[Risks factors associated with intra-partum foetal mortality in pre-term infants].

PubMed

Zeballos Sarrato, Susana; Villar Castro, Sonia; Ramos Navarro, Cristina; Zeballos Sarrato, Gonzalo; Sánchez Luna, Manuel

2017-03-01

Pre-term delivery is one of the leading causes of foetal and perinatal mortality. However, perinatal risk factors associated with intra-partum foetal death in preterm deliveries have not been well studied. To analyse foetal mortality and perinatal risk factors associated with intra-partum foetal mortality in pregnancies of less than 32 weeks gestational age. The study included all preterm deliveries between 22 and 31 +1 weeks gestational age (WGA), born in a tertiary-referral hospital, over a period of 7 years (2008-2014). A logistic regression model was used to identify perinatal risk factors associated with intra-partum foetal mortality (foetal malformations and chromosomal abnormalities were excluded). During the study period, the overall foetal mortality was 63.1% (106/168) (≥22 weeks of gestation) occurred in pregnancies of less than 32 WGA. A total of 882 deliveries between 22 and 31+6 weeks of gestation were included for analysis. The rate of foetal mortality was 11.3% (100/882). The rate of intra-partum foetal death was 2.6% (23/882), with 78.2% (18/23) of these cases occurring in hospitalised pregnancies. It was found that Assisted Reproductive Techniques, abnormal foetal ultrasound, no administration of antenatal steroids, lower gestational age, and small for gestational age, were independent risk factors associated with intra-partum foetal mortality. This study showed that there is a significant percentage intra-partum foetal mortality in infants between 22 and 31+6 WGA. The analysis of intrapartum mortality and risk factors associated with this mortality is of clinical and epidemiological interest to optimise perinatal care and improve survival of preterm infants. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Antenatal diagnosis and management of foetal intestinal volvulus.

PubMed

Yip, K W; Cheng, Y K Y; Leung, T Y

2017-04-01

In-utero intestinal volvulus is a rare but potential life threatening foetal complications. It is a surgical emergency and delay in diagnosis or treatment can increase the morbidity and mortality to the foetus. We report a case of mild foetal bowel dilatation diagnosed at 21 weeks of gestation. She was closely follow up and at 31 weeks of gestation, in-utero intestinal volvulus was diagnosed with the characteristic 'whirlpool' sign on ultrasound examination. This case emphasises the importance of early recognition and quick decision to delivery when intestinal volvulus is diagnosed. This enabled early surgical intervention to prevent further foetal morbidity.

Replacement of Lost Lgr5-Positive Stem Cells through Plasticity of Their Enterocyte-Lineage Daughters.

PubMed

Tetteh, Paul W; Basak, Onur; Farin, Henner F; Wiebrands, Kay; Kretzschmar, Kai; Begthel, Harry; van den Born, Maaike; Korving, Jeroen; de Sauvage, Frederic; van Es, Johan H; van Oudenaarden, Alexander; Clevers, Hans

2016-02-04

Intestinal crypts display robust regeneration upon injury. The relatively rare secretory precursors can replace lost stem cells, but it is unknown if the abundant enterocyte progenitors that express the Alkaline phosphate intestinal (Alpi) gene also have this capacity. We created an Alpi-IRES-CreERT2 (Alpi(CreER)) knockin allele for lineage tracing. Marked clones consist entirely of enterocytes and are all lost from villus tips within days. Genetic fate-mapping of Alpi(+) cells before or during targeted ablation of Lgr5-expressing stem cells generated numerous long-lived crypt-villus "ribbons," indicative of dedifferentiation of enterocyte precursors into Lgr5(+) stems. By single-cell analysis of dedifferentiating enterocytes, we observed the generation of Paneth-like cells and proliferative stem cells. We conclude that the highly proliferative, short-lived enterocyte precursors serve as a large reservoir of potential stem cells during crypt regeneration. Copyright © 2016 Elsevier Inc. All rights reserved.

Foetal mortality, infant mortality, and age of parents. An overview.

PubMed

Gourbin, C

2005-11-01

This review article examines the relationship between late foetal and infant mortality, and age of parents. The highest risks are observed at older maternal ages for foetal mortality and at both extremes of reproductive ages for infant mortality. For infant morbidity, the role of intermediate variables is discussed. Increasing paternal age seems to be related to higher foetal and neonatal mortality.

[Intrapartum foetal monitoring: from stethoscope to ST analysis of the ECG].

PubMed

Westerhuis, Michelle E M H; Strasser, Sanne M; Moons, Karel G M; Mol, Ben Willem J; Visser, Gerard H A; Kwee, Anneke

2009-01-01

Since the 1970s, intrapartum monitoring of the distressed foetus has been managed by continuous registration of the foetal heart rate, together with uterine activity (cardiotocogram; CTG). Use of CTG without additional foetal information leads to unnecessary interventions because of the high number of false-positive signals. Foetal blood sampling (FBS) is a solution to this problem, but is not always consistently carried out. Automated ST analysis of the foetal electrocardiogram (STAN method), combined with the CTG, may lead to reduction of metabolic acidosis, fewer interventions and fewer foetal blood samples. A disadvantage of application of the STAN method is that it is based on visual interpretation of the CTG, with large inter- and intraobserver variability. In spite of this shortcoming the method may be promising.

Non-invasive tool for foetal sex determination in early gestational age.

PubMed

Mortarino, M; Garagiola, I; Lotta, L A; Siboni, S M; Semprini, A E; Peyvandi, F

2011-11-01

Free foetal DNA in maternal blood during early pregnancy is an ideal source of foetal genetic material for non-invasive prenatal diagnosis. The aim of this study was to evaluate the use of free foetal DNA analysis at early gestational age as pretest for the detection of specific Y-chromosome sequences in maternal plasma of women who are carriers of X-linked disorders, such as haemophilia. Real-time quantitative PCR analysis of maternal plasma was performed for the detection of the SRY or DYS14 sequence. A group of 208 pregnant women, at different gestational periods from 4 to 12 weeks, were tested to identify the optimal period to obtain an adequate amount of foetal DNA for prenatal diagnosis. Foetal gender was determined in 181 pregnant women sampled throughout pregnancy. Pregnancy outcome and foetal gender were confirmed using karyotyping, ultrasonography or after birth. The sensitivity, which was low between 4th and 7th week (mean 73%), increased significantly after 7+1th weeks of gestation (mean 94%). The latter sensitivity after 7+1th week of gestation is associated to a high specificity (100%), with an overall accuracy of 96% for foetal gender determination. This analysis demonstrates that foetal gender determination in maternal plasma is reliable after the 9th week of gestation and it can be used, in association with ultrasonography, for screening to determine the need for chorionic villus sampling for prenatal diagnosis of X-linked disorders, such as haemophilia. © 2011 Blackwell Publishing Ltd.

NON-INVASIVE MONITORING OF FOETAL ANAEMIA IN KELL SENSITIZED PREGNANCY.

PubMed

Memon, Zaibunnisa; Sheikh, Sana Sadiq

2015-01-01

We report a case of Kell sensitized pregnancy with good neonatal outcome. Anti-K antibodies were detected in maternal serum in early pregnancy as a part of routine antibody screening test. The middle cerebral artery doppler monitoring and serial titers were carried out to screen for foetal anaemia. Despite of rising antibody titers, serial middle cerebral artery doppler was normal and did not showed foetal anaemia. The pregnancy was carried out till term and patient delivered at 37 weeks of pregnancy with no evidence of foetal anaemia. This case underlines the need of general screening on rare antibodies in all pregnant women and that non-invasive monitoring of foetal anaemia can be done with anti-k titers and middle cerebral artery Doppler.

Leptin accelerates enterocyte turnover during methotrexate-induced intestinal mucositis in a rat.

PubMed

Sukhotnik, Igor; Mogilner, Jorge G; Shteinberg, Dan; Karry, Rahel; Lurie, Michael; Ure, Benno M; Shaoul, Ron; Coran, Arnold G

2009-05-01

Gastrointestinal mucositis occurs as a consequence of cytotoxic treatment. In the present study, we tested whether leptin can protect gut epithelial cells from methotrexate (MTX)-induced intestinal damage. Non-pretreated and pretreated with MTX Caco-2 cells were incubated with increasing concentrations of leptin for 24 h. Cell proliferation and apoptosis were assessed using FACS analysis. Adult rats were divided into three experimental groups: Control rats; MTX-rats were treated with a single dose of MTX, and MTX-LEP rats were also treated with leptin for 3 d. Intestinal mucosal damage (Park score), mucosal structural changes (bowel and mucosal weight, mucosal DNA and protein content, villus height and crypt depth), enterocyte proliferation, and enterocyte apoptosis were measured at sacrifice. RT-PCR was used to determine the level of bax and bcl-2 mRNA expression. In the vitro experiment, treatment with leptin of Caco-2 cells pre-treated with MTX resulted in a significant stimulation of cell proliferation and inhibition of cell apoptosis in a dose-dependent manner. In the vivo experiment, MTX-LEP rats demonstrated a greater jejunal and ileal bowel and mucosal weight, mucosal DNA and protein, villus height and crypt depth, as well as a greater enterocyte proliferation index compared to MTX-animals. MTX-LEP rats also showed a trend toward an increase in enterocyte apoptosis that was accompanied by an increase in bax mRNA and decrease in bcl-2 mRNA expression. In conclusion, leptin enhances proliferation and decreases apoptosis in Caco-2 cells pretreated with MTX. In a rat model of MTX-induced mucositis, treatment with leptin improves intestinal recovery and enhances enterocyte turnover.

[Analysis of Foetal Heart Rate Data using Complex Software: Comparison of Recurrence Plot of Foetal Heart Rate with the Course of Pregnancy -].

PubMed

Jörn, H; Morgenstern, B; Wassenberg, B; Rath, W

2004-08-01

Is it useful to further analyse foetal heart rate to improve the prediction of pregnancy complications? The analysis of the foetal heart rate is usually based on the variability of the heart rate, i. e. the more variable the heart rate presents - except a decrease - the better the condition of the foetus is. The same concept is applied in our own analysis which differs only in the presentation of the data. We analysed 25 non-stress-tests from unselected third trimester pregnancies using sophisticated software. The recurrence plot (RP) is able to rearrange data from foetal heart rate monitoring in order to make the heart rate variability visible. We developed criteria for a normal and an abnormal test result describing the structure of the diagram to predict an uneventful and a high-risk pregnancy, respectively. 11 out of 11 patients with uneventful course and outcome of pregnancy showed a coarse and blurred RP pattern. 12 out of 14 (86 %) patients developing either intrauterine growth retardation or preeclampsia and requiring caesarean section because of foetal heart rate abnormalities showed a fine and clear RP pattern. Our preliminary results show that it makes sense to further evaluate foetal heart rate variability in order to predict pregnancy complications. Computer programs including the algorithms needed (calculation of the recurrence plot) are not expensive and easy to handle. A widespread use of these programs represents the basis requirement for large controlled clinical trials.

Lxr-driven enterocyte lipid droplet formation delays transport of ingested lipids.

PubMed

Cruz-Garcia, Lourdes; Schlegel, Amnon

2014-09-01

Liver X receptors (Lxrs) are master regulators of cholesterol catabolism, driving the elimination of cholesterol from the periphery to the lumen of the intestine. Development of pharmacological agents to activate Lxrs has been hindered by synthetic Lxr agonists' induction of hepatic lipogenesis and hypertriglyceridemia. Elucidating the function of Lxrs in regulating enterocyte lipid handling might identify novel aspects of lipid metabolism that are pharmacologically amenable. We took a genetic approach centered on the single Lxr gene nr1h3 in zebrafish to study the role of Lxr in enterocyte lipid metabolism. Loss of nr1h3 function causes anticipated gene regulatory changes and cholesterol intolerance, collectively reflecting high evolutionary conservation of zebrafish Lxra function. Intestinal nr1h3 activation delays transport of absorbed neutral lipids, with accumulation of neutral lipids in enterocyte cytoplasmic droplets. This delay in transport of ingested neutral lipids protects animals from hypercholesterolemia and hepatic steatosis induced by a high-fat diet. On a gene regulatory level, Lxra induces expression of acsl3a, which encodes acyl-CoA synthetase long-chain family member 3a, a lipid droplet-anchored protein that directs fatty acyl chains into lipids. Forced overexpression of acls3a in enterocytes delays, in part, the appearance of neutral lipids in the vasculature of zebrafish larvae. Activation of Lxr in the intestine cell-autonomously regulates the rate of delivery of absorbed lipids by inducting a temporary lipid intestinal droplet storage depot. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

A PC-aided optical foetal heart rate detection system.

PubMed

Oweis, Rami J; As'ad, Hala; Aldarawsheh, Amany; Al-Khdeirat, Rawan; Lwissy, Kaldoun

2014-01-01

Safe monitoring of foetal heart rate is a valuable tool for the healthy evolution and wellbeing of both foetus and mother. This paper presents a non-invasive optical technique that allows for foetal heart rate detection using a photovoltaic infrared (IR) detector placed on the mother's abdomen. The system presented here consists of a photoplethysmography (PPG) circuit, abdomen circuit and a personal computer equipped with MATLAB. A near IR beam having a wavelength of 880 nm is transmitted through the mother's abdomen and foetal tissue. The received abdominal signal that conveys information pertaining to the mother and foetal heart rate is sensed by a low noise photodetector. The PC receives the signal through the National Instrumentation Data Acquisition Card (NIDAQ). After synchronous detection of the abdominal and finger PPG signals, the designed MATLAB-based software saves, analyses and extracts information related to the foetal heart rate. Extraction is carried out using recursive least squares adaptive filtration. Measurements on eight pregnant women with gestational periods ranging from 35-39 weeks were performed using the proposed system and CTG. Results show a correlation coefficient of 0.978 and a correlation confidence interval between 88-99.6%. The t test results in a p value of 0.034, which is less than 0.05. Low power, low cost, high signal-to-noise ratio, reduction of ambient light effect and ease of use are the main characteristics of the proposed system.

Maternal-foetal attachment during early pregnancy in Taiwanese women pregnant by in vitro fertilization.

PubMed

Kuo, Pi-Chao; Bowers, Beverly; Chen, Yueh-Chih; Chen, Chung-Hey; Tzeng, Ya-Ling; Lee, Maw-Sheng

2013-11-01

The aim of this study was to investigate maternal-foetal attachment at 9, 12 and 20 weeks gestation and to identify factors that influenced maternal-foetal attachment in Taiwanese women who conceived by in vitro fertilization. Development of maternal-foetal attachment is an important part of taking on the maternal role. However, evidence about maternal-foetal attachment after assisted conception is inconclusive. A longitudinal design with repeated measures. A prospective, longitudinal design with repeated measures was used. Over an 18-month period in 2006-2008, a convenience sample of 160 women who conceived after undergoing successful in vitro fertilization were recruited from a major infertility care centre in Taiwan. Data were collected by self-reported measures, including: (1) Maternal-Foetal Attachment Scale; (2) Symptoms Checklist; (3) Pregnancy-related Anxiety Scale; (4) Social Support Apgar; (5) Chinese childbearing attitude Questionnaire; and (6) Awareness of Foetus Scale. The selected instruments to measure each variable were administered to participants at 9, 12 and 20 weeks gestation. Maternal-foetal attachment increased as pregnancy progressed from 9 to 20 weeks gestation. General linear mixed model showed predictors of maternal-foetal attachment included Chinese childbearing attitude, awareness of the foetus, and social support. Health provider awareness of cultural influences on the development of early maternal-foetal attachment of women pregnant by in vitro fertilization is needed. Prenatal education in early pregnancy might incorporate more information about foetal development to allow the mother to visualize her unborn child. Providing social support for women who were conceived by in vitro fertilization is beneficial to the development of maternal-foetal attachment. © 2013 Blackwell Publishing Ltd.

Approximate distribution of dose among foetal organs for radioiodine uptake via placenta transfer

NASA Astrophysics Data System (ADS)

Millard, R. K.; Saunders, M.; Palmer, A. M.; Preece, A. W.

2001-11-01

Absorbed radiation doses to internal foetal organs were calculated according to the medical internal radiation dose (MIRD) technique in this study. Anthropomorphic phantoms of the pregnant female as in MIRDOSE3 enabled estimation of absorbed dose to the whole foetus at two stages of gestation. Some foetal organ self-doses could have been estimated by invoking simple spherical models for thyroid, liver, etc, but we investigated the use of the MIRDOSE3 new-born phantom as a surrogate for the stage 3 foetus, scaled to be compatible with total foetal body mean absorbed dose/cumulated activity. We illustrate the method for obtaining approximate dose distribution in the foetus near term following intake of 1 MBq of 123I, 124I, 125I or 131I as sodium iodide by the mother using in vivo biodistribution data examples from a good model of placenta transfer. Doses to the foetal thyroid of up to 1.85 Gy MBq-1 were predicted from the 131I uptake data. Activity in the foetal thyroid was the largest contributor to absorbed dose in the foetal body, brain, heart and thymus. Average total doses to the whole foetus ranged from 0.16 to 1.2 mGy MBq-1 for stages 1 and 3 of pregnancy using the MIRDOSE3 program, and were considerably higher than those predicted from the maternal contributions alone. Doses to the foetal thymus and stomach were similar, around 2-3 mGy MBq-1. Some foetal organ doses from the radioiodides were ten times higher than to the corresponding organs of the mother, and up to 100 times higher to the thyroid. The fraction of activity uptakes in foetal organs were distributed similarly to the maternal ones.

[Analysis of free foetal DNA in maternal plasma using STR loci].

PubMed

Vodicka, R; Vrtel, R; Procházka, M; Santavá, A; Dusek, L; Vrbická, D; Singh, R; Krejciríková, E; Schneiderová, E; Santavý, J

2006-01-01

Problems of maternal and foetal genotype differentiation of maternal plasma in pregnant women are solved generally by real-time systems. In this case the specific probes are used to distinguish particular genotype. Mostly gonosomal sequences are utilised to recognise the male foetus. This work describes possibilities in free foetal DNA detection and quantification by STR. Artificial genotype mixtures ranging from 0,2 % to 100 % to simulate maternal and paternal genotypes and 27 DNA samples from pregnant women in different stage of pregnancy were used for DNA quantification and detection. Foetal genotype was confirmed by biological father genotyping. The detection was performed in STR from 21st chromosome Down syndrome (DS) responsible region by innovated (I) QF PCR which allows to reveal and quantify even very rare DNA mosaics. The STR quantification was assessed in artificial mixtures of genotypes and discriminability of particular genotypes was on the level of few percent. Foetal DNA was detected in 74 % of tested samples. The IQF PCR application in quantification and differentiation between maternal and foetal genotypes by STR loci could have importance in non-invasive prenatal diagnostics as another possible marker for DS risk assessment.

Effect of malaria in pregnancy on foetal cortical brain development: a longitudinal observational study.

PubMed

Rijken, Marcus J; de Wit, Merel Charlotte; Mulder, Eduard J H; Kiricharoen, Suporn; Karunkonkowit, Noaeni; Paw, Tamalar; Visser, Gerard H A; McGready, Rose; Nosten, François H; Pistorius, Lourens R

2012-07-02

Malaria in pregnancy has a negative impact on foetal growth, but it is not known whether this also affects the foetal nervous system. The aim of this study was to examine the effects of malaria on foetal cortex development by three-dimensional ultrasound. Brain images were acquired using a portable ultrasound machine and a 3D ultrasound transducer. All recordings were analysed, blinded to clinical data, using the 4D view software package. The foetal supra-tentorial brain volume was determined and cortical development was qualitatively followed by scoring the appearance and development of six sulci. Multilevel analysis was used to study brain volume and cortical development in individual foetuses. Cortical grading was possible in 161 out of 223 (72%) serial foetal brain images in pregnant women living in a malaria endemic area. There was no difference between foetal cortical development or brain volumes at any time in pregnancy between women with immediately treated malaria infections and non-infected pregnancies. The percentage of images that could be graded was similar to other neuro-sonographic studies. Maternal malaria does not have a gross effect on foetal brain development, at least in this population, which had access to early detection and effective treatment of malaria.

Epidermal growth factor selectively enhances functional enterocyte adaptation after massive small bowel resection.

PubMed

Dunn, J C; Parungo, C P; Fonkalsrud, E W; McFadden, D W; Ashley, S W

1997-01-01

After massive small bowel resection, the intestine adapts to compensate. In addition to proliferation, enterocytes also undergo selective functional adaptation. In this study we examined the effect of intraperitoneal administration of epidermal growth factor (EGF) on the expression of the brush border dissacharidase sucrase, the sodium glucose cotransporter (SGLT1), and the sodium-potassium ATPase pump (NaK ATPase) by enterocytes in the remnant intestine after massive small bowel resection. Adult Lewis rats underwent either ileal transection or 70% proximal intestinal resection. These animals were subdivided into groups that received either saline or EGF intraperitoneally for 1 week. Ilea from each group were harvested 4 weeks postoperatively. Enterocytes were separated from these segments by calcium chelation. The total protein from the isolated cells was subjected to Western blot analysis. Administration of EGF to animals that underwent transection did not significantly alter the expression of sucrase, SGLT1, or NaK ATPase. After intestinal resection, the expressions of sucrase and SGLT1 were significantly increased. The combination of EGF administration and intestinal resection resulted in a further increase in SGLT1 expression. The intraperitoneal administration of EGF selectively enhanced the expression of SGLT1 by enterocytes after massive small bowel resection. Administration of EGF to sham-operated animals did not have similar effects. These results suggest that EGF augments the adaptive response and may therefore have a therapeutic role in the management of patients with short bowel syndrome.

Age-Dependent Enterocyte Invasion and Microcolony Formation by Salmonella

PubMed Central

Zhang, Kaiyi; Dupont, Aline; Torow, Natalia; Gohde, Fredrik; Leschner, Sara; Lienenklaus, Stefan; Weiss, Siegfried; Brinkmann, Melanie M.; Kühnel, Mark; Hensel, Michael; Fulde, Marcus; Hornef, Mathias W.

2014-01-01

The coordinated action of a variety of virulence factors allows Salmonella enterica to invade epithelial cells and penetrate the mucosal barrier. The influence of the age-dependent maturation of the mucosal barrier for microbial pathogenesis has not been investigated. Here, we analyzed Salmonella infection of neonate mice after oral administration. In contrast to the situation in adult animals, we observed spontaneous colonization, massive invasion of enteroabsorptive cells, intraepithelial proliferation and the formation of large intraepithelial microcolonies. Mucosal translocation was dependent on enterocyte invasion in neonates in the absence of microfold (M) cells. It further resulted in potent innate immune stimulation in the absence of pronounced neutrophil-dominated pathology. Our results identify factors of age-dependent host susceptibility and provide important insight in the early steps of Salmonella infection in vivo. We also present a new small animal model amenable to genetic manipulation of the host for the analysis of the Salmonella enterocyte interaction in vivo. PMID:25210785

Transepithelial glucose transport and Na+/K+ homeostasis in enterocytes: an integrative model

PubMed Central

Drengstig, Tormod; Ruoff, Peter

2014-01-01

The uptake of glucose and the nutrient coupled transcellular sodium traffic across epithelial cells in the small intestine has been an ongoing topic in physiological research for over half a century. Driving the uptake of nutrients like glucose, enterocytes must have regulatory mechanisms that respond to the considerable changes in the inflow of sodium during absorption. The Na-K-ATPase membrane protein plays a major role in this regulation. We propose the hypothesis that the amount of active Na-K-ATPase in enterocytes is directly regulated by the concentration of intracellular Na+ and that this regulation together with a regulation of basolateral K permeability by intracellular ATP gives the enterocyte the ability to maintain ionic Na+/K+ homeostasis. To explore these regulatory mechanisms, we present a mathematical model of the sodium coupled uptake of glucose in epithelial enterocytes. Our model integrates knowledge about individual transporter proteins including apical SGLT1, basolateral Na-K-ATPase, and GLUT2, together with diffusion and membrane potentials. The intracellular concentrations of glucose, sodium, potassium, and chloride are modeled by nonlinear differential equations, and molecular flows are calculated based on experimental kinetic data from the literature, including substrate saturation, product inhibition, and modulation by membrane potential. Simulation results of the model without the addition of regulatory mechanisms fit well with published short-term observations, including cell depolarization and increased concentration of intracellular glucose and sodium during increased concentration of luminal glucose/sodium. Adding regulatory mechanisms for regulation of Na-K-ATPase and K permeability to the model show that our hypothesis predicts observed long-term ionic homeostasis. PMID:24898586

Non-invasive Foetal ECG – a Comparable Alternative to the Doppler CTG?

PubMed Central

Reinhard, J.; Louwen, F.

2012-01-01

This review discusses the alternative of using the non-invasive foetal ECG compared with the conventionally used Doppler CTG. Non-invasive abdominal electrocardiograms (ECG) have been approved for clinical routine since 2008; subsequently they were also approved for antepartum and subpartum procedures. The first study results have been published. Non-invasive foetal ECG is especially indicated during early pregnancy, while the Doppler CTG is recommended for the vernix period. Beyond the vernix period no difference has been recorded in the success rate of either approach. The foetal ECG signal quality is independent of the BMI, whereas the success rate of the Doppler CTG is diminished with an increased BMI. During the first stage of labour, non-invasive foetal ECG demonstrates better signal quality; however during the second stage of labour no difference has been identified between the methods. PMID:25308981

Communication Profile of Primary School-Aged Children with Foetal Growth Restriction

ERIC Educational Resources Information Center

Partanen, Lea Aulikki; Olsén, Päivi; Mäkikallio, Kaarin; Korkalainen, Noora; Heikkinen, Hanna; Heikkinen, Minna; Yliherva, Anneli

2017-01-01

Foetal growth restriction is associated with problems in neurocognitive development. In the present study, prospectively collected cohorts of foetal growth restricted (FGR) and appropriate for gestational age grown (AGA) children were examined at early school-age by using the Children's Communication Checklist-2 (CCC-2) to test the hypothesis that…

Blockade of cholesterol absorption by ezetimibe reveals a complex homeostatic network in enterocytes[S

PubMed Central

Engelking, Luke J.; McFarlane, Matthew R.; Li, Christina K.; Liang, Guosheng

2012-01-01

Enterocyte cholesterol homeostasis reflects aggregated rates of sterol synthesis, efflux, and uptake from plasma and gut lumen. Cholesterol synthesis and LDL uptake are coordinately regulated by sterol regulatory element-binding proteins (SREBP), whereas sterol efflux is regulated by liver X receptors (LXR). How these processes are coordinately regulated in enterocytes, the site of cholesterol absorption, is not well understood. Here, we treat mice with ezetimibe to investigate the effect of blocking cholesterol absorption on intestinal SREBPs, LXRs, and their effectors. Ezetimibe increased nuclear SREBP-2 8-fold. HMG-CoA reductase (HMGR) and LDL receptor (LDLR) mRNA levels increased less than 3-fold, whereas their protein levels increased 30- and 10-fold, respectively. Expression of inducible degrader of LDLR (IDOL), an LXR-regulated gene that degrades LDLRs, was reduced 50% by ezetimibe. Coadministration of ezetimibe with the LXR agonist T0901317 abolished the reduction in IDOL and prevented the increase in LDLR protein. Ezetimibe-stimulated LDLR expression was independent of proprotein convertase subtilisin/kexin type 9 (PSCK9), a protein that degrades LDLRs. To maintain cholesterol homeostasis in the face of ezetimibe, enterocytes boost LDL uptake by increasing LDLR number, and they boost sterol synthesis by increasing HMGR and other cholesterologenic genes. These studies reveal a hitherto undescribed homeostatic network in enterocytes triggered by blockade of cholesterol absorption. PMID:22523394

Arginine for gestating sows and foetal development: A systematic review.

PubMed

Palencia, J Y P; Lemes, M A G; Garbossa, C A P; Abreu, M L T; Pereira, L J; Zangeronimo, M G

2018-02-01

The use of functional amino acids during pregnancy has been linked to improved reproduction in mammals. In this context, arginine is a precursor in the synthesis of numerous molecules, such as nitric oxide and polyamines, which play an important role during reproduction. However, contradictory studies are found in the literature, particularly regarding the amount of supplementation and the period of pregnancy in which it is used. The objective of this study was to evaluate the effects of dietary arginine supplementation for pregnant sows on foetal development via a systematic review. The search for papers was performed during the month of December 2015, in the databases ISI Web of Science, Science Direct, Scopus, and SciELO. From a total of 5675 returned studies, only 13 papers were selected after applying selection criteria. Most (47%) of the studies that evaluated the effects of dietary arginine supplementation on foetal development in pigs used 1% arginine. Supplementation was initiated in the first third of pregnancy in 47% of tests, including in both primiparous and multiparous sows. These studies showed positive results for embryo survival and foetal development, evidenced by the increase in placental weight and the number and weight of piglets born alive. Of all evaluated studies, 53% showed benefits on foetal development. It is concluded that supplementing dietary arginine in gestating sows can benefit embryo survival and foetal development. However, to establish a supplementation plan with this amino acid, aspects related to the period of pregnancy, supplementation levels, and source of arginine must be well defined. © 2017 Blackwell Verlag GmbH.

Foetal hepatic progenitor cells assume a cholangiocytic cell phenotype during two-dimensional pre-culture.

PubMed

Anzai, Kazuya; Chikada, Hiromi; Tsuruya, Kota; Ida, Kinuyo; Kagawa, Tatehiro; Inagaki, Yutaka; Mine, Tesuya; Kamiya, Akihide

2016-06-23

Liver consists of parenchymal hepatocytes and other cells. Liver progenitor cell (LPC) is the origin of both hepatocytes and cholangiocytic cells. The analyses of mechanism regulating differentiation of LPCs into these functional cells are important for liver regenerative therapy using progenitor cells. LPCs in adult livers were found to form cysts with cholangiocytic characteristics in 3D culture. In contrast, foetal LPCs cannot form these cholangiocytic cysts in the same culture. Thus, the transition of foetal LPCs into cholangiocytic progenitor cells might occur during liver development. Primary CD45(-)Ter119(-)Dlk1(+) LPCs derived from murine foetal livers formed ALBUMIN (ALB)(+)CYTOKERATIN (CK)19(-) non-cholangiocytic cysts within 3D culture. In contrast, when foetal LPCs were pre-cultured on gelatine-coated dishes, they formed ALB(-)CK19(+) cholangiocytic cysts. When hepatocyte growth factor or oncostatin M, which are inducers of hepatocytic differentiation, was added to pre-culture, LPCs did not form cholangiocytic cysts. These results suggest that the pre-culture on gelatine-coated dishes changed the characteristics of foetal LPCs into cholangiocytic cells. Furthermore, neonatal liver progenitor cells were able to form cholangiocytic cysts in 3D culture without pre-culture. It is therefore possible that the pre-culture of mid-foetal LPCs in vitro functioned as a substitute for the late-foetal maturation step in vivo.

Effect of oral glutamine on enterocyte turnover during methotrexate-induced mucositis in rats.

PubMed

Sukhotnik, Igor; Mogilner, Jorge G; Karry, Rahel; Shamian, Benhoor; Lurie, Michael; Kokhanovsky, Natalie; Ure, Benno M; Coran, Arnold G

2009-01-01

The objective of this study was to evaluate the effects of oral glutamine in preventing intestinal mucosal damage caused by methotrexate (MTX) in rats. Male Sprague-Dawley rats were divided into 3 experimental groups: control rats, rats treated intraperitoneally with MTX (MTX rats) and rats treated with oral glutamine in the drinking water (2%) 72 h following intraperitoneal injection of a single dose of MTX (MTX-glutamine rats). Intestinal mucosal damage (Park's injury score), mucosal structural changes, enterocyte proliferation and enterocyte apoptosis were determined 72 h following MTX injection. RT-PCR was used to determine Bax and Bcl-2 mRNA expression. MTX-glutamine rats demonstrated greater jejunal and ileal mucosal weight and mucosal DNA, greater ileal villus height and crypt depth, and a greater index of proliferation in the jejunum and ileum compared to MTX animals. A significant decrease in enterocyte apoptosis in the ileum of MTX-glutamine rats (vs. MTX) was accompanied by decreased Bax and increased Bcl-2 mRNA expression. Treatment with oral glutamine prevents mucosal injury and improves intestinal recovery following MTX injury in the rat.

Kinetic studies of the murine foetal thymus using vincristine sulphate.

PubMed

Riches, A C; Carr, H M; McQueen, L; Thomas, D B

1981-01-01

The turnover time of the foetal thymus has been evaluated in CD1 mice using the metaphase arrest drug vincristine sulphate and also by direct cell counting and found to be 18 h (range 12--26) and 11.9 h (range 10.9--13.1) respectively. Vincristine sulphate can be used for cell kinetic studies on foetal thymus provided an appropriate dose (5 mgm per kgm body weight given intravenously) and time scale (less than 1 hour after injection) are used for these measurements. These conditions are different from those used for adult tissues. Using 125I-iododeoxyuridine uptake measurements, it was found that vincristine sulphate suppressed DNA synthesis in the foetal thymus but not in the maternal thymus at this dose. Only the G2 cohort of cells in the thymus entered mitosis.

[Occiput posterior presentation at delivery: Materno-foetal outcomes and predictive factors of rotation].

PubMed

Othenin-Girard, V; Boulvain, M; Guittier, M-J

2018-02-01

To describe the maternal and foetal outcomes of an occiput posterior foetal position at delivery; to evaluate predictive factors of anterior rotation during labour. Descriptive retrospective analysis of a cohort of 439 women with foetuses in occiput posterior position during labour. Logistic regression analysis to quantify the effect of factors that may favour anterior rotation. Most of foetuses (64%) do an anterior rotation during labour and 13% during the expulsive phase. The consequences of a persistent foetal occiput posterior position during delivery are a significantly increased average time of second stage labour compared to others positions (65.19minutes vs. 43.29, P=0.001, respectively); a higher percentage of caesarean sections (72.0% versus 4.7%, P<0.001) and instrumental delivery (among low-birth deliveries, 60.7% versus 25.2%, P<0.001); more frequent third-degree perineal tears (14.3% vs. 0.6%, P<0.001) and more abundant blood loss (560mL versus 344mL, P<0.001). In a multi-variable model including nulliparity, station of the presenting part and degree of flexion of the foetal head at complete dilatation, the only predictive factor independent of rotation at delivery is a good flexion of the foetal head at complete dilatation, which multiplies the anterior rotation probability by six. A good flexion of the foetal head is significantly associated with anterior rotation. Other studies exploring ways to increase anterior rotation during labour are needed to reduce the very high risk of caesarean section and instrumentation associated with the foetal occiput posterior position. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Foetal haemoglobin concentration at postmenstrual age is unaffected by gestational age at birth.

PubMed

Watanabe, Yuki; Osawa, Kayo; Sato, Itsuko; Iwatani, Sota; Kono, Ruri; Hayakawa, Ikuyo; Hayashi, Nobuhide; Iijima, Kazumoto; Saegusa, Jun; Morioka, Ichiro

2018-05-01

Background Our aim was to determine whether the postnatal age or postmenstrual age is a more appropriate criterion for evaluating foetal haemoglobin concentrations. Methods Blood samples ( n = 1095) were obtained from 394 infants and were divided into two groups based on gestational age at birth: <37 weeks ( n = 491) and ≥37 weeks ( n = 604). (1) Foetal haemoglobin concentrations divided by one month at age after birth were compared between the groups. (2) Foetal haemoglobin concentrations divided into ≤9 months from last menstruation and one month thereafter were compared between the groups. Results In samples from infants ≥37 weeks' gestational age at birth, the median foetal haemoglobin concentrations were 69.5%, 21.4% and 3.6% at 0-1 month, 2-3 months and ≥5 months after birth, respectively. The median foetal haemoglobin concentrations in infants <37 weeks' gestational age at birth were 75.5%, 62.7% and 5.1% at 0-1 month, 2-3 months and ≥5 months after birth, respectively. The median foetal haemoglobin concentrations in infants <37 weeks' gestational age at birth were significantly higher than that in infants ≥37 weeks' gestational age at birth at all postnatal age points. (2) There was no significant difference between the groups at all age points after nine months of postmenstrual age: 72.5 and 75.3% at 9-10 months, 25.1 and 26.6% at 11-12 months and 5.5 and 4.6% at >13 months after last menstruation in infants ≥37 and <37 weeks' gestational age at birth, respectively. Conclusions Evaluation of foetal haemoglobin concentrations at postmenstrual age is unaffected by gestational age at birth.

Glutamate and CO2 production from glutamine in incubated enterocytes of adult and very old rats.

PubMed

Meynial-Denis, Dominique; Bielicki, Guy; Beaufrère, Anne-Marie; Mignon, Michelle; Mirand, Philippe Patureau; Renou, Jean-Pierre

2013-04-01

Glutamine is the major fuel for enterocytes and promotes the growth of intestinal mucosa. Although oral glutamine exerts a positive effect on intestinal villus height in very old rats, how glutamine is used by enterocytes is unclear. Adult (8 months) and very old (27 months) female rats were exposed to intermittent glutamine supplementation for 50% of their age lifetime. Treated rats received glutamine added to their drinking water, and control rats received water alone. Jejunal epithelial cells (~300×10(6) cells) were incubated in oxygenated Krebs-Henseleit buffer for 30 min containing [1-(13)C] glutamine (~17 M) for analysis of glutamine metabolites by (13)C nuclear magnetic resonance ((13)C NMR). An aliquot fraction was incubated in the presence of [U-(14)C] glutamine to measure produced CO2. Glutamine pretreatment increased glutamate production and decreased CO2 production in very old rats. The ratio CO2/glutamate, which was very high in control very old rats, was similar at both ages after glutamine pretreatment, as if enterocytes from very old rats recovered the metabolic abilities of enterocytes from adult rats. Our results suggest that long-term treatment with glutamine started before advanced age (a) prevented the loss of rat body weight without limiting sarcopenia and (b) had a beneficial effect on enterocytes from very old rats probably by favoring the role of glutamate as a precursor for glutathione, arginine and proline biosynthesis, which was not detected in (13)C NMR spectra in our experimental conditions. Copyright © 2013 Elsevier Inc. All rights reserved.

Maternal 25-hydroxyvitamin D is inversely correlated with foetal serotonin.

PubMed

Murthi, Padma; Davies-Tuck, Miranda; Lappas, Martha; Singh, Harmeet; Mockler, Joanne; Rahman, Rahana; Lim, Rebecca; Leaw, Bryan; Doery, James; Wallace, Euan M; Ebeling, Peter R

2017-03-01

Maternal vitamin D deficiency during pregnancy has been linked to impaired neurocognitive development in childhood. The mechanism by which vitamin D affects childhood neurocognition is unclear but may be via interactions with serotonin, a neurotransmitter involved in foetal brain development. In this study, we aimed to explore associations between maternal and foetal vitamin D concentrations, and foetal serotonin concentrations at term. Serum 25-hydroxyvitamin D (25(OH)D, nmol/l) and serotonin (5-HT, nmol/l) concentrations were measured in maternal and umbilical cord blood from mother-infant pairs (n = 64). Association between maternal 25(OH)D, cord 25(OH)D and cord serotonin was explored using linear regression, before and after adjusting for maternal serotonin levels. We also assessed the effects of siRNA knockdown of the vitamin D receptor (VDR) and administration of 10 nm 1,25-dihydroxyvitamin D 3 on serotonin secretion in human umbilical vein endothelial cells (HUVECs) in vitro. We observed an inverse relationship between both maternal and cord 25(OH)D concentrations with cord serotonin concentrations. The treatment of HUVECs with 1,25-dihydroxyvitamin D 3 in vitro decreased the release of serotonin (193·9 ±14·8 nmol/l vs 458·9 ± 317·5 nmol/l, control, P < 0·05). Conversely, inactivation of VDR increased serotonin release in cultured HUVECs. These observations provide the first evidence of an inverse relationship between maternal 25(OH)D and foetal serotonin concentrations. We propose that maternal vitamin D deficiency increases foetal serotonin concentrations and thereby contributes to longer-term neurocognitive impairment in infants and children. © 2016 John Wiley & Sons Ltd.

Carbachol-induced MUC17 endocytosis is concomitant with NHE3 internalization and CFTR membrane recruitment in enterocytes.

PubMed

Pelaseyed, Thaher; Gustafsson, Jenny K; Gustafsson, Ida J; Ermund, Anna; Hansson, Gunnar C

2013-08-15

We have reported that transmembrane mucin MUC17 binds PDZ protein PDZK1, which retains MUC17 apically in enterocytes. MUC17 and transmembrane mucins MUC3 and MUC12 are suggested to build the enterocyte apical glycocalyx. Carbachol (CCh) stimulation of the small intestine results in gel-forming mucin secretion from goblet cells, something that requires adjacent enterocytes to secrete chloride and bicarbonate for proper mucin formation. Surface labeling and confocal imaging demonstrated that apically expressed MUC17 in Caco-2 cells and Muc3(17) in murine enterocytes were endocytosed upon stimulation with CCh. Relocation of MUC17 in response to CCh was specific as MUC3 and MUC12 did not relocate following CCh stimulation. MUC17 colocalized with PDZK1 under basal conditions, while MUC17 relocated to the terminal web and into early endosomes after CCh stimulation. CCh stimulation concomitantly internalized the Na(+/)H(+) exchanger 3 (NHE3) and recruited cystic fibrosis transmembrane conductance regulator (CFTR) to the apical membranes, a process that was important for CFTR-mediated bicarbonate secretion necessary for proper gel-forming mucin unfolding. The reason for the specific internalization of MUC17 is not understood, but it could limit the diffusion barrier for ion secretion caused by the apical enterocyte glycocalyx or alternatively act to sample luminal bacteria. Our results reveal well-orchestrated mucus secretion and trafficking of ion channels and the MUC17 mucin.

Three-hour analysis of non-invasive foetal sex determination: application of Plexor chemistry.

PubMed

Pietropolli, Adalgisa; Capogna, Maria Vittoria; Cascella, Raffaella; Germani, Chiara; Bruno, Valentina; Strafella, Claudia; Sarta, Simona; Ticconi, Carlo; Marmo, Giusy; Gallaro, Sara; Longo, Giuliana; Marsella, Luigi Tonino; Novelli, Antonio; Novelli, Giuseppe; Piccione, Emilio; Giardina, Emiliano

2016-04-04

The knowledge of the individual genetic "status" in the prenatal era is particularly relevant in the case of positive family history for genetic diseases, in advanced maternal age and in the general screening for foetal abnormalities. In this context, here, we report an innovative molecular assay which utilizes the cell-free foetal DNA (cffDNA) as a source for the early and fast detection of the foetal sex. The study involved 132 pregnant women in their first 3 months of pregnancy, who agreed to give a blood sample. All the collected samples were immediately subjected to the separation of the plasma, which was utilized for the extraction of the cffDNA. Successively, the extracted cffDNA was analysed by a quantitative PCR (qPCR) method based on Plexor-HY chemistry, which is able to simultaneously identify, quantify and discriminate the autosomal DNA from the sex-linked DNA. Overall, the Plexor-HY assay demonstrated to be sensitive and specific for the determination of low-template DNA, such as the cffDNA. In fact, the Plexor-HY assay has been successfully performed in all the samples, identifying 70 males and 62 females. As the foetal sex can be provided in 120 min just by utilizing a maternal blood sample as cffDNA source, the assay represents a very fast, safe and non-invasive prenatal method. The possibility of determining the foetal sex in the early prenatal life consents the application of our assay as a helpful screening test for subjects and families at risk of sex-linked disorders. Moreover, the early knowledge of the foetal sex may be of great help even for the specialist, who might promptly advise the patients concerning the foetal risk of inheriting sex-linked disorders and the clinical utility of performing an invasive prenatal diagnosis.

Dgat1 and Dgat2 regulate enterocyte triacylglycerol distribution and alter proteins associated with cytoplasmic lipid droplets in response to dietary fat

PubMed Central

Hung, Yu-Han; Carreiro, Alicia L.; Buhman, Kimberly K.

2017-01-01

Enterocytes, the absorptive cells of the small intestine, mediate efficient absorption of dietary fat (triacylglycerol, TAG). The digestive products of dietary fat are taken up by enterocytes, re-esterified into TAG, and packaged on chylomicrons (CMs) for secretion into blood or temporarily stored within cytoplasmic lipid droplets (CLDs). Altered enterocyte TAG distribution impacts susceptibility to high fat diet associated diseases, but molecular mechanisms directing TAG toward these fates are unclear. Two enzymes, acyl CoA: diacylglycerol acyltransferase 1 (Dgat1) and Dgat2, catalyze the final, committed step of TAG synthesis within enterocytes. Mice with intestine-specific overexpression of Dgat1 (Dgat1Int) or Dgat2 (Dgat2Int), or lack of Dgat1 (Dgat1−/−), were previously found to have altered intestinal TAG secretion and storage. We hypothesized that varying intestinal Dgat1 and Dgat2 levels alters TAG distribution in subcellular pools for CM synthesis as well as the morphology and proteome of CLDs. To test this we used ultrastructural and proteomic methods to investigate intracellular TAG distribution and CLD-associated proteins in enterocytes from Dgat1Int, Dgat2Int, and Dgat1−/− mice 2 hours after a 200 μl oral olive oil gavage. We found that varying levels of intestinal Dgat1 and Dgat2 altered TAG pools involved in CM assembly and secretion, the number or size of CLDs present in enterocytes, and the enterocyte CLD proteome. Overall, these results support a model where Dgat1 and Dgat2 function coordinately to regulate the process of dietary fat absorption by preferentially synthesizing TAG for incorporation into distinct subcellular TAG pools in enterocytes. PMID:28249764

Dgat1 and Dgat2 regulate enterocyte triacylglycerol distribution and alter proteins associated with cytoplasmic lipid droplets in response to dietary fat.

PubMed

Hung, Yu-Han; Carreiro, Alicia L; Buhman, Kimberly K

2017-06-01

Enterocytes, the absorptive cells of the small intestine, mediate efficient absorption of dietary fat (triacylglycerol, TAG). The digestive products of dietary fat are taken up by enterocytes, re-esterified into TAG, and packaged on chylomicrons (CMs) for secretion into blood or temporarily stored within cytoplasmic lipid droplets (CLDs). Altered enterocyte TAG distribution impacts susceptibility to high fat diet associated diseases, but molecular mechanisms directing TAG toward these fates are unclear. Two enzymes, acyl CoA: diacylglycerol acyltransferase 1 (Dgat1) and Dgat2, catalyze the final, committed step of TAG synthesis within enterocytes. Mice with intestine-specific overexpression of Dgat1 (Dgat1 Int ) or Dgat2 (Dgat2 Int ), or lack of Dgat1 (Dgat1 -/- ), were previously found to have altered intestinal TAG secretion and storage. We hypothesized that varying intestinal Dgat1 and Dgat2 levels alters TAG distribution in subcellular pools for CM synthesis as well as the morphology and proteome of CLDs. To test this we used ultrastructural and proteomic methods to investigate intracellular TAG distribution and CLD-associated proteins in enterocytes from Dgat1 Int , Dgat2 Int , and Dgat1 -/- mice 2h after a 200μl oral olive oil gavage. We found that varying levels of intestinal Dgat1 and Dgat2 altered TAG pools involved in CM assembly and secretion, the number or size of CLDs present in enterocytes, and the enterocyte CLD proteome. Overall, these results support a model where Dgat1 and Dgat2 function coordinately to regulate the process of dietary fat absorption by preferentially synthesizing TAG for incorporation into distinct subcellular TAG pools in enterocytes. Copyright © 2017 Elsevier B.V. All rights reserved.

Genotyping approach for non-invasive foetal RHD detection in an admixed population

PubMed Central

Boggione, Carolina Trucco; Luján Brajovich, Melina E.; Mattaloni, Stella M.; Di Mónaco, René A.; García Borrás, Silvia E.; Biondi, Claudia S.; Cotorruelo, Carlos M.

2017-01-01

Background Non-invasive foetal RHD genotyping can predict haemolytic disease of the foetus and the newborn in pregnancies with anti-D alloantibodies and also avoid antenatal anti-D prophylaxis in pregnant women carrying an RHD negative foetus. Considering that the Argentine genetic background is the result of generations of intermixing between several ethnic groups, we evaluated the diagnostic performance of a non-invasive foetal RHD determination strategy to guide targeted antenatal RhD immunoprophylaxis. This algorithm is based on the analysis of four regions of the RHD gene in cell-free foetal DNA in maternal plasma and maternal and paternal RHD genotyping. Materials and methods DNA from 298 serologically D negative pregnant women between 19–28 weeks gestation were RHD genotyped. Foetal RHD status was determined by real-time PCR in 296 maternal plasma samples. In particular cases, RHDΨ and RHD-CE-Ds alleles were investigated in paternal DNA. Umbilical cord blood was collected at birth, and serological and molecular studies were performed. Results Of the 298 maternal samples, 288 were D−/RHD− and 10 D−/RHD+ (2 RHD*DAR; 5 RHD-CE-Ds; 3 RHDΨ). Plasma from RHD*DAR carriers was not analysed. Real-time PCR showed 210 RHD+ and 78 RHD− foetuses and 8 inconclusive results. In this latter group, paternal molecular studies were useful to report a RHD negative status in 5 foetuses while only 3 remained inconclusive. All the results, except one false positive due to a silent allele (RHD[581insG]), agreed with the neonatal typing performed in cord blood. Discussion The protocol used for non-invasive prenatal RHD genotyping proved to be suitable to determine foetal RHD status in our admixed population. The knowledge of the genetic background of the population under study and maternal and paternal molecular analysis can reduce the number of inconclusive results when investigating foetal RHD status. PMID:27136427

Enterocyte protein tyrosine nitration in response to Eimeria infection in broilers

USDA-ARS?s Scientific Manuscript database

Activation of pathogen-sensing mechanisms in intestinal cells initiate the generation of pathway effectors that perturb normal nutritional enterocyte (ETC) functions. Among the conserved pathway mediator molecules generated are nitric oxide (NO) and superoxide anion (SOA) which are known to interac...

Role of calbindin-D9k in buffering cytosolic free Ca2+ ions in pig duodenal enterocytes.

PubMed

Schröder, B; Schlumbohm, C; Kaune, R; Breves, G

1996-05-01

1. The aim of the present study was to test whether the vitamin D-dependent Ca(2+)-binding protein calbindin-D9k could function as an important cytosolic Ca2+ buffer in duodenal enterocytes while facilitating transepithelial active transport of Ca2+ ions. For the investigations we used dual-wavelength, fluorescence ratio imaging, with fura-2 as the Ca(2+)-sensitive dye, to measure changes in cytosolic concentrations of free Ca2+ ions ([Ca2+]i) in isolated pig duodenal enterocytes affected by different cytosolic calbindin-D9k concentrations. 2. Epithelial cells were obtained from weaned piglets with normal calbindin-D9k concentrations (con-piglets), from piglets with low calbindin-D9k levels due to inherited calcitriol deficiency caused by defective renal 25-hydroxycholecalciferol D3-1 alpha-hydroxylase activity (def-piglets), and from piglets with reconstituted calbindin-D9k concentrations, i.e. def-animals treated with high doses of vitamin D3 which elevated plasma calcitriol levels by extrarenal production (def-D3-piglets). Basal levels of [Ca2+]i ranged between 170 and 205 nM and did not differ significantly between the groups. 3. After addition of 5 mM theophylline, the [Ca2+]i in enterocytes from con-piglets doubled during the 10 min incubation. This effect, however, was three times higher in enterocytes from def-piglets compared with those from con-piglets. Similar results were obtained after 4 min incubation of enterocytes from con- and def-piglets in the presence of 1 microM ionomycin. In preparations from def-D3-piglets, ionomycin-induced increases in [Ca2+]i were significantly lower compared with enterocytes from def-piglets and were not different from the control values. 4. From the results, substantial support is given for the hypothesis that one of the major functions of mucosal calbindin-D9k is the effective buffering of Ca2+ ions.

Role of calbindin-D9k in buffering cytosolic free Ca2+ ions in pig duodenal enterocytes.

PubMed Central

Schröder, B; Schlumbohm, C; Kaune, R; Breves, G

1996-01-01

1. The aim of the present study was to test whether the vitamin D-dependent Ca(2+)-binding protein calbindin-D9k could function as an important cytosolic Ca2+ buffer in duodenal enterocytes while facilitating transepithelial active transport of Ca2+ ions. For the investigations we used dual-wavelength, fluorescence ratio imaging, with fura-2 as the Ca(2+)-sensitive dye, to measure changes in cytosolic concentrations of free Ca2+ ions ([Ca2+]i) in isolated pig duodenal enterocytes affected by different cytosolic calbindin-D9k concentrations. 2. Epithelial cells were obtained from weaned piglets with normal calbindin-D9k concentrations (con-piglets), from piglets with low calbindin-D9k levels due to inherited calcitriol deficiency caused by defective renal 25-hydroxycholecalciferol D3-1 alpha-hydroxylase activity (def-piglets), and from piglets with reconstituted calbindin-D9k concentrations, i.e. def-animals treated with high doses of vitamin D3 which elevated plasma calcitriol levels by extrarenal production (def-D3-piglets). Basal levels of [Ca2+]i ranged between 170 and 205 nM and did not differ significantly between the groups. 3. After addition of 5 mM theophylline, the [Ca2+]i in enterocytes from con-piglets doubled during the 10 min incubation. This effect, however, was three times higher in enterocytes from def-piglets compared with those from con-piglets. Similar results were obtained after 4 min incubation of enterocytes from con- and def-piglets in the presence of 1 microM ionomycin. In preparations from def-D3-piglets, ionomycin-induced increases in [Ca2+]i were significantly lower compared with enterocytes from def-piglets and were not different from the control values. 4. From the results, substantial support is given for the hypothesis that one of the major functions of mucosal calbindin-D9k is the effective buffering of Ca2+ ions. PMID:8734984

Time-series analysis of ruminant foetal wastage at a slaughterhouse in North Central Nigeria between 2001 and 2012.

PubMed

Alhaji, Nma B; Odetokun, Ismail A; Shittu, Aminu; Onyango, Joshua; Chafe, Umar M; Abubakar, Muhammed S; Muraina, Issa A; Fasina, Folorunso O; Lee, Hu Suk

2015-12-15

In developing countries, foetal wastage from slaughtered ruminants and the associated economic losses appear to be substantial. However, only a limited number of studies have comprehensively evaluated these trends. In the current study, secondary (retrospective) and primary data were collected and evaluated to estimate the prevalence of foetal wastage from cattle, sheep and goats slaughtered at an abattoir in Minna, Nigeria, over a 12-year period (January 2001-December 2012). Time-series modelling revealed substantial differences in the rate of foetal wastage amongst the slaughtered species, with more lambs having been wasted than calves or kids. Seasonal effects seem to influence rates of foetal wastage and certain months in the year appear to be associated with higher odds of foetal wastage. Improved management systems are suggested to reduce the risk of foetal losses.

Parental decision-making after ultrasound diagnosis of a serious foetal abnormality.

PubMed

Bijma, Hilmar H; Wildschut, Hajo I J; van der Heide, Agnes; Passchier, Jan; Wladimiroff, Juriy W; van der Maas, Paul J

2005-01-01

The purpose of this article is to provide clinicians who are involved in the field of foetal medicine with a comprehensive overview of theories that are relevant for the parental decision-making process after ultrasound diagnosis of a serious foetal abnormality. Since little data are available of parental decision-making after ultrasound diagnosis of foetal abnormality, we reviewed the literature on parental decision-making in genetic counselling of couples at increased genetic risk together with the literature on general decision-making theories. The findings were linked to the specific situation of parental decision-making after an ultrasound diagnosis of foetal abnormality. Based on genetic counselling studies, several cognitive mechanisms play a role in parental decision-making regarding future pregnancies. Parents often have a binary perception of risk. Probabilistic information is translated into two options: the child will or will not be affected. The graduality of chance seems to be of little importance in this process. Instead, the focus shifts to the possible consequences for future family life. General decision-making theories often focus on rationality and coherence of the decision-making process. However, studies of both the influence of framing and the influence of stress indicate that emotional mechanisms can have an important and beneficial function in the decision-making process. Cognitive mechanisms that are elicited by emotions and that are not necessarily rational can have an important and beneficial function in parental decision-making after ultrasound diagnosis of a foetal abnormality. Consequently, the process of parental decision-making should not solely be assessed on the basis of its rationality, but also on the basis of the parental emotional outcome. Copyright (c) 2005 S. Karger AG, Basel.

Does ultrasonographic foetal head position prior to induction of labour predict the outcome of delivery?

PubMed

Verhoeven, Corine J M; Mulders, Leon G M; Oei, S Guid; Mol, Ben Willem J

2012-10-01

To examine the capacity of pre-induction sonographic assessment of occipital position of the foetal head to predict the outcome of delivery, and to assess whether sonographic foetal head position before induction of labour is related to foetal presentation at delivery. A prospective cohort study was conducted in the Máxima Medical Centre, The Netherlands. We included consecutive women in whom labour was induced. Immediately prior to induction a transabdominal ultrasound was performed to determine the position of the foetal occiput. The primary outcome was mode of delivery. We recorded maternal demographics, labour and delivery characteristics, maternal and neonatal outcomes. The association between position of the foetal head before induction of labour and the occurrence of caesarean section was addressed using univariable and logistic regression analysis. From the 50 of the 183 foetuses that started labour in occipitoposterior position, 11 persisted in occipitoposterior position until birth, whereas from the 120 foetuses that were in occipitoanterior position before induction, three children were born in an occipitoposterior position. Although we found a difference in caesarean section rate between OP position and OA position of the foetal head at sonography prior to induction, this was not statistically significant (14% versus 6.7%, OR 2.3, 95% CI 0.78-6.7). Our study demonstrates that OP position prior to labour induction does not affect mode of delivery. Sonographic assessment of the position of the foetal head prior to labour induction should not be introduced in clinical practice. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Regulatory T cells, maternal-foetal immune tolerance and recurrent miscarriage: new therapeutic challenging opportunities.

PubMed

Alijotas-Reig, Jaume; Melnychuk, Taisiia; Gris, Josep Maria

2015-03-15

Because maternal alloreactive lymphocytes are not depleted during pregnancy, local and/or systemic mechanisms have to play a key role in altering the maternal immune response. Peripheral T regulatory cells (pTregs) at the maternal-foetal interface are necessary in situ to prevent early abortion, but only those pTregs that have been previously exposed to paternal alloantigens. It has been showed that pregnancy selectively stimulates the accumulation of maternal Foxp3(+)CD4(+)CD25(+) (Foxp3Tregs) cells with foetal specificity. Interestingly, after delivery, foetal-specific pTregs persist at elevated levels, maintain tolerance to pre-existing foetal antigen, and rapidly re-accumulate during subsequent pregnancy. pTreg up-regulation could be hypothesized as a possible future therapeutic strategy in humans. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Enterocyte fatty acid-binding proteins (FABPs): different functions of liver and intestinal FABPs in the intestine.

PubMed

Gajda, Angela M; Storch, Judith

2015-02-01

Fatty acid-binding proteins (FABP) are highly abundant cytosolic proteins that are expressed in most mammalian tissues. In the intestinal enterocyte, both liver- (LFABP; FABP1) and intestinal FABPs (IFABP; FABP2) are expressed. These proteins display high-affinity binding for long-chain fatty acids (FA) and other hydrophobic ligands; thus, they are believed to be involved with uptake and trafficking of lipids in the intestine. In vitro studies have identified differences in ligand-binding stoichiometry and specificity, and in mechanisms of FA transfer to membranes, and it has been hypothesized that LFABP and IFABP have different functions in the enterocyte. Studies directly comparing LFABP- and IFABP-null mice have revealed markedly different phenotypes, indicating that these proteins indeed have different functions in intestinal lipid metabolism and whole body energy homeostasis. In this review, we discuss the evolving knowledge of the functions of LFABP and IFABP in the intestinal enterocyte. Copyright © 2014 Elsevier Ltd. All rights reserved.

Enterocyte-afferent nerve interactions in dietary fat sensing.

PubMed

Mansouri, A; Langhans, W

2014-09-01

The central nervous system (CNS) constantly monitors nutrient availability in the body and, in particular, in the gastrointestinal (GI) tract to regulate nutrient and energy homeostasis. Extrinsic parasympathetic and sympathetic nerves are crucial for CNS nutrient sensing in the GI tract. These extrinsic afferent nerves detect the nature and amount of nutrients present in the GI tract and relay the information to the brain, which controls energy intake and expenditure accordingly. Dietary fat and fatty acids are sensed through various direct and indirect mechanisms. These sensing processes involve the binding of fatty acids to specific G protein-coupled receptors expressed either on the afferent nerve fibres or on the surface of enteroendocrine cells that release gut peptides, which themselves can modulate afferent nerve activity through their cognate receptors or have endocrine effects directly on the brain. Further dietary fat sensing mechanisms that are related to enterocyte fat handling and metabolism involve the release of several possible chemical mediators such as fatty acid ethanolamides or apolipoprotein A-IV. We here present evidence for yet another mechanism that may be based on ketone bodies resulting from enterocyte oxidation of dietary fat-derived fatty acids. The presently available evidence suggests that sympathetic rather than vagal afferents are involved, but further experiments are necessary to critically examine this concept. © 2014 John Wiley & Sons Ltd.

Computerised electronic foetal heart rate monitoring in labour: automated contraction identification.

PubMed

Georgieva, A; Payne, S J; Redman, C W G

2009-12-01

The foetal heart rate (FHR) response to uterine contractions is crucial to detect foetal distress by electronic FHR monitoring during labour. We are developing a new automated system (OxSys) for decision support in labour, using the Oxford database of intrapartum FHR records. We describe here a novel technique for automated detection of uterus contractions. In addition, we present a comparison of the new method with four other computerised approaches. During training, OxSys achieved sensitivity above 95% and positive predictive value (PPV) of up to 90% for traces of good quality. During testing, OxSys achieved sensitivity = 87% and PPV = 75%. For comparison, a second clinical expert obtained sensitivity = 93% and PPV = 80%, and all other computerised approaches achieved lower values. It was concluded that the proposed method can be employed with confidence in our study on foetal health assessment in labour and future OxSys development.

Sonographic correlation of foetal neck circumference and area with gestational age among pregnant women in Port Harcourt, Nigeria.

PubMed

Abonyi, Obinna Everistus; Eze, Charles Ugwoke; Onwuzu, Sobechukwu W I

2017-11-01

The purpose of this study was to create a reference range nomogram of foetal neck circumference (FNC) and foetal neck area (FNA) in a Nigerian population using polynomial regression models. This cross-sectional study involved 723 pregnant women between 14 and 40 weeks of gestation. Axial measurements of the FNC and FNA were obtained in three measurements and the mean taken as the final value and the 5th, 50th and 95th percentiles for each foetal gestational age (FGA) were calculated. FNC and FNA correlated strongly with FGA, biparietal diameter, abdominal circumference, head circumference, and femoral length. Cubic models fitted the FNC vs FGA, and FNA vs. FGA values, and the mathematical relationships are given as: [Formula: see text] [Formula: see text] [Formula: see text]. Nomograms of FNC and FNA are thus generated. Impact statement The foetal neck circumference (FNC) and foetal neck area (FNA) can serve as predictors of foetal gestational age (FGA) since they correlate strongly and positively with FGA and known biometric parameters. The measurements obtained vary with the population studied. This study provides a nomogram of the FNA and FNC for an African population. The values correlate with that of the Caucasian population up to 32 weeks FGA. Interestingly, FNA and FNC measurements demonstrate high correlation but poor agreement in measurements between sonographers. Even though FNA and FNC could be used as predictors of foetal gestational age, the measurements vary significantly between sonographers. This is attributable to the difficulty in obtaining a satisfactory axial view of foetal neck, which is dependent on foetal presentation.

Effects of gestational and pregestational diabetes mellitus on the foetal heart: a cross-sectional study.

PubMed

Dervisoglu, Pinar; Kosecik, Mustafa; Kumbasar, Serkan

2018-04-01

We examined the foetal cardiac structural and functional characteristics in diabetic pregnancies versus non-diabetic, healthy pregnancies. Between August 2015 and April 2016, 32 pregnant women with pregestational diabetes, 36 pregnant women with gestational diabetes, and 42 healthy pregnant women were scheduled to have foetal echocardiograms to assess cardiac structure and function. In the diabetic groups, the foetal interventricular septum (IVS) thickness was significantly greater than in non-diabetics (p < .05) but none had an IVS >2 SD from normal. The peak velocity of tricuspid E, and the E/A ratio were significantly lower in the diabetic groups (p < .05). Tricuspid valve E a values and the E a /A a ratio were lower in the diabetic group than in the control group (p < .05) but there was no significant difference between the pre-GDM and GDM groups (p > .05). Interventricular septal hypertrophy is the most common structural abnormality in diabetic pregnancies. These changes do not pose a risk to the foetal unless they cause functional impairment. Thus, we believe that it is important for diabetic pregnant women to be monitored for foetal cardiac diastolic dysfunction. Impact statement What is already known on this subject? Pregestational insulin-dependent diabetes mellitus is a relatively common condition in pregnancy, affecting up to 0.5% of the pregnant population. Foetuses of diabetic mothers are at an increased risk of perinatal morbidity and death. Gestational diabetes mellitus is under-recognised and affects up to 4% of pregnancies. Although diabetes mellitus is known to increase the risk of cardiovascular defects and structural changes (myocardial hypertrophy and diastolic dysfunction) due to foetal hyperglycaemia and hyperinsulinism, similar data in women with gestational diabetes is scarce. Moreover, the effect of maternal hyperglycaemia on foetal cardiac structure and function is unclear because of discordant results from previous

Sex-dependent effect of a low neurosteroid environment and intrauterine growth restriction on foetal guinea pig brain development.

PubMed

Kelleher, Meredith A; Palliser, Hannah K; Walker, David W; Hirst, Jonathan J

2011-03-01

Progesterone and its neuroactive metabolite, allopregnanolone, are present in high concentrations during pregnancy, but drop significantly following birth. Allopregnanolone influences foetal arousal and enhances cognitive and behavioural recovery following traumatic brain injury. Inhibition of allopregnanolone synthesis increases cell death in foetal animal brains with experimental hypoxia. We hypothesised that complications during pregnancy, such as early or preterm loss of placental steroids and intrauterine growth restriction (IUGR), would disrupt the foetal neurosteroid system, contributing to poor neurodevelopmental outcomes. This study aimed to investigate the effects of chronic inhibition of allopregnanolone synthesis before term and IUGR on developmental processes in the foetal brain. Guinea pig foetuses were experimentally growth restricted at mid-gestation and treated with finasteride, an inhibitor of allopregnanolone synthesis. Finasteride treatment reduced foetal brain allopregnanolone concentrations by up to 75% and was associated with a reduction in myelin basic protein (MBP) (P = 0.001) and an increase in glial fibrillary acidic protein expression in the subcortical white matter brain region (P < 0.001). IUGR resulted in decreased MBP expression (P < 0.01) and was associated with a reduction in the expression of steroidogenic enzyme 5α-reductase (5αR) type 2 in the foetal brain (P = 0.061). Brain levels of 5αR1 were higher in male foetuses (P = 0.008). Both IUGR and reduced foetal brain concentrations of allopregnanolone were associated with altered expression of myelination and glial cell markers within the developing foetal brain. The potential role of neurosteroids in protecting and regulating neurodevelopmental processes in the foetal brain may provide new directions for treatment of neurodevelopmental disorders in infants who are exposed to perinatal insults and pathologies.

Shiga toxin 1 interaction with enterocytes causes apical protein mistargeting through the depletion of intracellular galectin-3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Laiko, Marina; Murtazina, Rakhilya; Malyukova, Irina

Shiga toxins (Stx) 1 and 2 are responsible for intestinal and systemic sequelae of infection by enterohemorrhagic Escherichia coli (EHEC). However, the mechanisms through which enterocytes are damaged remain unclear. While secondary damage from ischemia and inflammation are postulated mechanisms for all intestinal effects, little evidence excludes roles for more primary toxin effects on intestinal epithelial cells. We now document direct pathologic effects of Stx on intestinal epithelial cells. We study a well-characterized rabbit model of EHEC infection, intestinal tissue and stool samples from EHEC-infected patients, and T84 intestinal epithelial cells treated with Stx1. Toxin uptake by intestinal epithelial cellsmore » in vitro and in vivo causes galectin-3 depletion from enterocytes by increasing the apical galectin-3 secretion. This Shiga toxin-mediated galectin-3 depletion impairs trafficking of several brush border structural proteins and transporters, including villin, dipeptidyl peptidase IV, and the sodium-proton exchanger 2, a major colonic sodium absorptive protein. The mistargeting of proteins responsible for the absorptive function might be a key event in Stx1-induced diarrhea. These observations provide new evidence that human enterocytes are directly damaged by Stx1. Conceivably, depletion of galectin-3 from enterocytes and subsequent apical protein mistargeting might even provide a means whereby other pathogens might alter intestinal epithelial absorption and produce diarrhea.« less

Substance P and central respiratory activity: a comparative in vitro study on foetal and newborn rat.

PubMed

Ptak, K; Di Pasquale, E; Monteau, R

1999-05-14

Experiments were performed in vitro on foetal (embryonic days 18 to 21, E18-21) and newborn rat (postnatal days 0 to 3, P0-3) brainstem spinal cord preparations to analyse the perinatal developmental changes in the effects induced by substance P. Superfusion of the preparations with SP-containing artificial cerebrospinal fluid (aCSF) induced significant increase in the respiratory frequency of newborn rats (10-9 M), whereas concentration up to 10-7 M induced no change in foetal preparations. A whole cell patch clamp approach was used to record intracellularly from phrenic motoneurones. In newborn or E20-21 foetal rats SP-containing aCSF depolarised the phrenic motoneurones, increased their input resistance, reduced the rheobase current and shifted the frequency-intensity curves upward. In E18 foetal rats, no change was evoked by SP. A peptidase inhibitor mixture was used to block the enzymatic degradation of endogenous SP. This mixture was ineffective in changing the respiratory frequency in newborn and foetal preparations. In newborn rat phrenic motoneurones, the peptidase inhibitor mixture induced changes similar to those caused by SP but no change was induced in foetal rats. These results indicate that SP may modulate (i) the activity of the respiratory rhythm generator in newborn but not in foetal rats, and (ii) the activity of phrenic motoneurones at E20, E21 and in newborn rats but not at E18. Results obtained using the peptidase inhibitor mixture suggest that endogenous SP is probably not involved in the control of the respiratory rhythm in the prenatal period, but may influence the activity of the phrenic motoneurones after birth. Copyright 1999 Elsevier Science B.V.

Differentiation of rat brown adipocytes during late foetal development: role of insulin-like growth factor I.

PubMed Central

Teruel, T; Valverde, A M; Alvarez, A; Benito, M; Lorenzo, M

1995-01-01

Rat brown adipocytes at day 22 of foetal development showed greater size, higher mitochondria content and larger amounts of lipids, as determined by flow cytometry, than 20-day foetal cells. Simultaneously, an inhibition on the percentage of brown adipocytes into S+G2/M phases of the cell cycle was observed between days 20 and 22 of foetal development. The expression of several adipogenesis-related genes, such as fatty acid synthase, malic enzyme, glucose-6-phosphate dehydrogenase and insulin-regulated glucose transporter, increased at the end of foetal life in brown adipose tissue. In addition, the lipogenic enzyme activities and the lipogenic flux increased during late foetal development, resulting in mature brown adipocytes showing a multilocular fat droplet phenotype. Concurrently, brown adipocytes induced the expression of the uncoupling protein (UP) mRNA and UP protein, as visualized by immunofluorescence. The three isoforms of CCAAT enhancer-binding proteins (C/EBPs) were expressed at the mRNA level in brown adipose tissue at day 20. C/EBP alpha decreased and C/EBP beta and delta increased their expression between days 20 and 22 of foetal development, respectively. Brown adipose tissue constitutively expressed insulin-like growth factor I (IGF-I) and IGF-I receptor (IGF-IR) mRNAs. Moreover, IGF-IR mRNA content increased between days 20 and 22 in parallel with the occurrence of tissue differentiation. Images Figure 2 Figure 3 Figure 4 PMID:7575409

Machine learning for the automatic localisation of foetal body parts in cine-MRI scans

NASA Astrophysics Data System (ADS)

Bowles, Christopher; Nowlan, Niamh C.; Hayat, Tayyib T. A.; Malamateniou, Christina; Rutherford, Mary; Hajnal, Joseph V.; Rueckert, Daniel; Kainz, Bernhard

2015-03-01

Being able to automate the location of individual foetal body parts has the potential to dramatically reduce the work required to analyse time resolved foetal Magnetic Resonance Imaging (cine-MRI) scans, for example, for use in the automatic evaluation of the foetal development. Currently, manual preprocessing of every scan is required to locate body parts before analysis can be performed, leading to a significant time overhead. With the volume of scans becoming available set to increase as cine-MRI scans become more prevalent in clinical practice, this stage of manual preprocessing is a bottleneck, limiting the data available for further analysis. Any tools which can automate this process will therefore save many hours of research time and increase the rate of new discoveries in what is a key area in understanding early human development. Here we present a series of techniques which can be applied to foetal cine-MRI scans in order to first locate and then differentiate between individual body parts. A novel approach to maternal movement suppression and segmentation using Fourier transforms is put forward as a preprocessing step, allowing for easy extraction of short movements of individual foetal body parts via the clustering of optical flow vector fields. These body part movements are compared to a labelled database and probabilistically classified before being spatially and temporally combined to give a final estimate for the location of each body part.

Susceptibility of porcine ileal enterocytes to the cytotoxin of Serpulina hyodysenteriae and the resolution of the epithelial lesions: an electron microscopic study.

PubMed

Bland, A P; Frost, A J; Lysons, R J

1995-01-01

The cytotoxin from Serpulina hyodysenteriae was injected into ileal loops of eight germ-free pigs, and the effects on the villi were observed after 1, 3, and 18 hours of exposure. The mature vacuolated villus enterocytes of the proximal part of the absorptive villi were most susceptible to the lethal effects of the cytotoxin and were extensively exfoliated. The enterocytes at the base of the villi, the goblet cells, and the follicle-associated epithelium of the dome villi, particularly the M cells, were less affected. As the enterocytes were shed, the villi progressively shortened and the basement membrane became extensively folded. The absorptive villi were markedly stunted at 3 hours, and flattened globlet cells predominated at the site of restitution of the lesion. The myofibroblasts were also damaged, apparently subsequent to the exfoliation of the enterocytes. There was no further damage at 18 hours. The absorptive villi were stunted and were devoid of the large interstitial spaces of the normal lamina propria; the enterocytes were generally columnar, and at the apex of each villus there was an accumulation of goblet cells. There was a preponderance of M cells at the apices of the dome villi. Restitution of the lesions was not as rapid as observed in in vitro systems. The changes observed indicated that as the proximal enterocytes of the absorptive villi were shed, the loss of hydrostatic forces in the lamina propria allowed the myofibroblasts to collapse the villi by progressively retracting the basement membrane. This reduced the surface area to be covered during restitution. Resolution of the lesions was still incomplete after 18 hours.

Foetal Antiepileptic Drug Exposure and Verbal versus Non-Verbal Abilities at Three Years of Age

ERIC Educational Resources Information Center

Meador, Kimford J.; Baker, Gus A.; Browning, Nancy; Cohen, Morris J.; Clayton-Smith, Jill; Kalayjian, Laura A.; Kanner, Andres; Liporace, Joyce D.; Pennell, Page B.; Privitera, Michael; Loring, David W.

2011-01-01

We previously reported that foetal valproate exposure impairs intelligence quotient. In this follow-up investigation, we examined dose-related effects of foetal antiepileptic drug exposure on verbal and non-verbal cognitive measures. This investigation is an ongoing prospective observational multi-centre study in the USA and UK, which has enrolled…

Preliminary evaluation of foetal liver volume by three-dimensional ultrasound in women with gestational diabetes mellitus.

PubMed

İlhan, Gülşah; Gültekin, Hüseyin; Kubat, Ayça; Gokmen Karasu, Ayse Filiz; Güngör, Emre Sinan; Zebitay, Galip Ali; Verit Atmaca, Fatma Ferda

2018-03-19

The aim of the study was to assess the standard foetal biometric measurements and foetal liver volume (FLV) in pregnancies complicated by gestational diabetes mellitus (GDM) at the time of GDM screening and to compare the results with foetuses in normal pregnancies. Ninety-seven pregnant women with normal singleton uncomplicated pregnancies between 24 and 28 weeks of gestation were allocated into GDM (+) (n: 33) and GDM (-) (n: 64) groups based on their 75 g oral glucose tolerance test results. Foetal biometric measurements and FLV measurements of the groups were compared. Although there were no significant differences in the standard biometric measurements between the two groups, FLV was significantly higher in the women with GDM (p < .01). The ROC analysis implied that with a cut-off value of FLV of 32.72 cm 3 for GDM prediction, the sensitivity was 78.8% and specificity was 56.3%. We suggest that FLV measurements during the second-trimester ultrasound scanning may be a tool for the prediction of GDM in the obstetric population. Impact statement What is already known on this subject? GDM is an important pregnancy disease, because of its possible foetal and maternal complications. Besides the standard biometric measurements, some other foetal body dimensions such as the anterior abdominal wall thickness, skinfold thickness, adipose tissue thickness, Wharton's jelly thickness, foetal liver length and foetal liver volume (FLV) have been evaluated as ultrasound parameters of glycaemic control. While the evaluation of foetal liver dimensions has a role in identifying foetal growth acceleration, previous studies addressed patients with insulin-dependent diabetes mellitus rather than gestational diabetes mellitus, utilised two-dimensional ultrasound and did not argue the diagnostic value of these findings. What do the results of this study add? In our study, besides the standard biometric measurements, the FLV measurements were evaluated by a three

Assessment of growth dynamics of human cranium middle fossa in foetal period.

PubMed

Skomra, Andrzej; Kędzia, Alicja; Dudek, Krzysztof; Bogacz, Wiesław

2014-01-01

Available literature analysis demonstrated smallness of studies of cranial base. The goal of the study was to analyse the medial fossa of the human cranium in the foetal period against other fossae. Survey material consisted of 110 human foetuses at a morphological age of 16-28 weeks of foetal life, CRL 98-220 mm. Anthropological, preparation method, reverse method and statistical analysis were utilized. The survey incorporated the following computer programmes: Renishaw, TraceSurf, AutoCAD, CATIA. The reverse method seems especially interesting (impression with polysiloxane (silicone elastomer of high adhesive power used in dentistry) with 18 D 4823 activator. Elicited impression accurately reflected complex shape of cranium base. On assessing the relative rate of cranium medial fossa, the rate was found to be stable (linear model) for the whole of the analysed period and is 0.19%/week, which stands for the gradual and steady growth of the middle fossa in relation to the whole of the cranium base. At the same time, from the 16th till 28th week of foetal life, relative volume of the cranium middle fossa increases more intensively than cranium anterior fossa, whereas the cranium middle fossa volume as compared with the cranium posterior fossa is definitely slower. In the analysed period, the growth rate of the cranium base middle fossa was bigger in the 4th and 5th weeks than in the 6th and 7th weeks of foetal life. The investigations revealed cranium base asymmetry of the left side. Furthermore, the anterior fossae volume on the left side is significantly bigger than the one of the fossae on the right side. Volume growth rate is more intensive in the 4th and 5th than in the 6th and 7th weeks of foetal life. In the examined period, the relative growth rate of cranium base middle fossa is 0.19%/week and it is stable - linear model. The study revealed correlations in the form of mathematical models, which enabled foetuses age assessment.

Surface immunoglobulin on cultured foetal mouse thymocytes

PubMed Central

Haustein, D.; Mandel, T. E.

1979-01-01

Organ cultures of 14–15 day foetal mouse thymus were used as a source of non-neoplastic differentiating T cells, free of contaminating B cells. Viable cells obtained from such cultured thymuses were radio-iodinated and immunoglobulins (Ig) were isolated by co-precipitation from the 125I-labelled cell-surface proteins released during 1 h of incubation at 37°. The precipitates, both reduced and unreduced, were then analysed by polyacrylamide gel electrophoresis. The unreduced material migrated in a 5% gel as a single peak with a mobility slightly faster than that of mouse IgG. After reduction, however, two peaks were obtained (in a 10% gel), one corresponding in migration to mouse light chain and the other which moved slightly faster than mouse μ chain. This pattern was identical with that previously seen for both surface Ig of normal mouse thymocytes and neoplastic T lymphoma cells. Uncultured, 15 day foetal thymocytes did not produce any detectable co-precipitated cell surface material. Ig detected in these experiments was therefore produced during in vitro culture by non-neoplastic T cells in a system free of contaminating B cells and mouse serum proteins. PMID:315364

Direct effects of fermented cow's milk product with Lactobacillus paracasei CBA L74 on human enterocytes.

PubMed

Paparo, L; Aitoro, R; Nocerino, R; Fierro, C; Bruno, C; Canani, R Berni

2018-01-29

Cow's milk fermented with Lactobacillus paracasei CBA L74 (FM-CBAL74) exerts a preventive effect against infectious diseases in children. We evaluated if this effect is at least in part related to a direct modulation of non-immune and immune defence mechanisms in human enterocytes. Human enterocytes (Caco-2) were stimulated for 48 h with FM-CBAL74 at different concentrations. Cell growth was assessed by colorimetric assay; cell differentiation (assessed by lactase expression), tight junction proteins (zonula occludens1 and occludin), mucin 2, and toll-like receptor (TRL) pathways were analysed by real-time PCR; innate immunity peptide synthesis, beta-defensin-2 (HBD-2) and cathelicidin (LL-37) were evaluated by ELISA. Mucus layer thickness was analysed by histochemistry. FMCBA L74 stimulated cell growth and differentiation, tight junction proteins and mucin 2 expression, and mucus layer thickness in a dose-dependent fashion. A significant stimulation of HBD-2 and LL-37 synthesis, associated with a modulation of TLR pathway, was also observed. FM-CBAL74 regulates non-immune and immune defence mechanisms through a direct interaction with the enterocytes. These effects could be involved in the preventive action against infectious diseases demonstrated by this fermented product in children.

Evolution of ventriculomegaly: comparison between foetal MR imaging and postnatal diagnostic imaging.

PubMed

Mehrabi, Sara; Adami, Alessia; Ventriglia, Anna; Zantedeschi, Lisa; Franchi, Massimo; Manfredi, Riccardo

2013-10-01

We evaluated the evolution of ventriculomegaly (VM) by comparing foetal magnetic resonance imaging (MRI) with postnatal transcranial ultrasonography (US) and/or encephalic MRI. Between January 2006 and April 2011, 70 foetuses with a mean gestational age of 28 weeks and 4 days (range, 18-36) weeks with VM on foetal MRI were assessed in this prospective study. Half-Fourier rapid acquisition with relaxation enhancement (RARE) T2-weighted, T1-weighted and diffusion-weighted (DWI) images along the three orthogonal planes according to the longitudinal axis of the mother, and subsequently of the foetal brain, were acquired. Quantitative image analysis included the transverse diameter of lateral ventricles in axial and coronal planes. Qualitative image analysis included searching for associated structural anomalies. Thirty-four of 70 patients with a diagnosis of VM on foetal MRI underwent postnatal imaging. Twenty-five of those 34 (73%) had mild, four (12%) had moderate and five (15%) had severe VM on MRI. Normalisation of the diameter of lateral ventricles was observed in 16 of the 34 (47%) newborns. Among these 16, 13 (81%) had mild and three (19%) had moderate VM (two isolated and one associated VM). VM stabilisation was observed in 16 of the 34 (47%) babies. Among them, 11 (69%) had mild (eight isolated and three associated), one (6%) had moderate associated and four (25%) had severe associated VM. Progression from mild to severe (associated) VM was observed in two of the 34 (6%) babies. The absence of associated anomalies and a mild VM are favourable prognostic factors in the evolution of VM.

Associations Between Maternal-Foetal Attachment and Infant Developmental Outcomes: A Systematic Review.

PubMed

Branjerdporn, Grace; Meredith, Pamela; Strong, Jenny; Garcia, Jenniffer

2017-03-01

Objectives Infant developmental outcomes may be influenced by a range of prenatal maternal characteristics. While there is some evidence to suggest that maternal-foetal attachment may be associated with infant developmental outcomes, there is a need to systematically review this evidence to guide future research and clinical practice. Methods Five electronic databases were systematically scanned. Key journals and reference lists were hand-searched. Papers were included if: (1) pregnant women were assessed for maternal-foetal attachment; (2) the infants were later assessed, under 2 years old, for any developmental outcome (e.g., social-emotional, cognition, motor, language, adaptive behaviour); and (3) they were published in English. Two independent reviewers used the STROBE checklist to appraise the quality of each paper. Results Of the 968 papers identified, eight were included in the review, and four of these were of low quality (<60 %) based on the STROBE. The developmental domains that were examined included: infant temperament (n = 5), adaptive behaviour (e.g., colic, sleep) (n = 2), and milestone attainment (n = 1). There is some evidence to suggest that lower maternal-foetal attachment is related to suboptimal developmental outcomes. However, these results should be interpreted with caution due to the limited and low quality studies available. Conclusions Although maternal-foetal attachment may be associated with infant developmental outcomes, future research is required which: (1) considers a range of developmental outcomes, (2) has increased scientific rigour, (3) assesses mother-infant dyads at different prenatal and postnatal time points, and (4) examines different target populations.

Development of somatosensory-evoked potentials in foetal sheep: effects of betamethasone.

PubMed

Anegroaie, P; Frasch, M G; Rupprecht, S; Antonow-Schlorke, I; Müller, T; Schubert, H; Witte, O W; Schwab, M

2017-05-01

Antenatal glucocorticoids are used to accelerate foetal lung maturation in babies threatened with premature labour. We examined the influence of glucocorticoids on functional and structural maturation of the central somatosensory pathway in foetal sheep. Somatosensory-evoked potentials (SEP) reflect processing of somatosensory stimuli. SEP latencies are determined by afferent stimuli transmission while SEP amplitudes reveal cerebral processing. After chronic instrumentation of foetal sheep, mothers received saline (n = 9) or three courses of betamethasone (human equivalent dose of 2 × 110 μg kg -1 betamethasone i.m. 24 h apart, n = 12) at 0.7, 0.75 and 0.8 of gestational age. Trigeminal SEP were evoked prior to, 4 and 24 h after each injection and at 0.8 of gestational age before brains were histologically processed. Somatosensory-evoked potentials were already detectable at 0.7 of gestation age. The early and late responses N20 and N200 were the only reproducible peaks over the entire study period. With advancing gestational age, SEP latencies decreased but amplitudes remained unchanged. Acutely, betamethasone did not affect SEP latencies and amplitudes 4 and 24 h following administration. Chronically, betamethasone delayed developmental decrease in the N200 but not N20 latency by 2 weeks without affecting amplitudes. In parallel, betamethasone decreased subcortical white matter myelination but did not affect network formation and synaptic density in the somatosensory cortex. Somatosensory stimuli are already processed by the foetal cerebral cortex at the beginning of the third trimester. Subsequent developmental decrease in SEP latencies suggests ongoing maturation of afferent sensory transmission. Antenatal glucocorticoids affect structural and functional development of the somatosensory system with specific effects at subcortical level. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

The effects of pentobarbitone and pethidine on foetal breathing movements in sheep.

