatitis A virus (HAV) RNA was extracted from blood serum, reverse transcribed into cDNA and quantified by Real-Time polymerase chain reaction and was genotyped. RESULTS: Among 11 patients, 10 could be analyzed completely. Of these, 3 had severe acute hepatitis (s-AH) and the remainder had a self-limited acute hepatitis A (AHA), with one patient with fulminant disease (encephalopathy Grade IV) dying on the 4th d. The ALT level was significantly higher both in AHA (1070.9 +/- 894.3; P = 0.0014) and s-AH (1713.9 +/- 886.3; P = 0.001) compared to normal controls (23.6 +/- 7.2). The prothrombin time in s-AH patients (21.0 +/- 2.0; P = 0.02) was significantly higher than in AHA (14.3 +/- 1.1; P = 0.44). The CD4(+)/CD8(+) ratio in AHA patients (1.17 +/- 0.11; P = 0.22) and s-AH (0.83 +/- 0.12; P = 0.0002) were lower than seen in normal healthy controls (1.52). Self-limited cases had peak viral load at the beginning of analysis while in s-AH patients this occurred at the 15th or 30th d. In acute and severe groups, one patient each belonged to genotype IA, with the remaining 8 cases belonging to genotype IIIA. The only fulminant hepatic failure case belonged to genotype IA. HAV viral load and ALT values collected during the entire course of the self-limited infection were directly correlated but this was not the case for s-AH patients. CONCLUSION: Based on a small-scale study, the persistently higher viral load of s-AH might be due to diminished cellular immunity and hemolysis. The duration of viremia was dependent on the host, as the viral genotype had no apparent role in clinical outcome of AVH and s-AH cases.

Short Pulse of Clinical Concentration of Bevacizumab Modulates Human Retinal Pigment Epithelial Functionality.

PURPOSE: Cross-talk between Notch signaling and vascular endothelial growth factor (VEGF) is a major driver of angiogenesis. Here we investigated the temporal effect of bevacizumab (BEV) on Notch signaling and the functional features of cultured primary retinal pigment epithelial (PRPE) cells. METHODS: Human (cadaver) PRPE cells were treated with clinical concentrations of BEV (0.25 mg/mL). Notch signaling pathway receptors, ligands, and downstream target genes were analyzed with quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation along with phagocytosis and transmembrane potential was analyzed by fluorescent activated cell sorter (FACS) and immunofluorescence. RESULTS: Bevacizumab-treated PRPE cultures revealed a significant temporal downregulation of notch4 (P < 0.05) and Delta-like-4 (P < 0.005) gene (16% reduced) and protein (29.7% reduced) expression only at the 2-hour exposure, though secreted VEGF levels were significantly blocked (P < 0.005) at all the time points (2, 4, 6 hours). Further, a significant downregulation (P < 0.005) in cell cycle (reduced by 34.1%) and a concurrent (P < 0.005) upregulation of F-actin staining (increased by 2.5-fold) could be detected. Bevacizumab-treated PRPE cells revealed an elevated transmembrane potential (by 63%) and significant decrease (P < 0.01) in phagocytosis (by 19.25%) in comparison to untreated controls. CONCLUSIONS: There is temporal interaction between BEV and the Notch signaling pathway, specifically with Notch4 and Delta-like-ligand-4 in PRPE cultures. This transient decrease in Notch signaling can impact the functionality of RPE cells. These findings can help to provide a better understanding of the effect of long-term usage of anti-VEGF agents in the treatment of retinal degenerative and vitreoretinopathy diseases.

Computational Docking Study of p7 Ion Channel from HCV Genotype 3 and Genotype 4 and Its Interaction with Natural Compounds.

