A successful pregnancy outcome following embolisation for post modified Manchester Fothergill haemorrhage: an interesting case report

Genital prolapse is one of the most common disorder affecting women of varying age group; though it typically affects older and parous women. Malfunction of the pelvic support is the most common cause of this disorder. Increasing age and excess weight are established risk factors for pelvic organ prolapse.In young nulliparous women conservative surgery is preferred to preserve the fertility of the patient. The approach of surgery can be either vaginal or abdominal depending on the classification of prolapse. We reported a rare case of a 36-year-old P1L0 (IUFD1) A1 with cervical elongation who was apprehensive to have a child. She was managed at our institute and had a successful pregnancy outcome in spite of undergoing embolization for secondary haemorrhage following modified Manchester-Fothergill operation

Quali-Quantitative Analysis by LC/DAD and GPC of the Polyphenols ofUva Di Troia Canosina Grape Seeds for the Development of an IndustrialNutraceutical Product

The quali-quantitative determination of the principal components of "uva di Troia canosina" seed extracts by LC/ DAD analysis and the optimization of the extraction and purification processes for the development of an industrial nutraceutical product, are described. Two different fractions of seeds collected at different stages of fermentation were compared: "Tesi" 2 when there is a spontaneous stratification of the seeds at the bottom of the recipient and "Tesi" 4 at the end of fermentation. Percolation was applied and compared to maceration and the purification step carefully evaluated to obtain extracts free of contaminant species endowed with polyphenolic content comparable to commercial preparations such as Leucoselect® (Indena, SpA, Italy), Vitis Vinifera extract 95% (seeds), Vitis Vinifera dry extract 95%, Biovin grape seed and vinasse extract. (Farmalabor, Italy). In particular, "Tesi" 2 extract obtained by percolation and purified with a LLE extraction with ethyl acetate showed a polyphenolic content similar to Leucoselect®. From the quantitative analyses it was evident, as expected, that "Tesi"2 has a higher polyphenolic content compared to "Tesi" 4, because during vinification the must extracts polyphenols from the seeds. On the other hand, "Tesi" 4 is particularly convenient since it is easily obtained and very economical, being a waste product. The residual content of organic solvents (ethanol and ethyl acetate) and water was assessed in the grape extracts according to ICH rules by means respectively of HS/GC and Karl Fisher titration in order to meet the requirements for commercialization. Furthermore, the high molecular weight polyphenolic fraction of our extracts was investigated through gel permeation chromatography (GPC) and compared to that of Leucoselect®

Nicotine-induced survival signaling in lung cancer cells is dependent on their p53 status while its down-regulation by curcumin is independent

<p>Abstract</p> <p>Background</p> <p>Lung cancer is the most lethal cancer and almost 90% of lung cancer is due to cigarette smoking. Even though nicotine, one of the major ingredients of cigarette smoke and the causative agent for addiction, is not a carcinogen by itself, several investigators have shown that nicotine can induce cell proliferation and angiogenesis. We observed that the proliferative index of nicotine is different in the lung cancer cell lines H1299 (p53-/-) and A549 (p53+/+) which indicates that the mode of up-regulation of survival signals by nicotine might be different in cells with and without p53.</p> <p>Results</p> <p>While low concentrations of nicotine induced activation of NF-κB, Akt, Bcl2, MAPKs, AP1 and IAPs in H1299, it failed to induce NF-κB in A549, and compared to H1299, almost 100 times higher concentration of nicotine was required to induce all other survival signals in A549. Transfection of WT-p53 and DN-p53 in H1299 and A549 respectively, reversed the mode of activation of survival signals. Curcumin down-regulated all the survival signals induced by nicotine in both the cells, irrespective of their p53 status. The hypothesis was confirmed when lower concentrations of nicotine induced NF-κB in two more lung cancer cells, Hop-92 and NCI-H522 with mutant p53 status. Silencing of p53 in A549 using siRNA made the cells susceptible to nicotine-induced NF-κB nuclear translocation as in A549 DN-p53 cells.</p> <p>Conclusions</p> <p>The present study reveals a detrimental role of nicotine especially in lung cancer patients with impaired p53 status and identifies curcumin as a potential chemopreventive.</p

Milk flow pattern, somatic cell count and teat apex score in primiparous dairy cows at the beginning of lactation

The aim of the study was to investigate the relationships between milk flow traits, milk Somatic Cell Count (SCC) and teat apex score in primiparous cows during the first 120 days of lactation. A total of 82 primiparous Holstein cows were randomly selected in 6 herds characterized by different milking machines and management. The cows were monitored monthly during the first 120 days of lactation. Each month, milk flow curves of the whole udder of each primiparous cow were registered with continuous electronic milk flow meters (Lactocorder), quarter milk samples were aseptically collected, somatic cells were counted, and teat apex scores were assessed. Quarter milk samples were divided in two groups according to SCC: 200,000 cells/ml, respectively. At udder level each cow was classified as low SCC (LSCC) when all quarters had 10 SCC; P<0.05). Moreover, primiparous cows with at least one HSCC control had a significant increase in peak milk flow during the first four months of lactation, while the other cows showed only a slight increase. Teat apex scores significantly increased in both groups of primiparous cows as lactation progressed but values in subjects always classified as LSCC animals were constantly lower with respect to cows with at least one HSCC control. The results obtained in this study support the relationship between SCC, teat apex score and milk flow traits

