Ambulatory human chorionic gonadotrophin (hCG) testing: a verification of two hCG point of care devices.

OBJECTIVES: Quantitative human chorionic gonadotropin (hCG) measurements are used to manage women classified with a pregnancy of unknown location (PUL). Two point of care testing (POCT) devices that quantify hCG are commercially available. We verified the i-STAT 1 (Abbott) and the AQT 90 FLEX (Radiometer) prior to use in PUL triage. METHODS: Tests for precision, external quality assurance (EQA), correlation, hook effect and recovery were undertaken alongside a POCT usability assessment during this prospective multi-center verification. RESULTS: Coefficients of variation ranged between 4.0 and 5.1 % for the three i-STAT 1 internal quality control (IQC) solutions and between 6.8 and 7.3 % for the two AQT IQC solutions. Symmetric differences in POCT EQA results when compared with laboratory and EQA stock values ranged between 3.2 and 24.5 % for the i-STAT 1 and between 3.3 and 36.9 % for the AQT. Correlation coefficients (i-STAT 1: 0.96, AQT: 0.99) and goodness of fit curves (i-STAT 1: 0.92, AQT: 0.99) were excellent when using suitable whole blood samples. An hCG hook effect was noted with the i-STAT 1 between 572,194 and 799,089 IU/L, lower than the hook effect noted with the AQT, which was between 799,089 and 1,619,309 IU/L. When hematocrit concentration was considered in sample types validated for use with each device, hCG recovery was 108 % with the i-STAT 1 and 98 % with the AQT. The i-STAT 1 scored lower on usability overall (90/130) than the AQT (121/130, p<0.001, Mann-Whitney). CONCLUSIONS: Both hCG POCT devices were verified for use in clinical practice. Practical factors must also be considered when choosing which device to use in each unit.

Is there a role for carbetocin in the prophylaxis of postpartum obstetric haemorrhage?

Postpartum haemorrhage is a common complication of pregnancy, most commonly due to uterine atony. Uterotonics have a vital role in preventing postpartum haemorrhage but the choice of the most effective agent with the fewest adverse effects is a subject of debate. Carbetocin, a synthetic analogue of oxytocin has been available in the UK since 2007 but is not currently widely used. It has a longer duration of action than oxytocin, which avoids the need for an infusion and as it is heat-stable it can be stored at room temperature. Current UK clinical guidelines, based on the results of older meta-analyses, do not recommend carbetocin as a first-line agent. A Cochrane review, published in 2018, ranked carbetocin in the top three drug regimens for preventing postpartum haemorrhage and an international consensus statement on uterotonic use for caesarean birth concluded that carbetocin may become the preferred drug for caesarean birth, by reducing the need for additional uterotonics. The higher cost of carbetocin when compared with oxytocin is a limiting factor, but the significant healthcare costs of a postpartum haemorrhage and the physiological impact of this event suggests it a reasonable alternative to consider, especially if ergometrine is contraindicated or in those who are undergoing a caesarean birth or are at high risk of bleeding.

Immunotherapy to improve pregnancy outcome in women with abnormal natural killer cell levels/activity and recurrent miscarriage or implantation failure: A systematic review and meta-analysis.

There is a trend towards offering immunotherapy to women with unexplained reproductive failure based on abnormal Natural Killer (NK) cell levels. Previous systematic reviews evaluating immunotherapy usage have not focused on women with abnormal level of NK cells. To address the gap in literature, this systematic review aims to evaluate the efficacy of immunotherapy to improve pregnancy outcome in women with recurrent miscarriage (RM) or implantation failure (RIF) specifically selected based on abnormal levels and/or activity of NK cells. Six databases were searched for peer-reviewed studies following PRISMA guidelines. Risk of bias assessment was conducted using RoB2 for randomized controlled trials (RCT) and ROBINS-I for non-RCT. Of 1025 studies identified, seven studies on intravenous immunoglobulin (IVIG) (four), prednisolone (one), etanercept (one) and intralipid (one) were included. Meta-analysis of the non-RCT IVIG studies (557 participants; 312 intervention, 245 controls) showed livebirth in favour of intervention (RR 2.57; 95 % CI = 1.79-3.69; p < 0.05), however there were significant heterogeneity (I2 = 62 %) and moderate to severe risk of bias in these studies. Individual RCTs reported improved livebirth outcome in etanercept, intralipid and prednisolone and this was significant in the former two (p < 0.05). In conclusion, there may be some benefit of immunotherapy, but paucity of high quality evidence means that it is not possible to support the use of immunotherapy even when selected based on abnormal NK cell level/activity. Further research with application of scientifically validated immunological biomarkers in well-planned large scale RCTs will determine whether immunotherapy is beneficial in this subpopulation of women.