PubMed Central

Boddy, K; Dawes, G S; Fisher, R L; Pinter, S; Robinson, J S

1976-01-01

1 Small doses of pentobarbitone (4 mg/kg i.v.) administered to sheep in the last third of pregancy had little overt effect on the mothers. In the foetus they caused arrest of breathing movements, an alteration in the character of the electrocorticogram and cardiovascular changes which varied with gestational age. 2 In contrast, relatively large doses of pethidine (100-200 mg) admininstered to the mother had no consistent effect on normal foetal breathing movements, though they abolished the foetal response to hypercapnia. 3 The results are discussed in relation to feotal sleep state. PMID:7337

Evaluation of Interruption Behavior by Naive Encoders.

ERIC Educational Resources Information Center

Coon, Christine A.; Schwanenflugel, Paula J.

1996-01-01

Determines the characteristics of interactions that influence judgments of interruption behavior in naive observers. Asks subjects to decide whether an example of an interruption was an interruption and then rate it in terms of how "good" or "bad" it was. Finds that naive observers use some of the same features described in…

Temporary hindlimb paresis following dystocia due to foetal macrosomia in a Celebes crested macaque (Macaca nigra).

PubMed

Debenham, John James; Bettembourg, Vanessa; Østevik, Liv; Modig, Michaela; Jâderlund, Karin Hultin; Lervik, Andreas

2017-04-01

A multiparous Celebes crested macaque presented with dystocia due to foetal macrosomia, causing foetal mortality and hindlimb paresis. After emergency caesarean section, recovery of motor function took 1 month before hindlimbs were weight bearing and 2 months before re-integration with the troop. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Risk of Erectile Dysfunction in Transfusion-naive Thalassemia Men

PubMed Central

Chen, Yu-Guang; Lin, Te-Yu; Lin, Cheng-Li; Dai, Ming-Shen; Ho, Ching-Liang; Kao, Chia-Hung

2015-01-01

Abstract Based on the mechanism of pathophysiology, thalassemia major or transfusion-dependent thalassemia patients may have an increased risk of developing organic erectile dysfunction resulting from hypogonadism. However, there have been few studies investigating the association between erectile dysfunction and transfusion-naive thalassemia populations. We constructed a population-based cohort study to elucidate the association between transfusion-naive thalassemia populations and organic erectile dysfunction This nationwide population-based cohort study involved analyzing data from 1998 to 2010 obtained from the Taiwanese National Health Insurance Research Database, with a follow-up period extending to the end of 2011. We identified men with transfusion-naive thalassemia and selected a comparison cohort that was frequency-matched with these according to age, and year of diagnosis thalassemia at a ratio of 1 thalassemia man to 4 control men. We analyzed the risks for transfusion-naive thalassemia men and organic erectile dysfunction by using Cox proportional hazards regression models. In this study, 588 transfusion-naive thalassemia men and 2337 controls were included. Total 12 patients were identified within the thalassaemia group and 10 within the control group. The overall risks for developing organic erectile dysfunction were 4.56-fold in patients with transfusion-naive thalassemia men compared with the comparison cohort after we adjusted for age and comorbidities. Our long-term cohort study results showed that in transfusion-naive thalassemia men, there was a higher risk for the development of organic erectile dysfunction, particularly in those patients with comorbidities. PMID:25837766

Developmental origins of adult health and disease: the role of periconceptional and foetal nutrition.

PubMed

McMillen, I Caroline; MacLaughlin, Severence M; Muhlhausler, Beverly S; Gentili, Sheridan; Duffield, Jaime L; Morrison, Janna L

2008-02-01

The 'developmental origins of adult health and disease' hypothesis stated that environmental factors, particularly maternal undernutrition, act in early life to programme the risks for adverse health outcomes, such as cardiovascular disease, obesity and the metabolic syndrome in adult life. Early physiological tradeoffs, including activation of the foetal hypothalamo-pituitary-adrenal (HPA) axis, confer an early fitness advantage such as foetal survival, while incurring delayed health costs. We review the evidence that such tradeoffs are anticipated from conception and that the periconceptional nutritional environment can programme the developmental trajectory of the stress axis and the systems that maintain and regulate arterial blood pressure. There is also evidence that restriction of placental growth and function, results in an increased dependence of the maintenance of arterial blood pressure on the sequential recruitment of the sympathetic nervous system and HPA axis. While the 'early origins of adult disease' hypothesis has focussed on the impact of maternal undernutrition, an increase in maternal nutritional intake and in maternal body mass intake has become more prevalent in developed countries. Exposure to overnutrition in foetal life results in a series of central and peripheral neuroendocrine responses that in turn programme development of the fat cell and of the central appetite regulatory system. While the physiological responses to foetal undernutrition result in the physiological trade off between foetal survival and poor health outcomes that emerge after reproductive senescence, exposure to early overnutrition results in poor health outcomes that emerge in childhood and adolescence. Thus, the effects of early overnutrition can directly impact on reproductive fitness and on the health of the next generation. In this context, the physiological responses to relative overnutrition in early life may directly contribute to an intergenerational cycle of

Determination of first pregnancy and foetal measurements in Egyptian Baladi goats (Capra hircus).

PubMed

Amer, Hussein A

2008-01-01

This study was conducted using B-mode transrectal (TR) and transabdominal (TA) ultrasonography to determine early pregnancy and fetometry. A total of 110 does aged between 8 and 36 months were used. The detection of early pregnancy and foetal number was measured. The relationship between gestation age and crown-rump length (CRL) and bi-parietal diameter (BPD) was determined from days 40 to 109 of gestation. The accuracy of foetal sexing was determined by differentiation of genital tubercle (GT) from days 40 to 109 of gestation and then followed up after birth. The examination revealed 95.5% of does were pregnant, with 100% accuracy in detecting pregnancy for positive cases. The foetal number was 45.7% and 54.3% for single and twins/triplets. The TR probe enabled more reliable and early recognition of foetal fluid (5 days) and heart beats (4 days) than the TA probe. The TR observation of heart beats is recommended as conclusive evidence of the presence of a live foetus. The TA convex probe was used from days 40-89 to measure CRL and from days 40-109 to measure BPD. The relation between gestational age and CRL or BPD were highly significant (p<0.0001). The accuracy of sex identification among the three groups was not significantly (p>0.05) higher in single, compared to multiple pregnancies. In total, 83.3% and 70.2% of single and twins and triplets were sexed. After birth, one case was misdiagnosed by ultrasound, i.e. 83.3% (single) and 68.4% (twins and triplets) were sexed. However, identification of GT in male foetuses was possible from day 40 onwards. From a total 105 scanned does, 80 (76.2%) were sexed and 75.2% of cases were sexed after birth. B-mode real-time ultrasonography is recommended as a reliable means that can be used in field conditions to provide early detection of gestation as early as 19-27 days after mating, for CRL or BPD measuring and foetal sexing from day 40 of gestation onwards.

Smoking, physical exercise, BMI and late foetal death: a study within the Danish National Birth Cohort.

PubMed

Morales-Suárez-Varela, Maria; Nohr, Ellen A; Bech, Bodil H; Wu, Chunsen; Olsen, Jørn

2016-10-01

The aim of this paper was to estimate the effect of maternal and paternal smoking on foetal death (miscarriage and stillbirth) and to estimate potential interactions with physical exercise and pre-pregnancy body mass index. We selected 87,930 pregnancies from the population-based Danish National Birth Cohort. Information about lifestyle, occupational, medical and obstetric factors was obtained from a telephone interview and data on pregnancy outcomes came from the Danish population based registries. Cox regression was used to estimate the hazard ratios (adjusted for potential confounders) for predominantly late foetal death (miscarriage and stillbirth). An interaction contrast ratio was used to assess potential effect measure modification of smoking by physical exercise and body mass index. The adjusted hazard ratio of foetal death was 1.22 (95 % CI 1.02-1.46) for couples where both parents smoked compared to non-smoking parents (miscarriage: 1.18, 95 % CI 0.96-1.44; stillbirth: 1.32, 95 % CI 0.93-1.89). On the additive scale, we detected a small positive interaction for stillbirth between smoking and body mass index (overweight women). In conclusion, smoking during pregnancy was associated with a slightly higher hazard ratio for foetal death if both parents smoked. This study suggests that smoking may increase the negative effect of a high BMI on foetal death, but results were not statistically significant for the interaction between smoking and physical exercise.

Erythroid differentiation ability of butyric acid analogues: identification of basal chemical structures of new inducers of foetal haemoglobin.

PubMed

Bianchi, Nicoletta; Chiarabelli, Cristiano; Zuccato, Cristina; Lampronti, Ilaria; Borgatti, Monica; Amari, Gabriele; Delcanale, Maurizio; Chiavilli, Francesco; Prus, Eugenia; Fibach, Eitan; Gambari, Roberto

2015-04-05

Several investigations have demonstrated a mild clinical status in patients with β-globin disorders and congenital high persistence of foetal haemoglobin. This can be mimicked by a pharmacological increase of foetal γ-globin genes expression and foetal haemoglobin production. Our goal was to apply a multistep assay including few screening methods (benzidine staining, RT-PCR and HPLC analyses) and erythroid cellular model systems (the K562 cell line and erythroid precursors collected from peripheral blood) to select erythroid differentiation agents with foetal haemoglobin inducing potential. With this methodology, we have identified a butyric acid derivative, namely the 4174 cyclopropanecarboxylic acid compound, able to induce erythroid differentiation without antiproliferative effect in K562 cells and increase of γ-globin gene expression in erythroid precursor cells. The results are relevant for pharmacological treatments of haemoglobinopathies, including β-thalassaemia and sickle cell anaemia. Copyright © 2015 Elsevier B.V. All rights reserved.

Potential combined effects of maternal smoking and coffee intake on foetal death within the Danish National Birth Cohort.

PubMed

Morales-Suárez-Varela, Maria; Nohr, Ellen A; Olsen, Jørn; Bech, Bodil H

2018-04-01

Several studies have linked coffee intake and smoking to foetal death, but a possible interaction between both exposures remains unknown. We studied, within the Danish National Birth Cohort, the potential interaction between smoking and coffee drinking while pregnant on the risk of foetal (early and late) death. The study included 90 086 pregnant women, with information about their smoking habit and coffee intake in early pregnancy, and several potential confounding factors. Interaction was studied by calculating both the hazard ratio (HR) in Cox's regression (linear and smoothed restricted cubic spline) and the interaction contrast ratio (ICR). Women who neither smoked nor drank coffee were used as the reference group. Drinking more than 3 cups/d of coffee was associated with the highest risk of foetal death, spontaneous abortion and stillbirth for all smoking status (non-smoker, ≤10 or > 10 cigarettes/d). Among smokers, the combination with drinking <3 cups/d of coffee presented the lowest HRa for foetal death, spontaneous abortion and stillbirth. The ICRs were negative when considering smokers who had a coffee intake up to 3 cups/d, but they were positive for those who had a higher coffee intake, suggesting the effect of coffee intake may be non-linear. Our results suggest that the combined effect of smoking and coffee intake during pregnancy on the risk of foetal death is coffee-dose-dependent. A low coffee intake may reduce the risk of foetal death associated with smoking while a high coffee intake increases the risk.

Human Naive T Cells Express Functional CXCL8 and Promote Tumorigenesis.

PubMed

Crespo, Joel; Wu, Ke; Li, Wei; Kryczek, Ilona; Maj, Tomasz; Vatan, Linda; Wei, Shuang; Opipari, Anthony W; Zou, Weiping

2018-05-25

Naive T cells are thought to be functionally quiescent. In this study, we studied and compared the phenotype, cytokine profile, and potential function of human naive CD4 + T cells in umbilical cord and peripheral blood. We found that naive CD4 + T cells, but not memory T cells, expressed high levels of chemokine CXCL8. CXCL8 + naive T cells were preferentially enriched CD31 + T cells and did not express T cell activation markers or typical Th effector cytokines, including IFN-γ, IL-4, IL-17, and IL-22. In addition, upon activation, naive T cells retained high levels of CXCL8 expression. Furthermore, we showed that naive T cell-derived CXCL8 mediated neutrophil migration in the in vitro migration assay, supported tumor sphere formation, and promoted tumor growth in an in vivo human xenograft model. Thus, human naive T cells are phenotypically and functionally heterogeneous and can carry out active functions in immune responses. Copyright © 2018 by The American Association of Immunologists, Inc.

Successful treatment of complex traumatic and surgical wounds with a foetal bovine dermal matrix.

PubMed

Hayn, Ernesto

2014-12-01

A foetal bovine dermal repair scaffold (PriMatrix, TEI Biosciences) was used to treat complex surgical or traumatic wounds where the clinical need was to avoid skin flaps and to build new tissue in the wound that could be reepithelialised from the wound margins or closed with a subsequent application of a split-thickness skin graft (STSG). Forty-three consecutive cases were reviewed having an average size of 79·3 cm(2) , 50% of which had exposed tendon and/or bone. In a subset of wounds (44·7%), the implantation of the foetal dermal collagen scaffold was also augmented with negative pressure wound therapy (NPWT). Complete wound healing was documented in over 80% of the wounds treated, whether the wound was treated with the foetal bovine dermal scaffold alone (95·2%) or when supplemented with NPWT (82·4%). The scaffold successfully incorporated into wounds with exposed tendon and/or bone to build vascularised, dermal-like tissue. The new tissue in the wound supported STSGs however, in the majority of the cases (88·3%); wound closure was achieved through reepithelialisation of the incorporated dermal scaffold by endogenous wound keratinocytes. The foetal bovine dermal repair scaffold was found to offer an effective alternative treatment strategy for definitive closure of challenging traumatic or surgical wounds on patients who were not suitable candidates for tissue flaps. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Intestinal surfactant permeation enhancers and their interaction with enterocyte cell membranes in a mucosal explant system.

PubMed

Danielsen, E Michael; Hansen, Gert H

2017-07-03

Intestinal permeation enhancers (PEs) are agents aimed to improve oral delivery of therapeutic drugs with poor bioavailability. The main permeability barrier for oral delivery is the intestinal epithelium, and PEs act to increase the paracellular and/or transcellular passage of drugs. Transcellular passage can be achieved by cell membrane permeabilization and/or by endocytic uptake and subsequent transcytosis. One broad class of PEs is surfactants which act by inserting into the cell membrane, thereby perturbing its integrity, but little is known about how the dynamics of the membrane are affected. In the present work, the interaction of the surfactants lauroyl-L-carnitine, 1-decanoyl-rac-glycerol, and nonaethylene glycol monododecyl ether with the intestinal epithelium was studied in organ cultured pig jejunal mucosal explants. As expected, at 2 mM, these agents rapidly permeabilized the enterocytes for the fluorescent polar tracer lucifer yellow, but surprisingly, they all also blocked both constitutive -and receptor-mediated pathways of endocytosis from the brush border, indicating a complete arrest of apical membrane trafficking. At the ultrastructural level, the PEs caused longitudinal fusion of brush border microvilli. Such a membrane fusogenic activity could also explain the observed formation of vesicle-like structures and large vacuoles along the lateral cell membranes of the enterocytes induced by the PEs. We conclude that the surfactant action of the PEs selected in this study not only permeabilized the enterocytes, but profoundly changed the dynamic properties of their constituent cell membranes.

Sex Differences in the Association between Foetal Growth and Child Attention at Age Four: Specific Vulnerability of Girls

ERIC Educational Resources Information Center

Murray, Elizabeth; Matijasevich, Alicia; Santos, Iná S.; Barros, Aluísio J. D.; Anselmi, Luciana; Barros, Fernando C.; Stein, Alan

2015-01-01

Background: Recent evidence suggests that impaired foetal growth may provide an early indication of increased risk of child attention problems. However, despite both foetal growth and child attention problems differing by sex, few studies have examined sex differences in this association. Furthermore, no studies have been conducted in low- and…

Modeling of drug-mediated CYP3A4 induction by using human iPS cell-derived enterocyte-like cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Negoro, Ryosuke; Takayama, Kazuo; The Keihanshin Consortium for Fostering the Next Generation of Global Leaders in Research

Many drugs have potential to induce the expression of drug-metabolizing enzymes, particularly cytochrome P450 3A4 (CYP3A4), in small intestinal enterocytes. Therefore, a model that can accurately evaluate drug-mediated CYP3A4 induction is urgently needed. In this study, we overlaid Matrigel on the human induced pluripotent stem cells-derived enterocyte-like cells (hiPS-ELCs) to generate the mature hiPS-ELCs that could be applied to drug-mediated CYP3A4 induction test. By overlaying Matrigel in the maturation process of enterocyte-like cells, the gene expression levels of intestinal markers (VILLIN, sucrase-isomaltase, intestine-specific homeobox, caudal type homeobox 2, and intestinal fatty acid-binding protein) were enhanced suggesting that the enterocyte-like cellsmore » were maturated by Matrigel overlay. The percentage of VILLIN-positive cells in the hiPS-ELCs found to be approximately 55.6%. To examine the CYP3A4 induction potential, the hiPS-ELCs were treated with various drugs. Treatment with dexamethasone, phenobarbital, rifampicin, or 1α,25-dihydroxyvitamin D3 resulted in 5.8-fold, 13.4-fold, 9.8-fold, or 95.0-fold induction of CYP3A4 expression relative to that in the untreated controls, respectively. These results suggest that our hiPS-ELCs would be a useful model for CYP3A4 induction test. - Highlights: • The hiPS-ELCs were matured by Matrigel overlay. • The hiPS-ELCs expressed intestinal nuclear receptors, such as PXR, GR and VDR. • The hiPS-ELC is a useful model for the drug-mediated CYP3A4 induction test.« less

Inhibition of mitogen-activated protein kinase kinase, DNA methyltransferase, and transforming growth factor-β promotes differentiation of human induced pluripotent stem cells into enterocytes.

PubMed

Kodama, Nao; Iwao, Takahiro; Kabeya, Tomoki; Horikawa, Takashi; Niwa, Takuro; Kondo, Yuki; Nakamura, Katsunori; Matsunaga, Tamihide

2016-06-01

We previously reported that small-molecule compounds were effective in generating pharmacokinetically functional enterocytes from human induced pluripotent stem (iPS) cells. In this study, to determine whether the compounds promote the differentiation of human iPS cells into enterocytes, we investigated the effects of a combination of mitogen-activated protein kinase kinase (MEK), DNA methyltransferase (DNMT), and transforming growth factor (TGF)-β inhibitors on intestinal differentiation. Human iPS cells cultured on feeder cells were differentiated into endodermal cells by activin A. These endodermal-like cells were then differentiated into intestinal stem cells by fibroblast growth factor 2. Finally, the cells were differentiated into enterocyte cells by epidermal growth factor and small-molecule compounds. After differentiation, mRNA expression levels and drug-metabolizing enzyme activities were measured. The mRNA expression levels of the enterocyte marker sucrase-isomaltase and the major drug-metabolizing enzyme cytochrome P450 (CYP) 3A4 were increased by a combination of MEK, DNMT, and TGF-β inhibitors. The mRNA expression of CYP3A4 was markedly induced by 1α,25-dihydroxyvitamin D3. Metabolic activities of CYP1A1/2, CYP2B6, CYP2C9, CYP2C19, CYP3A4/5, UDP-glucuronosyltransferase, and sulfotransferase were also observed in the differentiated cells. In conclusion, MEK, DNMT, and TGF-β inhibitors can be used to promote the differentiation of human iPS cells into pharmacokinetically functional enterocytes. Copyright © 2016 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Foetal Testosterone, Social Relationships, and Restricted Interests in Children

ERIC Educational Resources Information Center

Knickmeyer, Rebecca; Baron-Cohen, Simon; Raggatt, Peter; Taylor, Kevin

2005-01-01

Background: Sex-differences exist in some areas of human social behaviour. In animals, foetal testosterone (fT) plays a central role in organising the brain and in later social behaviour. fT has also been implicated in language development, eye-contact, and spatial ability in humans. Methods: Fifty-eight children (35 male and 23 female), whose fT…

Enterocyte-specific epidermal growth factor prevents barrier dysfunction and improves mortality in murine peritonitis.

PubMed

Clark, Jessica A; Gan, Heng; Samocha, Alexandr J; Fox, Amy C; Buchman, Timothy G; Coopersmith, Craig M

2009-09-01

Systemic administration of epidermal growth factor (EGF) decreases mortality in a murine model of septic peritonitis. Although EGF can have direct healing effects on the intestinal mucosa, it is unknown whether the benefits of systemic EGF in peritonitis are mediated through the intestine. Here, we demonstrate that enterocyte-specific overexpression of EGF is sufficient to prevent intestinal barrier dysfunction and improve survival in peritonitis. Transgenic FVB/N mice that overexpress EGF exclusively in enterocytes (IFABP-EGF) and wild-type (WT) mice were subjected to either sham laparotomy or cecal ligation and puncture (CLP). Intestinal permeability, expression of the tight junction proteins claudins-1, -2, -3, -4, -5, -7, and -8, occludin, and zonula occludens-1; villus length; intestinal epithelial proliferation; and epithelial apoptosis were evaluated. A separate cohort of mice was followed for survival. Peritonitis induced a threefold increase in intestinal permeability in WT mice. This was associated with increased claudin-2 expression and a change in subcellular localization. Permeability decreased to basal levels in IFABP-EGF septic mice, and claudin-2 expression and localization were similar to those of sham animals. Claudin-4 expression was decreased following CLP but was not different between WT septic mice and IFABP-EGF septic mice. Peritonitis-induced decreases in villus length and proliferation and increases in apoptosis seen in WT septic mice did not occur in IFABP-EGF septic mice. IFABP-EGF mice had improved 7-day mortality compared with WT septic mice (6% vs. 64%). Since enterocyte-specific overexpression of EGF is sufficient to prevent peritonitis-induced intestinal barrier dysfunction and confers a survival advantage, the protective effects of systemic EGF in septic peritonitis appear to be mediated in an intestine-specific fashion.

Sex differences in the association between foetal growth and child attention at age four: specific vulnerability of girls.

PubMed

Murray, Elizabeth; Matijasevich, Alicia; Santos, Iná S; Barros, Aluísio J D; Anselmi, Luciana; Barros, Fernando C; Stein, Alan

2015-12-01

Recent evidence suggests that impaired foetal growth may provide an early indication of increased risk of child attention problems. However, despite both foetal growth and child attention problems differing by sex, few studies have examined sex differences in this association. Furthermore, no studies have been conducted in low- and middle-income countries, where there are higher rates of perinatal problems. This study aimed to test for sex differences in the association between foetal growth indices and attention problems at age four, in a large, prospective birth cohort from a middle-income country. A total of 3,749 neonates from the 2004 Pelotas birth cohort (Brazil) with foetal growth indices collected at birth [low birthweight (LBW), small-for-gestational age (SGA), head circumference (HC), head circumference-to-abdominal circumference ratio (HC/AC) and ponderal index (PI)], were assessed for attention problems using the Child Behaviour Checklist at age four. Ordinal logistic regression with successive adjustment for maternal, demographic, gestational, perinatal and child nutrition/mother-child morbidity, was conducted separately for girls and boys. In girls, attention difficulties were associated with being born SGA (OR = 1.40, CI = 1.08-1.82, p = .012), with a small HC (OR = 1.52, CI = 1.11-2.08, p = .009), or with a low PI (OR = 1.29, CI = 1.08-1.54, p = .005). There were no associations identified between attention difficulties and any foetal growth indices in boys. Our results show that girls with impaired foetal growth may be particularly at risk of attention difficulties in childhood. This is consistent with emerging research that female foetuses may be more vulnerable to certain suboptimal intrauterine environments, inducing epigenetic changes that lead to disturbed growth and long-term developmental impairment. © 2015 Association for Child and Adolescent Mental Health.

A foetal tile from an archaeological site: anthropological investigation of human remains recovered in a medieval cemetery in Northern Italy.

PubMed

Licata, Marta; Rossetti, Chiara; Tosi, Adelaide; Badino, Paola

2018-06-01

The recovery of foetal remains is very sporadic in archaeology, especially due the scarce degree of bone mineralisation. This paper presents the singular archaeological discovery of a foetal tile preserving the bone remains, object of our anthropological examination. The foetal tile was discovered during an archaeological excavation in a medieval site (Northern Italy). The tile was analysed by CT scan and later, human remains were anthropologically examined. The archaeological investigation revealed a special ritual destined to foetuses while forensic anthropological analysis allowed estimating the gestational age near to 21-24 weeks.

Transport of selenium across the plasma membrane of primary hepatocytes and enterocytes of rainbow trout.

PubMed

Misra, Sougat; Kwong, Raymond W M; Niyogi, Som

2012-05-01

Transport of essential solutes across biological membranes is one of the fundamental characteristics of living cells. Although selenium is an essential micronutrient, little is known about the cellular mechanisms of chemical species-specific selenium transport in fish. We report here the kinetic and pharmacological transport characteristics of selenite and its thiol (glutathione and l-cysteine) derivatives in primary cultures of hepatocytes and isolated enterocytes of rainbow trout. Findings from the current study suggest an apparent low-affinity linear transport system for selenite in both cell types. However, we recorded high-affinity Hill kinetics (K(d)=3.61±0.28 μmol l(-1)) in enterocytes exposed to selenite in the presence of glutathione. The uptake of selenite in the presence of thiols was severalfold higher than uptake of selenite alone (at equimolar concentration) in both hepatocytes and enterocytes. Cellular accumulation of selenium was found to be energy independent. Interestingly, we observed a decrease in selenite transport with increasing pH, whereas selenite uptake increased with increasing pH in the presence glutathione in both cell types. The cellular uptake of selenite demonstrated a pronounced competitive interaction with a structurally similar compound, sulfite. The uptake of selenite as well as its thiol derivatives was found to be sensitive to the anion transport blocker DIDS, irrespective of the cell type. Inorganic mercury (Hg(2+)) elicited an inhibition of selenite transport in both cell types, but augmented the transport of reduced forms of selenite in hepatocytes. Based on the substrate choice and comparable pharmacological properties, we advocate that multiple anion transport systems are probably involved in the cellular transport of selenite in fish.

Derivation of novel human ground state naive pluripotent stem cells.

PubMed

Gafni, Ohad; Weinberger, Leehee; Mansour, Abed AlFatah; Manor, Yair S; Chomsky, Elad; Ben-Yosef, Dalit; Kalma, Yael; Viukov, Sergey; Maza, Itay; Zviran, Asaf; Rais, Yoach; Shipony, Zohar; Mukamel, Zohar; Krupalnik, Vladislav; Zerbib, Mirie; Geula, Shay; Caspi, Inbal; Schneir, Dan; Shwartz, Tamar; Gilad, Shlomit; Amann-Zalcenstein, Daniela; Benjamin, Sima; Amit, Ido; Tanay, Amos; Massarwa, Rada; Novershtern, Noa; Hanna, Jacob H

2013-12-12

Mouse embryonic stem (ES) cells are isolated from the inner cell mass of blastocysts, and can be preserved in vitro in a naive inner-cell-mass-like configuration by providing exogenous stimulation with leukaemia inhibitory factor (LIF) and small molecule inhibition of ERK1/ERK2 and GSK3β signalling (termed 2i/LIF conditions). Hallmarks of naive pluripotency include driving Oct4 (also known as Pou5f1) transcription by its distal enhancer, retaining a pre-inactivation X chromosome state, and global reduction in DNA methylation and in H3K27me3 repressive chromatin mark deposition on developmental regulatory gene promoters. Upon withdrawal of 2i/LIF, naive mouse ES cells can drift towards a primed pluripotent state resembling that of the post-implantation epiblast. Although human ES cells share several molecular features with naive mouse ES cells, they also share a variety of epigenetic properties with primed murine epiblast stem cells (EpiSCs). These include predominant use of the proximal enhancer element to maintain OCT4 expression, pronounced tendency for X chromosome inactivation in most female human ES cells, increase in DNA methylation and prominent deposition of H3K27me3 and bivalent domain acquisition on lineage regulatory genes. The feasibility of establishing human ground state naive pluripotency in vitro with equivalent molecular and functional features to those characterized in mouse ES cells remains to be defined. Here we establish defined conditions that facilitate the derivation of genetically unmodified human naive pluripotent stem cells from already established primed human ES cells, from somatic cells through induced pluripotent stem (iPS) cell reprogramming or directly from blastocysts. The novel naive pluripotent cells validated herein retain molecular characteristics and functional properties that are highly similar to mouse naive ES cells, and distinct from conventional primed human pluripotent cells. This includes competence in the generation

Pregnancy IFN-gamma responses to foetal alloantigens are altered by maternal allergy and gravidity status.

PubMed

Breckler, L A; Hale, J; Taylor, A; Dunstan, J A; Thornton, C A; Prescott, S L

2008-11-01

During pregnancy, variations in maternal-foetal cellular interactions may influence immune programming. This study was carried out to determine if maternal responses to foetal alloantigens are altered by maternal allergic disease and/or previous pregnancies. For this cohort study, peripheral blood was collected from allergic (n = 69) and nonallergic (n = 63) pregnant women at 20, 30, 36-week gestation and 6-week postpartum (pp). Cord blood was collected at delivery. Mixed lymphocyte reactions were used to measure maternal cytokine responses [interleukin-6 (IL-6), IL-10, IL-13 and (interferon-gamma) IFN-gamma] at each time point towards foetal mononuclear cells. Maternal cytokine responses during pregnancy (20, 30 and 36 weeks) were suppressed compared to the responses at 6-week pp. The ratio of maternal IFN-gamma/IL-13 and IFN-gamma/IL-10 responses were lower during pregnancy. Allergic mothers had lower IFN-gamma responses at each time-point during pregnancy with the greatest difference in responses observed at 36-week gestation. When allergic and nonallergic women were further stratified by gravidity group, IFN-gamma responses of allergic multigravid mothers were significantly lower than nonallergic multigravid mothers during pregnancy. During normal pregnancy, peripheral T-cell cytokine responses to foetal alloantigens may be altered by both allergic status of the mother and previous pregnancies. These factors could influence the cytokine milieu experienced by the foetus and will be further explored in the development of allergic disease during early life.

Shaping the Future for Children with Foetal Alcohol Spectrum Disorders

ERIC Educational Resources Information Center

Blackburn, Carolyn; Carpenter, Barry; Egerton, Jo

2010-01-01

This article describes work undertaken in connection with an ongoing research project funded by the Training and Development Agency for Schools. It illustrates the educational implications of foetal alcohol spectrum disorders (FASD) and its implications for the educational workforce in seeking to meet the needs of those children who are affected.

The Preference for Symmetry in Flower-Naive and Not-so-Naive Bumblebees

ERIC Educational Resources Information Center

Plowright, C. M. S.; Evans, S. A.; Leung, J. Chew; Collin, C. A.

2011-01-01

Truly flower-naive bumblebees, with no prior rewarded experience for visits on any visual patterns outside the colony, were tested for their choice of bilaterally symmetric over asymmetric patterns in a radial-arm maze. No preference for symmetry was found. Prior training with rewarded black and white disks did, however, lead to a significant…

Adaptation of enterocytic Caco-2 cells to glucose modulates triacylglycerol-rich lipoprotein secretion through triacylglycerol targeting into the endoplasmic reticulum lumen

PubMed Central

Pauquai, Thomas; Bouchoux, Julien; Chateau, Danielle; Vidal, Romain; Rousset, Monique; Chambaz, Jean; Demignot, Sylvie

2006-01-01

Enterocytes are responsible for the absorption of dietary lipids, which involves TRL [TG (triacylglycerol)-rich lipoprotein] assembly and secretion. In the present study, we analysed the effect on TRL secretion of Caco-2 enterocyte adaptation to a differential glucose supply. We showed that TG secretion in cells adapted to a low glucose supply for 2 weeks after confluence was double that of control cells maintained in high-glucose-containing medium, whereas the level of TG synthesis remained similar in both conditions. This increased secretion resulted mainly from an enlargement of the mean size of the secreted TRL. The increased TG availability for TRL assembly and secretion was not due to an increase in the MTP (microsomal TG transfer protein) activity that is required for lipid droplet biogenesis in the ER (endoplasmic reticulum) lumen, or to the channelling of absorbed fatty acids towards the monoacylglycerol pathway for TG synthesis. Interestingly, by electron microscopy and subcellular fractionation studies, we observed, in the low glucose condition, an increase in the TG content available for lipoprotein assembly in the ER lumen, with the cytosolic/microsomal TG levels being verapamil-sensitive. Overall, we demonstrate that Caco-2 enterocytes modulate TRL secretion through TG partitioning between the cytosol and the ER lumen according to the glucose supply. Our model will help in identifying the proteins involved in the control of the balance between TRL assembly and cytosolic lipid storage. This mechanism may be a way for enterocytes to regulate TRL secretion after a meal, and thus impact on our understanding of post-prandial hypertriglyceridaemia. PMID:16393142

Naive Probability: A Mental Model Theory of Extensional Reasoning.

ERIC Educational Resources Information Center

Johnson-Laird, P. N.; Legrenzi, Paolo; Girotto, Vittorio; Legrenzi, Maria Sonino; Caverni, Jean-Paul

1999-01-01

Outlines a theory of naive probability in which individuals who are unfamiliar with the probability calculus can infer the probabilities of events in an "extensional" way. The theory accommodates reasoning based on numerical premises, and explains how naive reasoners can infer posterior probabilities without relying on Bayes's theorem.…

Flagellar Cap Protein FliD Mediates Adherence of Atypical Enteropathogenic Escherichia coli to Enterocyte Microvilli

PubMed Central

Sampaio, Suely C. F.; Luiz, Wilson B.; Vieira, Mônica A. M.; Ferreira, Rita C. C.; Garcia, Bruna G.; Sinigaglia-Coimbra, Rita; Sampaio, Jorge L. M.; Ferreira, Luís C. S.

2016-01-01

The expression of flagella correlates with different aspects of bacterial pathogenicity, ranging from adherence to host cells to activation of inflammatory responses by the innate immune system. In the present study, we investigated the role of flagella in the adherence of an atypical enteropathogenic Escherichia coli (aEPEC) strain (serotype O51:H40) to human enterocytes. Accordingly, isogenic mutants deficient in flagellin (FliC), the flagellar structural subunit; the flagellar cap protein (FliD); or the MotAB proteins, involved in the control of flagellar motion, were generated and tested for binding to differentiated Caco-2 cells. Binding of the aEPEC strain to enterocytes was significantly impaired in strains with the fliC and fliD genes deleted, both of which could not form flagella on the bacterial surface. A nonmotile but flagellated MotAB mutant also showed impaired adhesion to Caco-2 cells. In accordance with these observations, adhesion of aEPEC strain 1711-4 to Caco-2 cells was drastically reduced after the treatment of Caco-2 cells with purified FliD. In addition, incubation of aEPEC bacteria with specific anti-FliD serum impaired binding to Caco-2 cells. Finally, incubation of Caco-2 cells with purified FliD, followed by immunolabeling, showed that the protein was specifically bound to the microvillus tips of differentiated Caco-2 cells. The aEPEC FliD or anti-FliD serum also reduced the adherence of prototype typical enteropathogenic, enterohemorrhagic, and enterotoxigenic E. coli strains to Caco-2 cells. In conclusion, our findings further strengthened the role of flagella in the adherence of aEPEC to human enterocytes and disclosed the relevant structural and functional involvement of FliD in the adhesion process. PMID:26831466

Influence of gravidity and foetal gender on the value of screening variables in the first trimester of pregnancy.

PubMed

Illescas, Tamara; Fernández, Cristina; Ortega, Dolores; de la Puente, Miriam; Coronado, Pluvio; Montalvo, Joaquín

2013-03-01

Combined screening for chromosome abnormalities in the first trimester of pregnancy is based on maternal age, nuchal translucency (NT) and biochemical markers (PAPP-A and free β-hCG). We sought to assess the value of the variables used in the combined screening strategy taking into account maternal gravidity and foetal gender. Between July 1999 and December 2009, a total of 21,193 singleton pregnancies were screened for aneuploidy in the first trimester, in the Hospital Clínico San Carlos (Madrid, Spain). In the original database foetal gender data were available in 4370 euploid cases, and there were 2343 women with at least two consecutive pregnancies. We conducted a retrospective assessment of ultrasound and biochemical markers taking into account foetal gender and maternal gravidity, and evaluated the effect on the performance of screening, in terms of detection rates and false positive rates. Information on pregnancy outcome was obtained from the hospital's intranet medical records or by contacting the patient by telephone postpartum. Karyotype was ascertained by amniocentesis or chorionic villus sampling, and euploid status was assumed in newborns with normal phenotype. Student's t-tests (paired or unpaired as appropriate) were applied to the data, and the Bland-Altmann method was applied in evaluating individual differences in markers between successive gestations. PAPP-A decreased significantly between the first and the second pregnancy (p<0.01). PAPP-A and free β-hCG values were significantly higher (p=0.04 and p<0.01 respectively) and NT was lower (p=0.02) in pregnancies with a female foetus. Correlations between the biochemical variables in relation to gravidity and foetal gender can introduce a bias in the calculated risk of chromosome abnormalities. Differences in NT measurements with respect to foetal gender do not seem to be of clinical importance. NT is independent of gravidity so routine use of NT compensates for the influence of these maternal-foetal

The effect of amino acids and dipeptides on sodium-ion transport in rat enterocytes.

PubMed

Cheeseman, C I; Devlin, D

1985-02-14

Sodium efflux from isolated intestinal epithelial cells was measured during incubation with several different free amino acids and dipeptides. L-Leucine, which is cotransported with sodium across the brush border membrane, significantly stimulated the total sodium efflux and almost all of this increase involved the ouabain-sensitive flux, i.e., the active component. In contrast, glycyl-L-leucine had little or no effect on active sodium efflux either in the presence or absence of 0.1 mM bestatin, a peptide hydrolase inhibitor. A second dipeptide L-carnosine (beta-alanyl-L-histidine) which is poorly hydrolysed by enterocytes also had no effect upon sodium efflux. However, glycylglycine, which has been shown to be cotransported with sodium, did stimulate the ionic efflux. In addition, measurement of sodium uptake by sheets of small intestine showed that glycyl-L-leucine, carnosine and glycyl-L-proline failed to increase the uptake of the ion, while glycylglycine did significantly stimulate sodium uptake. These data indicate that some dipeptides are not cotransported with sodium, while others are. This suggests that there may well be multiple peptide transporters with very different characteristics in the brush border membrane of enterocytes.

Apoptosis of enterocytes and nitration of junctional complex proteins promote alcohol-induced gut leakiness and liver injury.

PubMed

Cho, Young-Eun; Yu, Li-Rong; Abdelmegeed, Mohamed A; Yoo, Seong-Ho; Song, Byoung-Joon

2018-07-01

Binge alcohol exposure causes gut leakiness, contributing to increased endotoxemia and inflammatory liver injury, although the molecular mechanisms are still elusive. This study was aimed at investigating the roles of apoptosis of enterocytes and nitration followed by degradation of intestinal tight junction (TJ) and adherens junction (AJ) proteins in binge alcohol-induced gut leakiness. The levels of intestinal (ileum) junctional complex proteins, oxidative stress markers and apoptosis-related proteins in rodents, T84 colonic cells and autopsied human ileums were determined by immunoblot, immunoprecipitation, immunofluorescence, and mass-spectral analyses. Binge alcohol exposure caused apoptosis of gut enterocytes with elevated serum endotoxin and liver injury. The levels of intestinal CYP2E1, iNOS, nitrated proteins and apoptosis-related marker proteins were significantly elevated in binge alcohol-exposed rodents. Differential, quantitative mass-spectral analyses of the TJ-enriched fractions of intestinal epithelial layers revealed that several TJ, AJ and desmosome proteins were decreased in binge alcohol-exposed rats compared to controls. Consistently, the levels of TJ proteins (claudin-1, claudin-4, occludin and zonula occludens-1), AJ proteins (β-catenin and E-cadherin) and desmosome plakoglobin were very low in binge alcohol-exposed rats, wild-type mice, and autopsied human ileums but not in Cyp2e1-null mice. Additionally, pretreatment with specific inhibitors of CYP2E1 and iNOS prevented disorganization and/or degradation of TJ proteins in alcohol-exposed T84 colonic cells. Furthermore, immunoprecipitation followed by immunoblot confirmed that intestinal TJ and AJ proteins were nitrated and degraded via ubiquitin-dependent proteolysis, resulting in their decreased levels. These results demonstrated for the first time the critical roles of CYP2E1, apoptosis of enterocytes, and nitration followed by ubiquitin-dependent proteolytic degradation of the

Evaluation of the foetal time to death in mice after application of direct and indirect euthanasia methods.

PubMed

Muñoz-Mediavilla, C; Cámara, J A; Salazar, S; Segui, B; Sanguino, D; Mulero, F; de la Cueva, E; Blanco, I

2016-04-01

Directive 2010/63/EU on the protection of animals used for scientific purposes requires that the killing of mammal foetuses during the last third of their gestational period should be accomplished through effective and humane methods. The fact that murine foetuses are resistant to hypoxia-mediated euthanasia renders the current euthanasia methods ineffective or humane for the foetuses when these methods are applied to pregnant female mice. We have assessed the time to death of foetuses after performing either indirect (dam euthanasia) or direct (via intraplacental injection--a new approach to euthanasia) euthanasia methods in order to determine a euthanasia method that is appropriate, ethical and efficient for the killing of mouse foetuses. The respective times to death of foetuses after performing the three most commonly used euthanasia methods (namely cervical dislocation, CO2inhalation and intraperitoneal sodium pentobarbital administration) were recorded. Absence of foetal heartbeat was monitored via ultrasound. We consider that the most effective and humane method of foetal euthanasia was the one able to achieve foetal death within the shortest possible period of time. Among the indirect euthanasia methods assessed, the administration of a sodium pentobarbital overdose to pregnant female mice was found to be the fastest for foetuses, with an average post-treatment foetal death of approximately 29.8 min. As for the direct euthanasia method assessed, foetal time to death after intraplacental injection of sodium pentobarbital was approximately 14 min. Significant differences among the different mouse strains employed were found. Based on the results obtained in our study, we consider that the administration of a sodium pentobarbital overdose by intraplacental injection to be an effective euthanasia method for murine foetuses. © The Author(s) 2015.

An open-source framework for stress-testing non-invasive foetal ECG extraction algorithms.

PubMed

Andreotti, Fernando; Behar, Joachim; Zaunseder, Sebastian; Oster, Julien; Clifford, Gari D

2016-05-01

Over the past decades, many studies have been published on the extraction of non-invasive foetal electrocardiogram (NI-FECG) from abdominal recordings. Most of these contributions claim to obtain excellent results in detecting foetal QRS (FQRS) complexes in terms of location. A small subset of authors have investigated the extraction of morphological features from the NI-FECG. However, due to the shortage of available public databases, the large variety of performance measures employed and the lack of open-source reference algorithms, most contributions cannot be meaningfully assessed. This article attempts to address these issues by presenting a standardised methodology for stress testing NI-FECG algorithms, including absolute data, as well as extraction and evaluation routines. To that end, a large database of realistic artificial signals was created, totaling 145.8 h of multichannel data and over one million FQRS complexes. An important characteristic of this dataset is the inclusion of several non-stationary events (e.g. foetal movements, uterine contractions and heart rate fluctuations) that are critical for evaluating extraction routines. To demonstrate our testing methodology, three classes of NI-FECG extraction algorithms were evaluated: blind source separation (BSS), template subtraction (TS) and adaptive methods (AM). Experiments were conducted to benchmark the performance of eight NI-FECG extraction algorithms on the artificial database focusing on: FQRS detection and morphological analysis (foetal QT and T/QRS ratio). The overall median FQRS detection accuracies (i.e. considering all non-stationary events) for the best performing methods in each group were 99.9% for BSS, 97.9% for AM and 96.0% for TS. Both FQRS detections and morphological parameters were shown to heavily depend on the extraction techniques and signal-to-noise ratio. Particularly, it is shown that their evaluation in the source domain, obtained after using a BSS technique, should be

Rescue cerclage when foetal membranes prolapse into the vagina.

PubMed

Bayrak, Mehmet; Gul, Ahmet; Goynumer, Gokhan

2017-05-01

A cross-sectional study was conducted to evaluate the efficacy of rescue cerclage in patients with a dilated cervix and prolapsed foetal membranes. Thirty-five patients presenting with cervical dilatation and prolapsed foetal membranes were included in the study. A McDonald cerclage was placed in 27 patients. The duration of pregnancy prolongation and the number of deliveries after 28 weeks were evaluated. The median prolongation of pregnancy after cerclage placement differed significantly between the cerclage and bed-rest groups (64 days versus 13.5 days). Of the 27 patients who had cerclage, 17 (63%) delivered after 28 weeks of gestation, whereas all patients in the bed-rest group delivered before 28 weeks of gestation. The take-home baby rate was 63% in the cerclage group. When pregnancies were complicated by cervical dilatation with membrane prolapse into the vagina, placement of a McDonald cerclage in appropriately selected patients can be a beneficial therapeutic option. Impact statement Although the effectiveness and safety of rescue cerclage is controversial, our study provides strong support for the notion that cervical cerclage accompanied by long-term broad-spectrum antibiotics improves the perinatal outcomes in singleton gestations with membrane prolapsed into the vagina. Further prospective randomised trial is required to prove these findings.

Training residents to be factually accurate and articulate: A case study using foetal heart rate monitoring nomenclature.

PubMed

Stohl, Hindi E; Miller, David A

2016-10-01

Careful communication between members of the obstetric team about intrapartum foetal heart rate is critical for clinical management and patient safety. This study evaluated the benefits of two testing modalities in assessing resident physician knowledge of the 2008 NICHD nomenclature. Multiple-choice (MC) and short-answer (SA) examinations were administered to Obstetrics and Gynecology resident physicians before an educational intervention and then immediately after the training, at 6 months and at 12 months. Test scores on both the MC and the SA examinations improved after the training session. The improvement was sustained over the course of the study. Residents performed higher on the MC examination than on the SA test. This study suggests that formalised teaching in foetal heart rate monitoring improves resident physician knowledge of the NICHD nomenclature and that SA examinations may better discriminate between residents who are and are not able to accurately articulate foetal heart rate monitoring terminology.

Noninvasive prenatal exclusion of haemoglobin Bart's using foetal DNA from maternal plasma.

PubMed

Ho, Sherry S Y; Chong, Samuel S C; Koay, Evelyn S C; Ponnusamy, Sukumar; Chiu, Lily; Chan, Yiong Huak; Rauff, Mary; Baig, Sonia; Chan, Jerry; Su, Lin Lin; Biswas, Arijit; Hahn, Sinuhe; Choolani, Mahesh

2010-01-01

Prenatal diagnosis of alpha-thalassaemia requires invasive testing associated with a risk of miscarriage. Cell-free foetal DNA in maternal plasma presents an alternative source of foetal genetic material for noninvasive prenatal diagnosis. We aimed to exclude HbBart's noninvasively by detection of unaffected paternal alleles in maternal plasma using quantitative fluorescence PCR (QF-PCR). Microsatellite markers (16PTEL05, 16PTEL06) within the breakpoint regions of -(SEA), -(FIL) and -(THAI) deletions were analysed using QF-PCR of maternal plasma from 30 families. In this blinded study, genotypes were confirmed using conventional PCR. Maternal plasma from two known cases of HbBart's were also analysed. HbBart's was excluded in 10 out of 30 (33.3%, 95% CI, 17.3-52.8%) mothers by identifying the presence of nondeleted paternally inherited fetal alleles; either only 16PTEL05 (n = 1) or only 16PTEL06 (n = 4), or both (n = 5), and confirmed through direct analysis of fetal DNA. Paternally inherited foetal alleles of 16PTEL05 and 16PTEL06 were not detected in maternal plasma of the two known HbBarts cases. False negatives were excluded with the detection of paternally inherited fetal control marker, D21S1270 in maternal plasma. We show proof-of-principle that such a test can accurately exclude HbBart's in the foetus by identifying the nondeleted paternally inherited fetal alleles in maternal plasma in one out of three pregnancies, avoiding invasive testing in these pregnancies. Copyright (c) 2009 John Wiley & Sons, Ltd.

Challenges in nourishing the intrauterine growth-restricted foetus - Lessons learned from studies in the intrauterine growth-restricted foetal sheep.

PubMed

Hay, William W; Brown, Laura D; Rozance, Paul J; Wesolowski, Stephanie R; Limesand, Sean W

2016-08-01

Previous attempts to improve growth and development of the intrauterine growth-restricted (IUGR) foetus during pregnancy have not worked or caused harm. Our research identifies tissue-specific mechanisms underlying foetal growth restriction and then tests strategies to improve growth and ameliorate many of the metabolic problems before the infant is born. The goal of our studies is to reduce the impact of foetal growth restriction at critical stages of development on the lifelong complications of IUGR offspring. Defining specific mechanisms that cause growth restriction in the foetus might identify specific nutrients and hormones that could be given to the mother to improve foetal growth and reduce metabolic complications, using strategies first tested in our IUGR animal model. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Phthalate-Induced Pathology in the Foetal Testis Involves More Than Decreased Testosterone Production

EPA Science Inventory

Foetal exposure to phthalates is known to adversely impact male reproductive development and function. Developmental anomalies of reproductive tract have been attributed to impaired testosterone synthesis. However, species differences in the ability to produce testosterone have...

Characterization of the Proteome of Cytoplasmic Lipid Droplets in Mouse Enterocytes after a Dietary Fat Challenge

PubMed Central

D’Aquila, Theresa; Sirohi, Devika; Grabowski, Jeffrey M.; Hedrick, Victoria E.; Paul, Lake N.; Greenberg, Andrew S.; Kuhn, Richard J.; Buhman, Kimberly K.

2015-01-01

Dietary fat absorption by the small intestine is a multistep process that regulates the uptake and delivery of essential nutrients and energy. One step of this process is the temporary storage of dietary fat in cytoplasmic lipid droplets (CLDs). The storage and mobilization of dietary fat is thought to be regulated by proteins that associate with the CLD; however, mechanistic details of this process are currently unknown. In this study we analyzed the proteome of CLDs isolated from enterocytes harvested from the small intestine of mice following a dietary fat challenge. In this analysis we identified 181 proteins associated with the CLD fraction, of which 37 are associated with known lipid related metabolic pathways. We confirmed the localization of several of these proteins on or around the CLD through confocal and electron microscopy, including perilipin 3, apolipoprotein A-IV, and acyl-CoA synthetase long-chain family member 5. The identification of the enterocyte CLD proteome provides new insight into potential regulators of CLD metabolism and the process of dietary fat absorption. PMID:25992653

Do the Naive Know Best? The Predictive Power of Naive Ratings of Couple Interactions

ERIC Educational Resources Information Center

Baucom, Katherine J. W.; Baucom, Brian R.; Christensen, Andrew

2012-01-01

We examined the utility of naive ratings of communication patterns and relationship quality in a large sample of distressed couples. Untrained raters assessed 10-min videotaped interactions from 134 distressed couples who participated in both problem-solving and social support discussions at each of 3 time points (pre-therapy, post-therapy, and…

Dietary starch breakdown product sensing mobilizes and apically activates α-glucosidases in small intestinal enterocytes.

PubMed

Chegeni, Mohammad; Amiri, Mahdi; Nichols, Buford L; Naim, Hassan Y; Hamaker, Bruce R

2018-02-20

Dietary starch is finally converted to glucose for absorption by the small intestine mucosal α-glucosidases (sucrase-isomaltase [SI] and maltase-glucoamylase), and control of this process has health implications. Here, the molecular mechanisms were analyzed associated with starch-triggered maturation and transport of SI. Biosynthetic pulse-chase in Caco-2 cells revealed that the high MW SI species (265 kDa) induced by maltose (an α-amylase starch digestion product) had a higher rate of early trafficking and maturation compared with a glucose-induced SI (245 kDa). The maltose-induced SI was found to have higher affinity to lipid rafts, which are associated with enhanced targeting to the apical membrane and higher activity. Accordingly, in situ maltose-hydrolyzing action was enhanced in the maltose-treated cells. Thus, starch digestion products at the luminal surface of small intestinal enterocytes are sensed and accelerate the intracellular processing of SI to enhance starch digestion capacity in the intestinal lumen.-Chegeni, M., Amiri, M., Nichols, B. L., Naim, H. Y., Hamaker, B. R. Dietary starch breakdown product sensing mobilizes and apically activates α-glucosidases in small intestinal enterocytes.

Imaging putative foetal cerebral blood oxygenation using susceptibility weighted imaging (SWI).

PubMed

Yadav, Brijesh Kumar; Krishnamurthy, Uday; Buch, Sagar; Jella, Pavan; Hernandez-Andrade, Edgar; Yeo, Lami; Korzeniewski, Steven J; Trifan, Anabela; Hassan, Sonia S; Haacke, E Mark; Romero, Roberto; Neelavalli, Jaladhar

2018-05-01

To evaluate the magnetic susceptibility, ∆χ v , as a surrogate marker of venous blood oxygen saturation, S v O 2 , in second- and third-trimester normal human foetuses. Thirty-six pregnant women, having a mean gestational age (GA) of 31 2/7 weeks, underwent magnetic resonance imaging (MRI). Susceptibility-weighted imaging (SWI) data from the foetal brain were acquired. ∆χ v of the superior sagittal sinus (SSS) was quantified using MR susceptometry from the intra-vascular phase measurements. Assuming the magnetic property of foetal blood, ∆χ do , is the same as that of adult blood, S v O 2 was derived from the measured Δχ v . The variation of ∆χ v and S v O 2 , as a function of GA, was statistically evaluated. The mean ∆χ v in the SSS in the second-trimester (n = 8) and third-trimester foetuses (n = 28) was found to be 0.34± 0.06 ppm and 0.49 ±0.05 ppm, respectively. Correspondingly, the derived S v O 2 values were 69.4% ±3.27% and 62.6% ±3.25%. Although not statistically significant, an increasing trend (p = 0.08) in Δχ v and a decreasing trend (p = 0.22) in S v O 2 with respect to advancing gestation was observed. We report cerebral venous blood magnetic susceptibility and putative oxygen saturation in healthy human foetuses. Cerebral oxygen saturation in healthy human foetuses, despite a slight decreasing trend, does not change significantly with advancing gestation. • Cerebral venous magnetic susceptibility and oxygenation in human foetuses can be quantified. • Cerebral venous oxygenation was not different between second- and third-trimester foetuses. • Foetal cerebral venous oxygenation does not change significantly with advancing gestation.

Blocking the recruitment of naive CD4+ T cells reverses immunosuppression in breast cancer

PubMed Central

Su, Shicheng; Liao, Jianyou; Liu, Jiang; Huang, Di; He, Chonghua; Chen, Fei; Yang, LinBing; Wu, Wei; Chen, Jianing; Lin, Ling; Zeng, Yunjie; Ouyang, Nengtai; Cui, Xiuying; Yao, Herui; Su, Fengxi; Huang, Jian-dong; Lieberman, Judy; Liu, Qiang; Song, Erwei

2017-01-01

The origin of tumor-infiltrating Tregs, critical mediators of tumor immunosuppression, is unclear. Here, we show that tumor-infiltrating naive CD4+ T cells and Tregs in human breast cancer have overlapping TCR repertoires, while hardly overlap with circulating Tregs, suggesting that intratumoral Tregs mainly develop from naive T cells in situ rather than from recruited Tregs. Furthermore, the abundance of naive CD4+ T cells and Tregs is closely correlated, both indicating poor prognosis for breast cancer patients. Naive CD4+ T cells adhere to tumor slices in proportion to the abundance of CCL18-producing macrophages. Moreover, adoptively transferred human naive CD4+ T cells infiltrate human breast cancer orthotopic xenografts in a CCL18-dependent manner. In human breast cancer xenografts in humanized mice, blocking the recruitment of naive CD4+ T cells into tumor by knocking down the expression of PITPNM3, a CCL18 receptor, significantly reduces intratumoral Tregs and inhibits tumor progression. These findings suggest that breast tumor-infiltrating Tregs arise from chemotaxis of circulating naive CD4+ T cells that differentiate into Tregs in situ. Inhibiting naive CD4+ T cell recruitment into tumors by interfering with PITPNM3 recognition of CCL18 may be an attractive strategy for anticancer immunotherapy. PMID:28290464

N-acetylcysteine stimulates protein synthesis in enterocytes independently of glutathione synthesis.

PubMed

Yi, Dan; Hou, Yongqing; Wang, Lei; Long, Minhui; Hu, Shengdi; Mei, Huimin; Yan, Liqiong; Hu, Chien-An Andy; Wu, Guoyao

2016-02-01

Dietary supplementation with N-acetylcysteine (NAC) has been reported to improve intestinal health and treat gastrointestinal diseases. However, the underlying mechanisms are not fully understood. According to previous reports, NAC was thought to exert its effect through glutathione synthesis. This study tested the hypothesis that NAC enhances enterocyte growth and protein synthesis independently of cellular glutathione synthesis. Intestinal porcine epithelial cells were cultured for 3 days in Dulbecco's modified Eagle medium containing 0 or 100 μM NAC. To determine a possible role for GSH (the reduced form of glutathione) in mediating the effect of NAC on cell growth and protein synthesis, additional experiments were conducted using culture medium containing 100 μM GSH, 100 μM GSH ethyl ester (GSHee), diethylmaleate (a GSH-depletion agent; 10 μM), or a GSH-synthesis inhibitor (buthionine sulfoximine, BSO; 20 μM). NAC increased cell proliferation, GSH concentration, and protein synthesis, while inhibiting proteolysis. GSHee enhanced cell proliferation and GSH concentration without affecting protein synthesis but inhibited proteolysis. Conversely, BSO or diethylmaleate reduced cell proliferation and GSH concentration without affecting protein synthesis, while promoting protein degradation. At the signaling level, NAC augmented the protein abundance of total mTOR, phosphorylated mTOR, and phosphorylated 70S6 kinase as well as mRNA levels for mTOR and p70S6 kinase in IPEC-1 cells. Collectively, these results indicate that NAC upregulates expression of mTOR signaling proteins to stimulate protein synthesis in enterocytes independently of GSH generation. Our findings provide a hitherto unrecognized biochemical mechanism for beneficial effects of NAC in intestinal cells.

Controversies and considerations regarding the termination of pregnancy for Foetal Anomalies in Islam

PubMed Central

2014-01-01

Background Approximately one-fourth of all the inhabitants on earth are Muslims. Due to unprecedented migration, physicians are often confronted with cultures other than their own that adhere to different pdigms. Discussion In Islam, and most religions, abortion is forbidden. Islam is considerably liberal concerning abortion, which is dependent on (i) the threat of harm to mothers, (ii) the status of the pregnancy before or after ensoulment (on the 120th day of gestation), and (iii) the presence of foetal anomalies that are incompatible with life. Considerable variation in religious edicts exists, but most Islamic scholars agree that the termination of a pregnancy for foetal anomalies is allowed before ensoulment, after which abortion becomes totally forbidden, even in the presence of foetal abnormalities; the exception being a risk to the mother’s life or confirmed intrauterine death. Summary The authors urge Muslim law makers to also consider abortion post ensoulment if it is certain that the malformed foetus will decease soon after birth or will be severely malformed and physically and mentally incapacitated after birth to avoid substantial hardship that may continue for years for mothers and family members. The authors recommend that an institutional committee governed and monitored by a national committee make decisions pertaining to abortion to ensure that ethics are preserved and mistakes are prevented. Anomalous foetuses must be detected at the earliest possible time to enable an appropriate medical intervention prior to the 120th day. PMID:24499356

Controversies and considerations regarding the termination of pregnancy for foetal anomalies in Islam.

PubMed

Al-Matary, Abdulrahman; Ali, Jaffar

2014-02-05

Approximately one-fourth of all the inhabitants on earth are Muslims. Due to unprecedented migration, physicians are often confronted with cultures other than their own that adhere to different paradigms. In Islam, and most religions, abortion is forbidden. Islam is considerably liberal concerning abortion, which is dependent on (i) the threat of harm to mothers, (ii) the status of the pregnancy before or after ensoulment (on the 120th day of gestation), and (iii) the presence of foetal anomalies that are incompatible with life. Considerable variation in religious edicts exists, but most Islamic scholars agree that the termination of a pregnancy for foetal anomalies is allowed before ensoulment, after which abortion becomes totally forbidden, even in the presence of foetal abnormalities; the exception being a risk to the mother's life or confirmed intrauterine death. The authors urge Muslim law makers to also consider abortion post ensoulment if it is certain that the malformed foetus will decease soon after birth or will be severely malformed and physically and mentally incapacitated after birth to avoid substantial hardship that may continue for years for mothers and family members. The authors recommend that an institutional committee governed and monitored by a national committee make decisions pertaining to abortion to ensure that ethics are preserved and mistakes are prevented. Anomalous foetuses must be detected at the earliest possible time to enable an appropriate medical intervention prior to the 120th day.

Naive Juveniles Are More Likely to Become Breeders after Witnessing Predator Mobbing.

PubMed

Griesser, Michael; Suzuki, Toshitaka N

2017-01-01

Responding appropriately during the first predatory attack in life is often critical for survival. In many social species, naive juveniles acquire this skill from conspecifics, but its fitness consequences remain virtually unknown. Here we experimentally demonstrate how naive juvenile Siberian jays (Perisoreus infaustus) derive a long-term fitness benefit from witnessing knowledgeable adults mobbing their principal predator, the goshawk (Accipiter gentilis). Siberian jays live in family groups of two to six individuals that also can include unrelated nonbreeders. Field observations showed that Siberian jays encounter predators only rarely, and, indeed, naive juveniles do not respond to predator models when on their own but do when observing other individuals mobbing them. Predator exposure experiments demonstrated that naive juveniles had a substantially higher first-winter survival after observing knowledgeable group members mobbing a goshawk model, increasing their likelihood of acquiring a breeding position later in life. Previous research showed that naive individuals may learn from others how to respond to predators, care for offspring, or choose mates, generally assuming that social learning has long-term fitness consequences without empirical evidence. Our results demonstrate a long-term fitness benefit of vertical social learning for naive individuals in the wild, emphasizing its evolutionary importance in animals, including humans.

Diagnostic nomenclature for foetal alcohol spectrum disorders: the continuing challenge of causality.

PubMed

Miller, A R

2013-11-01

Prenatal alcohol exposure is a risk factor for neurologically based cognitive and adaptive disability. Diagnostic nomenclature for prenatally exposed children with cognitive and adaptive disability who lack features for foetal alcohol syndrome (FAS) or partial FAS includes the terms alcohol-related neurodevelopmental disorder (ARND) and foetal alcohol spectrum disorder(s) (FASD). Although these terms are now widely used, this paper argues that both are problematic. ARND is flawed by unjustifiably turning a risk factor into a causal factor and shrouding the result in terminological ambiguity, while FASD is not appropriate as a clinical label, and its use as a proxy for ARND deflects critical attention from the causal inferencing that is integral to diagnosing children with an alcohol-related teratogenic condition. Existing nomenclature is at odds with logical and evidence-based diagnosing and also has implications for interpretation of epidemiological data. Diagnostic nomenclature that is not tightly linked to causal inference is preferable at the present stage of this field's development. © 2013 John Wiley & Sons Ltd.

Understanding of the naive Bayes classifier in spam filtering

NASA Astrophysics Data System (ADS)

Wei, Qijia

2018-05-01

Along with the development of the Internet, the information stream is experiencing an unprecedented burst. The methods of information transmission become more and more important and people receiving effective information is a hot topic in the both research and industry field. As one of the most common methods of information communication, email has its own advantages. However, spams always flood the inbox and automatic filtering is needed. This paper is going to discuss this issue from the perspective of Naive Bayes Classifier, which is one of the applications of Bayes Theorem. Concepts and process of Naive Bayes Classifier will be introduced, followed by two examples. Discussion with Machine Learning is made in the last section. Naive Bayes Classifier has been proved to be surprisingly effective, with the limitation of the interdependence among attributes which are usually email words or phrases.

A mixture model for bovine abortion and foetal survival.

PubMed

Hanson, Timothy; Bedrick, Edward J; Johnson, Wesley O; Thurmond, Mark C

2003-05-30

The effect of spontaneous abortion on the dairy industry is substantial, costing the industry on the order of US dollars 200 million per year in California alone. We analyse data from a cohort study of nine dairy herds in Central California. A key feature of the analysis is the observation that only a relatively small proportion of cows will abort (around 10;15 per cent), so that it is inappropriate to analyse the time-to-abortion (TTA) data as if it were standard censored survival data, with cows that fail to abort by the end of the study treated as censored observations. We thus broaden the scope to consider the analysis of foetal lifetime distribution (FLD) data for the cows, with the dual goals of characterizing the effects of various risk factors on (i). the likelihood of abortion and, conditional on abortion status, on (ii). the risk of early versus late abortion. A single model is developed to accomplish both goals with two sets of specific herd effects modelled as random effects. Because multimodal foetal hazard functions are expected for the TTA data, both a parametric mixture model and a non-parametric model are developed. Furthermore, the two sets of analyses are linked because of anticipated dependence between the random herd effects. All modelling and inferences are accomplished using modern Bayesian methods. Copyright 2003 John Wiley & Sons, Ltd.

Two separate defects affecting true naive or virtual memory T cell precursors combine to reduce naive T cell responses with aging.

PubMed

Renkema, Kristin R; Li, Gang; Wu, Angela; Smithey, Megan J; Nikolich-Žugich, Janko

2014-01-01

Naive T cell responses are eroded with aging. We and others have recently shown that unimmunized old mice lose ≥ 70% of Ag-specific CD8 T cell precursors and that many of the remaining precursors acquire a virtual (central) memory (VM; CD44(hi)CD62L(hi)) phenotype. In this study, we demonstrate that unimmunized TCR transgenic (TCRTg) mice also undergo massive VM conversion with age, exhibiting rapid effector function upon both TCR and cytokine triggering. Age-related VM conversion in TCRTg mice directly depended on replacement of the original TCRTg specificity by endogenous TCRα rearrangements, indicating that TCR signals must be critical in VM conversion. Importantly, we found that VM conversion had adverse functional effects in both old wild-type and old TCRTg mice; that is, old VM, but not old true naive, T cells exhibited blunted TCR-mediated, but not IL-15-mediated, proliferation. This selective proliferative senescence correlated with increased apoptosis in old VM cells in response to peptide, but decreased apoptosis in response to homeostatic cytokines IL-7 and IL-15. Our results identify TCR as the key factor in differential maintenance and function of Ag-specific precursors in unimmunized mice with aging, and they demonstrate that two separate age-related defects--drastic reduction in true naive T cell precursors and impaired proliferative capacity of their VM cousins--combine to reduce naive T cell responses with aging.

A cross-cultural study on surrogate mother's empathy and maternal-foetal attachment.

PubMed

Lorenceau, Ellen Schenkel; Mazzucca, Luis; Tisseron, Serge; Pizitz, Todd D

2015-06-01

Traditional and gestational surrogate mothers assist infertile couples by carrying their children. In 2005, a meta-analysis on surrogacy was conducted but no study had examined empathy and maternal-foetal attachment of surrogate mothers. Assessments of surrogate mothers show no sign of psychopathology, but one study showed differences on several MMPI-2 scales compared to a normative sample: surrogate mothers identified with stereotypically masculine traits such as assertiveness and competition. They had a higher self-esteem and lower levels of anxiety and depression. To determine if there is a difference in empathy and maternal-foetal attachment of surrogate mothers compared to a comparison group of mothers. Three groups of European traditional and gestational surrogate mothers (n=10), Anglo-Saxon traditional and gestational surrogate mothers (n=34) and a European normative sample of mothers (n=32) completed four published psychometric instruments: the Interpersonal Reactivity Index (empathy index), the Hospital Anxiety and Depressions Scale and the MC20, a social desirability scale. Pregnant surrogate mothers filled the Maternal Antenatal Attachment Scale (n=11). Statistical non-parametric analyses of variance were conducted. Depending on cultural background, surrogate mothers present differences in terms of empathy, anxiety and depression, social desirability and quality of attachment to the foetus compared to a normative sample. Environment plays a role for traditional and gestational surrogacy. Surrogate mothers of both groups are less anxious and depressed than normative samples. Maternal-foetal attachment is strong with a slightly lower quality of attachment. Surrogate mother's empathy indexes are similar to normative samples, sometimes higher. Copyright © 2014 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

Effects of captopril on the human foetal placental circulation: an interaction with bradykinin and angiotensin I.

PubMed Central

de Moura, R; Lopes, M A

1995-01-01

1. The mechanism underlying the foetal toxicity induced by captopril is not well understood. Since bradykinin and angiotensin II appear to be important in the regulation of the placental circulation, experiments were performed to assess the effects of captopril on the vascular actions of these peptides on the human foetal placental circulation. 2. Full-term human placentas, obtained from normal pregnancy, were perfused with a modified Tyrode solution bubbled with O2 using a pulsatile pump. The placental perfusion pressure was measured with a Statham pressure transducer and recorded continuously on a Hewlett-Packard polygraph. 3. Bradykinin (0.1, 0.3 and 1.0 nmol) injected into the placental arterial circulation produced an increase in placental perfusion pressure in all experiments. This effect of bradykinin was significantly inhibited by indomethacin (3 x 10(-7) M). 4. Captopril (10(-7) M) significantly potentiated the pressor effect of bradykinin on the human placental circulation (n = 6). This effect of captopril was reversed by indomethacin (3 x 10(-7) M). 5. Angiotensin I (n = 6) and angiotensin II (n = 6), injected into the placental arterial circulation, both produced dose-dependent increases in placental perfusion pressure. The dose-response curves to angiotensin I (n = 6) were significantly displaced to the right by captopril in a concentration-dependent manner. 6. We suggest that the toxic effects of captopril on the foetus, rather than reflecting an inhibition of angiotensin II formation, may instead be related to a potentiation of the vasoconstrictor effect of bradykinin on the foetal placental circulation, thereby reducing blood flow and causing foetal damage. The reasons for this are discussed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7669485

Naive Theories of Social Groups

ERIC Educational Resources Information Center

Rhodes, Marjorie

2012-01-01

Four studies examined children's (ages 3-10, Total N = 235) naive theories of social groups, in particular, their expectations about how group memberships constrain social interactions. After introduction to novel groups of people, preschoolers (ages 3-5) reliably expected agents from one group to harm members of the other group (rather than…

A Diagnostically Promising Technique for Tallying Nominal Reference Errors in the Narratives of School-Aged Children with Foetal Alcohol Spectrum Disorders (FASD)

ERIC Educational Resources Information Center

Thorne, John C.; Coggins, Truman

2008-01-01

Background: Foetal Alcohol Spectrum Disorders (FASD) include the range of disabilities that occur in children exposed to alcohol during pregnancy, with Foetal Alcohol Syndrome (FAS) on the severe end of the spectrum. Clinical research has documented a range of cognitive, social, and communication deficits in FASD and it indicates the need for…

Stem cells from foetal adnexa and fluid in domestic animals: an update on their features and clinical application.

PubMed

Iacono, E; Rossi, B; Merlo, B

2015-06-01

Over the past decade, stem cell research has emerged as an area of major interest for its potential in regenerative medicine applications. This is in constant need of new cell sources to conceive regenerative medicine approaches for diseases that are still without therapy. Scientists drew the attention towards alternative sources such as foetal adnexa and fluid, as these sources possess many advantages: first of all, cells can be extracted from discarded foetal material and it is non-invasive and inexpensive for the patient; secondly, abundant stem cells can be obtained; and finally, these stem cell sources are free from ethical considerations. Cells derived from foetal adnexa and fluid preserve some of the characteristics of the primitive embryonic layers from which they originate. Many studies have demonstrated the differentiation potential in vitro and in vivo towards mesenchymal and non-mesenchymal cell types; in addition, the immune-modulatory properties make these cells a good candidate for allo- and xenotransplantation. Naturally occurring diseases in domestic animals can be more ideal as disease model of human genetic and acquired diseases and could help to define the potential therapeutic use efficiency and safety of stem cells therapies. This review offers an update on the state of the art of characterization of domestic animals' MSCs derived from foetal adnexa and fluid and on the latest findings in pre-clinical or clinical setting of the stem cell populations isolated from these sources. © 2015 Blackwell Verlag GmbH.

Pedagogically Bereft! Improving Learning Outcomes for Children with Foetal Alcohol Spectrum Disorders

ERIC Educational Resources Information Center

Carpenter, Barry

2011-01-01

Foetal alcohol spectrum disorder (FASD) is the most common non-genetic cause of learning disability, affecting around 1% of live births in Europe, and costing an estimated $2.9 million per individual across their lifespan. In adulthood, non-reversible brain damage is often compounded by secondary disabilities in adulthood, such as mental health…

Metabolism of sn-1(3)-Monoacylglycerol and sn-2-Monoacylglycerol in Caecal Enterocytes and Hepatocytes of Brown Trout (Salmo trutta).

PubMed

Li, Keshuai; Olsen, Rolf Erik

2017-01-01

sn-2-Monoacylglycerol (2-MAG) and sn-1(3)-monoacylglycerol [1(3)-MAG] are important but yet little studied intermediates in lipid metabolism. The current study compared the metabolic fate of 2-MAG and 1(3)-MAG in isolated caecal enterocytes and hepatocytes of brown trout (Salmo trutta). 1(3)-Oleoyl [9,10-3H(N)]-glycerol and 2-Oleoyl [9,10-3H(N)]-glycerol were prepared by pancreatic lipase digestion of triolein [9,10-3H(N)]. The 1(3)-MAG and 2-MAG were efficiently absorbed by enterocytes and hepatocytes at similar rates. The 2-MAG was quickly resynthesized into TAG through the monoacylglycerol acyltransferase (EC: 2.3.1.22, MGAT) pathway in both tissues, whereas 1(3)-MAG was processed into TAG and phospholipids at a much slower rate, suggesting 2-MAG was the preferred substrates for MGAT. Further analysis showed that 1(3)-MAG was synthesized into 1,3-DAG, but there were no accumulation of 1,3-DAG in either enterocytes or hepatocytes, which contrasts that of mammalian studies. Some of the 1(3)-MAG may be acylated to 1,2(2,3)-DAG and then utilized for TAG synthesis. Alternatively, 1(3)-MAG can be hydrolyzed to free fatty acid and glycerol, and re-synthesized into TAG through the glycerol-3-phosphate (Gro-3-P) pathway. The overall data suggested that the limiting step of the intracellular 1(3)-MAG metabolism is the conversion of 1(3)-MAG itself.

Chinese moral perspectives on abortion and foetal life: an historical account.

PubMed

Nie, Jing-Bao

2002-10-01

It is accepted wisdom that, at the present time as well as historically, the typical Chinese attitude toward abortion is very permissive or 'liberal'. It has been widely perceived that Chinese people usually do not consider abortion morally problematic and that they think a human life starts at birth. As part of a bigger research project on Chinese views and experiences of abortion, this article represents a revisionist historical account of Chinese moral perspectives on abortion and foetal life. By presenting Buddhist and Confucian views of abortion, traditional Chinese medical understandings of foetal life, the possible moral foundation of a 'conservative' Confucian position, and some historical features of abortion laws and policies in twentieth-century China, this paper shows that blanket assumptions that the Chinese view of abortion has always been permissive are historically unfounded. As in the present, there existed different and opposing views about abortion in history, and many Chinese, not only Buddhists but also Confucians, believed that deliberately terminating pregnancy is to destroy a human life which starts far earlier than at birth. The current dominant and official line on the subject does not necessarily accord with historical Chinese values and practices.

THE EFFECT OF ANTISERUM, ALONE AND WITH HYDROCORTISONE, ON FOETAL MOUSE BONES IN CULTURE

PubMed Central

Fell, Honor B.; Weiss, L.

1965-01-01

1. The effects of normal rabbit serum and of rabbit antiserum to whole foetal mouse tissues, on the isolated limb bones of late foetal mice were studied in organ culture, and the influence of hydrocortisone on these effects was investigated. 2. Unheated normal serum caused slight loss of metachromatic material from the cartilage matrix, and some resorption of both cartilage and bone. 3. In unheated antiserum to foetal mouse tissues, the terminal cartilage was smaller and less metachromatic than in paired controls in normal serum, while osteoclasis was so intense that in many explants the bone had almost disappeared. The amount of necrosis varied with different batches of antiserum. 4. The changes produced by normal serum and antiserum could be largely prevented by heating the sera to 57°C for 45 minutes. 5. The effects could also be inhibited by the addition of hydrocortisone to the unheated sera; as little as 0.1 µg hydrocortisone per ml of medium had a well marked protective action. 6. It is suggested that (a) unheated antiserum causes a release of lysosomal enzymes with consequent breakdown of intercellular material, (b) this release is due to an indirect action on the lysosome via an increased permeability of the cell membrane, (c) hydrocortisone does not affect the antigen-antibody reaction, but inhibits the autolytic changes that normally follow this reaction, possibly by stabilising both the lysosomal and cell membranes. PMID:14276776

The relationship between maternal body composition in early pregnancy and foetal mid-thigh soft-tissue thickness in the third trimester in a high-risk obstetric population.

PubMed

Anglim, Breffini; Farah, Nadine; O'Connor, Clare; Daly, Niamh; Kennelly, Mairead M; Turner, Michael J

2017-07-01

Maternal obesity is an emerging challenge in contemporary obstetrics. To date there has been no study analysing the relationship between specific maternal body composition measurements and foetal soft-tissue measurements. The aim of this study was to determine whether measurement of maternal body composition at booking predicts foetal soft-tissue trajectories in the third trimester. We analysed the relationship between foetal thigh in the third trimester and both maternal BMI and body composition using the Tanita digital scales in the first trimester. Foetal subcutaneous thigh tissue measurements were obtained at intervals of 28, 32 and 36 weeks of gestation. A total of 160 women were identified. There was a direct correlation between MTST at 36 weeks and BMI (p = .002). There was a positive correlation between MTST at 36 weeks and leg fat mass (p = .13) and leg fat free mass (p = .013). There was a positive correlation between arm fat free mass and MTST at 36 weeks. We showed there is an association between maternal fat distribution and foetal subcutaneous thigh tissue measurements. MTST may be more useful in determining if a child is at risk of macrosomia. Impact statement Previous studies have suggested that maternal obesity programmes intrauterine foetal adiposity and growth. The aim of this study was to examine the relationship in a high-risk obstetric population between measurements of maternal body composition in early pregnancy and the assessment of foetal adiposity in the third trimester using serial ultrasound measurements of mid-thigh soft-tissue thickness. BMI is only a surrogate measurement of fat and does not measure fat distribution. Our study shows the distribution of both maternal fat and fat-free mass in early pregnancy may be positively associated with foetal soft-tissue measurements in the third trimester. Maternal arthropometric measurements other than BMI may help predict babies at risk of macrosomia and neonatal adiposity.

Naive Theory of Biology: The Pre-School Child's Explanation of Death

ERIC Educational Resources Information Center

Vlok, Milandre; de Witt, Marike W.

2012-01-01

This article explains the naive theory of biology that the pre-school child uses to explain the cause of death. The empirical investigation showed that the young participants do use a naive theory of biology to explain function and do make reference to "vitalistic causality" in explaining organ function. Furthermore, most of these…

Human fetal enterocytes in vitro: modulation of the phenotype by extracellular matrix.

PubMed Central

Sanderson, I R; Ezzell, R M; Kedinger, M; Erlanger, M; Xu, Z X; Pringault, E; Leon-Robine, S; Louvard, D; Walker, W A

1996-01-01

The differentiation of small intestinal epithelial cells may require stimulation by microenvironmental factors in vivo. In this study, the effects of mesenchymal and luminal elements in nonmalignant epithelia] cells isolated from the human fetus were studied in vitro. Enterocytes from the human fetus were cultured and microenvironmental factors were added in stages, each stage more closely approximating the microenvironment in vivo. Four stages were examined: epithelial cells derived on plastic from intestinal culture and grown as a cell clone, the same cells grown on connective tissue support, primary epithelial explants grown on fibroblasts with a laminin base, and primary epithelial explants grown on fibroblasts and laminin with n-butyrate added to the incubation medium. The epithelial cell clone dedifferentiated when grown on plastic; however, the cells expressed cytokeratins and villin as evidence of their epithelial cell origin. Human connective tissue matrix from Engelbreth-Holm-Swarm sarcoma cells (Matrigel) modulated their phenotype: alkaline phosphatase activity increased, microvilli developed on their apical surface, and the profile of insulin-like growth factor binding proteins resembled that secreted by differentiated enterocytes. Epithelial cells taken directly from the human fetus as primary cultures and grown as explants on fibroblasts and laminin expressed greater specific enzyme activities in brush border membrane fractions than the cell clone. These activities were enhanced by the luminal molecule sodium butyrate. Thus the sequential addition of connective tissue and luminal molecules to nonmalignant epithelia] cells in vitro induces a spectrum of changes in the epithelial cell phenotype toward full differentiation. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:8755542

Effect of transforming growth factor-alpha on enterocyte apoptosis is correlated with EGF receptor expression along the villus-crypt axis during methotrexate-induced intestinal mucositis in a rat.

PubMed

Sukhotnik, Igor; Shteinberg, Dan; Ben Lulu, Shani; Bashenko, Yulia; Mogilner, Jorge G; Ure, Benno M; Shaoul, Ron; Coran, Arnold G

2008-11-01

The purpose of the present study was to evaluate the effect of transforming-growth factor-alpha (TGF-alpha) on enterocyte apoptosis following methotrexate (MTX) induced intestinal mucositis in a rat and in Caco-2 cells. Non-pretreated and pretreated with MTX Caco-2 cells were incubated with increasing concentrations of TGF-alpha. Cell apoptosis was determined by FACS cytometry. Adult rats were divided into four groups: Control, Control-TGF-alpha, MTX, and MTX- TGF-alpha rats. Three days later rats were sacrificed. Enterocyte apoptosis were measured at sacrifice. RT-PCR and Western Blotting was used to determine the level of Bax and Bcl-2 mRNA and protein. Real time PCR was used to measure epidermal growth factor receptor (EGFr) expression along the villus-crypt axis. The in vitro experiment has shown that treatment with TGF-alpha of Caco-2 cells results in a significant inhibition of cell apoptosis in a dose-dependent manner. In vivo experiment, a decreased levels of apoptosis in MTX- TGF-alpha rats corresponded with the decrease in Bax and with the increase in Bcl-2 at both mRNA and protein levels. The inhibiting effect of TGF-alpha on enterocyte apoptosis was strongly correlated with EGFr expression along the villus-crypt axis. In conclusion, treatment with TGF-alpha inhibits enterocyte apoptosis following MTX- injury in the rat.

Spectrum of prenatally detected central nervous system malformations: Neural tube defects continue to be the leading foetal malformation.

PubMed

Siddesh, Anjurani; Gupta, Geetika; Sharan, Ram; Agarwal, Meenal; Phadke, Shubha R

2017-04-01

Prenatal diagnosis of malformations is an important method of prevention and control of congenital anomalies with poor prognosis. Central nervous system (CNS) malformations amongst these are the most common. The information about the prevalence and spectrum of prenatally detected malformations is crucial for genetic counselling and policymaking for population-based preventive programmes. The objective of this study was to study the spectrum of prenatally detected CNS malformations and their association with chromosomal abnormalities and autopsy findings. This retrospective study was conducted in a tertiary care hospital in north India from January 2007 to December 2013. The details of cases with prenatally detected CNS malformations were collected and were related with the foetal chromosomal analysis and autopsy findings. Amongst 6044 prenatal ultrasonographic examinations performed; 768 (12.7%) had structural malformations and 243 (31.6%) had CNS malformations. Neural tube defects (NTDs) accounted for 52.3 per cent of CNS malformations and 16.5 per cent of all malformations. The other major groups of prenatally detected CNS malformations were ventriculomegaly and midline anomalies. Chromosomal abnormalities were detected in 8.2 per cent of the 73 cases studied. Foetal autopsy findings were available for 48 foetuses. Foetal autopsy identified additional findings in eight foetuses and the aetiological diagnosis changed in two of them (4.2%). Amongst prenatally detected malformations, CNS malformations were common. NTD, which largely is a preventable anomaly, continued to be the most common group. Moreover, 60 per cent of malformations were diagnosed after 20 weeks, posing legal issues. Chromosomal analysis and foetal autopsy are essential for genetic counselling based on aetiological diagnosis.

Inhibition of PIM1 kinase attenuates inflammation-induced pro-labour mediators in human foetal membranes in vitro.