A prediction rule for lack of achievement of inactive disease with methotrexate as the sole disease-modifying antirheumatic therapy in juvenile idiopathic arthritis

Background: To investigate the frequency of achievement of inactive disease (ID) in children with juvenile idiopathic arthritis (JIA) treated with methotrexate (MTX) as the sole disease-modifyng antirheumatic (DMARD) therapy and to develop a prediction model for lack of attainment of ID. Methods: The clinical charts of consecutive patients started with MTX as the sole DMARD between 2000 and 2013 were reviewed. Patient follow-up was censored at first episode of ID or, in case ID was not reached, at last follow-up visit or when a biologic DMARD was prescribed. The characteristic at MTX start of patients who achieved or did not achieve ID were compared with univariate and multivariable analyses. Regression coefficients (\u3b2) of variables that entered the best-fitting logistic regression model were converted and summed to obtain a "prediction score" for lack of achievement of ID. Results: A total of 375 patients were included in the study. During MTX administration, 8.8% were given systemic corticosteroids and 44.1% intra-articular corticosteroids. After MTX start, 229 (61%) patients achieved ID after a median of 1.7 years, whereas 146 patients (39%) did not reach ID after a median of 1.2 years. On multivariable analysis, independent correlations with lack of achievement of ID were identified for the disease categories of systemic arthritis, enthesitis-related arthritis (ERA) and polyarthritis and C-reactive protein (CRP) &gt; 1.4 mg/dl. The prediction score ranged from 0 to 3 and its cutoff that discriminated best between patients who achieved or did not achieve ID was &gt; 0.5. The categories of systemic arthritis or ERA, both of which had a score greater than 0.5, were sufficient alone to predict a lower likelihood to reach ID. Polyarthritis and increased CRP, whose score was 0.5, assumed a predictive value only when present in association. Conclusion: A conventional treatment regimen based on MTX as the sole DMARD led to achievement of ID in a sizeable proportion of children with JIA. Our findings help to outline the characteristics of patients who may deserve a synthetic DMARD other than MTX or the introduction of a biologic DMARD from disease outset

Rituximab Unveils Hypogammaglobulinemia and Immunodeficiency in Children with Autoimmune Cytopenia

BACKGROUND: Rituximab (RTX; anti-CD20 mAb) is a treatment option in children with refractory immune thrombocytopenia, autoimmune hemolytic anemia (AHA), and Evans syndrome (ES). Prevalence and clinical course of RTX-induced hypogammaglobulinemia in these patients are poorly known. OBJECTIVE: To evaluate the prevalence and risk factors for persistent hypogammaglobulinemia (PH) after RTX use. METHODS: Clinical and immunologic data from children treated with RTX for immune thrombocytopenia, AHA, and ES were collected from 16 Italian centers and 1 UK center at pre-RTX time point (0), +6 months, and yearly, up to 4 years post-RTX. Patients with previously diagnosed malignancy or primary immune deficiency (PID) were excluded. RESULTS: We analyzed 53 children treated with RTX for immune thrombocytopenia (n = 36), AHA (n = 13), and ES (n = 4). Median follow-up was 30 months (range, 12-48). Thirty-two percent of patients (17 of 53) experienced PH, defined as IgG levels less than 2 SD for age at last follow-up (>12 months after RTX). Significantly delayed B-cell recovery was observed in children experiencing PH (hazard ratio, 0.55; P < .05), and 6 of 17 (35%) patients had unresolved B-cell lymphopenia at last follow-up. PH was associated with IgA and IgM deficiency, younger age at RTX use (51 vs 116 months; P < .01), a diagnosis of AHA/ES, and better response to RTX. Nine patients with PH (9 of 17 [53%]) were eventually diagnosed with a PID. CONCLUSIONS: Post-RTX PH is a frequent condition in children with autoimmune cytopenia; a sizable proportion of patients with post-RTX PH were eventually diagnosed with a PID. In-depth investigation for PID is therefore recommended in these patients

Prevalence of contagious and environmental mastitis-causing bacteria in bulk tank milk and its relationships with milking practices of dairy cattle herds in São Miguel Island (Azores)

This study aimed to assess the degree of contamination of bulk tank milk (BTM) by Staphylococcus spp. and coliform bacteria and to identify major milking practices that help perpetuate them in dairy cattle herds in São Miguel Island. In July 2014, BTM was sampled and a survey concerning local milking practices was conducted on 100 herds. Semi quantitative multiplex polymerase chain reaction detected coagulase-negative staphylococci, Escherichia coli, Staphylococcus aureus, and other coliform bacteria (Klebsiella oxytoca, Klebsiella pneumoniae, andSerratia marcescens) in 100, 75, 59, and 35 % of BTM, respectively. According to multivariable univariate models, on herds not using hot water for cleaning the milking machine and teat liners, there was at least 3.4 more odds (P<0.01) to have S. aureus or coliform bacteria contamination in BTM. The likelihoodoffinding S.aureus inBTMwas higher(P<0.001)on herds without high hygiene during milking, when milking mastitic cows at the end, on abrupt cessation of milking at dry-off, and official milk control implementation. The glove use also favored (odds ratio (OR) 5.8; P<0.01)thedetection ofcoliformbacteriainBTM.Poormilkingpracticesidentified in this study should be avoided in order to decrease S. aureus and coliform bacteria contamination of BTM. Other factors associated with milk quality in São Miguel Island also should be further investigated