Dietary intake of 20 polyphenol subclasses in a cohort of UK women.

BACKGROUND: Establishing and linking the proposed health benefits of dietary polyphenols to their consumption requires measurement of polyphenol intake in appropriate samples and an understanding of factors that influence their intake in the general population. METHODS: This study examined polyphenol intake estimated from 3- and 7-day food diaries in a sample of 246 UK women aged 18-50 years. Estimation of the intake of 20 polyphenol subclasses commonly present in foods consumed by the sample studied was done using Phenol-Explorer(®) and USDA polyphenol databases. Women were participants in the Leeds Women's Wellbeing Study (LWW) (n = 143), a dietary intervention study aimed at overweight women (mean age 37.2 ± 9.4 years; mean BMI 30.8 ± 3.1 kg/m(2)), and the Diet and Health Study (DH) (n = 103) which aimed to examine the relationship between polyphenol intake and cognitive function (mean age 25.0 ± 9.0 years; mean BMI 24.5 ± 4.6 kg/m(2)). RESULTS: The estimated intake of polyphenol subclasses was significantly different between the two samples (p < 0.01) with consumption of 1292 ± 844 and 808 ± 680 mg/day for the LWW and DH groups, respectively. Flavanols and hydroxycinnamic acids were the most important contributors to the polyphenols consumed by both groups, owing to tea and coffee consumption. Other major polyphenol food sources included fruits, vegetables and processed foods. CONCLUSION: Older women consumed more polyphenol-containing foods and beverages, which was due to the higher coffee and tea consumption amongst the LWW participants.

Serum Human Chorionic Gonadotropin (ß- hCG) Clearance Curves in Women with Successfully Expectantly Managed Tubal Ectopic Pregnancies: A Retrospective Cohort Study.

OBJECTIVE: To establish clearance curves for serum ß -hCG in women with successfully expectantly managed tubal ectopic pregnancies. DESIGN: Retrospective cohort study. Non- viable tubal ectopic pregnancy was diagnosed on transvaginal ultrasound. If initial serum ß hCG was less than 5000 IU/L and patients were asymptomatic, expectant management was offered. Patients underwent serial ß hCG measurements until serum ß hCG was less than 20 IU/l, or the urine pregnancy test was negative. SETTING: Early Pregnancy and Gynaecology Assessment Unit, Kings College Hospital, London (December 1998 to July 2006). PATIENTS: We included 161 women with diagnosed non-viable tubal ectopic pregnancy who underwent successful expectant management. MAIN OUTCOME MEASURE: Serum ß hCG level. RESULTS: Mean initial serum ß- hCG was 488 IU/L (41 - 4883) and median serum ß hCG clearance time was 19 days (5 - 82). The average half-life of ß hCG clearance was 82.5 hours (±SD 50.2) in patients with steadily declining serum ß- hCG levels compared to 106.7 hours (±SD 72.0) in patients with primarily plateauing ß-hCG levels in the declining phase. However, these differences were not significant (p>0.05). CONCLUSION: We identified a median follow-up of 19 days until serum ß hCG clearance in women with tubal ectopic pregnancy and successful expectant management. Although non- significant, women with initially plateauing serum ß hCG showed a longer follow-up time until clearance compared to women with steadily declining ß hCG levels. This information may serve as a guideline enabling clinicians to predict the length of follow-up for women with tubal ectopic pregnancy and expectant management.

Fruit intake and cardiovascular disease mortality in the UK Women's Cohort Study.