PubMed

Lim, Ratana; Barker, Gillian; Lappas, Martha

2017-06-01

Does proviral integration site for Moloney murine leukaemic virus (PIM)1 kinase play a role in regulating the inflammatory processes of human labour and delivery? PIM1 kinase plays a critical role in foetal membranes in regulating pro-inflammatory and pro-labour mediators. Infection and inflammation have strong causal links to preterm delivery by stimulating pro-inflammatory cytokines and collagen degrading enzymes, which can lead to rupture of membranes. PIM1 has been shown to have a role in immune regulation and inflammation in non-gestational tissues; however, its role has not been explored in the field of human labour. PIM1 expression was analysed in myometrium and/or foetal membranes obtained at term and preterm (n = 8-9 patients per group). Foetal membranes, freshly isolated amnion cells and primary myometrial cells were used to investigate the effect of PIM1 inhibition on pro-labour mediators (n = 5 patients per treatment group). Foetal membranes, from term and preterm, were obtained from non-labouring and labouring women, and from preterm pre-labour rupture of membranes (PPROM) (n = 9 per group). Amnion was collected from women with and without preterm chorioamnionitis (n = 8 per group). Expression of PIM1 kinase was determined by qRT-PCR and western blotting. To determine the effect of PIM1 kinase inhibition on the expression of pro-inflammatory and pro-labour mediators induced by bacterial products lipopolysaccharide (LPS) (10 μg/ml) and flagellin (1 μg/ml) and pro-inflammatory cytokine tumour necrosis factor (TNF) (10 ng/ml), chemical inhibitors SMI-4a (20 μM) and AZD1208 (50 μM) were used in foetal membrane explants and siRNA against PIM1 was used in primary amnion cells. Statistical significance was set at P < 0.05. PIM1 expression was significantly increased in foetal membranes after spontaneous term labour compared to no labour at term and in amnion with preterm chorioamnionitis compared to preterm with no chorioamnionitis. There was no

The Role of Wnt/β-Catenin Signaling in Enterocyte Turnover during Methotrexate-Induced Intestinal Mucositis in a Rat

PubMed Central

Sukhotnik, Igor; Geyer, Tatiana; Pollak, Yulia; Mogilner, Jorge G.; Coran, Arnold G.; Berkowitz, Drora

2014-01-01

Background/Aims Intestinal mucositis is a common side-effect in patients who receive aggressive chemotherapy. The Wnt signaling pathway is critical for establishing and maintaining the proliferative compartment of the intestine. In the present study, we tested whether Wnt/β-catenin signaling is involved in methotrexate (MTX)-induced intestinal damage in a rat model. Methods Non-pretreated and pretreated with MTX Caco-2 cells were evaluated for cell proliferation and apoptosis using FACS analysis. Adult rats were divided into three experimental groups: Control rats; MTX-2 animals were treated with a single dose of MTX given IP and were sacrificed on day 2, and MTX-4 rats were treated with MTX similar to group B and were sacrificed on day 4. Intestinal mucosal damage, mucosal structural changes, enterocyte proliferation, and enterocyte apoptosis were measured at sacrifice. Real Time PCR and Western blot was used to determine the level of Wnt/β-catenin related genes and protein expression. Results In the vitro experiment, treatment with MTX resulted in marked decrease in early cell proliferation rates following by a 17-fold increase in late cell proliferation rates compared to early proliferation. Treatment with MTX resulted in a significant increase in early and late apoptosis compared to Caco-2 untreated cells. In the vivo experiment, MTX-2 and MTX-4 rats demonstrated intestinal mucosal hypoplasia. MTX-2 rats demonstrated a significant decrease in FRZ-2, Wnt 3A Wnt 5A, β-catenin, c-myc mRNA expression and a significant decrease in β-catenin and Akt protein levels compared to control animals. Four days following MTX administration, rats demonstrated a trend toward a restoration of Wnt/β-catenin signaling especially in ileum. Conclusions Wnt/β-catenin signaling is involved in enterocyte turnover during MTX-induced intestinal mucositis in a rat. PMID:25375224

FATAL FOETAL ABNORMALITY, IRISH CONSTITUTIONAL LAW, AND MELLET v IRELAND.

PubMed

de Londras, Fiona

2016-12-27

Under the Irish Constitution abortion is allowed only where the life of the pregnant woman is at risk. The provision in question, Article 40.3.3 (or the 8th Amendment) has long been criticised for failing to respect women's autonomy, and in Mellet v Ireland, the UN Human Rights Committee found that Amanda Jane Mellet, who travelled to Liverpool to access abortion following a finding that her foetus suffered a fatal abnormality, had suffered a violation of her rights under the International Covenant on Civil and Political Rights (ICCPR). In this commentary I demonstrate the value of Mellet when compared to the possible legal findings in such circumstances under both the Constitution and the European Convention on Human Rights, and argue that the findings are not restricted to cases of fatal foetal abnormality. Rather, the Committee's decision illustrates the suffering that all women in Ireland who travel to access abortion experience, arguably constituting a violation of their right to be free from cruel, inhuman, and degrading treatment. On that reading, Mellet signifies the need to implement a comprehensive rethink of Irish abortion law including, but going beyond, access to abortion in cases of fatal foetal abnormality. © The Author 2016. Published by Oxford University Press; all rights reserved. For Permissions, please email: journals.permissions@oup.com.

Calcium-mediated shaping of naive CD4 T-cell phenotype and function

PubMed Central

Guichard, Vincent; Bonilla, Nelly; Durand, Aurélie; Audemard-Verger, Alexandra; Guilbert, Thomas; Martin, Bruno

2017-01-01

Continuous contact with self-major histocompatibility complex ligands is essential for the survival of naive CD4 T cells. We have previously shown that the resulting tonic TCR signaling also influences their fate upon activation by increasing their ability to differentiate into induced/peripheral regulatory T cells. To decipher the molecular mechanisms governing this process, we here focus on the TCR signaling cascade and demonstrate that a rise in intracellular calcium levels is sufficient to modulate the phenotype of mouse naive CD4 T cells and to increase their sensitivity to regulatory T-cell polarization signals, both processes relying on calcineurin activation. Accordingly, in vivo calcineurin inhibition leads the most self-reactive naive CD4 T cells to adopt the phenotype of their less self-reactive cell-counterparts. Collectively, our findings demonstrate that calcium-mediated activation of the calcineurin pathway acts as a rheostat to shape both the phenotype and effector potential of naive CD4 T cells in the steady-state. PMID:29239722

LORETA functional imaging in antipsychotic-naive and olanzapine-, clozapine- and risperidone-treated patients with schizophrenia.

PubMed

Tislerova, Barbora; Brunovsky, Martin; Horacek, Jiri; Novak, Tomas; Kopecek, Miloslav; Mohr, Pavel; Krajca, Vladimír

2008-01-01

The aim of our study was to detect changes in the distribution of electrical brain activity in schizophrenic patients who were antipsychotic naive and those who received treatment with clozapine, olanzapine or risperidone. We included 41 subjects with schizophrenia (antipsychotic naive = 11; clozapine = 8; olanzapine = 10; risperidone = 12) and 20 healthy controls. Low-resolution brain electromagnetic tomography was computed from 19-channel electroencephalography for the frequency bands delta, theta, alpha-1, alpha-2, beta-1, beta-2 and beta-3. We compared antipsychotic-naive subjects with healthy controls and medicated patients. (1) Comparing antipsychotic-naive subjects and controls we found a general increase in the slow delta and theta frequencies over the fronto-temporo-occipital cortex, particularly in the temporolimbic structures, an increase in alpha-1 and alpha-2 in the temporal cortex and an increase in beta-1 and beta-2 in the temporo-occipital and posterior limbic structures. (2) Comparing patients who received clozapine and those who were antipsychotic naive, we found an increase in delta and theta frequencies in the anterior cingulate and medial frontal cortex, and a decrease in alpha-1 and beta-2 in the occipital structures. (3) Comparing patients taking olanzapine with those who were antipsychotic naive, there was an increase in theta frequencies in the anterior cingulum, a decrease in alpha-1, beta-2 and beta-3 in the occipital cortex and posterior limbic structures, and a decrease in beta-3 in the frontotemporal cortex and anterior cingulum. (4) In patients taking risperidone, we found no significant changes from those who were antipsychotic naive. Our results in antipsychotic-naive patients are in agreement with existing functional findings. Changes in those taking clozapine and olanzapine versus those who were antipsychotic naive suggest a compensatory mechanism in the neurobiological substrate for schizophrenia. The lack of difference in

Infrared Spectroscopy as a Tool to Study the Antioxidant Activity of Polyphenolic Compounds in Isolated Rat Enterocytes

PubMed Central

Barraza-Garza, Guillermo; Castillo-Michel, Hiram; de la Rosa, Laura A.; Martinez-Martinez, Alejandro; Pérez-León, Jorge A.; Cotte, Marine; Alvarez-Parrilla, Emilio

2016-01-01

The protective effect of different polyphenols, catechin (Cat), quercetin (Qc) (flavonoids), gallic acid (GA), caffeic acid (CfA), chlorogenic acid (ChA) (phenolic acids), and capsaicin (Cap), against H2O2-induced oxidative stress was evaluated in rat enterocytes using Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) Spectroscopy and Fourier Transform Infrared Microspectroscopy (FTIRM), and results were compared to standard lipid peroxidation techniques: conjugated dienes (CD) and Thiobarbituric Acid Reactive Substances (TBARS). Analysis of ATR-FTIR and FTIRM spectral data allowed the simultaneous evaluation of the effects of H2O2 and polyphenols on lipid and protein oxidation. All polyphenols showed a protective effect against H2O2-induced oxidative stress in enterocytes, when administered before or after H2O2. Cat and capsaicin showed the highest protective effect, while phenolic acids had weaker effects and Qc presented a mild prooxidative effect (IR spectral profile of biomolecules between control and H2O2-treated cells) according to FTIR analyses. These results demonstrated the viability to use infrared spectroscopy to evaluate the oxidant and antioxidant effect of molecules in cell systems assays. PMID:27213031

Criteria-based audit to improve quality of care of foetal distress: standardising obstetric care at a national referral hospital in a low resource setting, Tanzania.

PubMed

Mgaya, Andrew H; Litorp, Helena; Kidanto, Hussein L; Nyström, Lennarth; Essén, Birgitta

2016-11-08

In Tanzania, substandard intrapartum management of foetal distress contributes to a third of perinatal deaths, and the majority are term deliveries. We conducted a criteria-based audit with feedback to determine whether standards of diagnosis and management of foetal distress would be improved in a low-resource setting. During 2013-2015, a criteria-based audit was performed at the national referral hospital in Dar es Salaam. Case files of deliveries with a diagnosis of foetal distress were identified and audited. Two registered nurses under supervision of a nurse midwife, a specialist obstetrician and a consultant obstetrician, reviewed the case files. Criteria for standard diagnosis and management of foetal distress were developed based on international and national guidelines, and literature reviews, and then, stepwise applied, in an audit cycle. During the baseline audit, substandard care was identified, and recommendations for improvement of care were proposed and implemented. The effect of the implementations was assessed by the differences in percentage of standard diagnosis and management between the baseline and re-audit, using Chi-square test or Fisher's exact test, when appropriate. In the baseline audit and re-audit, 248 and 251 deliveries with a diagnosis of foetal distress were identified and audited, respectively. The standard of diagnosis increased significantly from 52 to 68 % (p < 0.001). Standards of management improved tenfold from 0.8 to 8.8 % (p < 0.001). Improved foetal heartbeat monitoring using a Fetal Doppler was the major improvement in diagnoses, while change of position of the mother and reduced time interval from decision to perform caesarean section to delivery were the major improvements in management (all p < 0.001). Percentage of cases with substandard diagnosis and management was significantly reduced in both referred public and non-referred private patients (all p ≤ 0.01) but not in non-referred public and

Fatty acid binding proteins have the potential to channel dietary fatty acids into enterocyte nuclei.

PubMed

Esteves, Adriana; Knoll-Gellida, Anja; Canclini, Lucia; Silvarrey, Maria Cecilia; André, Michèle; Babin, Patrick J

2016-02-01

Intracellular lipid binding proteins, including fatty acid binding proteins (FABPs) 1 and 2, are highly expressed in tissues involved in the active lipid metabolism. A zebrafish model was used to demonstrate differential expression levels of fabp1b.1, fabp1b.2, and fabp2 transcripts in liver, anterior intestine, and brain. Transcription levels of fabp1b.1 and fabp2 in the anterior intestine were upregulated after feeding and modulated according to diet formulation. Immunofluorescence and electron microscopy immunodetection with gold particles localized these FABPs in the microvilli, cytosol, and nuclei of most enterocytes in the anterior intestinal mucosa. Nuclear localization was mostly in the interchromatin space outside the condensed chromatin clusters. Native PAGE binding assay of BODIPY-FL-labeled FAs demonstrated binding of BODIPY-FLC(12) but not BODIPY-FLC(5) to recombinant Fabp1b.1 and Fabp2. The binding of BODIPY-FLC(12) to Fabp1b.1 was fully displaced by oleic acid. In vivo experiments demonstrated, for the first time, that intestinal absorption of dietary BODIPY-FLC(12) was followed by colocalization of the labeled FA with Fabp1b and Fabp2 in the nuclei. These data suggest that dietary FAs complexed with FABPs are able to reach the enterocyte nucleus with the potential to modulate nuclear activity. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

The Persistence of "Solid" and "Liquid" Naive Conceptions: A Reaction Time Study

ERIC Educational Resources Information Center

Babai, Reuven; Amsterdamer, Anat

2008-01-01

The study explores whether the naive concepts of "solid" and "liquid" persist in adolescence. Accuracy of responses and reaction times where measured while 41 ninth graders classified different solids (rigid, non-rigid and powders) and different liquids (runny, dense) into solid or liquid. The results show that these naive conceptions affect…

Nitric oxide synthase expression in foetal placentas of cows with retained fetal membranes.

PubMed

Shixin, Fu; Li, Zhang; Chunhai, Luo; Chuang, Xu; Cheng, Xia; Zhe, Wang; Xiaobing, Li

2011-10-01

The objectives of this study were to investigate relationship of retained fetal membranes (RFM) to expression of NOS and NOS mRNA and to analyze pathohistological changes and the distribution of nitric oxide synthase (NOS) in foetal placentas of cows with RFM. Twenty cows were assigned to two groups, a control group (no retained fetal membranes, NRFM, n = 10) and a diseased group (RFM, n = 10). The endpoint method was used to detect the nitric oxide (NO) content and nitric oxide synthase (NOS) activity in foetal placental tissue fluid and the fluorescent quantitation PCR was used to measure the expression of NOS mRNA. Immunohistochemistry and hematoxylin-eosin staining were used to observe pathohistological changes. Tissue from RFM cows showed fibronecrosis of the chorionic villi, and a decreased number of trophoblastic cells. The majority of trophoblastic cells displayed vacuolar degeneration. Interstitium vessels were distended and congested. Expression of induced nitric oxide synthase (iNOS) protein and iNOS mRNA was significantly higher (P < 0.05) in the cytoplasm of placental villus trophoblastic cells in the RFM group. But expression of endothelial nitric oxide synthase (eNOS) protein and eNOS mRNA was significantly lower (P<0.05) in the RFM group. The NO content and NOS activity of cows with RFM were significantly higher (P < 0.05). A high expression of iNOS protein and iNOS mRNA in the cow foetal placenta could produce high content of NO, which might inhibit uterine contraction. So over expression of iNOS protein and iNOS mRNA might be an important agent of retained fetal membranes in cows, and it may be a potential diagnosis biomarker. Copyright © 2010 Elsevier Ltd. All rights reserved.

Experimental Type 2 Diabetes Induces Enzymatic Changes in Isolated Rat Enterocytes

PubMed Central

Martínez, Isabel M.; Morales, Inmaculada; García-Pino, Guadalupe; Campillo, José E.

2003-01-01

Diabetes in humans and in experimental animals produces changes in the function and structure of the small intestine. The authors determined the activity of intestinal disaccharidases (maltase and sucrase) and of 6-phosphofructo-1-kinase (PFK-1) in enterocytes isolated from the small intestine of male Wistar rats (2.5 to 3 months old) with experimental nonobese type 2 diabetes, induced by streptozotocin (STZ) injection on the day of birth (n0-STZ) or on the 5th day of life (n5-STZ), with different degrees of hyperglycemia and insulinemia (n0-STZ and n5-STZ models). The glycemia (mmol/L) of the diabetic rats (n0-STZ: 8.77 ± 0.47; n5-STZ: 20.83 ± 0.63) was higher (P < .01) than that of the nondiabetic (ND) rats (5.99 ± 0.63); on the contrary, the insulinemia (ng/mL) was significantly lower in both n0-STZ (1.74 ± 0.53; P < .05) and n5-STZ (1.12 ± 0.44; P < .01) diabetic rats than in normal rats (3.77 ± 0.22). The sucrase and maltase activities (U/g protein) in diabetic rats (n0-STZ: 89 ± 9 and 266 ± 12; n5-STZ: 142 ± 23 and 451 ± 57) were significantly higher than those in the ND group (66 ± 5 and 228 ± 22). The PFK-1 activities (mU/mg protein) in the diabetic models (n0-STZ: 14.89 ± 1.51; n5-STZ: 13.35 ± 3.12) were significantly lower (P < .05) than in ND rats (20.54 ± 2.83). The data demonstrated enzymatic alterations in enterocytes isolated fromthe small intestine of n0-STZ rats that are greater (P < .05) than in the more hyperglycemic and hypoinsulinemic n5-STZ animals. The results also show that nonobese type 2–like diabetes in the rat produces modifications that favor an increase in glucose absorption rates. PMID:14630573

Foetal and adult human CYP3A isoforms in the bioactivation of organophosphorothionate insecticides.

PubMed

Buratti, Franca M; Leoni, Claudia; Testai, Emanuela

2006-12-15

In humans organophosphorothionate pesticides (OPT) prenatal exposure has been demonstrated. Since OPT-induced neurodevelopmental effects may be due to in situ bioactivation by foetal enzymes, the catalytic activity of the foetal CYP3A7 toward chlorpyrifos (CPF), parathion (PAR), malathion (MAL) and fenthion (FEN) has been assessed by using recombinant enzymes. A comparison with the adult isoforms CYP3A4 and CYP3A5 has been also carried out. CYP3A7 was able to produce significant levels of oxon or sulfoxide from the four OPTs in the range of tested concentrations (0.05-200 microM). When the efficiencies of CYP3A isoforms were compared, the ranking, expressed as CLi values, were: CPF=3A4>3A5>3A7; PAR=3A4>3A7>3A5; MAL=3A4>3A7>3A5; FEN (sulfoxide formation)=3A4>3A5>3A7. The CYP3A5 efficiency appeared to be more dependent on the single insecticide than its related isozyme CYP3A4. Our results indicate that the levels of toxic metabolite formed in situ by CYP3A7 from CPF, MAL and PAR but not from FEN have the chance to inhibit acetylcholinesterase, following prenatal exposure to OPTs. However, due to the smaller weight of foetal liver, the contribution to total OPT biotransformation is relatively low. On the other hand, our results clearly indicate that at low CPF concentrations, the formation of the non-toxic metabolites is highly favoured in the foetus.

What Fits into a Mirror: Naive Beliefs about the Field of View

ERIC Educational Resources Information Center

Bianchi, Ivana; Savardi, Ugo

2012-01-01

Research on naive physics and naive optics have shown that people hold surprising beliefs about everyday phenomena that are in contrast with what they see. In this article, we investigated what adults expect to be the field of view of a mirror from various viewpoints. The studies presented here confirm that humans have difficulty dealing with the…

Impaired processing speed and attention in first-episode drug naive schizophrenia with deficit syndrome.

PubMed

Chen, Ce; Jiang, Wenhui; Zhong, Na; Wu, Jin; Jiang, Haifeng; Du, Jiang; Li, Ye; Ma, Xiancang; Zhao, Min; Hashimoto, Kenji; Gao, Chengge

2014-11-01

Although first-episode drug naive patients with schizophrenia are known to show cognitive impairment, the cognitive performances of these patients, who suffer deficit syndrome, compared with those who suffer non-deficit syndrome is undetermined. The aim of this study was to compare cognitive performances in first-episode drug-naive schizophrenia with deficit syndrome or non-deficit syndrome. First-episode drug naive patients (n=49) and medicated patients (n=108) with schizophrenia, and age, sex, and education matched healthy controls (n=57 for the first-episode group, and n=128 for the medicated group) were enrolled. Patients were divided into deficit or non-deficit syndrome groups, using the Schedule for Deficit Syndrome. Cognitive performance was assessed using the CogState computerized cognitive battery. All cognitive domains in first-episode drug naive and medicated patients showed significant impairment compared with their respective control groups. Furthermore, cognitive performance in first-episode drug naive patients was significantly worse than in medicated patients. Interestingly, the cognitive performance markers of processing speed and attention, in first-episode drug naive patients with deficit syndrome, were both significantly worse than in equivalent patients without deficit syndrome. In contrast, no differences in cognitive performance were found between the two groups of medicated patients. In conclusion, this study found that first-episode drug naive schizophrenia with deficit syndrome showed significantly impaired processing speed and attention, compared with patients with non-deficit syndrome. These findings highlight processing speed and attention as potential targets for pharmacological and psychosocial interventions in first-episode schizophrenia with deficit syndrome, since these domains are associated with social outcomes. Copyright © 2014 Elsevier B.V. All rights reserved.

Heme oxygenase-1 is a critical regulator of nitric oxide production in enterohemorrhagic Escherichia coli-infected human enterocytes.

PubMed

Vareille, Marjolaine; Rannou, François; Thélier, Natacha; Glasser, Anne-Lise; de Sablet, Thibaut; Martin, Christine; Gobert, Alain P

2008-04-15

Enterohemorrhagic Escherichia coli (EHEC) are the causative agent of hemolytic-uremic syndrome. In the first stage of the infection, EHEC interact with human enterocytes to modulate the innate immune response. Inducible NO synthase (iNOS)-derived NO is a critical mediator of the inflammatory response of the infected intestinal mucosa. We therefore aimed to analyze the role of EHEC on iNOS induction in human epithelial cell lines. In this regard, we show that EHEC down-regulate IFN-gamma-induced iNOS mRNA expression and NO production in Hct-8, Caco-2, and T84 cells. This inhibitory effect occurs through the decrease of STAT-1 activation. In parallel, we demonstrate that EHEC stimulate the rapid inducible expression of the gene hmox-1 that encodes for the enzyme heme oxygenase-1 (HO-1). Knock-down of hmox-1 gene expression by small interfering RNA or the blockade of HO-1 activity by zinc protoporphyrin IX abrogated the EHEC-dependent inhibition of STAT-1 activation and iNOS mRNA expression in activated human enterocytes. These results highlight a new strategy elaborated by EHEC to control the host innate immune response.

Rapid spread and association of Schmallenberg virus with ruminant abortions and foetal death in Austria in 2012/2013.

PubMed

Steinrigl, Adolf; Schiefer, Peter; Schleicher, Corina; Peinhopf, Walter; Wodak, Eveline; Bagó, Zoltán; Schmoll, Friedrich

2014-10-15

Schmallenberg virus (SBV) has emerged in summer-autumn 2011 in north-western Europe. Since then, SBV has been continuously spreading over Europe, including Austria, where antibodies to SBV, as well as SBV genome, were first detected in autumn 2012. This study was performed to demonstrate the dynamics of SBV spread within Austria, after its probable first introduction in summer 2012. True seroprevalence estimates for cattle and small ruminates were calculated to demonstrate temporal and regional differences of infection. Furthermore, the probability of SBV genome detection in foetal tissues of aborted or stillborn cattle and small ruminants as well as in allantoic fluid samples from cows with early foetal losses was retrospectively assessed. SBV first reached Austria most likely in July-August 2012, as indicated by retrospective detection of SBV antibodies and SBV genome in archived samples. From August to October 2012, a rapid increase in seroprevalence to over 98% in cattle and a contemporaneous peak in the detection of SBV genome in foetal tissues and allantoic fluid samples was noted, indicating widespread acute infections. Notably, foetal malformations were absent in RT-qPCR positive foetuses at this time of the epidemic. SBV spread within Austrian cattle reached a plateau phase as early as October 2012, without significant regional differences in SBV seroprevalence (98.4-100%). Estimated true seroprevalences among small ruminates were comparatively lower than in cattle and regionally different (58.3-95.6% in October 2012), potentially indicating an eastward spread of the infection, as well as different infection dynamics between cattle and small ruminants. Additionally, the probability of SBV genome detection over time differed significantly between small ruminant and cattle samples subjected to RT-qPCR testing. Copyright © 2014 Elsevier B.V. All rights reserved.

Classification of caesarean section and normal vaginal deliveries using foetal heart rate signals and advanced machine learning algorithms.

PubMed

Fergus, Paul; Hussain, Abir; Al-Jumeily, Dhiya; Huang, De-Shuang; Bouguila, Nizar

2017-07-06

Visual inspection of cardiotocography traces by obstetricians and midwives is the gold standard for monitoring the wellbeing of the foetus during antenatal care. However, inter- and intra-observer variability is high with only a 30% positive predictive value for the classification of pathological outcomes. This has a significant negative impact on the perinatal foetus and often results in cardio-pulmonary arrest, brain and vital organ damage, cerebral palsy, hearing, visual and cognitive defects and in severe cases, death. This paper shows that using machine learning and foetal heart rate signals provides direct information about the foetal state and helps to filter the subjective opinions of medical practitioners when used as a decision support tool. The primary aim is to provide a proof-of-concept that demonstrates how machine learning can be used to objectively determine when medical intervention, such as caesarean section, is required and help avoid preventable perinatal deaths. This is evidenced using an open dataset that comprises 506 controls (normal virginal deliveries) and 46 cases (caesarean due to pH ≤ 7.20-acidosis, n = 18; pH > 7.20 and pH < 7.25-foetal deterioration, n = 4; or clinical decision without evidence of pathological outcome measures, n = 24). Several machine-learning algorithms are trained, and validated, using binary classifier performance measures. The findings show that deep learning classification achieves sensitivity = 94%, specificity = 91%, Area under the curve = 99%, F-score = 100%, and mean square error = 1%. The results demonstrate that machine learning significantly improves the efficiency for the detection of caesarean section and normal vaginal deliveries using foetal heart rate signals compared with obstetrician and midwife predictions and systems reported in previous studies.

'Educated' dendritic cells act as messengers from memory to naive T helper cells.

PubMed

Alpan, Oral; Bachelder, Eric; Isil, Eda; Arnheiter, Heinz; Matzinger, Polly

2004-06-01

Ingested antigens lead to the generation of effector T cells that secrete interleukin 4 (IL-4) rather than interferon-gamma (IFN-gamma) and are capable of influencing naive T cells in their immediate environment to do the same. Using chimeric mice generated by aggregation of two genotypically different embryos, we found that the conversion of a naive T cell occurs only if it can interact with the same antigen-presenting cell, although not necessarily the same antigen, as the effector T cell. Using a two-step culture system in vitro, we found that antigen-presenting dendritic cells can act as 'temporal bridges' to relay information from orally immunized memory CD4 T cells to naive CD4 T cells. The orally immunized T cells use IL-4 and IL-10 (but not CD40 ligand) to 'educate' dendritic cells, which in turn induce naive T cells to produce the same cytokines as those produced by the orally immunized memory T cells.

Effects of water temperature and diets containing palm oil on fatty acid desaturation and oxidation in hepatocytes and intestinal enterocytes of rainbow trout (Oncorhynchus mykiss).

PubMed

Tocher, Douglas R; Fonseca-Madrigal, Jorge; Dick, James R; Ng, Wing-Keong; Bell, J Gordon; Campbell, Patrick J

2004-01-01

Food grade fisheries have reached their sustainable limits while aquaculture production has increased to meet consumer demands. However, for growth in aquaculture to continue and utilise sustainable, feeding ingredients, alternatives to fish oil (FO), the predominant lipid component of fish diets, must be developed. Therefore, there is currently considerable interest in the regulation of fatty acid metabolism in fish in order to determine strategies for the best use of plant oils in diets for commercially important cultured fish species. Plant oils are characteristically rich in C18 polyunsaturated fatty acids (PUFA) but devoid of C20 and C22 highly unsaturated fatty acids (HUFA) found in FO. The fatty acyl desaturase enzyme activities involved in the biosynthesis of HUFA from PUFA are known to be under nutritional regulation and can be increased in fish fed diets rich in plant oils. However, fatty acid desaturase activity is also known to be modulated by water temperature in fish. The present study aimed to investigate the interaction between water temperature and diet in the regulation of fatty acid metabolism in rainbow trout. Trout, acclimatized to 7, 11 or 15 degrees C, were fed for 4 weeks on diets in which the FO was replaced in a graded manner by palm oil. At the end of the trial, fatty acyl desaturation/elongation and beta-oxidation activities were determined in isolated hepatocytes and intestinal enterocytes using [1-14C]18:3n-3 as substrate, and samples of liver were collected for analysis of lipid and fatty acid composition. The most obvious effect of temperature was that fatty acid desaturation/elongation and beta-oxidation were reduced in both hepatocytes and intestinal enterocytes from fish maintained at the highest water temperature (15 degrees C). There were differences between the two tissues with the highest desaturation/elongation and beta-oxidation activities tending to be in fish held at 11 degrees C in the case of hepatocytes, but 7 degrees C

Top predators affect the composition of naive protist communities, but only in their early-successional stage.

PubMed

Zander, Axel; Gravel, Dominique; Bersier, Louis-Félix; Gray, Sarah M

2016-02-01

Introduced top predators have the potential to disrupt community dynamics when prey species are naive to predation. The impact of introduced predators may also vary depending on the stage of community development. Early-succession communities are likely to have small-bodied and fast-growing species, but are not necessarily good at defending against predators. In contrast, late-succession communities are typically composed of larger-bodied species that are more predator resistant relative to small-bodied species. Yet, these aspects are greatly neglected in invasion studies. We therefore tested the effect of top predator presence on early- and late-succession communities that were either naive or non-naive to top predators. We used the aquatic community held within the leaves of Sarracenia purpurea. In North America, communities have experienced the S. purpurea top predator and are therefore non-naive. In Europe, this predator is not present and its niche has not been filled, making these communities top-predator naive. We collected early- and late-succession communities from two non-naive and two naive sites, which are climatically similar. We then conducted a common-garden experiment, with and without the presence of the top predator, in which we recorded changes in community composition, body size spectra, bacterial density, and respiration. We found that the top predator had no statistical effect on global measures of community structure and functioning. However, it significantly altered protist composition, but only in naive, early-succession communities, highlighting that the state of community development is important for understanding the impact of invasion.

Children and Adolescents' Understandings of Family Resemblance: A Study of Naive Inheritance Concepts

ERIC Educational Resources Information Center

Williams, Joanne M.

2012-01-01

This paper aims to provide developmental data on two connected naive inheritance concepts and to explore the coherence of children's naive biology knowledge. Two tasks examined children and adolescents' (4, 7, 10, and 14 years) conceptions of phenotypic resemblance across kin (in physical characteristics, disabilities, and personality traits). The…

Germline mutations in RYR1 are associated with foetal akinesia deformation sequence/lethal multiple pterygium syndrome.

PubMed

McKie, Arthur B; Alsaedi, Atif; Vogt, Julie; Stuurman, Kyra E; Weiss, Marjan M; Shakeel, Hassan; Tee, Louise; Morgan, Neil V; Nikkels, Peter G J; van Haaften, Gijs; Park, Soo-Mi; van der Smagt, Jasper J; Bugiani, Marianna; Maher, Eamonn R

2014-12-05

Foetal akinesia deformation sequence syndrome (FADS) is a genetically heterogeneous disorder characterised by the combination of foetal akinesia and developmental defects which may include pterygia (joint webbing). Traditionally multiple pterygium syndrome (MPS) has been divided into two forms: prenatally lethal (LMPS) and non-lethal Escobar type (EVMPS) types. Interestingly, FADS, LMPS and EVMPS may be allelic e.g. each of these phenotypes may result from mutations in the foetal acetylcholine receptor gamma subunit gene (CHRNG). Many cases of FADS and MPS do not have a mutation in a known FADS/MPS gene and we undertook molecular genetic studies to identify novel causes of these phenotypes. After mapping a novel locus for FADS/LMPS to chromosome 19, we identified a homozygous null mutation in the RYR1 gene in a consanguineous kindred with recurrent LMPS pregnancies. Resequencing of RYR1 in a cohort of 66 unrelated probands with FADS/LMPS/EVMPS (36 with FADS/LMPS and 30 with EVMPS) revealed two additional homozygous mutations (in frame deletions). The overall frequency of RYR1 mutations in probands with FADS/LMPS was 8.3%. Our findings report, for the first time, a homozygous RYR1 null mutation and expand the range of RYR1-related phenotypes to include early lethal FADS/LMPS. We suggest that RYR1 mutation analysis should be performed in cases of severe FADS/LMPS even in the absence of specific histopathological indicators of RYR1-related disease.

Fatty acid binding proteins have the potential to channel dietary fatty acids into enterocyte nuclei[S

PubMed Central

Esteves, Adriana; Knoll-Gellida, Anja; Canclini, Lucia; Silvarrey, Maria Cecilia; André, Michèle; Babin, Patrick J.

2016-01-01

Intracellular lipid binding proteins, including fatty acid binding proteins (FABPs) 1 and 2, are highly expressed in tissues involved in the active lipid metabolism. A zebrafish model was used to demonstrate differential expression levels of fabp1b.1, fabp1b.2, and fabp2 transcripts in liver, anterior intestine, and brain. Transcription levels of fabp1b.1 and fabp2 in the anterior intestine were upregulated after feeding and modulated according to diet formulation. Immunofluorescence and electron microscopy immunodetection with gold particles localized these FABPs in the microvilli, cytosol, and nuclei of most enterocytes in the anterior intestinal mucosa. Nuclear localization was mostly in the interchromatin space outside the condensed chromatin clusters. Native PAGE binding assay of BODIPY-FL-labeled FAs demonstrated binding of BODIPY-FLC12 but not BODIPY-FLC5 to recombinant Fabp1b.1 and Fabp2. The binding of BODIPY-FLC12 to Fabp1b.1 was fully displaced by oleic acid. In vivo experiments demonstrated, for the first time, that intestinal absorption of dietary BODIPY-FLC12 was followed by colocalization of the labeled FA with Fabp1b and Fabp2 in the nuclei. These data suggest that dietary FAs complexed with FABPs are able to reach the enterocyte nucleus with the potential to modulate nuclear activity. PMID:26658423

A comparative study of the spatial distribution of mast cells and microvessels in the foetal, adult human thymus and thymoma.

PubMed

Raica, Marius; Cimpean, Anca Maria; Nico, Beatrice; Guidolin, Diego; Ribatti, Domenico

2010-02-01

Mast cells (MCs) are widely distributed in human and animal tissues and have been shown to play an important role in angiogenesis in normal and pathological conditions. Few data are available about the relationship between MCs and blood vessels in the normal human thymus, and there are virtually no data about their distribution and significance in thymoma. The aim of this study was to analyse the spatial distribution of MCs and microvessels in the normal foetal and adult thymus and thymoma. Twenty biopsy specimens of human thymus, including foetal and adult normal thymus and thymoma were analysed. Double staining with CD34 and mast cell tryptase was used to count both mast cells and microvessels in the same fields. Computer-assisted image analysis was performed to characterize the spatial distribution of MCs and blood vessels in selected specimens. Results demonstrated that MCs were localized exclusively to the medulla. Their number was significantly higher in thymoma specimens as compared with adult and foetal normal specimens respectively. In contrast the microvessel area was unchanged. The analysis of the spatial distribution and relationship between MCs and microvessels revealed that only in the thymoma specimens was there a significant spatial association between MCs and microvessels. Overall, these data suggest that MCs do not contribute significantly to the development of the vascular network in foetal and adult thymus, whereas in thymoma they show a close relationship to blood vessels. This could be an expression of their involvement not only in endothelial cells but also in tumour cell proliferation.

No histologic evidence of foetal cardiotoxicity following exposure to maternal hydroxychloroquine.

PubMed

Friedman, Deborah; Lovig, Leif; Halushka, Marc; Clancy, Robert M; Izmirly, Peter M; Buyon, Jill P

2017-01-01

It is currently recommended that hydroxychloroquine (HCQ) be maintained during pregnancy in patients with systemic lupus erythematosus. Recent data suggest that this Toll-like receptor inhibitor may also reduce the recurrence rate of anti-SSA/Ro associated congenital heart block (CHB). This case report describes a unique situation in which a CHB-afflicted, HCQ-exposed pregnancy was electively terminated. The heart did not reveal any characteristic features of cardiotoxicity, providing further evidence supporting the safety of foetal exposure to HCQ.

Protection against endotoxin-induced foetal resorption in mice by desferrioxamine and ebselen.

PubMed Central

Gower, J. D.; Baldock, R. J.; O'Sullivan, A. M.; Doré, C. J.; Coid, C. R.; Green, C. J.

1990-01-01

Endotoxin was administered to mice on their 13th day of pregnancy at doses which caused the resorption of approximately 50% of the implanted foetuses. The iron chelator desferrioxamine was found to significantly inhibit the percentage of resorptions induced by endotoxin in a dose-dependent manner. The highest dose of desferrioxamine (5 mg) given intravenously 30 min prior to, immediately after, and 4 and 24 h after endotoxin inoculation, reduced the percentage of resorptions from 56.9 to 17.9%. Administration of the novel selenium-containing compound ebselen, which is both an antioxidant and an inhibitor of leukotriene synthesis, was also found to significantly protect against endotoxin-induced foetal resorptions, reducing the percentage of resorbed foetuses from 52.9 to 26.0% when given at a dose of 50 mg/kg (s.c.) at the time of endotoxin inoculation and 24 and 48 h following. Both these compounds also significantly reduced the increase in spleen weights observed when the mice were given endotoxin. These results provide evidence that the iron-catalysed production of hydroxyl radicals from other oxygen-derived species and the formation of leukotrienes play an important role in the mechanism by which endotoxin causes foetal resorptions in the mouse. PMID:2205283

Methylation-reprogrammed Wnt/β-catenin signalling mediated prenatal hypoxia-induced brain injury in foetal and offspring rats.

PubMed

Zhang, Yingying; Zhang, Mengshu; Li, Lingjun; Wei, Bin; He, Axin; Lu, Likui; Li, Xiang; Zhang, Lubo; Xu, Zhice; Sun, Miao

2018-05-28

Prenatal hypoxia (PH) is a common pregnancy complication, harmful to brain development. This study investigated whether and how PH affected Wnt pathway in the brain. Pregnant rats were exposed to hypoxia (10.5% O 2 ) or normoxia (21% O 2 ; Control). Foetal brain weight and body weight were decreased in the PH group, the ratio of brain weight to body weight was increased significantly. Prenatal hypoxia increased mRNA expression of Wnt3a, Wnt7a, Wnt7b and Fzd4, but not Lrp6. Activated β-catenin protein and Fosl1 expression were also significantly up-regulated. Increased Hif1a expression was found in the PH group associated with the higher Wnt signalling. Among 5 members of the Sfrp family, Sfrp4 was down-regulated. In the methylation-regulating genes, higher mRNA expressions of Dnmt1 and Dnmt3b were found in the PH group. Sodium bisulphite and sequencing revealed hyper-methylation in the promoter region of Sfrp4 gene in the foetal brain, accounting for its decreased expression and contributing to the activation of the Wnt-Catenin signalling. The study of PC12 cells treated with 5-aza further approved that decreased methylation could result in the higher Sfrp4 expression. In the offspring hippocampus, protein levels of Hif1a and mRNA expression of Sfrp4 were unchanged, whereas Wnt signal pathway was inhibited. The data demonstrated that PH activated the Wnt pathway in the foetal brain, related to the hyper-methylation of Sfrp4 as well as Hif1a signalling. Activated Wnt signalling might play acute protective roles to the foetal brain in response to hypoxia, also would result in disadvantageous influence on the offspring in long-term. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

IL-7-Induced Proliferation of Human Naive CD4 T-Cells Relies on Continued Thymic Activity.

PubMed

Silva, Susana L; Albuquerque, Adriana S; Matoso, Paula; Charmeteau-de-Muylder, Bénédicte; Cheynier, Rémi; Ligeiro, Dário; Abecasis, Miguel; Anjos, Rui; Barata, João T; Victorino, Rui M M; Sousa, Ana E

2017-01-01

Naive CD4 T-cell maintenance is critical for immune competence. We investigated here the fine-tuning of homeostatic mechanisms of the naive compartment to counteract the loss of de novo CD4 T-cell generation. Adults thymectomized in early childhood during corrective cardiac surgery were grouped based on presence or absence of thymopoiesis and compared with age-matched controls. We found that the preservation of the CD31 - subset was independent of the thymus and that its size is tightly controlled by peripheral mechanisms, including prolonged cell survival as attested by Bcl-2 levels. Conversely, a significant contraction of the CD31 + naive subset was observed in the absence of thymic activity. This was associated with impaired responses of purified naive CD4 T-cells to IL-7, namely, in vitro proliferation and upregulation of CD31 expression, which likely potentiated the decline in recent thymic emigrants. Additionally, we found no apparent constraint in the differentiation of naive cells into the memory compartment in individuals completely lacking thymic activity despite upregulation of DUSP6 , a phosphatase associated with increased TCR threshold. Of note, thymectomized individuals featuring some degree of thymopoiesis were able to preserve the size and diversity of the naive CD4 compartment, further arguing against complete thymectomy in infancy. Overall, our data suggest that robust peripheral mechanisms ensure the homeostasis of CD31 - naive CD4 pool and point to the requirement of continuous thymic activity to the maintenance of IL-7-driven homeostatic proliferation of CD31 + naive CD4 T-cells, which is essential to secure T-cell diversity throughout life.

Are foetal ultrasonographic and maternal blood progesterone measurements near parturition reliable predictors of the time of birth in the domestic cat?

PubMed

Keiser, R; Reichler, I M; Balogh, O

2017-06-01

In cats, accuracy of parturition day prediction by ultrasonographic measurement of foetal structures is decreasing towards the end of gestation. Foetal measurements during the last days of pregnancy are scarce. We determined foetal biparietal, abdominal and eye diameter (BPD, AD and ED, respectively) by ultrasonography as well as maternal blood progesterone (P4) within five days of delivery to predict parturition date and calculate accuracy of prediction. Foetal BPD at birth was compared with newborn kitten head diameter (HD). Kitten HD, crown-rump length (CRL) and body weight were compared by breed and gender. Ultrasonography measurements were carried out on the day of parturition in 14 queens, and on days 62-63 after the first mating and repeated 24-72 hr later in ten other cats. Accuracy of parturition day prediction using BPD and AD was determined based on the equations of Beccaglia et al. (2008) Veterinary Research Communications, 32(Suppl 1), S99 and Garcia Mitacek et al. (2015) Theriogenology, 84, 1131. Progesterone was measured at the time of presentation and repeated 24-72 hr later if parturition did not occur. Data were analysed with linear regression, t test, Mann-Whitney U test, one-way anova and Kruskal-Wallis test. There was a moderate relationship between BPD, days before birth (DBB) and litter size. AD and DBB had a low agreement, and ED was not associated with DBB. BPD at birth was significantly related to HD. The accuracy of parturition day prediction using BPD and AD was 27-53% and 17-35%, respectively. Kitten HD was associated with body weight, and both were inversely related to litter size. Newborn biometric measurements differed by breed but not by gender. Progesterone decreased towards parturition and reached 3.18 ± 1.68 ng/ml on the day of delivery. In conclusion, close to birth, the combination of foetal ultrasonography and maternal blood P4 rather than each as a sole predictor of parturition is recommended. © 2017 Blackwell Verlag

Clinical associations of maternal thyroid function with foetal brain development: Epidemiological interpretation and overview of available evidence.

PubMed

Korevaar, Tim I M; Tiemeier, Henning; Peeters, Robin P

2018-04-24

Thyroid hormone is an important regulator of early brain development, particularly during early stages of gestation during which foetal thyroid hormone availability depends on the maternal transfer of thyroid hormones. There is a wide range of experimental studies showing that low maternal thyroid hormone availability is associated with suboptimal brain development parameters. While few clinical studies have shown that overt maternal hypothyroidism is associated with lower child IQ, the question whether more subclinical changes in maternal thyroid function could also lead to suboptimal foetal brain development. In this review, we put the latter studies in perspective and discuss their interpretation from an epidemiological and clinical perspective. Furthermore, we extend this discussion to also include future perspective and identify important knowledge gaps in the field. © 2018 John Wiley & Sons Ltd.

Risk of erectile dysfunction in transfusion-naive thalassemia men: a nationwide population-based retrospective cohort study.

PubMed

Chen, Yu-Guang; Lin, Te-Yu; Lin, Cheng-Li; Dai, Ming-Shen; Ho, Ching-Liang; Kao, Chia-Hung

2015-04-01

Based on the mechanism of pathophysiology, thalassemia major or transfusion-dependent thalassemia patients may have an increased risk of developing organic erectile dysfunction resulting from hypogonadism. However, there have been few studies investigating the association between erectile dysfunction and transfusion-naive thalassemia populations. We constructed a population-based cohort study to elucidate the association between transfusion-naive thalassemia populations and organic erectile dysfunction. This nationwide population-based cohort study involved analyzing data from 1998 to 2010 obtained from the Taiwanese National Health Insurance Research Database, with a follow-up period extending to the end of 2011. We identified men with transfusion-naive thalassemia and selected a comparison cohort that was frequency-matched with these according to age, and year of diagnosis thalassemia at a ratio of 1 thalassemia man to 4 control men. We analyzed the risks for transfusion-naive thalassemia men and organic erectile dysfunction by using Cox proportional hazards regression models. In this study, 588 transfusion-naive thalassemia men and 2337 controls were included. Total 12 patients were identified within the thalassaemia group and 10 within the control group. The overall risks for developing organic erectile dysfunction were 4.56-fold in patients with transfusion-naive thalassemia men compared with the comparison cohort after we adjusted for age and comorbidities. Our long-term cohort study results showed that in transfusion-naive thalassemia men, there was a higher risk for the development of organic erectile dysfunction, particularly in those patients with comorbidities.

Acute Effects of Sugars and Artificial Sweeteners on Small Intestinal Sugar Transport: A Study Using CaCo-2 Cells As an In Vitro Model of the Human Enterocyte

PubMed Central

2016-01-01

Background The gastrointestinal tract is responsible for the assimilation of nutrients and plays a key role in the regulation of nutrient metabolism and energy balance. The molecular mechanisms by which intestinal sugar transport are regulated are controversial. Based on rodent studies, two models currently exist that involve activation of the sweet-taste receptor, T1R2/3: an indirect model, whereby luminal carbohydrates activate T1R2/3 expressed on enteroendocrine cells, resulting in the release of gut peptides which in turn regulate enterocyte sugar transport capacity; and a direct model, whereby T1R2/3 expressed on the enterocyte regulates enterocyte function. Aims To study the direct model of intestinal sugar transport using CaCo-2 cells, a well-established in vitro model of the human enterocyte. Methods Uptake of 10mM 14C D-Glucose and D-Fructose into confluent CaCo-2/TC7 cells was assessed following 3hr preincubation with sugars and artificial sweeteners in the presence and absence of the sweet taste receptor inhibitor, lactisole. Expression of the intestinal sugar transporters and sweet-taste receptors were also determined by RT-PCR. Results In response to short term changes in extracellular glucose and glucose/fructose concentrations (2.5mM to 75mM) carrier-mediated sugar uptake mediated by SGLT1 and/or the facilitative hexose transporters (GLUT1,2,3 and 5) was increased. Lactisole and artificial sweeteners had no effect on sugar transport regulated by glucose alone; however, lactisole increased glucose transport in cells exposed to glucose/fructose. RT-PCR revealed Tas1r3 and SGLT3 gene expression in CaCo-2/TC7 cells, but not Tas1r2. Conclusions In the short term, enterocyte sugar transport activities respond directly to extracellular glucose levels, but not fructose or artificial sweeteners. We found no evidence of a functional heterodimeric sweet taste receptor, T1R2/3 in CaCo-2 cells. However, when glucose/fructose is administered together there is an

Acute Effects of Sugars and Artificial Sweeteners on Small Intestinal Sugar Transport: A Study Using CaCo-2 Cells As an In Vitro Model of the Human Enterocyte.

PubMed

O'Brien, Patrick; Corpe, Christopher Peter

2016-01-01

The gastrointestinal tract is responsible for the assimilation of nutrients and plays a key role in the regulation of nutrient metabolism and energy balance. The molecular mechanisms by which intestinal sugar transport are regulated are controversial. Based on rodent studies, two models currently exist that involve activation of the sweet-taste receptor, T1R2/3: an indirect model, whereby luminal carbohydrates activate T1R2/3 expressed on enteroendocrine cells, resulting in the release of gut peptides which in turn regulate enterocyte sugar transport capacity; and a direct model, whereby T1R2/3 expressed on the enterocyte regulates enterocyte function. To study the direct model of intestinal sugar transport using CaCo-2 cells, a well-established in vitro model of the human enterocyte. Uptake of 10mM 14C D-Glucose and D-Fructose into confluent CaCo-2/TC7 cells was assessed following 3hr preincubation with sugars and artificial sweeteners in the presence and absence of the sweet taste receptor inhibitor, lactisole. Expression of the intestinal sugar transporters and sweet-taste receptors were also determined by RT-PCR. In response to short term changes in extracellular glucose and glucose/fructose concentrations (2.5mM to 75mM) carrier-mediated sugar uptake mediated by SGLT1 and/or the facilitative hexose transporters (GLUT1,2,3 and 5) was increased. Lactisole and artificial sweeteners had no effect on sugar transport regulated by glucose alone; however, lactisole increased glucose transport in cells exposed to glucose/fructose. RT-PCR revealed Tas1r3 and SGLT3 gene expression in CaCo-2/TC7 cells, but not Tas1r2. In the short term, enterocyte sugar transport activities respond directly to extracellular glucose levels, but not fructose or artificial sweeteners. We found no evidence of a functional heterodimeric sweet taste receptor, T1R2/3 in CaCo-2 cells. However, when glucose/fructose is administered together there is an inhibitory effect on glucose transport

Evaluation of the impact of chitosan/DNA nanoparticles on the differentiation of human naive CD4+ T cells

NASA Astrophysics Data System (ADS)

Liu, Lanxia; Bai, Yuanyuan; Zhu, Dunwan; Song, Liping; Wang, Hai; Dong, Xia; Zhang, Hailing; Leng, Xigang

2011-06-01

Chitosan (CS) is one of the most widely studied polymers in non-viral gene delivery since it is a cationic polysaccharide that forms nanoparticles with DNA and hence protects the DNA against digestion by DNase. However, the impact of CS/DNA nanoparticle on the immune system still remains poorly understood. Previous investigations did not found CS/DNA nanoparticles had any significant impact on the function of human and murine macrophages. To date, little is known about the interaction between CS/DNA nanoparticles and naive CD4+ T cells. This study was designed to investigate whether CS/DNA nanoparticles affect the initial differentiation direction of human naive CD4+ T cells. The indirect impact of CS/DNA nanoparticles on naive CD4+ T cell differentiation was investigated by incubating the nanoparticles with human macrophage THP-1 cells in one chamber of a transwell co-incubation system, with the enriched human naive CD4+ T cells being placed in the other chamber of the transwell. The nanoparticles were also co-incubated with the naive CD4+ T cells to explore their direct impact on naive CD4+ T cell differentiation by measuring the release of IL-4 and IFN-γ from the cells. It was demonstrated that CS/DNA nanoparticles induced slightly elevated production of IL-12 by THP-1 cells, possibly owing to the presence of CpG motifs in the plasmid. However, this macrophage stimulating activity was much less significant as compared with lipopolysaccharide and did not impact on the differentiation of the naive CD4+ T cells. It was also demonstrated that, when directly exposed to the naive CD4+ T cells, the nanoparticles induced neither the activation of the naive CD4+ T cells in the absence of recombinant cytokines (recombinant human IL-4 or IFN-γ) that induce naive CD4+ T cell polarization, nor any changes in the differentiation direction of naive CD4+ T cells in the presence of the corresponding cytokines.

Telomere length dynamics differ in foetal and early post-natal human leukocytes in a longitudinal study.

PubMed

Holmes, Denise K; Bellantuono, Ilaria; Walkinshaw, Steve A; Alfirevic, Zarko; Johnston, Tracey A; Subhedar, Nimish V; Chittick, Rachel; Swindell, Richard; Wynn, Robert F

2009-06-01

Haemopoietic stem cells (HSC) undergo a process of self renewal to constantly maintain blood cell turnover. However, it has become apparent that adult HSC lose their self-renewal ability with age. Telomere shortening in peripheral blood leukocytes has been seen to occur with age and it has been associated with loss of HSC proliferative capacity and cellular ageing. In contrast foetal HSC are known to have greater proliferative capacity than post-natal stem cells. However it is unknown whether they undergo a similar process of telomere shortening. In this study we show a more accentuated rate of telomere loss in leukocytes from pre term infants compared to human foetuses of comparable age followed longitudinally for 8-12 weeks in a longitudinal study. Our results point to a difference in HSC behaviour between foetal and early postnatal life which is independent of age but may be influenced by events at birth itself.

Improving Naive Bayes with Online Feature Selection for Quick Adaptation to Evolving Feature Usefulness

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pon, R K; Cardenas, A F; Buttler, D J

The definition of what makes an article interesting varies from user to user and continually evolves even for a single user. As a result, for news recommendation systems, useless document features can not be determined a priori and all features are usually considered for interestingness classification. Consequently, the presence of currently useless features degrades classification performance [1], particularly over the initial set of news articles being classified. The initial set of document is critical for a user when considering which particular news recommendation system to adopt. To address these problems, we introduce an improved version of the naive Bayes classifiermore » with online feature selection. We use correlation to determine the utility of each feature and take advantage of the conditional independence assumption used by naive Bayes for online feature selection and classification. The augmented naive Bayes classifier performs 28% better than the traditional naive Bayes classifier in recommending news articles from the Yahoo! RSS feeds.« less

Cinnamon extract attenuates TNF-alpha-induced intestinal lipoprotein ApoB48 overproduction by regulating inflammatory, insulin, and lipoprotein pathways in enterocytes

USDA-ARS?s Scientific Manuscript database

We evaluated whether a water extract of cinnamon (CE = Cinnulin PF®) attenuates the dyslipidemia induced by TNF-alpha in Triton WR-1339-treated hamsters, and whether CE inhibited the over-secretion of apoB48-induced by TNF-alpha in enterocytes in a 35S-labelling study. In vivo, oral treatment with C...

Transcriptional Modulation of Genes Encoding Structural Characteristics of Differentiating Enterocytes During Development of a Polarized Epithelium In Vitro

PubMed Central

Halbleib, Jennifer M.; Sääf, Annika M.

2007-01-01

Although there is considerable evidence implicating posttranslational mechanisms in the development of epithelial cell polarity, little is known about the patterns of gene expression and transcriptional regulation during this process. We characterized the temporal program of gene expression during cell–cell adhesion–initiated polarization of human Caco-2 cells in tissue culture, which develop structural and functional polarity similar to that of enterocytes in vivo. A distinctive switch in gene expression patterns occurred upon formation of cell–cell contacts between neighboring cells. Expression of genes involved in cell proliferation was down-regulated concomitant with induction of genes necessary for functional specialization of polarized epithelial cells. Transcriptional up-regulation of these latter genes correlated with formation of important structural and functional features in enterocyte differentiation and establishment of structural and functional cell polarity; components of the apical microvilli were induced as the brush border formed during polarization; as barrier function was established, expression of tight junction transmembrane proteins peaked; transcripts encoding components of the apical, but not the basal-lateral trafficking machinery were increased during polarization. Coordinated expression of genes encoding components of functional cell structures were often observed indicating temporal control of expression and assembly of multiprotein complexes. PMID:17699590

The interaction of F4 fimbriae with porcine enterocytes as analysed by surface plasmon resonance.

PubMed

Verdonck, Frank; Cox, Eric; Vancaeneghem, Sabine; Goddeeris, Bruno M

2004-07-01

Fimbriae often play a prominent role in anchoring bacterial cells to host tissue and mediate the first step in pathogenesis. As a consequence, there is a continuous development of new strategies to block the binding of fimbriae to their specific receptor on host cells. The present study demonstrates the specific interaction of F4 (K88) fimbriae and porcine enterocytes using a real-time biomolecular interaction analysis system (BIAcore 3000), based on the principles of surface plasmon resonance (SPR). This method offers new opportunities to screen therapeutics for prevention of adhesion and subsequent disease without receptor purification.

Foetal blood flow measured using phase contrast cardiovascular magnetic resonance--preliminary data comparing 1.5 T with 3.0 T.

PubMed

Tsai-Goodman, Beverly; Zhu, Meng Yuan; Al-Rujaib, Mashael; Seed, Mike; Macgowan, Christopher K

2015-04-18

Phase contrast cardiovascular magnetic resonance (PC CMR) has emerged as a clinical tool for blood flow quantification but its use in the foetus has been hampered by the need for gating with the foetal heart beat. The previously described metric optimized gating (MOG) technique has been successfully used to measure foetal blood flow in late gestation foetuses on a 1.5 T CMR magnet. However, there is increasing interest in performing foetal cardiac imaging using 3.0 T CMR. We describe our pilot investigation of foetal blood flow measured using 3.0 T CMR. Foetal blood flows were quantified in 5 subjects at late gestational age (35-38 weeks). Three were normal pregnancies and two were pregnancies with ventricular size discrepancy. Data were obtained at 1.5 T and 3.0 T using a previously described PC CMR protocol. After reconstruction using MOG, blood flow was quantified independently by two observers. Intra- and inter-observer reproducibility of flow measurements at the two field strengths was assessed by Pearson correlation coefficient (R(2)), linear regression and Bland Altman analysis. PC CMR flow measurements were obtained in 36 of 40 target vessels. Strong intra-observer agreement was obtained between measurements at each field strength (R(2) = 0.78, slope = 0.83 ± 0.11), with a mean bias of -1 ml/min/kg and 95% confidence limits of ±71 ml/min/kg. Inter-observer agreement was similarly high for measurements at both 1.5 T (R(2) = 0.86, slope = 0.95 ± 0.13, bias = 6 ± 52 ml/min/kg) and 3.0 T (R(2) = 0.88, slope = 0.94 ± 0.13, bias = 4 ± 47 ml/min/kg). Across all PC CMR measurements, SNR per pixel was expectedly higher at 3.0 T relative to 1.5 T (165 ± 50%). The relative differences in flow measurements between observers were low (range: 4-16%) except for pulmonary blood flow which showed much higher variability at 1.5 T (34%) versus that at 3.0 T (11%). This was attributed to the poorly

The increasing incidence of foetal echogenic congenital lung malformations: an observational study.

PubMed

Stocker, Linden J; Wellesley, Diana G; Stanton, Michael P; Parasuraman, Rajeswari; Howe, David T

2015-02-01

The aim of this study was to investigate the incidence of congenital lung malformations over the past 19 years. Congenital lung malformations (CLM) are a heterogeneous group of lung abnormalities. The antenatal diagnosis is important for foetal and neonatal management but there have been no studies examining whether the reported incidence of this abnormality is constant. A retrospective cross-sectional study of cases identified from the Wessex Antenatally Detected Anomalies (WANDA) register 1994-2012. One hundred and thirty-three cases of CLM in 524 372 live and stillbirths were identified. All but seven were identified on antenatal ultrasound. During the early registry (1994-1998) the average incidence of CLM was 1.27 per 10,000 births. By the last 4 years (2008-2012) this had risen to 4.15 per 10,000 births, with a progressive increase during the intervening years. There was over a three-fold increase in the antenatally detected CLM in the Wessex region 1994-2012. Comparison with the antenatal detection of diaphragmatic hernia suggests that this is a true rise in incidence rather than an artefactual increase due to increased antenatal recognition secondary to improved ultrasound resolution and operator experience. These results have clinical and cost implications for practitioners of foetal medicine, neonatology and paediatric surgery services. © 2014 John Wiley & Sons, Ltd.

Placental weight and foetal growth rate as predictors of ischaemic heart disease in a Swedish cohort.

PubMed

Heshmati, A; Koupil, I

2014-06-01

Studies on placental size and cardiovascular disease have shown inconsistent results. We followed 10,503 men and women born in Uppsala, Sweden, 1915-1929 from 1964 to 2008 to assess whether birth characteristics, including placental weight and placenta/birth weight ratio, were predictive of future ischaemic heart disease (IHD). Adjustments were made for birth cohort, age, sex, mother's parity, birth weight, gestational age and social class at birth. Placental weight and birth weight were negatively associated with IHD. The effect of placental weight on IHD was stronger in individuals from medium social class at birth and in those with low education. Men and women from non-manual social class at birth had the lowest risk for IHD as adults. We conclude that low foetal growth rate rather than placental weight was more predictive of IHD in the Swedish cohort. However, the strong effect of social class at birth on risk for IHD did not appear to be mediated by foetal growth rate.

The Hayflick Limit May Determine the Effective Clonal Diversity of Naive T Cells.

PubMed

Ndifon, Wilfred; Dushoff, Jonathan

2016-06-15

Having a large number of sufficiently abundant T cell clones is important for adequate protection against diseases. However, as shown in this paper and elsewhere, between young adulthood and >70 y of age the effective clonal diversity of naive CD4/CD8 T cells found in human blood declines by a factor of >10. (Effective clonal diversity accounts for both the number and the abundance of T cell clones.) The causes of this observation are incompletely understood. A previous study proposed that it might result from the emergence of certain rare, replication-enhancing mutations in T cells. In this paper, we propose an even simpler explanation: that it results from the loss of T cells that have attained replicative senescence (i.e., the Hayflick limit). Stochastic numerical simulations of naive T cell population dynamics, based on experimental parameters, show that the rate of homeostatic T cell proliferation increases after the age of ∼60 y because naive T cells collectively approach replicative senescence. This leads to a sharp decline of effective clonal diversity after ∼70 y, in agreement with empirical data. A mathematical analysis predicts that, without an increase in the naive T cell proliferation rate, this decline will occur >50 yr later than empirically observed. These results are consistent with a model in which exhaustion of the proliferative capacity of naive T cells causes a sharp decline of their effective clonal diversity and imply that therapeutic potentiation of thymopoiesis might either prevent or reverse this outcome. Copyright © 2016 by The American Association of Immunologists, Inc.

Incidence of Obstetric and Foetal Complications during Labor and Delivery at a Community Health Centre, Midwives Obstetric Unit of Durban, South Africa

PubMed Central

Hoque, Monjurul

2011-01-01

The objectives of this retrospective cohort study were to estimate the incidence of obstetric complications during labor and delivery and their demographic predictors. A total of 2706 pregnant women were consecutively admitted to a midwife obstetric unit with labor pain between January and December 2007 constituted the sample. Among them 16% were diagnosed with obstetrical and foetal complications. The most frequently observed foetal and obstetric complications were foetal distress (35.5/1000) and poor progress of labor (28.3/1000), respectively. Primigravid and grandmultiparity women were 12 (OR = 11.89) and 5 (OR = 4.575) times, respectively, more likely to have complications during labor and delivery. Women without antenatal care had doubled (OR = 1.815, 95% CI, 1.310; 2.515) the chance of having complications. Mothers age <20 years was protective (OR = 0.579, 95% CI, 0.348; 0.963) of complications during delivery compared to women who were ≥35 years. National and local policies and intervention programmes must address the need of the risk groups of pregnant women during labor and delivery. PMID:21822497

Combination of three-dimensional ultrasound measurement of foetal adrenal gland enlargement and placental alpha microglobulin-1 for the prediction of the timing of delivery within seven days in women with threatened preterm labour and preterm labour.

PubMed

Santipap, Monchai; Phupong, Vorapong

2018-03-23

The aim of this study was to predict the timing of delivery within seven days in singleton pregnant women with threatened preterm labour and preterm labour by using a three-dimensional (3D) ultrasound measurement of foetal adrenal gland volume enlargement, a foetal zone enlargement and cervicovaginal placental alpha microglobulin-1 (PAMG-1) test. This prospective cohort study included singleton pregnant women at 22-36 +6  weeks of gestation who presented with threatened preterm labour and with preterm labour. Transabdominal 3D ultrasound measurement of the whole foetal adrenal gland and of the foetal adrenal zone were performed. Qualitative cervicovaginal PAMG-1 detection was performed at the same time. One hundred and fifty-four pregnant women were included into the study. Eighty-four pregnant women had threatened preterm labour and seventy pregnant women had preterm labour. Twenty-nine pregnant women (18%) delivered within seven days. Use of foetal adrenal gland volume enlargement, foetal zone enlargement and the PAMG-1 test in combination increased sensitivity; if one parameter was positive, the sensitivity, specificity, positive predictive value and negative predictive value were 82.8%, 27.2%, 20.9% and 87.2%, respectively, in the prediction of the timing of delivery within seven days. The combination of foetal adrenal gland enlargement and PAMG-1 increased sensitivity for the prediction of the timing of delivery within seven days in pregnant women presenting with threatened preterm labour and preterm labour. Impact Statement What is already known on this subject? An increased foetal adrenal gland volume is significantly correlated with the risk of preterm birth. What do the results of this study add? The combination of a foetal adrenal gland enlargement and a placental alpha microglobulin-1 increased sensitivity for the prediction of the timing of delivery within seven days in pregnant women presenting with threatened preterm labour and preterm labour

Transforming growth factor-alpha stimulates enterocyte proliferation and accelerates intestinal recovery following methotrexate-induced intestinal mucositis in a rat and a cell culture model.

PubMed

Sukhotnik, Igor; Shteinberg, Dan; Ben Lulu, Shani; Bashenko, Yulia; Mogilner, Jorge G; Ure, Benno M; Shaoul, Ron; Shamian, Benhoor; Coran, Arnold G

2008-12-01

Recent evidence suggests that transforming growth factor-alpha (TGF-alpha) enhances enterocyte proliferation and exerts a gut trophic effect. The purpose of the present study was to evaluate the effect of TGF-alpha on enterocyte proliferation and intestinal recovery following methotrexate (MTX)-induced intestinal mucositis in rats and in Caco-2 cells. Nonpretreated Caco-2 cells and those pretreated with MTX were incubated with increasing concentrations of TGF-alpha. Cell proliferation was determined by FACS cytometry. Adult rats were divided into three groups: control rats treated with vehicle, MTX rats treated with one dose (20 microg/kg) of MTX given intraperitoneally, and MTX-TGF-alpha rats treated with one dose of MTX followed by two doses of TGF-alpha (75 microg/kg a day). Three days after MTX injection, rats were sacrificed. Intestinal mucosal damage (Park's score), mucosal structural changes, and enterocyte proliferation were measured at sacrifice. Western blotting was used to determine the level of extracellular signal-related kinase (ERK) protein, a marker of cell proliferation. A nonparametric Kruskal-Wallis ANOVA test was used for statistical analysis with P value less than 0.05 considered statistically significant. The in vitro experiment demonstrated that treatment with TGF-alpha of Caco-2 cells resulted in a significant stimulation of cell proliferation in a dose-dependent manner. The in vivo experiment showed that treatment with TGF-alpha resulted in a significant increase in bowel and mucosal weight, DNA and protein content in jejunum and ileum, villus height in jejunum and ileum, crypt depth in ileum, and increased cell proliferation in jejunum and ileum compared to the MTX group. MTX-TGF-alpha rats also had a significantly lower intestinal injury score in ileum when compared to MTX animals. The increase in levels of cell proliferation in MTX-TGF-alpha rats corresponded with the increase in ERK protein levels in intestinal mucosa. Treatment with

Naive B cells generate regulatory T cells in the presence of a mature immunologic synapse.

PubMed

Reichardt, Peter; Dornbach, Bastian; Rong, Song; Beissert, Stefan; Gueler, Faikah; Loser, Karin; Gunzer, Matthias

2007-09-01

Naive B cells are ineffective antigen-presenting cells and are considered unable to activate naive T cells. However, antigen-specific contact of these cells leads to stable cell pairs that remain associated over hours in vivo. The physiologic role of such pairs has not been evaluated. We show here that antigen-specific conjugates between naive B cells and naive T cells display a mature immunologic synapse in the contact zone that is absent in T-cell-dendritic-cell (DC) pairs. B cells induce substantial proliferation but, contrary to DCs, no loss of L-selectin in T cells. Surprisingly, while DC-triggered T cells develop into normal effector cells, B-cell stimulation over 72 hours induces regulatory T cells inhibiting priming of fresh T cells in a contact-dependent manner in vitro. In vivo, the regulatory T cells home to lymph nodes where they potently suppress immune responses such as in cutaneous hypersensitivity and ectopic allogeneic heart transplant rejection. Our finding might help to explain old observations on tolerance induction by B cells, identify the mature immunologic synapse as a central functional module of this process, and suggest the use of naive B-cell-primed regulatory T cells, "bTregs," as a useful approach for therapeutic intervention in adverse adaptive immune responses.

Naive T-cell receptor transgenic T cells help memory B cells produce antibody

PubMed Central

Duffy, Darragh; Yang, Chun-Ping; Heath, Andrew; Garside, Paul; Bell, Eric B

2006-01-01

Injection of the same antigen following primary immunization induces a classic secondary response characterized by a large quantity of high-affinity antibody of an immunoglobulin G class produced more rapidly than in the initial response – the products of memory B cells are qualitatively distinct from that of the original naive B lymphocytes. Very little is known of the help provided by the CD4 T cells that stimulate memory B cells. Using antigen-specific T-cell receptor transgenic CD4 T cells (DO11.10) as a source of help, we found that naive transgenic T cells stimulated memory B cells almost as well (in terms of quantity and speed) as transgenic T cells that had been recently primed. There was a direct correlation between serum antibody levels and the number of naive transgenic T cells transferred. Using T cells from transgenic interleukin-2-deficient mice we showed that interleukin-2 was not required for a secondary response, although it was necessary for a primary response. The results suggested that the signals delivered by CD4 T cells and required by memory B cells for their activation were common to both antigen-primed and naive CD4 T cells. PMID:17067314

Vitamin D inhibits lipopolysaccharide-induced inflammatory response potentially through the Toll-like receptor 4 signalling pathway in the intestine and enterocytes of juvenile Jian carp (Cyprinus carpio var. Jian).

PubMed

Jiang, Jun; Shi, Dan; Zhou, Xiao-Qiu; Yin, Long; Feng, Lin; Jiang, Wei-Dan; Liu, Yang; Tang, Ling; Wu, Pei; Zhao, Ye

2015-11-28

The present study was conducted to investigate the anti-inflammatory effect of vitamin D both in juvenile Jian carp (Cyprinus carpio var. Jian) in vivo and in enterocytes in vitro. In primary enterocytes, exposure to 10 mg lipopolysaccharide (LPS)/l increased lactate dehydrogenase activity in the culture medium (P<0·05) and resulted in a significant loss of cell viability (P<0·05). LPS exposure increased (P<0·05) the mRNA expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-8), which was decreased by pre-treatment with 1,25-dihydroxyvitamin D (1,25D3) in a dose-dependent manner (P<0·05). Further results showed that pre-treatment with 1,25D3 down-regulated Toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (Myd88) and NF-κB p65 mRNA expression (P<0·05), suggesting potential mechanisms against LPS-induced inflammatory response. In vivo, intraperitoneal injection of LPS significantly increased TNF-α, IL-1β, IL-6 and IL-8 mRNA expression in the intestine of carp (P<0·05). Pre-treatment of fish with vitamin D3 protected the fish intestine from the LPS-induced increase of TNF-α, IL-1β, IL-6 and IL-8 mainly by downregulating TLR4, Myd88 and NF-κB p65 mRNA expression (P<0·05). These observations suggest that vitamin D could inhibit LPS-induced inflammatory response in juvenile Jian carp in vivo and in enterocytes in vitro. The anti-inflammatory effect of vitamin D is mediated at least in part by TLR4-Myd88 signalling pathways in the intestine and enterocytes of juvenile Jian carp.

Patients with mild enteropathy have apoptotic injury of enterocytes similar to that in advanced enteropathy in celiac disease.

PubMed

Das, Prasenjit; Gahlot, Gaurav P S; Mehta, Ritu; Makharia, Archita; Verma, Anil K; Sreenivas, Vishnubhatla; Panda, Subrat K; Ahuja, Vineet; Gupta, Siddhartha Datta; Makharia, Govind K

2016-11-01

Severity of villous atrophy in celiac disease (CeD) is the cumulative effect of enterocyte loss and cell regeneration. Gluten-free diet has been shown to benefit even in patients having a positive anti-tissue transglutaminase (tTG) antibody titre and mild enteropathy. We explored the balance between mucosal apoptotic enterocyte loss and cell regeneration in mild and advanced enteropathies. Duodenal biopsies from patients with mild enteropathy (Marsh grade 0 and 1) (n=26), advanced enteropathy (Marsh grade ≥2) (n=41) and control biopsies (n=12) were subjected to immunohistochemical staining for end-apoptotic markers (M30, H2AX); markers of cell death (perforin, annexin V); and cell proliferation (Ki67). Composite H-scores based on the intensity and distribution of markers were compared. End-apoptotic markers and marker of cell death (perforin) were significantly up-regulated in both mild and advanced enteropathies, in comparison to controls; without any difference between mild and advanced enteropathies. Ki67 labelling index was significantly higher in crypts of mild enteropathy, in comparison to controls, suggesting maintained regenerative activity in the former. Even in patients with mild enteropathy, the rate of apoptosis is similar to those with advanced enteropathy. These findings suggest the necessity of reviewing the existing practice of not treating patients with mild enteropathy. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

IL-21 sustains CD28 expression on IL-15-activated human naive CD8+ T cells.

PubMed

Alves, Nuno L; Arosa, Fernando A; van Lier, René A W

2005-07-15

Human naive CD8+ T cells are able to respond in an Ag-independent manner to IL-7 and IL-15. Whereas IL-7 largely maintains CD8+ T cells in a naive phenotype, IL-15 drives these cells to an effector phenotype characterized, among other features, by down-regulation of the costimulatory molecule CD28. We evaluated the influence of the CD4+ Th cell-derived common gamma-chain cytokine IL-21 on cytokine-induced naive CD8+ T cell activation. Stimulation with IL-21 did not induce division and only slightly increased IL-15-induced proliferation of naive CD8+ T cells. Strikingly, however, IL-15-induced down-modulation of CD28 was completely prevented by IL-21 at the protein and transcriptional level. Subsequent stimulation via combined TCR/CD3 and CD28 triggering led to a markedly higher production of IL-2 and IFN-gamma in IL-15/IL-21-stimulated cells compared with IL-15-stimulated T cells. Our data show that IL-21 modulates the phenotype of naive CD8+ T cells that have undergone IL-15 induced homeostatic proliferation and preserves their responsiveness to CD28 ligands.

Left Ventricular Strain in Chemotherapy-Naive and Radiotherapy-Naive Patients With Cancer.

PubMed

Tadic, Marijana; Genger, Martin; Baudisch, Ana; Kelle, Sebastian; Cuspidi, Cesare; Belyavskiy, Evgeny; Burkhardt, Franziska; Venneri, Lucia; Attanasio, Philipp; Pieske, Burkert

2018-03-01

We sought to investigate left ventricular (LV) function and mechanics in patients with cancer before they received chemotherapy or radiotherapy, as well as the relationship between cancer and reduced LV multidirectional strain in the whole study population. The retrospective study involved 122 chemotherapy- and radiotherapy-naive patients with cancer and 45 age- and sex-matched controls with a cardiovascular risk profile similar to that of the patients with cancer. All the patients underwent echocardiographic examination before introduction of chemotherapy or radiotherapy. LV longitudinal (-19.1% ± 2.1% vs -17.8% ± 3.5%; P = 0.022), circumferential (-22.9% ± 3.5% vs -20.1% ± 4.1%; P < 0.001), and radial (40.5% ± 8.8% vs 35.2% ± 10.7%; P = 0.004) strain was significantly lower in the patients with cancer than in the control group. Endocardial and midmyocardial longitudinal LV strain was significantly reduced in the patients with cancer compared with the controls, whereas epicardial longitudinal strain was similar between these groups. Endocardial, midmyocardial, and epicardial circumferential strain was significantly lower in the chemotherapy- or radiotherapy-naive patients with cancer than in the controls. Cancer was associated with reduced longitudinal (odds ratio [OR], 9.0; 95% confidence interval [CI], 2.20-23.50; P < 0.001), reduced circumferential (OR, 7.1; 95% CI, 3.80-20.40; P < 0.001), and reduced radial strain (OR, 7.2; 95% CI, 3.41-25.10; P < 0.001) independent of age, sex, body mass index, diabetes, and hypertension. LV mechanics was impaired in the patients with cancer compared with the controls even before initiation of chemotherapy and radiotherapy. Cancer and hypertension were associated with reduced LV multidirectional strain independent of other clinical parameters. The present results indicate that cancer itself potentially induces cardiac remodelling independent of chemotherapy and radiotherapy. Copyright © 2017 Canadian

Hydroxypropyl-sulfobutyl-β-cyclodextrin improves the oral bioavailability of edaravone by modulating drug efflux pump of enterocytes.

PubMed

Rong, Wen-Ting; Lu, Ya-Peng; Tao, Qing; Guo, Miao; Lu, Yu; Ren, Yong; Yu, Shu-Qin

2014-02-01

The objective of the study was to evaluate the effect of hydroxypropyl-sulfobutyl-β-cyclodextrin (HP-SBE-βCD) on the bioavailability and intestinal absorption of edaravone, and identify its mechanism of action. We devised HP-SBE-βCD as a carrier and modulator of P-glycoprotein (Pgp) efflux pump, and edaravone as a model drug, and prepared edaravone/HP-SBE-βCD inclusion complex. HP-SBE-βCD improved the water solubility and enhanced the bioavailability of edaravone by 10.3-fold in rats. Then, in situ single-pass intestinal perfusion showed that HP-SBE-βCD had an effect of improving the permeability and inhibiting the efflux of edaravone. Furthermore, the effects of HP-SBE-βCD on Pgp were achieved through interfering with the lipid raft and depleting the cholesterol of enterocytes membrane. From the results, we presented the novel mechanisms. First, edaravone/HP-SBE-βCD had a lower release from the inclusion compound to protect edaravone from the low pH of the stomach. Then, HP-SBE-βCD modulated the membrane microenvironment of intestinal absorption epithelial cells. At last, the result was that HP-SBE-βCD enhanced the absorption of edaravone by interfering with Pgp. In conclusion, HP-SBE-βCD improves the bioavailability of drug not only because of its enhancing water solubility of the drug, but also because it modulates the Pgp-mediated efflux from enterocytes. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Offspring Hormones Reflect the Maternal Prenatal Social Environment: Potential for Foetal Programming?

PubMed Central

Meise, Kristine; von Engelhardt, Nikolaus; Forcada, Jaume; Hoffman, Joseph Ivan

2016-01-01

Females of many species adaptively program their offspring to predictable environmental conditions, a process that is often mediated by hormones. Laboratory studies have shown, for instance, that social density affects levels of maternal cortisol and testosterone, leading to fitness-relevant changes in offspring physiology and behaviour. However, the effects of social density remain poorly understood in natural populations due to the difficulty of disentangling confounding influences such as climatic variation and food availability. Colonially breeding marine mammals offer a unique opportunity to study maternal effects in response to variable colony densities under similar ecological conditions. We therefore quantified maternal and offspring hormone levels in 84 Antarctic fur seals (Arctocephalus gazella) from two closely neighbouring colonies of contrasting density. Hair samples were used as they integrate hormone levels over several weeks or months and therefore represent in utero conditions during foetal development. We found significantly higher levels of cortisol and testosterone (both P < 0.001) in mothers from the high density colony, reflecting a more stressful and competitive environment. In addition, offspring testosterone showed a significant positive correlation with maternal cortisol (P < 0.05). Although further work is needed to elucidate the potential consequences for offspring fitness, these findings raise the intriguing possibility that adaptive foetal programming might occur in fur seals in response to the maternal social environment. They also lend support to the idea that hormonally mediated maternal effects may depend more strongly on the maternal regulation of androgen rather than cortisol levels. PMID:26761814

Oral exposure to cylindrospermopsin in pregnant rats: reproduction and foetal toxicity studies.

PubMed

Sibaldo de Almeida, Cristhiano; Costa de Arruda, Andrea Caroline; Caldas de Queiroz, Erika; Matias de Lima Costa, Haline Tereza; Barbosa, Patrícia Fernandes; Araújo Moura Lemos, Telma Maria; Oliveira, Cláudia Nunes; Pinto, Ernani; Schwarz, Aline; Kujbida, Paula

2013-11-01

Cylindrospermopsin (CYN) induces toxicity in pregnant mice when administered intraperitoneally. This study investigated whether oral exposure to CYN (0.03, 0.3 and 3 μg/kg) during pregnancy causes toxic effects and impairs gestation in rats. The results of reproductive performance and teratology studies were similar between the control and experimental dams. Our findings suggest that CYN consumption within the guideline values for drinking water is not able to promote foetal toxicity or alterations in rat reproductive performance. Copyright © 2013 Elsevier Ltd. All rights reserved.

The prevalence of the maxillo-septal syndrome in Anglo-Saxon and Romano-British skulls and foetal specimens.

PubMed

Griffin, C J

1978-04-01

Seventy-three pre-medieval British skulls were examined and the maxillo-septal syndrome was found in 42. Ten foetal specimens of crown rump length greater than 40 mm were also examined and the syndrome was found in three specimens. Deflection of the nasal septum was present in 56 specimens.

Blood-brain barrier and foetal-onset hydrocephalus, with a view on potential novel treatments beyond managing CSF flow.

PubMed

Guerra, M; Blázquez, J L; Rodríguez, E M

2017-07-13

Despite decades of research, no compelling non-surgical therapies have been developed for foetal hydrocephalus. So far, most efforts have pointed to repairing disturbances in the cerebrospinal fluid (CSF) flow and to avoid further brain damage. There are no reports trying to prevent or diminish abnormalities in brain development which are inseparably associated with hydrocephalus. A key problem in the treatment of hydrocephalus is the blood-brain barrier that restricts the access to the brain for therapeutic compounds or systemically grafted cells. Recent investigations have started to open an avenue for the development of a cell therapy for foetal-onset hydrocephalus. Potential cells to be used for brain grafting include: (1) pluripotential neural stem cells; (2) mesenchymal stem cells; (3) genetically-engineered stem cells; (4) choroid plexus cells and (5) subcommissural organ cells. Expected outcomes are a proper microenvironment for the embryonic neurogenic niche and, consequent normal brain development.

Are 3D ultrasound and office hysteroscopy useful for the assessment of uterine cavity after late foetal loss?

PubMed

Thellier, E; Levaillant, J-M; Pourcelot, A-G; Houllier, M; Fernandez, H; Capmas, P

2018-05-01

To assess the efficacy of office hysteroscopy and 3D ultrasound for the diagnostic of uterine anomalies after late foetal loss. This retrospective observational study took place in the gynaecologic unit of a teaching hospital from 2009 to 2014. Women with late foetal loss (<22 weeks of gestation) had an office hysteroscopy and 3D ultrasound within three months after delivery. The results of the ultrasound and hysteroscopy were recorded and compared. Eighty women were included with a mean age of 29.8 years (28.2-31.4). Forty-seven women had both hysteroscopy and 3D ultrasound, and a uterine cavity's anomaly (bicornuate uterus, T-Shape uterus and septate uterus) was found in ten women (21%) at 3D sonography and in 13 women (28%) at office hysteroscopy. Concordance between the two exams was very good with a kappa at 0.83. In three cases, a uterine cavity's anomaly was found at hysteroscopy whereas sonography was normal. Anomalies at ultrasound (uterine cavity's anomaly, myometrium anomaly or ovarian anomaly) were found in 27.6% of cases. Both 3D ultrasound and office hysteroscopy are useful for assessment of the uterine cavity after late foetal loss. The application of these two exams is important, as hysteroscopy is generally used for assessment of the uterine cavity and endometrium, while 3D ultrasound is generally used to identify the precise type of uterine malformation and for the examination of the myometrium and annexes. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Children's Conceptions of Mental Illness: A Naive Theory Approach

ERIC Educational Resources Information Center

Fox, Claudine; Buchanan-Barrow, Eithne; Barrett, Martyn

2010-01-01

This paper reports two studies that investigated children's conceptions of mental illness using a naive theory approach, drawing upon a conceptual framework for analysing illness representations which distinguishes between the identity, causes, consequences, curability, and timeline of an illness. The studies utilized semi-structured interviewing…

Mathematical Model of Naive T Cell Division and Survival IL-7 Thresholds.

PubMed

Reynolds, Joseph; Coles, Mark; Lythe, Grant; Molina-París, Carmen

2013-01-01

We develop a mathematical model of the peripheral naive T cell population to study the change in human naive T cell numbers from birth to adulthood, incorporating thymic output and the availability of interleukin-7 (IL-7). The model is formulated as three ordinary differential equations: two describe T cell numbers, in a resting state and progressing through the cell cycle. The third is introduced to describe changes in IL-7 availability. Thymic output is a decreasing function of time, representative of the thymic atrophy observed in aging humans. Each T cell is assumed to possess two interleukin-7 receptor (IL-7R) signaling thresholds: a survival threshold and a second, higher, proliferation threshold. If the IL-7R signaling strength is below its survival threshold, a cell may undergo apoptosis. When the signaling strength is above the survival threshold, but below the proliferation threshold, the cell survives but does not divide. Signaling strength above the proliferation threshold enables entry into cell cycle. Assuming that individual cell thresholds are log-normally distributed, we derive population-average rates for apoptosis and entry into cell cycle. We have analyzed the adiabatic change in homeostasis as thymic output decreases. With a parameter set representative of a healthy individual, the model predicts a unique equilibrium number of T cells. In a parameter range representative of persistent viral or bacterial infection, where naive T cell cycle progression is impaired, a decrease in thymic output may result in the collapse of the naive T cell repertoire.

Highly efficient gene transfer in naive human T cells with a murine leukemia virus-based vector.

PubMed

Dardalhon, V; Jaleco, S; Rebouissou, C; Ferrand, C; Skander, N; Swainson, L; Tiberghien, P; Spits, H; Noraz, N; Taylor, N

2000-08-01

Retroviral vectors based on the Moloney murine leukemia virus (MuLV) have become the primary tool for gene delivery into hematopoietic cells, but clinical trials have been hampered by low transduction efficiencies. Recently, we and others have shown that gene transfer of MuLV-based vectors into T cells can be significantly augmented using a fibronectin-facilitated protocol. Nevertheless, the relative abilities of naive (CD45RA(+)) and memory (CD45RO(+)) lymphocyte subsets to be transduced has not been assessed. Although naive T cells demonstrate a restricted cytokine profile following antigen stimulation and a decreased susceptibility to infection with human immunodeficiency virus, it was not clear whether they could be efficiently infected with a MuLV vector. This study describes conditions that permitted gene transfer of an enhanced green fluorescent protein-expressing retroviral vector in more than 50% of naive umbilical cord (UC) blood and peripheral blood (PB) T cells following CD3/CD28 ligation. Moreover, treatment of naive T cells with interleukin-7 resulted in the maintenance of a CD45RA phenotype and gene transfer levels approached 20%. Finally, it was determined that parameters for optimal transduction of CD45RA(+) T cells isolated from PB and UC blood differed: transduction of the UC cells was significantly increased by the presence of autologous mononuclear cells (24.5% versus 56.5%). Because naive T cells harbor a receptor repertoire that allows them to respond to novel antigens, the development of protocols targeting their transduction is crucial for gene therapy applications. This approach will also allow the functions of exogenous genes to be evaluated in primary nontransformed naive T cells.

Naive vs. Sophisticated Methods of Forecasting Public Library Circulations.

ERIC Educational Resources Information Center

Brooks, Terrence A.

1984-01-01

Two sophisticated--autoregressive integrated moving average (ARIMA), straight-line regression--and two naive--simple average, monthly average--forecasting techniques were used to forecast monthly circulation totals of 34 public libraries. Comparisons of forecasts and actual totals revealed that ARIMA and monthly average methods had smallest mean…

Qualitative and quantitative ultrasound attributes of maternal-foetal structures in pregnant ewes.