BACKGROUND: The current standard care therapy for hepatitis C virus (HCV) infection consists of two regimes, namely interferon-based and interferon-free treatments. The treatment through the combination of ribavirin and pegylated interferon is expensive, only mildly effective, and is associated with severe side effects. In 2011, two direct-acting antiviral (DAA) drugs, boceprevir and telaprevir, were licensed that have shown enhanced sustained virologic response (SVR) in phase III clinical trial, however, these interferon-free treatments are more sensitive to HCV genotype 1 infection. The variable nature of HCV, and the limited number of inhibitors developed thus aim in expanding the repertoire of available drug targets, resulting in targeting the virus assembly therapeutically. AIM: We conducted this study to predict the 3D structure of the p7 protein from the HCV genotypes 3 and 4. Approximately 63 amino acid residues encoded in HCV render this channel sensitive to inhibitors, making p7 a promising target for novel therapies. HCV p7 protein forms a small membrane known as viroporin, and is essential for effective self-assembly of large channels that conduct cation assembly and discharge infectious virion particles. METHOD: In this study, we screened drugs and flavonoids known to disrupt translation and production of HCV proteins, targeted against the active site of p7 residues of HCV genotype 3 (GT3) (isolatek3a) and HCV genotype 4a (GT4) (isolateED43). Furthermore, we conducted a quantitative structure-activity relationship and docking interaction study. RESULTS: The drug NB-DNJ formed the highest number of hydrogen bond interactions with both modeled p7 proteins with high interaction energy, followed by BIT225. A flavonoid screen demonstrated that Epigallocatechin gallate (EGCG), nobiletin, and quercetin, have more binding modes in GT3 than in GT4. Thus, the predicted p7 protein molecule of HCV from GT3 and GT4 provides a general avenue to target structure-based antiviral compounds. CONCLUSIONS: We hypothesize that the inhibitors of viral p7 identified in this screen may be a new class of potent agents, but further confirmation in vitro and in vivo is essential. This structure-guided drug design for both GT3 and GT4 can lead to the identification of drug-like natural compounds, confirming p7 as a new target in the rapidly increasing era of HCV.

Zinc in CSF of patients with febrile convulsion.

OBJECTIVE: This prospective study was carried out from July-December 1999 to see the status of zinc in CSF of children with febrile convulsion and to compare this to that of control. METHODS: Forty-two cases of febrile convulsion and 30 controls (fever without convulsion) were enrolled into the study. CSF zinc was estimated by atomic absorption spectrophotometry (AAS) in Atomic Energy Center, Dhaka and compared between the two groups. RESULTS: The mean zinc level in CSF in the study sample was 40.19mgm/L and that in control was 74.98mgm/L. This difference was statistically significant (p<0.001). CONCLUSION: The study concludes that a significantly lower of zinc exists in CSF of children with febrile. However no relationship was found between CSF zinc status with age, sex, degree & duration of fever and time of lumbar puncture after convulsion.

RETRACTED: Oral dydrogesterone treatment during early pregnancy to prevent recurrent pregnancy loss and its role in modulation of cytokine production: a double-blind, randomized, parallel, placebo-controlled trial.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the ASRM Publications Committee. The Committee reviewed concerns related to the accuracy of data reported in Table 2 and the authors acknowledged significant errors that could not be corrected because they were unable to provide the original data. As the Committee cannot vouch for the accuracy of the data, we have issued a retraction of this article.

In silico studies of medicinal compounds against hepatitis C capsid protein from north India.

Hepatitis viral infection is a leading cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Over one million people are estimated to be persistently infected with hepatitis C virus (HCV) worldwide. As capsid core protein is the key element in spreading HCV; hence, it is considered to be the superlative target of antiviral compounds. Novel drug inhibitors of HCV are in need to complement or replace the current treatments such as pegylated interferon's and ribavirin as they are partially booming and beset with various side effects. Our study was conducted to predict 3D structure of capsid core protein of HCV from northern part of India. Core, the capsid protein of HCV, handles the assembly and packaging of HCV RNA genome and is the least variable of all the ten HCV proteins among the six HCV genotypes. Therefore, we screened four phytochemicals inhibitors that are known to disrupt the interactions of core and other HCV proteins such as (a) epigallocatechin gallate (EGCG), (b) ladanein, (c) naringenin, and (d) silybin extracted from medicinal plants; targeted against active site of residues of HCV-genotype 3 (G3) (Q68867) and its subtypes 3b (Q68861) and 3g (Q68865) from north India. To study the inhibitory activity of the recruited flavonoids, we conducted a quantitative structure-activity relationship (QSAR). Furthermore, docking interaction suggests that EGCG showed a maximum number of hydrogen bond (H-bond) interactions with all the three modeled capsid proteins with high interaction energy followed by naringenin and silybin. Thus, our results strongly correlate the inhibitory activity of the selected bioflavonoid. Finally, the dynamic predicted capsid protein molecule of HCV virion provides a general avenue to target structure-based antiviral compounds that support the hypothesis that the screened inhibitors for viral capsid might constitute new class of potent agents but further confirmation is necessary using in vitro and in vivo studies.