In observational studies, fruit intake is associated with a reduced risk of cardiovascular disease (CVD), though fruit type has been less frequently explored. The aim of the current study was to explore the association between total fruit and fruit subgroup intake according to polyphenol content and CVD mortality in the UK Women's Cohort Study. Total fruit intake (g/day) derived from a 217-item food frequency questionnaire was obtained from 30,458 women (aged 35-69 years) at baseline from 1995-1998. Fruit intakes were sub-categorised according to similarities in polyphenol profile from Phenol Explorer, including berries, citrus, drupes, pomes and tropical fruits. Mortality events were derived from the NHS Central Register. During the mean follow-up period of 16.7 years, 286 fatal CVD deaths [138 coronary heart disease (CHD), 148 stroke] were observed. Survival analysis was conducted using participants free from history of CVD at baseline. Total fruit intake was associated with lower risk of CVD and CHD mortality, with a 6-7 % reduction in risk for each 80 g/day portion consumed (99 % CI 0.89, 1.00 and 0.85, 1.01 respectively). Concerning particular fruit types, the direction of the associations tended to be inverse, but point estimates and tests for trend were not generally statistically significant. However, women in the highest intake group of grapes and citrus experienced a significant reduction in risk of CVD and stroke respectively compared with non-consumers [HR 0.56 (99 % CI 0.32, 0.98) and 0.34 (0.14, 0.82) respectively]. These findings support promoted guidelines encouraging fruit consumption for health in women, but do not provide strong evidence to suggest that fruit type is as important.

Transport of trans-tiliroside (kaempferol-3-ß-D-(6"-p-coumaroyl-glucopyranoside) and related flavonoids across Caco-2 cells, as a model of absorption and metabolism in the small intestine.

1. Absorption and metabolism of tiliroside (kaempferol 3-ß-D-(6"-p-coumaroyl)-glucopyranoside) and its related compounds kaempferol, kaempferol-3-glucoside and p-coumaric acid were investigated in the small intestinal Caco-2 cell model. Apparent permeation (Papp) was determined as 0.62 × 10(-6) cm/s, 3.1 × 10(-6) cm/s, 0 and 22.8 × 10(-6) cm/s, respectively. 2. Mechanistic study showed that the transportation of tiliroside, kaempferol-3-glucoside and p-coumaric acid in Caco-2 model were transporter(s) involved, while transportation of kaempferol was solely by passive diffusion mechanism. 3. Efflux transporters, multi-drug-resistance-associated protein-2 (MRP2), were shown to play a role in limiting the uptake of tiliroside. Inhibitors of MRP2, (MK571 and rifampicin) and co-incubation with kaempferol (10 µM), increased transfer from the apical to the basolateral side by three to five fold. 4. Metabolites of kaempferol-3-glucoside and p-coumaric acid were not detected in the current Caco-2 model, while tiliroside was metabolised to a limited extent, with two tiliroside mono-glucuronides identified; and kaempferol was metabolised to a higher extent, with three mono-glucuronides and two mono-sulfates identified. 5. In conclusion, tiliroside was metabolised and transported across Caco-2 cell membrane to a limited extent. Transportation could be increased by applying MRP2 inhibitors or co-incubation with kaempferol. It is proposed that tiliroside can be absorbed by human; future pharmacokinetics studies are warranted in order to determine the usefulness of tiliroside as a bioactive agent.

Phytonutrient intakes in relation to European fruit and vegetable consumption patterns observed in different food surveys.