PubMed

da Silva, Pda; Uscategui, Rar; Santos, Vjc; Taira, A R; Mariano, Rsg; Rodrigues, Mgk; Simões, Apr; Maronezi, M C; Avante, M L; Vicente, Wrr; Feliciano, Mar

2018-06-01

The aim of this study was to examine foetal organs and placental tissue to establish a correlation between the changes in the composition of these structures associated with their maturation and the ultrasonographic characteristics of the images. Twenty-four pregnant ewes were included in the study. Ultrasonography assessments were performed in B-mode, from the ninth gestational week until parturition. The lungs, liver and kidneys of foetuses and placentomes were located in transverse and longitudinal sections to evaluate the echogenicity (hypoechoic, isoechoic, hyperechoic or mixed) and echotexture (homogeneous and heterogeneous) of the tissues of interest. For quantitative evaluation of the ultrasonographic characteristics, it was performed a computerized image analysis using a commercial software (Image ProPlus ® ). Mean numerical pixel values (NPVs), pixel heterogeneity (standard deviation of NPVs) and minimum and maximum pixel values were measured by selecting five circular regions of interest in each assessed tissue. All evaluated tissues presented significant variations in the NPVs, except for the liver. Pulmonary NPVmean, NPVmin and NPVmax decreased gradually through gestational weeks. The renal parameters gradually decreased with the advancement of the gestational weeks until the 17th week and later stabilized. The placentome NPVmean, NPVmin and NPVmax decreased gradually over the course of weeks. The hepatic tissue did not show echogenicity and echotexture variations and presented medium echogenicity and homogeneous echotexture throughout the experimental period. It was concluded that pixels numerical evaluation of maternal-foetal tissues was applicable and allowed the identification of quantitative ultrasonographic characteristics showing changes in echogenicity related to gestational age. © 2018 Blackwell Verlag GmbH.

Is there a relationship between foetal position and both preferred lying posture after birth and pattern of subsequent postural deformity in non-ambulant people with cerebral palsy?

PubMed

Porter, D; Michael, S; Kirkwood, C

2010-09-01

A pattern of postural deformity was observed in a previous study that included an association between direction of spinal curvature and direction of windsweeping with more windswept deformities occurring to the right and lateral spinal curvatures occurring convex to the left. The direction of this pattern was found to be associated with preferred lying posture in early life. The aim of this study was to test the association between foetal position and both the preferred lying posture after birth, and the direction of subsequent postural deformity in non-ambulant children with cerebral palsy (CP). A retrospective cohort study was carried out involving 60 participants at level five on the gross motor function classification for CP. Foetal position during the last month of pregnancy was taken from antenatal records and parents were interviewed to identify preferred lying posture in the first year of life. At the time of the physical assessment ages ranged from 1 year and 1 month to 19 years with a median age of 13 years and 1 month. Foetal presentation was found to be associated with the preferred lying posture with participants carried in a left occipito-anterior/lateral position more likely to adopt a supine head right lying posture, and vice versa. An association was also observed between the foetal position and asymmetrical postural deformity occurring later in life with participants carried in a left occipito-anterior/lateral presentation more likely to have a convex left spinal curve, a lower left pelvic obliquity, and a windswept hip pattern to the right. Clinicians should be aware of the association between foetal presentation, asymmetrical lying posture, and the direction of subsequent postural deformity for severely disabled children. A hypothesis is described that might help to explain these findings.

Inhibition of IKKβ in enterocytes exacerbates sepsis-induced intestinal injury and worsens mortality.

PubMed

Dominguez, Jessica A; Samocha, Alexandr J; Liang, Zhe; Burd, Eileen M; Farris, Alton B; Coopersmith, Craig M

2013-10-01

Nuclear factor-κB is a critical regulator of cell-survival genes and the host inflammatory response. The purpose of this study was to investigate the role of enterocyte-specific NF-kB in sepsis through selective ablation of IkB kinase. Prospective, randomized controlled study. Animal laboratories in university medical centers. Mice lacking functional NF-kB in their intestinal epithelium (Vil-Cre/Ikkβ) and wild-type mice were subjected to sham laparotomy or cecal ligation and puncture. Animals were killed at 24 hours or followed 7 days for survival. Septic wild-type mice had decreased villus length compared with sham mice, whereas villus atrophy was further exacerbated in septic Vil-Cre/Ikkβ mice. Sepsis induced an increase in intestinal epithelial apoptosis compared with sham mice, which was further exacerbated in Vil-Cre/Ikkβ mice. Sepsis induced intestinal hyperpermeability in wild-type mice compared with sham mice, which was further exacerbated in septic Vil-Cre/Ikkβ mice. This was associated with increased intestinal expression of claudin-2 in septic wild-type mice, which was further increased in septic Vil-Cre/Ikkβ mice. Both, pro-inflammatory and anti-inflammatory cytokines were increased in serum following cecal ligation and puncture, and interleukin 10 and monocyte chemoattractant protein-1 levels were higher in septic Vil-Cre/Ikkβ mice than in septic wild-type mice. All septic mice were bacteremic, but no differences in bacterial load were identified between wild-type and Vil-Cre/Ikkβ mice. To determine the functional significance of these results, animals were followed for survival. Septic wild-type mice had lower mortality than septic Vil-Cre/Ikkβ mice (47% vs 80%, p<0.05). Antitumor necrosis factor administration decreased intestinal apoptosis, permeability, and mortality in wild-type septic mice, and a similar improvement in intestinal integrity and survival were seen when antitumor necrosis factor was given to Vil-Cre/Ikkβ mice. Enterocyte

Inhibition of IKKß in enterocytes exacerbates sepsis-induced intestinal injury and worsens mortality

PubMed Central

Dominguez, Jessica A.; Samocha, Alexandr J.; Liang, Zhe; Burd, Eileen M.; Farris, Alton B.; Coopersmith, Craig M.

2013-01-01

Objective NF-kB is a critical regulator of cell survival genes and the host inflammatory response. The purpose of this study was to investigate the role of enterocyte-specific NF-kB in sepsis through selective ablation of IkB kinase (IKK)-ß. Design Prospective, randomized, controlled study. Setting Animal laboratories in university medical centers. Subjects and Interventions Mice lacking functional NF-kB in their intestinal epithelium (Vil-Cre/Ikkßf/Δ) and wild type (WT) mice were subjected to sham laparotomy or cecal ligation and puncture (CLP). Animals were sacrified at 24 hours or followed seven days for survival. Measurements and Main Results Septic WT mice had decreased villus length compared to sham mice while villus atrophy was further exacerbated in septic Vil-Cre/Ikkßf/Δ mice. Sepsis induced an increase in intestinal epithelial apoptosis compared to sham mice which was further exacerbated in Vil-Cre/Ikkßf/Δ mice. Sepsis induced intestinal hyperpermeability in WT mice compared to sham mice, which was further exacerbated in septic Vil-Cre/Ikkßf/Δ mice. This was associated with increased intestinal expression of claudin-2 in septic WT mice, which was further increased in septic Vil-Cre/Ikkßf/Δ mice. Both, pro-inflammatory and anti-inflammatory cytokines were increased in serum following CLP, and IL-10 and MCP-1 levels were higher in septic Vil-Cre/Ikkßf/Δ mice than septic WT mice. All septic mice were bacteremic, but no differences in bacterial load were identified between WT and Vil-Cre/Ikkßf/Δ mice. To determine the functional significance of these results, animals were followed for survival. Septic WT mice had lower mortality than septic Vil-Cre/Ikkßf/Δ mice (47% vs. 80%, p<0.05). Anti-TNF administration decreased intestinal apoptosis, permeability and mortality in WT septic mice and a similar improvement in intestinal integrity and survival were seen when anti-TNF was given to Vil-Cre/Ikkßf/Δ mice. Conclusions Enterocyte-specific NF

[Physical activity by pregnant women and its influence on maternal and foetal parameters; a systematic review].

PubMed

Aguilar Cordero, M J; Sánchez López, A M; Rodríguez Blanque, R; Noack Segovia, J P; Pozo Cano, M D; López-Contreras, G; Mur Villar, N

2014-10-01

Regular physical activity is known to be very beneficial to health. While it is important at all stages of life, during pregnancy doubts may arise about the suitability of physical exercise, as well as the type of activity, its frequency, intensity and duration. To analyse major studies on the influence of physical activity on maternal and foetal parameters. Systematic review of physical activity programmes for pregnant women and the results achieved, during pregnancy, childbirth and postpartum. 45 items were identified through an automated database search in PubMed, Scopus and Google Scholar, carried out from October 2013 to March 2014. In selecting the items, the criteria applied included the usefulness and relevance of the subject matter and the credibility or experience of the research study authors. The internal and external validity of each of the articles reviewed was taken into account. The results of the review highlight the importance of physical activity during pregnancy, and show that the information currently available can serve as an initial benchmark for further investigation into the impact of regular physical exercise, in an aquatic environment, on maternal-foetal health. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Telomerase Is Involved in IL-7-Mediated Differential Survival of Naive and Memory CD4+ T Cells1

PubMed Central

Yang, Yinhua; An, Jie; Weng, Nan-ping

2008-01-01

IL-7 plays an essential role in T cell maintenance and survival. The survival effect of IL-7 is thought to be mediated through regulation of Bcl2 family proteins. After a comparative analysis of IL-7-induced growth and cell death of human naive and memory CD4+ T cells, we observed that more memory CD4+ T cells underwent cell division and proceeded to apoptosis than naive cells in response to IL-7. However, IL-7-induced expressions of Bcl2 family members (Bcl2, Bcl-xL, Bax, and Bad) were similar between naive and memory cells. Instead, we found that IL-7 induced higher levels of telomerase activity in naive cells than in memory cells, and the levels of IL-7-induced telomerase activity had a significant inverse correlation with cell death in CD4+ T cells. Furthermore, we showed that reducing expression of telomerase reverse transcriptase and telomerase activity significantly increased cell death of IL-7-cultured CD4+ T cells. Together, these findings demonstrate that telomerase is involved in IL-7-mediated differential survival of naive and memory CD4+ T cells. PMID:18322183

[Foetal therapy for Down syndrome: a pro-active ethical reflection].

PubMed

de Wert, G M W R; Dondorp, W J

2016-01-01

Prenatal screening for Down syndrome has to date focused on facilitating the informed choice to continue or not with a pregnancy. The non-invasive prenatal test (NIPT) for Down syndrome does potentially offer the option to apply foetal neurocognitive therapy for Down syndrome (FTDS). Current research in animal models looks promising and therefore a proactive ethical reflection in relation to clinical trials is urgently needed. This discussion includes an exploration of the ethical aspects of FTDS. There seem to be no convincing a priori objections on the basis of the social model of disability. Arguments in terms of (respect for) autonomy, wellbeing and justice seem to in principle support such therapy. Still, both the conditions for sound clinical trials and the implications of possible effective therapy for current prenatal screening need further scrutiny.

Diagnosis of combined faults in Rotary Machinery by Non-Naive Bayesian approach

NASA Astrophysics Data System (ADS)

Asr, Mahsa Yazdanian; Ettefagh, Mir Mohammad; Hassannejad, Reza; Razavi, Seyed Naser

2017-02-01

When combined faults happen in different parts of the rotating machines, their features are profoundly dependent. Experts are completely familiar with individuals faults characteristics and enough data are available from single faults but the problem arises, when the faults combined and the separation of characteristics becomes complex. Therefore, the experts cannot declare exact information about the symptoms of combined fault and its quality. In this paper to overcome this drawback, a novel method is proposed. The core idea of the method is about declaring combined fault without using combined fault features as training data set and just individual fault features are applied in training step. For this purpose, after data acquisition and resampling the obtained vibration signals, Empirical Mode Decomposition (EMD) is utilized to decompose multi component signals to Intrinsic Mode Functions (IMFs). With the use of correlation coefficient, proper IMFs for feature extraction are selected. In feature extraction step, Shannon energy entropy of IMFs was extracted as well as statistical features. It is obvious that most of extracted features are strongly dependent. To consider this matter, Non-Naive Bayesian Classifier (NNBC) is appointed, which release the fundamental assumption of Naive Bayesian, i.e., the independence among features. To demonstrate the superiority of NNBC, other counterpart methods, include Normal Naive Bayesian classifier, Kernel Naive Bayesian classifier and Back Propagation Neural Networks were applied and the classification results are compared. An experimental vibration signals, collected from automobile gearbox, were used to verify the effectiveness of the proposed method. During the classification process, only the features, related individually to healthy state, bearing failure and gear failures, were assigned for training the classifier. But, combined fault features (combined gear and bearing failures) were examined as test data. The achieved

Comparison of Naive Bayes and Decision Tree on Feature Selection Using Genetic Algorithm for Classification Problem

NASA Astrophysics Data System (ADS)

Rahmadani, S.; Dongoran, A.; Zarlis, M.; Zakarias

2018-03-01

This paper discusses the problem of feature selection using genetic algorithms on a dataset for classification problems. The classification model used is the decicion tree (DT), and Naive Bayes. In this paper we will discuss how the Naive Bayes and Decision Tree models to overcome the classification problem in the dataset, where the dataset feature is selectively selected using GA. Then both models compared their performance, whether there is an increase in accuracy or not. From the results obtained shows an increase in accuracy if the feature selection using GA. The proposed model is referred to as GADT (GA-Decision Tree) and GANB (GA-Naive Bayes). The data sets tested in this paper are taken from the UCI Machine Learning repository.

Ensemble of Chaotic and Naive Approaches for Performance Enhancement in Video Encryption.

PubMed

Chandrasekaran, Jeyamala; Thiruvengadam, S J

2015-01-01

Owing to the growth of high performance network technologies, multimedia applications over the Internet are increasing exponentially. Applications like video conferencing, video-on-demand, and pay-per-view depend upon encryption algorithms for providing confidentiality. Video communication is characterized by distinct features such as large volume, high redundancy between adjacent frames, video codec compliance, syntax compliance, and application specific requirements. Naive approaches for video encryption encrypt the entire video stream with conventional text based cryptographic algorithms. Although naive approaches are the most secure for video encryption, the computational cost associated with them is very high. This research work aims at enhancing the speed of naive approaches through chaos based S-box design. Chaotic equations are popularly known for randomness, extreme sensitivity to initial conditions, and ergodicity. The proposed methodology employs two-dimensional discrete Henon map for (i) generation of dynamic and key-dependent S-box that could be integrated with symmetric algorithms like Blowfish and Data Encryption Standard (DES) and (ii) generation of one-time keys for simple substitution ciphers. The proposed design is tested for randomness, nonlinearity, avalanche effect, bit independence criterion, and key sensitivity. Experimental results confirm that chaos based S-box design and key generation significantly reduce the computational cost of video encryption with no compromise in security.

Naive (commonsense) geography and geobrowser usability after ten years of Google Earth

NASA Astrophysics Data System (ADS)

Hamerlinck, J. D.

2016-04-01

In 1995, the concept of ‘naive geography’ was formally introduced as an area of cognitive geographic information science representing ‘the body of knowledge that people have about the surrounding geographic world’ and reflecting ‘the way people think and reason about geographic space and time, both consciously and subconsciously’. The need to incorporate such commonsense knowledge and reasoning into design of geospatial technologies was identified but faced challenges in formalizing these relationships and processes in software implementation. Ten years later, the Google Earth geobrowser was released, marking the beginning of a new era of open access to, and application of, geographic data and information in society. Fast-forward to today, and the opportunity presents itself to take stock of twenty years of naive geography and a decade of the ubiquitous virtual globe. This paper introduces an ongoing research effort to explore the integration of naive (or commonsense) geography concepts in the Google Earth geobrowser virtual globe and their possible impact on Google Earth's usability, utility, and usefulness. A multi-phase methodology is described, combining usability reviews and usability testing with use-case scenarios involving the U.S.-Canadian Yellowstone to Yukon Initiative. Initial progress on a usability review combining cognitive walkthroughs and heuristics evaluation is presented.

Ensemble of Chaotic and Naive Approaches for Performance Enhancement in Video Encryption

PubMed Central

Chandrasekaran, Jeyamala; Thiruvengadam, S. J.

2015-01-01

Owing to the growth of high performance network technologies, multimedia applications over the Internet are increasing exponentially. Applications like video conferencing, video-on-demand, and pay-per-view depend upon encryption algorithms for providing confidentiality. Video communication is characterized by distinct features such as large volume, high redundancy between adjacent frames, video codec compliance, syntax compliance, and application specific requirements. Naive approaches for video encryption encrypt the entire video stream with conventional text based cryptographic algorithms. Although naive approaches are the most secure for video encryption, the computational cost associated with them is very high. This research work aims at enhancing the speed of naive approaches through chaos based S-box design. Chaotic equations are popularly known for randomness, extreme sensitivity to initial conditions, and ergodicity. The proposed methodology employs two-dimensional discrete Henon map for (i) generation of dynamic and key-dependent S-box that could be integrated with symmetric algorithms like Blowfish and Data Encryption Standard (DES) and (ii) generation of one-time keys for simple substitution ciphers. The proposed design is tested for randomness, nonlinearity, avalanche effect, bit independence criterion, and key sensitivity. Experimental results confirm that chaos based S-box design and key generation significantly reduce the computational cost of video encryption with no compromise in security. PMID:26550603

[Effects of simultaneous transplant of foetal mesencephalic cells in the striatum and the subthalamic nucleus of hemiparkinsonian rats].

PubMed

Pavón-Fuentes, N; Macías-González, R; Blanco-Lezcano, L; Alvarez-González, L; Martínez-Martí, L; Castillo-Díaz, L; De La Cuétara Bernal, K; Díaz, C; Lorigados-Pedre, L; Coro, Y; García-Varona, A Y; Rosillo, J C; Díaz, E

The main strategy followed in neural transplants as a method of treatment for Parkinson s disease, both experimental and clinical, has been to introduce foetal mesencephalic cells into the target area: the striatum. However, when the dopaminergic cells in the substantia nigra degenerate, not only is the dopaminergic innervation of the striatum affected but also other nuclei: globus pallidus, substantia nigra, substantia nigra pars reticulata and subthalamic nucleus. A series of data from pharmacological and physiological studies offer strong evidence that the dopamine released in these nuclei may play an important role in regulating the output nuclei of the basal ganglia. To evaluate the effect of transplanting foetal mesencephalic cells on the behaviour of 6 OH DA rats when introduced into the striatum and the subthalamic nucleus. 6 OH DA was used to induce lesions in the substantia nigra of rats, which were divided into several experimental groups. The rotating activity induced by D amphetamine (5 mg/kg, intraperitoneally) and apomorphine (0.05 mg/kg, subcutaneously) was evaluated before and three months after the transplant in all the experimental groups, except in the control group of healthy rats. The hemiparkinsonian rats received a total of 350,000 foetal ventral mesencephalic cells, which were implanted within small deposits in the striatum (8) and in the subthalamic nucleus (4). Rotation induced by both drugs was significantly lower (p= 0.05) in animals that had had dopaminergic cells transplanted into the striatum body. No significant improvement in this behaviour was to be found when transplants were limited to just the subthalamus or, simultaneously, also to the striatum. A significant increase in rotating behaviour induced by apomorphine was observed in the group which received a transplant in just the subthalamus.

Three Naive Questions: Addressed to the Modern Educational Optimism

ERIC Educational Resources Information Center

Krstic, Predrag

2016-01-01

This paper aims to question anew the popular and supposedly self-evident affirmation of education, in its modern incarnation as in its historical notion. The "naive" questions suggest that we have recently taken for granted that education ought to be for the masses, that it ought to be upbringing, and that it is better than ignorance.…

1H-NMR-Based Metabolic Profiling of Maternal and Umbilical Cord Blood Indicates Altered Materno-Foetal Nutrient Exchange in Preterm Infants

PubMed Central

Küster, Alice; Guignard, Nadia; Alexandre–Gouabau, Marie-Cécile; Darmaun, Dominique; Robins, Richard J.

2012-01-01

Background Adequate foetal growth is primarily determined by nutrient availability, which is dependent on placental nutrient transport and foetal metabolism. We have used 1H nuclear magnetic resonance (NMR) spectroscopy to probe the metabolic adaptations associated with premature birth. Methodology The metabolic profile in 1H NMR spectra of plasma taken immediately after birth from umbilical vein, umbilical artery and maternal blood were recorded for mothers delivering very-low-birth-weight (VLBW) or normo-ponderal full-term (FT) neonates. Principal Findings Clear distinctions between maternal and cord plasma of all samples were observed by principal component analysis (PCA). Levels of amino acids, glucose, and albumin-lysyl in cord plasma exceeded those in maternal plasma, whereas lipoproteins (notably low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) and lipid levels were lower in cord plasma from both VLBW and FT neonates. The metabolic signature of mothers delivering VLBW infants included decreased levels of acetate and increased levels of lipids, pyruvate, glutamine, valine and threonine. Decreased levels of lipoproteins glucose, pyruvate and albumin-lysyl and increased levels of glutamine were characteristic of cord blood (both arterial and venous) from VLBW infants, along with a decrease in levels of several amino acids in arterial cord blood. Conclusion These results show that, because of its characteristics and simple non-invasive mode of collection, cord plasma is particularly suited for metabolomic analysis even in VLBW infants and provides new insights into the materno-foetal nutrient exchange in preterm infants. PMID:22291897

A scoring system predicting the clinical course of CLPB defect based on the foetal and neonatal presentation of 31 patients.

PubMed

Pronicka, Ewa; Ropacka-Lesiak, Mariola; Trubicka, Joanna; Pajdowska, Magdalena; Linke, Markus; Ostergaard, Elsebet; Saunders, Carol; Horsch, Sandra; van Karnebeek, Clara; Yaplito-Lee, Joy; Distelmaier, Felix; Õunap, Katrin; Rahman, Shamima; Castelle, Martin; Kelleher, John; Baris, Safa; Iwanicka-Pronicka, Katarzyna; Steward, Colin G; Ciara, Elżbieta; Wortmann, Saskia B

2017-11-01

Recently, CLPB deficiency has been shown to cause a genetic syndrome with cataracts, neutropenia, and 3-methylglutaconic aciduria. Surprisingly, the neurological presentation ranges from completely unaffected to patients with virtual absence of development. Muscular hypo- and hypertonia, movement disorder and progressive brain atrophy are frequently reported. We present the foetal, peri- and neonatal features of 31 patients, of which five are previously unreported, using a newly developed clinical severity scoring system rating the clinical, metabolic, imaging and other findings weighted by the age of onset. Our data are illustrated by foetal and neonatal videos. The patients were classified as having a mild (n = 4), moderate (n = 13) or severe (n = 14) disease phenotype. The most striking feature of the severe subtype was the neonatal absence of voluntary movements in combination with ventilator dependency and hyperexcitability. The foetal and neonatal presentation mirrored the course of disease with respect to survival (current median age 17.5 years in the mild group, median age of death 35 days in the severe group), severity and age of onset of all findings evaluated. CLPB deficiency should be considered in neonates with absence of voluntary movements, respiratory insufficiency and swallowing problems, especially if associated with 3-methylglutaconic aciduria, neutropenia and cataracts. Being an important differential diagnosis of hyperekplexia (exaggerated startle responses), we advise performing urinary organic acid analysis, blood cell counts and ophthalmological examination in these patients. The neonatal presentation of CLPB deficiency predicts the course of disease in later life, which is extremely important for counselling.

Intra-articular clearance of labeled dextrans from naive and arthritic rat knee joints.

PubMed

Mwangi, Timothy K; Berke, Ian M; Nieves, Eduardo H; Bell, Richard D; Adams, Samuel B; Setton, Lori A

2018-05-26

Determine the effects of arthritis on the trans-synovial clearance of small and large model compounds following local delivery to the knee joint in a rat model. Intra-articular delivery was studied in rat knee joints in an osteoarthritis model of joint instability (medial collateral ligament and meniscus transection model or MMT). Fluorescently-labeled 10 kDa or 500 kDa dextran was injected in the arthritic or unoperated control (naive) joints 3 weeks after surgical destabilization, and the temporal clearance pattern was evaluated via in vivo regional fluorescence imaging, dextran concentrations in plasma and draining lymph nodes, and by quantification of fluorescence in histological synovium sections. Together these data were used to evaluate the effect of osteoarthritis and solute size on the rate of drug clearance from the joint. Clearance of 10 kDa dextran from the joint space quantified using in vivo fluorescence imaging of the knee joint region was not significantly different between naive and MMT joints. In contrast, clearance of 500 kDa dextran was significantly reduced for MMT joints when compared to naive joints by fluorescence in vivo imaging. Drug accumulation in lymph nodes and plasma were lower for the 500 kDa dextran as compared to 10 kDa dextran, and lymph node levels were further reduced with the presence of osteoarthritis. Furthermore, synovium was significantly thicker in MMT joints than in naive joints and image analysis of joint tissue sections revealed different trans-synovial distributions of 10 and 500 kDa dextran. Large macromolecules were retained in the arthritic joint longer than in the healthy joint, while smaller molecules were cleared similarly in healthy and arthritic joints. In vivo fluorescence imaging, plasma and lymph node concentrations, and spatial distributions of drug fluorescence identified differences in higher molecular weight clearance between naive and arthritic disease states. Findings may relate to a

PREDICTIVE ACCURACY OF TRANSCEREBELLAR DIAMETER IN COMPARISON WITH OTHER FOETAL BIOMETRIC PARAMETERS FOR GESTATIONAL AGE ESTIMATION AMONG PREGNANT NIGERIAN WOMEN.

PubMed

Adeyekun, A A; Orji, M O

2014-04-01

To compare the predictive accuracy of foetal trans-cerebellar diameter (TCD) with those of other biometric parameters in the estimation of gestational age (GA). A cross-sectional study. The University of Benin Teaching Hospital, Nigeria. Four hundred and fifty healthy singleton pregnant women, between 14-42 weeks gestation. Trans-cerebellar diameter (TCD), biparietal diameter (BPD), femur length (FL), abdominal circumference (AC) values across the gestational age range studied. Correlation and predictive values of TCD compared to those of other biometric parameters. The range of values for TCD was 11.9 - 59.7mm (mean = 34.2 ± 14.1mm). TCD correlated more significantly with menstrual age compared with other biometric parameters (r = 0.984, p = 0.000). TCD had a higher predictive accuracy of 96.9% ± 12 days), BPD (93.8% ± 14.1 days). AC (92.7% ± 15.3 days). TCD has a stronger predictive accuracy for gestational age compared to other routinely used foetal biometric parameters among Nigerian Africans.

Expert and Naive Raters Using the PAG: Does it Matter?

ERIC Educational Resources Information Center

Cornelius, Edwin T.; And Others

1984-01-01

Questions the observed correlation between job experts and naive raters using the Position Analysis Questionnaire (PAQ); and conducts a replication of the Smith and Hakel study (1979) with college students (N=39). Concluded that PAQ ratings from job experts and college students are not equivalent and therefore are not interchangeable. (LLL)

Right lateralized white matter abnormalities in first-episode, drug-naive paranoid schizophrenia.

PubMed

Guo, Wenbin; Liu, Feng; Liu, Zhening; Gao, Keming; Xiao, Changqing; Chen, Huafu; Zhao, Jingping

2012-11-30

Numerous studies in first-episode schizophrenia suggest the involvement of white matter (WM) abnormalities in multiple regions underlying the pathogenesis of this condition. However, there has never been a neuroimaging study in patients with first-episode, drug-naive paranoid schizophrenia by using tract-based spatial statistics (TBSS) method. Here, we used diffusion tensor imaging (DTI) with TBSS method to investigate the brain WM integrity in patients with first-episode, drug-naive paranoid schizophrenia. Twenty patients with first-episode, drug-naive paranoid schizophrenia and 26 healthy subjects matched with age, gender, and education level were scanned with DTI. An automated TBSS approach was employed to analyze the data. Voxel-wise statistics revealed that patients with paranoid schizophrenia had decreased fractional anisotropy (FA) values in the right superior longitudinal fasciculus (SLF) II, the right fornix, the right internal capsule, and the right external capsule compared to healthy subjects. Patients did not have increased FA values in any brain regions compared to healthy subjects. There was no correlation between the FA values in any brain regions and patient demographics and the severity of illness. Our findings suggest right-sided alterations of WM integrity in the WM tracts of cortical and subcortical regions may play an important role in the pathogenesis of paranoid schizophrenia. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Where does distance matter? Distance to the closest maternity unit and risk of foetal and neonatal mortality in France.

PubMed

Pilkington, Hugo; Blondel, Béatrice; Drewniak, Nicolas; Zeitlin, Jennifer

2014-12-01

The number of maternity units has declined in France, raising concerns about the possible impact of increasing travel distances on perinatal health outcomes. We investigated impact of distance to closest maternity unit on perinatal mortality. Data from the French National Vital Statistics Registry were used to construct foetal and neonatal mortality rates over 2001-08 by distance from mother's municipality of residence and the closest municipality with a maternity unit. Data from French neonatal mortality certificates were used to compute neonatal death rates after out-of-hospital birth. Relative risks by distance were estimated, adjusting for individual and municipal-level characteristics. Seven percent of births occurred to women residing at ≥30 km from a maternity unit and 1% at ≥45 km. Foetal and neonatal mortality rates were highest for women living at <5 km from a maternity unit. For foetal mortality, rates increased at ≥45 km compared with 5-45 km. In adjusted models, long distance to a maternity unit had no impact on overall mortality but women living closer to a maternity unit had a higher risk of neonatal mortality. Neonatal deaths associated with out-of-hospital birth were rare but more frequent at longer distances. At the municipal-level, higher percentages of unemployment and foreign-born residents were associated with increased mortality. Overall mortality was not associated with living far from a maternity unit. Mortality was elevated in municipalities with social risk factors and located closest to a maternity unit, reflecting the location of maternity units in deprived areas with risk factors for poor outcome. © The Author 2014. Published by Oxford University Press on behalf of the European Public Health Association.

Thinking Process of Naive Problem Solvers to Solve Mathematical Problems

ERIC Educational Resources Information Center

Mairing, Jackson Pasini

2017-01-01

Solving problems is not only a goal of mathematical learning. Students acquire ways of thinking, habits of persistence and curiosity, and confidence in unfamiliar situations by learning to solve problems. In fact, there were students who had difficulty in solving problems. The students were naive problem solvers. This research aimed to describe…

The Profession of Psychology Scale: Sophisticated and Naive Students' Responses

ERIC Educational Resources Information Center

Rosenthal, Gary T.; Soper, Barlow; Rachal, Chris; McKnight, Richard R.; Price, A. W.

2004-01-01

The Profession of Psychology Scale (Rosenthal, McKnight & Price, 2001) was used to investigate whether taking more psychology courses results in a more accurate understanding of what is required to become a psychologist. Data indicate that though misconceptions exist in both Naive students (those who had not completed any psychology courses) and…

IL-15 induces antigen-independent expansion and differentiation of human naive CD8+ T cells in vitro.

PubMed

Alves, Nuno L; Hooibrink, Berend; Arosa, Fernando A; van Lier, René A W

2003-10-01

Recent studies in mice have shown that although interleukin 15 (IL-15) plays an important role in regulating homeostasis of memory CD8+ T cells, it has no apparent function in controlling homeostatic proliferation of naive T cells. We here assessed the influence of IL-15 on antigen-independent expansion and differentiation of human CD8+ T cells. Both naive and primed human T cells divided in response to IL-15. In this process, naive CD8+ T cells successively down-regulated CD45RA and CD28 but maintained CD27 expression. Concomitant with these phenotypic changes, naive cells acquired the ability to produce interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha), expressed perforin and granzyme B, and acquired cytotoxic properties. Primed CD8+ T cells, from both noncytotoxic (CD45RA-CD27+) and cytotoxic (CD45RA+CD27-) subsets, responded to IL-15 and yielded ample numbers of cytokine-secreting and cytotoxic effector cells. In summary, all human CD8+ T-cell subsets had the ability to respond to IL-15, which suggests a generic influence of this cytokine on CD8+ T-cell homeostasis in man.

Naive and effector B-cell subtypes are increased in chronic rhinosinusitis with polyps.

PubMed

Miljkovic, Dijana; Psaltis, Alkis; Wormald, Peter-John; Vreugde, Sarah

2018-01-01

Recent studies demonstrated that B cells and their chemoattractants are elevated in the nasal mucosa of patients with chronic rhinosinusitis (CRS) with nasal polyposis (CRSwNP). However, the presence of naive B cells and of plasmablasts and memory B-cell subsets in the mucosa and periphery of the same patient with CRS is yet to be characterized. Here we sought to quantify naive, plasmablasts, and memory B cells in mucosal tissue and peripheral blood of patients with CRSwNP, patients with CRS without nasal polyps (CRSsNP), and control patients. Polyps, mucosa, and peripheral blood samples were prospectively collected from the patients with CRS and from the non-CRS controls. We used flow cytometry to distinguish among naive, plasmablast, and memory B cells in sinus tissue and peripheral blood. A total of 45 patients were recruited for the study. The patients with CRSwNP had significantly increased mucosal B-cell numbers versus the controls (3.39 ± 4.05% versus 0.39 ± 1.05% of live cells; p < 0.01, Kruskal-Wallis test), which included naive B cells (0.61 ± 0.94 versus 0.11 ± 0.24% of live cells; p < 0.03, Kruskal-Wallis test), plasmablasts (0.06 ± 0.26 versus 0.00 ± 0.00% of live cells; p < 0.055, Kruskal-Wallis test), and memory B cells (0.62 ± 1.26 versus 0.05 ± 0.15% of live cells; p < 0.02, Kruskal-Wallis test). Our study identified increased frequencies of different B-cell subtypes in the mucosa of patients with CRSwNP but not in the peripheral blood. We also found that patients with CRSwNP had significantly increased B-cell subtypes compared with the patients with CRSsNP and the controls. These results implied a potential role for mucosal B cells in the ongoing inflammation in patients with CRSwNP.

Influence of Maternal Obesity and Gestational Weight Gain on Maternal and Foetal Lipid Profile.

PubMed

Cinelli, Giulia; Fabrizi, Marta; Ravà, Lucilla; Ciofi Degli Atti, Marta; Vernocchi, Pamela; Vallone, Cristina; Pietrantoni, Emanuela; Lanciotti, Rosalba; Signore, Fabrizio; Manco, Melania

2016-06-15

Fatty acids (FAs) are fundamental for a foetus's growth, serving as an energy source, structural constituents of cellular membranes and precursors of bioactive molecules, as well as being essential for cell signalling. Long-chain polyunsaturated FAs (LC-PUFAs) are pivotal in brain and visual development. It is of interest to investigate whether and how specific pregnancy conditions, which alter fatty acid metabolism (excessive pre-pregnancy body mass index (BMI) or gestational weight gain (GWG)), affect lipid supply to the foetus. For this purpose, we evaluated the erythrocyte FAs of mothers and offspring (cord-blood) at birth, in relation to pre-pregnancy BMI and GWG. A total of 435 mothers and their offspring (237 males, 51%) were included in the study. Distribution of linoleic acid (LA) and α-linolenic acid (ALA), and their metabolites, arachidonic acid, dihomogamma linoleic (DGLA) and ecosapentanoic acid, was significantly different in maternal and foetal erythrocytes. Pre-pregnancy BMI was significantly associated with maternal percentage of MUFAs (Coeff: -0.112; p = 0.021), LA (Coeff: -0.033; p = 0.044) and DHA (Coeff. = 0.055; p = 0.0016); inadequate GWG with DPA (Coeff: 0.637; p = 0.001); excessive GWG with docosaexahenoic acid (DHA) (Coeff. = -0.714; p = 0.004). Moreover, pre-pregnancy BMI was associated with foetus percentage of PUFAs (Coeff: -0.172; p = 0.009), omega 6 (Coeff: -0.098; p = 0.015) and DHA (Coeff: -0.0285; p = 0.036), even after adjusting for maternal lipids. Our findings show that maternal GWG affects maternal but not foetal lipid profile, differently from pre-pregnancy BMI, which influences both.

State intervention in pregnancy: Should the law respond thus to the problem of Foetal Alcohol Spectrum Disorder?

PubMed

Gordon, Emily

2015-09-01

Maternal consumption of alcohol during pregnancy poses a serious threat to the life and health of unborn children. A submission to the Queensland Child Protection Commission of Inquiry proposed that the State's Child Protection Act be extended to allow intervention to protect unborn children, with a court empowered to order that the mother be taken into care pending birth, or otherwise impose conditions upon conduct. This article considers whether or not the law in Australia should respond to the problem of Foetal Alcohol Spectrum Disorder by allowing the involuntary treatment and detention of pregnant women. The focus, is upon intervention in response to existing pregnancies. Using a utilitarian critical framework, this article evaluates the merits of creating powers to compel treatment and detain in light of current legal principles relating to maternal autonomy and the legal position of the foetus. The common law position is considered, as well as current legislation allowing intervention in autonomous decision-making and whether or not these statutes may be enlivened to prevent foetal harm. This article suggests that permitting involuntary treatment and detention would be a significant policy change. It weighs up benefits and potential harms in considering whether or not such action would result in the most "good".

A Workshop for High School Students on Naive Set Theory

ERIC Educational Resources Information Center

Wegner, Sven-Ake

2014-01-01

In this article we present the prototype of a workshop on naive set theory designed for high school students in or around the seventh year of primary education. Our concept is based on two events which the author organized in 2006 and 2010 for students of elementary school and high school, respectively. The article also includes a practice report…

Sepsis reveals compartment-specific responses in intestinal proliferation and apoptosis in transgenic mice whose enterocytes re-enter the cell cycle.

PubMed

Lyons, John D; Klingensmith, Nathan J; Otani, Shunsuke; Mittal, Rohit; Liang, Zhe; Ford, Mandy L; Coopersmith, Craig M

2017-12-01

Cell production and death are tightly regulated in the rapidly renewing gut epithelium, with proliferation confined to crypts and apoptosis occurring in villi and crypts. This study sought to determine how stress alters these compartmentalized processes. Wild-type mice made septic via cecal ligation and puncture had decreased crypt proliferation and increased crypt and villus apoptosis. Fabpi -TAg mice expressing large T-antigen solely in villi had ectopic enterocyte proliferation with increased villus apoptosis in unmanipulated animals. Septic fabpi -TAg mice had an unexpected increase in villus proliferation compared with unmanipulated littermates, whereas crypt proliferation was decreased. Cell cycle regulators cyclin D1 and cyclin D2 were decreased in jejunal tissue in septic transgenic mice. In contrast, villus and crypt apoptosis were increased in septic fabpi -TAg mice. To examine the relationship between apoptosis and proliferation in a compartment-specific manner, fabpi -TAg mice were crossed with fabpl -Bcl-2 mice, resulting in expression of both genes in the villus but Bcl-2 alone in the crypt. Septic bi-transgenic animals had decreased crypt apoptosis but had a paradoxical increase in villus apoptosis compared with septic fabpi -TAg mice, associated with decreased proliferation in both compartments. Thus, sepsis unmasks compartment-specific proliferative and apoptotic regulation that is not present under homeostatic conditions.-Lyons, J. D., Klingensmith, N. J., Otani, S., Mittal, R., Liang, Z., Ford, M. L., Coopersmith, C. M. Sepsis reveals compartment-specific responses in intestinal proliferation and apoptosis in transgenic mice whose enterocytes re-enter the cell cycle. © FASEB.

Recent discoveries on absorption of dietary fat: Presence, synthesis, and metabolism of cytoplasmic lipid droplets within enterocytes.

PubMed

D'Aquila, Theresa; Hung, Yu-Han; Carreiro, Alicia; Buhman, Kimberly K

2016-08-01

Dietary fat provides essential nutrients, contributes to energy balance, and regulates blood lipid concentrations. These functions are important to health, but can also become dysregulated and contribute to diseases such as obesity, diabetes, cardiovascular disease, and cancer. Within enterocytes, the digestive products of dietary fat are re-synthesized into triacylglycerol, which is either secreted on chylomicrons or stored within cytoplasmic lipid droplets (CLDs). CLDs were originally thought to be inert stores of neutral lipids, but are now recognized as dynamic organelles that function in multiple cellular processes in addition to lipid metabolism. This review will highlight recent discoveries related to dietary fat absorption with an emphasis on the presence, synthesis, and metabolism of CLDs within this process. Copyright © 2016 Elsevier B.V. All rights reserved.

Foetal exposure to food and environmental carcinogens in human beings.

PubMed

Myöhänen, Kirsi; Vähäkangas, Kirsi

2012-02-01

Exposure to many different chemicals during pregnancy through maternal circulation is possible. Transplacental transfer of xenobiotics can be demonstrated using human placental perfusion. Also, placental perfusion can give information about the placental kinetics as well as metabolism and accumulation in the placenta because it retains the tissue structure and function. Although human placental perfusion has been used extensively to study the transplacental transfer of drugs, the information on food and environmental carcinogens is much more limited. This review deals with the foetal exposure to food and environmental carcinogens in human beings. In particular, human transplacental transfer of the food carcinogens such as acrylamide, glycidamide and nitrosodimethylamine are in focus. Because these carcinogens are genotoxic, the functional capacity of human placenta to induce DNA adduct formation or metabolize these above mentioned CYP2E1 substrates is of interest in this context. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

Psychiatric disease in late adolescence and young adulthood. Foetal programming by maternal hypothyroidism?

PubMed

Andersen, Stine Linding; Olsen, Jørn; Wu, Chun Sen; Laurberg, Peter

2014-07-01

Lack of maternal thyroid hormones during foetal brain development may lead to structural abnormalities in the brain. We hypothesized that maternal hypothyroidism during the pregnancy could programme the foetus to development of psychiatric disease later in life. Danish nationwide register study. Singletons live-born 1980-1990. Cox proportional hazards model was used to estimate adjusted hazard ratio (aHR) with 95% confidence interval for offspring redemption of ≥2 prescriptions of a psychiatric drug from age 15 to 31 years. Among 542 100 adolescents and young adults included, altogether 3979 (0·7%) were born to mothers with hypothyroidism registered before 1996. In crude analyses, the use of a psychiatric drug was more frequent in late adolescence and young adulthood when the mother had hypothyroidism (P < 0·001); however, several possible confounders had to be taken into account. For example, mothers with hypothyroidism often also had a psychiatric registration (38·5% vs 27·7%, P < 0·001) and the use of psychiatric drugs changed over time. After adjustment for confounders including birth year, maternal age and maternal psychiatric history, maternal hypothyroidism was associated with an increased risk of having redeemed prescriptions of anxiolytics [aHR 1·23 (1·03-1·48)] and antipsychotics [aHR 1·22 (1·03-1·44)] in late adolescence and young adulthood. For antidepressants, aHR was 1·07 (0·98-1·17). The association between maternal hypothyroidism and the use of a psychiatric drug in late adolescence and young adulthood was partly confounded by maternal psychiatric history, but foetal programming by maternal hypothyroidism may be part of the mechanisms leading to the use of anxiolytics and antipsychotics. © 2014 John Wiley & Sons Ltd.

Foetal loss and enhanced fertility observed in mice treated with Zidovudine or Nevirapine.

PubMed

Onwuamah, Chika K; Ezechi, Oliver C; Herbertson, Ebiere C; Audu, Rosemary A; Ujah, Innocent A O; Odeigah, Peter G C

2014-01-01

Health concerns for HIV-infected persons on antiretroviral therapy (ART) have moved from morbidity to the challenges of long-term ART. We investigated the effect of Zidovudine or Nevirapine on reproductive capacity across two mouse generations. A prospective mouse study with drugs administered through one spermatogenic cycle. Mouse groups (16 males and 10 females) were given Zidovudine or Nevirapine for 56 days. Males were mated to untreated virgin females to determine dominant lethal effects. Twenty females (10 treated and 10 untreated) mated with the treated males per dose and gave birth to the F1 generation. Parental mice were withdrawn from drugs for one spermatogenic cycle and mated to the same dams to ascertain if effects are reversible. The F1 generation were exposed for another 56 days and mated to produce the F2 generation. Foetal loss was indicated in the dominant lethal assay as early as four weeks into drug administration to the males. At the first mating of the parental generation to produce the F1 generation, births from 10 dams/dose when the 'father-only' was exposed to Zidovudine (10, 100 and 250 mg/kg) was 3, 2 and 1 while it was 7, 1 and 4 respectively when 'both-parents' were exposed. Similarly births from the parental generation first mating when the 'father-only' was exposed to Nevirapine (5, 50 and 150 mg/kg) was 2, 2 and 0 while it was 6, 5 and 9 respectively when 'both-parents' were exposed. However, fertility was not significantly different neither by dose nor by the parental exposure. The F1 mice mated to produce the F2 generation recorded only one birth. The dominant lethal analysis showed foetal loss occurred when the "fathers-only" were treated while fertility was enhanced when "both-parents" were on therapy at the time of mating.

HIV-1 drug resistance mutations emerging on darunavir therapy in PI-naive and -experienced patients in the UK.

PubMed

El Bouzidi, Kate; White, Ellen; Mbisa, Jean L; Sabin, Caroline A; Phillips, Andrew N; Mackie, Nicola; Pozniak, Anton L; Tostevin, Anna; Pillay, Deenan; Dunn, David T

2016-12-01

Darunavir is considered to have a high genetic barrier to resistance. Most darunavir-associated drug resistance mutations (DRMs) have been identified through correlation of baseline genotype with virological response in clinical trials. However, there is little information on DRMs that are directly selected by darunavir in clinical settings. We examined darunavir DRMs emerging in clinical practice in the UK. Baseline and post-exposure protease genotypes were compared for individuals in the UK Collaborative HIV Cohort Study who had received darunavir; analyses were stratified for PI history. A selection analysis was used to compare the evolution of subtype B proteases in darunavir recipients and matched PI-naive controls. Of 6918 people who had received darunavir, 386 had resistance tests pre- and post-exposure. Overall, 2.8% (11/386) of these participants developed emergent darunavir DRMs. The prevalence of baseline DRMs was 1.0% (2/198) among PI-naive participants and 13.8% (26/188) among PI-experienced participants. Emergent DRMs developed in 2.0% of the PI-naive group (4 mutations) and 3.7% of the PI-experienced group (12 mutations). Codon 77 was positively selected in the PI-naive darunavir cases, but not in the control group. Our findings suggest that although emergent darunavir resistance is rare, it may be more common among PI-experienced patients than those who are PI-naive. Further investigation is required to explore whether codon 77 is a novel site involved in darunavir susceptibility. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

Edoxaban vs. warfarin in vitamin K antagonist experienced and naive patients with atrial fibrillation†.

PubMed

O'Donoghue, Michelle L; Ruff, Christian T; Giugliano, Robert P; Murphy, Sabina A; Grip, Laura T; Mercuri, Michele F; Rutman, Howard; Shi, Minggao; Kania, Grzegorz; Cermak, Ondrej; Braunwald, Eugene; Antman, Elliott M

2015-06-14

Edoxaban is an oral, once-daily factor Xa inhibitor that is non-inferior to well-managed warfarin in patients with atrial fibrillation (AF) for the prevention of stroke and systemic embolic events (SEEs). We examined the efficacy and safety of edoxaban vs. warfarin in patients who were vitamin K antagonist (VKA) naive or experienced. ENGAGE AF-TIMI 48 randomized 21 105 patients with AF at moderate-to-high risk of stroke to once-daily edoxaban vs. warfarin. Subjects were followed for a median of 2.8 years. The primary efficacy endpoint was stroke or SEE. As a pre-specified subgroup, we analysed outcomes for those with or without prior VKA experience (>60 consecutive days). Higher-dose edoxaban significantly reduced the risk of stroke or SEE in patients who were VKA naive [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.56-0.90] and was similar to warfarin in the VKA experienced (HR 1.01, 95% CI 0.82-1.24; P interaction = 0.028). Lower-dose edoxaban was similar to warfarin for stroke or SEE prevention in patients who were VKA naive (HR 0.92, 95% CI 0.73-1.15), but was inferior to warfarin in those who were VKA experienced (HR 1.31, 95% 1.08-1.60; P interaction = 0.019). Both higher-dose and lower-dose edoxaban regimens significantly reduced the risk of major bleeding regardless of prior VKA experience (P interaction = 0.90 and 0.71, respectively). In patients with AF, edoxaban appeared to demonstrate greater efficacy compared with warfarin in patients who were VKA naive than VKA experienced. Edoxaban significantly reduced major bleeding compared with warfarin regardless of prior VKA exposure. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Oral immunisation of naive and primed animals with transgenic potato tubers expressing LT-B.

PubMed

Lauterslager, T G; Florack, D E; van der Wal, T J; Molthoff, J W; Langeveld, J P; Bosch, D; Boersma, W J; Hilgers, L A

2001-03-21

The efficacy of edible vaccines produced in potato tubers was examined in mice. Transgenic plants were developed by Agrobacterium tumefaciens-mediated transformation. The antigen selected was the non-toxic B subunit of the Escherichia coli enterotoxin (recLT-B). A synthetic gene coding for recLT-B was made and optimised for expression in potato tubers and accumulation in the endoplasmic reticulum. Introduction of this gene under control of the tuber-specific patatin promoter in potato plants resulted in the production of functional, i.e. Gm1-binding, recLT-B pentamers in tubers. Selected tubers containing about 13 microg of recLT-B per gram fresh weight were used for immunisation. Subcutaneous immunisation with an extract of recLT-B tubers yielded high antibody titres in serum that were similar to those obtained with bacterial recLT-B. The efficacy of oral administration of recLT-B tubers was determined by measuring mucosal and systemic immune responses in naive and primed mice. Animals were primed by subcutaneous injection of an extract of recLT-B tuber plus adjuvant. Naive and primed mice were fed 5 g of tubers ( approximately 65 microg of recLT-B) or were intubated intragastrically with 0.4 ml of tuber extract ( approximately 2 microg of recLT-B). In naive mice, feeding recLT-B tubers or intubation of tuber extract did not induce detectable anti-LT antibody titres. In primed animals, however, oral immunisation resulted in significant anti-LT IgA antibody responses in serum and faeces. Intragastric intubation of tuber extract revealed higher responses than feeding of tubers. These results indicate clearly that functional recLT-B can be produced in potato tubers, that this recombinant protein is immunogenic and that oral administration thereof elicits both systemic and local IgA responses in parentally primed, but not naive, animals.

Naive and effector B-cell subtypes are increased in chronic rhinosinusitis with polyps

PubMed Central

Miljkovic, Dijana; Psaltis, Alkis; Wormald, Peter-John

2018-01-01

Background: Recent studies demonstrated that B cells and their chemoattractants are elevated in the nasal mucosa of patients with chronic rhinosinusitis (CRS) with nasal polyposis (CRSwNP). However, the presence of naive B cells and of plasmablasts and memory B-cell subsets in the mucosa and periphery of the same patient with CRS is yet to be characterized. Objective: Here we sought to quantify naive, plasmablasts, and memory B cells in mucosal tissue and peripheral blood of patients with CRSwNP, patients with CRS without nasal polyps (CRSsNP), and control patients. Methods: Polyps, mucosa, and peripheral blood samples were prospectively collected from the patients with CRS and from the non-CRS controls. We used flow cytometry to distinguish among naive, plasmablast, and memory B cells in sinus tissue and peripheral blood. Results: A total of 45 patients were recruited for the study. The patients with CRSwNP had significantly increased mucosal B-cell numbers versus the controls (3.39 ± 4.05% versus 0.39 ± 1.05% of live cells; p < 0.01, Kruskal-Wallis test), which included naive B cells (0.61 ± 0.94 versus 0.11 ± 0.24% of live cells; p < 0.03, Kruskal-Wallis test), plasmablasts (0.06 ± 0.26 versus 0.00 ± 0.00% of live cells; p < 0.055, Kruskal-Wallis test), and memory B cells (0.62 ± 1.26 versus 0.05 ± 0.15% of live cells; p < 0.02, Kruskal-Wallis test). Conclusion: Our study identified increased frequencies of different B-cell subtypes in the mucosa of patients with CRSwNP but not in the peripheral blood. We also found that patients with CRSwNP had significantly increased B-cell subtypes compared with the patients with CRSsNP and the controls. These results implied a potential role for mucosal B cells in the ongoing inflammation in patients with CRSwNP. PMID:29336281

The Effect of Naive Ideas on Students' Reasoning about Electricity and Magnetism

ERIC Educational Resources Information Center

Leppavirta, Johanna

2012-01-01

Traditional multiple-choice concept inventories measure students' critical conceptual understanding and are designed to reveal students' naive or alternate ideas. The overall scores, however, give little information about the state of students' knowledge and the consistency of reasoning. This study investigates whether students have consistent…

CD72 ligation regulates defective naive newborn B cell responses.

PubMed

Howard, L M; Reen, D J

1997-02-01

The biological basis for reduced Ig production by naive newborn B cells compared to adult peripheral blood B cells is not fully understood. In a Con A + IL-2 T cell-dependent system using "competent" adult T cells, adult B cells produced large amounts of IgM, IgG, and IgA, while cord B cells were restricted to low levels of only IgM production. Cord B cell activation was also diminished. The contribution of specific B-T cell contact-mediated events to the diminished cord B cell response in this system, using mAbs to CD40, CD28, CD80, and CD72, were investigated, as well as regulation of B cell Ig production by cytokines. alphaCD72 ligation increased cord B cell activation and IgM production, but did not affect adult B cells. Blocking alphaCD40 mAb inhibited cord B cell Ig production completely, but only partly inhibited adult B cell Ig production even at high concentration, suggesting a greater sensitivity of cord B cells to disruption of the CD40-CD40L interaction. Addition of IL-10 did not increase cord B cell Ig production, while adult B cell Ig production was increased. However, combined addition of IL-10 and alphaCD72 significantly increased cord B cell Ig production over that in the presence of either alphaCD72 or IL-10 alone, but had no effect on adult B cells over that of IL-10 alone. These data suggest that the diminished T cell-dependent response of cord B cells is due to reduced or absent CD72 ligation. CD72 ligation plays an important role in the induction of primary responses by naive B cells. CD72 modulation of naive B cell sensitivity to IL-10 stimulation may have implications in the induction of class switch, which is deficient in newborn B cells. Since all T cells express CD5 constitutively, these data also suggest the existence of another ligand for CD72.

Children's Naive Theories of Intelligence Influence Their Metacognitive Judgments

ERIC Educational Resources Information Center

Miele, David B.; Son, Lisa K.; Metcalfe, Janet

2013-01-01

Recent studies have shown that the metacognitive judgments adults infer from their experiences of encoding effort vary in accordance with their naive theories of intelligence. To determine whether this finding extends to elementary schoolchildren, a study was conducted in which 27 third graders (M[subscript age] = 8.27) and 24 fifth graders…

Recent thymic emigrants and mature naive T cells exhibit differential DNA methylation at key cytokine loci.

PubMed

Berkley, Amy M; Hendricks, Deborah W; Simmons, Kalynn B; Fink, Pamela J

2013-06-15

Recent thymic emigrants (RTEs) are the youngest T cells in the lymphoid periphery and exhibit phenotypic and functional characteristics distinct from those of their more mature counterparts in the naive peripheral T cell pool. We show in this study that the Il2 and Il4 promoter regions of naive CD4(+) RTEs are characterized by site-specific hypermethylation compared with those of both mature naive (MN) T cells and the thymocyte precursors of RTEs. Thus, RTEs do not merely occupy a midpoint between the thymus and the mature T cell pool, but represent a distinct transitional T cell population. Furthermore, RTEs and MN T cells exhibit distinct CpG DNA methylation patterns both before and after activation. Compared with MN T cells, RTEs express higher levels of several enzymes that modify DNA methylation, and inhibiting methylation during culture allows RTEs to reach MN T cell levels of cytokine production. Collectively, these data suggest that the functional differences that distinguish RTEs from MN T cells are influenced by epigenetic mechanisms and provide clues to a mechanistic basis for postthymic maturation.

Fuzzy Naive Bayesian model for medical diagnostic decision support.

PubMed

Wagholikar, Kavishwar B; Vijayraghavan, Sundararajan; Deshpande, Ashok W

2009-01-01

This work relates to the development of computational algorithms to provide decision support to physicians. The authors propose a Fuzzy Naive Bayesian (FNB) model for medical diagnosis, which extends the Fuzzy Bayesian approach proposed by Okuda. A physician's interview based method is described to define a orthogonal fuzzy symptom information system, required to apply the model. For the purpose of elaboration and elicitation of characteristics, the algorithm is applied to a simple simulated dataset, and compared with conventional Naive Bayes (NB) approach. As a preliminary evaluation of FNB in real world scenario, the comparison is repeated on a real fuzzy dataset of 81 patients diagnosed with infectious diseases. The case study on simulated dataset elucidates that FNB can be optimal over NB for diagnosing patients with imprecise-fuzzy information, on account of the following characteristics - 1) it can model the information that, values of some attributes are semantically closer than values of other attributes, and 2) it offers a mechanism to temper exaggerations in patient information. Although the algorithm requires precise training data, its utility for fuzzy training data is argued for. This is supported by the case study on infectious disease dataset, which indicates optimality of FNB over NB for the infectious disease domain. Further case studies on large datasets are required to establish utility of FNB.

Phosphate-dependent glutaminase in enterocyte mitochondria and its regulation by ammonium and other ions.

PubMed

Masola, B; Zvinavashe, E

2003-06-01

The effects of ammonium and other ions on phosphate dependent glutaminase (PDG) activity in intact rat enterocyte mitochondria were investigated. Sulphate and bicarbonate activated the enzyme in absence and presence of added phosphate. In presence of 10 mM phosphate, ammonium at concentrations <1 mM inhibited the enzyme. This inhibition was reversed by increased concentration of phosphate or sulphate. The inhibition of PDG by ammonium in presence of 10 mM phosphate was biphasic with respect to glutamine concentration, its effect being through a lowering of V(max) at glutamine concentration of

DEXAMETHASONE IMPLANT FOR DIABETIC MACULAR EDEMA IN NAIVE COMPARED WITH REFRACTORY EYES: The International Retina Group Real-Life 24-Month Multicenter Study. The IRGREL-DEX Study.

PubMed

Iglicki, Matias; Busch, Catharina; Zur, Dinah; Okada, Mali; Mariussi, Miriana; Chhablani, Jay Kumar; Cebeci, Zafer; Fraser-Bell, Samantha; Chaikitmongkol, Voraporn; Couturier, Aude; Giancipoli, Ermete; Lupidi, Marco; Rodríguez-Valdés, Patricio J; Rehak, Matus; Fung, Adrian Tien-Chin; Goldstein, Michaella; Loewenstein, Anat

2018-04-24

To investigate efficacy and safety of repeated dexamethasone (DEX) implants over 24 months, in diabetic macular edema (DME) eyes that were treatment naive compared with eyes refractory to anti-vascular endothelial growth factor treatment, in a real-life environment. This multicenter international retrospective study assessed best-corrected visual acuity and central subfield thickness (CST) of naive and refractory eyes to anti-vascular endothelial growth factor injections treated with dexamethasone implants. Safety data (intraocular pressure rise and cataract surgery) were recorded. A total of 130 eyes from 125 patients were included. Baseline best-corrected visual acuity and CST were similar for naive (n = 71) and refractory eyes (n = 59). Both groups improved significantly in vision after 24 months (P < 0.001). However, naive eyes gained statistically significantly more vision than refractory eyes (+11.3 ± 10.0 vs. 7.3 ± 2.7 letters, P = 0.01) and were more likely to gain ≥10 letters (OR 3.31, 95% CI 1.19-9.24, P = 0.02). At 6, 12, and 24 months, CST was significantly decreased compared with baseline in both naive and refractory eyes; however, CST was higher in refractory eyes than in naive eyes (CST 279 ± 61 vs. 313 ± 125 μm, P = 0.10). Over a follow-up of 24 months, vision improved in diabetic macular edema eyes after treatment with dexamethasone implants, both in eyes that were treatment naive and eyes refractory to anti-vascular endothelial growth factor treatment; however, improvement was greater in naive eyes.

Nicotinic Acid Adenine Dinucleotide Phosphate Plays a Critical Role in Naive and Effector Murine T Cells but Not Natural Regulatory T Cells*

PubMed Central

Ali, Ramadan A.; Camick, Christina; Wiles, Katherine; Walseth, Timothy F.; Slama, James T.; Bhattacharya, Sumit; Giovannucci, David R.; Wall, Katherine A.

2016-01-01

Nicotinic acid adenine dinucleotide phosphate (NAADP), the most potent Ca2+ mobilizing second messenger discovered to date, has been implicated in Ca2+ signaling in some lymphomas and T cell clones. In contrast, the role of NAADP in Ca2+ signaling or the identity of the Ca2+ stores targeted by NAADP in conventional naive T cells is less clear. In the current study, we demonstrate the importance of NAADP in the generation of Ca2+ signals in murine naive T cells. Combining live-cell imaging methods and a pharmacological approach using the NAADP antagonist Ned-19, we addressed the involvement of NAADP in the generation of Ca2+ signals evoked by TCR stimulation and the role of this signal in downstream physiological end points such as proliferation, cytokine production, and other responses to stimulation. We demonstrated that acidic compartments in addition to the endoplasmic reticulum were the Ca2+ stores that were sensitive to NAADP in naive T cells. NAADP was shown to evoke functionally relevant Ca2+ signals in both naive CD4 and naive CD8 T cells. Furthermore, we examined the role of this signal in the activation, proliferation, and secretion of effector cytokines by Th1, Th2, Th17, and CD8 effector T cells. Overall, NAADP exhibited a similar profile in mediating Ca2+ release in effector T cells as in their counterpart naive T cells and seemed to be equally important for the function of these different subsets of effector T cells. This profile was not observed for natural T regulatory cells. PMID:26728458

Homeostasis of naive and memory CD4+ T cells: IL-2 and IL-7 differentially regulate the balance between proliferation and Fas-mediated apoptosis.

PubMed

Jaleco, Sara; Swainson, Louise; Dardalhon, Valérie; Burjanadze, Maryam; Kinet, Sandrina; Taylor, Naomi

2003-07-01

Cytokines play a crucial role in the maintenance of polyclonal naive and memory T cell populations. It has previously been shown that ex vivo, the IL-7 cytokine induces the proliferation of naive recent thymic emigrants (RTE) isolated from umbilical cord blood but not mature adult-derived naive and memory human CD4(+) T cells. We find that the combination of IL-2 and IL-7 strongly promotes the proliferation of RTE, whereas adult CD4(+) T cells remain relatively unresponsive. Immunological activity is controlled by a balance between proliferation and apoptotic cell death. However, the relative contributions of IL-2 and IL-7 in regulating these processes in the absence of MHC/peptide signals are not known. Following exposure to either IL-2 or IL-7 alone, RTE, as well as mature naive and memory CD4(+) T cells, are rendered only minimally sensitive to Fas-mediated cell death. However, in the presence of the two cytokines, Fas engagement results in a high level of caspase-dependent apoptosis in both RTE as well as naive adult CD4(+) T cells. In contrast, equivalently treated memory CD4(+) T cells are significantly less sensitive to Fas-induced cell death. The increased susceptibility of RTE and naive CD4(+) T cells to Fas-induced apoptosis correlates with a significantly higher IL-2/IL-7-induced Fas expression on these T cell subsets than on memory CD4(+) T cells. Thus, IL-2 and IL-7 regulate homeostasis by modulating the equilibrium between proliferation and apoptotic cell death in RTE and mature naive and memory T cell subsets.

Cinnamon polyphenols regulate multiple metabolic pathways involved in insulin signaling and intestinal lipoprotein metabolism of small intestinal enterocytes.

PubMed

Qin, Bolin; Dawson, Harry D; Schoene, Norberta W; Polansky, Marilyn M; Anderson, Richard A

2012-01-01

Increasing evidence suggests that dietary factors may affect the expression of multiple genes and signaling pathways, which regulate intestinal lipoprotein metabolism. The small intestine is actively involved in the regulation of dietary lipid absorption, intracellular transport, and metabolism and is closely linked to systemic lipid metabolism. Cinnamon polyphenols have been shown to improve glucose, insulin, and lipid metabolism and improve inflammation in cell culture, animal, and human studies. However, little is known of the effects of an aqueous cinnamon extract (CE) on the regulation of genes and signaling pathways related to intestinal metabolism. The aim of the study was to investigate the effects of a CE on the primary enterocytes of chow-fed rats. Freshly isolated intestinal enterocytes were used to investigate apolipoprotein-B48 secretion by immunoprecipitation; gene expressions by quantitative reverse transcriptase-polymerase chain reaction and the protein and phosphorylation levels were evaluated by western blot and flow cytometric analyses. Ex vivo, the CE significantly decreased the amount of apolipoprotein-B48 secretion into the media, inhibited the mRNA expression of genes of the inflammatory cytokines, interleukin-1β, interleukin-6, and tumor necrosis factor-α, and induced the expression of the anti-inflammatory gene, Zfp36. CE also increased the mRNA expression of genes leading to increased insulin sensitivity, including Ir, Irs1, Irs2, Pi3k, and Akt1, and decreased Pten expression. CE also inhibited genes associated with increased cholesterol, triacylglycerols, and apolipoprotein-B48 levels, including Abcg5, Npc1l1, Cd36, Mttp, and Srebp1c, and facilitated Abca1 expression. CE also stimulated the phospho-p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and extracellular-signal-regulated kinase expressions determined by flow cytometry, with no changes in protein levels. These results demonstrate that the CE regulates genes

Proteins involved in uptake, intracellular transport and basolateral secretion of fat-soluble vitamins and carotenoids by mammalian enterocytes.

PubMed

Reboul, Emmanuelle; Borel, Patrick

2011-10-01

Our understanding of the molecular mechanisms responsible for fat-soluble vitamin uptake and transport at the intestinal level has advanced considerably over the past decade. On one hand, it has long been considered that vitamin D and E as well as β-carotene (the main provitamin A carotenoid in human diet) were absorbed by a passive diffusion process, although this could not explain the broad inter-individual variability in the absorption efficiency of these molecules. On the other hand, it was assumed that preformed vitamin A (retinol) and vitamin K1 (phylloquinone) absorption occurred via energy-dependent processes, but the transporters involved have not yet been identified. The recent discovery of intestinal proteins able to facilitate vitamin E and carotenoid uptake and secretion by the enterocyte has spurred renewed interest in studying the fundamental mechanisms involved in the absorption of these micronutrients. The proteins identified so far are cholesterol transporters such as SR-BI (scavenger receptor class B type I), CD36 (cluster determinant 36), NPC1L1 (Niemann-Pick C1-like 1) or ABCA1 (ATP-Binding Cassette A1) displaying a broad substrate specificity, but it is likely that other membrane proteins are also involved. After overviewing the metabolism of fat-soluble vitamins and carotenoids in the human upper gastrointestinal lumen, we will focus on the putative or identified proteins participating in the intestinal uptake, intracellular transport and basolateral secretion of these fat-soluble vitamins and carotenoids, and outline the uncertainties that need to be explored in the future. Identifying the proteins involved in intestinal uptake and transport of fat-soluble vitamins and carotenoids across the enterocyte is of great importance, especially as some of them are already targets for the development of drugs able to slow cholesterol absorption. Indeed, these drugs may also interfere with lipid vitamin uptake. A better understanding of the molecular

The utilization of health care services by children with Foetal Alcohol Syndrome in the Western Cape, South Africa.

PubMed

Credé, Sarah; Sinanovic, Edina; Adnams, Colleen; London, Leslie

2011-06-01

The rates of Foetal Alcohol Syndrome (FAS) and Partial Foetal Alcohol Spectrum (PFAS) in South Africa are the highest reported worldwide. There is a paucity of research examining the health care costs of caring for children with FAS or PFAS in this country. A cross-sectional analytical study was conducted using an interviewer-administered questionnaire amongst caregivers of children (0-12 years) with FAS/PFAS in the Western Cape to estimate the utilization of health care services; the annual direct and indirect health care costs per child as well as the total cost to society for providing health care services to children with FAS/PFAS. It was found that the median number of annual visits to public health care facilities per child was 8 (IQR 4 to 14). The total average annual cost per child was $1039.38 (95% CI: $808.68; $1270.07) and the total annual societal cost for the Western Cape was $70,960,053.68 (95% CI: $5,528,895.48; $86,709,971.13). Caregivers in receipt of a social support grant reported spending significantly less on health care for a child with FAS/PFAS (Fisher's exact p=0.004). These study results confirm the significant burden of FAS/PFAS on the Western Cape economy and the health care system which has significant implications for FAS prevention. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Association of prenatal antibiotics with foetal size and cord blood leptin and adiponectin.

PubMed

Mueller, N T; Rifas-Shiman, S L; Blaser, M J; Gillman, M W; Hivert, M-F

2017-04-01

Early postnatal antibiotic use has been shown to promote excess weight gain, but it is unclear whether intrauterine exposure to antibiotics is associated with foetal growth and adiposity. The objective of this study was to examine associations of antibiotic prescription in each trimester of pregnancy with foetal size and adipokine levels at birth. In 2128 pregnant women from the pre-birth Project Viva cohort, from electronic medical records, we estimated antibiotic prescribing by timing during pregnancy. Outcomes were sex-specific birth weight-for-gestational-age z-score (BW/GA-z) and levels of umbilical cord leptin and adiponectin. We used linear regression models adjusted for maternal age, pre-pregnancy body mass index, parity, race/ethnicity, education, smoking during pregnancy, household income and child sex and additionally adjusted cord blood leptin and adiponectin models for gestation length. Of the 2128 women in our sample, 643 (30.2%) were prescribed with oral antibiotics during pregnancy. Mean (standard deviation) BW/GA-z was 0.17 (0.97), cord blood leptin was 9.0 ng mL -1 (6.6) and cord blood adiponectin was 28.8 ng mL -1 (6.8). Overall, antibiotic prescription in pregnancy was associated with lower BW/GA-z [multivariable adjusted β -0.11; 95% confidence interval {CI} -0.20, -0.01]. In trimester-specific analyses, only second trimester antibiotic prescription was associated with lower BW/GA-z (β -0.23; 95% CI -0.37, -0.08). Overall, antibiotic prescription in pregnancy was not associated with cord blood leptin or adiponectin levels. However, in trimester-specific analyses, third trimester antibiotic prescription was associated with higher cord blood leptin (β 2.28 ng mL -1 ; 95% CI 0.38, 4.17). Antibiotics in mid-pregnancy were associated with lower birth weight for gestational age, whereas third trimester antibiotics were associated with higher cord blood leptin. © 2016 World Obesity Federation.

Impairment of DNA Methylation Maintenance Is the Main Cause of Global Demethylation in Naive Embryonic Stem Cells.

PubMed

von Meyenn, Ferdinand; Iurlaro, Mario; Habibi, Ehsan; Liu, Ning Qing; Salehzadeh-Yazdi, Ali; Santos, Fátima; Petrini, Edoardo; Milagre, Inês; Yu, Miao; Xie, Zhenqing; Kroeze, Leonie I; Nesterova, Tatyana B; Jansen, Joop H; Xie, Hehuang; He, Chuan; Reik, Wolf; Stunnenberg, Hendrik G

2016-06-16

Global demethylation is part of a conserved program of epigenetic reprogramming to naive pluripotency. The transition from primed hypermethylated embryonic stem cells (ESCs) to naive hypomethylated ones (serum-to-2i) is a valuable model system for epigenetic reprogramming. We present a mathematical model, which accurately predicts global DNA demethylation kinetics. Experimentally, we show that the main drivers of global demethylation are neither active mechanisms (Aicda, Tdg, and Tet1-3) nor the reduction of de novo methylation. UHRF1 protein, the essential targeting factor for DNMT1, is reduced upon transition to 2i, and so is recruitment of the maintenance methylation machinery to replication foci. Concurrently, there is global loss of H3K9me2, which is needed for chromatin binding of UHRF1. These mechanisms synergistically enforce global DNA hypomethylation in a replication-coupled fashion. Our observations establish the molecular mechanism for global demethylation in naive ESCs, which has key parallels with those operating in primordial germ cells and early embryos. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Impaired P600 in neuroleptic naive patients with first-episode schizophrenia.

PubMed

Papageorgiou, C; Kontaxakis, V P; Havaki-Kontaxaki, B J; Stamouli, S; Vasios, C; Asvestas, P; Matsopoulos, G K; Kontopantelis, E; Rabavilas, A; Uzunoglu, N; Christodoulou, G N

2001-09-17

Deficits of working memory (WM) are recognized as an important pathological feature in schizophrenia. Since the P600 component of event related potentials has been hypothesized that represents aspects of second-pass parsing processes of information processing, and is related to WM, the present study focuses on P600 elicited during a WM test in drug-naive first-episode schizophrenics (FES) compared to healthy controls. We examined 16 drug-naive first-episode schizophrenic patients and 23 healthy controls matched for age and sex. Compared with controls schizophrenic patients showed reduced P600 amplitude on left temporoparietal region and increased P600 amplitude on left occipital region. With regard to the latency, the patients exhibited significantly prolongation on right temporoparietal region. The obtained pattern of differences classified correctly 89.20% of patients. Memory performance of patients was also significantly impaired relative to controls. Our results suggest that second-pass parsing process of information processing, as indexed by P600, elicited during a WM test, is impaired in FES. Moreover, these findings lend support to the view that the auditory WM in schizophrenia involves or affects a circuitry including temporoparietal and occipital brain areas.

Nicotinic Acid Adenine Dinucleotide Phosphate Plays a Critical Role in Naive and Effector Murine T Cells but Not Natural Regulatory T Cells.

PubMed

Ali, Ramadan A; Camick, Christina; Wiles, Katherine; Walseth, Timothy F; Slama, James T; Bhattacharya, Sumit; Giovannucci, David R; Wall, Katherine A

2016-02-26

Nicotinic acid adenine dinucleotide phosphate (NAADP), the most potent Ca(2+) mobilizing second messenger discovered to date, has been implicated in Ca(2+) signaling in some lymphomas and T cell clones. In contrast, the role of NAADP in Ca(2+) signaling or the identity of the Ca(2+) stores targeted by NAADP in conventional naive T cells is less clear. In the current study, we demonstrate the importance of NAADP in the generation of Ca(2+) signals in murine naive T cells. Combining live-cell imaging methods and a pharmacological approach using the NAADP antagonist Ned-19, we addressed the involvement of NAADP in the generation of Ca(2+) signals evoked by TCR stimulation and the role of this signal in downstream physiological end points such as proliferation, cytokine production, and other responses to stimulation. We demonstrated that acidic compartments in addition to the endoplasmic reticulum were the Ca(2+) stores that were sensitive to NAADP in naive T cells. NAADP was shown to evoke functionally relevant Ca(2+) signals in both naive CD4 and naive CD8 T cells. Furthermore, we examined the role of this signal in the activation, proliferation, and secretion of effector cytokines by Th1, Th2, Th17, and CD8 effector T cells. Overall, NAADP exhibited a similar profile in mediating Ca(2+) release in effector T cells as in their counterpart naive T cells and seemed to be equally important for the function of these different subsets of effector T cells. This profile was not observed for natural T regulatory cells. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Interleukin-7 induces HIV replication in primary naive T cells through a nuclear factor of activated T cell (NFAT)-dependent pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Managlia, Elizabeth Z.; Landay, Alan; Al-Harthi, Lena

2006-07-05

Interleukin (IL)-7 plays several roles critical to T cell maturation, survival, and homeostasis. Because of these functions, IL-7 is under investigation as an immune-modulator for therapeutic use in lymphopenic clinical conditions, including HIV. We reported that naive T cells, typically not permissive to HIV, can be productively infected when pre-treated with IL-7. We evaluated the mechanism by which IL-7-mediates this effect. IL-7 potently up-regulated the transcriptional factor NFAT, but had no effect on NF{kappa}B. Blocking NFAT activity using a number of reagents, such as Cyclosporin A, FK-506, or the NFAT-specific inhibitor known as VIVIT peptide, all markedly reduced IL-7-mediated inductionmore » of HIV replication in naive T cells. Additional neutralization of cytokines present in IL-7-treated cultures and/or those that have NFAT-binding sequences within their promotors indicated that IL-10, IL-4, and most significantly IFN{gamma}, all contribute to IL-7-induction of HIV productive replication in naive T cells. These data clarify the mechanism by which IL-7 can overcome the block to HIV productive infection in naive T cells, despite their quiescent cell status. These findings are relevant to the treatment of HIV disease and understanding HIV pathogenesis in the naive CD4+ T cell compartment, especially in light of the vigorous pursuit of IL-7 as an in vivo immune modulator.« less

Clinical and Mucosal Immune Correlates of HIV-1 Semen Levels in Antiretroviral-Naive Men

PubMed Central

Marsh, Angie K.; Huibner, Sanja; Shahabi, Kamnoosh; Liu, Cindy; Contente, Tania; Nagelkerke, Nico J. D.; Kovacs, Colin; Benko, Erika; Price, Lance; MacDonald, Kelly S.; Kaul, Rupert

2017-01-01

Abstract Background. This study was done to characterize parameters associated with semen human immunodeficiency virus (HIV)-1 ribonucleic acid (RNA) viral load (VL) variability in HIV-infected, therapy-naive men. Methods. Paired blood and semen samples were collected from 30 HIV-infected, therapy-naive men who have sex with men, and 13 participants were observed longitudinally for up to 1 year. Human immunodeficiency virus RNA, bacterial load by 16S RNA, herpesvirus (Epstein-Barr virus and cytomegalovirus [CMV]) shedding, and semen cytokines/chemokines were quantified, and semen T-cell subsets were assessed by multiparameter flow cytometry. Results. Semen HIV RNA was detected at 93% of visits, with >50% of men shedding high levels of virus (defined as >5000 copies/mL). In the baseline cross-sectional analysis, an increased semen HIV VL correlated with local CMV reactivation, the semen bacterial load, and semen inflammatory cytokines, particularly interleukin (IL)-8. T cells in semen were more activated than blood, and there was an increased frequency of Th17 cells and γδ-T-cells. Subsequent prospective analysis demonstrated striking interindividual variability in HIV and CMV shedding patterns, and only semen IL-8 levels and the blood VL were independently associated with semen HIV levels. Conclusions. Several clinical and immune parameters were associated with increased HIV semen levels in antiretroviral therapy-naive men, with induction of local proinflammatory cytokines potentially acting as a common pathway. PMID:28534034

Benefits of Docosahexaenoic Acid, Folic Acid, Vitamin D and Iodine on Foetal and Infant Brain Development and Function Following Maternal Supplementation during Pregnancy and Lactation

PubMed Central

Morse, Nancy L.

2012-01-01

Scientific literature is increasingly reporting on dietary deficiencies in many populations of some nutrients critical for foetal and infant brain development and function. Purpose: To highlight the potential benefits of maternal supplementation with docosahexaenoic acid (DHA) and other important complimentary nutrients, including vitamin D, folic acid and iodine during pregnancy and/or breast feeding for foetal and/or infant brain development and/or function. Methods: English language systematic reviews, meta-analyses, randomised controlled trials, cohort studies, cross-sectional and case-control studies were obtained through searches on MEDLINE and the Cochrane Register of Controlled Trials from January 2000 through to February 2012 and reference lists of retrieved articles. Reports were selected if they included benefits and harms of maternal supplementation of DHA, vitamin D, folic acid or iodine supplementation during pregnancy and/or lactation. Results: Maternal DHA intake during pregnancy and/or lactation can prolong high risk pregnancies, increase birth weight, head circumference and birth length, and can enhance visual acuity, hand and eye co-ordination, attention, problem solving and information processing. Vitamin D helps maintain pregnancy and promotes normal skeletal and brain development. Folic acid is necessary for normal foetal spine, brain and skull development. Iodine is essential for thyroid hormone production necessary for normal brain and nervous system development during gestation that impacts childhood function. Conclusion: Maternal supplementation within recommended safe intakes in populations with dietary deficiencies may prevent many brain and central nervous system malfunctions and even enhance brain development and function in their offspring. PMID:22852064

Brentuximab vedotin (SGN-35) in patients with transplant-naive relapsed/refractory Hodgkin lymphoma.

PubMed

Sasse, Stephanie; Rothe, Achim; Goergen, Helen; Eichenauer, Dennis A; Lohri, Andreas; Kreher, Stephan; Jäger, Ulrich; Bangard, Christopher; Kuhnert, Georg; Böll, Boris; von Tresckow, Bastian; Engert, Andreas

2013-10-01

Only limited data are available on the role of brentuximab vedotin (SGN-35) in transplant-naive relapsed or refractory patients with Hodgkin lymphoma (HL). We thus retrospectively analyzed 14 patients with primary refractory or relapsed HL who were treated with brentuximab vedotin as single agent in a named patient program, who had not received prior high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT) due to refractory disease (n = 9), comorbidity (n = 4) and unknown reasons (n = 1). Brentuximab vedotin resulted in an overall response rate of 71% (10/14) with five complete responses (CRs). Five of those patients with refractory disease and four patients with relevant comorbidity responded. Consolidating ASCT (n = 4) or allogeneic SCT (n = 1) was performed in five patients. Median progression-free survival (PFS) was 9 months and the median overall survival (OS) was not reached. These data indicate the therapeutic efficacy of brentuximab vedotin in chemotherapy-refractory transplant-naive patients with HL.

Le syndrome d’alcoolisme foetal

PubMed Central

2002-01-01

L’alcool est un tératogène physique et comportemental. Le syndrome d’alcoolisme foetal (SAF) est un trouble courant mais encore sous-diagnostiqué découlant de la consommation d’alcool par la mère pendant la grossesse. Bien qu’il puisse être prévenu, le SAF est également invalidant. Même si le SAF est présent dans tous les groupes socioéconomiques du Canada, sa prévalence est élevée dans certaines communautés inuites et des Premières nations du Canada. Le présent énoncé porte sur la prévention, le diagnostic, le dépistage précoce et la prise en charge du SAF par les professionnels de la santé. La prévention du SAF doit s’effectuer à deux échelons. La prévention primaire consiste à éliminer le SAF par une formation en classe ou dans la collectivité et à inciter les femmes à éviter de consommer de l’alcool avant la conception et pendant la grossesse. La prévention secondaire consiste à repérer les femmes qui boivent pendant leur grossesse et à réduire leur consommation. Le présent énoncé décrit plusieurs stratégies de dépistage, dont la stratégie T-ACE (tolérance-agacement, réduction, éveil). Les dispensateurs de soins devraient recommander l’abstinence dès la première visite prénatale. Un envoi rapide en consultation en vue de traiter l’alcoolisme est recommandé pour les femmes enceintes incapables d’arrêter de boire. Le présent énoncé décrit le diagnostic de SAF, de SAF partiel ou atypique, d’anomalies congénitales et de troubles neurodéveloppementaux reliés à l’alcool. En cas d’exposition à l’alcool in utero, un diagnostic de SAF devrait être envisagé en présence d’un retard de croissance courant ou antérieur, de certaines anomalies faciales touchant la lèvre supérieure et les yeux et d’anomalies neurodéveloppementales. Ces caractéristiques sont mieux quantifiées au moyen d’une méthode diagnostique à quatre chiffres. Des stratégies de dépistage précoce des

Genetic characterization and antiretroviral resistance mutations among treatment-naive HIV-infected individuals in Jiaxing, China.

PubMed

Guo, Jinlei; Yan, Yong; Zhang, Jiafeng; Ji, Jimei; Ge, Zhijian; Ge, Rui; Zhang, Xiaofei; Wang, Henghui; Chen, Zhongwen; Luo, Jianyong

2017-03-14

The aim of this study was to characterize HIV-1 genotypes and antiretroviral resistance mutations among treatment-naive HIV-infected individuals in Jiaxing, China. The HIV-1 partial polymerase (pol) genes in 93 of the 99 plasma samples were successfully amplified and analyzed. Phylogenetic analysis revealed the existence of five HIV-1 genotypes, of which the most prevalent genotype was CRF01_AE (38.7%), followed by CRF07_BC (34.4%), CRF08_BC (16.1%), subtype B/B' (5.4%), and CRF55_01B (2.1%). Besides, three types of unique recombination forms (URFs) were also observed, including C/F2/A1, CRF01_AE/B, and CRF08_BC/CRF07_BC. Among 93 amplicons, 46.2% had drug resistance-associated mutations, including 23.7% for protease inhibitors (PIs) mutations, 1.1% for nucleoside reverse transcriptase inhibitors (NRTIs) mutations, and 20.4% for non-nucleoside reverse transcriptase inhibitors (NNRTIs) mutations. Six (6.5%) out of 93 treatment-naive subjects were identified to be resistant to one or more NNRTIs, while resistance to NRTIs or PIs was not observed. Our study showed the genetic diversity of HIV-1 strains circulating in Jiaxing and a relative high proportion of antiretroviral resistance mutations among treatment-naive patients, indicating a serious challenge for HIV prevention and treatment program.

A Combined Omics Approach to Generate the Surface Atlas of Human Naive CD4+ T Cells during Early T-Cell Receptor Activation*

PubMed Central

Graessel, Anke; Hauck, Stefanie M.; von Toerne, Christine; Kloppmann, Edda; Goldberg, Tatyana; Koppensteiner, Herwig; Schindler, Michael; Knapp, Bettina; Krause, Linda; Dietz, Katharina; Schmidt-Weber, Carsten B.; Suttner, Kathrin

2015-01-01

Naive CD4+ T cells are the common precursors of multiple effector and memory T-cell subsets and possess a high plasticity in terms of differentiation potential. This stem-cell-like character is important for cell therapies aiming at regeneration of specific immunity. Cell surface proteins are crucial for recognition and response to signals mediated by other cells or environmental changes. Knowledge of cell surface proteins of human naive CD4+ T cells and their changes during the early phase of T-cell activation is urgently needed for a guided differentiation of naive T cells and may support the selection of pluripotent cells for cell therapy. Periodate oxidation and aniline-catalyzed oxime ligation technology was applied with subsequent quantitative liquid chromatography-tandem MS to generate a data set describing the surface proteome of primary human naive CD4+ T cells and to monitor dynamic changes during the early phase of activation. This led to the identification of 173 N-glycosylated surface proteins. To independently confirm the proteomic data set and to analyze the cell surface by an alternative technique a systematic phenotypic expression analysis of surface antigens via flow cytometry was performed. This screening expanded the previous data set, resulting in 229 surface proteins, which were expressed on naive unstimulated and activated CD4+ T cells. Furthermore, we generated a surface expression atlas based on transcriptome data, experimental annotation, and predicted subcellular localization, and correlated the proteomics result with this transcriptional data set. This extensive surface atlas provides an overall naive CD4+ T cell surface resource and will enable future studies aiming at a deeper understanding of mechanisms of T-cell biology allowing the identification of novel immune targets usable for the development of therapeutic treatments. PMID:25991687

Maternal-foetal attachment independently predicts the quality of maternal-infant bonding and post-partum psychopathology.