The semisynthetic flavonoid monoHER sensitises human soft tissue sarcoma cells to doxorubicin-induced apoptosis via inhibition of nuclear factor-κB

Background:Despite therapeutic advances, the prognosis of patients with metastatic soft tissue sarcoma (STS) remains extremely poor. The results of a recent clinical phase II study, evaluating the protective effects of the semisynthetic flavonoid 7-mono-O-(beta-hydroxyethyl)-rutoside (monoHER) on doxorubicin-induced cardiotoxicity, suggest that monoHER enhances the antitumour activity of doxorubicin in STSs.Methods:To molecularly explain this unexpected finding, we investigated the effect of monoHER on the cytotoxicity of doxorubicin, and the potential involvement of glutathione (GSH) depletion and nuclear factor-kappaB (NF-kappaB) inactivation in the chemosensitising effect of monoHER.Results:MonoHER potentiated the antitumour activity of doxorubicin in the human liposarcoma cell line WLS-160. Moreover, the combination of monoHER with doxorubicin induced more apoptosis in WLS-160 cells compared with doxorubicin alone. MonoHER did not reduce intracellular GSH levels. On the other hand, monoHER pretreatment significantly reduced doxorubicin-induced NF-kappaB activation.Conclusion:These results suggest that reduction of doxorubicin-induced NF-kappaB activation by monoHER, which sensitises cancer cells to apoptosis, is involved in the chemosensitising effect of monoHER in human liposarcoma cells

Inferring stabilizing mutations from protein phylogenies : application to influenza hemagglutinin

One selection pressure shaping sequence evolution is the requirement that a protein fold with sufficient stability to perform its biological functions. We present a conceptual framework that explains how this requirement causes the probability that a particular amino acid mutation is fixed during evolution to depend on its effect on protein stability. We mathematically formalize this framework to develop a Bayesian approach for inferring the stability effects of individual mutations from homologous protein sequences of known phylogeny. This approach is able to predict published experimentally measured mutational stability effects (ΔΔG values) with an accuracy that exceeds both a state-of-the-art physicochemical modeling program and the sequence-based consensus approach. As a further test, we use our phylogenetic inference approach to predict stabilizing mutations to influenza hemagglutinin. We introduce these mutations into a temperature-sensitive influenza virus with a defect in its hemagglutinin gene and experimentally demonstrate that some of the mutations allow the virus to grow at higher temperatures. Our work therefore describes a powerful new approach for predicting stabilizing mutations that can be successfully applied even to large, complex proteins such as hemagglutinin. This approach also makes a mathematical link between phylogenetics and experimentally measurable protein properties, potentially paving the way for more accurate analyses of molecular evolution

The association between exposure to social media alcohol marketing and youth alcohol use behaviors in India and Australia

© 2018 The Author(s). Background: Alcohol marketing on social networking sites (SNS) is associated with alcohol use among young people. Alcohol companies adapt their online marketing content to specific national contexts and responses to such content differ by national settings. However, there exists very little academic work comparing the association between alcohol marketing on SNS and alcohol use among young people in different national settings and across different SNS. Therefore, we aimed to extend the limited existing work by investigating and comparing the association between self-reported exposure to alcohol marketing on three leading SNS (Facebook, YouTube, and Twitter) and alcohol use among young people in diverse national contexts (India and Australia). Methods: Cross-sectional, self-report data were obtained from a convenience sample of 631 respondents (330 in India; 301 in Australia) aged 13-25 years via online surveys. Respondents answered questions on their drinking behaviors and involvement with alcohol marketing on SNS. Results: Many respondents from both countries reported interacting with alcohol content online, predominantly on Facebook, followed by YouTube and then Twitter. The interaction was primarily in the forms of posting/liking/sharing/commenting on items posted on alcohol companies' social media accounts, viewing the event page/attending the event advertised by an alcohol company via social media, and/or accessing an alcohol website. Multivariate analyses demonstrated significant associations between respondents' interaction with alcohol content and drinking levels, with effects differing by SNS, demographic group, and country. For example, having friends who shared alcohol-related content was an important predictor of usual alcohol consumption for Indian respondents (p &lt;.001), whereas posting alcohol-related information themselves was a stronger predictor among Australians (p &lt;.001). Conclusions: The results suggest that interaction with alcohol-related content on SNS is associated with young people's alcohol use behaviors and that these behaviors vary by national settings. This study extends previous work by demonstrating this connection across varying social media platforms and national contexts. The results highlight the need to formulate and implement strategies to effectively regulate the SNS alcohol marketing, especially among younger SNS users