Fruit and vegetables make an important contribution to health, partly due to the composition of phytonutrients, such as carotenoids and polyphenols. The aim of the present study was to quantify the intake of fruit and vegetables across different European countries using food consumption data of increasing complexity: food balance sheets (FBS); the European Food Safety Authority (EFSA) Comprehensive Database; individual food consumption data from the UK National Diet and Nutrition Survey (NDNS). Across Europe, the average consumption of fruit and vegetables ranged from 192 to 824 g/d (FBS data). Based on EFSA data, nine out of fourteen countries consumed < 400 g/d (recommended by the WHO), although even in the highest-consuming countries such as Spain, 36 % did not reach the target intake. In the UK, the average consumption of fruit and vegetables was 310 g/d (NDNS data). Generally, phytonutrient intake increased in accordance with fruit and vegetable intake across all European countries with the exception of lycopene (from tomatoes), which appeared to be higher in some countries that consumed less fruit and vegetables. There were little differences in the average intake of flavanols, flavonols and lycopene in those who did or did not meet the 400 g/d recommendation in the UK. However, average intakes of carotenoid, flavanone, anthocyanidin and ellagic acid were higher in those who consumed >400 g/d of fruit and vegetables compared with those who did not. Overall, intakes of phytonutrients are highly variable, suggesting that while some individuals obtain healthful amounts, there may be others who do not gain all the potential benefits associated with phytonutrients in the diet.

Ultrasound imaging in the management of bleeding and pain in early pregnancy.

Bleeding and pain are experienced by 20% of women during the first trimester of pregnancy. Although most pregnancies complicated by pain and bleeding tend to progress normally, these symptoms are distressing for woman, and they are also associated with an increased risk of miscarriage and ectopic pregnancy. Ultrasound is the first and often the only diagnostic modality that is used to determine location of early pregnancy and to assess its health. Ultrasound is an accurate, safe, painless and relatively inexpensive diagnostic tool, which all contributed to its widespread use in early pregnancy. Pain and bleeding in early pregnancy are sometimes caused by concomitant gynaecological, gastrointestinal, and urological problems, which could also be detected on ultrasound scan. In women with suspected intra-abdominal bleeding, ultrasound scan can be used to detect the presence of blood and provide information about the extent of bleeding. In this chapter, we comprehensively review the use of ultrasound in the diagnosis and management of early pregnancy complications. We include information about the diagnosis of gynaecological and other pelvic abnormalities, which could cause pain or bleeding in pregnancy. We also provide a summary of the current views on the safety of ultrasound in early pregnancy.

Getting the 'blues': the existence, diffusion and influence of pornography on young peoples' sexual health in Sierra Leone.

While substantial research has examined the effects of pornography on young people in developed societies, existing studies fall short in addressing how sexually-explicit material affects young people in developing countries. The importance of such knowledge increases as the globalising effects of technology expand young peoples' access and exposure to pornography. During the summer of 2012, a study was undertaken in Sierra Leone examining factors affecting young peoples' sexual and reproductive health. The research assessed the influence of HIV knowledge, communication about sex, civil war and contraception myths on sexual behaviours, while remaining open to unanticipated factors. During data collection, respondents identified pornography, also called blues, as an influential factor, detailing its newfound accessibility driven by improved access to information and communication technologies in the country. Respondents also addressed several presumed ways in which pornography impacts young peoples' decisions about sexual health. The following study examines perceived effects of young peoples' exposure to pornography based on existing literature. It then outlines the findings of research conducted in Sierra Leone, drawing on primary data from the respondents and relevant published literature and concludes with proposals for addressing its negative effects.

Occupational stress and employee turnover.

Questionnaire data captured in January-March 2007 were examined in relation to turnover in males and females during the next five years. In general, most of the workplace stressors (such as role conflict or peer support) were not antecedents of turnover in any group. Junior personnel with psychological strain in 2007 had an increased risk of turnover in the next five years. Low commitment to the service in 2007 increased the odds of turnover in male and female juniors and in female officers. Female juniors with less effective skills for coping with stress and who exercised less frequently on a weekly basis were more likely to leave. An incidental finding was that the odds of turnover were three times greater in female officers with children than in female officers with no children. Stress management interventions focusing on effective coping and sports and exercise participation which are targeted appropriately may improve retention.

Mesenchymal stromal cells augment CD4+ and CD8+ T-cell proliferation through a CCL2 pathway.