PubMed

Petri, Eleonora; Palagini, Laura; Bacci, Olivia; Borri, Chiara; Teristi, Valentina; Corezzi, Camilla; Faraoni, Sara; Antonelli, Paolo; Cargioli, Claudio; Banti, Susanna; Perugi, Giulio; Mauri, Mauro

2017-08-21

The aim of this study was to evaluate the association of maternal antenatal attachment and post-partum psychopathology, maternal-infant bonding, while checking for antenatal psychopathology, for lifetime psychiatric diagnosis and for the known risk factors for peripartum depression. One hundred and six women recruited at the first month of pregnancy (T0) were evaluated with the structured interview for DSM-IV TR (SCID-I) to assess the presence of lifetime psychiatric diagnosis and with the Perinatal Depression Predictor Inventory-Revised (PDPI-R), the Edinburgh Postnatal Depression Scale (EPDS), and the State-Trait Anxiety Inventory (STAI). At the sixth month of pregnancy (T1) and at the first month post-partum (T2), all patients were evaluated with the PDPI-R, the EPDS, the STAI, at T1, with the Maternal Antenatal Attachment Scale (MAAS), and at T2 with the Maternal Postnatal Attachment Scale (MPAS). Multivariate regression analyses showed that maternal-foetal attachment was the variable most significantly associated with postnatal symptoms of depression and anxiety and with quality of maternal-infant attachment. The logistic regression analyses showed that antenatal attachment may predict postnatal depressive and anxiety symptoms (respectively, OR: 0.83 - IC [0.74 - 0.95], p = .005, OR: 0.88 - IC [0.79 - 0.98], p = .02), and the quality of maternal postnatal attachment (OR: 1.17 - IC [1.08 - 1.27], p < .001), also after taking into account the known risk factors for perinatal depression, the sociodemographic variables and lifetime psychiatric diagnosis. The quality of maternal-foetal bonding may independently predict the quality of maternal-infant attachment and post-partum depressive and anxiety symptoms. A comprehensive assessment of maternal risk factors for perinatal psychopathology during pregnancy should include the evaluation of antenatal attachment that could be modifiable by specific interventions promoting the quality of maternal

Cardiac re-entry dynamics and self-termination in DT-MRI based model of Human Foetal Heart

NASA Astrophysics Data System (ADS)

Biktasheva, Irina V.; Anderson, Richard A.; Holden, Arun V.; Pervolaraki, Eleftheria; Wen, Fen Cai

2018-02-01

The effect of human foetal heart geometry and anisotropy on anatomy induced drift and self-termination of cardiac re-entry is studied here in MRI based 2D slice and 3D whole heart computer simulations. Isotropic and anisotropic models of 20 weeks of gestational age human foetal heart obtained from 100μm voxel diffusion tensor MRI data sets were used in the computer simulations. The fiber orientation angles of the heart were obtained from the orientation of the DT-MRI primary eigenvectors. In a spatially homogeneous electrophysiological monodomain model with the DT-MRI based heart geometries, cardiac re-entry was initiated at a prescribed location in a 2D slice, and in the 3D whole heart anatomy models. Excitation was described by simplified FitzHugh-Nagumo kinetics. In a slice of the heart, with propagation velocity twice as fast along the fibres than across the fibers, DT-MRI based fiber anisotropy changes the re-entry dynamics from pinned to an anatomical re-entry. In the 3D whole heart models, the fiber anisotropy changes cardiac re-entry dynamics from a persistent re-entry to the re-entry self-termination. The self-termination time depends on the re-entry’s initial position. In all the simulations with the DT-MRI based cardiac geometry, the anisotropy of the myocardial tissue shortens the time to re-entry self-termination several folds. The numerical simulations depend on the validity of the DT-MRI data set used. The ventricular wall showed the characteristic transmural rotation of the helix angle of the developed mammalian heart, while the fiber orientation in the atria was irregular.

Maternal Geophagy of Calabash Chalk on Foetal Cerebral Cortex Histomorphology.

PubMed

Ekanem, Theresa Bassey; Ekong, Moses Bassey; Eluwa, Mokutima Amarachi; Igiri, Anozeng Oyono; Osim, Eme Efiom

2015-01-01

Calabash chalk, a kaolin-base substance is a common geophagic material mostly consumed by pregnant women. This study investigated its effect on the histomorphology of the foetal cerebral cortex. Twelve gestating Wistar rats were divided equally into groups 1 and 2. On pregnancy day seven (PD7), group 2 animals were administered 200 mg/kg body weight of calabash chalk suspension, while group 1 animals served as the control and received 1 ml of distilled water, by oral gavages and for 14 days (PD7-PD20). On PD21, the dams were sacrificed, and the foetuses removed, examined for gross malformations, weighed and culled to two foetuses per mother. Their whole brains were excised, weighed and preserved using 10% buffered formalin, and routinely processed by haematoxylin and eosin, and Luxol fast blue methods. The foetuses showed no morphological change, but their mean body weights was higher (p=0.0001). Histomorphological sections of the cerebral cortex showed hypertrophy and hyperplasia of cells in all the cortical layers, with less demonstrated Nissl and higher (p=0.001) cellular population compared with the control group. Calabash chalk cause body weight increase and histomorphological changes in the cerebral cortex of foetuses.

Exploring the Autonomous Economic World of Children: A Mixed Methods Study of Kids' Naive Economic Theories Incorporating Ethnographic and Behavioral Economics Methodologies

ERIC Educational Resources Information Center

Jennings, Amanda Brooke

2017-01-01

Children construct meaning from their economic experiences in the form of naive theories and use these theories to explain the relationships between their actions and the outcomes. Inevitably, due to their lack of economic literacy, these theories will be incomplete. Through curriculum design that acknowledges and addresses these naive theories,…

In Vitro Measles Virus Infection of Human Lymphocyte Subsets Demonstrates High Susceptibility and Permissiveness of both Naive and Memory B Cells

PubMed Central

Laksono, Brigitta M.; Grosserichter-Wagener, Christina; de Vries, Rory D.; Langeveld, Simone A. G.; Brem, Maarten D.; van Dongen, Jacques J. M.; Koopmans, Marion P. G.

2018-01-01

ABSTRACT Measles is characterized by a transient immune suppression, leading to an increased risk of opportunistic infections. Measles virus (MV) infection of immune cells is mediated by the cellular receptor CD150, expressed by subsets of lymphocytes, dendritic cells, macrophages, and thymocytes. Previous studies showed that human and nonhuman primate memory T cells express higher levels of CD150 than naive cells and are more susceptible to MV infection. However, limited information is available about the CD150 expression and relative susceptibility to MV infection of B-cell subsets. In this study, we assessed the susceptibility and permissiveness of naive and memory T- and B-cell subsets from human peripheral blood or tonsils to in vitro MV infection. Our study demonstrates that naive and memory B cells express CD150, but at lower frequencies than memory T cells. Nevertheless, both naive and memory B cells proved to be highly permissive to MV infection. Furthermore, we assessed the susceptibility and permissiveness of various functionally distinct T and B cells, such as helper T (TH) cell subsets and IgG- and IgA-positive memory B cells, in peripheral blood and tonsils. We demonstrated that TH1TH17 cells and plasma and germinal center B cells were the subsets most susceptible and permissive to MV infection. Our study suggests that both naive and memory B cells, along with several other antigen-experienced lymphocytes, are important target cells of MV infection. Depletion of these cells potentially contributes to the pathogenesis of measles immune suppression. IMPORTANCE Measles is associated with immune suppression and is often complicated by bacterial pneumonia, otitis media, or gastroenteritis. Measles virus infects antigen-presenting cells and T and B cells, and depletion of these cells may contribute to lymphopenia and immune suppression. Measles has been associated with follicular exhaustion in lymphoid tissues in humans and nonhuman primates, emphasizing

Improving external cephalic version for foetal breech presentation.

PubMed

Zandstra, H; Mertens, H J M M

2013-01-01

If success rate of external cephalic version (ECV) increases, the rate of primary caesarean sections -declines. The aims of this retrospective cohort study were to evaluate the ECV and to identify factors associated with the success rate of ECV for breech presentation at term. The second aim of this study was to analyse the outcome of labour of all patients with a foetus in breech near term. All women with a foetus in breech near or at term were included. Logistic regression analyses were -performed to identify the association between patient characteristics and success rate of ECV. The overall rate of successful ECV's was 19%. Foetal and maternal complications after ECV were negligible. BMI, type of breech and amount of amniotic fluid were significantly correlated with a successful ECV. The rate of primary caesarean sections for the group of patients who underwent an ECV was lower than the rate in the group who did not (52.9% vs. 79.6%). The rate of spontaneous deliveries was increased after ECV (36% versus 12%). After successful ECV the rate of spontaneous deliveries was 75%; after unsuccessful ECV 26.8%. The overall rate of successful ECV was low (19%). BMI, type of breech and amount of amniotic fluid were significantly correlated with a successful ECV. The rate of primary caesarean sections was significantly lower in patients with ECV (52.9% versus 79.6%). The rate of spontaneous deliveries was significantly higher (36% -versus 12%).

Achieving ventricular rate control using metoprolol in β-blocker-naive patients vs patients on chronic β-blocker therapy.

PubMed

Kuang, Patricia; Mah, Nathan D; Barton, Cassie A; Miura, Andrea J; Tanas, Laura R; Ran, Ran

2016-03-01

The objective of the study is to evaluate the difference in ventricular rate control using an intravenous (IV) metoprolol regimen commonly used in clinical practice in patients receiving chronic β-blocker therapy compared to patients considered β-blocker naive admitted to the emergency department (ED) for atrial fibrillation (AF) with rapid ventricular rate. A single-center retrospective cohort study of adult ED patients who were admitted with a rapid ventricular rate of 120 beats per minute (bpm) or greater and treated with IV metoprolol was performed. Rate control was defined as either a decrease in ventricular rate to less than 100 bpm or a 20% decrease in heart rate to less than 120 bpm after metoprolol administration. Patient demographics, differences in length of stay, and adverse events were recorded. A total of 398 patients were included in the study, with 79.4% (n=316) receiving chronic β-blocker therapy. Patients considered to be β-blocker naive were more likely to achieve successful rate control with IV metoprolol compared to patients on chronic β-blocker therapy (56.1% vs 42.4%; P=.03). β-Blocker-naive status was associated with a shorter length of stay in comparison to patients receiving chronic β-blocker therapy (1.79 vs 2.64 days; P<.01). Intravenous metoprolol for the treatment of atrial fibrillation with rapid ventricular rate was associated with a higher treatment response in patients considered β-blocker naive compared to patients receiving chronic β-blocker therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Foetal Alcohol Spectrum Disorders: A consideration of sentencing and unreliable confessions.

PubMed

Douglas, Heather

2015-12-01

While Foetal Alcohol Spectrum Disorders (FASDs) are now a strong focus of policy-makers throughout Australia, they have received strikingly little consideration in Australian criminal courts. Many people who have an FASD are highly suggestible, have difficulty linking their actions to consequences, controlling impulses and remembering things, and thus FASD raises particular issues for appropriate sentencing and the admissibility of evidence. This article considers the approach of Australian criminal courts to FASD. It reviews the recent case of AH v Western Australia which exemplifies the difficulties associated with appropriate sentencing in cases where the accused is likely to have an FASD. The article also considers the implications for Australian courts of the New Zealand case of Pora v The Queen, recently heard by the Privy Council. In this case, the Privy Council accepted expert evidence that people with FASD may confabulate evidence, potentially making their testimony unreliable. The article concludes with an overview of developments in criminal policy and legal response in relation to FASD in the United States, Canada and Australia.

Anterior Cingulate Volumetric Alterations in Treatment-Naive Adults with ADHD: A Pilot Study

ERIC Educational Resources Information Center

Makris, Nikos; Seidman, Larry J.; Valera, Eve M.; Biederman, Joseph; Monuteaux, Michael C.; Kennedy, David N.; Caviness, Verne S., Jr.; Bush, George; Crum, Katherine; Brown, Ariel B.; Faraone, Stephen V.

2010-01-01

Objective: We sought to examine preliminary results of brain alterations in anterior cingulate cortex (ACC) in treatment-naive adults with ADHD. The ACC is a central brain node for the integration of cognitive control and allocation of attention, affect and drive. Thus its anatomical alteration may give rise to impulsivity, hyperactivity and…

KLF4 Nuclear Export Requires ERK Activation and Initiates Exit from Naive Pluripotency.

PubMed

Dhaliwal, Navroop K; Miri, Kamelia; Davidson, Scott; Tamim El Jarkass, Hala; Mitchell, Jennifer A

2018-04-10

Cooperative action of a transcription factor complex containing OCT4, SOX2, NANOG, and KLF4 maintains the naive pluripotent state; however, less is known about the mechanisms that disrupt this complex, initiating exit from pluripotency. We show that, as embryonic stem cells (ESCs) exit pluripotency, KLF4 protein is exported from the nucleus causing rapid decline in Nanog and Klf4 transcription; as a result, KLF4 is the first pluripotency transcription factor removed from transcription-associated complexes during differentiation. KLF4 nuclear export requires ERK activation, and phosphorylation of KLF4 by ERK initiates interaction of KLF4 with nuclear export factor XPO1, leading to KLF4 export. Mutation of the ERK phosphorylation site in KLF4 (S132) blocks KLF4 nuclear export, the decline in Nanog, Klf4, and Sox2 mRNA, and differentiation. These findings demonstrate that relocalization of KLF4 to the cytoplasm is a critical first step in exit from the naive pluripotent state and initiation of ESC differentiation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Prevalence of Dyslipidemia Among Antiretroviral-Naive HIV-Infected Individuals in China

PubMed Central

Shen, Yinzhong; Wang, Jiangrong; Wang, Zhenyan; Qi, Tangkai; Song, Wei; Tang, Yang; Liu, Li; Zhang, Renfang; Lu, Hongzhou

2015-01-01

Abstract Little is known about the epidemiological features of dyslipidemia among antiretroviral-naive HIV-infected individuals in China. We used a cross-sectional study design to estimate the prevalence of dyslipidemia in this population, and to identify risk factors associated with the presence of dyslipidemia. One thousand five hundred and eighteen antiretroviral-naive HIV-infected individuals and 347 HIV-negative subjects in China were enrolled during 2009 to 2010. Demographics and medical histories were recorded. After an overnight fast, serum samples were collected to measure lipid levels. Factors associated with the presence of dyslipidemia were analyzed by logistic regression. Mean total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL) levels were lower in HIV-positive than HIV-negative subjects, but mean triglyceride (TG) was higher in HIV-positive subjects. The overall prevalence of dyslipidemia in HIV-positive and HIV-negative groups did not differ (75.6% vs. 73.7%, P = 0.580). However, the prevalence of high TC (8.4% vs. 28.2%, P < 0.001) and high LDL (8.5% vs. 62.6%, P < 0.001) was lower in HIV-positive than HIV-negative subjects, and the prevalence of high TG (33.9% vs. 17.0%, P < 0.001) and low HDL (59.6% vs. 11.2%, P < 0.001) was higher in HIV-positive than HIV-negative subjects. Logistic analysis showed that HIV positivity was significantly associated with both an increased risk of high TG and low HDL and a decreased risk of high TC and high LDL. The mean levels of TC, of LDL and of HDL showed an increasing trend with increasing CD4 count in HIV-positive subjects. Multivariable logistic regression found that lower CD4 count was significantly associated with both an increased risk of high TG and low HDL and a decreased risk of high TC in HIV-positive subjects. Among antiretroviral-naive HIV-infected Chinese adults, there was a high prevalence of dyslipidemia characterized by

Naive Bayes as opinion classifier to evaluate students satisfaction based on student sentiment in Twitter Social Media

NASA Astrophysics Data System (ADS)

Candra Permana, Fahmi; Rosmansyah, Yusep; Setiawan Abdullah, Atje

2017-10-01

Students activity on social media can provide implicit knowledge and new perspectives for an educational system. Sentiment analysis is a part of text mining that can help to analyze and classify the opinion data. This research uses text mining and naive Bayes method as opinion classifier, to be used as an alternative methods in the process of evaluating studentss satisfaction for educational institution. Based on test results, this system can determine the opinion classification in Bahasa Indonesia using naive Bayes as opinion classifier with accuracy level of 84% correct, and the comparison between the existing system and the proposed system to evaluate students satisfaction in learning process, there is only a difference of 16.49%.

The impact of delayed maternity on foetal growth in Spain: An assessment by population attributable fraction.

PubMed

Varea, Carlos; Terán, José Manuel; Bernis, Cristina; Bogin, Barry

2017-09-18

Delayed childbearing is considered a risk factor for maternal-foetal health. As in other higher-income countries, in Spain age at maternity has steadily increased during the last two decades. To quantify the impact of the delay in the age at maternity on small for gestational age (SGA) categories of <3rd, 3rd-5th and 5th-10th percentiles. 2,672,350 singleton live births born to Spanish mothers in 2007-2015 were analysed. Adjusted relative risk was calculated to estimate the adjusted partial population attributable fractions (PAF p ) for mothers aged 35-39 and ≥40 years for each category of SGA considering the interaction between age at maternity and parity. Primipara 35-39 years old mothers have the highest PAF p in the three categories of SGA, with the maximum value for SGA <3rd percentile (2.57%, 95% CI 2.25, 2.88). PAF p for both primipara and multipara ≥40 years old mothers were less than 1%. PAF p for primipara older mothers increased significantly in 2007-2015 for the three categories of SGA, more clearly among those aged 35-39 years. The contribution of multipara mothers of both age groups did not increase significantly during the period. Delayed maternity is a significant adjusted risk factor for SGA, contributing to the increase of its prevalence. However, results also suggest a limited clinical impact of delayed maternity on foetal growth. Positive changes in maternal profile associated with the shift in maternal age might contribute to explain the limited impact of mothers aged 35 years and older on negative birth outcome in Spain. Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

In Vitro Measles Virus Infection of Human Lymphocyte Subsets Demonstrates High Susceptibility and Permissiveness of both Naive and Memory B Cells.

PubMed

Laksono, Brigitta M; Grosserichter-Wagener, Christina; de Vries, Rory D; Langeveld, Simone A G; Brem, Maarten D; van Dongen, Jacques J M; Katsikis, Peter D; Koopmans, Marion P G; van Zelm, Menno C; de Swart, Rik L

2018-04-15

Measles is characterized by a transient immune suppression, leading to an increased risk of opportunistic infections. Measles virus (MV) infection of immune cells is mediated by the cellular receptor CD150, expressed by subsets of lymphocytes, dendritic cells, macrophages, and thymocytes. Previous studies showed that human and nonhuman primate memory T cells express higher levels of CD150 than naive cells and are more susceptible to MV infection. However, limited information is available about the CD150 expression and relative susceptibility to MV infection of B-cell subsets. In this study, we assessed the susceptibility and permissiveness of naive and memory T- and B-cell subsets from human peripheral blood or tonsils to in vitro MV infection. Our study demonstrates that naive and memory B cells express CD150, but at lower frequencies than memory T cells. Nevertheless, both naive and memory B cells proved to be highly permissive to MV infection. Furthermore, we assessed the susceptibility and permissiveness of various functionally distinct T and B cells, such as helper T (T H ) cell subsets and IgG- and IgA-positive memory B cells, in peripheral blood and tonsils. We demonstrated that T H 1T H 17 cells and plasma and germinal center B cells were the subsets most susceptible and permissive to MV infection. Our study suggests that both naive and memory B cells, along with several other antigen-experienced lymphocytes, are important target cells of MV infection. Depletion of these cells potentially contributes to the pathogenesis of measles immune suppression. IMPORTANCE Measles is associated with immune suppression and is often complicated by bacterial pneumonia, otitis media, or gastroenteritis. Measles virus infects antigen-presenting cells and T and B cells, and depletion of these cells may contribute to lymphopenia and immune suppression. Measles has been associated with follicular exhaustion in lymphoid tissues in humans and nonhuman primates, emphasizing the

Atypical enteropathogenic Escherichia coli that contains functional locus of enterocyte effacement genes can be attaching-and-effacing negative in cultured epithelial cells.

PubMed

Rocha, Sérgio P D; Abe, Cecilia M; Sperandio, Vanessa; Bando, Silvia Y; Elias, Waldir P

2011-05-01

Enteropathogenic Escherichia coli (EPEC) induces a characteristic histopathology on enterocytes known as the attaching-and-effacing (A/E) lesion, which is triggered by proteins encoded by the locus of enterocyte effacement (LEE). EPEC is currently classified as typical EPEC (tEPEC) and atypical EPEC (aEPEC), based on the presence or absence of the EPEC adherence factor plasmid, respectively. Here we analyzed the LEE regions of three aEPEC strains displaying the localized adherence-like (LAL), aggregative adherence (AA), and diffuse adherence (DA) patterns on HEp-2 cells as well as one nonadherent (NA) strain. The adherence characteristics and the ability to induce A/E lesions were investigated with HeLa, Caco-2, T84, and HT29 cells. The adherence patterns and fluorescent actin staining (FAS) assay results were reproducible with all cell lines. The LEE region was structurally intact and functional in all strains regardless of their inability to cause A/E lesions. An EspF(U)-expressing plasmid (pKC471) was introduced into all strains, demonstrating no influence of this protein on either the adherence patterns or the capacity to cause A/E of the adherent strains. However, the NA strain harboring pKC471 expressed the LAL pattern and was able to induce A/E lesions on HeLa cells. Our data indicate that FAS-negative aEPEC strains are potentially able to induce A/E in vivo, emphasizing the concern about this test for the determination of aEPEC virulence. Also, the presence of EspF(U) was sufficient to provide an adherent phenotype for a nonadherent aEPEC strain via the direct or indirect activation of the LEE4 and LEE5 operons.

Foetal exposure to maternal stressful events increases the risk of having asthma and atopic diseases in childhood.

PubMed

de Marco, Roberto; Pesce, Giancarlo; Girardi, Paolo; Marchetti, Pierpaolo; Rava, Marta; Ricci, Paolo; Marcon, Alessandro

2012-12-01

The natural history of asthma and atopic diseases begins in utero. Studies investigating the influence of foetal exposure to maternal stressful life events during pregnancy (SLEP) on asthma and atopic diseases are lacking. To test whether the children of mothers who had experienced SLEP are at an increased risk for asthma, atopic eczema and allergic rhinitis. The association between maternal SLEP (at least one among: divorce, mourning or loss of the job) and the occurrence of asthma and atopic diseases in childhood was studied in a population (n = 3854) of children, aged 3-14 yrs, living in Northern Italy. The parents filled in a standardized questionnaire about the children's health and the events occurred to their mothers during pregnancy. Three hundred and thirty-three (9%) of the mothers experienced SLEP. Their children had a statistically significantly higher lifetime prevalence of wheezing (31.6% vs. 23.1%), asthma (8.9% vs. 5.6%), allergic rhinitis (10.9% vs. 7.3%) and atopic eczema (29.7% vs. 21.1%) than those of mothers without SLEP. After adjusting for potential confounders, the foetal exposure to SLEP was positively associated with wheezing (OR: 1.41, 95% CI: 1.03-1.94), asthma (OR: 1.71, 95% CI: 1.02-2.89), allergic rhinitis (OR: 1.75, 95% CI: 1.08-2.84) and atopic eczema (OR: 1.53, 95% CI: 1.11-2.10). The children of mothers who had experienced SLEP were at a moderately increased risk of having wheezing, asthma, eczema and allergic rhinitis during their childhood. Maternal stress during pregnancy might enhance the expression of asthma and atopic phenotypes in children. © 2012 John Wiley & Sons A/S.

Assessment of foetal wellbeing in pregnant women subjected to pelvic floor muscle training: a controlled randomised study.

PubMed

Okido, Marcos Massaru; Valeri, Fabiana Lellis; Martins, Wellington Paula; Ferreira, Cristine Homsi Jorge; Duarte, Geraldo; Cavalli, Ricardo Carvalho

2015-10-01

The objective was to assess foetal wellbeing in pregnant women subjected to pelvic floor muscle training (PFMT) by evaluating the acute and chronic effects of the procedure using the Doppler method. Ninety-six primigravidae with singleton pregnancies and at a low risk of pregnancy complications were randomised to either intervention with PFMT or no intervention. The final analysis included 26 women in the intervention group and 33 in the control group. Women from the intervention group were subjected to a daily PFMT program. Evidence of possible foetal risk was assessed by Doppler and the control group received standard care. The protocol was conducted from 20 to 36 weeks' gestation. The pulsatility indices (PI) of the uterine, umbilical and middle cerebral arteries were determined at 28, 32 and 36 weeks' gestation. The acute effects were determined by comparing the values obtained before and after exercise in the group subjected to PFMT and the chronic effects were determined by comparing the resting values of the trained group with those of the control group. The results obtained showed normal values for the three gestational ages in both groups, with no difference between groups. Comparison before and after exercise showed a significant decline in the PI of uterine artery at 36 weeks without changes in the flow of umbilical and middle cerebral arteries. Pelvic floor muscle training in low-risk primigravidae with singleton pregnancies was associated with a significant decline in PI of the uterine artery after exercise, while no significant changes in the flow of the middle cerebral and umbilical arteries were found. The PFMT may be recommended to women as a first-line measure to prevent of urinary incontinence during pregnancy.

Maraviroc: perspectives for use in antiretroviral-naive HIV-1-infected patients.

PubMed

Vandekerckhove, Linos; Verhofstede, Chris; Vogelaers, Dirk

2009-06-01

Maraviroc (Pfizer's UK-427857, Selzentry or Celsentri outside the USA) is the first agent in the new class of oral HIV-1 entry inhibitors to acquire approval by the US Food and Drug Administration and the European Medicine Agency. Considering the mechanism of action, it is expected that this drug will be effective only in a subpopulation of HIV-1-infected people, namely those harbouring the R5 virus. The favourable toxicity profile of the drug has been demonstrated in Phase III clinical trials in treatment-naive (MERIT) and treatment-experienced (MOTIVATE) patients. In the latter population, maraviroc showed a superior antiviral efficacy and immunological activity compared with optimized backbone therapy + placebo. However, in MERIT, a prospective double-blind, randomized trial in treatment-naive patients, maraviroc + zidovudine/lamivudine failed to prove non-inferiority to efavirenz + zidovudine/lamivudine as standard of care regimen in the 48 week intention-to-treat analysis. Using an assay with higher sensitivity for minority CXCR4-using (X4) HIV variants (the enhanced Trofile assay-Monogram), non-inferiority was reached for the maraviroc- versus efavirenz-based combination. These data indicate the important impact of the sensitivity of tropism testing on treatment outcome of maraviroc-containing regimens. This paper discusses both the prospective and retrospective analyses of the MERIT data and highlights the impact of these results on daily practice in HIV care.

Improving external cephalic version for foetal breech presentation

PubMed Central

Zandstra, H.; Mertens, H.J.M.M.

2013-01-01

Objectives: If success rate of external cephalic version (ECV) increases, the rate of primary caesarean sections declines. The aims of this retrospective cohort study were to evaluate the ECV and to identify factors associated with the success rate of ECV for breech presentation at term. The second aim of this study was to analyse the outcome of labour of all patients with a foetus in breech near term. Methods: All women with a foetus in breech near or at term were included. Logistic regression analyses were performed to identify the association between patient characteristics and success rate of ECV. Results: The overall rate of successful ECV’s was 19%. Foetal and maternal complications after ECV were negligible. BMI, type of breech and amount of amniotic fluid were significantly correlated with a successful ECV. The rate of primary caesarean sections for the group of patients who underwent an ECV was lower than the rate in the group who did not (52.9% vs. 79.6%). The rate of spontaneous deliveries was increased after ECV (36% versus 12%). After successful ECV the rate of spontaneous deliveries was 75%; after unsuccessful ECV 26.8%. Conclusion: The overall rate of successful ECV was low (19%). BMI, type of breech and amount of amniotic fluid were significantly correlated with a successful ECV. The rate of primary caesarean sections was significantly lower in patients with ECV (52.9% versus 79.6%). The rate of spontaneous deliveries was significantly higher (36% versus 12%). PMID:24753933

Deficiency in DNA damage response of enterocytes accelerates intestinal stem cell aging in Drosophila.

PubMed

Park, Joung-Sun; Jeon, Ho-Jun; Pyo, Jung-Hoon; Kim, Young-Shin; Yoo, Mi-Ae

2018-03-07

Stem cell dysfunction is closely linked to tissue and organismal aging and age-related diseases, and heavily influenced by the niche cells' environment. The DNA damage response (DDR) is a key pathway for tissue degeneration and organismal aging; however, the precise protective role of DDR in stem cell/niche aging is unclear. The Drosophila midgut is an excellent model to study the biology of stem cell/niche aging because of its easy genetic manipulation and its short lifespan. Here, we showed that deficiency of DDR in Drosophila enterocytes (ECs) accelerates intestinal stem cell (ISC) aging. We generated flies with knockdown of Mre11 , Rad50 , Nbs1 , ATM , ATR , Chk1 , and Chk2 , which decrease the DDR system in ECs. EC-specific DDR depletion induced EC death, accelerated the aging of ISCs, as evidenced by ISC hyperproliferation, DNA damage accumulation, and increased centrosome amplification, and affected the adult fly's survival. Our data indicated a distinct effect of DDR depletion in stem or niche cells on tissue-resident stem cell proliferation. Our findings provide evidence of the essential role of DDR in protecting EC against ISC aging, thus providing a better understanding of the molecular mechanisms of stem cell/niche aging.

Postsurgical prescriptions for opioid naive patients and association with overdose and misuse: retrospective cohort study

PubMed Central

Agniel, Denis; Beam, Andrew; Yorkgitis, Brian; Bicket, Mark; Homer, Mark; Fox, Kathe P; Knecht, Daniel B; McMahill-Walraven, Cheryl N; Palmer, Nathan; Kohane, Isaac

2018-01-01

Abstract Objective To quantify the effects of varying opioid prescribing patterns after surgery on dependence, overdose, or abuse in an opioid naive population. Design Retrospective cohort study. Setting Surgical claims from a linked medical and pharmacy administrative database of 37 651 619 commercially insured patients between 2008 and 2016. Participants 1 015 116 opioid naive patients undergoing surgery. Main outcome measures Use of oral opioids after discharge as defined by refills and total dosage and duration of use. The primary outcome was a composite of misuse identified by a diagnostic code for opioid dependence, abuse, or overdose. Results 568 612 (56.0%) patients received postoperative opioids, and a code for abuse was identified for 5906 patients (0.6%, 183 per 100 000 person years). Total duration of opioid use was the strongest predictor of misuse, with each refill and additional week of opioid use associated with an adjusted increase in the rate of misuse of 44.0% (95% confidence interval 40.8% to 47.2%, P<0.001), and 19.9% increase in hazard (18.5% to 21.4%, P<0.001), respectively. Conclusions Each refill and week of opioid prescription is associated with a large increase in opioid misuse among opioid naive patients. The data from this study suggest that duration of the prescription rather than dosage is more strongly associated with ultimate misuse in the early postsurgical period. The analysis quantifies the association of prescribing choices on opioid misuse and identifies levers for possible impact. PMID:29343479

Virological Failure and HIV-1 Drug Resistance Mutations among Naive and Antiretroviral Pre-Treated Patients Entering the ESTHER Program of Calmette Hospital in Cambodia

PubMed Central

Limsreng, Setha; Him, Sovanvatey; Nouhin, Janin; Hak, Chanroeurn; Srun, Chanvatey; Viretto, Gerald; Ouk, Vara; Delfraissy, Jean Francois; Ségéral, Olivier

2014-01-01

Introduction In resource limited settings, patients entering an antiretroviral therapy (ART) program comprise ART naive and ART pre-treated patients who may show differential virological outcomes. Methods This retrospective study, conducted in 2010–2012 in the HIV clinic of Calmette Hospital located in Phnom Penh (Cambodia) assessed virological failure (VF) rates and patterns of drug resistance of naive and pre-treated patients. Naive and ART pre-treated patients were included when a Viral Load (VL) was performed during the first year of ART for naive subjects or at the first consultation for pre-treated individuals. Patients showing Virological failure (VF) (>1,000 copies/ml) underwent HIV DR genotyping testing. Interpretation of drug resistance mutations was done according to 2013 version 23 ANRS algorithms. Results On a total of 209 patients, 164 (78.4%) were naive and 45 (21.5%) were ART pre-treated. Their median initial CD4 counts were 74 cells/mm3 (IQR: 30–194) and 279 cells/mm3 (IQR: 103–455) (p<0.001), respectively. Twenty seven patients (12.9%) exhibited VF (95% CI: 8.6–18.2%), including 10 naive (10/164, 6.0%) and 17 pre-treated (17/45, 37.8%) patients (p<0.001). Among these viremic patients, twenty-two (81.4%) were sequenced in reverse transcriptase and protease coding regions. Overall, 19 (86.3%) harbored ≥1 drug resistance mutations (DRMs) whereas 3 (all belonging to pre-treated patients) harbored wild-types viruses. The most frequent DRMs were M184V (86.3%), K103N (45.5%) and thymidine analog mutations (TAMs) (40.9%). Two (13.3%) pre-treated patients harbored viruses that showed a multi-nucleos(t)ide resistance including Q151M, K65R, E33A/D, E44A/D mutations. Conclusion In Cambodia, VF rates were low for naive patients but the emergence of DRMs to NNRTI and 3TC occurred relatively quickly in this subgroup. In pre-treated patients, VF rates were much higher and TAMs were relatively common. HIV genotypic assays before ART initiation and for

Induction of cross-priming of naive CD8+ T lymphocytes by recombinant bacillus Calmette-Guerin that secretes heat shock protein 70-major membrane protein-II fusion protein.

PubMed

Mukai, Tetsu; Maeda, Yumi; Tamura, Toshiki; Matsuoka, Masanori; Tsukamoto, Yumiko; Makino, Masahiko

2009-11-15

Because Mycobacterium bovis bacillus Calmette-Guérin (BCG) unconvincingly activates human naive CD8(+) T cells, a rBCG (BCG-70M) that secretes a fusion protein comprising BCG-derived heat shock protein (HSP)70 and Mycobacterium leprae-derived major membrane protein (MMP)-II, one of the immunodominant Ags of M. leprae, was newly constructed to potentiate the ability of activating naive CD8(+) T cells through dendritic cells (DC). BCG-70M secreted HSP70-MMP-II fusion protein in vitro, which stimulated DC to produce IL-12p70 through TLR2. BCG-70M-infected DC activated not only memory and naive CD8(+) T cells, but also CD4(+) T cells of both types to produce IFN-gamma. The activation of these naive T cells by BCG-70M was dependent on the MHC and CD86 molecules on BCG-70M-infected DC, and was significantly inhibited by pretreatment of DC with chloroquine. Both brefeldin A and lactacystin significantly inhibited the activation of naive CD8(+) T cells by BCG-70M through DC. Thus, the CD8(+) T cell activation may be induced by cross-presentation of Ags through a TAP- and proteosome-dependent cytosolic pathway. When naive CD8(+) T cells were stimulated by BCG-70M-infected DC in the presence of naive CD4(+) T cells, CD62L(low)CD8(+) T cells and perforin-producing CD8(+) T cells were efficiently produced. MMP-II-reactive CD4(+) and CD8(+) memory T cells were efficiently produced in C57BL/6 mice by infection with BCG-70M. These results indicate that BCG-70M activated DC, CD4(+) T cells, and CD8(+) T cells, and the combination of HSP70 and MMP-II may be useful for inducing better T cell activation.

Comparative Study of Oral and Vaginal Misoprostol for Induction of Labour, Maternal and Foetal Outcome

PubMed Central

Komala, Kambhampati; Reddy, Meherlatha; Quadri, Iqbal Jehan; B., Suneetha; V., Ramya

2013-01-01

Background: Misoprostol is a new promising agent for cervical ripening and induction of labour .The ideal dose, route and frequency of administration of misoprostol are still under investigation. Although, vaginal application of misoprostol has been validated as a reasonable mean of induction, there is a patient resistance to digital examination and there is a risk of ascending infection. For this reason, oral administration of misoprostol for cervical ripening and labour induction has been tried. Aims and Objectives: To compare 50μg of oral misoprostol versus 25μg of intravaginal misoprostol for induction of labour at term and maternal, foetal outcomes. Methods: Two hundred women who were at term, with indication for induction of labour and Bishop scores of ≤5 were randomly assigned to receive misoprostol 50μg or 25μg intravaginal, every 4-6 hours, for a maximum of 5 doses. In either group, pregnant females with inadequate uterine contractions despite being given maximum 5 doses of misoprostol, were augmented using oxytocin. The primary outcome measure was time-interval from induction to vaginal delivery and vaginal delivery rate within 24 hours. Results: The median induction to vaginal delivery time in oral group (12.92h) and vaginal group (14.04 h) was not significant. Oral misoprostol resulted in more number of vaginal deliveries as compared to vaginal misoprostol (94% as compared to 86%), which was not significant. There was a significantly higher incidence of uterine tachysystole in the vaginal group, as compared to oral group. There were no significant differences between the groups with respect to oxytocin augmentation, caesarean section rate, analgesic requirement and neonatal outcome. Conclusion: Oral misoprostol is as efficacious as vaginal misoprostol because of shorter induction delivery interval, lower caesarean section rates, and lower incidence of failed induction rates. Lower incidence of foetal distress and easy intake are observed if the

Cognitive Performance Under Electroconvulsive Therapy (ECT) in ECT-Naive Treatment-Resistant Patients With Major Depressive Disorder.

PubMed

Ziegelmayer, Christoph; Hajak, Göran; Bauer, Anne; Held, Marion; Rupprecht, Rainer; Trapp, Wolfgang

2017-06-01

Although electroconvulsive therapy (ECT) is considered a safe and highly effective treatment option for major depressive disorder, there are still some reservations with regard to possible adverse cognitive adverse effects. This is the case despite a large body of evidence showing that these deficits are transient and that there even seems to be a long-term improvement of cognitive functioning level. However, most data concerning cognitive adverse effects stem from studies using mixed samples of treatment-resistant and non-treatment-resistant as well as ECT-naive and non-ECT-naive subjects. Furthermore, neurocognitive measures might partly be sensitive to practice effects and improvements in depressive symptom level. We examined neurocognitive performance in a sample of 20 treatment-resistant and ECT-naive subjects using repeatable neurocognitive tests, whereas changes in depressive symptom level were controlled. Cognitive functioning level was assessed before (baseline), 1 week, and 6 months (follow-up 1 and 2) after (12 to) 15 sessions of unilateral ECT treatment. No adverse cognitive effects were observed in any of the cognitive domains examined. Instead, a significant improvement in verbal working memory performance was found from baseline to follow-up 2. When changes in depressive symptom levels were controlled statistically, this improvement was no longer seen. Although findings that ECT does not lead to longer lasting cognitive deficits caused by ECT were confirmed, our study adds evidence that previous results of a beneficial effect of ECT on cognition might be questioned.

Detergents enhance EspB secretion from Escherichia coli strains harboring the locus for the enterocyte effacement (LEE) gene.

PubMed

Nakasone, Noboru; Toma, Claudia; Higa, Naomi; Koizumi, Yukiko; Ogura, Yasunori; Suzuki, Toshihiko

2011-02-01

The effects of detergents (cholic acid, deoxycholic acid, Triton X-100, and Nonidet P-40) on the secretion of EspB from the locus for enterocyte effacement (LEE) gene-positive Escherichia coli strains were examined. Clinical isolates of eight EPEC strains and seven STEC strains were used to detect EspB after they had been cultivated in Luria-Bertani (LB) broth containing one of the detergents. When the bacteria were cultured in LB broth supplemented with one of the detergents, the amount of EspB produced was increased by 2-32-fold depending on the detergent and the strain used. EspB was detected in all strains when they were cultured in LB broth containing all of the detergents. The results obtained in this study can be applied to immunological diagnostic methods for detecting EspB and also to the production of EspB for research purposes. © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Naive-like Conversion Overcomes the Limited Differentiation Capacity of Induced Pluripotent Stem Cells*

PubMed Central

Honda, Arata; Hatori, Masanori; Hirose, Michiko; Honda, Chizumi; Izu, Haruna; Inoue, Kimiko; Hirasawa, Ryutaro; Matoba, Shogo; Togayachi, Sumie; Miyoshi, Hiroyuki; Ogura, Atsuo

2013-01-01

Although induced pluripotent stem (iPS) cells are indistinguishable from ES cells in their expression of pluripotent markers, their differentiation into targeted cells is often limited. Here, we examined whether the limited capacity of iPS cells to differentiate into neural lineage cells could be mitigated by improving their base-line level of pluripotency, i.e. by converting them into the so-called “naive” state. In this study, we used rabbit iPS and ES cells because of the easy availability of both cell types and their typical primed state characters. Repeated passages of the iPS cells permitted their differentiation into early neural cell types (neural stem cells, neurons, and glial astrocytes) with efficiencies similar to ES cells. However, unlike ES cells, their ability to differentiate later into neural cells (oligodendrocytes) was severely compromised. In contrast, after these iPS cells had been converted to a naive-like state, they readily differentiated into mature oligodendrocytes developing characteristic ramified branches, which could not be attained even with ES cells. These results suggest that the naive-like conversion of iPS cells might endow them with a higher differentiation capacity. PMID:23880763

Personality matters: individual variation in reactions of naive bird predators to aposematic prey.

PubMed

Exnerová, Alice; Svádová, Katerina Hotová; Fucíková, Eva; Drent, Pieter; Stys, Pavel

2010-03-07

Variation in reactions to aposematic prey is common among conspecific individuals of bird predators. It may result from different individual experience but it also exists among naive birds. This variation may possibly be explained by the effect of personality--a complex of correlated, heritable behavioural traits consistent across contexts. In the great tit (Parus major), two extreme personality types have been defined. 'Fast' explorers are bold, aggressive and routine-forming; 'slow' explorers are shy, non-aggressive and innovative. Influence of personality type on unlearned reaction to aposematic prey, rate of avoidance learning and memory were tested in naive, hand-reared great tits from two opposite lines selected for exploration (slow against fast). The birds were subjected to a sequence of trials in which they were offered aposematic adult firebugs (Pyrrhocoris apterus). Slow birds showed a greater degree of unlearned wariness and learned to avoid the firebugs faster than fast birds. Although birds of both personality types remembered their experience, slow birds were more cautious in the memory test. We conclude that not only different species but also populations of predators that differ in proportions of personality types may have different impacts on survival of aposematic insects under natural conditions.

Variation in the vitreoretinal configuration of Stage 4 retinopathy of prematurity in photocoagulated and treatment naive eyes undergoing vitrectomy

PubMed Central

Gadkari, Salil Sharad; Deshpande, Madan

2017-01-01

Purpose: We sought to document the difference in the vitreoretinal configuration of Stage 4 retinopathy of prematurity (ROP) in photocoagulated and treatment naive eyes undergoing vitrectomy and to correlate it with surgical complexity. Methods: Consecutive eyes posted for vitrectomy with Stage 4 ROP were documented preoperatively using a RetCam for the presence of peripheral traction (PT), presence of central traction just outside the arcades, and presence of traction extending to the lens. A note was made of the following intraoperative events: lensectomy, intraoperative bleeding, and iatrogenic breaks. Wilcoxon rank-sum test was used for analysis. Results: From a total of 46 eyes, 16 and 30 eyes were from the treated and treatment naive group, respectively. More eyes in the treated group had central (P < 0.0001) and lenticular traction (P = 0.022). More eyes in the untreated group had PT (P < 0.0001). A significant number of eyes without photocoagulation needed lensectomy (P = 0.042), and no difference in intraoperative bleeding (P = 0.94) was demonstrable. Iatrogenic retinotomy occurred in three eyes, all naive. Notably, age at surgery was more in the untreated group (P = 0.00008). Conclusion: Vasoproliferative activity in all retinopathies occurs at the junction of the ischemic and nonischemic retina. In the natural course of ROP, this takes place peripherally, at the ridge. In photocoagulated eyes, this junction is displaced posteriorly due to peripheral ablation. Treated eyes manifested with posterior proliferative changes and were more amenable to lens-sparing vitrectomy. Naive eyes were older when they underwent surgery to relieve PT with greater chances of lensectomy and iatrogenic breaks. PMID:28905829

Impact of the Data Collection on Adverse Events of Anti-HIV Drugs cohort study on abacavir prescription among treatment-naive, HIV-infected patients in Canada.

PubMed

Antoniou, Tony; Gillis, Jennifer; Loutfy, Mona R; Cooper, Curtis; Hogg, Robert S; Klein, Marina B; Machouf, Nima; Montaner, Julio S G; Rourke, Sean B; Tsoukas, Chris; Raboud, Janet M

2014-01-01

To evaluate the trends in abacavir (ABC) prescription among antiretroviral (ARV) medication-naive individuals following the presentation of the Data Collection on Adverse Events of Anti-HIV Drugs (DAD) cohort study. We conducted a retrospective cohort study of ARV medication-naive individuals in the Canadian Observational Cohort (CANOC). Between January 1, 2000, and February 28, 2010, a total of 7280 ARV medication-naive patients were included in CANOC. We observed a significant change in the proportion of new ABC prescriptions immediately following the release of DAD (-11%; 95% confidence interval [CI]: -20% to -2.4%) and in the months following the presentation of these data (-0.66% per month; 95% CI: -1.2% to -0.073%). A post-DAD presentation decrease in the odds of being prescribed ABC versus tenofovir (TDF) was observed (adjusted odds ratio, 0.72 per year, 95% CI: 0.54-0.97). Presentation of the DAD was associated with a significant decrease in ABC use among ARV medication-naive, HIV-positive patients initiating therapy.

Plasma homovanillic acid levels and therapeutic outcome in schizophrenics: comparisons of neuroleptic-naive first-episode patients and patients with disease exacerbation due to neuroleptic discontinuance.

PubMed

Akiyama, K; Tsuchida, K; Kanzaki, A; Ujike, H; Hamamura, T; Kondo, K; Mutoh, S; Miyanagi, K; Kuroda, S; Otsuki, S

1995-11-15

Plasma homovanillic acid (pHVA) levels were measured and the Brief Psychiatric Rating Scale (BPRS) scores were evaluated in 26 schizophrenic patients who had either never been medicated (neuroleptic-naive, first-episode subjects) or whose condition had become exacerbated following neuroleptic discontinuance (exacerbated subjects). All the subjects received medication with a fixed dose of a neuroleptic (haloperidol or fluphenazine, both 9 mg/day) for the first week and variable doses for the subsequent 4 weeks. In the neuroleptic-naive subjects, pHVA levels increased significantly 1 week after starting the protocol; this increase correlated significantly with clinical improvement of the BPRS positive symptom scores at week 5. In the neuroleptic-naive subjects, pHVA levels had declined to the baseline level by week 5. In the exacerbated subjects, there were no significant correlations between pHVA level changes at week 1 and later improvements of the BPRS positive symptom scores. These results suggest that the rise in pHVA levels occurring within 1 week after starting a fixed neuroleptic dose may predict a favorable clinical response in neuroleptic-naive schizophrenic patients.

Comparative analysis of drug resistance mutations in the human immunodeficiency virus reverse transcriptase gene in patients who are non-responsive, responsive and naive to antiretroviral therapy.

PubMed

Misbah, Mohammad; Roy, Gaurav; Shahid, Mudassar; Nag, Nalin; Kumar, Suresh; Husain, Mohammad

2016-05-01

Drug resistance mutations in the Pol gene of human immunodeficiency virus 1 (HIV-1) are one of the critical factors associated with antiretroviral therapy (ART) failure in HIV-1 patients. The issue of resistance to reverse transcriptase inhibitors (RTIs) in HIV infection has not been adequately addressed in the Indian subcontinent. We compared HIV-1 reverse transcriptase (RT) gene sequences to identify mutations present in HIV-1 patients who were ART non-responders, ART responders and drug naive. Genotypic drug resistance testing was performed by sequencing a 655-bp region of the RT gene from 102 HIV-1 patients, consisting of 30 ART-non-responding, 35 ART-responding and 37 drug-naive patients. The Stanford HIV Resistance Database (HIVDBv 6.2), IAS-USA mutation list, ANRS_09/2012 algorithm, and Rega v8.02 algorithm were used to interpret the pattern of drug resistance. The majority of the sequences (96 %) belonged to subtype C, and a few of them (3.9 %) to subtype A1. The frequency of drug resistance mutations observed in ART-non-responding, ART-responding and drug-naive patients was 40.1 %, 10.7 % and 20.58 %, respectively. It was observed that in non-responders, multiple mutations were present in the same patient, while in responders, a single mutation was found. Some of the drug-naive patients had more than one mutation. Thymidine analogue mutations (TAMs), however, were found in non-responders and naive patients but not in responders. Although drug resistance mutations were widely distributed among ART non-responders, the presence of resistance mutations in the viruses of drug-naive patients poses a big concern in the absence of a genotyping resistance test.

Efficacy and safety of misoprostol, dinoprostone and Cook's balloon for labour induction in women with foetal growth restriction at term.

PubMed

Duro-Gómez, Jorge; Garrido-Oyarzún, María Fernanda; Rodríguez-Marín, Ana Belén; de la Torre González, Antonio Jesús; Arjona-Berral, José Eduardo; Castelo-Branco, Camil

2017-10-01

To compare effectiveness and safety of dinoprostone, misoprostol and Cook's balloon as labour-inducing agents in women with intrauterine growth restriction (IUGR) at term. Retrospective cohort chart review of women diagnosed with foetal growth restriction at term in Reina Sofia Hospital, Cordoba, Spain from January 2014 to December 2015. Registration of baseline characteristics and method of induction was made. The main outcome was time from induction to delivery. Obstetric and perinatal outcomes were also collected. A total of 99 women were diagnosed with IUGR in the mentioned period. Of them, 21 women were induced with dinoprostone [dinoprostone group (DG)], 20 with misoprostol (MG) and in 58 with Cook's balloon (CG). Groups were homogeneous regarding pre-induction Bishop score and parity. The CG required more time (24.36 vs. 19.23 h; p = 0.02) and more oxytocin dose for conduction of labour from induction to delivery (6.75 vs. 1.24 mUI; p < 0.01) than DG. Moreover, the CG also needed more oxytocin than MG, 6.75 vs. 2.37 mUI (p < 0.001). Caesarean rate was 5, 14.9 and 17.3% in MG, DG and CG, respectively. No differences were observed in rates of uterine tachysystole, non-reassuring foetal status and neonatal adverse events. Prostaglandins were more effective than Cook's balloon to induce labour and achieve vaginal birth in this sample of women with IUGR at term, with a similar safety profile.

Acute cognitive impact of antiseizure drugs in naive rodents and corneal-kindled mice.

PubMed

Barker-Haliski, Melissa L; Vanegas, Fabiola; Mau, Matthew J; Underwood, Tristan K; White, H Steve

2016-09-01

Some antiseizure drugs (ASDs) are associated with cognitive liability in patients with epilepsy, thus ASDs without this risk would be preferred. Little comparative pharmacology exists with ASDs in preclinical models of cognition. Few pharmacologic studies exist on the acute effects in rodents with chronic seizures. Predicting risk for cognitive impact with preclinical models may supply valuable ASD differentiation data. ASDs (phenytoin [PHT]; carbamazepine [CBZ]; valproic acid [VPA]; lamotrigine [LTG]; phenobarbital [PB]; tiagabine [TGB]; retigabine [RTG]; topiramate [TPM]; and levetiracetam [LEV]) were administered equivalent to maximal electroshock median effective dose ([ED50]; mice, rats), or median dose necessary to elicit minimal motor impairment (median toxic dose [TD50]; rats). Cognition models with naive adult rodents were novel object/place recognition (NOPR) task with CF-1 mice, and Morris water maze (MWM) with Sprague-Dawley rats. Selected ASDs were also administered to rats prior to testing in an open field. The effect of chronic seizures and ASD administration on cognitive performance in NOPR was also determined with corneal-kindled mice. Mice that did not achieve kindling criterion (partially kindled) were included to examine the effect of electrical stimulation on cognitive performance. Sham-kindled and age-matched mice were also tested. No ASD (ED50) affected latency to locate the MWM platform; TD50 of PB, RTG, TPM, and VPA reduced this latency. In naive mice, CBZ and VPA (ED50) reduced time with the novel object. Of interest, no ASD (ED50) affected performance of fully kindled mice in NOPR, whereas CBZ and LEV improved cognitive performance of partially kindled mice. Standardized approaches to the preclinical evaluation of an ASD's potential cognitive impact are needed to inform drug development. This study demonstrated acute, dose- and model-dependent effects of therapeutically relevant doses of ASDs on cognitive performance of naive mice and

Is Children's Naive Knowledge Consistent?: A Comparison of the Concepts of Sound and Heat

ERIC Educational Resources Information Center

Lautrey, Jacques; Mazens, Karine

2004-01-01

The aim of this study was to shed some light on the organization of naive knowledge, and on the process of conceptual change in everyday physics, more specifically regarding the concepts of sound and heat. Eighty-three 8-year-old children were interviewed individually in order to see if they attributed the properties of objects (such as…

The reproducibility of adenosine monophosphate bronchial challenges in mild, steroid-naive asthmatics

PubMed Central

Singh, Dave; Fairwood, Jennifer; Murdoch, Robert; Weeks, Amanda; Russell, Paul; Roy, Kay; Langley, Steve; Woodcock, Ashley

2008-01-01

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Repeated adenosine monophosphate (AMP) challenges are used to assess drug effects in asthma clinical trials, but may be prone to tachyphylaxis when repeated at short intervals. Possible tachyphylaxis at 12- and 24-h intervals has not been studied. WHAT THIS STUDY ADDS Clinically relevant tachyphylaxis after repeated AMP challenges does not occur when repeated at 12- and 24-h intervals. AMP challenges at these intervals can be used to assess drug effects in clinical trials. AIMS Repeated adenosine monophosphate (AMP) challenges are used to assess drug efficacy in clinical trials of mild, steroid-naive asthmatics. Refractoriness has been reported after repeated challenges over short intervals. This study evaluated possible tachyphylaxis after repeated AMP challenges at 12 and 24 h in mild, steroid-naive asthmatics. METHODS This was an open, three-way crossover study. Twenty-six steroid-naive asthmatic subjects were randomized to the following AMP challenge regimens separated by 7–14 days: (A) challenge at 08.00 h, repeated 24 h later; (B) challenge at 08.00 h, repeated 12 and 24 h later; (C) challenge at 20.00 h, repeated 12 h later. Comparisons within day were assessed using 90% confidence intervals (CIs). Non-inferiority approach taken with 1 doubling concentration (DC) as a clinically relevant difference. RESULTS Regimen A: Significant increase in AMP reactivity at 24 h. Mean DC difference was 0.6 (90% CI 0.24, 0.96). Regimen B: No evidence of difference between AMP reactivity at 08.00 h and a repeated challenge 12 h later. Repeated challenge at 24 h caused a significant increase in provocation concentration (PC)20 compared with 12 h (mean DC difference 0.48, 90% CI 0.02, 0.95) and 0 h (mean DC difference 0.82, 90% CI 0.49, 1.14 – the upper CI exceeds the criteria of 1 DC). Challenge regimen C: No difference between challenges; mean DC difference of 0.28 (90% CI −0.2, 0.76). CONCLUSION The small decline in AMP

Experience of dolutegravir in HIV-infected treatment-naive patients from a tertiary care University Hospital in Ireland

PubMed Central

Waqas, Sarmad; O’Connor, Mairead; Levey, Ciara; Mallon, Paddy; Sheehan, Gerard; Patel, Anjali; Avramovic, Gordana; Lambert, John S

2016-01-01

Objective: Dolutegravir, an HIV integrase inhibitor, is a relatively new treatment option. To assess the tolerability, side effects, and time to viral decline to non-detectable in patients newly started on dolutegravir. Methods: Retrospective health care record of 61 consecutive HIV treatment-naive patients started on dolutegravir was reviewed and analysed on SPSS. Results: The mean initial viral load was 160826.05 copies/mL (range, 79–1,126,617 copies/mL). HIV viral load became non-detectable in 63.9% of patients on dolutegravir within 3 months. In all, 60.7% of patients reported no side effects on dolutegravir; 98.4% of the patients claimed full compliance to their antiretrovirals. Conclusion: Dolutegravir was found to be efficacious and well tolerated in HIV-infected treatment-naive patients. PMID:27826447

Strain differences in the neural, behavioral, and molecular correlates of sweet and salty taste in naive, ethanol- and sucrose-exposed P and NP rats

PubMed Central

Coleman, Jamison; Williams, Ashley; Phan, Tam-Hao T.; Mummalaneni, Shobha; Melone, Pamela; Ren, ZuoJun; Zhou, Huiping; Mahavadi, Sunila; Murthy, Karnam S.; Katsumata, Tadayoshi; DeSimone, John A.

2011-01-01

Strain differences between naive, sucrose- and ethanol-exposed alcohol-preferring (P) and alcohol-nonpreferring (NP) rats were investigated in their consumption of ethanol, sucrose, and NaCl; chorda tympani (CT) nerve responses to sweet and salty stimuli; and gene expression in the anterior tongue of T1R3 and TRPV1/TRPV1t. Preference for 5% ethanol and 10% sucrose, CT responses to sweet stimuli, and T1R3 expression were greater in naive P rats than NP rats. The enhancement of the CT response to 0.5 M sucrose in the presence of varying ethanol concentrations (0.5–40%) in naive P rats was higher and shifted to lower ethanol concentrations than NP rats. Chronic ingestion of 5% sucrose or 5% ethanol decreased T1R3 mRNA in NP and P rats. Naive P rats also demonstrated bigger CT responses to NaCl+benzamil and greater TRPV1/TRPV1t expression. TRPV1t agonists produced biphasic effects on NaCl+benzamil CT responses, enhancing the response at low concentrations and inhibiting it at high concentrations. The concentration of a TRPV1/TRPV1t agonist (Maillard reacted peptides conjugated with galacturonic acid) that produced a maximum enhancement in the NaCl+benzamil CT response induced a decrease in NaCl intake and preference in P rats. In naive P rats and NP rats exposed to 5% ethanol in a no-choice paradigm, the biphasic TRPV1t agonist vs. NaCl+benzamil CT response profiles were higher and shifted to lower agonist concentrations than in naive NP rats. TRPV1/TRPV1t mRNA expression increased in NP rats but not in P rats exposed to 5% ethanol in a no-choice paradigm. We conclude that P and NP rats differ in T1R3 and TRPV1/TRPV1t expression and neural and behavioral responses to sweet and salty stimuli and to chronic sucrose and ethanol exposure. PMID:21849614

Strain differences in the neural, behavioral, and molecular correlates of sweet and salty taste in naive, ethanol- and sucrose-exposed P and NP rats.

PubMed

Coleman, Jamison; Williams, Ashley; Phan, Tam-Hao T; Mummalaneni, Shobha; Melone, Pamela; Ren, Zuojun; Zhou, Huiping; Mahavadi, Sunila; Murthy, Karnam S; Katsumata, Tadayoshi; DeSimone, John A; Lyall, Vijay

2011-11-01

Strain differences between naive, sucrose- and ethanol-exposed alcohol-preferring (P) and alcohol-nonpreferring (NP) rats were investigated in their consumption of ethanol, sucrose, and NaCl; chorda tympani (CT) nerve responses to sweet and salty stimuli; and gene expression in the anterior tongue of T1R3 and TRPV1/TRPV1t. Preference for 5% ethanol and 10% sucrose, CT responses to sweet stimuli, and T1R3 expression were greater in naive P rats than NP rats. The enhancement of the CT response to 0.5 M sucrose in the presence of varying ethanol concentrations (0.5-40%) in naive P rats was higher and shifted to lower ethanol concentrations than NP rats. Chronic ingestion of 5% sucrose or 5% ethanol decreased T1R3 mRNA in NP and P rats. Naive P rats also demonstrated bigger CT responses to NaCl+benzamil and greater TRPV1/TRPV1t expression. TRPV1t agonists produced biphasic effects on NaCl+benzamil CT responses, enhancing the response at low concentrations and inhibiting it at high concentrations. The concentration of a TRPV1/TRPV1t agonist (Maillard reacted peptides conjugated with galacturonic acid) that produced a maximum enhancement in the NaCl+benzamil CT response induced a decrease in NaCl intake and preference in P rats. In naive P rats and NP rats exposed to 5% ethanol in a no-choice paradigm, the biphasic TRPV1t agonist vs. NaCl+benzamil CT response profiles were higher and shifted to lower agonist concentrations than in naive NP rats. TRPV1/TRPV1t mRNA expression increased in NP rats but not in P rats exposed to 5% ethanol in a no-choice paradigm. We conclude that P and NP rats differ in T1R3 and TRPV1/TRPV1t expression and neural and behavioral responses to sweet and salty stimuli and to chronic sucrose and ethanol exposure.

Computer assisted CT-guided stereotactic transplantation of foetal ventral mesencephalon to the caudate nucleus and putamen in Parkinson's disease.

PubMed

Molina, H; Quiñones, R; Ortega, I; Alvarez, L; Muñoz, J; Gonzalez, C; Suárez, C

1993-01-01

We report our preliminary results related to CT-guided stereotactic transplantation of foetal ventral mesencephalic cell suspension into the striatum of five patients with idiopathic Parkinson's disease. The mean age was 51 years, the evolution time of the disease ranged from 7 to 14 years, and all of them had motor complications associated with chronic L-dopa therapy. The patients were evaluated according to the Core Assessment Program for Intracerebral Transplantations (CAPIT) for one year before and three months after surgery. The postoperative clinical assessment demonstrated significant improvement of neurological symptoms and reduction of daily L-dopa dosage.

Probiotic Bacteria and their Supernatants Protect Enterocyte Cell Lines from Enteroinvasive Escherichia coli (EIEC) Invasion

PubMed Central

Khodaii, Zohreh; Ghaderian, Sayyed Mohammad Hossein; Natanzi, Mahboobeh Mehrabani

2017-01-01

Probiotic microorganisms have attracted a growing interest for prevention and therapy of gastrointestinal disorders. Many probiotic strains have been shown to inhibit growth and metabolic activity of enteropathogenic bacteria as well as their adhesion and invasion to intestinal cells. In the present study, we evaluated the interference of bacteria-free supernatants (BFS) of cultures belonging to sixteen strains of lactobacilli and bifidobacteria, with invasion of enteroinvasive Escherichia coli (EIEC) strain, using human colonic adenocarcinoma cell lines, T84 and Caco2 cells. To assess invasion of Caco-2 and T84 cells by EIEC, and measure the number of pathogens inside the enterocytes, the gentamicin protection assay was conducted. In addition, three different invasion inhibition assays were designed; namely co-incubation, pre-incubation and treatment with the BFS of probiotics. Data obtained and theoretical calculation showed that the most effective assay in the prevention of pathogen invasion was treatment with BFS. Besides, co-incubation assay was more valid than pre-incubation assay in invasion prevention. The obtained results suggest that probiotics may produce some metabolites that strongly prevent invasion of enteroinvasive E.coli into the small and large intestine. Also, probiotics are able to compete with or exclude pathogen invasion. PMID:29682490

Global Symmetries of Naive and Staggered Fermions in Arbitrary Dimensions

NASA Astrophysics Data System (ADS)

Kieburg, Mario; Würfel, Tim R.

2018-03-01

It is well-known that staggered fermions do not necessarily satisfy the same global symmetries as the continuum theory. We analyze the mechanism behind this phenomenon for arbitrary dimension and gauge group representation. For this purpose we vary the number of lattice sites between even and odd parity in each single direction. Since the global symmetries are manifest in the lowest eigenvalues of the Dirac operator, the spectral statistics and also the symmetry breaking pattern will be affected. We analyze these effects and compare our predictions with Monte-Carlo simulations of naive Dirac operators in the strong coupling limit. This proceeding is a summary of our work [1].

High-performance liquid chromatographic separation of human haemoglobins. Simultaneous quantitation of foetal and glycated haemoglobins.

PubMed

Bisse, E; Wieland, H

1988-12-29

A high-performance liquid chromatographic system, which uses a weak cation exchanger (PolyCATA) together with Bis-Tris buffer (pH 6.47-7.0) and sodium acetate gradients, is described. Samples from adults and newborns were analysed and a clean separation of many minor and major normal and abnormal haemoglobin (Hb) variants was greatly improved. The method allows the separation of minor foetal haemoglobin (HbF) variants and the simultaneous quantitation of HbF and glycated HbA. HbF values correlated well with those obtained by the alkali denaturation method (r = 0.997). The glycated haemoglobin (HbAIc) levels measured in patients with high HbF concentrations correlated with the total glycated haemoglobin determined by bioaffinity chromatography (r = 0.973). The procedure is useful for diagnostic applications and affords an effective and sensitive way of examining blood samples for haemoglobin abnormalities.

Classical Swine Fever Outbreak after Modified Live LOM Strain Vaccination in Naive Pigs, South Korea

PubMed Central

Je, Sang H.; Kwon, Taeyong; Yoo, Sung J.; Lee, Dong-Uk; Lee, SeungYoon; Richt, Juergen A.

2018-01-01

We report classical swine fever outbreaks occurring in naive pig herds on Jeju Island, South Korea, after the introduction of the LOM vaccine strain. Two isolates from sick pigs had >99% identity with the vaccine stain. LOM strain does not appear safe; its use in the vaccine should be reconsidered. PMID:29553332

Zeb1-Hdac2-eNOS circuitry identifies early cardiovascular precursors in naive mouse embryonic stem cells.

PubMed

Cencioni, Chiara; Spallotta, Francesco; Savoia, Matteo; Kuenne, Carsten; Guenther, Stefan; Re, Agnese; Wingert, Susanne; Rehage, Maike; Sürün, Duran; Siragusa, Mauro; Smith, Jacob G; Schnütgen, Frank; von Melchner, Harald; Rieger, Michael A; Martelli, Fabio; Riccio, Antonella; Fleming, Ingrid; Braun, Thomas; Zeiher, Andreas M; Farsetti, Antonella; Gaetano, Carlo

2018-03-29

Nitric oxide (NO) synthesis is a late event during differentiation of mouse embryonic stem cells (mESC) and occurs after release from serum and leukemia inhibitory factor (LIF). Here we show that after release from pluripotency, a subpopulation of mESC, kept in the naive state by 2i/LIF, expresses endothelial nitric oxide synthase (eNOS) and endogenously synthesizes NO. This eNOS/NO-positive subpopulation (ESNO+) expresses mesendodermal markers and is more efficient in the generation of cardiovascular precursors than eNOS/NO-negative cells. Mechanistically, production of endogenous NO triggers rapid Hdac2 S-nitrosylation, which reduces association of Hdac2 with the transcriptional repression factor Zeb1, allowing mesendodermal gene expression. In conclusion, our results suggest that the interaction between Zeb1, Hdac2, and eNOS is required for early mesendodermal differentiation of naive mESC.

Amino acid sequence and the cellular location of the Na(+)-dependent D-glucose symporters (SGLT1) in the ovine enterocyte and the parotid acinar cell.

PubMed Central

Tarpey, P S; Wood, I S; Shirazi-Beechey, S P; Beechey, R B

1995-01-01

The Na(+)-dependent D-glucose symporter has been shown to be located on the basolateral domain of the plasma membrane of ovine parotid acinar cells. This is in contrast to the apical location of this transporter in the ovine enterocyte. The amino acid sequences of these two proteins have been determined. They are identical. The results indicated that the signals responsible for the differential targeting of these two proteins to the apical and the basal domains of the plasma membrane are not contained within the primary amino acid sequence. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:7492327

Naive helper T cells from BCG-vaccinated volunteers produce IFN-gamma and IL-5 to mycobacterial antigen-pulsed dendritic cells.

PubMed

Kowalewicz-Kulbat, Magdalena; Kaźmierczak, Dominik; Donevski, Stefan; Biet, Franck; Pestel, Joël; Rudnicka, Wiesława

2008-01-01

Mycobacterium bovis bacillus Calmette-Guérin (BCG) is a live vaccine that has been used in routine vaccination against tuberculosis for nearly 80 years. However, its efficacy is controversial. The failure of BCG vaccination may be at least partially explained by the induction of poor or inappropriate host responses. Dendritic cells (DCs) are likely to play a key role in the induction of immune response to mycobacteria by polarizing the reactivity of T lymphocytes toward a Th1 profile, contributing to the generation of protective cellular immunity against mycobacteria. In this study we aimed to investigate the production of Th1 and Th2 cytokines by naive CD4+ T cells to mycobacterial antigen-pulsed DCs in the group of young, healthy BCG vaccinated volunteers. The response of naive helper T cells was compared with the response of total blood lymphocytes. Our present results clearly showed that circulating naive CD45RA+CD4+ lymphocytes from BCG-vaccinated subjects can become effector helper cells producing IFN-gamma and IL-5 under the stimulation by autologous dendritic cells presenting mycobacterial protein antigen-PPD or infected with live M. bovis BCG bacilli.

Characteristic appearances of fundus autofluorescence in treatment-naive and active polypoidal choroidal vasculopathy: a retrospective study of 170 patients.

PubMed

Zhao, Xinyu; Xia, Song; Chen, Youxin

2018-06-01

To investigate the characteristic appearances of fundus autofluorescence (FAF) in patients with treatment-naive and active polypoidal choroidal vasculopathy (PCV). Cases with the diagnosis of treatment-naive and active PCV from November 2012 to May 2017 at Peking Union Medical College Hospital were retrospectively reviewed. All patients underwent comprehensive ophthalmologic examination. Autofluorescence (AF) findings were described at the retinal sites of the corresponding lesions identified and diagnosed using indocyanine green angiography and spectral-domain optical coherence tomography. One hundred seventy patients with 192 affected eyes were included. The logMAR BCVA of the patients were 0.53 ± 0.28. The six AF patterns of 243 polypoidal lesions were confluent hypo-AF with hyper-AF ring (49.8%), confluent hypo-AF (22.6%), hyper-AF with hypo-AF ring (3.7%), granular hypo-AF (7.0%), blocked hypo-AF due to hemorrhage (8.6%), and polyps without apparent AF changes (8.2%). For 146 branching vascular networks (BVNs), 97.3% were granular hypo-AF, and others were blocked hypo-AF due to hemorrhage. In eyes with treatment-naive and active PCV, the polypoidal lesions and BVNs induce characteristic FAF changes. FAF images provide reliable adjunct reference for the diagnosis of PCV.

Foetal trauma, body memory and early infant communication: a case illustration.

PubMed

Merchant, John

2015-11-01

This paper presents the complex case of a male patient who started life as an unwanted pregnancy and adoptee in an era of socio-cultural shame and blame. When able to contact his birth mother later in life, he experienced a number of confronting synchronicities as well as visions which he felt were related to failed abortion attempts and to other pre- and post-natal events. The case material lends weight not only to Freud's, Ehrenwald's and FitzHerbert's assertions that the earliest form of mother-infant communications is telepathic in nature but that this mode of communication can be retained if emotional trauma inhibits normal developmental processes. Contemporary neuroscience research is presented supporting the hypothesis that emotional memory can become imbedded in the psyche/soma of the foetus. Such memory traces can later emerge into imagery and/or words if the traumatic impingement has been substantial enough and if other defensive strategies are in place. Clinical implications are then suggested regarding analysts' attention to the emotional conditions underpinning their patients' conceptions and foetal development; the connection to projective identification components of the countertransference as being aspects of the earliest telepathic mother/infant communication channel and the need for reductive analyses in analyst training programmes. © 2015, The Society of Analytical Psychology.

ZIKA VIRUS INFECTION; VERTICAL TRANSMISSION AND FOETAL CONGENITAL ANOMALIES.

PubMed

Abbasi, Aziz-un-Nisa

2016-01-01

Zika virus (ZIKV) is an arbovirus belonging to flaviviridae family that includes Dengue, West Nile, and Yellow Fever among others. Zika virus was first discovered in 1947 in Zika forest of Uganda. It is a vector borne disease, which has been sporadically reported mostly from Africa, Pacific islands and Southeast Asia since its discovery. ZIKV infection presents as a mild illness with symptoms lasting for several days to a week after the bite of an infected mosquito. Majority of the patients have low grade fever, rash, headaches, joints pain, myalgia, and flu like symptoms. Pregnant women are more vulnerable to ZIKV infection and serious congenital anomalies can occur in foetus through trans-placental transmission. The gestation at which infection is acquired is important. Zika virus infection acquired in early pregnancy poses greater risk. There is no evidence so far about transmission through breast milk. Foetal microcephaly, Gillian Barre syndrome and other neurological and autoimmune syndromes have been reported in areas where Zika outbreaks have occurred. As infection is usually very mild no specific treatment is required. Pregnant women may be advised to take rest, get plenty of fluids. For fever and pain they can take antipyretics like paracetamol. So far no specific drugs or vaccines are available against Zika Virus Infection so prevention is the mainstay against this diseases. As ZIKV infection is a vector borne disease, prevention can be a multi-pronged strategy. These entail vector control interventions, personal protection, environmental sanitation and health education among others.

Effect of tertiary multileaf collimator (MLC) on foetal dose during three-dimensional conformal radiation therapy (3DCRT) of a brain tumour during pregnancy.

PubMed

Sharma, Dayananda S; Jalali, Rakesh; Tambe, Chandrashekhar M; Animesh; Deshpande, Deepak D

2004-01-01

The aim of this work was to measure the dose to foetus both in vivo and in vitro during three-dimensional conformal radiation therapy (3DCRT) in a pregnant patient with a pituitary adenoma. The study was then extended to assess the components contributing to the foetal dose such as collimator scatter, internal scatter, head leakage, wedge scatter and multileaf collimator (MLC) effect. A 30-year-old pregnant woman with a non-functioning pituitary macroadenoma was planned for 3DCRT with 6MV X-ray using four equally weighted MLC-shaped non-coplanar wedged portals. In vivo dosimetry was carried out using thermoluminescent (TL) phosphor powder, which was placed at different positions on the patient, corresponding to different locations in the uterus and also at external os. In vitro measurements were also performed on a simulated phantom using the same set-up parameters and beam arrangement to verify the in vivo measured dose. Experiments were carried out to measure the respective contributions of different components towards peripheral dose. In vitro measured dose to foetus was found to be slightly more than that of in vivo measurement with a maximum of 0.044% of the prescribed dose of 45Gy, which corresponded to 0.0199+/-0.0008Gy. Thermoluminescence dosimeter (TLD) kept at the external os of the patient showed a dose of 0.031% of the prescribed dose. Among the various components of the peripheral dose (foetal dose) measured, head leakage was found to be the leading cause contributing 52%, followed by wedge scatter (31%), collimator scatter (14%) and internal scatter (13%). The use of MLC reduced not only the volume of normal brain irradiation as compared to open fields but also the peripheral dose by 10%. Radiotherapy of brain tumours during pregnancy poses a unique clinical situation and decisions to deliver radiotherapy should be taken after detailed in vitro and in vivo dosimetric measurements. Our findings suggest that the beam arrangement using 3-4-fields

Establishment and characterisation of a novel bovine SV40 large T-antigen-transduced foetal hepatocyte-derived cell line.

PubMed

Gleich, Alexander; Kaiser, Bastian; Schumann, Julia; Fuhrmann, Herbert

2016-06-01

Due to lack of in vitro models for bovine hepatocytes apart from primary cells, there is demand for a bovine hepatocyte-derived cell line. Transduction of bovine foetal hepatocytes with SV40 large T-antigen was performed using the vector pRetro-E2 SV40. Phase contrast microscopy was carried out to evaluate morphology. Immunofluorescence staining was conducted to study expression of keratins, tight junction proteins zona occludens-1 and claudin-1, glucose transporter-2 and P-glycoprotein as well as phosphoenolpyruvate carboxykinase. Urea and triglyceride production was quantified photometrically. Histochemical staining of glycogen by Periodic acid-Schiff stain and of lipids with Oil red O was performed after 24 h incubation with 20 mM glucose and 85 μM palmitic acid, respectively. Gene expression analysis of hepatocyte-typical genes was conducted by reverse transcription PCR. We obtained a SV40LTAg-transduced extended passage cell line, referred to as BFH12. Polygonal growth, keratins, tight junction proteins zona occludens-1 and claudin-1 and glucose transporter-2 as well as P-glycoprotein and phosphoenolpyruvate carboxykinase were attested positively. Urea production calculated as cell-specific rate was 14.2 ± 2.0 fmol/h (early passage) and 17.6 ± 3.7 fmol/h (late passage). Cell-specific triglyceride production was 1.6 ± 0.5 fmol/h (early passage) and 2.1 ± 0.3 fmol/h (late passage). Additionally, cells were positive for glycogen and lipid storage and showed a gene expression pattern resembling foetal hepatocytes. With the properties described here, the novel cell line BFH12 is a hepatocyte-derived cell line which can be used as an in vitro whole cell model.

Phenotypic and Genotypic Shifts in Hepatitis B Virus in Treatment-Naive Patients, Taiwan, 2008-2012.

PubMed

Yeh, Chau-Ting; Liang, Kung-Hao; Chang, Ming-Ling; Hsu, Chao-Wei; Chen, Yi-Cheng; Lin, Chih-Lang; Lin, Wey-Ran; Lai, Ming-Wei

2017-05-01

We examined the characteristic changes of hepatitis B virus (HBV) in antiviral drug treatment-naive patients referred for pretreatment evaluation in Taiwan during 2008-2012. Over time, we observed substantial decreases in the prevalence of HBV e antigen (HBeAg) and increasing prevalence of the precore G1899A mutation and HBV-DNA levels in HBeAg-positive patients.

Insulin sensitivity and beta-cell function in protease inhibitor-treated and -naive human immunodeficiency virus-infected children.

PubMed

Bitnun, Ari; Sochett, Etienne; Dick, Paul T; To, Teresa; Jefferies, Craig; Babyn, Paul; Forbes, Jack; Read, Stanley; King, Susan M

2005-01-01

Previous pediatric studies have failed to demonstrate a clear association between protease inhibitor (PI) therapy and abnormal glucose homeostasis in HIV-infected children. To define more precisely the impact of PI therapy on glucose homeostasis in this population, we performed the insulin-modified frequent-sampling iv glucose tolerance test on 33 PI-treated and 15 PI-naive HIV-infected children. Other investigations included fasting serum lipids; glucose, insulin, and C-peptide; single-slice abdominal computed tomography; and, in a subset of PI-treated children, an oral glucose tolerance test. There were no differences between the two groups with respect to fasting serum insulin or C-peptide, homeostatic model assessment insulin resistance, or quantitative insulin sensitivity check index. The mean insulin sensitivity index of PI-treated and PI-naive children was 6.93 +/- 6.37 and 10.58 +/- 12.93 x 10(-4)min(-1) [microU/ml](-1), respectively (P = 0.17). The mean disposition index for the two groups was 1840 +/- 1575 and 3708 +/- 3005 x 10(-4)min(-1) (P = 0.013), respectively. After adjusting for potential confounding variables using multiple regression analysis, the insulin sensitivity index and disposition index of PI-treated children were significantly lower than that of PI-naive children (P = 0.01 for both). In PI-treated but not PI-naive children, insulin sensitivity correlated inversely with visceral adipose tissue area (r = -0.43, P = 0.01) and visceral to sc adipose tissue ratio (r = -0.49, P = 0.004). Mildly impaired glucose tolerance was noted in four of 21 PI-treated subjects tested. Our results demonstrate not only that PI therapy reduces insulin sensitivity in HIV-infected children but also that it impairs the beta-cell response to this reduction in insulin sensitivity and, in a subset of children, leads to the development of impaired glucose tolerance. The presence of insulin resistance, dyslipidemia, and the significant correlation of reduced insulin

Differential effects of ibogaine on local cerebral glucose utilization in drug-naive and morphine-dependent rats.

PubMed

Levant, Beth; Pazdernik, Thomas L

2004-04-02

Ibogaine, a hallucinogenic indole alkaloid, has been proposed as a treatment for addiction to opioids and other drugs of abuse. The mechanism for its putative anti-addictive effects is unknown. In this study, the effects of ibogaine on local cerebral glucose utilization (LCGU) were determined in freely moving, drug-naive, or morphine-dependent adult, male, Sprague-Dawley rats using the [(14)C]2-deoxyglucose (2-DG) method. Morphine-dependent rats were treated with increasing doses of morphine (5-25 mg/kg, s.c., b.i.d.) and then maintained at 25 mg/kg (b.i.d.) for 4-7 days. For the 2-DG procedure, rats were injected with saline or ibogaine (40 mg/kg, i.p.). 2-DG was administered 1 h after administration of ibogaine. The rate of LCGU was determined by quantitative autoradiography in 46 brain regions. In drug-naive animals, ibogaine produced significant increases in LCGU in the parietal, cingulate, and occipital cortices and cerebellum compared to controls consistent with its activity as a hallucinogen and a tremorogen. Morphine-dependent rats had only minor alterations in LCGU at the time assessed in this experiment. However, in morphine-dependent animals, ibogaine produced a global decrease in LCGU that was greatest in brain regions such as the lateral and medial preoptic areas, nucleus of the diagonal band, nucleus accumbens shell, inferior colliculus, locus coeruleus, and flocculus compared to morphine-dependent animals treated with saline. These findings indicate that ibogaine produces distinctly different effects on LCGU in drug-naive and morphine-dependent rats. This suggests that different mechanisms may underlie ibogaine's hallucinogenic and anti-addictive effects.

Content Abstract Classification Using Naive Bayes

NASA Astrophysics Data System (ADS)

Latif, Syukriyanto; Suwardoyo, Untung; Aldrin Wihelmus Sanadi, Edwin

2018-03-01

This study aims to classify abstract content based on the use of the highest number of words in an abstract content of the English language journals. This research uses a system of text mining technology that extracts text data to search information from a set of documents. Abstract content of 120 data downloaded at www.computer.org. Data grouping consists of three categories: DM (Data Mining), ITS (Intelligent Transport System) and MM (Multimedia). Systems built using naive bayes algorithms to classify abstract journals and feature selection processes using term weighting to give weight to each word. Dimensional reduction techniques to reduce the dimensions of word counts rarely appear in each document based on dimensional reduction test parameters of 10% -90% of 5.344 words. The performance of the classification system is tested by using the Confusion Matrix based on comparative test data and test data. The results showed that the best classification results were obtained during the 75% training data test and 25% test data from the total data. Accuracy rates for categories of DM, ITS and MM were 100%, 100%, 86%. respectively with dimension reduction parameters of 30% and the value of learning rate between 0.1-0.5.

Comparative immunolocalisation of perlecan with collagen II and aggrecan in human foetal, newborn and adult ovine joint tissues demonstrates perlecan as an early developmental chondrogenic marker.

PubMed

Smith, Susan M; Shu, Cindy; Melrose, James

2010-09-01

We undertook a comparative immunolocalisation study on type II collagen, aggrecan and perlecan in a number of 12- to 14-week-old human foetal and postnatal (7-19 months) ovine joints including finger, toe, knee, elbow, hip and shoulder. This demonstrated that perlecan followed a virtually identical immunolocalisation pattern to that of type II collagen in the foetal tissues, but a slightly divergent localisation pattern in adult tissues. Aggrecan was also localised in the cartilaginous joint tissues, which were clearly delineated by toluidine blue staining and the type II collagen immunolocalisations. It was also present in the capsular joint tissues and in ligaments and tendons in the joint, which stained poorly or not at all with toluidine blue. In higher power microscopic views, antibodies to perlecan also stained small blood vessels in the synovial lining tissues of the joint capsule; however, this was not discernable in low power macroscopic views where the immunolocalisation of perlecan to pericellular regions of cells within the cartilaginous rudiments was a predominant feature. Perlecan was also evident in small blood vessels in stromal connective tissues associated with the cartilage rudiments and with occasional nerves in the vicinity of the joint tissues. Perlecan was expressed by rounded cells in the enthesis attachment points of tendons to bone and in rounded cells in the inner third of the meniscus, which stained prominently with type II collagen and aggrecan identifying the chondrogenic background of these cells and local compressive loads. Flattened cells within the tendon and in the surface laminas of articular cartilages and the meniscus did not express perlecan. Collected evidence presented herein, therefore, indicates that besides being a basement membrane component, perlecan is also a marker of chondrogenic cells in prenatal cartilages. In postnatal cartilages, perlecan displayed a pericellular localisation pattern rather than the territorial

Long-Term Impacts of Foetal Malnutrition Followed by Early Postnatal Obesity on Fat Distribution Pattern and Metabolic Adaptability in Adult Sheep

PubMed Central

Khanal, Prabhat; Johnsen, Lærke; Axel, Anne Marie Dixen; Hansen, Pernille Willert; Kongsted, Anna Hauntoft; Lyckegaard, Nette Brinch; Nielsen, Mette Olaf

2016-01-01

We aimed to investigate whether over- versus undernutrition in late foetal life combined with obesity development in early postnatal life have differential implications for fat distribution and metabolic adaptability in adulthood. Twin-pregnant ewes were fed NORM (100% of daily energy and protein requirements), LOW (50% of NORM) or HIGH (150%/110% of energy/protein requirements) diets during the last trimester. Postnatally, twin-lambs received obesogenic (HCHF) or moderate (CONV) diets until 6 months of age, and a moderate (obesity correcting) diet thereafter. At 2½ years of age (adulthood), plasma metabolite profiles during fasting, glucose, insulin and propionate (in fed and fasted states) tolerance tests were examined. Organ weights were determined at autopsy. Early obesity development was associated with lack of expansion of perirenal, but not other adipose tissues from adolescence to adulthood, resulting in 10% unit increased proportion of mesenteric of intra-abdominal fat. Prenatal undernutrition had a similar but much less pronounced effect. Across tolerance tests, LOW-HCHF sheep had highest plasma levels of cholesterol, urea-nitrogen, creatinine, and lactate. Sex specific differences were observed, particularly with respect to fat deposition, but direction of responses to early nutrition impacts were similar. However, prenatal undernutrition induced greater metabolic alterations in adult females than males. Foetal undernutrition, but not overnutrition, predisposed for adult hypercholesterolaemia, hyperureaemia, hypercreatinaemia and hyperlactataemia, which became manifested only in combination with early obesity development. Perirenal expandability may play a special role in this context. Differential nutrition recommendations may be advisable for individuals with low versus high birth weights. PMID:27257993

A NAIVE BAYES SOURCE CLASSIFIER FOR X-RAY SOURCES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Broos, Patrick S.; Getman, Konstantin V.; Townsley, Leisa K.

2011-05-01

The Chandra Carina Complex Project (CCCP) provides a sensitive X-ray survey of a nearby starburst region over >1 deg{sup 2} in extent. Thousands of faint X-ray sources are found, many concentrated into rich young stellar clusters. However, significant contamination from unrelated Galactic and extragalactic sources is present in the X-ray catalog. We describe the use of a naive Bayes classifier to assign membership probabilities to individual sources, based on source location, X-ray properties, and visual/infrared properties. For the particular membership decision rule adopted, 75% of CCCP sources are classified as members, 11% are classified as contaminants, and 14% remain unclassified.more » The resulting sample of stars likely to be Carina members is used in several other studies, which appear in this special issue devoted to the CCCP.« less

Small molecule drug A-769662 and AMP synergistically activate naive AMPK independent of upstream kinase signaling.