Biomarkers for virus-induced hepatocellular carcinoma (HCC).

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and is advanced by severe viral hepatitis B or C (HBV or HCV) as well as alcoholic liver disease. Many patients with early disease are asymptomatic therefore HCC is frequently diagnosed late requiring costly surgical resection or transplantation. The available non-invasive detections systems are based on the clinical utility of alpha fetoprotein (AFP) measurement, together with ultrasound and other more sensitive imaging techniques. The hallmark of liver disease and its propensity to develop into fully blown HCC is depended on several factors including the host genetic make-up and immune responses. While common symptoms involve diarrhea, bone pain, dyspnea, intraperitoneal bleeding, obstructive jaundice, and paraneoplastic syndrome, the evolution of cell and immune markers is important to understand viral induced liver cancers in humans. The circulating miRNA, cell and immune based HCC biomarkers are imperative candidates to successfully develop strategies to restrain liver injury. The current molecular genetics and proteomic analysis have lead to the identification of number of key biomarkers for HCC for earlier diagnosis and more effective treatment of HCC patients. In this review article, we provide latest updates on the biomarkers of HBV or HCV-associated HCC and their co-evolutionary relationship with liver cancer.

Latent celiac disease in reproductive performance of women.

OBJECTIVE: To investigate the prevalence of positive serologic findings for celiac disease in Indian women with poor reproductive performance. DESIGN: Cross-sectional except that the women with intrauterine growth restriction were followed prospectively until delivery. SETTING: Department of Obstetrics and Gynecology of a tertiary teaching hospital, New Delhi. PATIENT(S): Eight hundred ninety-three women (104 women with idiopathic recurrent abortion, 104 women with unexplained stillbirth, 230 cases of unexplained infertility, 150 pregnant women with idiopathic intrauterine growth restriction, 305 control cases). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The presence of antigliadin IgA and IgG, anti-tissue transglutaminase IgA by ELISA, and IgA antiendomysium antibody by indirect immunofluorescence microscopy. RESULT(S): The seroprevalence of transglutaminase IgA was 6.70% in the group with recurrent abortion, 5.70% in the group with stillbirth, 5.65% in the group with infertility, 9.33% in the group with intrauterine growth restriction, and 1.30% in the control group. Rates of previous preterm births, low-birth-weight infants, and cesarean section were higher in seropositive women compared with seronegative subjects. CONCLUSION(S): Women having poor reproductive performance had subclinical celiac disease. The serology for celiac disease can be considered in idiopathic cases.

Duration of hepatitis E viremia in pregnancy.

OBJECTIVE: To investigate the duration of hepatitis E virus (HEV) infection in pregnant and non-pregnant women with acute viral hepatitis (AVH) or fulminant hepatic failure (FHF). METHODS: A prospective study conducted with 20 pregnant women with AVH, 20 non-pregnant women with AVH, 10 pregnant women with FHF, and 9 non-pregnant women with FHF-all with HEV infection. The women were followed up on day 7, 15, 30, 60, and 90 following recruitment for the presence of HEV-RNA. RESULTS: Of the 59 patients with HEV infection, only 2 (3.4%) revealed HEV viremia at day 30 and none of the patients was viremic at day 60 and day 90. The proportion of HEV viremia in pregnant women with AVH and FHF at day 15 was significantly higher than in non-pregnant women (88.3% vs 27.6%; P<0.001). Similarly, HEV viremia among patients with AVH was significantly higher in pregnant women compared with non-pregnant women (100% vs 55%; P<0.001). CONCLUSION: HEV viremia may be prolonged in pregnancy.