BACKGROUND AIMS: Mesenchymal stromal cells (MSC) derived from bone marrow are immunosuppressive in vitro and in vivo. Recent evidence, however, has shown that in certain settings, MSC can also be immunostimulatory. The mechanisms involved in this process are largely unknown. METHODS: Mouse spleen T cells were stimulated with allogeneic mixed lymphocyte reaction (MLR) or anti-CD3/CD28 beads and treated with autologous bone marrow MSC or MSC-conditioned medium. CD4+ and CD8+ T-cell proliferation was analyzed after treatment. RESULTS: We show that MSC have both suppressive and stimulatory functions toward T cells after stimulation with anti-CD3/CD28 beads or in an MLR. This depended on the ratio of MSC to responder T cells, with low numbers of MSC increasing and higher numbers inhibiting T-cell proliferation. Immunostimulatory function was mediated, in part, by soluble factors. MSC immunosuppression of the MLR was indirect and related to inhibition of antigen-presenting cell maturation. Direct effects of MSC-conditioned medium during anti-CD3/CD28 stimulated proliferation were entirely stimulatory and required the presence of the T-cell receptor. MSC supernatant contained both CCL2 and CCL5 at high levels, but only CCL2 level correlated with the ability to augment proliferation. An anti-CCL2 antibody blocked this proliferative activity. CONCLUSIONS: CCL2 plays an important role in the immunostimulatory function of MSC, and we further hypothesize that the immunomodulatory role of MSC is determined by a balance between inhibitory and stimulatory factors, suggesting the need for caution when these cells are investigated in clinical protocols.

Accident proneness revisited: the role of psychological stress and cognitive failure.

Understanding why accidents occur in the work place has a long and convoluted history. This paper adds to this corpus of research by investigating the relationship between an individual's level of cognitive failure, psychological stress, and work place accident occurrence. Retrospective analysis of accident-case individuals vs. control-match individuals on the General Health Questionnaire (GHQ) and Cognitive Failures Questionnaire (CFQ) was undertaken from amalgamated data of two Royal Navy databases. Individuals in the accident-case sub-sample had higher GHQ and CFQ scores when compared to matched-controls. Mediated regression analysis revealed high GHQ score predicted accidents but was transmitted through high CFQ scores. Individuals who are stressed are more likely to have an accident in the workplace because of a propensity for cognitive failures. A specific recommendation to reduce accident risk in the work-place is discussed.

Effects of pH on the ability of flavonoids to act as Pickering emulsion stabilizers.

The flavonoids tiliroside, rutin and naringin have been investigated as stabilizers of Pickering oil-in-water (O/W) emulsions. The mean droplet size of tetradecane emulsions was considerably smaller at higher pH, especially for rutin. The solubility of flavonoids in the aqueous phase was 4-6 times higher at pH 8 compared to pH 2 for tiliroside and rutin, although all absolute solubilities remained low (<1 mM). This agreed with a slight increase in surface activity of tiliroside and rutin at the O-W interface at pH 8 compared to pH 2. However, improved emulsion stabilization at higher pH is better explained by the significant increase in ζ-potential of the flavonoid particles to more negative values at pH 8, which will improve particle dispersion and increase the charge on the droplets stabilized by them. A buckwheat tea extract, rich in rutin, was also shown to be an effective stabilizer of sunflower O/W emulsions.

Flavanols and methylxanthines in commercially available dark chocolate: a study of the correlation with nonfat cocoa solids.

Intake of flavanols, a subgroup of dietary polyphenols present in many fruits and vegetables, may be associated with health benefits, particularly with reducing the risk of coronary diseases. Cocoa and chocolate products are rich in flavanol monomers, oligomers, and polymers (procyanidins). This study used normal phase HPLC to detect, identify, and quantify epicatechin, catechin, total monomers, procyanidin oligomers and polymers in 14 commercially available chocolate bars. In addition, methylxanthines (theobromine and caffeine) were also quantified. Nonfat cocoa solids (NFCS) were determined both gravimetrically and by calculation from theobromine contents. The flavanol levels of 12 commonly consumed brands of dark chocolate have been quantified and correlated with % theobromine and % NFCS. Epicatechin comprised the largest fraction of total chocolate flavonoids, with the remainder being catechin and procyanidins. Calculated NFCS did not reflect epicatechin (R(2) = 0.41) or total flavanol contents (R(2) = 0.49). Epicatechin (R(2) = 0.96) was a reliable marker of total flavanols, catechin (R(2) = 0.67) to a lesser extent. All dark chocolate tested contained higher levels of total flavanols (93.5-651.1 mg of epicatechin equiv/100 g of product) than a milk or a white "chocolate" (40.6 and 0.0 mg of epicatechin equiv/100 g, respectively). The amount and integrity of procyanidins often suffer in the manufacturing of chocolate, chiefly due to oxidation and alkalinization. In this study, the labeled cocoa content of the chocolate did not always reflect analyzed levels of flavonoids. Increasingly, high % NFCS is being used commercially to reflect chocolate quality. If the flavanol content of chocolate is accepted to be a key determinant of health benefits, then continued monitoring of flavanol levels in commercially available chocolate products may be essential for consumer assurance.