PubMed

Scott, John W; Ling, Naomi; Issa, Samah M A; Dite, Toby A; O'Brien, Matthew T; Chen, Zhi-Ping; Galic, Sandra; Langendorf, Christopher G; Steinberg, Gregory R; Kemp, Bruce E; Oakhill, Jonathan S

2014-05-22

The AMP-activated protein kinase (AMPK) is a metabolic stress-sensing αβγ heterotrimer responsible for energy homeostasis, making it a therapeutic target for metabolic diseases such as type 2 diabetes and obesity. AMPK signaling is triggered by phosphorylation on the AMPK α subunit activation loop Thr172 by upstream kinases. Dephosphorylated, naive AMPK is thought to be catalytically inactive and insensitive to allosteric regulation by AMP and direct AMPK-activating drugs such as A-769662. Here we show that A-769662 activates AMPK independently of α-Thr172 phosphorylation, provided β-Ser108 is phosphorylated. Although neither A-769662 nor AMP individually stimulate the activity of dephosphorylated AMPK, together they stimulate >1,000-fold, bypassing the requirement for β-Ser108 phosphorylation. Consequently A-769662 and AMP together activate naive AMPK entirely allosterically and independently of upstream kinase signaling. These findings have important implications for development of AMPK-targeting therapeutics and point to possible combinatorial therapeutic strategies based on AMP and AMPK drugs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ultrasound during mid-gestation: Agreement with physical foetal and placental measurements and use in predicting gestational age in sheep.

PubMed

Jones, A K; Gately, R E; McFadden, K K; Hoffman, M L; Pillai, S M; Zinn, S A; Govoni, K E; Reed, S A

2017-08-01

To determine the effects of poor maternal nutrition and litter size on foetal growth during mid-gestation, pregnant ewes (n = 82) were fed 100%, 60% or 140% of NRC TDN beginning at day 30.2 ± 0.2 of gestation. Transabdominal ultrasound was performed weekly between day 46.0 ± 0.4 and 86.0 ± 0.7 to monitor foetal heart width (HW), umbilical diameter (UMB), rib width (RW) and placentome outer (OD) and inner diameter (ID). Data were analysed with repeated-measures using the mixed procedure for effects of maternal diet, litter size and gestation, and equations predictive of gestational age were generated using the regression procedure. To determine the agreement of ultrasound measurement and actual size, ewes (n = 20-21) were euthanized at day 45 or 90 to obtain corresponding postmortem measurements for Bland-Altman analysis. The HW, UMB and placentome OD and ID increased with gestation (p < .0001) but were unaffected by maternal diet or litter size (p ≥ .12). Ultrasound underestimated postmortem measurements of HW (14.8%), UMB (7.3%), placentome OD (4.5%) and ID (37.3%) at day 90 of gestation. Ultrasound underestimated RW at day 45 (7.7%) but overestimated RW (23.8%) at day 90, indicating inconsistent bias when reporting RW by ultrasound. Combining the HW, UMB, RW and placentome OD generated the strongest equation predictive of gestational age (R 2  = .91). These findings indicate that during mid-gestation, maternal diet or litter size did not affect HW, UMB or placentome diameters and these factors can be used to estimate gestational age. © 2017 Blackwell Verlag GmbH.

miRNA profiling of human naive CD4 T cells links miR-34c-5p to cell activation and HIV replication.

PubMed

Amaral, Andreia J; Andrade, Jorge; Foxall, Russell B; Matoso, Paula; Matos, Ana M; Soares, Rui S; Rocha, Cheila; Ramos, Christian G; Tendeiro, Rita; Serra-Caetano, Ana; Guerra-Assunção, José A; Santa-Marta, Mariana; Gonçalves, João; Gama-Carvalho, Margarida; Sousa, Ana E

2017-02-01

Cell activation is a vital step for T-cell memory/effector differentiation as well as for productive HIV infection. To identify novel regulators of this process, we used next-generation sequencing to profile changes in microRNA expression occurring in purified human naive CD4 T cells in response to TCR stimulation and/or HIV infection. Our results demonstrate, for the first time, the transcriptional up-regulation of miR-34c-5p in response to TCR stimulation in naive CD4 T cells. The induction of this miR was further consistently found to be reduced by both HIV-1 and HIV-2 infections. Overexpression of miR-34c-5p led to changes in the expression of several genes involved in TCR signaling and cell activation, confirming its role as a novel regulator of naive CD4 T-cell activation. We additionally show that miR-34c-5p promotes HIV-1 replication, suggesting that its down-regulation during HIV infection may be part of an anti-viral host response. © 2016 The Authors.

Nociceptin/orphanin FQ decreases glutamate transmission and blocks ethanol-induced effects in the central amygdala of naive and ethanol-dependent rats.

PubMed

Kallupi, Marsida; Varodayan, Florence P; Oleata, Christopher S; Correia, Diego; Luu, George; Roberto, Marisa

2014-04-01

The central nucleus of the amygdala (CeA) mediates several addiction-related processes and nociceptin/orphanin FQ (nociceptin) regulates ethanol intake and anxiety-like behaviors. Glutamatergic synapses, in the CeA and throughout the brain, are very sensitive to ethanol and contribute to alcohol reinforcement, tolerance, and dependence. Previously, we reported that in the rat CeA, acute and chronic ethanol exposures significantly decrease glutamate transmission by both pre- and postsynaptic actions. In this study, using electrophysiological techniques in an in vitro CeA slice preparation, we investigated the effects of nociceptin on glutamatergic transmission and its interaction with acute ethanol in naive and ethanol-dependent rats. We found that nociceptin (100-1000 nM) diminished basal-evoked compound glutamatergic receptor-mediated excitatory postsynaptic potentials (EPSPs) and spontaneous and miniature EPSCs (s/mEPSCs) by mainly decreasing glutamate release in the CeA of naive rats. Notably, nociceptin blocked the inhibition induced by acute ethanol (44 mM) and ethanol blocked the nociceptin-induced inhibition of evoked EPSPs in CeA neurons of naive rats. In neurons from chronic ethanol-treated (ethanol-dependent) rats, the nociceptin-induced inhibition of evoked EPSP amplitude was not significantly different from that in naive rats. Application of [Nphe1]Nociceptin(1-13)NH2, a nociceptin receptor (NOP) antagonist, revealed tonic inhibitory activity of NOP on evoked CeA glutamatergic transmission only in ethanol-dependent rats. The antagonist also blocked nociceptin-induced decreases in glutamatergic responses, but did not affect ethanol-induced decreases in evoked EPSP amplitude. Taken together, these studies implicate a potential role for the nociceptin system in regulating glutamatergic transmission and a complex interaction with ethanol at CeA glutamatergic synapses.

High level of APOBEC3F/3G editing in HIV-2 DNA vif and pol sequences from antiretroviral-naive patients.

PubMed

Bertine, Mélanie; Charpentier, Charlotte; Visseaux, Benoit; Storto, Alexandre; Collin, Gilles; Larrouy, Lucile; Damond, Florence; Matheron, Sophie; Brun-Vézinet, Françoise; Descamps, Diane

2015-04-24

In HIV-1, hypermutation introduced by APOBEC3F/3G cytidine deaminase activity leads to defective viruses. In-vivo impact of APOBEC3F/3G editing on HIV-2 sequences remains unknown. The objective of this study was to assess the level of APOBEC3F/3G editing in HIV-2-infected antiretroviral-naive patients. Direct sequencing of vif and pol regions was performed on HIV-2 proviral DNA from antiretroviral-naive patients included in the French Agence Nationale de Recherches sur le SIDA et les hépatites virales CO5 HIV-2 cohort. Hypermutated sequences were identified using Hypermut2.0 program. HIV-1 proviral sequences from Genbank were also assessed. Among 82 antiretroviral-naive HIV-2-infected patients assessed, 15 (28.8%) and five (16.7%) displayed Vif proviral defective sequences in HIV-2 groups A and B, respectively. A lower proportion of defective sequences was observed in protease-reverse transcriptase region. A higher median number of G-to-A mutations was observed in HIV-2 group B than in group A, both in Vif and protease-reverse transcriptase regions (P = 0.02 and P = 0.006, respectively). Compared with HIV-1 Vif sequences, a higher number of Vif defective sequences was observed in HIV-2 group A (P = 0.00001) and group B sequences (P = 0.013). We showed for the first time a high level of APOBEC3F/3G editing in HIV-2 sequences from antiretroviral-naive patients. Our study reported a group effect with a significantly higher level of APOBEC3F/3G editing in HIV-2 group B than in group A sequences.

Biological effects of in vitro THz radiation exposure in human foetal fibroblasts.

PubMed

De Amicis, Andrea; Sanctis, Stefania De; Cristofaro, Sara Di; Franchini, Valeria; Lista, Florigio; Regalbuto, Elisa; Giovenale, Emilio; Gallerano, Gian Piero; Nenzi, Paolo; Bei, Roberto; Fantini, Massimo; Benvenuto, Monica; Masuelli, Laura; Coluzzi, Elisa; Cicia, Cristina; Sgura, Antonella

2015-11-01

In recent years, terahertz (THz) radiation has been widely used in a variety of applications: medical, security, telecommunications and military areas. However, few data are available on the biological effects of this type of electromagnetic radiation and the reported results, using different genetic or cellular assays, are quite discordant. This multidisciplinary study focuses on potential genotoxic and cytotoxic effects, evaluated by several end-points, associated with THz radiation. For this purpose, in vitro exposure of human foetal fibroblasts to low frequency THz radiation (0.1-0.15THz) was performed using a Compact Free Electron Laser. We did not observe an induction of DNA damage evaluated by Comet assay, phosphorylation of H2AX histone or telomere length modulation. In addiction, no induction of apoptosis or changes in pro-survival signalling proteins were detected. Moreover, our results indicated an increase in the total number of micronuclei and centromere positive micronuclei induction evaluated by CREST analysis, indicating that THz radiation could induce aneugenic rather than clastogenic effects, probably leading to chromosome loss. Furthermore, an increase of actin polymerization observed by ultrastructural analysis after THz irradiation, supports the hypothesis that an abnormal assembly of spindle proteins could lead to the observed chromosomal malsegregation. Copyright © 2015 Elsevier B.V. All rights reserved.

Fatal attraction: sexually cannibalistic invaders attract naive native mantids

PubMed Central

Fea, Murray P.; Stanley, Margaret C.; Holwell, Gregory I.

2013-01-01

Overlap in the form of sexual signals such as pheromones raises the possibility of reproductive interference by invasive species on similar, yet naive native species. Here, we test the potential for reproductive interference through heterospecific mate attraction and subsequent predation of males by females of a sexually cannibalistic invasive praying mantis. Miomantis caffra is invasive in New Zealand, where it is widely considered to be displacing the only native mantis species, Orthodera novaezealandiae, and yet mechanisms behind this displacement are unknown. We demonstrate that native males are more attracted to the chemical cues of introduced females than those of conspecific females. Heterospecific pairings also resulted in a high degree of mortality for native males. This provides evidence for a mechanism behind displacement that has until now been undetected and highlights the potential for reproductive interference to greatly influence the impact of an invasive species. PMID:24284560

Multilocus methylation analysis in a large cohort of 11p15-related foetal growth disorders (Russell Silver and Beckwith Wiedemann syndromes) reveals simultaneous loss of methylation at paternal and maternal imprinted loci.

PubMed

Azzi, Salah; Rossignol, Sylvie; Steunou, Virginie; Sas, Theo; Thibaud, Nathalie; Danton, Fabienne; Le Jule, Maryline; Heinrichs, Claudine; Cabrol, Sylvie; Gicquel, Christine; Le Bouc, Yves; Netchine, Irene

2009-12-15

Genomic imprinting plays an important role in mammalian development. Loss of imprinting (LOI) through loss (LOM) or gain (GOM) of methylation is involved in many human disorders and cancers. The imprinted 11p15 region is crucial for the control of foetal growth and LOI at this locus is implicated in two clinically opposite disorders: Beckwith Wiedemann syndrome (BWS) with foetal overgrowth associated with an enhanced tumour risk and Russell-Silver syndrome (RSS) with intrauterine and postnatal growth restriction. So far, only a few studies have assessed multilocus LOM in human imprinting diseases. To investigate multilocus LOI syndrome, we studied the methylation status of five maternally and two paternally methylated loci in a large series (n = 167) of patients with 11p15-related foetal growth disorders. We found that 9.5% of RSS and 24% of BWS patients showed multilocus LOM at regions other than ICR1 and ICR2 11p15, respectively. Moreover, over two third of multilocus LOM RSS patients also had LOM at a second paternally methylated locus, DLK1/GTL2 IG-DMR. No additional clinical features due to LOM of other loci were found suggesting an (epi)dominant effect of the 11p15 LOM on the clinical phenotype for this series of patients. Surprisingly, four patients displayed LOM at both ICR1 and ICR2 11p15. Three of them had a RSS and one a BWS phenotype. Our results show for the first time that multilocus LOM can also concern RSS patients. Moreover, LOM can involve both paternally and maternally methylated loci in the same patient.

Predicting Ecstasy Use among Young People at Risk: A Prospective Study of Initially Ecstasy-Naive Subjects

ERIC Educational Resources Information Center

Vervaeke, Hylke K.E.; Benschop, Annemieke; Van Den Brink, Wim; Korf, Dirk J.

2008-01-01

Our aim is to identify predictors of first-time ecstasy use in a prospective study among young people at risk. As part of the multidisciplinary Netherlands XTC Toxicity Study (NeXT), we monitored 188 subjects aged up to 18 years who were ecstasy-naive at baseline but seemed likely to start taking ecstasy in the near future. After an 11- to…

Antibody to soluble 1,3/1,6-beta-D-glucan, SCG in sera of naive DBA/2 mice.

PubMed

Harada, Toshie; Nagi Miura, Noriko; Adachi, Yoshiyuki; Nakajima, Mitsuhiro; Yadomae, Toshiro; Ohno, Naohito

2003-08-01

A branched beta-glucan from Sparassis crispa (SCG) is a major 6-branched 1,3-beta-D-glucan showing antitumor activity. In the present study, we examined the anti-SCG antibody in naive mice by ELISA. Using SCG coated plate, sera of naive DBA/1 and DBA/2 mice contained significantly higher titers of antibody than other strains of mice. Anti-SCG Ab titers of each DBA/1 and DBA/2 mice were significantly varied. Using various polysaccharide-coated plate, sera of DBA/2 mice also reacted with a beta-glucan from Candida spp. (CSBG) having 1,3-beta and 1,6-beta-glucosidic linkages. The SCG specific immunoglobulin (Ig) M but G was detected in sera. The reactivity of sera to coated SCG was neutralized by adding soluble SCG and CSBG as competitor. These results suggested that DBA/1 and DBA/2 strains carry specific and unique immunological characteristics to branched 1,3-/1,6-beta-glucan.

Maternal and foetal risk factor and complication with immediate outcome during hospital stay of very low birth weight babies.

PubMed

Mannan, M A; Jahan, N; Dey, S K; Uddin, M F; Ahmed, S

2012-10-01

This prospective study was done to find out the maternal and foetal risk factors and complications during hospital stay. It was conducted in Special Care Neonatal Unit (SCANU), Department of Child Health, Bangabandhu Memorial Hospital (BBMH), University of Science and Technology Chittagong (USTC) from1st October 2001 to 30th March 2002 and cases were 35 very low birth weight (VLBW) newborns. Common complications of VLBW babies of this series were frequent apnea (40%), Septicemia (25.71%), Hypothermia (17.14%), NEC (14.28%), Convulsion (11.43%), Hyper-bilirubinaemia (8.57%), Anemia (5.71%), IVH (5.71%), RDS (2.86%), HDN (2.86%), CCF (2.86%), ARF (2.86%), either alone or in combination with other clinical conditions. Newborns 62.86% male, 37.14% female & their mortality rate were 40.91% & 38.46% respectively; Preterm 88.57% & their mortality (41.93%) were higher than term babies (25.00%); AGA 62.86%, SGA 37.14% & mortality rate of AGA babies (45.46%) were higher than of SGA (30.77%) babies. The mortality rate of VLBW infants of teen age (≤ 18 years) mothers (57.14%) & high (≥ 30 years) aged mothers (50.00%) were higher than average (19-26 yrs) maternal age mothers (33.33%). Mortality rate was higher among the babies of primi (41.67%) than multiparous (36.36%), poor socioeconomic group (53.33%) than middle class (30.00%) & mothers on irregular ANC (47.83%) than regular ANC (25.00%). It has been also noted the mortality rate of home delivered babies (50.00%) higher than institutional delivered (34.78%) babies; higher in LUCS babies (46.15%) than normal vaginal delivered babies (31.58%); higher in the babies who had antenatal maternal problem (48.15%) than no maternal problems babies (12.50%); higher in the babies who had fetal distress (50.00%) and twin (46.67%) than no foetal risk factors (28.57%) during intrauterine life; higher in the babies who had problems at admission (46.67%) than no problems (35.00%); and mortality higher in twin (46.67%) than singleton

HBV genotypes and drug resistance mutations in antiretroviral treatment-naive and treatment-experienced HBV-HIV-coinfected patients.

PubMed

Archampong, Timothy Na; Boyce, Ceejay L; Lartey, Margaret; Sagoe, Kwamena W; Obo-Akwa, Adjoa; Kenu, Ernest; Blackard, Jason T; Kwara, Awewura

2017-01-01

The presence of HBV resistance mutations upon initiation or during antiretroviral therapy (ART) in HIV-coinfected patients is an important determinant of treatment response. The main objective of the study was to determine the prevalence of HBV resistance mutations in antiretroviral treatment-naive and treatment-experienced HBV-HIV-coinfected Ghanaian patients with detectable HBV viraemia. HBV-HIV-coinfected patients who were ART-naive or had received at least 9 months of lamivudine (3TC)-containing ART were enrolled in a cross-sectional study. Demographic and clinical data were collected and HBV DNA quantified. Partial HBV sequences were amplified by PCR and sequenced bi-directionally to obtain a 2.1-2.2 kb fragment for phylogenetic analysis of HBV genotypes and evaluation of drug resistance mutations. Of the 100 HBV-HIV-coinfected study patients, 75 were successfully PCR-amplified, and 63 were successfully sequenced. Of these 63 patients, 27 (42.9%) were ART-experienced and 58 (92.1%) had HBV genotype E. No resistance mutations were observed in the 36 ART-naive patients, while 21 (77.8%) of 27 treatment-experienced patients had resistance mutations. All patients with resistance mutations had no tenofovir in their regimens, and 80% of them had HIV RNA <40 copies/ml. The 3TC resistance mutations rtL180M and rtM204V were observed in 10 (47.6%) of the 21 patients, while 5 patients (23.8%) had rtV173L, rtL180M and rtM204V mutations. A high proportion of HBV-HIV-coinfected patients with detectable viraemia on 3TC-containing ART had resistance mutations despite good ART adherence as determined by HIV RNA suppression. This study emphasizes the need for dual therapy as part of a fully suppressive ART in all HBV-HIV-coinfected patients in Ghana.

Involvement of CRF2 signaling in enterocyte differentiation.

PubMed

Ducarouge, Benjamin; Pelissier-Rota, Marjolaine; Powell, Rebecca; Buisson, Alain; Bonaz, Bruno; Jacquier-Sarlin, Muriel

2017-07-28

To determine the role of corticotropin releasing factor receptor (CRF2) in epithelial permeability and enterocyte cell differentiation. For this purpose, we used rat Sprague Dawley and various colon carcinoma cell lines (SW620, HCT8R, HT-29 and Caco-2 cell lines). Expression of CRF2 protein was analyzed by fluorescent immunolabeling in normal rat colon and then by western blot in dissociated colonic epithelial cells and in the lysates of colon carcinoma cell lines or during the early differentiation of HT-29 cells (ten first days). To assess the impact of CRF2 signaling on colonic cell differentiation, HT-29 and Caco-2 cells were exposed to Urocortin 3 recombinant proteins (Ucn3, 100 nmol/L). In some experiments, cells were pre-exposed to the astressin 2b (A2b) a CRF2 antagonist in order to inhibit the action of Ucn3. Intestinal cell differentiation was first analyzed by functional assays: the trans-cellular permeability and the para-cellular permeability were determined by Dextran-FITC intake and measure of the transepithelial electrical resistance respectively. Morphological modifications associated to epithelial dysfunction were analyzed by confocal microscopy after fluorescent labeling of actin (phaloidin-TRITC) and intercellular adhesion proteins such as E-cadherin, p120ctn, occludin and ZO-1. The establishment of mature adherens junctions (AJ) was monitored by following the distribution of AJ proteins in lipid raft fractions, after separation of cell lysates on sucrose gradients. Finally, the mRNA and the protein expression levels of characteristic markers of intestinal epithelial cell (IEC) differentiation such as the transcriptional factor krüppel-like factor 4 (KLF4) or the dipeptidyl peptidase IV (DPPIV) were performed by RT-PCR and western blot respectively. The specific activities of DPPIV and alkaline phosphatase (AP) enzymes were determined by a colorimetric method. CRF2 protein is preferentially expressed in undifferentiated epithelial cells from

Involvement of CRF2 signaling in enterocyte differentiation

PubMed Central

Ducarouge, Benjamin; Pelissier-Rota, Marjolaine; Powell, Rebecca; Buisson, Alain; Bonaz, Bruno; Jacquier-Sarlin, Muriel

2017-01-01

AIM To determine the role of corticotropin releasing factor receptor (CRF2) in epithelial permeability and enterocyte cell differentiation. METHODS For this purpose, we used rat Sprague Dawley and various colon carcinoma cell lines (SW620, HCT8R, HT-29 and Caco-2 cell lines). Expression of CRF2 protein was analyzed by fluorescent immunolabeling in normal rat colon and then by western blot in dissociated colonic epithelial cells and in the lysates of colon carcinoma cell lines or during the early differentiation of HT-29 cells (ten first days). To assess the impact of CRF2 signaling on colonic cell differentiation, HT-29 and Caco-2 cells were exposed to Urocortin 3 recombinant proteins (Ucn3, 100 nmol/L). In some experiments, cells were pre-exposed to the astressin 2b (A2b) a CRF2 antagonist in order to inhibit the action of Ucn3. Intestinal cell differentiation was first analyzed by functional assays: the trans-cellular permeability and the para-cellular permeability were determined by Dextran-FITC intake and measure of the transepithelial electrical resistance respectively. Morphological modifications associated to epithelial dysfunction were analyzed by confocal microscopy after fluorescent labeling of actin (phaloidin-TRITC) and intercellular adhesion proteins such as E-cadherin, p120ctn, occludin and ZO-1. The establishment of mature adherens junctions (AJ) was monitored by following the distribution of AJ proteins in lipid raft fractions, after separation of cell lysates on sucrose gradients. Finally, the mRNA and the protein expression levels of characteristic markers of intestinal epithelial cell (IEC) differentiation such as the transcriptional factor krüppel-like factor 4 (KLF4) or the dipeptidyl peptidase IV (DPPIV) were performed by RT-PCR and western blot respectively. The specific activities of DPPIV and alkaline phosphatase (AP) enzymes were determined by a colorimetric method. RESULTS CRF2 protein is preferentially expressed in undifferentiated

DR3 regulation of apoptosis of naive T-lymphocytes in children with acute infectious mononucleosis.

PubMed

Filatova, Elena Nikolaevna; Anisenkova, Elena Viktorovna; Presnyakova, Nataliya Borisovna; Utkin, Oleg Vladimirovich

2016-09-01

Acute infectious mononucleosis (AIM) is a widespread viral disease that mostly affects children. Development of AIM is accompanied by a change in the ratio of immune cells. This is provided by means of different biological processes including the regulation of apoptosis of naive T-cells. One of the potential regulators of apoptosis of T-lymphocytes is a death receptor 3 (DR3). We have studied the role of DR3 in the regulation of apoptosis of naive CD4 + (nTh) and CD8 + (nCTL) T-cells in healthy children and children with AIM. In healthy children as well as in children with AIM, the activation of DR3 is accompanied by inhibition of apoptosis of nTh. In healthy children, the stimulation of DR3 resulted in the increase in apoptosis of nCTL. On the contrary, in children with AIM, the level of apoptosis of nCTL decreased after DR3 activation, which is a positive contribution to the antiviral immune response. In children with AIM, nCTL are characterized by reduced level of apoptosis as compared with healthy children. These results indicate that DR3 can be involved in the reduction of sensitivity of nCTL to apoptosis in children with AIM.

IL-2 Enhances Gut Homing Potential of Human Naive Regulatory T Cells Early in Life.

PubMed

Hsu, Peter S; Lai, Catherine L; Hu, Mingjing; Santner-Nanan, Brigitte; Dahlstrom, Jane E; Lee, Cheng Hiang; Ajmal, Ayesha; Bullman, Amanda; Arbuckle, Susan; Al Saedi, Ahmed; Gacis, Lou; Nambiar, Reta; Williams, Andrew; Wong, Melanie; Campbell, Dianne E; Nanan, Ralph

2018-06-15

Recent evidence suggests early environmental factors are important for gut immune tolerance. Although the role of regulatory T (Treg) cells for gut immune homeostasis is well established, the development and tissue homing characteristics of Treg cells in children have not been studied in detail. In this article, we studied the development and homing characteristics of human peripheral blood Treg cell subsets and potential mechanisms inducing homing molecule expression in healthy children. We found contrasting patterns of circulating Treg cell gut and skin tropism, with abundant β7 integrin + Treg cells at birth and increasing cutaneous lymphocyte Ag (CLA + ) Treg cells later in life. β7 integrin + Treg cells were predominantly naive, suggesting acquisition of Treg cell gut tropism early in development. In vitro, IL-7 enhanced gut homing but reduced skin homing molecule expression in conventional T cells, whereas IL-2 induced a similar effect only in Treg cells. This effect was more pronounced in cord compared with adult blood. Our results suggest that early in life, naive Treg cells may be driven for gut tropism by their increased sensitivity to IL-2-induced β7 integrin upregulation, implicating a potential role of IL-2 in gut immune tolerance during this critical period of development. Copyright © 2018 by The American Association of Immunologists, Inc.

A Discrete Choice Conjoint Experiment to Evaluate Parent Preferences for Treatment of Young, Medication Naive Children with ADHD

ERIC Educational Resources Information Center

Waschbusch, Daniel A.; Cunningham, Charles E.; Pelham, William E., Jr.; Rimas, Heather L.; Greiner, Andrew R.; Gnagy, Elizabeth M.; Waxmonsky, James; Fabiano, Gregory A.; Robb, Jessica A.; Burrows-MacLean, Lisa; Scime, Mindy; Hoffman, Martin T.

2011-01-01

The current study examined treatment preferences of 183 parents of young (average age = 5.8 years, SD = 0.6), medication naive children with ADHD. Preferences were evaluated using a discrete choice experiment in which parents made choices between different combinations of treatment characteristics, outcomes, and costs. Latent class analysis…

Acute Neuropsychological Effects of Methylphenidate in Stimulant Drug-Naive Boys with ADHD II--Broader Executive and Non-Executive Domains

ERIC Educational Resources Information Center

Rhodes, Sinead M.; Coghill, David R.; Matthews, Keith

2006-01-01

Background: Accumulating evidence supports methylphenidate-induced enhancement of neuropsychological functioning in attention deficit hyperactivity disorder (ADHD). The present study was designed to investigate the acute effects of the psychostimulant drug, methylphenidate (MPH), on neuropsychological performance in stimulant naive boys with ADHD.…

Background level of risk and the survival of predator-naive prey: can neophobia compensate for predator naivety in juvenile coral reef fishes?

PubMed

Ferrari, Maud C O; McCormick, Mark I; Meekan, Mark G; Chivers, Douglas P

2015-01-22

Neophobia--the generalized fear response to novel stimuli--provides the first potential strategy that predator-naive prey may use to survive initial predator encounters. This phenotype appears to be highly plastic and present in individuals experiencing high-risk environments, but rarer in those experiencing low-risk environments. Despite the appeal of this strategy as a 'solution' for prey naivety, we lack evidence that this strategy provides any fitness benefit to prey. Here, we compare the relative effect of environmental risk (high versus low) and predator-recognition training (predator-naive versus predator-experienced individuals) on the survival of juvenile fish in the wild. We found that juveniles raised in high-risk conditions survived better than those raised in low-risk conditions, providing the first empirical evidence that environmental risk, in the absence of any predator-specific information, affects the way naive prey survive in a novel environment. Both risk level and experience affected survival; however, the two factors did not interact, indicating that the information provided by both factors did not interfere or enhance each other. From a mechanistic viewpoint, this indicates that the combination of the two factors may increase the intensity, and hence efficacy, of prey evasion strategies, or that both factors provide qualitatively separate benefits that would result in an additive survival success.

Hippo, TGF-β, and Src-MAPK pathways regulate transcription of the upd3 cytokine in Drosophila enterocytes upon bacterial infection.

PubMed

Houtz, Philip; Bonfini, Alessandro; Liu, Xi; Revah, Jonathan; Guillou, Aurélien; Poidevin, Mickael; Hens, Korneel; Huang, Hsin-Yi; Deplancke, Bart; Tsai, Yu-Chen; Buchon, Nicolas

2017-11-01

Cytokine signaling is responsible for coordinating conserved epithelial regeneration and immune responses in the digestive tract. In the Drosophila midgut, Upd3 is a major cytokine, which is induced in enterocytes (EC) and enteroblasts (EB) upon oral infection, and initiates intestinal stem cell (ISC) dependent tissue repair. To date, the genetic network directing upd3 transcription remains largely uncharacterized. Here, we have identified the key infection-responsive enhancers of the upd3 gene and show that distinct enhancers respond to various stresses. Furthermore, through functional genetic screening, bioinformatic analyses and yeast one-hybrid screening, we determined that the transcription factors Scalloped (Sd), Mothers against dpp (Mad), and D-Fos are principal regulators of upd3 expression. Our study demonstrates that upd3 transcription in the gut is regulated by the activation of multiple pathways, including the Hippo, TGF-β/Dpp, and Src, as well as p38-dependent MAPK pathways. Thus, these essential pathways, which are known to control ISC proliferation cell-autonomously, are also activated in ECs to promote tissue turnover the regulation of upd3 transcription.

MRI/US fusion-guided prostate biopsy allows for equivalent cancer detection with significantly fewer needle cores in biopsy-naive men

PubMed Central

Yarlagadda, Vidhush K.; Lai, Win Shun; Gordetsky, Jennifer B.; Porter, Kristin K.; Nix, Jeffrey W.; Thomas, John V.; Rais-Bahrami, Soroush

2018-01-01

PURPOSE We aimed to investigate the efficiency and cancer detection of magnetic resonance imaging (MRI)/ultrasonography (US) fusion-guided prostate biopsy in a cohort of biopsy-naive men compared with standard-of-care systematic extended sextant transrectal ultrasonography (TRUS)-guided biopsy. METHODS From 2014 to 2016, 72 biopsy-naive men referred for initial prostate cancer evaluation who underwent MRI of the prostate were prospectively evaluated. Retrospective review was performed on 69 patients with lesions suspicious for malignancy who underwent MRI/US fusion-guided biopsy in addition to systematic extended sextant biopsy. Biometric, imaging, and pathology data from both the MRI-targeted biopsies and systematic biopsies were analyzed and compared. RESULTS There were no significant differences in overall prostate cancer detection when comparing MRI-targeted biopsies to standard systematic biopsies (P = 0.39). Furthermore, there were no significant differences in the distribution of severity of cancers based on grade groups in cases with cancer detection (P = 0.68). However, significantly fewer needle cores were taken during the MRI/US fusion-guided biopsy compared with systematic biopsy (63% less cores sampled, P < 0.001) CONCLUSION In biopsy-naive men, MRI/US fusion-guided prostate biopsy offers equal prostate cancer detection compared with systematic TRUS-guided biopsy with significantly fewer tissue cores using the targeted technique. This approach can potentially reduce morbidity in the future if used instead of systematic biopsy without sacrificing the ability to detect prostate cancer, particularly in cases with higher grade disease. PMID:29770762

Early Remission Is a Realistic Target in a Majority of Patients with DMARD-naive Rheumatoid Arthritis.

PubMed

Rannio, Tuomas; Asikainen, Juha; Kokko, Arto; Hannonen, Pekka; Sokka, Tuulikki

2016-04-01

We analyzed remission rates at 3 and 12 months in patients with rheumatoid arthritis (RA) who were naive for disease-modifying antirheumatic drugs (DMARD) and who were treated in a Finnish rheumatology clinic from 2008 to 2011. We compared remission rates and drug treatments between patients with RA and patients with undifferentiated arthritis (UA). Data from all DMARD-naive RA and UA patients from the healthcare district were collected using software that includes demographic and clinical characteristics, disease activity, medications, and patient-reported outcomes. Our rheumatology clinic applies the treat-to-target principle, electronic monitoring of patients, and multidisciplinary care. Out of 409 patients, 406 had data for classification by the 2010 RA criteria of the American College of Rheumatology/European League Against Rheumatism. A total of 68% were female, and mean age (SD) was 58 (16) years. Respectively, 56%, 60%, and 68% were positive for anticyclic citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF), and RF/anti-CCP, and 19% had erosive disease. The median (interquartile range) duration of symptoms was 6 (4-12) months. A total of 310 were classified as RA and 96 as UA. The patients with UA were younger, had better functional status and lower disease activity, and were more often seronegative than the patients with RA. The 28-joint Disease Activity Score (3 variables) remission rates of RA and UA patients at 3 months were 67% and 58% (p = 0.13), and at 12 months, 71% and 79%, respectively (p = 0.16). Sustained remission was observed in 57%/56% of RA/UA patients. Patients with RA used more conventional synthetic DMARD combinations than did patients with UA. None used biological DMARD at 3 months, and only 2.7%/1.1% of the patients (RA/UA) used them at 12 months (p = 0.36). Remarkably high remission rates are achievable in real-world DMARD-naive patients with RA or UA.

Structure of neuro-endocrine and neuro-epithelial interactions in human foetal pancreas.

PubMed

Krivova, Yuliya; Proshchina, Alexandra; Barabanov, Valeriy; Leonova, Olga; Saveliev, Sergey

2016-12-01

In the pancreas of many mammals including humans, endocrine islet cells can be integrated with the nervous system components into neuro-insular complexes. The mechanism of the formation of such complexes is not clearly understood. The present study evaluated the interactions between the nervous system components, epithelial cells and endocrine cells in the human pancreas. Foetal pancreas, gestational age 19-23 weeks (13 cases) and 30-34 weeks (7 cases), were studied using double immunohistochemical labeling with neural markers (S100 protein and beta III tubulin), epithelial marker (cytokeratin 19 (CK19)) and antibodies to insulin and glucagon. We first analyse the structure of neuro-insular complexes using confocal microscopy and provide immunohistochemical evidences of the presence of endocrine cells within the ganglia or inside the nerve bundles. We showed that the nervous system components contact with the epithelial cells located in ducts or in clusters outside the ductal epithelium and form complexes with separate epithelial cells. We observed CK19-positive cells inside the ganglia and nerve bundles which were located separately or were integrated with the islets. Therefore, we conclude that neuro-insular complexes may forms as a result of integration between epithelial cells and nervous system components at the initial stages of islets formation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Perinatal grief following a termination of pregnancy for foetal abnormality: the impact of coping strategies.

PubMed

Lafarge, Caroline; Mitchell, Kathryn; Fox, Pauline

2013-12-01

Pregnancy termination for foetal abnormality (TFA) can have significant psychological repercussions, but little is known about the coping strategies involved in dealing with TFA. This study examined the relationships between women's coping strategies and perinatal grief. A total of 166 women completed a survey online. Coping and perinatal grief were measured using the Brief COPE and Short Perinatal Grief Scales. Data were analysed through multiple regression analyses. Despite using mostly adaptive coping strategies, women's levels of grief were high and varied according to obstetric and termination variables. Grief was predicted by behavioural disengagement, venting, planning, religion, self-blame, being recently bereaved, being childless at the time of TFA, not having had children/being pregnant since TFA and uncertainty about the decision to terminate the pregnancy. Acceptance and positive reframing negatively predicted grief. Identifying women vulnerable to poor psychological adjustment and promoting coping strategies associated with lower levels of grief may be beneficial. This could be addressed through information provision and interventions such as Cognitive Behavioural Therapy or Acceptance and Commitment Therapy. © 2013 John Wiley & Sons, Ltd.

Microvillous inclusion disease: how to improve the prognosis of a severe congenital enterocyte disorder.

PubMed

Halac, Ugur; Lacaille, Florence; Joly, Francisca; Hugot, Jean-Pierre; Talbotec, Cécile; Colomb, Virginie; Ruemmele, Frank M; Goulet, Olivier

2011-04-01

Microvillous inclusion disease (MVID) is a rare congenital enterocyte disorder causing severe diarrhea and intestinal failure. The objective of this study was to analyze clinical evolution and the most frequent complications of MVID in children receiving parenteral nutrition (PN) and after small-bowel transplantation (SBTx) with the aim to improve treatment strategies and prognosis. From 1995 to 2009, 24 patients (16 boys, median follow-up 4.7 years, range: from birth to 23.5 years) with MVID were admitted to our unit. The recorded parameters included growth, neurological development, liver and renal functions, bone disease, and outcome. Almost half of the children were from consanguineous families from the Mediterranean area. All of the patients completely depended on PN. Four children died of PN complications before 4 years of age. Before or without SBTx, growth failure was common (mean height -2.5 standard deviations [SD]), as was developmental delay (12/24), liver (20/22 with fibrosis) or kidney disease (3/23 with moderate renal insufficiency), and osteoporosis (6/24). Thirteen children underwent SBTx (9 isolated, 4 combined with liver Tx) at a median age of 3.5 years. Follow-up after SBTx was 0.4 to 14 years. Patient survival rates were 63% without SBTx and 77% with SBTx. After SBTx, 4 children experienced catch-up growth. PN in MVID is difficult to manage and requires expertise. Despite improved results in expert centers, the risk of death or irreversible sequelae is higher with PN than after Tx. SBTx, despite being complicated, remains the only hope to improve the quality of life and long-term prognosis of these children.

Cells resembling intraventricular macrophages are present in the subretinal space of human foetal eyes.

PubMed

McMenamin, P G; Loeffler, K U

1990-06-01

The subretinal spaces (SRS) in 17 human foetal eyes were investigated by light microscopy and scanning and transmission electron microscopy. A hitherto undocumented group of pleomorphic cells was detected on the apical surface of the retinal pigment epithelium (RPE) and on the undersurface of the neural retina. These cells formed a regularly spaced array in the peripheral SRS, particularly in the most anterior portion nearest the ciliary body anlage. The morphology of the SRS cells ranged from a small round or ovoid form with a few short basal pseudopodia to an extremely flattened dendritic form. Ultrastructural features, such as large melanophagolysosomes, consistent with a phagocytic function, were observed in some cells. These SRS cells bore remarkable resemblance to epiplexus and supraependymal cells, considered to be the resident population of macrophages on the ventricular surfaces of the brain. This morphological parallelism, together with the anatomically homologous location, is strong evidence that SRS cells represent a normal population of macrophages in the developing human eye. No features consistent with an RPE or neuronal origin were observed. The possible role of these cells as transient phagocytes in the SRS with a possible destiny as retinal microglia is discussed.

RasGRP1 regulates antigen-induced developmental programming by naive CD8 T cells.

PubMed

Priatel, John J; Chen, Xiaoxi; Huang, Yu-Hsuan; Chow, Michael T; Zenewicz, Lauren A; Coughlin, Jason J; Shen, Hao; Stone, James C; Tan, Rusung; Teh, Hung Sia

2010-01-15

Ag encounter by naive CD8 T cells initiates a developmental program consisting of cellular proliferation, changes in gene expression, and the formation of effector and memory T cells. The strength and duration of TCR signaling are known to be important parameters regulating the differentiation of naive CD8 T cells, although the molecular signals arbitrating these processes remain poorly defined. The Ras-guanyl nucleotide exchange factor RasGRP1 has been shown to transduce TCR-mediated signals critically required for the maturation of developing thymocytes. To elucidate the role of RasGRP1 in CD8 T cell differentiation, in vitro and in vivo experiments were performed with 2C TCR transgenic CD8 T cells lacking RasGRP1. In this study, we report that RasGRP1 regulates the threshold of T cell activation and Ag-induced expansion, at least in part, through the regulation of IL-2 production. Moreover, RasGRP1(-/-) 2C CD8 T cells exhibit an anergic phenotype in response to cognate Ag stimulation that is partially reversible upon the addition of exogenous IL-2. By contrast, the capacity of IL-2/IL-2R interactions to mediate Ras activation and CD8 T cell expansion and differentiation appears to be largely RasGRP1-independent. Collectively, our results demonstrate that RasGRP1 plays a selective role in T cell signaling, controlling the initiation and duration of CD8 T cell immune responses.

Large-scale sequence and structural comparisons of human naive and antigen-experienced antibody repertoires.

PubMed

DeKosky, Brandon J; Lungu, Oana I; Park, Daechan; Johnson, Erik L; Charab, Wissam; Chrysostomou, Constantine; Kuroda, Daisuke; Ellington, Andrew D; Ippolito, Gregory C; Gray, Jeffrey J; Georgiou, George

2016-05-10

Elucidating how antigen exposure and selection shape the human antibody repertoire is fundamental to our understanding of B-cell immunity. We sequenced the paired heavy- and light-chain variable regions (VH and VL, respectively) from large populations of single B cells combined with computational modeling of antibody structures to evaluate sequence and structural features of human antibody repertoires at unprecedented depth. Analysis of a dataset comprising 55,000 antibody clusters from CD19(+)CD20(+)CD27(-) IgM-naive B cells, >120,000 antibody clusters from CD19(+)CD20(+)CD27(+) antigen-experienced B cells, and >2,000 RosettaAntibody-predicted structural models across three healthy donors led to a number of key findings: (i) VH and VL gene sequences pair in a combinatorial fashion without detectable pairing restrictions at the population level; (ii) certain VH:VL gene pairs were significantly enriched or depleted in the antigen-experienced repertoire relative to the naive repertoire; (iii) antigen selection increased antibody paratope net charge and solvent-accessible surface area; and (iv) public heavy-chain third complementarity-determining region (CDR-H3) antibodies in the antigen-experienced repertoire showed signs of convergent paired light-chain genetic signatures, including shared light-chain third complementarity-determining region (CDR-L3) amino acid sequences and/or Vκ,λ-Jκ,λ genes. The data reported here address several longstanding questions regarding antibody repertoire selection and development and provide a benchmark for future repertoire-scale analyses of antibody responses to vaccination and disease.

Undernutrition during foetal and post-natal life affects testicular structure and reduces the number of Sertoli cells in the adult rat.

PubMed

Genovese, P; Núñez, M E; Pombo, C; Bielli, A

2010-04-01

To test whether undernutrition during foetal to pre-pubertal life would have long lasting effects on testicular histology in adult male offspring, eleven adult Sprague-Dawley pregnant rats were divided into two groups: Control group, n = 4, fed ad libitum, during gestation and lactation (until 25 day post-partum). Underfed group pregnant females (n = 7) were kept in cages where only dams had access to food (standard rat chow, 33.5% of ad libitum intake of Control group pregnant dams). After parturition, litters were adjusted to either 14 (Underfed group) or eight (Control group) pups. Mothers were weighed weekly. At 25 day of age pups were weaned, housed at four animals per cage, fed ad libitum and weighed weekly until euthanized at 100 day of age. Testes were processed for standard histology and morphometrical evaluation. At weaning, mother weight was lower in underfed than in Control group (mean +/- SD): 214.1 +/- 26.2 g vs 361.9 +/- 33.1 g. Body weight at 100 days of age (254 +/- 26.9 g vs 342.4 +/- 10.2 g, p foetal to pubertal subnutrition is accompanied by changes in testicular structure and lower Sertoli cell numbers in adult life, strongly suggesting lower daily sperm production.

The Galileo Bias: A Naive Conceptual Belief That Influences People's Perceptions and Performance in a Ball-Dropping Task

ERIC Educational Resources Information Center

Oberle, Crystal D.; McBeath, Michael K.; Madigan, Sean C.; Sugar, Thomas G.

2005-01-01

This research introduces a new naive physics belief, the Galileo bias, whereby people ignore air resistance and falsely believe that all objects fall at the same rate. Survey results revealed that this bias is held by many and is surprisingly strongest for those with formal physics instruction. In 2 experiments, 98 participants dropped ball pairs…

Hydrocortisone-induced anti-inflammatory effects in immature human enterocytes depend on the timing of exposure.

PubMed

Rautava, Samuli; Walker, W Allan; Lu, Lei

2016-06-01

The immature human gut has a propensity to exaggerated inflammatory responses that are thought to play a role in the pathogenesis of necrotizing enterocolitis (NEC). Prenatal exposure to corticosteroids has been reported to reduce the risk of NEC, while postnatal dexamethasone treatment is associated with adverse neurodevelopmental outcomes in preterm infants. The aim of this study was to investigate the direct role of hydrocortisone in gene expression patterns and inflammatory responses in immature human enterocytes. Time-dependent hydrocortisone effects in nontransformed primary human fetal intestinal epithelial cell line H4 were investigated by cDNA microarray. Fetal intestinal organ culture and cell culture experiments were conducted. Inflammatory responses were induced by stimulation with IL-1β and TNF-α with and without hydrocortisone. IL-8 and IL-6 expression and secretion were measured as functional readout. Here we report time-dependent hydrocortisone-induced changes in gene expression patterns detected by cDNA microarray. Hydrocortisone significantly attenuated IL-1β-induced inflammatory responses in the immature human gut when administered at the time of the proinflammatory insult: IL-1β-induced IL-8 and IL-6 secretion in the fetal ileum as well as H4 cells were significantly reduced. Hydrocortisone also inhibited IL-8 secretion in response to TNF-α. In contrast, TNF-α-induced IL-8 secretion was not reduced in cells treated with hydrocortisone for 48 h before stimulation. Our observations provide a physiological basis for understanding the differential clinical effects of corticosteroids in the immature human gut depending on the timing of treatment. Copyright © 2016 the American Physiological Society.

Hydrocortisone-induced anti-inflammatory effects in immature human enterocytes depend on the timing of exposure

PubMed Central

Rautava, Samuli; Lu, Lei

2016-01-01

The immature human gut has a propensity to exaggerated inflammatory responses that are thought to play a role in the pathogenesis of necrotizing enterocolitis (NEC). Prenatal exposure to corticosteroids has been reported to reduce the risk of NEC, while postnatal dexamethasone treatment is associated with adverse neurodevelopmental outcomes in preterm infants. The aim of this study was to investigate the direct role of hydrocortisone in gene expression patterns and inflammatory responses in immature human enterocytes. Time-dependent hydrocortisone effects in nontransformed primary human fetal intestinal epithelial cell line H4 were investigated by cDNA microarray. Fetal intestinal organ culture and cell culture experiments were conducted. Inflammatory responses were induced by stimulation with IL-1β and TNF-α with and without hydrocortisone. IL-8 and IL-6 expression and secretion were measured as functional readout. Here we report time-dependent hydrocortisone-induced changes in gene expression patterns detected by cDNA microarray. Hydrocortisone significantly attenuated IL-1β-induced inflammatory responses in the immature human gut when administered at the time of the proinflammatory insult: IL-1β-induced IL-8 and IL-6 secretion in the fetal ileum as well as H4 cells were significantly reduced. Hydrocortisone also inhibited IL-8 secretion in response to TNF-α. In contrast, TNF-α-induced IL-8 secretion was not reduced in cells treated with hydrocortisone for 48 h before stimulation. Our observations provide a physiological basis for understanding the differential clinical effects of corticosteroids in the immature human gut depending on the timing of treatment. PMID:27056727

Tissue-nonspecific alkaline phosphatase is activated in enterocytes by oxidative stress via changes in glycosylation.

PubMed

López-Posadas, Rocío; González, Raquel; Ballester, Isabel; Martínez-Moya, Patricia; Romero-Calvo, Isabel; Suárez, María Dolores; Zarzuelo, Antonio; Martínez-Augustin, Olga; Sánchez de Medina, Fermín

2011-02-01

Intestinal inflammation produces an induction of alkaline phosphatase (AP) activity that is attributable in part to augmented expression, accompanied by a change in isoform, in epithelial cells. This study focuses on induction of AP in intestinal epithelial cells in vitro. Treatment with the oxidants H2O2, monochloramine, or tButOOH increases AP activity in vitro in Caco-2, HT29, and IEC18 cells. We selected IEC18 cells for further testing. Basal AP activity in IEC18 cells is of the tissue-nonspecific (bone-liver-kidney) type, as indicated by Northern and Western blot analysis. Oxidative stress augments AP activity and the sensitivity of the enzyme to levamisole, homoarginine, and heat in IEC18 cells. Increased immunoreactivity to tissue-nonspecific AP antibodies suggests an isoform shift from liver to either kidney or bone type. This effect occurs without changes at the mRNA level and is sensitive to tunicamycin, an inhibitor of N-glycosylation, and neuraminidase digestion. Saponin and deoxycholate produce similar effects to oxidants. Butyrate but not proinflammatory cytokines or LPS can induce a similar effect but without toxicity. The AP increase is not prevented by modulators of the MAPK, NF-κB, calcium, and cyclic adenosine monophosphate (cAMP) pathways, and is actually enhanced by actinomycin D via higher cell stress. Oxidative stress causes a distinct increase in enterocyte AP activity together with cell toxicity via changes in the glycosylation of the enzyme that correspond to a shift in isotype within the tissue-nonspecific paradigm. We speculate that this may have physiological implication for gut defense.

Abnormal default-mode network homogeneity and its correlations with personality in drug-naive somatization disorder at rest.

PubMed

Wei, Shubao; Su, Qinji; Jiang, Muliang; Liu, Feng; Yao, Dapeng; Dai, Yi; Long, Liling; Song, Yan; Yu, Miaoyu; Zhang, Zhikun; Zhao, Jingping; Guo, Wenbin

2016-03-15

While the default-mode network (DMN) appears to play a crucial role in patients suffering from somatization disorder (SD), the abnormalities of the network homogeneity (NH) of the DMN in SD patients have been poorly explored. The aim of this study is to examine DMN NH using an NH approach in patients suffering from SD at rest and determine its correlations with personality as measured by the Eysenck Personality Questionnaire (EPQ). A total of 25 drug-naive patients with SD and 28 sex-, age-, and education-matched healthy controls underwent functional magnetic resonance imaging scans at rest. The data were analyzed by an automated NH method. Patients showed increased NH in the left superior frontal gyrus and decreased NH in the bilateral precuneus. Moreover, a significantly negative correlation was observed between the NH values in the bilateral precuneus and the EPQ--Neuroticism scores. The present study should be considered preliminary due to a lenient, uncorrected threshold of p<0.01. The results suggest that abnormal DMN NH exists in drug-naive SD and further highlight the importance of the DMN in the pathophysiology of SD. Copyright © 2015 Elsevier B.V. All rights reserved.

Visual cortex activation in late-onset, Braille naive blind individuals: an fMRI study during semantic and phonological tasks with heard words.

PubMed

Burton, Harold; McLaren, Donald G

2006-01-09

Visual cortex activity in the blind has been shown in Braille literate people, which raise the question of whether Braille literacy influences cross-modal reorganization. We used fMRI to examine visual cortex activation during semantic and phonological tasks with auditory presentation of words in two late-onset blind individuals who lacked Braille literacy. Multiple visual cortical regions were activated in the Braille naive individuals. Positive BOLD responses were noted in lower tier visuotopic (e.g., V1, V2, VP, and V3) and several higher tier visual areas (e.g., V4v, V8, and BA 37). Activity was more extensive and cross-correlation magnitudes were greater during the semantic compared to the phonological task. These results with Braille naive individuals plausibly suggest that visual deprivation alone induces visual cortex reorganization. Cross-modal reorganization of lower tier visual areas may be recruited by developing skills in attending to selected non-visual inputs (e.g., Braille literacy, enhanced auditory skills). Such learning might strengthen remote connections with multisensory cortical areas. Of necessity, the Braille naive participants must attend to auditory stimulation for language. We hypothesize that learning to attend to non-visual inputs probably strengthens the remaining active synapses following visual deprivation, and thereby, increases cross-modal activation of lower tier visual areas when performing highly demanding non-visual tasks of which reading Braille is just one example.

Chloride secretion induced by rotavirus is oxidative stress-dependent and inhibited by Saccharomyces boulardii in human enterocytes.

PubMed

Buccigrossi, Vittoria; Laudiero, Gabriella; Russo, Carla; Miele, Erasmo; Sofia, Morena; Monini, Marina; Ruggeri, Franco Maria; Guarino, Alfredo

2014-01-01

Rotavirus (RV) infection causes watery diarrhea via multiple mechanisms, primarily chloride secretion in intestinal epithelial cell. The chloride secretion largely depends on non-structural protein 4 (NSP4) enterotoxic activity in human enterocytes through mechanisms that have not been defined. Redox imbalance is a common event in cells infected by viruses, but the role of oxidative stress in RV infection is unknown. RV SA11 induced chloride secretion in association with an increase in reactive oxygen species (ROS) in Caco-2 cells. The ratio between reduced (GSH) and oxidized (GSSG) glutathione was decreased by RV. The same effects were observed when purified NSP4 was added to Caco-2 cells. N-acetylcysteine (NAC), a potent antioxidant, strongly inhibited the increase in ROS and GSH imbalance. These results suggest a link between oxidative stress and RV-induced diarrhea. Because Saccharomyces boulardii (Sb) has been effectively used to treat RV diarrhea, we tested its effects on RV-infected cells. Sb supernatant prevented RV-induced oxidative stress and strongly inhibited chloride secretion in Caco-2 cells. These results were confirmed in an organ culture model using human intestinal biopsies, demonstrating that chloride secretion induced by RV-NSP4 is oxidative stress-dependent and is inhibited by Sb, which produces soluble metabolites that prevent oxidative stress. The results of this study provide novel insights into RV-induced diarrhea and the efficacy of probiotics.

Chloride Secretion Induced by Rotavirus Is Oxidative Stress-Dependent and Inhibited by Saccharomyces boulardii in Human Enterocytes

PubMed Central

Buccigrossi, Vittoria; Laudiero, Gabriella; Russo, Carla; Miele, Erasmo; Sofia, Morena; Monini, Marina; Ruggeri, Franco Maria; Guarino, Alfredo

2014-01-01

Rotavirus (RV) infection causes watery diarrhea via multiple mechanisms, primarily chloride secretion in intestinal epithelial cell. The chloride secretion largely depends on non-structural protein 4 (NSP4) enterotoxic activity in human enterocytes through mechanisms that have not been defined. Redox imbalance is a common event in cells infected by viruses, but the role of oxidative stress in RV infection is unknown. RV SA11 induced chloride secretion in association with an increase in reactive oxygen species (ROS) in Caco-2 cells. The ratio between reduced (GSH) and oxidized (GSSG) glutathione was decreased by RV. The same effects were observed when purified NSP4 was added to Caco-2 cells. N-acetylcysteine (NAC), a potent antioxidant, strongly inhibited the increase in ROS and GSH imbalance. These results suggest a link between oxidative stress and RV-induced diarrhea. Because Saccharomyces boulardii (Sb) has been effectively used to treat RV diarrhea, we tested its effects on RV-infected cells. Sb supernatant prevented RV-induced oxidative stress and strongly inhibited chloride secretion in Caco-2 cells. These results were confirmed in an organ culture model using human intestinal biopsies, demonstrating that chloride secretion induced by RV-NSP4 is oxidative stress-dependent and is inhibited by Sb, which produces soluble metabolites that prevent oxidative stress. The results of this study provide novel insights into RV-induced diarrhea and the efficacy of probiotics. PMID:24918938

Addition of docetaxel and/or zoledronic acid to standard of care for hormone-naive prostate cancer: a cost-effectiveness analysis.

PubMed

Zhang, Pengfei; Wen, Feng; Fu, Ping; Yang, Yu; Li, Qiu

2017-07-31

The effectiveness of the addition of docetaxel and/or zoledronic acid to the standard of care (SOC) for hormone-naive prostate cancer has been evaluated in the STAMPEDE trial. The object of the present analysis was to evaluate the cost-effectiveness of these treatment options in the treatment of advanced hormone-naive prostate cancer in China. A cost-effectiveness analysis using a Markov model was carried out from the Chinese societal perspective. The efficacy data were obtained from the STAMPEDE trial and health utilities were derived from previous studies. Transition probabilities were calculated based on the survival in each group. The primary endpoint in the analysis was the incremental cost-effectiveness ratio (ICER), and model uncertainties were explored by 1-way sensitivity analysis and probabilistic sensitivity analysis. SOC alone generated an effectiveness of 2.65 quality-adjusted life years (QALYs) at a lifetime cost of $20,969.23. At a cost of $25,001.34, SOC plus zoledronic acid was associated with 2.69 QALYs, resulting in an ICER of $100,802.75/QALY compared with SOC alone. SOC plus docetaxel gained an effectiveness of 2.85 QALYs at a cost of $28,764.66, while the effectiveness and cost data in the SOC plus zoledronic acid/docetaxel group were 2.78 QALYs and $32,640.95. Based on the results of the analysis, SOC plus zoledronic acid, SOC plus docetaxel, and SOC plus zoledronic acid/docetaxel are unlikely to be cost-effective options in patients with advanced hormone-naive prostate cancer compared with SOC alone.

Professional Stereotypes of Interprofessional Education Naive Pharmacy and Nursing Students.

PubMed

Thurston, Maria Miller; Chesson, Melissa M; Harris, Elaine C; Ryan, Gina J

2017-06-01

Objective. To assess and compare interprofessional education (IPE) naive pharmacy and nursing student stereotypes prior to completion of an IPE activity. Methods. Three hundred and twenty-three pharmacy students and 275 nursing students at Mercer University completed the Student Stereotypes Rating Questionnaire. Responses from pharmacy and nursing students were compared, and responses from different level learners within the same profession also were compared. Results. Three hundred and fifty-six (59.5%) students completed the survey. Pharmacy students viewed pharmacists more favorably than nursing students viewed pharmacists for all attributes except the ability to work independently. Additionally, nursing students viewed nurses less favorably than pharmacy students viewed nurses for academic ability and practical skills. There was some variability in stereotypes between professional years. Conclusion. This study confirms the existence of professional stereotypes, although overall student perceptions of their own profession and the other were generally positive.

Professional Stereotypes of Interprofessional Education Naive Pharmacy and Nursing Students

PubMed Central

Thurston, Maria Miller; Harris, Elaine C.; Ryan, Gina J.

2017-01-01

Objective. To assess and compare interprofessional education (IPE) naive pharmacy and nursing student stereotypes prior to completion of an IPE activity. Methods. Three hundred and twenty-three pharmacy students and 275 nursing students at Mercer University completed the Student Stereotypes Rating Questionnaire. Responses from pharmacy and nursing students were compared, and responses from different level learners within the same profession also were compared. Results. Three hundred and fifty-six (59.5%) students completed the survey. Pharmacy students viewed pharmacists more favorably than nursing students viewed pharmacists for all attributes except the ability to work independently. Additionally, nursing students viewed nurses less favorably than pharmacy students viewed nurses for academic ability and practical skills. There was some variability in stereotypes between professional years. Conclusion. This study confirms the existence of professional stereotypes, although overall student perceptions of their own profession and the other were generally positive. PMID:28720912

A Public Database of Memory and Naive B-Cell Receptor Sequences.

PubMed

DeWitt, William S; Lindau, Paul; Snyder, Thomas M; Sherwood, Anna M; Vignali, Marissa; Carlson, Christopher S; Greenberg, Philip D; Duerkopp, Natalie; Emerson, Ryan O; Robins, Harlan S

2016-01-01

The vast diversity of B-cell receptors (BCR) and secreted antibodies enables the recognition of, and response to, a wide range of epitopes, but this diversity has also limited our understanding of humoral immunity. We present a public database of more than 37 million unique BCR sequences from three healthy adult donors that is many fold deeper than any existing resource, together with a set of online tools designed to facilitate the visualization and analysis of the annotated data. We estimate the clonal diversity of the naive and memory B-cell repertoires of healthy individuals, and provide a set of examples that illustrate the utility of the database, including several views of the basic properties of immunoglobulin heavy chain sequences, such as rearrangement length, subunit usage, and somatic hypermutation positions and dynamics.

Finger Tapping-Related Activation Differences in Treatment-Naive Pediatric Tourette Syndrome: A Comparison of the Preferred and Nonpreferred Hand

ERIC Educational Resources Information Center

Roessner, Veit; Wittfoth, Matthias; August, Julia M.; Rothenberger, Aribert; Baudewig, Jurgen; Dechent, Peter

2013-01-01

Background: Disturbances of motor circuitry are commonly encountered in Tourette syndrome (TS). The aim of this study was to investigate simple motor performance differences between boys with TS and healthy controls. Methods: We attempted to provide insight into motor network alterations by studying a group of treatment-naive patients suffering…

Altered neural responses to heat pain in drug-naive patients with Parkinson disease.

PubMed

Forkmann, Katarina; Grashorn, Wiebke; Schmidt, Katharina; Fründt, Odette; Buhmann, Carsten; Bingel, Ulrike

2017-08-01

Pain is a frequent but still neglected nonmotor symptom of Parkinson disease (PD). However, neural mechanisms underlying pain in PD are poorly understood. Here, we explored whether the high prevalence of pain in PD might be related to dysfunctional descending pain control. Using functional magnetic resonance imaging we explored neural responses during the anticipation and processing of heat pain in 21 PD patients (Hoehn and Yahr I-III) and 23 healthy controls (HC). Parkinson disease patients were naive to dopaminergic medication to avoid confounding drug effects. Fifteen heat pain stimuli were applied to the participants' forearm. Intensity and unpleasantness ratings were provided for each stimulus. Subjective pain perception was comparable for PD patients and HC. Neural processing, however, differed between groups: PD patients showed lower activity in several descending pain modulation regions (dorsal anterior cingulate cortex [dACC], subgenual anterior cingulate cortex, and dorsolateral prefrontal cortex [DLPFC]) and lower functional connectivity between dACC and DLPFC during pain anticipation. Parkinson disease symptom severity was negatively correlated with dACC-DLPFC connectivity indicating impaired functional coupling of pain modulatory regions with disease progression. During pain perception PD patients showed higher midcingulate cortex activity compared with HC, which also scaled with PD severity. Interestingly, dACC-DLPFC connectivity during pain anticipation was negatively associated with midcingulate cortex activity during the receipt of pain in PD patients. This study indicates altered neural processing during the anticipation and receipt of experimental pain in drug-naive PD patients. It provides first evidence for a progressive decline in descending pain modulation in PD, which might be related to the high prevalence of pain in later stages of PD.

Regulation of Msx-1, Msx-2, Bmp-2 and Bmp-4 during foetal and postnatal mammary gland development.

PubMed

Phippard, D J; Weber-Hall, S J; Sharpe, P T; Naylor, M S; Jayatalake, H; Maas, R; Woo, I; Roberts-Clark, D; Francis-West, P H; Liu, Y H; Maxson, R; Hill, R E; Dale, T C

1996-09-01

Expression of the Msx-1 and Msx-2 homeobox genes have been shown to be coordinately regulated with the Bmp-2 and Bmp-4 ligands in a variety of developing tissues. Here we report that transcripts from all four genes are developmentally regulated during both foetal and postnatal mammary gland development. The location and time-course of the Bmp and Msx expression point to a role for Msx and Bmp gene products in the control of epithelial-mesenchymal interactions. Expression of Msx-2, but not Msx-1, Bmp-2 or Bmp-4 was decreased following ovariectomy, while expression of the human Msx-2 homologue was regulated by 17beta-oestradiol in the MCF-7 breast cancer cell line. The regulation of Msx-2 expression by oestrogen raises the possibility that hormonal regulation of mammary development is mediated through the control of epithelial-mesenchymal interactions.

Large-scale sequence and structural comparisons of human naive and antigen-experienced antibody repertoires

PubMed Central

DeKosky, Brandon J.; Lungu, Oana I.; Park, Daechan; Johnson, Erik L.; Charab, Wissam; Chrysostomou, Constantine; Kuroda, Daisuke; Ellington, Andrew D.; Ippolito, Gregory C.; Gray, Jeffrey J.; Georgiou, George

2016-01-01

Elucidating how antigen exposure and selection shape the human antibody repertoire is fundamental to our understanding of B-cell immunity. We sequenced the paired heavy- and light-chain variable regions (VH and VL, respectively) from large populations of single B cells combined with computational modeling of antibody structures to evaluate sequence and structural features of human antibody repertoires at unprecedented depth. Analysis of a dataset comprising 55,000 antibody clusters from CD19+CD20+CD27− IgM-naive B cells, >120,000 antibody clusters from CD19+CD20+CD27+ antigen–experienced B cells, and >2,000 RosettaAntibody-predicted structural models across three healthy donors led to a number of key findings: (i) VH and VL gene sequences pair in a combinatorial fashion without detectable pairing restrictions at the population level; (ii) certain VH:VL gene pairs were significantly enriched or depleted in the antigen-experienced repertoire relative to the naive repertoire; (iii) antigen selection increased antibody paratope net charge and solvent-accessible surface area; and (iv) public heavy-chain third complementarity-determining region (CDR-H3) antibodies in the antigen-experienced repertoire showed signs of convergent paired light-chain genetic signatures, including shared light-chain third complementarity-determining region (CDR-L3) amino acid sequences and/or Vκ,λ–Jκ,λ genes. The data reported here address several longstanding questions regarding antibody repertoire selection and development and provide a benchmark for future repertoire-scale analyses of antibody responses to vaccination and disease. PMID:27114511

HIV model incorporating differential progression for treatment-naive and treatment-experienced infectives.

PubMed

Chigidi, Esther; Lungu, Edward M

2009-07-01

We formulate an HIV/AIDS deterministic model which incorporates differential infectivity and disease progression for treatment-naive and treatment-experienced HIV/AIDS infectives. To illustrate our model, we have applied it to estimate adult HIV prevalence, the HIV population, the number of new infectives and the number of AIDS deaths for Botswana for the period 1984 to 2012. It is found that the prevalence peaked in the year 2000 and the HIV population is now decreasing. We have also found that under the current conditions, the reproduction number is Rc approximately 13, which is less than the 2004 estimate of Rc approximately equal 4 by [11] and [13]. The results in this study suggest that the HAART program has yielded positive results for Botswana.

Visual cortex activation in late-onset, Braille naive blind individuals: An fMRI study during semantic and phonological tasks with heard words

PubMed Central

Burton, Harold; McLaren, Donald G.

2013-01-01

Visual cortex activity in the blind has been shown in Braille literate people, which raise the question of whether Braille literacy influences cross-modal reorganization. We used fMRI to examine visual cortex activation during semantic and phonological tasks with auditory presentation of words in two late-onset blind individuals who lacked Braille literacy. Multiple visual cortical regions were activated in the Braille naive individuals. Positive BOLD responses were noted in lower tier visuotopic (e.g., V1, V2, VP, and V3) and several higher tier visual areas (e.g., V4v, V8, and BA 37). Activity was more extensive and cross-correlation magnitudes were greater during the semantic compared to the phonological task. These results with Braille naive individuals plausibly suggest that visual deprivation alone induces visual cortex reorganization. Cross-modal reorganization of lower tier visual areas may be recruited by developing skills in attending to selected non-visual inputs (e.g., Braille literacy, enhanced auditory skills). Such learning might strengthen remote connections with multisensory cortical areas. Of necessity, the Braille naive participants must attend to auditory stimulation for language. We hypothesize that learning to attend to non-visual inputs probably strengthens the remaining active synapses following visual deprivation, and thereby, increases cross-modal activation of lower tier visual areas when performing highly demanding non-visual tasks of which reading Braille is just one example. PMID:16198053

Psychological distress in corticosteroid-naive patients with systemic lupus erythematosus: A prospective cross-sectional study.

PubMed

Nishimura, K; Omori, M; Katsumata, Y; Sato, E; Kawaguchi, Y; Harigai, M; Yamanaka, H; Ishigooka, J

2016-04-01

Psychological distress, such as depression and anxiety, has been intensively studied in patients with systemic lupus erythematosus (SLE). However, those studies have mostly included patients who were treated with corticosteroids, which might themselves induce mood disturbances. We investigated psychological distress in corticosteroid-naive patients with SLE who did not exhibit any overt neuropsychiatric manifestations. Forty-three SLE in-patients with no current or past abnormal neuropsychiatric history participated in the study. Patients and 30 healthy control subjects with similar demographic and personality characteristics were administered a comprehensive battery of psychological/neuropsychological tests. The Profile of Mood States (POMS) was used to assess depression and anxiety. Results of clinical, laboratory, and neurological tests were compared with regard to their presence. Prevalence of depression was higher in patients (n = 11, 25.6%) than in controls (n = 2, 6.7%; p = 0.035), although prevalence of anxiety did not differ across groups (patients: 34.9%, n = 15; controls: 16.7%, n = 5; p = 0.147). Using multiple logistic regression analysis, we identified avoidance coping methods (OR, 1.3; 95% CI 1.030-1.644; p = 0.027) as an independent risk factor for depression. Our results indicate that depression presents more frequently in corticosteroid-naive patients with early-stage, active SLE than in the normal population, but anxiety does not. Depression may be related to psychological reactions to suffering from the disease. © The Author(s) 2015.

1H magnetic resonance spectroscopy evidence for occipital involvement in treatment-naive paediatric obsessive-compulsive disorder.

PubMed

Ljungberg, Maria; Nilsson, Marie K L; Melin, Karin; Jönsson, Lars; Carlsson, Arvid; Carlsson, Åsa; Forssell-Aronsson, Eva; Ivarsson, Tord; Carlsson, Maria; Starck, Göran

2017-06-01

Obsessive-compulsive disorder (OCD) is a chronic psychiatric disorder leading to considerable distress and disability. Therapies are effective in a majority of paediatric patients, however, many only get partial response. It is therefore important to study the underlying pathophysiology of the disorder. 1H magnetic resonance spectroscopy (MRS) was used to study the concentration of brain metabolites in four different locations (cingulate gyrus and sulcus, occipital cortex, thalamus and right caudate nucleus). Treatment-naive children and adolescents with OCD (13 subjects) were compared with a group of healthy age- and gender-matched subjects (11 subjects). Multivariate analyses were performed on the concentration values. No separation between controls and patients was found. However, a correlation between metabolite concentrations and symptom severity as measured with the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) was found. Strongest was the correlation with the CY-BOCS obsession subscore and aspartate and choline in the caudate nucleus (positively correlated with obsessions), lipids at 2 and 0.9 ppm in thalamus, and occipital glutamate+glutamine, N-acetylaspartate and myo-inosytol (negatively correlated with obsessions). The observed correlations between 1H MRS and CY-BOCS in treatment-naive patients further supports an occipital involvement in OCD. The results are consistent with our previous study on adult OCD patients. The 1H MRS data were not supportive of a separation between the patient and control groups.

Children's Naive Concepts of OCD and How They Are Affected by Biomedical Versus Cognitive Behavioural Psychoeducation.

PubMed

Butlin, B; Wilson, C

2018-04-04

How we conceptualize mental health conditions is important as it impacts on a wide range of mediators of treatment outcome. We do not know how children intuitively conceptualize obsessive-compulsive disorder (OCD), nor do we know the relative impact of biomedical or cognitive behavioural conceptual explanations, yet both are being widely used in psychoeducation for children with OCD. This study identified children's naive concepts of OCD, and the comparative impact of biomedical versus cognitive behavioural psychoeducation on perceived prognosis. A within- and between-subjects experimental design was used. After watching a video of a young person describing their OCD, 202 children completed a questionnaire examining their concepts of the condition. They repeated the questionnaire following a second equivalent video, this time preceded by either biomedical or cognitive behavioural psychoeducation. Participants' naive concepts of OCD reflected predominant models of OCD in healthcare. Even at the minimal dose of psychoeducation, participants' conceptualizations of OCD changed. Prior exposure to OCD resulted in a stronger alignment with the biomedical model. Exposure to biomedical psychoeducation resulted in participants predicting a slower recovery with less chance of complete remission. Psychoeducation for childhood OCD is impactful. Despite its wide use by clinicians and mental health services, biomedical psychoeducation appears to have deleterious effects. Children's concepts of OCD merit attention but caution should be applied in how they are targeted.

[Voxel-Based Morphometry in Medicated-naive Boys with Attention-deficit/hyperactivity Disorder(ADHD)].

PubMed

Liu, Qi; Chen, Lizhou; Li, Fei; Chen, Ying; Guo, Lanting; Gong, Qiyong; Huang, Xiaoqi

2016-06-01

Attention-deficit/hyperactivity disorder(ADHD)is one of the most common neuro-developmental disorders occurring in childhood,characterized by symptoms of age-inappropriate inattention,hyperactivity/impulsivity,and the prevalence is higher in boys.Although gray matter volume deficits have been frequently reported for ADHD children via structural magnetic resonance imaging,few of them had specifically focused on male patients.The present study aimed to explore the alterations of gray matter volumes in medicated-naive boys with ADHD via a relatively new voxel-based morphometry technique.According to the criteria of DSM-IV-TR,43medicated-naive ADHD boys and 44age-matched healthy boys were recruited.The magnetic resonance image(MRI)scan was performed via a 3T MRI system with three-dimensional(3D)spoiled gradient recalled echo(SPGR)sequence.Voxel-based morphometry with diffeomorphic anatomical registration through exponentiated lie algebra in SPM8 was used to preprocess the3DT1-weighted images.To identify gray matter volume differences between the ADHD and the controls,voxelbased analysis of whole brain gray matter volumes between two groups were done via two sample t-test in SPM8 with age as covariate,threshold at P<0.001.Finally,compared to the controls,significantly reduced gray matter volumes were identified in the right orbitofrontal cortex(peak coordinates[-2,52,-25],t=4.01),and bilateral hippocampus(Left:peak coordinates[14,0,-18],t=3.61;Right:peak coordinates[-14,15,-28],t=3.64)of ADHD boys.Our results demonstrated obvious reduction of whole brain gray matter volumes in right orbitofrontal cortex and bilateral hippocampus in boys with ADHD.This suggests that the abnormalities of prefrontal-hippocampus circuit may be the underlying cause of the cognitive dysfunction and abnormal behavioral inhibition in medicatednaive boys with ADHD.

Impairment of Swimming Motility by Antidiarrheic Lactobacillus acidophilus Strain LB Retards Internalization of Salmonella enterica Serovar Typhimurium within Human Enterocyte-Like Cells▿

PubMed Central

Liévin-Le Moal, Vanessa; Amsellem, Raymonde; Servin, Alain L.

2011-01-01

We report that both culture and the cell-free culture supernatant (CFCS) of Lactobacillus acidophilus strain LB (Lactéol Boucard) have the ability (i) to delay the appearance of Salmonella enterica serovar Typhimurium strain SL1344-induced mobilization of F-actin and, subsequently, (ii) to retard cell entry by S. Typhimurium SL1344. Time-lapse imaging and Western immunoblotting showed that S. Typhimurium SL1344 swimming motility, as represented by cell tracks of various types, was rapidly but temporarily blocked without affecting the expression of FliC flagellar propeller protein. We show that the product(s) secreted by L. acidophilus LB that supports the inhibitory activity is heat stable and of low molecular weight. The product(s) caused rapid depolarization of the S. Typhimurium SL1344 cytoplasmic membrane without affecting bacterial viability. We identified inhibition of swimming motility as a newly discovered mechanism by which the secreted product(s) of L. acidophilus strain LB retards the internalization of the diarrhea-associated pathogen S. enterica serovar Typhimurium within cultured human enterocyte-like cells. PMID:21825295

Foetal hypothalamic and pituitary expression of gonadotrophin-releasing hormone and galanin systems is disturbed by exposure to sewage sludge chemicals via maternal ingestion.

PubMed

Bellingham, M; Fowler, P A; Amezaga, M R; Whitelaw, C M; Rhind, S M; Cotinot, C; Mandon-Pepin, B; Sharpe, R M; Evans, N P

2010-06-01

Animals and humans are chronically exposed to endocrine disrupting chemicals (EDCs) that are ubiquitous in the environment. There are strong circumstantial links between environmental EDC exposure and both declining human/wildlife reproductive health and the increasing incidence of reproductive system abnormalities. The verification of such links, however, is difficult and requires animal models exposed to 'real life', environmentally relevant concentrations/mixtures of environmental contaminants (ECs), particularly in utero, when sensitivity to EC exposure is high. The present study aimed to determine whether the foetal sheep reproductive neuroendocrine axis, particularly gondotrophin-releasing hormone (GnRH) and galaninergic systems, were affected by maternal exposure to a complex mixture of chemicals, applied to pasture, in the form of sewage sludge. Sewage sludge contains high concentrations of a spectrum of EDCs and other pollutants, relative to environmental concentrations, but is frequently recycled to land as a fertiliser. We found that foetuses exposed to the EDC mixture in utero through their mothers had lower GnRH mRNA expression in the hypothalamus and lower GnRH receptor (GnRHR) and galanin receptor (GALR) mRNA expression in the hypothalamus and pituitary gland. Strikingly, this, treatment had no significant effect on maternal GnRH or GnRHR mRNA expression, although GALR mRNA expression within the maternal hypothalamus and pituitary gland was reduced. The present study clearly demonstrates that the developing foetal neuroendocrine axis is sensitive to real-world mixtures of environmental chemicals. Given the important role of GnRH and GnRHR in the regulation of reproductive function, its known role programming role in utero, and the role of galanin in the regulation of many physiological/neuroendocrine systems, in utero changes in the activity of these systems are likely to have long-term consequences in adulthood and represent a novel pathway through

Identification of HIV infection-related DNA methylation sites and advanced epigenetic aging in HIV-positive, treatment-naive U.S. veterans.

PubMed

Nelson, Kristin N; Hui, Qin; Rimland, David; Xu, Ke; Freiberg, Matthew S; Justice, Amy C; Marconi, Vincent C; Sun, Yan V

2017-02-20

HIV-positive individuals are at higher risk than healthy persons for aging-related diseases, including myocardial infarction and non-AIDS defining cancers. Recent evidence suggests that HIV infection may modulate changes in the host cell epigenome, and these changes represent a potential mechanism through which HIV infection accelerates aging. We assessed the difference in DNA methylation (DNAm) age, an aging marker involving multiple age-related cytosine-guanine dinucleotide (CpG) sites, among antiretroviral treatment (ART)-naive HIV-positive and HIV-negative individuals in a cohort of veterans from the Veterans Aging Cohort Study. Peripheral blood samples were collected from 19 ART-naive, HIV-positive, and 19 HIV-negative male participants, matched by age and race. Blood samples were collected from HIV-positive participants 7-11 years after ART initiation. We compared DNAm age between HIV-positive and HIV-negative groups at baseline and between HIV-positive patients at baseline and follow-up. We also performed an epigenome-wide analysis to identify CpG methylation sites associated with HIV infection. DNAm age in HIV-positive individuals is, on average, 11.2 years higher than HIV study participants at baseline, and two of 10 HIV-positive individuals showed an increase in DNAm age after ART initiation. Epigenome-wide association studies showed an association of HIV infection with one site, in gene VPS37B, which approached statistical significance in our cohort (P = 3.30 × 10, Bonferroni-corrected threshold = 1.22 × 10) and was replicated in a second, larger cohort. ART treatment-naive HIV-positive individuals have significantly older DNAm age compared to HIV-negative individuals in the Veterans Aging Cohort Study cohort. Longitudinal changes in DNAm age are highly variable across individuals after initiation of antiretroviral therapy.

Tonic LAT-HDAC7 Signals Sustain Nur77 and Irf4 Expression to Tune Naive CD4 T Cells.

PubMed

Myers, Darienne R; Lau, Tannia; Markegard, Evan; Lim, Hyung W; Kasler, Herbert; Zhu, Minghua; Barczak, Andrea; Huizar, John P; Zikherman, Julie; Erle, David J; Zhang, Weiguo; Verdin, Eric; Roose, Jeroen P

2017-05-23

CD4 + T cells differentiate into T helper cell subsets in feedforward manners with synergistic signals from the T cell receptor (TCR), cytokines, and lineage-specific transcription factors. Naive CD4 + T cells avoid spontaneous engagement of feedforward mechanisms but retain a prepared state. T cells lacking the adaptor molecule LAT demonstrate impaired TCR-induced signals yet cause a spontaneous lymphoproliferative T helper 2 (T H 2) cell syndrome in mice. Thus, LAT constitutes an unexplained maintenance cue. Here, we demonstrate that tonic signals through LAT constitutively export the repressor HDAC7 from the nucleus of CD4 + T cells. Without such tonic signals, HDAC7 target genes Nur77 and Irf4 are repressed. We reveal that Nur77 suppresses CD4 + T cell proliferation and uncover a suppressive role for Irf4 in T H 2 polarization; halving Irf4 gene-dosage leads to increases in GATA3 + and IL-4 + cells. Our studies reveal that naive CD4 + T cells are dynamically tuned by tonic LAT-HDAC7 signals. Published by Elsevier Inc.

Immunological unresponsiveness in mice. II. Cellular basis of immunological unresponsiveness induced in foetal and neonatal mice by transfer of human gamma-globulin by the maternal route.

PubMed Central

Shinka, S; Komatsu, T; Dohi, Y; Amano, T

1979-01-01

The cellular basis of the mechanism of immunological tolerance to human gamma-globulin (H gamma G) induced in foetal and neonatal mice by materno-foetal or materno-neonatal transfer after a single injection of tolerogen (deaggregated H gamma G) into the mothers was investigated using a cell transfer system and assays of passive haemagglutinating antibodies and plaque-forming cells to H gamma G. The results demonstrated that B cells are mainly involved in the tolerance induced on the fourteenth day of gestation, whereas inactivation of T cells may account for the tolerance induced on the eighteenth day of gestation and in the neonatal stage. Treatment of the mothers with tolerogen and then anti-H gamma G serum reduced the tolerance induced on the fourteenth day of gestation, but did not affect that induced on the eighteenth day of gestation and in the neonatal stage. Cell transfer experiments showed that B-cell tolerance induced on the fourteenth day of gestation was prevented by passive antibody, while T-cell tolerance induced on the eighteenth day of gestation and in the neonatal stage was not affected by passive antibody. Assay of the anti-DNP antibody response after immunization with DNP10-H gamma G showed that treatment of mice with the tolerogen on the eighteenth day of gestation, but not the fourteenth day of gestation, inactivated H gamma G-reactive helper cells. The significance of these results is discussed in relation to the results of the cell transfer experiments described as above. PMID:89080

A contribution to the discussion concerning the variability of the third peroneal muscle: an anatomical analysis on the basis of foetal material.

PubMed

Domagała, Z; Gworys, B; Kreczyńska, B; Mogbel, S

2006-11-01

The aim of the work was to make a systemic study of the variability of the human musculus peroneus tertius during the foetal period. Examination was made of 193 foetuses of ages ranging from 84 to 256 days after conception. The results obtained indicated that the musculus peroneus tertius was present in 83.16% of the human foetuses studied and that its intrauterine development was progressive and almost proportional. Previous studies have not revealed dimorphic or bilateral differences with respect to any of the features examined. On the basis of the examinations and bibliographical data a uniform typology of the musculus peroneus tertius variants was created and three final types were distinguished: the pithecogenic (44% cases), eugenic (34% cases) and progenic (22% cases).

A Systematic Review of Known Mechanisms of Hydroxyurea-induced Foetal Haemoglobin for Treatment of Sickle Cell Disease

PubMed Central

Pule, Gift D.; Mowla, Shaheen; Novitzky, Nicolas; Wiysonge, Charles S.; Wonkam, Ambroise

2016-01-01

Aims To report on molecular mechanisms of foetal haemoglobin (HbF) induction by hydroxyurea (HU) for the treatment of Sickle Cell Disease (SCD). Study Design Systematic review. Results Studies have provided consistent associations between genomic variations in HbF-promoting loci and variable HbF level in response to HU. Numerous signal transduction pathways have been implicated, through the identification of key genomic variants in BCL11A, HBS1L-MYB, SAR1 or XmnI polymorphism that predispose the response to the treatment, and signal transduction pathways, that modulate γ-globin expression (cAMP/cGMP; Giα/JNK/Jun; methylation and microRNA). Three main molecular pathways have been reported: 1) Epigenetic modifications, transcriptional events and signalling pathways involved in HU-mediated response, 2) Signalling pathways involving HU-mediated response and 3) Post-transcriptional pathways (regulation by microRNAs). Conclusions The complete picture of HU-mediated mechanisms of HbF production in SCD remains elusive. Research on post-transcriptional mechanisms could lead to therapeutic targets that may minimize alterations to the cellular transcriptome. PMID:26327494

Decreased glutathione levels and impaired antioxidant enzyme activities in drug-naive first-episode schizophrenic patients

PubMed Central

2011-01-01

Background The aim of this study was to determine glutathione levels and antioxidant enzyme activities in the drug-naive first-episode patients with schizophrenia in comparison with healthy control subjects. Methods It was a case-controlled study carried on twenty-three patients (20 men and 3 women, mean age = 29.3 ± 7.5 years) recruited in their first-episode of schizophrenia and 40 healthy control subjects (36 men and 9 women, mean age = 29.6 ± 6.2 years). In patients, the blood samples were obtained prior to the initiation of neuroleptic treatments. Glutathione levels: total glutathione (GSHt), reduced glutathione (GSHr) and oxidized glutathione (GSSG) and antioxidant enzyme activities: superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) were determined by spectrophotometry. Results GSHt and reduced GSHr were significantly lower in patients than in controls, whereas GSSG was significantly higher in patients. GPx activity was significantly higher in patients compared to control subjects. CAT activity was significantly lower in patients, whereas the SOD activity was comparable to that of controls. Conclusion This is a report of decreased plasma levels of GSHt and GSHr, and impaired antioxidant enzyme activities in drug-naive first-episode patients with schizophrenia. The GSH deficit seems to be implicated in psychosis, and may be an important indirect biomarker of oxidative stress in schizophrenia early in the course of illness. Finally, our results provide support for further studies of the possible role of antioxidants as neuroprotective therapeutic strategies for schizophrenia from early stages. PMID:21810251

White matter integrity in alcohol-naive youth with a family history of alcohol use disorders

PubMed Central

Squeglia, L. M.; Jacobus, J.; Brumback, T.; Meloy, M. J.; Tapert, S. F.