Particle-stabilizing effects of flavonoids at the oil-water interface.

It has been shown that some common food flavonoids can act as excellent stabilizers of oil-in-water emulsions through their adsorption as water-insoluble particles to the surface of the oil droplets, i.e., Pickering emulsions are formed. Flavonoids covering a wide range of octanol-water partition coefficients (P) were screened for emulsification behavior by low shear mixing of flavonoid+n-tetradecane in a vortex mixer. Most flavonoids with very high or very low P values were not good emulsifiers, although there were exceptions, such as tiliroside, which is very insoluble in water. When a high shear jet homogenizer was used with 20 vol% oil in the presence of 1 mM tiliroside, rutin, or naringin, much finer emulsions were produced: the average droplet sizes (d32) were 16, 6, and 5 µm, respectively. These results may be highly significant with respect to the delivery of such insoluble compounds to the gut, as well as their digestion and absorption.

Nível de expressão tumoral da indoleamine 2, 3-dioxigenase (IDO)como marcador biológico e preditor de metástase em pacientes com tumor carcinoide típico broncopulmonar / Tumor expression level of indoleamine 2, 3 dioxygenase as biological marker and metastasis predictor in patients with typical bronchopulmonary carcinoid tumors

Os tumores carcinoides típicos broncopulmonares (TCTB) são considerados neoplasias bem diferenciadas e as menos agressivas dentro do espectro dos tumores neuroendócrinos. Entretanto, metástases linfonodais e hematogênicas tem sido encontradas em número considerável de casos e não existem, até o momento, estudos relacionados aos mecanismos de escape imune tumoral em TCTB. Alguns trabalhos tem relacionado a expressão da enzima indoleamine 2,3-dioxigenase (IDO) em células neoplásicas como fator responsável pela aquisição de tolerância tumoral. Além disso, os níveis de infiltração linfocitária intratumoral parecem estar associados com prognóstico e sobrevida nesses tumores. O principal objetivo deste estudo foi determinar os níveis de expressão intratumorais da IDO e sua possível aplicação como marcador biológico de metástases em TCTB. Além disso, também foi estabelecido o padrão de infiltração linfocitária intratumoral e analisada sua provável correlação com os níveis de expressão da IDO. Portanto, realizou-se uma coorte retrospectiva multicêntrica no qual 64 pacientes submetidos à cirurgia de ressecção de TCTB entre 1981 e 2003 foram selecionados. O período de seguimento pós-operatório foi de 5 anos e a ocorrência de metástases linfonodais (hilar ou mediastinal) e hematogênicas foi avaliada através de tomografia computadorizada. Os níveis da expressão da IDO e de infiltração linfocitária intratumoral foram avaliados através de estudo imunohistoquímico. Os resultados obtidos mostraram que dos 64 pacientes selecionados, 17 (26.5%) apresentaram qualquer tipo de metátases durante o estudo: linfonodal, hematogênica ou ambas. A expressão da IDO foi encontrada em níveis diferentes de intensidade em mais de 80% das células dos TBCT. Entretanto, a análise univariada não mostrou nenhuma diferença significante na expressão da IDO entre grupos com e sem metástase (p=0,9 e p=0,3 pela análise semi-quantitativa e quantitativa, respectivamente). A quantificação dos...

Typical bronchopulmonary carcinoid tumors (TBCT) are considered the less aggressive neoplasm within the spectrum of neuroendocrine tumors. However, regional nodes and haematogenic metastasis occur in a considerable rate and no data regarding immune escape mechanisms in these tumors are available. Some studies have implicated indoleamine 2,3 dioxygenase (IDO) expression in malignant cells as the responsible for tumor tolerance. Also, levels of tumor infiltrating lymphocytes (TILs) seem to be related with prognosis and survival. Our aim in this study was to determine intratumoral IDO expression levels and the value of this variable as a predictive marker of TBCT metastasis. Thus, TILs pattern was determined and correlation with intratumoral IDO expression analyzed. For this purpose, a multicenter retrospective cohort study was performed and 64 patients operated on for TBCT between 1981 and 2003 were enrolled. Follow-up period was 5 years and regional or haematogenic metastasis was assessed by computerized tomography (CT) scan. Levels of IDO expression and TILs were assessed by immunohistochemical study. The results obtained showed that of all 64 patients, 17 (26,5%) presented with any metastasis during the study: regional nodes, haematogenic or both. IDO expression was found in different intensity levels in over 80% of TBCT cells. However, univariate analysis showed no significant difference in IDO expression between groups with and without metastasis (p=0,9 and p=0,3 for semi-quantitative and quantitative analysis respectively). TILs quantification in all studied groups demonstrated predominance of CD8+ TILs when compared to CD4+ TILs (p<0,01). No difference in CD8+ TILs was found between groups with and without metastasis (p=0,98). However CD4+ TILs quantification was null in the groups with any metastasis (p=0,01), and regional nodes metastasis (p=0,02). No correlation between IDO expression levels and TILs was identified in all analyzed groups(r= -0,2)...

Effects of Diffuse Colonization of Grape Berries by Uncinula necator on Bunch Rots, Berry Microflora, and Juice and Wine Quality.

ABSTRACT Production of grape (principally cultivars of Vitis vinifera) for high-quality wines requires a high level of suppression of powdery mildew (Uncinula necator syn. Erysiphe necator). Severe infection of either fruit or foliage has well-documented and deleterious effects upon crop and wine quality. We found that berries nearly immune to infection by U. necator due to the development of ontogenic resistance may still support diffuse and inconspicuous mildew colonies when inoculated approximately 3 weeks post-bloom. Fruit with diffuse mildew colonies appear to be healthy and free of powdery mildew in late-season vineyard assessments with the naked eye. Nonetheless, presence of these colonies on berries was associated with (i) elevated populations of spoilage microorganisms; (ii) increased evolution of volatile ethyl acetate, acetic acid, and ethanol; (iii) increased infestation by insects known to be attracted to the aforementioned volatiles; (iv) increased rotting by Botrytis cinerea; and (v) increased frequency of perceived defects in wines prepared from fruit supporting diffuse powdery mildew colonies. Prevention of diffuse infection requires extending fungicidal protection until fruit are fully resistant to infection. Despite a perceived lack of improvement in disease control due to the insidious nature of diffuse powdery mildew, potential deleterious effects upon crop and wine quality thereby would be avoided.

Xanthine oxidase activity in vitro: effects of food extracts and components.

There is significant interest in the direct antioxidant activities of dietary polyphenols, due to associations between consumption of polyphenol-rich foods, such as fruits and vegetables, and decreased incidence of oxidative-stress related disease. However, indirect antioxidant action, such as the inhibition of ROS-producing enzymes, may be equally relevant to health benefits through a general reduction in oxidative stress in vivo. To this end, the effects of food extracts and individual compounds on the in vitro activity of xanthine oxidase (XO) were assessed, many for the first time. Several compounds were shown to be potent inhibitors in vitro, including hesperetin and theaflavin-3,3'-digallate with IC50 values of 39 and 49 microM, respectively. Of the extracts, cranberry juice, purple grape juice, and black tea were the most potent, with IC50 values of 2.4, 3.5, and 5.8% of extracts, respectively. Some samples were shown to promote XO activity over the concentration ranges tested, including orange juice and pink grapefruit juice. Certain "inhibitors", such as purple grape juice and black tea, promoted XO activity at low concentration. The possible role of dietary inhibitors of XO in reducing oxidative stress in vivo is discussed.