2014-01-01

Background Understanding pre-existing neural vulnerabilities found in youth who are family history positive (FHP) for alcohol use disorders could help inform preventative interventions created to delay initiation age and escalation of heavy drinking. The goal of this study was to compare indices of white matter integrity using diffusion tensor imaging (DTI) between FHP and family history negative (FHN) youth using a sample of 94 alcohol-naive adolescents and to examine if differences were associated with global and domain-specific cognitive functioning. Method Participants were 48 FHP and 46 FHN demographically matched, healthy, substance-naive 12- to 14-year-olds (54% female) recruited from local middle schools. Participants completed a neuropsychological test battery and magnetic resonance imaging session, including DTI. Results FHP youth had higher fractional anisotropy and axial diffusivity, and lower radial and mean diffusivity, than FHN youth in 19 clusters spanning projection, association and interhemispheric white matter tracts. Findings were replicated after controlling for age, gender, socio-economic status, grade and pubertal development. Groups did not differ significantly on global or domain-specific neuropsychological test scores. Conclusions FHP teens showed higher white matter integrity, but similar cognitive functioning, to FHN youth. More mature neural features could be related to more precocious behaviors, such as substance use initiation, in FHP youth. Future research exploring white matter maturation before and after substance use initiation will help elucidate the neuro-developmental trajectories in youth at risk for substance use disorders, to inform preventive efforts and better understand the sequelae of adolescent alcohol and drug use. PMID:25066702

CD95 co-stimulation blocks activation of naive T cells by inhibiting T cell receptor signaling

PubMed Central

Lindquist, Jonathan A.; Arhel, Nathalie; Felder, Edward; Karl, Sabine; Haas, Tobias L.; Fulda, Simone; Walczak, Henning; Kirchhoff, Frank; Debatin, Klaus-Michael

2009-01-01

CD95 is a multifunctional receptor that induces cell death or proliferation depending on the signal, cell type, and cellular context. Here, we describe a thus far unknown function of CD95 as a silencer of T cell activation. Naive human T cells triggered by antigen-presenting cells expressing a membrane-bound form of CD95 ligand (CD95L) or stimulated by anti-CD3 and -CD28 antibodies in the presence of recombinant CD95L had reduced activation and proliferation, whereas preactivated, CD95-sensitive T cells underwent apoptosis. Triggering of CD95 during T cell priming interfered with proximal T cell receptor signaling by inhibiting the recruitment of ζ-chain–associated protein of 70 kD, phospholipase-γ, and protein kinase C-θ into lipid rafts, thereby preventing their mutual tyrosine protein phosphorylation. Subsequently, Ca2+ mobilization and nuclear translocation of transcription factors NFAT, AP1, and NF-κB were strongly reduced, leading to impaired cytokine secretion. CD95-mediated inhibition of proliferation in naive T cells could not be reverted by the addition of exogenous interleukin-2 and T cells primed by CD95 co-stimulation remained partially unresponsive upon secondary T cell stimulation. HIV infection induced CD95L expression in primary human antigeen-presenting cells, and thereby suppressed T cell activation, suggesting that CD95/CD95L-mediated silencing of T cell activation represents a novel mechanism of immune evasion. PMID:19487421

Investigate-and-redesign tasks as a context for learning and doing science and technology: A study of naive, novice and expert high school and adult designers doing product comparisons and redesign tasks

NASA Astrophysics Data System (ADS)

Crismond, David Paul

This thesis studied high school students and adults with varying degrees of design experience doing two technology investigate-and-redesign (I&R) tasks. Each involved subjects investigating products, designing experiments to compare them fairly, and then redesigning the devices. A total of 25 pairs of subjects participated in this investigation and included naive and novice high school designers, as well as naive, novice, and expert adult designers. Subjects of similar age and design experience worked in same-gender teams and met for two 2-hour sessions. The essential research question of this thesis was: "What process skills and concepts do naive, novice and expert designers use and learn when investigating devices, designing experiments, and redesigning the devices?" Three methodologies were used to gather and analyze the data: clinical interviewing (Piaget, 1929/1960), protocol analysis (Ericsson & Simon, 1984) and interaction analysis (Jordan and Henderson, 1995). The thesis provides composite case-studies of 10 of the 50 test sessions, buttressed by descriptions of performance trends for all subjects. Given the small sample sizes involved, the findings are by necessity tentative and not supported by statistical analysis: (1) I&R activities are engaging, less time-intensive complements to design-and-build tasks, which involve simple mechanical devices and carry with them a host of potential "alternative understandings" in science and technology. Much gets learned during these tasks, more involving "device knowledge" and "device inquiry skills" than "big ideas" in science and technology. (2) Redesign tasks scaffold naive and novice designers to improved performance in the multidimensional and context-specific activity of design. The performances of naive and novice designers were more like that of expert designers when redesigning existing devices than when doing start-from-scratch designing. (3) Conceptual redesign involved more analysis- than synthesis

Effect of Lactobacillus plantarum Tennozu-SU2 on Salmonella Typhimurium Infection in Human Enterocyte-Like HT-29-Luc Cells and BALB/c Mice.

PubMed

Hirano, Shino; Yokota, Yasushi; Eda, Mika; Kuda, Takashi; Shikano, Ayane; Takahashi, Hajime; Kimura, Bon

2017-03-01

The probiotic properties and inhibitory effect on Salmonella Typhimurium adhesion on human enterocyte-like HT-29-Luc cells of three Lactobacillus plantarum strains isolated from fermented fish, beach sand and a coastal plant were determined. Compared with the type strain L. plantarum NBRC 15891 T , which was isolated from pickled cabbage, L. plantarum Tennozu-SU2 isolated from the acorn of a coastal tree showed high autoaggregation in de Man, Rogosa and Sharpe (MRS) broth and an antagonistic effect against S. Typhimurium in brain heart infusion (BHI) broth. Furthermore, heat-killed L. plantarum Tennozu-SU2 cells inhibited S. Typhimurium adhesion on HT-29-Luc cells. Both live and heat-killed L. plantarum Tennozu-SU2 cells showed an inhibitory effect on gut colonisation in BALB/c mice, as assessed by viable Salmonella count in faecal samples and by invasion into liver and spleen tissues. The properties shown in this study suggest that L. plantarum Tennozu-SU2 is useful as a starter and probiotic bacteria in functional food material.

Resting-state cerebellar-cerebral networks are differently affected in first-episode, drug-naive schizophrenia patients and unaffected siblings.

PubMed

Guo, Wenbin; Liu, Feng; Chen, Jindong; Wu, Renrong; Zhang, Zhikun; Yu, Miaoyu; Xiao, Changqing; Zhao, Jingping

2015-11-26

Dysconnectivity hypothesis posits that schizophrenia is a disorder with dysconnectivity of the cortico-cerebellar-thalamic-cortical circuit (CCTCC). However, it remains unclear to the changes of the cerebral connectivity with the cerebellum in schizophrenia patients and unaffected siblings. Forty-nine patients with first-episode, drug-naive schizophrenia patients, 46 unaffected siblings of schizophrenia patients and 46 healthy controls participated in the study. Seed-based resting-state functional connectivity approach was employed to analyze the data. Compared with the controls, the patients and the siblings share increased default-mode network (DMN) seed - right Crus II connectivity. The patients have decreased right dorsal attention network (DAN) seed - bilateral cerebellum 4,5 connectivity relative to the controls. By contrast, the siblings exhibit increased FC between the right DAN seed and the right cerebellum 6 and right cerebellum 4,5 compared to the controls. No other abnormal connectivities (executive control network and salience network) are observed in the patients/siblings relative to the controls. There are no correlations between abnormal cerebellar-cerebral connectivities and clinical variables. Cerebellar-cerebral connectivity of brain networks within the cerebellum are differently affected in first-episode, drug-naive schizophrenia patients and unaffected siblings. Increased DMN connectivity with the cerebellum may serve as potential endophenotype for schizophrenia.

Resting-state cerebellar-cerebral networks are differently affected in first-episode, drug-naive schizophrenia patients and unaffected siblings

PubMed Central

Guo, Wenbin; Liu, Feng; Chen, Jindong; Wu, Renrong; Zhang, Zhikun; Yu, Miaoyu; Xiao, Changqing; Zhao, Jingping

2015-01-01

Dysconnectivity hypothesis posits that schizophrenia is a disorder with dysconnectivity of the cortico-cerebellar-thalamic-cortical circuit (CCTCC). However, it remains unclear to the changes of the cerebral connectivity with the cerebellum in schizophrenia patients and unaffected siblings. Forty-nine patients with first-episode, drug-naive schizophrenia patients, 46 unaffected siblings of schizophrenia patients and 46 healthy controls participated in the study. Seed-based resting-state functional connectivity approach was employed to analyze the data. Compared with the controls, the patients and the siblings share increased default-mode network (DMN) seed – right Crus II connectivity. The patients have decreased right dorsal attention network (DAN) seed – bilateral cerebellum 4,5 connectivity relative to the controls. By contrast, the siblings exhibit increased FC between the right DAN seed and the right cerebellum 6 and right cerebellum 4,5 compared to the controls. No other abnormal connectivities (executive control network and salience network) are observed in the patients/siblings relative to the controls. There are no correlations between abnormal cerebellar-cerebral connectivities and clinical variables. Cerebellar-cerebral connectivity of brain networks within the cerebellum are differently affected in first-episode, drug-naive schizophrenia patients and unaffected siblings. Increased DMN connectivity with the cerebellum may serve as potential endophenotype for schizophrenia. PMID:26608842

You are what your mother eats: evidence for maternal preconception diet influencing foetal sex in humans.

PubMed

Mathews, Fiona; Johnson, Paul J; Neil, Andrew

2008-07-22

Facultative adjustment of sex ratios by mothers occurs in some animals, and has been linked to resource availability. In mammals, the search for consistent patterns is complicated by variations in mating systems, social hierarchies and litter sizes. Humans have low fecundity, high maternal investment and a potentially high differential between the numbers of offspring produced by sons and daughters: these conditions should favour the evolution of facultative sex ratio variation. Yet little is known of natural mechanisms of sex allocation in humans. Here, using data from 740 British women who were unaware of their foetus's gender, we show that foetal sex is associated with maternal diet at conception. Fifty six per cent of women in the highest third of preconceptional energy intake bore boys, compared with 45% in the lowest third. Intakes during pregnancy were not associated with sex, suggesting that the foetus does not manipulate maternal diet. Our results support hypotheses predicting investment in costly male offspring when resources are plentiful. Dietary changes may therefore explain the falling proportion of male births in industrialized countries. The results are relevant to the current debate about the artificial selection of offspring sex in fertility treatment and commercial 'gender clinics'.

Increased anterior default-mode network homogeneity in first-episode, drug-naive major depressive disorder: A replication study.

PubMed

Guo, Wenbin; Cui, Xilong; Liu, Feng; Chen, Jindong; Xie, Guangrong; Wu, Renrong; Zhang, Zhikun; Chen, Huafu; Zhao, Jingping

2018-01-01

Abnormal default-mode network (DMN) homogeneity has been involved in the neurophysiology of major depressive disorder (MDD) with inconsistent findings. The inconsistency may be due to clinical and methodological variability, and the reproducibility of the findings is limited. The present study aimed to examine alterations of the DMN homogeneity in two independent samples of patients with first-episode, drug-naive MDD. The samples included 59 patients with MDD and 31 comparison subjects from Sample 1 and 29 patients with MDD and 24 comparison subjects from Sample 2. Network homogeneity (NH) was computed with an overlapping technique, which was employed to define brain regions with abnormal NH common to the MDD samples. Compared with comparison subjects, patients with MDD exhibited increased NH in an overlapped brain region of the left superior medial prefrontal cortex (MPFC). No correlations were found between abnormal NH and HAMD total/subscale scores in the patients of each sample and in the combined patients from both samples. This study is the first to examine alterations of DMN homogeneity in first-episode, drug-naive patients with MDD in two independent samples by using an overlapping technique. Patients with MDD exhibit increased NH in an overlapped region in the anterior DMN. The present study thus highlights the importance of the DMN in the neurophysiology of MDD. Copyright © 2017 Elsevier B.V. All rights reserved.

Short-lived brain state after cued motor imagery in naive subjects.

PubMed

Pfurtscheller, G; Scherer, R; Müller-Putz, G R; Lopes da Silva, F H

2008-10-01

Multi-channel electroencephalography recordings have shown that a visual cue, indicating right hand, left hand or foot motor imagery, can induce a short-lived brain state in the order of about 500 ms. In the present study, 10 able-bodied subjects without any motor imagery experience (naive subjects) were asked to imagine the indicated limb movement for some seconds. Common spatial filtering and linear single-trial classification was applied to discriminate between two conditions (two brain states: right hand vs. left hand, left hand vs. foot and right hand vs. foot). The corresponding classification accuracies (mean +/- SD) were 80.0 +/- 10.6%, 83.3 +/- 10.2% and 83.6 +/- 8.8%, respectively. Inspection of central mu and beta rhythms revealed a short-lasting somatotopically specific event-related desynchronization (ERD) in the upper mu and/or beta bands starting approximately 300 ms after the cue onset and lasting for less than 1 s.

Chemokine (C-C motif) receptor 5-using envelopes predominate in dual/mixed-tropic HIV from the plasma of drug-naive individuals.

PubMed

Irlbeck, David M; Amrine-Madsen, Heather; Kitrinos, Kathryn M; Labranche, Celia C; Demarest, James F

2008-07-31

HIV-1 utilizes CD4 and either chemokine (C-C motif) receptor 5 (CCR5) or chemokine (C-X-C motif) receptor 4 (CXCR4) to gain entry into host cells. Small molecule CCR5 antagonists are currently being developed for the treatment of HIV-1 infection. Because HIV-1 may also use CXCR4 for entry, the use of CCR5 entry inhibitors is controversial for patients harboring CCR5-using and CXCR4-using (dual/mixed-tropic) viruses. The goal of the present study was to determine the proportion of CCR5-tropic and CXCR4-tropic viruses in dual/mixed-tropic virus isolates from drug-naïve patients and the phenotypic and genotypic relationships of viruses that use CCR5 or CXCR4 or both. Fourteen antiretroviral-naive HIV-1-infected patients were identified as having population coreceptor tropism readout of dual/mixed-tropic viruses. Intrapatient comparisons of coreceptor tropism and genotype of env clones were conducted on plasma virus from each patient. Population HIV-1 envelope tropism and susceptibility to the CCR5 entry inhibitor, aplaviroc, were performed using the Monogram Biosciences Trofile Assay. Twelve env clones from each patient were analyzed for coreceptor tropism, aplaviroc sensitivity, genotype, and intrapatient phylogenetic relationships. Viral populations from antiretroviral-naive patients with dual/mixed-tropic virus are composed primarily of CCR5-tropic env clones mixed with those that use both coreceptors (R5X4-tropic) and, occasionally, CXCR4-tropic env clones. Interestingly, the efficiency of CXCR4 use by R5X4-tropic env clones varied with their genetic relationships to CCR5-tropic env clones from the same patient. These data show that the majority of viruses in these dual/mixed-tropic populations use CCR5 and suggest that antiretroviral-naive patients may benefit from combination therapy that includes CCR5 entry inhibitors.

Infliximab plus methotrexate is superior to methotrexate alone in the treatment of psoriatic arthritis in methotrexate-naive patients: the RESPOND study

PubMed Central

Baranauskaite, Asta; Raffayová, Helena; Kungurov, NV; Kubanova, Anna; Venalis, Algirdas; Helmle, Laszlo; Srinivasan, Shankar; Nasonov, Evgeny; Vastesaeger, Nathan

2012-01-01

Objective To compare the efficacy and safety of treatment with infliximab plus methotrexate with methotrexate alone in methotrexate-naive patients with active psoriatic arthritis (PsA). Methods In this open-label study, patients 18 years and older with active PsA who were naive to methotrexate and not receiving disease-modifying therapy (N=115) were randomly assigned (1:1) to receive either infliximab (5 mg/kg) at weeks 0, 2, 6 and 14 plus methotrexate (15 mg/week); or methotrexate (15 mg/week) alone. The primary assessment was American College of Rheumatology (ACR) 20 response at week 16. Secondary outcome measures included psoriasis area and severity index (PASI), disease activity score in 28 joints (DAS28) and dactylitis and enthesitis assessments. Results At week 16, 86.3% of patients receiving infliximab plus methotrexate and 66.7% of those receiving methotrexate alone achieved an ACR20 response (p<0.02). Of patients whose baseline PASI was 2.5 or greater, 97.1% receiving infliximab plus methotrexate compared with 54.3% receiving methotrexate alone experienced a 75% or greater improvement in PASI (p<0.0001). Improvements in C-reactive protein levels, DAS28 response and remission rates, dactylitis, fatigue and morning stiffness duration were also significantly greater in the group receiving infliximab. In the infliximab plus methotrexate group, 46% (26/57) had treatment-related adverse events (AE) and two patients had serious AE, compared with 24% with AE (13/54) and no serious AE in the methotrexate-alone group. Conclusions Treatment with infliximab plus methotrexate in methotrexate-naive patients with active PsA demonstrated significantly greater ACR20 response rates and PASI75 improvement compared with methotrexate alone and was generally well tolerated. This trial is registered in the US National Institutes of Health clinicaltrials.gov database, identifier NCT00367237. PMID:21994233

Increased naive CD4+ and B lymphocyte subsets are associated with body mass loss and drive relative lymphocytosis in anorexia nervosa patients.

PubMed

Elegido, Ana; Graell, Montserrat; Andrés, Patricia; Gheorghe, Alina; Marcos, Ascensión; Nova, Esther

2017-03-01

Anorexia nervosa (AN) is an atypical form of malnutrition with peculiar changes in the immune system. We hypothesized that different lymphocyte subsets are differentially affected by malnutrition in AN, and thus, our aim was to investigate the influence of body mass loss on the variability of lymphocyte subsets in AN patients. A group of 66 adolescent female patients, aged 12-17 years, referred for their first episode of either AN or feeding or eating disorders not elsewhere classified were studied upon admission (46 AN-restricting subtype, 11 AN-binge/purging subtype, and 9 feeding or eating disorders not elsewhere classified). Ninety healthy adolescents served as controls. White blood cells and lymphocyte subsets were analyzed by flow cytometry. Relationships with the body mass index (BMI) z score were assessed in linear models adjusted by diagnostic subtype and age. Leukocyte numbers were lower in AN patients than in controls, and relative lymphocytosis was observed in AN-restricting subtype. Lower CD8 + , NK, and memory CD8 + counts were found in eating disorder patients compared with controls. No differences were found for CD4 + counts or naive and memory CD4 + subsets between the groups. Negative associations between lymphocyte percentage and the BMI z score, as well as between the B cell counts, naive CD4 + percentage and counts, and the BMI z score, were found. In conclusion, increased naive CD4 + and B lymphocyte subsets associated with body mass loss drive the relative lymphocytosis observed in AN patients, which reflects an adaptive mechanism to preserve the adaptive immune response. Copyright © 2017 Elsevier Inc. All rights reserved.

[Plasticity of bacterial genomes: pathogenicity islands and the locus of enterocyte effacement (LEE)].

PubMed

Kirsch, Petra; Jores, Jörg; Wieler, Lothar H

2004-01-01

Many bacterial virulence attributes, like toxins, adhesins, invasins, iron uptake systems, are encoded within specific regions of the bacterial genome. These in size varying regions are termed pathogenicity islands (PAIs) since they confer pathogenic properties to the respective micro-organism. Per definition PAIs are exclusively found in pathogenic strains and are often inserted near transfer-RNA genes. Nevertheless, non-pathogenic bacteria also possess foreign DNA elements that confer advantageous features, leading to improved fitness. These additional DNA elements as well as PAIs are termed genomic islands and were acquired during bacterial evolution. Significant G+C content deviation in pathogenicity islands with respect to the rest of the genome, the presence of direct repeat sequences at the flanking regions, the presence of integrase gene determinants as other mobility features,the particular insertion site (tRNA gene) as well as the observed genetic instability suggests that pathogenicity islands were acquired by horizontal gene transfer. PAIs are the fascinating proof of the plasticity of bacterial genomes. PAIs were originally described in human pathogenic Escherichia (E.) coli strains. In the meantime PAIs have been found in various pathogenic bacteria of humans, animals and even plants. The Locus of Enterocyte Effacement (LEE) is one particular widely distributed PAI of E coli. In addition, it also confers pathogenicity to the related species Citrobacter (C.) rodentium and Escherichia (E.) alvei. The LEE is an important virulence feature of several animal pathogens. It is an obligate PAI of all animal and human enteropathogenic E. coli (EPEC), and most enterohaemorrhegic E. coli (EHEC) also harbor the LEE. The LEE encodes a type III secretion system, an adhesion (intimin) that mediates the intimate contact between the bacterium and the epithelial cell, as well as various proteins which are secreted via the type III secretion system. The LEE encoded

Immunogenicity and safety of the 13-valent Pneumococcal Conjugate vaccine in 23-valent pneumococcal polysaccharide vaccine-naive and pre-immunized patients under treatment with chronic haemodialysis: a longitudinal quasi-experimental phase IV study.

PubMed

Vandecasteele, S J; De Bacquer, D; Caluwe, R; Ombelet, S; Van Vlem, B

2018-01-01

To benchmark the immunogenicity of pneumococcal conjugated vaccine (PCV-13) versus pneumococcal polysaccharide vaccine (PPV-23) in haemodialysis patients pre-vaccinated or not with PPV-23. The study is a longitudinal quasi-experimental phase IV study in chronic haemodialysis patients aged ≥50 years. Total (ELISA) and functional (opsonophagocytic assay) antibodies after pneumococcal vaccination were quantified at baseline, and after 28 and 365 days. Of 201 eligible patients, 155 were included. Patients were divided in four groups. PPV-23 naive patients were randomized to PPV-23 (40) or PCV-13 (40) vaccination. PPV-23-pre-vaccinated patients were categorized as being vaccinated more (40) or less (35) than 4 years before the study and all received PCV-13. Patients among the four groups had a significant ELISA antibody response for most serotypes that remained significant up to day 365 versus baseline. In PPV-23-naive patients, ELISA antibody titres were significantly higher among PCV-13 versus PPV-23 recipients for six serotypes (1.85-2.34-fold) after 28 days, and remained significantly higher for one serotype (6A, 1.57-fold) after 365 days. Following PCV-13 vaccination, increase in ELISA antibody titres was significantly higher among PPV-23-naive versus PPV-23-pre-vaccinated patients for 12 serotypes after 28 days (1.68-7.74-fold) and remained significantly higher in ten serotypes (1.44-3.29-fold) after 365 days. Immune response after PPV-23 and PCV-13 remains significant for at least 1 year in non-PPV-23-pre-vaccinated patients. Among vaccine-naive haemodialysis patients PCV-13 seems more immunogenic than PPV-23. Immune response to PCV-13 is weaker in PPV-23-pre-vaccinated compared with vaccine-naive patients. Copyright © 2017. Published by Elsevier Ltd.

High Prevalence of HIV Low Abundance Drug-Resistant Variants in a Treatment-Naive Population in North Rift Kenya.

PubMed

Cheriro, Winfrida; Kiptoo, Michael; Kikuvi, Gideon; Mining, Simeon; Emonyi, Wilfred; Songok, Elijah

2015-12-01

The advent of antiretroviral treatment (ART) has resulted in a dramatic reduction in AIDS-related morbidity and mortality. However, the emergence and spread of antiretroviral drug resistance (DR) threaten to negatively impact treatment regimens and compromise efforts to control the epidemic. It is recommended that surveillance of drug resistance occur in conjunction with scale-up efforts to ensure that appropriate first-line therapy is offered relative to the resistance that exists. However, standard resistance testing methods used in Sub-Saharan Africa rely on techniques that do not include low abundance DR variants (LADRVs) that have been documented to contribute to treatment failure. The use of next generation sequencing (NGS) has been shown to be more sensitive to LADRVS. We have carried out a preliminary investigation using NGS to determine the prevalence of LDRVS among a drug-naive population in North Rift Kenya. Antiretroviral-naive patients attending a care clinic in North Rift Kenya were requested to provide and with consent provided blood samples for DR analysis. DNA was extracted and amplified and nested PCR was conducted on the pol RT region using primers tagged with multiplex identifiers (MID). Resulting PCR amplicons were purified, quantified, and pyrosequenced using a GS FLX Titanium PicoTiterPlate (Roche). Valid pyrosequencing reads were aligned with HXB-2 and the frequency and distribution of nucleotide and amino acid changes were determined using an in-house Perl script. DR mutations were identified using the IAS-USA HIV DR mutation database. Sixty samples were successfully sequenced of which 26 were subtype A, 9 were subtype D, 2 were subtype C, and the remaining were recombinants. Forty-six (76.6%) had at least one drug resistance mutation, with 25 (41.6%) indicated as major and the remaining 21 (35%) indicated as minor. The most prevalent mutation was NRTI position K219Q/R (11/46, 24%) followed by NRTI M184V (5/46, 11%) and NNRTI K103N (4/46, 9

Cross-Priming of Naive Cd8 T Cells against Melanoma Antigens Using Dendritic Cells Loaded with Killed Allogeneic Melanoma Cells

PubMed Central

Berard, Frederic; Blanco, Patrick; Davoust, Jean; Neidhart-Berard, Eve-Marie; Nouri-Shirazi, Mahyar; Taquet, Nicolas; Rimoldi, Donata; Cerottini, Jean Charles; Banchereau, Jacques; Palucka, A. Karolina

2000-01-01

The goal of tumor immunotherapy is to elicit immune responses against autologous tumors. It would be highly desirable that such responses include multiple T cell clones against multiple tumor antigens. This could be obtained using the antigen presenting capacity of dendritic cells (DCs) and cross-priming. That is, one could load the DC with tumor lines of any human histocompatibility leukocyte antigen (HLA) type to elicit T cell responses against the autologous tumor. In this study, we show that human DCs derived from monocytes and loaded with killed melanoma cells prime naive CD45RA+CD27+CD8+ T cells against the four shared melanoma antigens: MAGE-3, gp100, tyrosinase, and MART-1. HLA-A201+ naive T cells primed by DCs loaded with HLA-A201− melanoma cells are able to kill several HLA-A201+ melanoma targets. Cytotoxic T lymphocyte priming towards melanoma antigens is also obtained with cells from metastatic melanoma patients. This demonstration of cross-priming against shared tumor antigens builds the basis for using allogeneic tumor cell lines to deliver tumor antigens to DCs for vaccination protocols. PMID:11104796

Targeted Help for Spoken Dialogue Systems: Intelligent Feedback Improves Naive Users' Performance

NASA Technical Reports Server (NTRS)

Hockey, Beth Ann; Lemon, Oliver; Campana, Ellen; Hiatt, Laura; Aist, Gregory; Hieronymous, Jim; Gruenstein, Alexander; Dowding, John

2003-01-01

We present experimental evidence that providing naive users of a spoken dialogue system with immediate help messages related to their out-of-coverage utterances improves their success in using the system. A grammar-based recognizer and a Statistical Language Model (SLM) recognizer are run simultaneously. If the grammar-based recognizer suceeds, the less accurate SLM recognizer hypothesis is not used. When the grammar-based recognizer fails and the SLM recognizer produces a recognition hypothesis, this result is used by the Targeted Help agent to give the user feed-back on what was recognized, a diagnosis of what was problematic about the utterance, and a related in-coverage example. The in-coverage example is intended to encourage alignment between user inputs and the language model of the system. We report on controlled experiments on a spoken dialogue system for command and control of a simulated robotic helicopter.

DETECTION OF TREATMENT-NAIVE CHOROIDAL NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION BY SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PubMed

Ahmed, Daniel; Stattin, Martin; Graf, Alexandra; Forster, Julia; Glittenberg, Carl; Krebs, Ilse; Ansari-Shahrezaei, Siamak

2017-09-04

To compare the detection rate of choroidal neovascularization (CNV) in treatment-naive neovascular age-related macular degeneration by swept source optical coherence tomography angiography (SS-OCTA, Topcon's DRI Triton) working at 1,050 nm wavelength versus fluorescence angiography. Cross-sectional analysis of 156 eyes (107 neovascular age-related macular degeneration and 49 dry AMD) in 98 patients, previously diagnosed by multimodal imaging using fluorescein (FA) and indocyanine green angiography (Heidelberg's Spectralis) in a tertiary retina center, evaluated by SS-OCTA 4.5 mm × 4.5 mm and 6 mm × 6 mm macular cubes. Main outcome measures were sensitivity and specificity of SS-OCTA in AMD. Potential factors influencing CNV detection rate were analyzed. Swept source optical coherence tomography angiography detected CNV in 81 of 107 eyes, resulting in a sensitivity of 75.7%. In 49 eyes with dry AMD, no CNV could be identified (specificity 100%). A statistical significance was calculated for nondetection of treatment-naive CNV by SS-OCTA in pigment epithelial detachment over 400 μm (P = 0.0238). Topcon's SS-OCTA was not able to detect all CNV lesions. Large pigment epithelial detachments were associated with signal loss. Fluorescence angiography still remains the gold standard, but the tested SS-OCTA device can be considered as a feasible additional diagnostic tool in AMD.

Cytopenias among ART-naive patients with advanced HIV disease on enrolment to care and treatment services at a tertiary hospital in Tanzania: A cross-sectional study.

PubMed

Gunda, Daniel W; Godfrey, Kahamba G; Kilonzo, Semvua B; Mpondo, Bonaventura C

2017-03-01

HIV/AIDS causes high morbidity and mortality through both immunosuppression and complications not directly related to immunosuppression. Haematological abnormalities, including various cytopenias, occur commonly in HIV through immune and non-immune pathways. Though these complications could potentially cause serious clinical implications, published literature on the magnitude of this problem and its associated factors in Tanzania is scarce. This study aimed at determining the prevalence and risk factors of HIV-associated cytopenias among ART-naive patients enrolling for care and treatment services at Bugando Care and Treatment Centre (CTC) in Mwanza, Tanzania. This was a cross-sectional clinic-based study done between March 2015 and February 2016, involving all antiretroviral therapy (ART)-naive adult HIV-positive patients enrolling for care and treatment services at Bugando CTC. Patients younger than 18 years and those with missing data were excluded. Data were analysed using Stata version 11 to determine the prevalence and risk factors of cytopenias. A total of 1205 ART-naive patients were included. Median age was 41 years (interquartile range [IQR] 32 to 48). Most participants were female (n = 789; 65.6%), with a female-to-male ratio of 2:1. The median baseline CD4 count was 200 cells/µL (IQR 113 to 439). About half (49%) of the study participants had baseline CD4 counts less than 200 cells/µL. Anaemia, leucopenia, and thrombocytopenia were found in 704 (58.4%), 285 (23.6%), and 174 (14.4%) participants, respectively, and these were strongly associated with advanced HIV infection. The magnitude of cytopenias is high among ART-naive HIV-positive adults, and cytopenias are more marked with advanced HIV infection. Early diagnosis of HIV and timely initiation of ART could potentially reduce the number of people living with advanced HIV disease and its associated complications, including the cytopenias investigated in this study. Patients with cytopenias should

Effectiveness and safety of an abacavir/lamivudine + rilpivirine regimen for the treatment of HIV-1 infection in naive patients.

PubMed

Curran, Adrian; Rojas, Jhon; Cabello, Alfonso; Troya, Jesús; Imaz, Arkaitz; Domingo, Pere; Martinez, Esteban; Ryan, Pablo; Górgolas, Miguel; Podzamczer, Daniel; Knobel, Hernando; Gutiérrez, Félix; Ribera, Esteban

2016-12-01

To describe the effectiveness and safety of an abacavir/lamivudine + rilpivirine regimen in naive HIV-1-infected patients, as there is a lack of data with this combination. This was an observational, retrospective, multicentre study in eight Spanish hospitals. All antiretroviral-naive patients ≥18 years old and starting abacavir/lamivudine + rilpivirine were included. Effectiveness (ITT and on-treatment) and safety (adverse events and laboratory parameters) were assessed during follow-up. Values are expressed as n (%) or median (IQR). The Wilcoxon signed-rank test was used to compare baseline and 6 and 12 month values. Eighty-four patients were included [93% males, age = 36 (30-45) years]. Time since HIV diagnosis was 12 (4-35) months. Fifty-one per cent of patients had comorbidities. Baseline CD4+ was 425 (340-519) cells/mm 3 and baseline HIV-RNA was 19 000 (9500-42 000) copies/mL. Median follow-up was 18 (9-22) months; 100% and 68% patients with at least 6 and 12 months, respectively. At 6 and 12 months effectiveness was 94% and 86% by ITT analysis and 96% and 97% by on-treatment analysis. At 12 months, there were significant increases in CD4+ (+262 cell/mm 3 ) and HDL cholesterol (+4 mg/dL) and a significant decrease in the total cholesterol/HDL cholesterol ratio (-0.2). There were two (2.4%) virological failures (HIV-RNA 50-100 copies/mL); one patient later achieving virological suppression without changing the treatment. Six patients (7.1%) changed treatment due to reasons other than virological failure or side effects. One patient discontinued treatment due to gastrointestinal complaints attributed to abacavir/lamivudine. Abacavir/lamivudine + rilpivirine was an effective and safe option in a selected group of HIV-1-infected treatment-naive patients. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Bidirectional Causal Connectivity in the Cortico-Limbic-Cerebellar Circuit Related to Structural Alterations in First-Episode, Drug-Naive Somatization Disorder

PubMed Central

Li, Ranran; Liu, Feng; Su, Qinji; Zhang, Zhikun; Zhao, Jin; Wang, Ying; Wu, Renrong; Zhao, Jingping; Guo, Wenbin

2018-01-01

Background: Anatomical and functional deficits in the cortico-limbic-cerebellar circuit are involved in the neurobiology of somatization disorder (SD). The present study was performed to examine causal connectivity of the cortico-limbic-cerebellar circuit related to structural deficits in first-episode, drug-naive patients with SD at rest. Methods: A total of 25 first-episode, drug-naive patients with SD and 28 healthy controls underwent structural and resting-state functional magnetic resonance imaging. Voxel-based morphometry and Granger causality analysis (GCA) were used to analyze the data. Results: Results showed that patients with SD exhibited decreased gray matter volume (GMV) in the right cerebellum Crus I, and increased GMV in the left anterior cingulate cortex (ACC), right middle frontal gyrus (MFG), and left angular gyrus. Causal connectivity of the cortico-limbic-cerebellar circuit was partly affected by structural alterations in the patients. Patients with SD showed bidirectional cortico-limbic connectivity abnormalities and bidirectional cortico-cerebellar and limbic-cerebellar connectivity abnormalities. The mean GMV of the right MFG was negatively correlated with the scores of the somatization subscale of the symptom checklist-90 and persistent error response of the Wisconsin Card Sorting Test (WCST) in the patients. A negative correlation was observed between increased driving connectivity from the right MFG to the right fusiform gyrus/cerebellum IV, V and the scores of the Eysenck Personality Questionnaire extraversion subscale. The mean GMV of the left ACC was negatively correlated with the WCST number of errors and persistent error response. Negative correlation was found between the causal effect from the left ACC to the right middle temporal gyrus and the scores of WCST number of categories achieved. Conclusions: Our findings show the partial effects of structural alterations on the cortico-limbic-cerebellar circuit in first-episode, drug-naive

Evaluation of the skin sensitization potential of chemicals using expression of co-stimulatory molecules, CD54 and CD86, on the naive THP-1 cell line.

PubMed

Yoshida, Y; Sakaguchi, H; Ito, Y; Okuda, M; Suzuki, H

2003-04-01

It has been known that dendritic cells (DCs) including Langerhans cells (LCs) play a critical role in the skin sensitization process. Many attempts have been made to develop in vitro sensitization tests that employ DCs derived from peripheral blood mononuclear cells (PBMC-DC) or CD34+ hematopoietic progenitor cells (CD34+ HPC) purified from cord blood or bone marrow. However, the use of the DCs in in vitro methods has been difficult due to the nature of these cells such as low levels in the source and/or donor-to-donor variability. In our studies, we employed the human monocytic leukemia cell line, THP-1, in order to avoid some of these difficulties. At the start, we examined whether treatment of the cells with various cytokines could produce DCs from THP-1. Treatment of THP-1 cells with cytokines such as GM-CSF, IL-4, TNF-alpha, and/or PMA did induce some phenotypic changes in THP-1 cells that were characteristic of DCs. Subsequently, responses to a known sensitizer, dinitrochlorobenzene (DNCB), and a non-sensitizer, dimethyl sulfoxide (DMSO) or sodium lauryl sulfate (SLS), on the expression of co-stimulatory molecules, CD54 and CD86, were examined between the naive cells and the cytokine-treated cells. Interestingly, the naive THP-1 cells responded only to DNCB and the response to the sensitizer was more distinct than cytokine-treated THP-1 cells. Similar phenomena were also observed in the human myeloid leukemia cell line, KG-1. Furthermore, with treatment of DNCB, naive THP-1 cells showed augmented expression of HLA, CD80 and secretion of IL-1 beta. The response of THP-1 cells to a sensitizer was similar to that of LCs/DCs. Upon demonstrating the differentiation of monocyte cells in our system, we then evaluated a series of chemicals, including known sensitizers and non-sensitizers, for their potential to augment CD54 and CD86 expression on naive THP-1 cells. Indeed, known sensitizers such as PPD and 2-MBT significantly augmented CD54 and CD86 expression in a

Effect of Micronutrient Supplementation on Disease Progression in Asymptomatic, Antiretroviral-Naive, HIV-Infected Adults in Botswana A Randomized Clinical Trial

PubMed Central

Baum, Marianna K.; Campa, Adriana; Lai, Shenghan; Martinez, Sabrina Sales; Tsalaile, Lesedi; Burns, Patricia; Farahani, Mansour; Li, Yinghui; van Widenfelt, Erik; Page, John Bryan; Bussmann, Hermann; Fawzi, Wafaie W.; Moyo, Sikhulele; Makhema, Joseph; Thior, Ibou; Essex, Myron; Marlink, Richard

2015-01-01

IMPORTANCE Micronutrient deficiencies occur early in human immunodeficiency virus (HIV) infection, and supplementation with micronutrients may be beneficial; however, its effectiveness has not been investigated early in HIV disease among adults who are antiretroviral therapy (ART) naive. OBJECTIVE To investigate whether long-term micronutrient supplementation is effective and safe in delaying disease progression when implemented early in adults infected with HIV subtype C who are ART-naive. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of supplementation with either daily multivitamins (B vitamins and vitamins C and E), seleniumalone, or multivitamins with selenium vs placebo inafactorial design for 24 months. The study was conducted in 878 patients infected with HIV subtype C with a CD4 cell count greater than 350/μL who were not receiving ART at Princess Marina Hospital in Gaborone, Botswana, between December 2004 and July 2009. INTERVENTIONS Daily oral supplements of B vitamins and vitamins C and E, selenium alone, or multivitamins plus selenium, compared with placebo. MAIN OUTCOMES AND MEASURES Reaching a CD4 cell count less than 200/μL until May 2008; after this date, reaching a CD4 cell count of 250/μL or less, consistent with the standard of care in Botswana for initiation of ART at the time of the study. RESULTS There were 878 participants enrolled and randomized into the study. All participants were ART-naive throughout the study. In intent-to-treat analysis, participants receiving the combined supplement of multivitamins plus selenium had a significantly lower risk vs placebo of reaching CD4 cell count 250/μL or less (adjusted hazard ratio [HR], 0.46; 95% CI, 0.25-0.85; P = .01; absolute event rate [AER], 4.79/100 person-years; censoring rate, 0.92; 17 events; placebo AER, 9.22/100 person-years; censoring rate, 0.85; 32 events). Multivitamins plus selenium in a single supplement, vs placebo, also reduced the risk of secondary events of

Effect of micronutrient supplementation on disease progression in asymptomatic, antiretroviral-naive, HIV-infected adults in Botswana: a randomized clinical trial.

PubMed

Baum, Marianna K; Campa, Adriana; Lai, Shenghan; Sales Martinez, Sabrina; Tsalaile, Lesedi; Burns, Patricia; Farahani, Mansour; Li, Yinghui; van Widenfelt, Erik; Page, John Bryan; Bussmann, Hermann; Fawzi, Wafaie W; Moyo, Sikhulele; Makhema, Joseph; Thior, Ibou; Essex, Myron; Marlink, Richard

2013-11-27

Micronutrient deficiencies occur early in human immunodeficiency virus (HIV) infection, and supplementation with micronutrients may be beneficial; however, its effectiveness has not been investigated early in HIV disease among adults who are antiretroviral therapy (ART) naive. To investigate whether long-term micronutrient supplementation is effective and safe in delaying disease progression when implemented early in adults infected with HIV subtype C who are ART-naive. Randomized clinical trial of supplementation with either daily multivitamins (B vitamins and vitamins C and E), selenium alone, or multivitamins with selenium vs placebo in a factorial design for 24 months. The study was conducted in 878 patients infected with HIV subtype C with a CD4 cell count greater than 350/μL who were not receiving ART at Princess Marina Hospital in Gaborone, Botswana, between December 2004 and July 2009. Daily oral supplements of B vitamins and vitamins C and E, selenium alone, or multivitamins plus selenium, compared with placebo. Reaching a CD4 cell count less than 200/μL until May 2008; after this date, reaching a CD4 cell count of 250/μL or less, consistent with the standard of care in Botswana for initiation of ART at the time of the study. There were 878 participants enrolled and randomized into the study. All participants were ART-naive throughout the study. In intent-to-treat analysis, participants receiving the combined supplement of multivitamins plus selenium had a significantly lower risk vs placebo of reaching CD4 cell count 250/μL or less (adjusted hazard ratio [HR], 0.46; 95% CI, 0.25-0.85; P = .01; absolute event rate [AER], 4.79/100 person-years; censoring rate, 0.92; 17 events; placebo AER, 9.22/100 person-years; censoring rate, 0.85; 32 events). Multivitamins plus selenium in a single supplement, vs placebo, also reduced the risk of secondary events of combined outcomes for disease progression (CD4 cell count ≤250/μL, AIDS-defining conditions, or

Randomized study of repaglinide alone and in combination with metformin in Chinese subjects with type 2 diabetes naive to oral antidiabetes therapy.

PubMed

Wang, Weiqing; Bu, Ruifang; Su, Qing; Liu, Jianying; Ning, Guang

2011-12-01

The aim of this research is to determine efficacy and safety of repaglinide alone and in combination with metformin in Chinese subjects with type 2 diabetes naive to oral antidiabetes therapy. A 16-week, open-label, randomized, active-controlled, parallel-group trial was carried out. Subjects were randomized (1:1) to repaglinide 1 mg t.i.d. (maximum dose, 4 mg t.i.d.) or repaglinide plus metformin 1 mg/500 mg t.i.d. (maximum dose, 4 mg/500 mg t.i.d.). Eligible subjects (18 - 75 years old) had type 2 diabetes, A1C > 8.5%, BMI ≤ 35 kg/m(2), and were naive to oral antidiabetes agents. The primary outcome was A1C reduction. Secondary end points included fasting plasma glucose (FPG), 2-h postprandial glucose (PPG), and 7-point plasma glucose. Baseline characteristics (repaglinide/metformin, n = 218; repaglinide-only, n = 214) were similar between groups. Mean A1C reduction (± SD) was 4.51 ± 1.64% (combination) and 4.05 ± 1.59% (monotherapy). Estimated mean treatment difference for repaglinide/metformin versus repaglinide-only was -0.30% (95% CI -0.49 to -0.11; p < 0.01). Combination treatment demonstrated significant improvements versus monotherapy in FPG, 7-point plasma glucose, and lunchtime and dinnertime 2-h PPG (all p < 0.05). Hypoglycemia rates were 2.04 (combination) versus 1.35 (monotherapy) events/subject-year (p = 0.058). Adverse events were comparable between groups. Repaglinide plus metformin and repaglinide alone provided significant improvements in glycemic control and were well tolerated in Chinese patients naive to treatment with oral antidiabetes agents. Combination therapy with repaglinide plus metformin showed superiority to repaglinide monotherapy in this population. Limitations of this study are that subjects were newly diagnosed and had high mean baseline A1C, which may affect generalizability of results.

Impact of food on the pharmacokinetics of first-line anti-TB drugs in treatment-naive TB patients: a randomized cross-over trial.

PubMed

Saktiawati, Antonia M I; Sturkenboom, Marieke G G; Stienstra, Ymkje; Subronto, Yanri W; Sumardi; Kosterink, Jos G W; van der Werf, Tjip S; Alffenaar, Jan-Willem C

2016-03-01

Concomitant food intake influences pharmacokinetics of first-line anti-TB drugs in healthy volunteers. However, in treatment-naive TB patients who are starting with drug treatment, data on the influence of food intake on the pharmacokinetics are absent. This study aimed to quantify the influence of food on the pharmacokinetics of isoniazid, rifampicin, ethambutol and pyrazinamide in TB patients starting anti-TB treatment. A prospective randomized cross-over pharmacokinetic study was conducted in treatment-naive adults with drug-susceptible TB. They received isoniazid, rifampicin and ethambutol intravenously and oral pyrazinamide on day 1, followed by oral administration of these drugs under fasted and fed conditions on two consecutive days. Primary outcome was the bioavailability while fasting and with concomitant food intake. This study was registered with clinicaltrials.gov identifier NCT02121314. Twenty subjects completed the study protocol. Absolute bioavailability in the fasted state and the fed state was 93% and 78% for isoniazid, 87% and 71% for rifampicin and 87% and 82% for ethambutol. Food decreased absolute bioavailability of isoniazid and rifampicin by 15% and 16%, respectively. Pyrazinamide AUC0-24 was comparable for the fasted state (481 mg·h/L) and the fed state (468 mg·h/L). Food lowered the maximum concentrations of isoniazid, rifampicin and pyrazinamide by 42%, 22% and 10%, respectively. Time to maximum concentration was delayed for isoniazid, rifampicin and pyrazinamide. The pharmacokinetics of ethambutol were unaffected by food. Food decreased absolute bioavailability and maximum concentration of isoniazid and rifampicin, but not of ethambutol or pyrazinamide, in treatment-naive TB patients. In patients prone to low drug exposure, this may further compromise treatment efficacy and increase the risk of acquired drug resistance. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial

Cost of speech-language interventions for children and youth with foetal alcohol spectrum disorder in Canada.

PubMed

Popova, Svetlana; Lange, Shannon; Burd, Larry; Shield, Kevin; Rehm, Jürgen

2014-12-01

This study, which is part of a large economic project on the overall burden and cost associated with Foetal Alcohol Spectrum Disorder (FASD) in Canada, estimated the cost of 1:1 speech-language interventions among children and youth with FASD for Canada in 2011. The number of children and youth with FASD and speech-language disorder(s) (SLD), the distribution of the level of severity, and the number of hours needed to treat were estimated using data from the available literature. 1:1 speech-language interventions were computed using the average cost per hour for speech-language pathologists. It was estimated that ˜ 37,928 children and youth with FASD had SLD in Canada in 2011. Using the most conservative approach, the annual cost of 1:1 speech-language interventions among children and youth with FASD is substantial, ranging from $72.5 million to $144.1 million Canadian dollars. Speech-language pathologists should be aware of the disproportionate number of children and youth with FASD who have SLD and the need for early identification to improve access to early intervention. Early identification and access to high quality services may have a role in decreasing the risk of developing the secondary disabilities and in reducing the economic burden of FASD on society.

You are what your mother eats: evidence for maternal preconception diet influencing foetal sex in humans

PubMed Central

Mathews, Fiona; Johnson, Paul J; Neil, Andrew

2008-01-01

Facultative adjustment of sex ratios by mothers occurs in some animals, and has been linked to resource availability. In mammals, the search for consistent patterns is complicated by variations in mating systems, social hierarchies and litter sizes. Humans have low fecundity, high maternal investment and a potentially high differential between the numbers of offspring produced by sons and daughters: these conditions should favour the evolution of facultative sex ratio variation. Yet little is known of natural mechanisms of sex allocation in humans. Here, using data from 740 British women who were unaware of their foetus's gender, we show that foetal sex is associated with maternal diet at conception. Fifty six per cent of women in the highest third of preconceptional energy intake bore boys, compared with 45% in the lowest third. Intakes during pregnancy were not associated with sex, suggesting that the foetus does not manipulate maternal diet. Our results support hypotheses predicting investment in costly male offspring when resources are plentiful. Dietary changes may therefore explain the falling proportion of male births in industrialized countries. The results are relevant to the current debate about the artificial selection of offspring sex in fertility treatment and commercial ‘gender clinics’. PMID:18430648

Gut Microbial Diversity in Antibiotic-Naive Children After Systemic Antibiotic Exposure: A Randomized Controlled Trial.

PubMed

Doan, Thuy; Arzika, Ahmed M; Ray, Kathryn J; Cotter, Sun Y; Kim, Jessica; Maliki, Ramatou; Zhong, Lina; Zhou, Zhaoxia; Porco, Travis C; Vanderschelden, Benjamin; Keenan, Jeremy D; Lietman, Thomas M

2017-05-01

Antibiotic exposure can alter the gut microbiome. We evaluate the effects of azithromycin on the gut microbiome diversity of children from an antibiotic-naive community in Niger. A population-based sample of 80 children aged 1-60 months in the Dosso region of Niger was randomized to receive a single dose of either oral azithromycin or placebo. Fecal samples were collected immediately before treatment and 5 days after treatment for 16S rRNA gene sequencing. The prespecified outcome was α-diversity (inverse Simpson's α-diversity index), with secondary outcomes of β and γ Simpson's and Shannon's diversities. At 5 days after treatment, 40 children aged 1-60 months were analyzed in the azithromycin-treated group and 40 children in the placebo-treated group. Diversity of the gut microbiome was significantly lower in the treated group (inverse Simpson's α-diversity, 5.03; 95% confidence interval [CI], 4.08-6.14) than in the placebo group (6.91; 95% CI, 5.82-8.21; P = .03). Similarly, the Shannon's α-diversity was lower in the treated group (10.60; 95% CI, 8.82-12.36) than the placebo group (15.42; 95% CI, 13.24-17.80; P = .004). Simpson's community-level (γ) diversity decreased with azithromycin exposure from 17.72 (95% CI, 13.80-20.21) to 10.10 (95% CI, 7.80-11.40; P = .00008), although β-diversity was not significantly reduced (2.56, 95% CI, 1.88-3.12; to 2.01, 95% CI, 1.46-2.51; P = .26). Oral administration of azithromycin definitively decreases the diversity of the gut microbiome of children in an antibiotic-naive community. NCT02048007. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Visualizing Non Infectious and Infectious Anopheles gambiae Blood Feedings in Naive and Saliva-Immunized Mice

PubMed Central

Choumet, Valerie; Attout, Tarik; Chartier, Loïc; Khun, Huot; Sautereau, Jean; Robbe-Vincent, Annie; Brey, Paul; Huerre, Michel; Bain, Odile

2012-01-01

Background Anopheles gambiae is a major vector of malaria and lymphatic filariasis. The arthropod-host interactions occurring at the skin interface are complex and dynamic. We used a global approach to describe the interaction between the mosquito (infected or uninfected) and the skin of mammals during blood feeding. Methods Intravital video microscopy was used to characterize several features during blood feeding. The deposition and movement of Plasmodium berghei sporozoites in the dermis were also observed. We also used histological techniques to analyze the impact of infected and uninfected feedings on the skin cell response in naive mice. Results The mouthparts were highly mobile within the skin during the probing phase. Probing time increased with mosquito age, with possible effects on pathogen transmission. Repletion was achieved by capillary feeding. The presence of sporozoites in the salivary glands modified the behavior of the mosquitoes, with infected females tending to probe more than uninfected females (86% versus 44%). A white area around the tip of the proboscis was observed when the mosquitoes fed on blood from the vessels of mice immunized with saliva. Mosquito feedings elicited an acute inflammatory response in naive mice that peaked three hours after the bite. Polynuclear and mast cells were associated with saliva deposits. We describe the first visualization of saliva in the skin by immunohistochemistry (IHC) with antibodies directed against saliva. Both saliva deposits and sporozoites were detected in the skin for up to 18 h after the bite. Conclusion This study, in which we visualized the probing and engorgement phases of Anopheles gambiae blood meals, provides precise information about the behavior of the insect as a function of its infection status and the presence or absence of anti-saliva antibodies. It also provides insight into the possible consequences of the inflammatory reaction for blood feeding and pathogen transmission. PMID

Which thoughts can kill a boxer? naive theories about cognitive and emotional antecedents of suicide.

PubMed

Spörrle, Matthias; Försterling, Friedrich

2007-12-01

We investigated naive theories regarding the association among beliefs, emotions and behaviours to test Rational Emotive Behaviour Therapy's (REBT) assumption that rational cognitions and adaptive emotions lead to functional behaviours whereas irrational cognitions and maladaptive emotions trigger dysfunctional reactions. We applied an experimental between-subjects design. Participants read newspaper articles about the defeat of a boxer. In one condition, the authentic article informed participants that he committed suicide and in the other, a fictitious article about the same defeat described the athlete as successfully continuing his career. Different question formats were employed to assess participants' assumptions about the stimulus person's defeat-related cognitions and emotions: rating scales, sentence completion and free responses. Participants assumed significantly more irrational beliefs (e.g. I absolutely have to win) on the side of the boxer in the suicide scenario than in the non-suicide version. This finding was obtained by directive and non-directive assessment methods. Additionally, participants expected the suicidal stimulus person to be experiencing maladaptive emotions (e.g. depression, guilt) whereas a successful resumption of his career lead to expectations of adaptive affects (e.g. sadness, concern). Ratings of the functionality revealed that sadness, fear, annoyance and concern were expected to be more functional than depression, anxiety, rage and guilt. The results show that naive psychological theories about the antecedents of dysfunctional behaviour are in accordance with theoretical assumptions of REBT: Irrational beliefs are viewed to be connected with maladaptive emotions and to result in dysfunctional behaviour, and adaptive emotions are thought to be of higher functional value than their maladaptive counterparts. The use of different question formats and a between-subject design excluded that results are due to methodological

Visualizing non infectious and infectious Anopheles gambiae blood feedings in naive and saliva-immunized mice.

PubMed

Choumet, Valerie; Attout, Tarik; Chartier, Loïc; Khun, Huot; Sautereau, Jean; Robbe-Vincent, Annie; Brey, Paul; Huerre, Michel; Bain, Odile

2012-01-01

Anopheles gambiae is a major vector of malaria and lymphatic filariasis. The arthropod-host interactions occurring at the skin interface are complex and dynamic. We used a global approach to describe the interaction between the mosquito (infected or uninfected) and the skin of mammals during blood feeding. Intravital video microscopy was used to characterize several features during blood feeding. The deposition and movement of Plasmodium berghei sporozoites in the dermis were also observed. We also used histological techniques to analyze the impact of infected and uninfected feedings on the skin cell response in naive mice. The mouthparts were highly mobile within the skin during the probing phase. Probing time increased with mosquito age, with possible effects on pathogen transmission. Repletion was achieved by capillary feeding. The presence of sporozoites in the salivary glands modified the behavior of the mosquitoes, with infected females tending to probe more than uninfected females (86% versus 44%). A white area around the tip of the proboscis was observed when the mosquitoes fed on blood from the vessels of mice immunized with saliva. Mosquito feedings elicited an acute inflammatory response in naive mice that peaked three hours after the bite. Polynuclear and mast cells were associated with saliva deposits. We describe the first visualization of saliva in the skin by immunohistochemistry (IHC) with antibodies directed against saliva. Both saliva deposits and sporozoites were detected in the skin for up to 18 h after the bite. This study, in which we visualized the probing and engorgement phases of Anopheles gambiae blood meals, provides precise information about the behavior of the insect as a function of its infection status and the presence or absence of anti-saliva antibodies. It also provides insight into the possible consequences of the inflammatory reaction for blood feeding and pathogen transmission.

Anomalous single-subject based morphological cortical networks in drug-naive, first-episode major depressive disorder.

PubMed

Chen, Taolin; Kendrick, Keith M; Wang, Jinhui; Wu, Min; Li, Kaiming; Huang, Xiaoqi; Luo, Yuejia; Lui, Su; Sweeney, John A; Gong, Qiyong

2017-05-01

Major depressive disorder (MDD) has been associated with disruptions in the topological organization of brain morphological networks in group-level data. Such disruptions have not yet been identified in single-patients, which is needed to show relations with symptom severity and to evaluate their potential as biomarkers for illness. To address this issue, we conducted a cross-sectional structural brain network study of 33 treatment-naive, first-episode MDD patients and 33 age-, gender-, and education-matched healthy controls (HCs). Weighted graph-theory based network models were used to characterize the topological organization of brain networks between the two groups. Compared with HCs, MDD patients exhibited lower normalized global efficiency and higher modularity in their whole-brain morphological networks, suggesting impaired integration and increased segregation of morphological brain networks in the patients. Locally, MDD patients exhibited lower efficiency in anatomic organization for transferring information predominantly in default-mode regions including the hippocampus, parahippocampal gyrus, precuneus and superior parietal lobule, and higher efficiency in the insula, calcarine and posterior cingulate cortex, and in the cerebellum. Morphological connectivity comparisons revealed two subnetworks that exhibited higher connectivity strength in MDD mainly involving neocortex-striatum-thalamus-cerebellum and thalamo-hippocampal circuitry. MDD-related alterations correlated with symptom severity and differentiated individuals with MDD from HCs with a sensitivity of 87.9% and specificity of 81.8%. Our findings indicate that single subject grey matter morphological networks are often disrupted in clinically relevant ways in treatment-naive, first episode MDD patients. Circuit-specific changes in brain anatomic network organization suggest alterations in the efficiency of information transfer within particular brain networks in MDD. Hum Brain Mapp 38

Drug resistance mutations in HIV type 1 isolates from naive patients eligible for first line antiretroviral therapy in JJ Hospital, Mumbai, India.

PubMed

Deshpande, Alake; Karki, Surendra; Recordon-Pinson, Patricia; Fleury, Herve J

2011-12-01

More than 50 HIV-1-infected patients, naive of antiretroviral therapy (ART) but eligible for first line ART in JJ Hospital, Mumbai, India were investigated for surveillance drug resistance mutations (SDRMs); all but one virus belonged to subtype C; we could observe SDRMs to nonnucleoside reverse transcriptase inhibitors and protease inhibitors in 9.6% of the patients.

Optimization of Candidate Selection Using Naive Bayes: Case Study in Company X

NASA Astrophysics Data System (ADS)

Kadar, JA; Agustono, D.; Napitupulu, D.

2018-01-01

This research was conducted as a decision-making system, and an alternative solution to complete the candidate assessment for a particular position. The human resources (HR) section on company X is responsible and initiative in selecting candidates in accordance with the assessment of their superiors. Selection by using the method of filling out the manager’s assessment questionnaire on the candidate’s subordinate. Three (3) managers have been determined to assess the 11 candidates for subordinates. By using questionnaire of quality classification of human resources and formula naive bayes it will get result which finally grouped using criteria scale as final grouping. The HR department has also determined that what is received is that which meets criteria 5. The result is three (3) candidates who can be proposed as candidates for certain positions in company X, and have met all required calculations. Furthermore the candidate will be given to management as an alternative input data in the selection of candidates.

Ultraviolet-C irradiation for inactivation of viruses in foetal bovine serum.

PubMed

Vaidya, Vivek; Dhere, Rajeev; Agnihotri, Snehal; Muley, Ravindra; Patil, Sanjay; Pawar, Amit

2018-07-05

Foetal Bovine Serum (FBS) and porcine trypsin are one of the essential raw materials used in the manufacturing of cell culture based viral vaccines. Being from animal origin, these raw materials can potentially contaminate the final product by known or unknown adventitious agents. The issue is more serious in case of live attenuated viral vaccines, where there is no inactivation step which can take care of such adventitious agents. It is essential to design production processes which can offer maximum viral clearance potential for animal origin products. Ultraviolet-C irradiation is known to inactivate various adventitious viral agents; however there are limited studies on ultraviolet inactivation of viruses in liquid media. We obtained a recently developed UVivatec ultraviolet-C (UV-C) irradiation based viral clearance system for evaluating its efficacy to inactivate selected model viruses. This system has a unique design with spiral path of liquid allowing maximum exposure to UV-C light of a short wavelength of 254 nm. Five live attenuated vaccine viruses and four other model viruses were spiked in tissue culture media and exposed to UV-C irradiation. The pre and post UV-C irradiation samples were analyzed for virus content to find out the extent of inactivation of various viruses. These experiments showed substantial log reduction for the majority of the viruses with few exceptions based on the characteristics of these viruses. Having known the effect of UV irradiation on protein structure, we also evaluated the post irradiation samples of culture media for growth promoting properties using one of the most fastidious human diploid cells (MRC-5). UV-C exposure did not show any notable impact on the nutritional properties of culture media. The use of an UV-C irradiation based system is considered to be promising approach to mitigate the risk of adventitious agents in cell culture media arising through animal derived products. Copyright © 2018 Elsevier Ltd. All

Effects of Alpha-Ketoglutarate on Glutamine Metabolism in Piglet Enterocytes in Vivo and in Vitro.

PubMed

He, Liuqin; Li, Huan; Huang, Niu; Tian, Junquan; Liu, Zhiqiang; Zhou, Xihong; Yao, Kang; Li, Tiejun; Yin, Yulong

2016-04-06

Alpha-ketoglutarate (AKG) plays a vital part in the tricarboxylic acid cycle and is a key intermediate in the oxidation of L-glutamine (Gln). The study was to evaluate effects of AKG on Gln metabolism in vivo and in vitro. A total of twenty-one piglets were weaned at 28 days with a mean body weight (BW) of 6.0 ± 0.2 kg, and randomly divided into 3 groups: corn soybean meal based diet (CON group); the basal diet with 1% alpha-ketoglutarate (AKG treatment group); and the basal diet with 1% L-glutamine (GLN treatment group). Intestinal porcine epithelial cells-1 (IPEC-1) were incubated to investigate effects of 0.5, 2, and 3 mM AKG addition on Gln metabolism. Our results showed that there were no differences (P > 0.05) among the 3 treatments in initial BW, final BW, and average daily feed intake. However, average daily gain (P = 0.013) and gain:feed (P = 0.041) of the AKG group were greater than those of the other two groups. In comparison with the CON group, the AKG and GLN groups exhibited an improvement in villus length, mucosal thickness, and crypt depth in the jejunum of piglets. Serum concentrations of Asp, Glu, Val, Ile, Tyr, Phe, Lys, and Arg in the piglets fed the 1% AKG or Gln diet were lower than those in the CON group. Compared with the CON group, the mRNA expression of jejunal and ileal amino acid (AA) transporters in the AKG and GLN groups were significantly increased (P < 0.05). Additionally, the in vitro study showed that the addition of 0.5, 2, and 3 mM AKG dose-dependently decreased (P < 0.05) the net utilization of Gln and formulation of ammonia, Glu, Ala, and Asp by IPEC-1. In conclusion, dietary AKG supplementation, as a replacement for Gln, could improve Gln metabolism in piglet enterocytes and enhance the utilization of AA.

Cultivation and qPCR Detection of Pathogenic and Antibiotic-Resistant Bacterial Establishment in Naive Broiler Houses.

PubMed

Brooks, J P; McLaughlin, M R; Adeli, A; Miles, D M

2016-05-01

Conventional commercial broiler production involves the rearing of more than 20,000 broilers in a single confined space for approximately 6.5 wk. This environment is known for harboring pathogens and antibiotic-resistant bacteria, but studies have focused on previously established houses with mature litter microbial populations. In the current study, a set of three naive houses were followed from inception through 11 broiler flocks and monitored for ambient climatic conditions, bacterial pathogens, and antibiotic resistance. Within the first 3 wk of the first flock cycle, 100% of litter samples were positive for and , whereas was cultivation negative but PCR positive. Antibiotic resistance genes were ubiquitously distributed throughout the litter within the first flock, approaching 10 to 10 genomic units g. Preflock litter levels were approximately 10 CFU g for heterotrophic plate count bacteria, whereas midflock levels were >10 colony forming units (CFU) g; other indicators demonstrated similar increases. The influence of intrahouse sample location was minor. In all likelihood, given that preflock levels were negative for pathogens and antibiotic resistance genes and 4 to 5 Log lower than flock levels for indicators, incoming birds most likely provided the colonizing microbiome, although other sources were not ruled out. Most bacterial groups experienced a cyclical pattern of litter contamination seen in other studies, whereas microbial stabilization required approximately four flocks. This study represents a first-of-its-kind view into the time required for bacterial pathogens and antibiotic resistance to colonize and establish in naive broiler houses. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Replication capacity in relation to immunologic and virologic outcomes in HIV-1-infected treatment-naive subjects.

PubMed

Skowron, Gail; Spritzler, John G; Weidler, Jodi; Robbins, Gregory K; Johnson, Victoria A; Chan, Ellen S; Asmuth, David M; Gandhi, Rajesh T; Lie, Yolanda; Bates, Michael; Pollard, Richard B

2009-03-01

To evaluate the association between baseline (BL) replication capacity (RC) (RCBL) and immunologic/virologic parameters (at BL and after 48 weeks on therapy) in HIV-1-infected subjects initiating antiretroviral therapy. RCBL was determined using a modified Monogram PhenoSense HIV drug susceptibility assay on plasma HIV-1 from 321 treatment-naive subjects from AIDS Clinical Trials Group 384. Univariate and multivariable analyses were performed to determine the association of RCBL with BL and on-therapy virologic and immunologic outcomes. Higher RCBL was associated with lower baseline CD4 (CD4BL) (r = -0.23, P < 0.0001), higher baseline HIV-1 RNA (r = 0.25, P < 0.0001), higher CD4BL activation percent (r = 0.23, P < 0.0001), and lower CD4BL memory count (r = -0.21, P = 0.0002). In a multivariable model, week 48 CD4 increase (DeltaCD448) was associated with lower CD4BL memory count and higher CD4BL-naive percent (P = 0.004, P = 0.015, respectively). The interaction between CD4BL and RCBL was significant (P = 0.018), with a positive association between RCBL and DeltaCD448 in subjects with higher CD4BL and a negative association at lower absCD4BL. At baseline, higher RC was significantly associated with higher HIV-1 RNA, higher CD4 cell activation, lower CD4 cell count, and lower CD4 memory cell count. These factors may interact, directly or indirectly, to modify the extent to which CD4 recovery occurs in patients starting antiretroviral therapy at different CD4BL counts.

Inhalation Anthrax (Ames aerosol) in Naive and Vaccinated New Zealand Rabbits: Characterizing the Spread of Bacteria from Lung Deposition to Bacteremia

DTIC Science & Technology

2012-06-28

York City anthrax investigation working group. (2003). Isolated case of bioterrorism-related inhalational anthrax, New York City , 2001. Emerg. Infect...ORIGINAL RESEARCH ARTICLE published: 28 June 2012 doi: 10.3389/fcimb.2012.00087 Inhalational anthrax(Ames aerosol) in naïve and vaccinated New ...Inhalation Antrax (Ames aerosol) In Naive and Vaccinated New Zealand Rabbits: Characterizing The Spread Of Bacteria From Lung Deposition To Bacteremia

Selective functional dysconnectivity of the dorsal-anterior subregion of the precuneus in drug-naive major depressive disorder.

PubMed

Zhu, Jiajia; Lin, Xiaodong; Lin, Chongguang; Zhuo, Chuanjun; Yu, Yongqiang

2018-01-01

Patients with major depressive disorder (MDD) have shown altered resting-state functional connectivity (rsFC) of the precuneus; however, it is unknown whether rsFC of the precuneus subregions is differentially affected in this disorder. In this study, we aimed to clarify this issue by comparing rsFC of each precuneus subregion between patients with MDD and healthy controls. Forty-seven drug-naive patients with MDD and 47 sex-, age- and education-matched healthy controls underwent resting-state functional magnetic resonance imaging (fMRI). The precuneus was divided into PCun-1 (dorsal-central portion; medial area 7), PCun-2 (dorsal-anterior portion; medial area 5), PCun-3 (dorsal-posterior portion; dorsomedial parietooccipital sulcus) and PCun-4 (ventral portion; area 31). The rsFC of each precuneus subregion was compared between the two groups. Compared with healthy controls, patients with MDD exhibited increased rsFC between the left PCun-2 and the right fusiform gyrus, lateral prefrontal cortex, sensorimotor cortex and supramarginal gyrus. No significant inter-group difference was observed in the rsFC of other precuneus subregions. In addition, there was no difference in gray matter volume of all the precuneus subregions between patients with MDD and healthy controls. Some of the patients had chronic MDD and relevant neuropsychological data were not collected. These findings suggest a selective functional dysconnectivity of the precuneus subregions in drug-naive MDD, characterized by the hyperconnnectivity between the dorsal-anterior subregion and regions involved in visual, executive control, sensorimotor and bottom-up attention functions. Copyright © 2017 Elsevier B.V. All rights reserved.

Antiretroviral drug resistance in HIV-1 therapy-naive patients in Cuba.

PubMed

Pérez, Lissette; Kourí, Vivian; Alemán, Yoan; Abrahantes, Yeisel; Correa, Consuelo; Aragonés, Carlos; Martínez, Orlando; Pérez, Jorge; Fonseca, Carlos; Campos, Jorge; Álvarez, Delmis; Schrooten, Yoeri; Dekeersmaeker, Nathalie; Imbrechts, Stijn; Beheydt, Gertjan; Vinken, Lore; Soto, Yudira; Álvarez, Alina; Vandamme, Anne-Mieke; Van Laethem, Kristel

2013-06-01

In Cuba, antiretroviral therapy rollout started in 2001 and antiretroviral therapy coverage has reached almost 40% since then. The objectives of this study were therefore to analyze subtype distribution, and level and patterns of drug resistance in therapy-naive HIV-1 patients. Four hundred and one plasma samples were collected from HIV-1 therapy-naive patients in 2003 and in 2007-2011. HIV-1 drug resistance genotyping was performed in the pol gene and drug resistance was interpreted according to the WHO surveillance drug-resistance mutations list, version 2009. Potential impact on first-line therapy response was estimated using genotypic drug resistance interpretation systems HIVdb version 6.2.0 and Rega version 8.0.2. Phylogenetic analysis was performed using Neighbor-Joining. The majority of patients were male (84.5%), men who have sex with men (78.1%) and from Havana City (73.6%). Subtype B was the most prevalent subtype (39.3%), followed by CRF20-23-24_BG (19.5%), CRF19_cpx (18.0%) and CRF18_cpx (10.3%). Overall, 29 patients (7.2%) had evidence of drug resistance, with 4.0% (CI 1.6%-4.8%) in 2003 versus 12.5% (CI 7.2%-14.5%) in 2007-2011. A significant increase in drug resistance was observed in recently HIV-1 diagnosed patients, i.e. 14.8% (CI 8.0%-17.0%) in 2007-2011 versus 3.8% (CI 0.9%-4.7%) in 2003 (OR 3.9, CI 1.5-17.0, p=0.02). The majority of drug resistance was restricted to a single drug class (75.8%), with 55.2% patients displaying nucleoside reverse transcriptase inhibitor (NRTI), 10.3% non-NRTI (NNRTI) and 10.3% protease inhibitor (PI) resistance mutations. Respectively, 20.7% and 3.4% patients carried viruses containing drug resistance mutations against NRTI+NNRTI and NRTI+NNRTI+PI. The first cases of resistance towards other drug classes than NRTI were only detected from 2008 onwards. The most frequent resistance mutations were T215Y/rev (44.8%), M41L (31.0%), M184V (17.2%) and K103N (13.8%). The median genotypic susceptibility score for the

Infectivity of Plasmodium falciparum in Malaria-Naive Individuals Is Related to Knob Expression and Cytoadherence of the Parasite

PubMed Central

Stanisic, Danielle I.; Gerrard, John; Fink, James; Griffin, Paul M.; Liu, Xue Q.; Sundac, Lana; Sekuloski, Silvana; Rodriguez, Ingrid B.; Pingnet, Jolien; Yang, Yuedong; Zhou, Yaoqi; Trenholme, Katharine R.; Wang, Claire Y. T.; Hackett, Hazel; Chan, Jo-Anne A.; Langer, Christine; Hanssen, Eric; Hoffman, Stephen L.; Beeson, James G.; McCarthy, James S.

2016-01-01

Plasmodium falciparum is the most virulent human malaria parasite because of its ability to cytoadhere in the microvasculature. Nonhuman primate studies demonstrated relationships among knob expression, cytoadherence, and infectivity. This has not been examined in humans. Cultured clinical-grade P. falciparum parasites (NF54, 7G8, and 3D7B) and ex vivo-derived cell banks were characterized. Knob and knob-associated histidine-rich protein expression, CD36 adhesion, and antibody recognition of parasitized erythrocytes (PEs) were evaluated. Parasites from the cell banks were administered to malaria-naive human volunteers to explore infectivity. For the NF54 and 3D7B cell banks, blood was collected from the study participants for in vitro characterization. All parasites were infective in vivo. However, infectivity of NF54 was dramatically reduced. In vitro characterization revealed that unlike other cell bank parasites, NF54 PEs lacked knobs and did not cytoadhere. Recognition of NF54 PEs by immune sera was observed, suggesting P. falciparum erythrocyte membrane protein 1 expression. Subsequent recovery of knob expression and CD36-mediated adhesion were observed in PEs derived from participants infected with NF54. Knobless cell bank parasites have a dramatic reduction in infectivity and the ability to adhere to CD36. Subsequent infection of malaria-naive volunteers restored knob expression and CD36-mediated cytoadherence, thereby showing that the human environment can modulate virulence. PMID:27382019

Efficacy and Safety of S-Amlodipine 2.5 and 5 mg/d in Hypertensive Patients Who Were Treatment-Naive or Previously Received Antihypertensive Monotherapy.

PubMed

Şen, Selçuk; Demir, Meral; Yiğit, Zerrin; Üresin, Ali Yağız

2018-07-01

The aim of the present study was to evaluate the efficacy and safety of S-amlodipine 2.5 and 5 mg/d in patients with hypertension who were treatment-naive or previously received antihypertensive monotherapy. During the 8-week treatment period, all patients received S-amlodipine 2.5 mg/d for the first 4 weeks, followed by S-amlodipine 5 mg/d for the second 4 weeks. For efficacy assessments, ambulatory and office blood pressure (BP) measurements were performed during the baseline, fourth-week, and eighth-week visits. For safety assessments, all adverse events and abnormal laboratory findings were recorded. This study is registered with ClinicalTrials.gov (NCT03038451). Of 43 patients evaluated at the screening visit, 33 were enrolled. In the treatment-naive arm, significant reductions in both office and ambulatory systolic BP (SBP) and diastolic BP (DBP) were observed with S-amlodipine 2.5 mg/d and additional significant reductions were achieved with dose titration (S-amlodipine 5 mg/d). At the end of the study, the rate of the treatment-naive patients with BP under control (SBP/DBP <140/90 mm Hg) was 53% with S-amlodipine 2.5 mg and increased to 78% with S-amlodipine 5 mg. For the noninferiority evaluation, S-amlodipine 2.5 and 5 mg/d treatments were generally noninferior to both office and ambulatory BP levels achieved with the medications that the patients received before participating in the study. Five nonserious adverse events likely to be associated with the study drug were observed. No serious adverse event was encountered. Consequently, S-amlodipine can be suggested as an effective and safe treatment option for patients with hypertension.

Impact of TSH during the first trimester of pregnancy on obstetric and foetal complications: Usefulness of 2.5 mIU/L cut-off value.

PubMed

Hernández, Marta; López, Carolina; Soldevila, Berta; Cecenarro, Laura; Martínez-Barahona, María; Palomera, Elisabet; Rius, Ferran; Lecube, Albert; Pelegay, Maria José; García, Jordi; Mauricio, Dídac; Puig Domingo, Manel

2018-05-01

An association of pregnancy outcomes with subclinical hypothyroidism has been reported; however, there still exists a strong controversy regarding whether subclinical hypothyroidism ought to be dealt with or not. The objective of the study was to evaluate the association of foetal-maternal complications with first trimester maternal Thyrotropin (TSH) values. A retrospective study in a single tertiary care hospital was performed. A total of 1981 pregnant women were studied during 2012. Thyrotropin (TSH) universal screening was performed between 9 and 12 weeks of gestation. Outcomes included foetal-maternal complications and newborn health parameters. Median TSH was 1.72 (0.99-2.61) mIU/L. The incidence of perinatal loss, miscarriage and stillbirth was 7.2%, 5.9% and 1.1%, respectively. Median TSH of women with and without miscarriage was 1.97 (1.29-3.28) vs 1.71 (0.96-2.58) mIU/L (P = .009). Incidence of pre-eclampsia was 3.2%; TSH in these women was 2.10 (1.40-2.74) vs 1.71 (0.98-2.59) mIU/L in those without (P = .027). TSH in women with dystocia in labour was 1.76 (1.00-2.53) vs 1.68 (0.94-2.59) mIU/L in those who gave birth with normal progression (P = .044). Women with TSH 2.5-5.1 mIU/L had a higher risk of perinatal loss [OR 1.589 (1.085-2.329)], miscarriage [OR 1.702 (1.126-2.572)] and premature birth [OR 1.39 (1.013-1.876)], adjusted by mother's age. There was no association with the other outcomes analysed. There is a positive association between maternal TSH in the first trimester of pregnancy and the incidence of perinatal loss and miscarriage. The TSH cut-off value of 2.5 mIU/L identified women with higher adverse pregnancy outcomes. © 2018 John Wiley & Sons Ltd.

Modelling foetal growth in a bi-ethnic sample: results from the Born in Bradford (BiB) birth cohort.

PubMed

Norris, Tom; Tuffnell, Derek; Wright, John; Cameron, Noël

2014-01-01

Attempts to explain the increased risk for metabolic disorders observed in South Asians have focused on the "South Asian" phenotype at birth and subsequent post-natal growth, with little research on pre-natal growth. To identify whether divergent growth patterns exist for foetal weight, head (HC) and abdominal circumferences (AC) in a sample of Pakistani and White British foetuses. Models were based on 5553 (weight), 5154 (HC) and 5099 (AC) foetuses from the Born in Bradford birth cohort. Fractional polynomials and mixed effects models were employed to determine growth patterns from ~15 weeks of gestation-birth. Pakistani foetuses were significantly smaller and lighter as early as 20 weeks. However, there was no ethnic difference in the growth patterns of weight and HC. For AC, Pakistani foetuses displayed a trend for reduced growth in the final trimester. As the pattern of weight and HC growth was not significantly different during the period under investigation, the mechanism culminating in the reduced Pakistani size at birth may act earlier in gestation. Reduced AC growth in Pakistanis may represent reduced growth of the visceral organs, with consequences for post-natal liver metabolism and renal function.

Genetic and environmental factors influencing first service conception rate and late embryonic/foetal mortality in low fertility dairy herds.

PubMed

Grimard, B; Freret, S; Chevallier, A; Pinto, A; Ponsart, C; Humblot, P

2006-01-01

The objective of this study was to identify factors affecting variation in conception rate to first artificial inseminations (AI) (CR: number of pregnant cows on D80-100/inseminated cows) and the incidence of embryonic/foetal loss (LEM) between 21 and 80 days of pregnancy (number of cows non-pregnant on D80-100/pregnant on D21) in 44 low fertility dairy herds of the west-central region of France. Reproductive status was assessed using progesterone milk concentration on D0 = Day of AI and D21-24, plasma PSPB concentration on D30-35, rectal palpation on D80-100 and observed return to oestrous. The final data set contained 1285 Prim'Holstein cows, 5.0% (64/1285) were inseminated in the luteal phase (progesterone > or = 3 ng/ml on D0), 61.3% (787/1285) were pregnant on D21-24 (progesterone < 3 ng/ml on D0 and > or = 5 ng/ml on D21-24), 15.4% lost their embryo/foetus between D21-24 and D80-100 (198/1285) and 45.8% (589/1285) were pregnant on D80-100. The incidence of late embryonic/foetal loss (LEM) was 25.2% (198/787). Multivariate logistic regression models including the random herd effect were used to analyse the relationship between AI centre, AI sire, cow's sire, parity, interval between calving and AI, milk production, milk protein content, body condition score (BCS) on D0, season of calving, season of AI, estimated genetic index on CR and LEM incidence. CR was significantly related to parity (p < 0.05), milk production after calving (p < 0.05) and estimated genetic value (p < 0.01). A significant difference in CR was observed for calving to AI interval > or = 70 days versus > or = 90 days, but the overall effect of the interval was not significant (p = 0.11). LEM incidence was affected by period of AI (p < 0.05), milk production (p < 0.05) and BCS (p < 0.05), but was not related to estimated genetic index. In conclusion, in these low fertility herds, the incidence of LEM was high and 25% of the cows lost their embryo after 21 days of pregnancy. LEM was affected

Naive Bayes Bearing Fault Diagnosis Based on Enhanced Independence of Data

PubMed Central

Zhang, Nannan; Wu, Lifeng; Yang, Jing; Guan, Yong

2018-01-01

The bearing is the key component of rotating machinery, and its performance directly determines the reliability and safety of the system. Data-based bearing fault diagnosis has become a research hotspot. Naive Bayes (NB), which is based on independent presumption, is widely used in fault diagnosis. However, the bearing data are not completely independent, which reduces the performance of NB algorithms. In order to solve this problem, we propose a NB bearing fault diagnosis method based on enhanced independence of data. The method deals with data vector from two aspects: the attribute feature and the sample dimension. After processing, the classification limitation of NB is reduced by the independence hypothesis. First, we extract the statistical characteristics of the original signal of the bearings effectively. Then, the Decision Tree algorithm is used to select the important features of the time domain signal, and the low correlation features is selected. Next, the Selective Support Vector Machine (SSVM) is used to prune the dimension data and remove redundant vectors. Finally, we use NB to diagnose the fault with the low correlation data. The experimental results show that the independent enhancement of data is effective for bearing fault diagnosis. PMID:29401730

Sentiment analysis system for movie review in Bahasa Indonesia using naive bayes classifier method

NASA Astrophysics Data System (ADS)

Nurdiansyah, Yanuar; Bukhori, Saiful; Hidayat, Rahmad

2018-04-01

There are many ways of implementing the use of sentiments often found in documents; one of which is the sentiments found on the product or service reviews. It is so important to be able to process and extract textual data from the documents. Therefore, we propose a system that is able to classify sentiments from review documents into two classes: positive sentiment and negative sentiment. We use Naive Bayes Classifier method in this document classification system that we build. We choose Movienthusiast, a movie reviews in Bahasa Indonesia website as the source of our review documents. From there, we were able to collect 1201 movie reviews: 783 positive reviews and 418 negative reviews that we use as the dataset for this machine learning classifier. The classifying accuracy yields an average of 88.37% from five times of accuracy measuring attempts using aforementioned dataset.

Patients with first-episode, drug-naive schizophrenia and subjects at ultra-high risk of psychosis shared increased cerebellar-default mode network connectivity at rest.

PubMed

Wang, Houliang; Guo, Wenbin; Liu, Feng; Wang, Guodong; Lyu, Hailong; Wu, Renrong; Chen, Jindong; Wang, Shuai; Li, Lehua; Zhao, Jingping

2016-05-18

Increased cerebellar-default mode network (DMN) connectivity has been observed in first-episode, drug-naive patients with schizophrenia. However, it remains unclear whether increased cerebellar-DMN connectivity starts earlier than disease onset. Thirty-four ultra-high risk (UHR) subjects, 31 first-episode, drug-naive patients with schizophrenia and 37 healthy controls were enrolled for a resting-state scan. The imaging data were analyzed using the seed-based functional connectivity (FC) method. Compared with the controls, UHR subjects and patients with schizophrenia shared increased connectivity between the right Crus I and bilateral posterior cingulate cortex/precuneus and between Lobule IX and the left superior medial prefrontal cortex. There are positive correlations between the right Crus I-bilateral precuneus connectivity and clinical variables (Structured Interview for Prodromal Syndromes/Positive and Negative Symptom Scale negative symptoms/total scores) in the UHR subjects. Increased cerebellar-DMN connectivity shared by the UHR subjects and the patients not only highlights the importance of the DMN in the pathophysiology of psychosis but also may be a trait alteration for psychosis.

CD4 T cells play important roles in maintaining IL-17-producing γδ T-cell subsets in naive animals.

PubMed

Do, Jeong-Su; Visperas, Anabelle; O'Brien, Rebecca L; Min, Booki

2012-04-01

A proportional balance between αβ and γδ T-cell subsets in the periphery is exceedingly well maintained by a homeostatic mechanism. However, a cellular mechanism underlying the regulation remains undefined. We recently reported that a subset of developing γδ T cells spontaneously acquires interleukin (IL)-17-producing capacity even within naive animals through a transforming growth factor (TGF)β1-dependent mechanism, thus considered 'innate' IL-17-producing cells. Here, we report that γδ T cells generated within αβ T cell (or CD4 T cell)-deficient environments displayed altered cytokine profiles; particularly, 'innate' IL-17 expression was significantly impaired compared with those in wild-type mice. Impaired IL-17 production in γδ T cells was directly related to CD4 T-cell deficiency, because depletion of CD4 T cells in wild-type mice diminished and adoptive CD4 T-cell transfer into T-cell receptor β-/- mice restored IL-17 expression in γδ T cells. CD4 T cell-mediated IL-17 expression required TGFβ1. Moreover, Th17 but not Th1 or Th2 effector CD4 T cells were highly efficient in enhancing γδ T-cell IL-17 expression. Taken together, our results highlight a novel CD4 T cell-dependent mechanism that shapes the generation of IL-17+ γδ T cells in naive settings.

Raltegravir versus Efavirenz regimens in treatment-naive HIV-1-infected patients: 96-week efficacy, durability, subgroup, safety, and metabolic analyses.

PubMed

Lennox, Jeffrey L; Dejesus, Edwin; Berger, Daniel S; Lazzarin, Adriano; Pollard, Richard B; Ramalho Madruga, Jose Valdez; Zhao, Jing; Wan, Hong; Gilbert, Christopher L; Teppler, Hedy; Rodgers, Anthony J; Barnard, Richard J O; Miller, Michael D; Dinubile, Mark J; Nguyen, Bach-Yen; Leavitt, Randi; Sklar, Peter

2010-09-01

We analyzed the 96-week results in the overall population and in prespecified subgroups from the ongoing STARTMRK study of treatment-naive HIV-infected patients. Eligible patients with HIV-1 RNA (vRNA) levels >5000 copies per milliliter and without baseline resistance to efavirenz, tenofovir, or emtricitabine were randomized in a double-blind noninferiority study to receive raltegravir or efavirenz, each combined with tenofovir/emtricitabine. At week 96 counting noncompleters as failures, 81% versus 79% achieved vRNA levels <50 copies per milliliter in the raltegravir and efavirenz groups, respectively [Delta (95% confidence interval) = 2% (-4 to 9), noninferiority P < 0.001]. Mean change in baseline CD4 count was 240 and 225 cells per cubic millimeter in the raltegravir and efavirenz groups, respectively [Delta (95% confidence interval) = 15 (-13 to 42)]. Treatment effects were consistent across prespecified baseline demographic and prognostic subgroups. Fewer drug-related clinical adverse events (47% versus 78%; P < 0.001) occurred in raltegravir than efavirenz recipients. Both regimens had modest effects on serum lipids and glucose levels and on body fat composition. When combined with tenofovir/emtricitabine in treatment-naive patients, raltegravir exhibited durable antiretroviral activity that was noninferior to the efficacy of efavirenz through 96 weeks of therapy. Subgroup analyses were generally consistent with the overall findings. Both regimens were well tolerated.

Whole-exome analysis of foetal autopsy tissue reveals a frameshift mutation in OBSL1, consistent with a diagnosis of 3-M Syndrome.

PubMed

Marshall, Christian R; Farrell, Sandra A; Cushing, Donna; Paton, Tara; Stockley, Tracy L; Stavropoulos, Dimitri J; Ray, Peter N; Szego, Michael; Lau, Lynette; Pereira, Sergio L; Cohn, Ronald D; Wintle, Richard F; Abuzenadah, Adel M; Abu-Elmagd, Muhammad; Scherer, Stephen W

2015-01-01

We report a consanguineous couple that has experienced three consecutive pregnancy losses following the foetal ultrasound finding of short limbs. Post-termination examination revealed no skeletal dysplasia, but some subtle proximal limb shortening in two foetuses, and a spectrum of mildly dysmorphic features. Karyotype was normal in all three foetuses (46, XX) and comparative genomic hybridization microarray analysis detected no pathogenic copy number variants. Whole-exome sequencing and genome-wide homozygosity mapping revealed a previously reported frameshift mutation in the OBSL1 gene (c.1273insA p.T425nfsX40), consistent with a diagnosis of 3-M Syndrome 2 (OMIM #612921), which had not been anticipated from the clinical findings. Our study provides novel insight into the early clinical manifestations of this form of 3-M syndrome, and demonstrates the utility of whole exome sequencing as a tool for prenatal diagnosis in particular when there is a family history suggestive of a recurrent set of clinical symptoms.

Candida species differ in their interactions with immature human gastrointestinal epithelial cells

PubMed Central

Falgier, Christina; Kegley, Sara; Podgorski, Heather; Heisel, Timothy; Storey, Kathleen; Bendel, Catherine M.; Gale, Cheryl A.

2011-01-01

Life-threatening gastrointestinal (GI) diseases of prematurity are highly associated with systemic candidiasis. This implicates the premature GI tract as an important site for invasion by Candida. Invasive interactions of Candida spp. with immature enterocytes have heretofore not been analyzed. Using a primary immature human enterocyte line, we compared the ability of multiple isolates of different Candida spp. to penetrate, injure, and induce a cytokine response from host cells. Of all the Candida spp. analyzed, C. albicans had the greatest ability to penetrate and injure immature enterocytes and to elicit interleukin-8 (IL-8) release (p < 0.01). In addition, C. albicans was the only Candida spp. to form filamentous hyphae when in contact with immature enterocytes. Similarly, a C. albicans mutant with defective hyphal morphogenesis and invasiveness had attenuated cytotoxicity for immature enterocytes (p < 0.003). Thus, hyphal morphogenesis correlates with immature enterocyte penetration, injury and inflammatory responses. Furthermore, variability in enterocyte injury was observed among hyphal-producing C. albicans strains suggesting that individual organism genotypes also influence host-pathogen interactions. Overall, the finding that Candida spp. differed in their interactions with immature enterocytes implicates that individual spp. may employ different pathogenesis mechanisms. PMID:21283049

Cyclic hydrostatic pressure stimulates enhanced bone development in the foetal chick femur in vitro.

PubMed

Henstock, J R; Rotherham, M; Rose, J B; El Haj, A J

2013-04-01

Mechanical loading of bone and cartilage in vivo results in the generation of cyclic hydrostatic forces as bone compression is transduced to fluid pressure in the canalicular network and the joint synovium. It has therefore been suggested that hydrostatic pressure is an important stimulus by which osteochondral cells and their progenitors sense and respond to mechanical loading in vivo. In this study, hydrostatic pressure regimes of 0-279kPa at 0.005-2Hz were applied to organotypically cultured ex vivo chick foetal femurs (e11) for 1hour per day in a custom designed bioreactor for 14days and bone formation assessed by X-ray microtomography and qualified by histology. We found that the mineralised portion of the developing femur cultured under any cyclic hydrostatic pressure regime was significantly larger and/or denser than unstimulated controls but that constant (non-cycling) hydrostatic pressure had no effect on bone growth. Further experiments showed that the increase in bone formation was directly proportional to stimulation frequency (R(2)=0.917), but independent of the magnitude of the pressure applied, whilst even very low frequencies of stimulation (0.005Hz) had significant effects on bone growth. Expression of Type-II collagen in both epiphyses and diaphysis was significantly upregulated (1.48-fold and 1.95-fold respectively), together with osteogenic genes (osteonectin and osteopontin) and the osteocyte maturation marker CD44. This work demonstrates that cyclic hydrostatic pressure promotes bone growth and mineralisation in a developmental model and supports the hypothesis that hydrostatic forces play an important role in regulating bone growth and remodelling in vivo. Copyright © 2013 Elsevier Inc. All rights reserved.

Risk Classification with an Adaptive Naive Bayes Kernel Machine Model.

PubMed

Minnier, Jessica; Yuan, Ming; Liu, Jun S; Cai, Tianxi

2015-04-22

Genetic studies of complex traits have uncovered only a small number of risk markers explaining a small fraction of heritability and adding little improvement to disease risk prediction. Standard single marker methods may lack power in selecting informative markers or estimating effects. Most existing methods also typically do not account for non-linearity. Identifying markers with weak signals and estimating their joint effects among many non-informative markers remains challenging. One potential approach is to group markers based on biological knowledge such as gene structure. If markers in a group tend to have similar effects, proper usage of the group structure could improve power and efficiency in estimation. We propose a two-stage method relating markers to disease risk by taking advantage of known gene-set structures. Imposing a naive bayes kernel machine (KM) model, we estimate gene-set specific risk models that relate each gene-set to the outcome in stage I. The KM framework efficiently models potentially non-linear effects of predictors without requiring explicit specification of functional forms. In stage II, we aggregate information across gene-sets via a regularization procedure. Estimation and computational efficiency is further improved with kernel principle component analysis. Asymptotic results for model estimation and gene set selection are derived and numerical studies suggest that the proposed procedure could outperform existing procedures for constructing genetic risk models.

Mucosal Expression of Type 2 and Type 17 Immune Response Genes Distinguishes Ulcerative Colitis From Colon-Only Crohn's Disease in Treatment-Naive Pediatric Patients.

PubMed

Rosen, Michael J; Karns, Rebekah; Vallance, Jefferson E; Bezold, Ramona; Waddell, Amanda; Collins, Margaret H; Haberman, Yael; Minar, Phillip; Baldassano, Robert N; Hyams, Jeffrey S; Baker, Susan S; Kellermayer, Richard; Noe, Joshua D; Griffiths, Anne M; Rosh, Joel R; Crandall, Wallace V; Heyman, Melvin B; Mack, David R; Kappelman, Michael D; Markowitz, James; Moulton, Dedrick E; Leleiko, Neal S; Walters, Thomas D; Kugathasan, Subra; Wilson, Keith T; Hogan, Simon P; Denson, Lee A

2017-05-01

There is controversy regarding the role of the type 2 immune response in the pathogenesis of ulcerative colitis (UC)-few data are available from treatment-naive patients. We investigated whether genes associated with a type 2 immune response in the intestinal mucosa are up-regulated in treatment-naive pediatric patients with UC compared with patients with Crohn's disease (CD)-associated colitis or without inflammatory bowel disease (IBD), and whether expression levels are associated with clinical outcomes. We used a real-time reverse-transcription quantitative polymerase chain reaction array to analyze messenger RNA (mRNA) expression patterns in rectal mucosal samples from 138 treatment-naive pediatric patients with IBD and macroscopic rectal disease, as well as those from 49 children without IBD (controls), enrolled in a multicenter prospective observational study from 2008 to 2012. Results were validated in real-time reverse-transcription quantitative polymerase chain reaction analyses of rectal RNA from an independent cohort of 34 pediatric patients with IBD and macroscopic rectal disease and 17 controls from Cincinnati Children's Hospital Medical Center. We measured significant increases in mRNAs associated with a type 2 immune response (interleukin [IL]5 gene, IL13, and IL13RA2) and a type 17 immune response (IL17A and IL23) in mucosal samples from patients with UC compared with patients with colon-only CD. In a regression model, increased expression of IL5 and IL17A mRNAs distinguished patients with UC from patients with colon-only CD (P = .001; area under the receiver operating characteristic curve, 0.72). We identified a gene expression pattern in rectal tissues of patients with UC, characterized by detection of IL13 mRNA, that predicted clinical response to therapy after 6 months (odds ratio [OR], 6.469; 95% confidence interval [CI], 1.553-26.94), clinical response after 12 months (OR, 6.125; 95% CI, 1.330-28.22), and remission after 12 months (OR, 5

Immune deficiency could be an early risk factor for altered insulin sensitivity in antiretroviral-naive HIV-1-infected patients: the ANRS COPANA cohort.

PubMed

Boufassa, Faroudy; Goujard, Cécile; Viard, Jean-Paul; Carlier, Robert; Lefebvre, Bénédicte; Yeni, Patrick; Bouchaud, Olivier; Capeau, Jacqueline; Meyer, Laurence; Vigouroux, Corinne

2012-01-01

The relationships between immunovirological status, inflammatory markers, insulin resistance and fat distribution have not been studied in recently diagnosed (<1 year) antiretroviral-naive HIV-1-infected patients. We studied 214 antiretroviral-naive patients at enrolment in the metabolic substudy of the ANRS COPANA cohort. We measured clinical, immunovirological and inflammatory parameters, glucose/insulin during oral glucose tolerance test (OGTT), adipokines, subcutaneous and visceral fat surfaces (subcutaneous adipose tissue [SAT] and visceral adipose tissue [VAT], assessed by computed tomography) and the body fat distribution based on dual-energy X-ray absorptiometry (DEXA). Median age was 36 years; 28% of the patients were female and 35% of sub-Saharan origin; 20% had low CD4(+) T-cell counts (≤200/mm(3)). Patients with low CD4(+) T-cell counts were older and more frequently of sub-Saharan Africa origin, had lower body mass index (BMI) but no different SAT/VAT ratio and fat distribution than other patients. They also had lower total, low-density lipoprotein and high-density lipoprotein cholesterolaemia, higher triglyceridaemia and post-OGTT glycaemia, higher markers of insulin resistance (insulin during OGTT and homeostasis model assessment of insulin resistance) and of inflammation (high-sensitivity C-reactive protein, IL-6, tumour necrosis factor (TNF)-α, sTNFR1 and sTNFR2). After adjustment for age, sex, geographic origin, BMI and waist circumference, increased insulin resistance was not related to any inflammatory marker. In multivariate analysis, low CD4(+) T-cell count was an independent risk factor for altered insulin sensitivity (β-coefficient for HOMA-IR: +0.90; P=0.001; CD4(+) T-cell count >500/mm(3) as the reference), in addition to older age (β: +0.26 for a 10-year increase; P=0.01) and higher BMI (β: +0.07 for a 1-kg/m(2) increase; P=0.003). In ART-naive patients, severe immune deficiency but not inflammation could be an early risk factor for

Assessment of foetal exposure to the homogeneous magnetic field harmonic spectrum generated by electricity transmission and distribution networks.

PubMed

Fiocchi, Serena; Liorni, Ilaria; Parazzini, Marta; Ravazzani, Paolo

2015-04-01

During the last decades studies addressing the effects of exposure to Extremely Low Frequency Electromagnetic Fields (ELF-EMF) have pointed out a possible link between those fields emitted by power lines and childhood leukaemia. They have also stressed the importance of also including in the assessment the contribution of frequency components, namely harmonics, other than the fundamental one. Based on the spectrum of supply voltage networks allowed by the European standard for electricity quality assessment, in this study the exposure of high-resolution three-dimensional models of foetuses to the whole harmonic content of a uniform magnetic field with a fundamental frequency of 50 Hz, was assessed. The results show that the main contribution in terms of induced electric fields to the foetal exposure is given by the fundamental frequency component. The harmonic components add some contributions to the overall level of electric fields, however, due to the extremely low permitted amplitude of the harmonic components with respect to the fundamental, their amplitudes are low. The level of the induced electric field is also much lower than the limits suggested by the guidelines for general public exposure, when the amplitude of the incident magnetic field is set at the maximum permitted level.

Review shows that early foetal alcohol exposure may cause adverse effects even when the mother consumes low levels.

PubMed

Sarman, Ihsan

2018-06-01

Studies are increasingly focusing on the effects of prenatal alcohol exposure (PAE) on child health. The aim of this review was to provide paediatricians with new insights to help them communicate key messages about avoiding alcohol during pregnancy. Inspired by the 7th International Conference on Fetal Alcohol Spectrum Disorder, which focused on integrating research, policy and practice, we studied English language papers published since 2010 on how early PAE triggered epigenetic mechanisms that had an impact on the development of some chronic diseases. We also report the findings of a human study using three-dimensional photography of the face to explore associations between PAE and craniofacial phenotyping. Animal models with different alcohol exposure patterns show that early PAE may lead to long-term chronic effects, due to developmental programming for some adult diseases in cardiovascular, metabolic and renal systems. The study with three-dimensional photographing is very promising in helping paediatricians to understand how even small amounts of PAE can affect craniofacial phenotyping. Even low levels of PAE can cause adverse foetal effects and not just in the brain. It is not currently possible to determine a safe period and level when alcohol consumption would not affect the foetus. ©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Assessment of Foetal Exposure to the Homogeneous Magnetic Field Harmonic Spectrum Generated by Electricity Transmission and Distribution Networks

PubMed Central

Fiocchi, Serena; Liorni, Ilaria; Parazzini, Marta; Ravazzani, Paolo

2015-01-01

During the last decades studies addressing the effects of exposure to Extremely Low Frequency Electromagnetic Fields (ELF-EMF) have pointed out a possible link between those fields emitted by power lines and childhood leukaemia. They have also stressed the importance of also including in the assessment the contribution of frequency components, namely harmonics, other than the fundamental one. Based on the spectrum of supply voltage networks allowed by the European standard for electricity quality assessment, in this study the exposure of high-resolution three-dimensional models of foetuses to the whole harmonic content of a uniform magnetic field with a fundamental frequency of 50 Hz, was assessed. The results show that the main contribution in terms of induced electric fields to the foetal exposure is given by the fundamental frequency component. The harmonic components add some contributions to the overall level of electric fields, however, due to the extremely low permitted amplitude of the harmonic components with respect to the fundamental, their amplitudes are low. The level of the induced electric field is also much lower than the limits suggested by the guidelines for general public exposure, when the amplitude of the incident magnetic field is set at the maximum permitted level. PMID:25837346

Dolutegravir-lamivudine as initial therapy in HIV-1 infected, ARV-naive patients, 48-week results of the PADDLE (Pilot Antiretroviral Design with Dolutegravir LamivudinE) study.

PubMed

Cahn, Pedro; Rolón, María José; Figueroa, María Inés; Gun, Ana; Patterson, Patricia; Sued, Omar

2017-05-09

A proof-of-concept study was designed to evaluate the antiviral efficacy, safety and tolerability of a two-drug regimen with dolutegravir 50 mg once daily (QD) plus lamivudine 300 mg once daily as initial highly active antiretroviral therapy (HAART) among antiretroviral (ARV)-naive patients. PADDLE is a pilot study including 20 treatment-naive adults. To be selected, participants had no IAS-USA-defined resistance, HIV-1 RNA ≤100,000 copies/mL at screening and negative HBsAg. Plasma viral load (pVL) was measured at baseline; days 2, 4, 7, 10, 14, 21 and 28; weeks 6, 8 and 12; and thereafter every 12 weeks up to 96 weeks. Primary endpoint was the proportion of patients with HIV-1 RNA <50 copies/mL in an intention to treat (ITT)-exposed analysis at 48 weeks (the FDA snapshot algorithm). Median HIV-1 RNA at entry was 24,128 copies/mL (interquartile range (IQR): 11,686-36,794). Albeit as per protocol, all patients had pVL ≤100,000 copies/mL at screening as required by inclusion criteria, four patients had ≥100,000 copies/mL at baseline. Median baseline CD4+ T-cell count was 507 per cubic millimetre (IQR: 296-517). A rapid decline in pVL was observed (median VL decay from baseline to week 12 was 2.74 logs). All patients were suppressed at week 8 onwards up to week 24. At week 48, 90% (18/20) reached the primary endpoint of a pVL <50 copies/mL. Median change in CD4 cell count between baseline and week 48 was 267 cells/mm 3 (IQR: 180-462). No major tolerability/toxicity issues were observed. Nineteen patients completed 48 weeks of the study, and one patient (with undetectable VL at last visit) committed suicide. One patient presented a low-level protocol-defined confirmed virological failure at week 36, being the only observed failure. This patient had pVL <50 copies/mL at the end-of-study visit without having changed the two-drug regimen. Observed failure rate was 5%. This is the first report of integrase strand transfer inhibitor/lamivudine dual regimen in

Volume and Asymmetry Abnormalities of Insula in Antipsychotic-Naive Schizophrenia: A 3-Tesla Magnetic Resonance Imaging Study

PubMed Central

Virupaksha, Harve Shanmugam; Kalmady, Sunil V.; Shivakumar, Venkataram; Arasappa, Rashmi; Venkatasubramanian, Ganesan; Gangadhar, Bangalore N.

2012-01-01

Context: Insula, which is a vital brain region for self-awareness, empathy, and sensory stimuli processing, is critically implicated in schizophrenia pathogenesis. Existing studies on insula volume abnormalities report inconsistent findings potentially due to the evaluation of ‘antipsychotic-treated’ schizophrenia patients as well as suboptimal methodology. Aim: To understand the role of insula in schizophrenia. Materials and Methods: In this first-time 3-T magnetic resonance imaging study, we examined antipsychotic-naive schizophrenic patients (N=30) and age-, sex-, handedness- and education-matched healthy controls (N=28). Positive and negative symptoms were scored with good interrater reliability (intraclass correlation coefficient (ICC)>0.9) by using the scales for negative and positive symptoms. Gray matter volume of insula and its anterior/posterior subregions were measured by using a three-dimensional, interactive, semiautomated software based on the valid method with good interrater reliability (ICC>0.85). Intracranial volume was automatically measured by using the FreeSurfer software. Results: Patients had significantly deficient gray matter volumes of left (F=33.4; P<0.00001) and right (F=11.9; P=0.001) insula after controlling for the effects of age, sex, and intracranial volume. Patients with predominantly negative symptoms had a significantly deficient right posterior insula volume than those with predominantly positive symptoms (F=6.3; P=0.02). Asymmetry index analysis revealed anterior insular asymmetry to be significantly reversed (right>left) in male patients in comparison with male controls (left>right) (t=2.7; P=0.01). Conclusions: Robust insular volume deficits in antipsychotic-naive schizophrenia support intrinsic role for insula in pathogenesis of this disorder. The first-time demonstration of a relationship between right posterior insular deficit and negative symptoms is in tune with the background neurobiological literature. Another

Volume and asymmetry abnormalities of insula in antipsychotic-naive schizophrenia: a 3-tesla magnetic resonance imaging study.

PubMed

Virupaksha, Harve Shanmugam; Kalmady, Sunil V; Shivakumar, Venkataram; Arasappa, Rashmi; Venkatasubramanian, Ganesan; Gangadhar, Bangalore N

2012-04-01

Insula, which is a vital brain region for self-awareness, empathy, and sensory stimuli processing, is critically implicated in schizophrenia pathogenesis. Existing studies on insula volume abnormalities report inconsistent findings potentially due to the evaluation of 'antipsychotic-treated' schizophrenia patients as well as suboptimal methodology. To understand the role of insula in schizophrenia. In this first-time 3-T magnetic resonance imaging study, we examined antipsychotic-naive schizophrenic patients (N=30) and age-, sex-, handedness- and education-matched healthy controls (N=28). Positive and negative symptoms were scored with good interrater reliability (intraclass correlation coefficient (ICC)>0.9) by using the scales for negative and positive symptoms. Gray matter volume of insula and its anterior/posterior subregions were measured by using a three-dimensional, interactive, semiautomated software based on the valid method with good interrater reliability (ICC>0.85). Intracranial volume was automatically measured by using the FreeSurfer software. Patients had significantly deficient gray matter volumes of left (F=33.4; P<0.00001) and right (F=11.9; P=0.001) insula after controlling for the effects of age, sex, and intracranial volume. Patients with predominantly negative symptoms had a significantly deficient right posterior insula volume than those with predominantly positive symptoms (F=6.3; P=0.02). Asymmetry index analysis revealed anterior insular asymmetry to be significantly reversed (right>left) in male patients in comparison with male controls (left>right) (t=2.7; P=0.01). Robust insular volume deficits in antipsychotic-naive schizophrenia support intrinsic role for insula in pathogenesis of this disorder. The first-time demonstration of a relationship between right posterior insular deficit and negative symptoms is in tune with the background neurobiological literature. Another novel observation of sex-specific anterior insular asymmetry

Apremilast monotherapy in DMARD-naive psoriatic arthritis patients: results of the randomized, placebo-controlled PALACE 4 trial

PubMed Central

Wells, Alvin F; Edwards, Christopher J; Kivitz, Alan J; Bird, Paul; Nguyen, Dianne; Paris, Maria; Teng, Lichen; Aelion, Jacob A

2018-01-01

Abstract Objectives The PALACE 4 trial evaluated apremilast monotherapy in patients with active PsA who were DMARD-naive. Methods Eligible patients were randomized (1:1:1) to placebo, apremilast 20 mg twice a day or apremilast 30 mg twice a day. At week 16 or 24, placebo patients were rerandomized to apremilast. Double-blind apremilast treatment continued to week 52, with extension up to 4 years. The primary endpoint was the proportion of patients achieving ⩾20% improvement in ACR response criteria (ACR20) at week 16; secondary endpoints included the mean change in the HAQ Disability Index (HAQ-DI) score at week 16. Results A total of 527 patients with mean disease duration of 3.4 years and high disease activity were randomized and received treatment. More apremilast patients achieved ACR20 response at week 16 [placebo, 15.9%; 20 mg, 28.0% (P = 0.0062); 30 mg, 30.7% (P = 0.0010)]. The mean HAQ-DI improvements were −0.17 (20 mg; P = 0.0008) and −0.21 (30 mg; P < 0.0001) vs 0.03 (placebo). Both apremilast doses showed significant ACR50 responses vs placebo at week 16 and improvements in secondary efficacy measures (swollen/tender joint counts) and psoriasis assessments, with sustained improvements through week 52. Common adverse events (AEs) over 52 weeks were diarrhoea, nausea, headache and upper respiratory tract infection; most events were mild or moderate. Serious AEs and AEs leading to discontinuation were comparable between groups. Laboratory abnormalities were infrequent and transient. Conclusions In DMARD-naive patients, apremilast monotherapy improved PsA signs/symptoms over 52 weeks and was generally well tolerated. Trial registration ClinicalTrials.gov (http://clinicaltrials.gov), NCT01307423. PMID:29635379

Short communication. Antiretroviral drug resistance among drug-naive HIV-1-infected individuals in Djibouti (Horn of Africa).

PubMed

Maslin, Jérôme; Rogier, Christophe; Caron, Melanie; Grandadam, Marc; Koeck, Jean-Louis; Nicand, Elisabeth

2005-01-01

To survey the frequency of genotypic antiretroviral resistance in drug-naive HIV-1-infected Djiboutians. A national study was conducted in the general population of Djibouti in March 2002 to determine HIV-1 seroprevalence. Blood samples were collected anonymously and plasma samples scoring positive for HIV-1 antibodies were tested for viral load. Genotypic studies were performed with viral RNA from plasma using the consensus technique of the Agence Nationale de Recherche sur le SIDA (www.hivfrenchresistance.org). Mutations were identified using the International AIDS Society-USA resistance panel and resistant virus was defined according to the ANRS algorithm. A panel of 2423 individuals representing the general population of Djibouti was included. Antibodies were detected in 53 of 2423 samples tested. The HIV-1 seroprevalence in the general population was 2.2%. Genotype C was the most prevalent, and the other isolates were CRF_02 AG, or subtype A or D. Forty-seven of the 53 samples were tested for genotypic resistance, and mutations concerning all three classes of antiretrovirals were found. The most frequent were secondary mutations associated with protease inhibitors (PIs): M36I, R41K and K20I/R. A few strains displayed primary mutations (the non-nucleoside reverse transcriptase inhibitor [NNRTI]-associated mutations K101E, K103T, L100I and G190V; the PI-associated mutation N88D; and the NRTI-associated mutation K65R). The presence of these mutations may be due to the transmission of strains from treated patients. Substantial polymorphism and a few primary mutations are found in HIV-1 non-B subtype isolates from Djiboutian antiretroviral-drug-naive individuals. This needs to be taken into account to adapt antiretroviral regimens and prophylactic schedules locally.

Cerebellar foliation in rats. 2. Effects of maternal malnutrition on the formation of fissures in foetal rats.

PubMed

Conradi, N G; Müntzing, K

1985-11-01

The effects of maternal malnutrition on the formation of cerebellar fissures was studied in foetal rats. The rats were given a diet containing either 14 (normal) or 7 (protein-deprived) per cent protein by weight from two weeks before conception and throughout gestation. The first day with a sperm-positive vaginal smear was designated as Embryonic day 1 (E 1). Foetuses were examined on days E 19 to 22. In seventy-five foetuses, a sagittal slice of the cerebellum, 3-4 mm thick was embedded in Sorvall embedding medium. Sagittal sections, 2 micron thick were cut at levels 100 micron apart through the specimen. Sixty-three foetuses were examined for presence of cerebellar fissures only after filling their vascular system with ink-gelatin and cutting serial sagittal frozen sections, 100 micron thick. A morphological comparison of the foliation in normal and malnourished foetuses suggested a slight delay in the malnourished ones, albeit the earliest fissures were visible on the same day as in normal foetuses. The existence of a developmental alteration due to malnutrition was demonstrated by a decrease in the length of the pial surface and a surface folding index day on E 22. The alteration is discussed in relation to previously reported changes in cerebellar development during malnutrition, such as delayed Purkinje cell formation and alterations in proliferation/differentiation in the EGL.

Efficacy and Safety of Apremilast in Systemic- and Biologic-Naive Patients With Moderate Plaque Psoriasis: 52-Week Results of UNVEIL.

PubMed

Stein Gold, Linda; Bagel, Jerry; Lebwohl, Mark; Jackson, J Mark; Chen, Rongdean; Goncalves, Joana; Levi, Eugenia; Duffin, Kristina Callis

2018-02-01

BACKGROUND: Many patients with moderate plaque psoriasis are undertreated despite broadening treatment options. In the phase IV UNVEIL study, oral apremilast demonstrated efficacy and safety in systemic-naive patients with chronic moderate plaque psoriasis with lower psoriasis-involved body surface area (BSA; 5%-10%) during the 16-week, double-blind, placebo-controlled phase. We describe efficacy and safety of apremilast in this population through week 52 in UNVEIL.

METHODS: Patients with moderate plaque psoriasis (BSA 5%-10%; static Physician's Global Assessment [sPGA] score of 3 [moderate]) and naive to systemic therapies for psoriasis were randomized (2:1) to receive apremilast 30 mg twice daily or placebo for 16 weeks. At week 16, patients continued on apremilast (apremilast/apremilast) or were switched from placebo to apremilast (placebo/apremilast) through week 52 (open-label apremilast treatment phase). Efficacy assessments included the product of sPGA and BSA (PGAxBSA) (mean percentage change from baseline; ≥75% reduction from baseline [PGAxBSA-75]), sPGA response (achievement of score of 0 [clear] or 1 [almost clear]), and the Dermatology Life Quality Index (DLQI; mean change from baseline).

RESULTS: A total of 136 patients completed the 52-week analysis period (placebo/apremilast, n=50/64; apremilast/apremilast, n=86/121). At week 52, improvements in all efficacy end points observed at week 16 were maintained in the apremilast/apremilast group (mean percentage change from baseline in PGAxBSA: -55.5%; PGAxBSA-75: 42.1%; sPGA response: 33.1%; mean change from baseline in DLQI score: -4.4); similar improvements emerged in the placebo/apremilast group after switching to apremilast. The most common adverse events (≥5% of patients) through week 52 were diarrhea (28.0%), nausea (19.0%), headache (15.2%), nasopharyngitis (10.4%), upper respiratory tract infection (7.1%), vomiting (5.7%), and decreased appetite (5.2%).

Ledipasvir-Sofosbuvir Plus Ribavirin in Treatment-Naive Patients With Hepatitis C Virus Genotype 3 Infection: An Open-Label Study.

PubMed

Feld, Jordan J; Ramji, Alnoor; Shafran, Stephen D; Willems, Bernard; Marotta, Paul; Huchet, Emmanuelle; Vachon, Marie-Louise; Svarovskaia, Evguenia S; Huang, K C; Hyland, Robert H; Yun, Chohee; Massetto, Benedetta; Brainard, Diana M; McHutchison, John G; Tam, Edward; Bailey, Robert; Cooper, Curtis; Yoshida, Eric M; Greenbloom, Susan; Elkhashab, Magdy; Borgia, Sergio; Swain, Mark G

2017-07-01

Patients chronically infected with genotype 3 hepatitis C virus (HCV) have faster disease progression and are less responsive to current direct-acting antiviral regimens than patients infected with other genotypes. We conducted an open-label trial to evaluate the safety, tolerability, and efficacy of ledipasvir and sofosbuvir plus ribavirin in patients with genotype 3 HCV infection. We enrolled treatment-naive patients with and without compensated cirrhosis at 15 sites in Canada. All patients were treated with ledipasvir-sofosbuvir (90 mg and 400 mg) plus weight-based ribavirin for 12 weeks. The primary endpoint was sustained virologic response 12 weeks after treatment (SVR12). Secondary endpoints included evaluation of baseline and treatment-emergent drug resistance. Of the 111 patients enrolled, 105 (95%) had subtype 3a HCV and 39 (35%) had compensated cirrhosis. SVR12 was achieved by 99 of 111 patients (89%; 95% confidence interval, 82%-94%). Of the 39 patients with cirrhosis, 31 (79%) achieved SVR12, compared with 68 of 72 (94%) patients without cirrhosis. No treatment-emergent resistance mutations occurred in those who failed treatment. One patient discontinued treatment due to liver cancer and died 22 days after treatment discontinuation. The most common adverse events were fatigue (51%), headache (36%), and nausea (23%). In this multicenter trial involving treatment-naive patients with genotype 3 HCV, 12 weeks of ledipasvir-sofosbuvir provided a high level of SVR in those without cirrhosis. NCT02413593. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Steady State Dendritic Cells Present Parenchymal Self-Antigen and Contribute to, but Are Not Essential for, Tolerization of Naive and Th1 Effector CD4 Cells1

PubMed Central

Hagymasi, Adam T.; Slaiby, Aaron M.; Mihalyo, Marianne A.; Qui, Harry Z.; Zammit, David J.; Lefrançois, Leo; Adler, Adam J.

2010-01-01

Bone marrow-derived APC are critical for both priming effector/memory T cell responses to pathogens and inducing peripheral tolerance in self-reactive T cells. In particular, dendritic cells (DC) can acquire peripheral self-Ags under steady state conditions and are thought to present them to cognate T cells in a default tolerogenic manner, whereas exposure to pathogen-associated inflammatory mediators during the acquisition of pathogen-derived Ags appears to reprogram DCs to prime effector and memory T cell function. Recent studies have confirmed the critical role of DCs in priming CD8 cell effector responses to certain pathogens, although the necessity of steady state DCs in programming T cell tolerance to peripheral self-Ags has not been directly tested. In the current study, the role of steady state DCs in programming self-reactive CD4 cell peripheral tolerance was assessed by combining the CD11c-diphtheria toxin receptor transgenic system, in which DC can be depleted via treatment with diphtheria toxin, with a TCR-transgenic adoptive transfer system in which either naive or Th1 effector CD4 cells are induced to undergo tolerization after exposure to cognate parenchymally derived self-Ag. Although steady state DCs present parenchymal self-Ag and contribute to the tolerization of cognate naive and Th1 effector CD4 cells, they are not essential, indicating the involvement of a non-DC tolerogenic APC population(s). Tolerogenic APCs, however, do not require the cooperation of CD4+CD25+ regulatory T cells. Similarly, DC were required for maximal priming of naive CD4 cells to vaccinia viral-Ag, but priming could still occur in the absence of DC. PMID:17641018

Genetic characterization of HIV-1 strains in Togo reveals a high genetic complexity and genotypic drug-resistance mutations in ARV naive patients.

PubMed

Yaotsè, Dagnra Anoumou; Nicole, Vidal; Roch, Niama Fabien; Mireille, Prince-David; Eric, Delaporte; Martine, Peeters

2009-07-01

In this study, the genetic diversity of HIV-1 and the presence of genotypic drug-resistance mutations in ARV naive patients in Lomé, the capital city of Togo, was documented for the first time. Between June 2006 and January 2007, 83 plasma samples were collected in Lomé from HIV-1 positive and antiretroviral (ARV) naive individuals. Pol (protease+RT) and env (V3-V5) regions were amplified and sequenced. Phylogenetic and recombination analyses were done to identify the HIV-1 variants. Pol sequences were then inspected to identify presence of drug-resistance mutations based on the WHO list recommended for epidemiological studies. A total of 75 plasma samples were amplified and sequenced in both genomic regions. The phylogenetic analysis showed that CRF02 (48.7% and 51.2%) and G (12.8% and 16.2%) were predominant, followed by A3 (6.4% and 6.2%) and CRF06 (3.8% and 12.5%) in pol and env, respectively. One strain was identified as CRF05 in pol and env. Two divergent subtype A strains in env were undetermined (U) in pol but clustered with a previously described complex recombinant strain, 99GR303. Overall, at least 23/83 (27.7%) strains were recombinant, 19 had a unique recombinant structure in pol, and 4 had discordant subtype/CRF designations between pol and env. The subtypes/CRFs involved in the recombination events corresponded to those already circulating as non-recombinant strains in the country. A total of 8 patients harbored strains with mutations associated to drug resistance: L90M (n=1), K103N (n=1), T69N (n=1), T215S (n=1), M41L (n=4). In this study we showed the complexity of the HIV-1 strains circulating in Togo and documented a relative high proportion of ARV naive patients with drug-resistance mutations. The high number of resistant strains observed in Togo needs further attention and additional studies are needed to confirm this trend especially because the national ART program experienced major problems to provide drugs on a regular base.

Naive scoring of human sleep based on a hidden Markov model of the electroencephalogram.

PubMed

Yaghouby, Farid; Modur, Pradeep; Sunderam, Sridhar

2014-01-01

Clinical sleep scoring involves tedious visual review of overnight polysomnograms by a human expert. Many attempts have been made to automate the process by training computer algorithms such as support vector machines and hidden Markov models (HMMs) to replicate human scoring. Such supervised classifiers are typically trained on scored data and then validated on scored out-of-sample data. Here we describe a methodology based on HMMs for scoring an overnight sleep recording without the benefit of a trained initial model. The number of states in the data is not known a priori and is optimized using a Bayes information criterion. When tested on a 22-subject database, this unsupervised classifier agreed well with human scores (mean of Cohen's kappa > 0.7). The HMM also outperformed other unsupervised classifiers (Gaussian mixture models, k-means, and linkage trees), that are capable of naive classification but do not model dynamics, by a significant margin (p < 0.05).

Analysis of weight changes after left gastric artery embolization in a cancer-naive population

PubMed Central

Kim, David J.; Raman, Hari S.; Salter, Amber; Ramaswamy, Raja; Gunn, Andrew J.; Weiss, Clifford R.; Akinwande, Olaguoke

2018-01-01

PURPOSE We aimed to evaluate weight changes after left gastric artery (LGA) embolization in a retrospective cancer-naive cohort. METHODS A retrospective study was conducted to identify patients who underwent LGA embolization for gastrointestinal bleeding (GI). Patients with known cancer diagnoses at the time of LGA embolization were excluded. Pre- and postprocedure weights were assessed. Statistical analysis was performed using paired t-test and Wilcoxon signed-rank test. RESULTS A total of 39 patients were identified. In 21 patients who had documented pre- and postprocedural weights, a median of 16.3 kg weight loss (P = 0.045) was observed over a median time of 12 months (range, 2–72). In patients who had pre- and postprocedure endoscopies (n=6), 2 had worsening ulcers following LGA embolization and 4 had stable or no abnormal findings. CONCLUSION Our preliminary observation suggests that LGA embolization is well tolerated and results in unintended weight loss. Larger studies are needed to confirm these preliminary findings. PMID:29757147

HIV type 1 genotypic variation in an antiretroviral treatment-naive population in southern India.

PubMed

Balakrishnan, Pachamuthu; Kumarasamy, Nagalingeswaran; Kantor, Rami; Solomon, Suniti; Vidya, Sundararajan; Mayer, Kenneth H; Newstein, Michael; Thyagarajan, Sadras P; Katzenstein, David; Ramratnam, Bharat

2005-04-01

Most studies of HIV-1 drug resistance have examined subtype B viruses; fewer data are available from developing countries, where non-B subtypes predominate. We determined the prevalence of mutations at protease and reverse transcriptase drug resistance positions in antiretroviral drug-naive individuals in southern India. The pol region of the genome was amplified from plasma HIV-1 RNA in 50 patients. All sequences clustered with HIV-1 subtype C. All patients had at least one protease and/or RT mutation at a known subtype B drug resistance position. Twenty percent of patients had mutations at major protease inhibitor resistance positions and 100% had mutations at minor protease inhibitor resistance positions. Six percent and 14% of patients had mutations at nucleoside reverse transcriptase inhibitor and/or nonnucleoside reverse transcriptase inhibitor resistance positions, respectively. Larger scale studies need to be undertaken to better define the genotypic variation of circulating Indian subtype C viruses and their potential impact on drug susceptibility and clinical outcome in treated individuals.

Optimization of a CRISPR/Cas9-mediated Knock-in Strategy at the Porcine Rosa26 Locus in Porcine Foetal Fibroblasts.

PubMed

Xie, Zicong; Pang, Daxin; Wang, Kankan; Li, Mengjing; Guo, Nannan; Yuan, Hongming; Li, Jianing; Zou, Xiaodong; Jiao, Huping; Ouyang, Hongsheng; Li, Zhanjun; Tang, Xiaochun

2017-06-08

Genetically modified pigs have important roles in agriculture and biomedicine. However, genome-specific knock-in techniques in pigs are still in their infancy and optimal strategies have not been extensively investigated. In this study, we performed electroporation to introduce a targeting donor vector (a non-linearized vector that did not contain a promoter or selectable marker) into Porcine Foetal Fibroblasts (PFFs) along with a CRISPR/Cas9 vector. After optimization, the efficiency of the EGFP site-specific knock-in could reach up to 29.6% at the pRosa26 locus in PFFs. Next, we used the EGFP reporter PFFs to address two key conditions in the process of achieving transgenic pigs, the limiting dilution method and the strategy to evaluate the safety and feasibility of the knock-in locus. This study demonstrates that we establish an efficient procedures for the exogenous gene knock-in technique and creates a platform to efficiently generate promoter-less and selectable marker-free transgenic PFFs through the CRISPR/Cas9 system. This study should contribute to the generation of promoter-less and selectable marker-free transgenic pigs and it may provide insights into sophisticated site-specific genome engineering techniques for additional species.

The processing of asparagine-linked oligosaccharides in HT-29 cells is a function of their state of enterocytic differentiation. An accumulation of Man9,8-GlcNAc2-Asn species is indicative of an impaired N-glycan trimming in undifferentiated cells.

PubMed

Ogier-Denis, E; Codogno, P; Chantret, I; Trugnan, G

1988-05-05

Studies on the regulation of the enterocytic differentiation of the human colon cancer cell line HT-29, which is differentiated in the absence (Glc-) but not in the presence of glucose (Glc+), have recently shown that the post-translational processing of sucrase-isomaltase and particularly its glycosylation vary as a function of cell differentiation (Trugnan G., Rousset, M., Chantret, I., Barbat, A., and Zweibaum, A. (1987) J. Cell Biol. 104, 1199-1205). Other studies indicate that in undifferentiated HT-29 Glc+ cells there is an accumulation of UDP-N-acetylhexosamine, which is involved in the glycosylation process (Wice, B. M., Trugnan, G., Pinto, M., Rousset, M., Chevalier, G., Dussaulx, E., Lacroix, B., and Zweibaum, A. (1985) J. Biol. Chem. 260, 139-146). The purpose of the present work is to investigate whether an overall alteration of protein glycosylation is associated with the inability of HT-29 cells to differentiate. At least three alterations are detected: (i) after a 10-min pulse, the incorporation of D-[2-3H]mannose in undifferentiated cells is severely reduced, compared to differentiated cells. (ii) After a 24-h period of labeling with D-[2-3H]mannose, undifferentiated cells accumulate more than 60% of the radioactivity in the high mannose glycopeptides, whereas differentiated HT-29 Glc- cells accumulate only 38%. (iii) The analysis of the high mannose oligosaccharides transferred "en bloc" from the lipid precursor shows that Man9,8-GlcNAc2 species accumulate in undifferentiated cells, whereas no such accumulation can be detected in differentiated cells. This glycosylation pattern is consistent with an impairment of the trimming of high mannose into complex glycans. It is concluded that N-glycan processing is correlated with the state of enterocytic differentiation of HT-29 cells.

Decrease in Numbers of Naive and Resting B Cells in HIV-Infected Kenyan Adults Leads to a Proportional Increase in Total and Plasmodium falciparum-Specific Atypical Memory B Cells.

PubMed

Frosch, Anne E; Odumade, Oludare A; Taylor, Justin J; Ireland, Kathleen; Ayodo, George; Ondigo, Bartholomew; Narum, David L; Vulule, John; John, Chandy C

2017-06-15

Human immunodeficiency virus type 1 (HIV-1) infection is associated with B cell activation and exhaustion, and hypergammaglobulinemia. How these changes influence B cell responses to coinfections such as malaria is poorly understood. To address this, we compared B cell phenotypes and Abs specific for the Plasmodium falciparum vaccine candidate apical membrane Ag-1 (AMA1) in HIV-infected and uninfected adults living in Kenya. Surprisingly, HIV-1 infection was not associated with a difference in serum AMA1-specific Ab levels. HIV-infected individuals had a higher proportion of total atypical and total activated memory B cells (MBCs). Using an AMA1 tetramer to detect AMA1-specific B cells, HIV-infected individuals were also shown to have a higher proportion of AMA1-specific atypical MBCs. However, this proportional increase resulted in large part from a loss in the number of naive and resting MBCs rather than an increase in the number of atypical and activated cells. The loss of resting MBCs and naive B cells was mirrored in a population of cells specific for an Ag to which these individuals were unlikely to have been chronically exposed. Together, the data show that changes in P. falciparum Ag-specific B cell subsets in HIV-infected individuals mirror those in the overall B cell population, and suggest that the increased proportion of atypical MBC phenotypes found in HIV-1-infected individuals results from the loss of naive and resting MBCs. Copyright © 2017 by The American Association of Immunologists, Inc.

Effect of sodium-alginate and laminaran on Salmonella Typhimurium infection in human enterocyte-like HT-29-Luc cells and BALB/c mice.

PubMed

Kuda, Takashi; Kosaka, Misa; Hirano, Shino; Kawahara, Miho; Sato, Masahiro; Kaneshima, Tai; Nishizawa, Makoto; Takahashi, Hajime; Kimura, Bon

2015-07-10

Brown algal polysaccharides such as alginate, polymers of uronic acids, and laminaran, beta-1,3 and 1,6-glucan, can be fermented by human intestinal microbiota. To evaluate the effects of these polysaccharides on infections caused by food poisoning pathogens, we investigated the adhesion and invasion of pathogens (Salmonella Typhimurium, Listeria monocytogenes and Vibrio parahaemolyticus) in human enterocyte-like HT-29-Luc cells and in infections caused in BALB/c mice. Both sodium Na-alginate and laminaran (0.1% each) inhibited the adhesion of the pathogens to HT-29-Luc cells by approximately 70-90%. The invasion of S. Typhimurium was also inhibited by approximately 70 and 80% by Na-alginate and laminaran, respectively. We observed that incubation with Na-alginate for 18 h increased the transepithelial electrical resistance of HT-29-Luc monolayer cells. Four days after inoculation with 7 log CFU/mouse of S. Typhimurium, the faecal pathogen count in mice that were not fed polysaccharides (control mice) was about 6.5 log CFU/g while the count in mice that were fed Na-alginate had decreased to 5.0 log CFU/g. The liver pathogen count, which was 4.1 log CFU/g in the control mice, was also decreased in mice that were fed Na-alginate. In contrast, the mice that were fed laminaran exhibited a more severe infection than that exhibited by control mice. Copyright © 2015 Elsevier Ltd. All rights reserved.

Foetal growth restriction is associated with poor reading and spelling skills at eight years to 10 years of age.

PubMed

Partanen, Lea; Korkalainen, Noora; Mäkikallio, Kaarin; Olsén, Päivi; Laukkanen-Nevala, Päivi; Yliherva, Anneli

2018-01-01

Foetal growth restriction (FGR) is associated with communication problems, which might lead to poor literacy skills. The reading and spelling skills of eight- to 10-year-old FGR children born at 24-40 gestational weeks were compared with those of their gestational age-matched, appropriately grown (AGA) peers. A prospectively collected cohort of 37 FGR and 31 AGA children was recruited prenatally at a Finnish tertiary care centre during 1998-2001. The children's reading and spelling skills were assessed using standardised tests for Finnish-speaking second and third graders. Significantly more children performed below the 10th percentile normal values for reading and spelling skills in the FGR group than in the AGA group. At nine years of age, the FGR children had significantly poorer performance in word reading skills and reading fluency, reading accuracy and reading comprehension than the AGA controls. No between-group differences were detected at eight years of age. FGR is associated with poor performance in reading and spelling skills. A third of the FGR children performed below the 10th percentile normal values at nine years of age. These results indicate a need to continuously evaluate linguistic and literacy skills as FGR children age to ensure optimal support. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Public foetal images and the regulation of middle-class pregnancy in the online media: a view from South Africa.

PubMed

Macleod, Catriona; Howell, Simon

2015-01-01

Ultrasonography images and their derivatives have been taken up in a range of 'public' spaces, including medical textbooks, the media, anti-abortion material, advertising, the Internet and public health facilities. Feminists have critiqued the personification of the foetus, the bifurcation of the woman's body and the reduction of the pregnant woman to a disembodied womb. What has received less attention is how these images frequently intersect with race, class, gender and heteronormativity in the creation of idealised and normative understandings of pregnancy. This paper focuses on the discursive positioning of pregnant women as 'mothers' and foetuses as 'babies' in online media targeted at a South African audience, where race and class continue to intersect in complex ways. We show how the ontologically specific understandings of 'mummies' and 'babies' emerge through the use of foetal images to construct specific understandings of the 'ideal' pregnancy. In the process, pregnant women are made responsible for ensuring that their pregnancy conforms to these ideals, which includes the purchasing of the various goods advertised by the websites. Not only does this point to a commodification of pregnancy, but also serves to reinforce a cultural understanding of White, middle-class pregnancy as constituting the normative 'correct' form of pregnancy.

Overexpression of the lamina proteins Lamin and Kugelkern induces specific ultrastructural alterations in the morphology of the nuclear envelope of intestinal stem cells and enterocytes.

PubMed

Petrovsky, Roman; Krohne, Georg; Großhans, Jörg

2018-03-01

The nuclear envelope has a stereotypic morphology consisting of a flat double layer of the inner and outer nuclear membrane, with interspersed nuclear pores. Underlying and tightly linked to the inner nuclear membrane is the nuclear lamina, a proteinous layer of intermediate filament proteins and associated proteins. Physiological, experimental or pathological alterations in the constitution of the lamina lead to changes in nuclear morphology, such as blebs and lobulations. It has so far remained unclear whether the morphological changes depend on the differentiation state and the specific lamina protein. Here we analysed the ultrastructural morphology of the nuclear envelope in intestinal stem cells and differentiated enterocytes in adult Drosophila flies, in which the proteins Lam, Kugelkern or a farnesylated variant of LamC were overexpressed. Surprisingly, we detected distinct morphological features specific for the respective protein. Lam induced envelopes with multiple layers of membrane and lamina, surrounding the whole nucleus whereas farnesylated LamC induced the formation of a thick fibrillary lamina. In contrast, Kugelkern induced single-layered and double-layered intranuclear membrane structures, which are likely be derived from infoldings of the inner nuclear membrane or of the double layer of the envelope. Copyright © 2018 Elsevier GmbH. All rights reserved.

Association of serum brain derived neurotropic factor with duration of drug-naive period and positive-negative symptom scores in drug naive schizophrenia.

PubMed

Bakirhan, Abdurrahim; Yalcin Sahiner, Safak; Sahiner, Ismail Volkan; Safak, Yasir; Goka, Erol

2017-01-01

The aim of this study was to compare the serum brain derived neurotropic factor (BNDF) levels of patients with schizophrenia who had never received an antipsychotic treatment with those of a control group. Also, to analyze the relationship between the Positive and Negative Symptom Scale (PANSS) scores and BDNF levels of the patients during the period they were drug-naive. The sample of the study comprised patients who presentedto the Psychiatry Clinic and were admitted after a distinctive schizophrenia diagnosis was made in accordance with the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) diagnosis classification and who were not using and never had any antipsychotic medicine. A total of 160 participants were included in the study, 80 of whom had schizophrenia patients and 80 constituted the age- and sex-matched healthy control group. Before the start of the treatment, the serum samples to be checked for the BDNF levels were collected from the patients. The difference between the average BDNF levels of the groups were statistically significant (t = -5.25; p˂.001). An analysis as to whether there was a relation between the BDNF levels and the drug-naïve duration indicated no correlations. An examination of the relationship between PANSS scores and BDNF levels of the patients yielded no correlations. Serum BDNF levels seem to be one of the indicators of schizophrenia and its progress; nevertheless, we still do not have sufficient information about this neurotropic factor. In light of our study, the neurodevelopmental changes that occur at disease onset of the illness prominently affect the progress of the illness, which highlights the importance of the treatment in the early stages.

Phase II study of cabozantinib in patients with progressive glioblastoma: subset analysis of patients naive to antiangiogenic therapy

PubMed Central

Drappatz, Jan; de Groot, John; Prados, Michael D; Reardon, David A; Schiff, David; Chamberlain, Marc; Mikkelsen, Tom; Desjardins, Annick; Holland, Jaymes; Ping, Jerry; Weitzman, Ron; Cloughesy, Timothy F

2018-01-01

Abstract Background Cabozantinib is a tyrosine kinase inhibitor with activity against vascular endothelial growth factor receptor 2 (VEGFR2) and MET that has demonstrated clinical activity in advanced solid tumors. This open-label, phase II trial evaluated cabozantinib in patients with recurrent or refractory glioblastoma (GBM). Methods Patients were initially enrolled at a starting dose of 140 mg/day, but the starting dose was amended to 100 mg/day because of toxicity. Treatment continued until disease progression or unacceptable toxicity. The primary endpoint was objective response rate assessed by an independent radiology facility using modified Response Assessment in Neuro-Oncology criteria. Additional endpoints included duration of response, 6-month and median progression-free survival, overall survival, and safety. Results Among 152 patients naive to prior antiangiogenic therapy, the objective response rate was 17.6% and 14.5% in the 140 mg/day and 100 mg/day groups, respectively, which did not meet the predefined statistical target for success. The proportions of patients alive and progression free at 6 months were 22.3% and 27.8%, respectively. Median progression-free survival was 3.7 months in both groups, and median overall survival was 7.7 months and 10.4 months, respectively. The incidence of grade 3/4 adverse events (AEs) was 79.4% and 84.7% in the 140 mg/day and 100 mg/day groups, respectively, and dose reductions due to AEs were experienced by 61.8% and 72.0%, respectively. Common grade 3/4 AEs included fatigue, diarrhea, and palmar-plantar erythrodysesthesia syndrome. Conclusions Cabozantinib showed evidence of clinical activity in patients with recurrent GBM naive to antiangiogenic therapy, although the predefined statistical target for success was not met. At the starting doses assessed, AEs were frequently managed with dose reductions. Clinical Trials Registration Number NCT00704288 (https://www.clinicaltrials.gov/ct2/show/NCT00704288) PMID

Using an Integrated Naive Bayes Calssifier for Crawling Relevent Data on the Web

NASA Astrophysics Data System (ADS)

Mihsra, A.

2015-12-01

In our experiments (at JPL, NASA) for DARPA Memex project, we wanted to crawl a large amount of data for various domains. A big challenge was data relevancy in the crawled data. More than 50% of the data was irrelevant to the domain at hand. One immediate solution was to use good seeds (seeds are the initial urls from where the program starts to crawl) and make sure that the crawl remains into the original host urls. This although a very efficient technique, fails under two conditions. One when you aim to reach deeper into the web; into new hosts (not in the seed list) and two when the website hosts myriad content types eg. a News website.The relevancy calculation used to be a post processing step i.e. once we had finished crawling, we trained a NaiveBayes Classifier and used it to find a rough relevancy of the web pages that we had. Integrating the relevancy into the crawling rather than after it was very important because crawling takes resources and time. To save both we needed to get an idea of relevancy of the whole crawl during run time and be able to steer its course accordingly. We use Apache Nutch as the crawler, which uses a plugin system to incorporate any new implementations and hence we built a plugin for Nutch.The Naive Bayes Parse Plugin works in the following way. It parses every page and decides, using a trained model (which is built in situ only once using the positive and negative examples given by the user in a very simple format), if it is relevant; If true, then it allows all the outlinks from that page to go to the next round of crawling; If not, then it gives the urls a second chance to prove themselves by checking some commonly expected words in the url relevant to that domain. This two tier system is very intuitive and efficient in focusing the crawl. In our initial test experiments over 100 seed urls, the results were astonishingly good with a recall of 98%.The same technique can be applied to geo-informatics. This will help scientists

Dolutegravir–lamivudine as initial therapy in HIV-1 infected, ARV-naive patients, 48-week results of the PADDLE (Pilot Antiretroviral Design with Dolutegravir LamivudinE) study

PubMed Central

Cahn, Pedro; Rolón, María José; Figueroa, María Inés; Gun, Ana; Patterson, Patricia; Sued, Omar

2017-01-01

Abstract Introduction: A proof-of-concept study was designed to evaluate the antiviral efficacy, safety and tolerability of a two-drug regimen with dolutegravir 50 mg once daily (QD) plus lamivudine 300 mg once daily as initial highly active antiretroviral therapy (HAART) among antiretroviral (ARV)-naive patients. Methods: PADDLE is a pilot study including 20 treatment-naive adults. To be selected, participants had no IAS-USA-defined resistance, HIV-1 RNA ≤100,000 copies/mL at screening and negative HBsAg. Plasma viral load (pVL) was measured at baseline; days 2, 4, 7, 10, 14, 21 and 28; weeks 6, 8 and 12; and thereafter every 12 weeks up to 96 weeks. Primary endpoint was the proportion of patients with HIV-1 RNA <50 copies/mL in an intention to treat (ITT)-exposed analysis at 48 weeks (the FDA snapshot algorithm). Results: Median HIV-1 RNA at entry was 24,128 copies/mL (interquartile range (IQR): 11,686–36,794). Albeit as per protocol, all patients had pVL ≤100,000 copies/mL at screening as required by inclusion criteria, four patients had ≥100,000 copies/mL at baseline. Median baseline CD4+ T-cell count was 507 per cubic millimetre (IQR: 296–517). A rapid decline in pVL was observed (median VL decay from baseline to week 12 was 2.74 logs). All patients were suppressed at week 8 onwards up to week 24. At week 48, 90% (18/20) reached the primary endpoint of a pVL <50 copies/mL. Median change in CD4 cell count between baseline and week 48 was 267 cells/mm3 (IQR: 180–462). No major tolerability/toxicity issues were observed. Nineteen patients completed 48 weeks of the study, and one patient (with undetectable VL at last visit) committed suicide. One patient presented a low-level protocol-defined confirmed virological failure at week 36, being the only observed failure. This patient had pVL <50 copies/mL at the end-of-study visit without having changed the two-drug regimen. Observed failure rate was 5%. This is the first report of integrase strand

[Dysfunctional resting-state connectivity of default mode network in adolescent patients with first-episode drug-naive major depressive disorder].

PubMed

Li, S Y; Zhu, Y; Wang, Y L; Lü, P P; Zuo, W B; Li, F Y

2017-12-05

Objective: To study resting-state functional connectivity (FC) of default mode network (DMN) in adolescent patients with first-episode drug-naive major depressive disorder (MDD). Methods: We enrolled thirty first-episode and drug-naive adolescent MDD patients and twenty-nine adolescent healthy control (HC) participants in the First Affiliated Hospital of Zhengzhou University. There were no differences in age, sex, and education between the MDD and HC group. Resting-state functional magnetic resonance images (fMRI) was performed. We selected posterior cingulate cortex (PCC) and medial prefrontal cortex (MPFC) of DMN as regions of interests (ROI). The differences of these regions from the whole brain functional connectivity were analyzed. The relations between abnormalities in FCs of DMN and clinical variables were further investigated. Results: Compared to the HCs, the MDD patients had congruently reduced FCs between the PCC and cerebellum, temporal cortices, occipital cortices, fusiform, dorsolateral prefrontal cortex. MPFC not only had reduced FCs with fusiform, temporal cortices, anterior cingulate cortex, but also had enhanced FCs with occipital cortices, parietal cortices, and precentral gyrus. In addition, the increased FC between the right MPFC and right precentral gyrus was positive correlated with Hamilton Rating Scale for Depression (HAMD) scores ( r =0.38, P =0.04). The reduced FC between the left middle temporal gyrus and left PCC as well as the enhanced FC between the right middle cingulum and right MPFC were positive correlated with the duration of depression since onset ( r =0.39, P =0.03; r =0.38, P =0.04). Conclusions: These findings show dysfunctional DMN connectivity of adolescent MDD patients. Neurodevelopmental abnormalities in DMN may present in adolescent MDD.

Subcutaneous immunoglobulin as first-line therapy in treatment-naive patients with chronic inflammatory demyelinating polyneuropathy: randomized controlled trial study.

PubMed

Markvardsen, L H; Sindrup, S H; Christiansen, I; Olsen, N K; Jakobsen, J; Andersen, H

2017-02-01

Subcutaneous immunoglobulin (SCIG) is effective as maintenance treatment in chronic inflammatory demyelinating polyneuropathy (CIDP). We investigated whether multiple subcutaneous infusions are as effective as conventional therapy with intravenous loading doses in treatment-naive patients with CIDP. Twenty patients fulfilling the clinical and electrophysiological criteria for CIDP were included and treated with either SCIG (0.4 g/kg/week) for 5 weeks or intravenous immunoglobulin (IVIG) (0.4 g/kg/day) for 5 days. After 10 weeks, patients were switched to the opposite treatment arm and followed for a further 10 weeks. All participants were evaluated at weeks 0, 2, 5 and 10 during both therapies. Primary outcome was combined isokinetic muscle strength (cIKS). Secondary outcomes were disability, clinical evaluation of muscle strength and the performance of various function tests. All participants received both therapies, 14 completing the protocol. Overall, cIKS increased by 7.4 ± 14.5% (P = 0.0003) during SCIG and by 6.9 ± 16.8% (P = 0.002) during IVIG, the effect being similar (P = 0.80). Improvement of cIKS peaked 2 weeks after IVIG and 5 weeks after SCIG. Disability improved during SCIG treatment only. Muscle strength determined by manual muscle testing improved after 5 and 10 weeks during SCIG but only after 5 weeks during IVIG. The remaining parameters improved equally during both treatments. Plasma immunoglobulin G levels at baseline and improvement of cIKS were related. In treatment-naive patients with CIDP, short-lasting SCIG and IVIG therapy improve motor performance to a similar degree, but with earlier maximal improvement following IVIG than SCIG treatment. © 2016 EAN.

Evidence of a dissociation pattern in resting-state default mode network connectivity in first-episode, treatment-naive major depression patients.

PubMed

Zhu, Xueling; Wang, Xiang; Xiao, Jin; Liao, Jian; Zhong, Mingtian; Wang, Wei; Yao, Shuqiao

2012-04-01

Imaging studies have shown that major depressive disorder (MDD) is associated with altered activity patterns of the default mode network (DMN). However, the neural correlates of the resting-state DMN and MDD-related pathopsychological characteristics, such as depressive rumination and overgeneral autobiographical memory (OGM) phenomena, still remain unclear. Using independent component analysis, we analyzed resting-state functional magnetic resonance imaging data obtained from 35 first-episode, treatment-naive young adults with MDD and from 35 matched healthy control subjects. Patients with MDD exhibited higher levels of rumination and OGM than did the control subjects. We observed increased functional connectivity in the anterior medial cortex regions (especially the medial prefrontal cortex and anterior cingulate cortex) and decreased functional connectivity in the posterior medial cortex regions (especially the posterior cingulate cortex/precuneus) in MDD patients compared with control subjects. In the depressed group, the increased functional connectivity in the anterior medial cortex correlated positively with rumination score, while the decreased functional connectivity in the posterior medial cortex correlated negatively with OGM score. We report dissociation between anterior and posterior functional connectivity in resting-state DMNs of first-episode, treatment-naive young adults with MDD. Increased functional connectivity in anterior medial regions of the resting-state DMN was associated with rumination, whereas decreased functional connectivity in posterior medial regions was associated with OGM. These results provide new evidence for the importance of the DMN in the pathophysiology of MDD and suggest that abnormal DMN activity may be an MDD trait. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Timing of dialysis initiation in transplant-naive and failed transplant patients

PubMed Central

Molnar, Miklos Z.; Ojo, Akinlolu O.; Bunnapradist, Suphamai; Kovesdy, Csaba P.; Kalantar-Zadeh, Kamyar

2017-01-01

Over the past two decades, most guidelines have advocated early dialysis initiation on the basis of studies showing improved survival in patients starting dialysis early. These recommendations led to an increase in the proportion of patients initiating dialysis with an estimated glomerular filtration rate (eGFR) >10 ml/min/1.73 m2, from 20% in 1996 to 52% in 2008. During this period, patients starting dialysis with an eGFR ≥15 ml/min/1.73 m2 increased from 4% to 17%. However, recent studies have failed to substantiate a benefit of early dialysis initiation and some data have suggested worse outcomes in patients starting dialysis with a higher eGFR. Several reasons for this seemingly paradoxical observation have been suggested, including the fact that patients requiring early dialysis are likely to have more severe symptoms and comorbidities, leading to confounding by indication, as well as biological mechanisms that causally relate early dialysis therapy to adverse outcomes. Dialysis reinitiation in patients with a failing renal allograft encounters similar problems. However, unique factors associated with a failed allograft means that the optimal timing of dialysis initiation in failed transplant patients might differ from that in transplant-naive patients. In this Review, we will discuss studies of dialysis initiation and compare risks and benefits of early versus late dialysis therapy. PMID:22371250

Decreased resting-state interhemispheric coordination in first-episode, drug-naive paranoid schizophrenia.

PubMed

Guo, Wenbin; Xiao, Changqing; Liu, Guiying; Wooderson, Sarah C; Zhang, Zhikun; Zhang, Jian; Yu, Liuyu; Liu, Jianrong

2014-01-03

Dysconnectivity hypothesis posits that schizophrenia relates to abnormalities in neuronal connectivity. However, little is known about the alterations of the interhemispheric resting-state functional connectivity (FC) in patients with paranoid schizophrenia. In the present study, we used a newly developed voxel-mirrored homotopic connectivity (VMHC) method to investigate the interhemispheric FC of the whole brain in patients with paranoid schizophrenia at rest. Forty-nine first-episode, drug-naive patients with paranoid schizophrenia and 50 age-, gender-, and education-matched healthy subjects underwent a resting-state functional magnetic resonance imaging (fMRI) scans. An automated VMHC approach was used to analyze the data. Patients exhibited lower VMHC than healthy subjects in the precuneus (PCu), the precentral gyrus, the superior temporal gyrus (STG), the middle occipital gyrus (MOG), and the fusiform gyrus/cerebellum lobule VI. No region showed greater VMHC in the patient group than in the control group. Significantly negative correlation was observed between VMHC in the precentral gyrus and the PANSS positive/total scores, and between VMHC in the STG and the PANSS positive/negative/total scores. Our results suggest that interhemispheric resting-state FC of VMHC is reduced in paranoid schizophrenia with clinical implications for psychiatric symptomatology thus further contribute to the dysconnectivity hypothesis of schizophrenia. © 2013.

Data mining for dengue hemorrhagic fever (DHF) prediction with naive Bayes method

NASA Astrophysics Data System (ADS)

Arafiyah, Ria; Hermin, Fariani

2018-01-01

Handling of infectious diseases is determined by the accuracy and speed of diagnosis. Government through the Regulation of the Minister of Health of the Republic of Indonesia No. 82 of 2014 on the Control of Communicable Diseases establishes Dengue Hemorrhagic Fever (DHF) has made DHF prevention a national priority. Various attempts were made to overcome this misdiagnosis. The treatment and diagnosis of DHF using ANFIS has result an application program that can decide whether a patient has dengue fever or not [1]. An expert system of dengue prevention by using ANFIS has predict the weather and the number of sufferers [2]. The large number of data on DHF often cannot affect a person in making decisions. The use of data mining method, able to build data base support in decision makers diagnose DHF disease [3]. This study predicts DHF with the method of Naive Bayes. Parameter of The input variable is the patient’s medical data (temperature, spotting, bleeding, and tornuine test) and the output variable suffers from DBD or not while the system output is diagnosis of the patient suffering from DHF or not. Result of model test by using tools of Orange 3.4.5 obtained level of precision model is 77,3%.

CD4:8 ratio >5 is associated with a dominant naive T-cell phenotype and impaired physical functioning in CMV-seropositive very elderly people: results from the BELFRAIL study.

PubMed

Adriaensen, Wim; Derhovanessian, Evelyna; Vaes, Bert; Van Pottelbergh, Gijs; Degryse, Jean-Marie; Pawelec, Graham; Hamprecht, Klaus; Theeten, Heidi; Matheï, Catharina

2015-02-01

A subset of older people is at increased risk of hospitalization and dependency. Emerging evidence suggests that immunosenescence reflected by an inverted CD4:8 ratio and cytomegalovirus (CMV) seropositivity plays an important role in the pathophysiology of functional decline. Nevertheless, the relation between CD4:8 ratio and functional outcome has rarely been investigated. Here, CD4:8 ratio and T-cell phenotypes of 235 community-dwelling persons aged ≥81.5 years in the BELFRAIL study and 25 younger persons (mean age 28.5 years) were analyzed using polychromatic flow cytometry. In the elderly persons, 7.2% had an inverted CD4:8 ratio, which was associated with CMV seropositivity, less naive, and more late-differentiated CD4+ and CD8+ T cells. However, 32.8% had a CD4:8 ratio >5, a phenotype associated with a higher proportion of naive T cells and absent in young donors. In CMV seropositives, this subgroup had lower proportions of late-differentiated CD4+ and CD8+ T cells and weaker anti-CMV immunoglobulin G reactivity. This novel naive T-cell-dominated phenotype was counterintuitively associated with a higher proportion of those with impaired physical functioning in the very elderly people infected with CMV. This underscores the notion that in very elderly people, not merely CMV infection but also the state of its accompanying immune dysregulation is of crucial importance with regard to physical impairment. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

HIV-1 drug resistance in antiretroviral-naive individuals with HIV-1-associated tuberculous meningitis initiating antiretroviral therapy in Vietnam.

PubMed

Thao, Vu P; Le, Thuy; Török, Estee M; Yen, Nguyen T B; Chau, Tran T H; Jurriaans, Suzanne; van Doorn, H Rogier; van Doorn, Rogier H; de Jong, Menno D; Farrar, Jeremy J; Dunstan, Sarah J

2012-01-01

Access to antiretroviral therapy (ART) for HIV-infected individuals in Vietnam is rapidly expanding, but there are limited data on HIV drug resistance (HIVDR) to guide ART strategies. We retrospectively conducted HIVDR testing in 220 ART-naive individuals recruited to a randomized controlled trial of immediate versus deferred ART in individuals with HIV-associated tuberculous meningitis in Ho Chi Minh City (HCMC) from 2005-2008. HIVDR mutations were identified by population sequencing of the HIV pol gene and were defined based on 2009 WHO surveillance drug resistance mutations (SDRMs). We successfully sequenced 219/220 plasma samples of subjects prior to ART; 218 were subtype CRF01_AE and 1 was subtype B. SDRMs were identified in 14/219 (6.4%) subjects; 8/14 were resistant to nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs; T69D, L74V, V75M, M184V/I and K219R), 5/14 to non-nucleoside reverse transcriptase inhibitors (NNRTIs; K103N, V106M, Y181C, Y188C and G190A), 1/14 to both NRTIs and NNRTIs (D67N and Y181C) and none to protease inhibitors. After 6 months of ART, eight subjects developed protocol-defined virological failure. HIVDR mutations were identified in 5/8 subjects. All five had mutations with high-level resistance to NNRTIs and three had mutations with high-level resistance to NRTIs. Due to a high early mortality rate (58%), the effect of pre-existing HIVDR mutations on treatment outcome could not be accurately assessed. The prevalence of WHO SDRMs in ART-naive individuals with HIV-associated tuberculous meningitis in HCMC from 2005-2008 is 6.4%. The SDRMs identified conferred resistance to NRTIs and/or NNRTIs, reflecting the standard first-line ART regimens in Vietnam.

Time to viral load suppression in antiretroviral-naive and -experienced HIV-infected pregnant women on highly active antiretroviral therapy: implications for pregnant women presenting late in gestation.

PubMed

Aziz, N; Sokoloff, A; Kornak, J; Leva, N V; Mendiola, M L; Levison, J; Feakins, C; Shannon, M; Cohan, D

2013-11-01

To compare time to achieve viral load <400 copies/ml and <1000 copies/ml in HIV-infected antiretroviral (ARV) -naive versus ARV-experienced pregnant women on highly active antiretroviral therapy (HAART). Retrospective cohort study. Three university medical centers, USA. HIV-infected pregnant women initiated or restarted on HAART during pregnancy. We calculated time to viral load <400 copies/ml and <1000 copies/ml in HIV-infected pregnant women on HAART who reported at least 50% adherence, stratifying based on previous ARV exposure history. Time to HIV viral load <400 copies/ml and <1000 copies/ml. We evaluated 138 HIV-infected pregnant women, comprising 76 ARV-naive and 62 ARV-experienced. Ninety-three percent of ARV-naive women achieved a viral load < 400 copies/ml during pregnancy compared with 92% of ARV-experienced women (P = 0.82). The median number of days to achieve a viral load < 400 copies/ml in the ARV-naive cohort was 25.0 (range 3.5-133; interquartile range 16-34) days compared with 27.0 (range 8-162.5; interquartile range 18.5-54.3) days in the ARV-experienced cohort (P = 0.02). In a multiple predictor analysis, women with higher adherence (adjusted relative hazard [aRH] per 10% increase in adherence 1.29, 95% confidence interval [CI] 1.08-1.54, P = 0.01) and receiving a non-nucleotide reverse transcriptase inhibitor (NNRTI) -based regimen (aRH 2.48, 95% CI 1.33-4.63, P = 0.01) were more likely to achieve viral load <400 copies/ml earlier. Increased baseline HIV log10 viral load was associated with a later time of achieving viral load <400 copies/ml (aRH 0.60, 95% CI 0.39-0.92, P = 0.02). In a corresponding model of time to achieve viral load <1000 copies/ml, adherence (aRH per 10% increase in adherence 1.79, 95% CI 1.34-2.39, P < 0.001), receipt of NNRTI (aRH 2.95, 95% CI 1.23-7.06, P = 0.02), and CD4 cell count (aRH per 50 count increase in CD4 1.12, 95% CI 1.03-1.22, P = 0.01) were associated with an earlier time to achieve viral load below this

Serological markers of enterocyte damage and apoptosis in patients with celiac disease, autoimmune diabetes mellitus and diabetes mellitus type 2.

PubMed

Hoffmanová, I; Sánchez, D; Hábová, V; Anděl, M; Tučková, L; Tlaskalová-Hogenová, H

2015-01-01

Impairment of mucosal barrier integrity of small intestine might be causative in immune-mediated gastrointestinal diseases. We tested the markers of epithelial apoptosis - cytokeratin 18 caspase-cleaved fragment (cCK-18), and enterocyte damage - intestinal fatty acid-binding protein (I-FABP) and soluble CD14 (sCD14) in sera of patients with untreated celiac disease (CLD), those on gluten-free diet (CLD-GFD), patients with autoimmune diabetes mellitus (T1D), T1D with insulitis (T1D/INS), and diabetes mellitus type 2 (T2D). We found elevated levels of cCK-18 (P<0.001), I-FABP (P<0.01) and sCD14 (P<0.05) in CLD when compared to healthy controls. However, the levels of cCK-18 (P<0.01) and I-FABP (P<0.01) in CLD-GFD were higher when compared with controls. Interestingly, elevated levels of cCK-18 and I-FABP were found in T2D and T1D (P<0.001), and T1D/INS (P<0.01, P<0.001). Twenty-two out of 43 CLD patients were seropositive for cCK-18, 19/43 for I-FABP and 11/43 for sCD14; 9/30 of T2D patients were positive for cCK-18 and 5/20 of T1D/INS for sCD14, while in controls only 3/41 were positive for cCK-18, 3/41 for I-FABP and 1/41 for sCD14. We documented for the first time seropositivity for sCD14 in CLD and potential usefulness of serum cCK-18 and I-FABP as markers of gut damage in CLD, CLD-GFD, and diabetes.

Chronic lung disease of prematurity and early childhood wheezing: is foetal inflammatory response syndrome to blame?

PubMed

Dessardo, Nada Sindičić; Dessardo, Sandro; Mustać, Elvira; Banac, Srđan; Petrović, Oleg; Peter, Branimir

2014-09-01

Long-lasting respiratory symptoms have a huge impact on the quality of life in prematurely born children. We aimed to investigate the perinatal and maternal risk factors involved in the development of chronic respiratory morbidity in preterm infants, with an emphasis on the importance of Foetal Inflammatory Response Syndrome (FIRS). Prospective cohort study. Demographic, antenatal, delivery and outcomes data were collected from 262 infants with less than 32 completed weeks of gestational age, over a 10-year period. Presence of chronic lung disease of prematurity and early childhood wheezing. In multivariate logistic regression analysis the presence of FIRS appears to be the most important risk factor for both, chronic lung disease of prematurity (OR 31.05, 95% CI 10.7-87.75, p<0.001) and early childhood wheezing (OR 5.63, 95% CI 2.42-13.05, p=0.01). In the alternative regression model for early childhood wheezing, with chronic lung disease included as a variable, the statistical significance of FIRS completely vanished (OR 1.15, 95% CI 0.39-3.34, p=0.79), whilst chronic lung disease became the most important risk factor (OR 23.45, 95% CI 8.5-63.25, p<0.001). Prenatal and early neonatal events are of utmost importance in the development of chronic respiratory symptoms in children. The influence of FIRS on the development of chronic respiratory symptoms goes far beyond its impact on gestational age and may be related to direct inflammation-mediated lung tissue damage. CLD appears to be an intermittent step on the way from FIRS to ECW. Copyright © 2014 Elsevier Ltd. All rights reserved.

Alpinia katsumadai Extracts Inhibit Adhesion and Invasion of Campylobacter jejuni in Animal and Human Foetal Small Intestine Cell Lines.

PubMed

Pogačar, Maja Šikić; Klančnik, Anja; Bucar, Franz; Langerholc, Tomaž; Možina, Sonja Smole

2015-10-01

Alpinia katsumadai is used in traditional Chinese medicine for abdominal distention, pain, and diarrhoea. Campylobacter jejuni is the most common cause of bacterial food-borne diarrhoeal illnesses worldwide. Adhesion to gut epithelium is a prerequisite in its pathogenesis. The antimicrobial, cytotoxic, and anti-adhesive activities of a chemically characterised extract (SEE) and its residual material of hydrodistillation (hdSEE-R) from A. katsumadai seeds were evaluated against C. jejuni. Minimal inhibitory concentrations for SEE and hdSEE-R were 0.5 mg/mL and 0.25 mg/mL, respectively, and there was no cytotoxic influence in the anti-adhesion tests, as these were performed at much lower concentrations of these tested plant extracts. Adhesion of C. jejuni to pig (PSI) and human foetal (H4) small-intestine cell lines was significantly decreased at lower concentrations (0.2 to 50 µg/mL). In the same concentration range, the invasiveness of C. jejuni in PSI cells was reduced by 45% to 65% when they were treated with SEE or hdSEE-R. The hdSEE-R represents a bioactive waste with a high phenolic content and an anti-adhesive activity against C. jejuni and thus has the potential for use in pharmaceutical and food products. Copyright © 2015 John Wiley & Sons, Ltd.

Using trend templates in a neonatal seizure algorithm improves detection of short seizures in a foetal ovine model.

PubMed

Zwanenburg, Alex; Andriessen, Peter; Jellema, Reint K; Niemarkt, Hendrik J; Wolfs, Tim G A M; Kramer, Boris W; Delhaas, Tammo

2015-03-01

Seizures below one minute in duration are difficult to assess correctly using seizure detection algorithms. We aimed to improve neonatal detection algorithm performance for short seizures through the use of trend templates for seizure onset and end. Bipolar EEG were recorded within a transiently asphyxiated ovine model at 0.7 gestational age, a common experimental model for studying brain development in humans of 30-34 weeks of gestation. Transient asphyxia led to electrographic seizures within 6-8 h. A total of 3159 seizures, 2386 shorter than one minute, were annotated in 1976 h-long EEG recordings from 17 foetal lambs. To capture EEG characteristics, five features, sensitive to seizures, were calculated and used to derive trend information. Feature values and trend information were used as input for support vector machine classification and subsequently post-processed. Performance metrics, calculated after post-processing, were compared between analyses with and without employing trend information. Detector performance was assessed after five-fold cross-validation conducted ten times with random splits. The use of trend templates for seizure onset and end in a neonatal seizure detection algorithm significantly improves the correct detection of short seizures using two-channel EEG recordings from 54.3% (52.6-56.1) to 59.5% (58.5-59.9) at FDR 2.0 (median (range); p < 0.001, Wilcoxon signed rank test). Using trend templates might therefore aid in detection of short seizures by EEG monitoring at the NICU.

Effect of the spider toxin Tx3-3 on spinal processing of sensory information in naive and neuropathic rats: an in vivo electrophysiological study.

PubMed

Dalmolin, Gerusa D; Bannister, Kirsty; Gonçalves, Leonor; Sikandar, Shafaq; Patel, Ryan; Cordeiro, Marta do Nascimento; Gomez, Marcus Vinícius; Ferreira, Juliano; Dickenson, Anthony H

2017-07-01

Drugs that counteract nociceptive transmission in the spinal dorsal horn preferentially after nerve injury are being pursued as possible neuropathic pain treatments. In a previous behavioural study, the peptide toxin Tx3-3, which blocks P/Q- and R-type voltage-gated calcium channels, was effective in neuropathic pain models. In the present study, we aimed to investigate the effect of Tx3-3 on dorsal horn neuronal responses in rats under physiological conditions and neuropathic pain condition induced by spinal nerve ligation (SNL). In vivo electrophysiological recordings of dorsal horn neuronal response to electrical and natural (mechanical and thermal) stimuli were made in rats under normal physiological state (naive rats) or after the SNL model of neuropathic pain. Tx3-3 (0.3-100 pmol/site) exhibited greater inhibitory effect on electrical-evoked neuronal response of SNL rats than naive rats, inhibiting nociceptive C-fibre and Aδ-fibre responses only in SNL rats. The wind-up of neurones, a measurement of spinal cord hyperexcitability, was also more susceptible to a dose-related inhibition by Tx3-3 after nerve injury. Moreover, Tx3-3 exhibited higher potency to inhibit mechanical- and thermal-evoked neuronal response in conditions of neuropathy. Tx3-3 mediated differential inhibitory effect under physiological and neuropathic conditions, exhibiting greater potency in conditions of neuropathic pain.

Predictions of BuChE inhibitors using support vector machine and naive Bayesian classification techniques in drug discovery.

PubMed

Fang, Jiansong; Yang, Ranyao; Gao, Li; Zhou, Dan; Yang, Shengqian; Liu, Ai-Lin; Du, Guan-hua

2013-11-25

Butyrylcholinesterase (BuChE, EC 3.1.1.8) is an important pharmacological target for Alzheimer's disease (AD) treatment. However, the currently available BuChE inhibitor screening assays are expensive, labor-intensive, and compound-dependent. It is necessary to develop robust in silico methods to predict the activities of BuChE inhibitors for the lead identification. In this investigation, support vector machine (SVM) models and naive Bayesian models were built to discriminate BuChE inhibitors (BuChEIs) from the noninhibitors. Each molecule was initially represented in 1870 structural descriptors (1235 from ADRIANA.Code, 334 from MOE, and 301 from Discovery studio). Correlation analysis and stepwise variable selection method were applied to figure out activity-related descriptors for prediction models. Additionally, structural fingerprint descriptors were added to improve the predictive ability of models, which were measured by cross-validation, a test set validation with 1001 compounds and an external test set validation with 317 diverse chemicals. The best two models gave Matthews correlation coefficient of 0.9551 and 0.9550 for the test set and 0.9132 and 0.9221 for the external test set. To demonstrate the practical applicability of the models in virtual screening, we screened an in-house data set with 3601 compounds, and 30 compounds were selected for further bioactivity assay. The assay results showed that 10 out of 30 compounds exerted significant BuChE inhibitory activities with IC50 values ranging from 0.32 to 22.22 μM, at which three new scaffolds as BuChE inhibitors were identified for the first time. To our best knowledge, this is the first report on BuChE inhibitors using machine learning approaches. The models generated from SVM and naive Bayesian approaches successfully predicted BuChE inhibitors. The study proved the feasibility of a new method for predicting bioactivities of ligands and discovering novel lead compounds.

Efficacy of metformin on glycemic control and weight in drug-naive type 2 diabetes mellitus patients: A systematic review and meta-analysis of placebo-controlled randomized trials.

PubMed

Piera-Mardemootoo, Carole; Lambert, Philippe; Faillie, Jean-Luc

2018-02-21

Metformin is recommended as the first-line treatment of type 2 diabetes mellitus. Despite its common use, few studies have been conducted to precisely measure the efficacy of metformin versus placebo as a first-line treatment. This study aims to assess the precise effects of metformin monotherapy on glycemic control and weight in drug-naive patients with type 2 diabetes mellitus. Medline ® and Cochrane databases were searched until March 19, 2016 to perform a systematic review and meta-analysis of placebo-controlled randomized trials evaluating metformin monotherapy in drug-naive patients with type 2 diabetes mellitus. Assessed outcomes include glycemic control (fasting plasma glucose, glycosated hemoglobin) and weight. Overall, 16 studies (1140 patients) were selected. Compared to placebo, metformin monotherapy was associated with decreased glycosated hemoglobin by 0.95% at 3 months (95% CI: 0.50 to 1.39, I 2 =87%) and 1.32% at 6 months (95% CI: 1.01 to 1.62, I 2 =71%), and decreased fasting plasma glucose by 1.92mmol/L at 1 month (95% CI: 0.11 to 3.74, I 2 =88%), 1.79mmol/L at 3 months (95% CI: 0.92 to 2.66, I 2 =88%) and 2.14mmol/L at 6 months (95% CI: 1.17 to 3.12, I 2 =82%). No significant difference was demonstrated for the comparisons of weight due to relatively small number of studies retrieved from the literature resulting in insufficient statistical power. This study provides the precise effects of metformin monotherapy regarding the decreases in fasting plasma glucose and glycosated hemoglobin that physician can expected in drug-naive patients with type 2 diabetes mellitus. No evidence was found for the effects on weight. Copyright © 2018 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

Brief Report: Geographical Variation in Prevalence of Cryptococcal Antigenemia Among HIV-Infected, Treatment-Naive Patients in Nigeria: A Multicenter Cross-Sectional Study.

PubMed

Ezeanolue, Echezona E; Nwizu, Chidi; Greene, Gregory S; Amusu, Olatilewa; Chukwuka, Chinwe; Ndembi, Nicaise; Smith, Rachel M; Chiller, Tom; Pharr, Jennifer; Kozel, Thomas R

2016-09-01

Worldwide, HIV-associated cryptococcal meningitis affects approximately 1 million persons and causes 600,000 deaths each year mostly in sub-Saharan Africa. Limited data exist on cryptococcal meningitis and antigenemia in Nigeria, and most studies are geographically restricted. We determined the prevalence of cryptococcal antigenemia (CrAg) among HIV-infected, treatment-naive individuals in Nigeria. This was a retrospective, cross-sectional study across 4 geographic regions in Nigeria. We performed CrAg testing using a lateral flow immunoassay on archived whole-blood samples collected from HIV-infected participants at US President's Emergency Plan for AIDS Relief (PEPFAR)-supported sites selected to represent the major geographical and ethnic diversity in Nigeria. Eligible samples were collected from consenting patients (>15 years) naive to antiretroviral therapy with CD4 count less than 200 cells per cubic millimeter and were stored in an -80°C freezer. A total of 2752 stored blood samples were retrospectively screened for CrAg. Most of the samples were from participants aged 30-44 years (57.6%), and 1570 (57.1%) were from women. The prevalence of CrAg positivity in specimens with CD4 <200 cells per cubic millimeter was 2.3% (95% confidence interval: 1.8% to 3.0%) and varied significantly across the 4 regions (P < 0.001). At 4.4% (3.2% to 5.9%), the South East contained the highest prevalence. The significant regional variation in CrAg prevalence found in Nigeria should be taken into consideration as plans are made to integrate routine screening into clinical care for HIV-infected patients.

Consistent Safety and Infectivity in Sporozoite Challenge Model of Plasmodium vivax in Malaria-Naive Human Volunteers

PubMed Central

Herrera, Sócrates; Solarte, Yezid; Jordán-Villegas, Alejandro; Echavarría, Juan Fernando; Rocha, Leonardo; Palacios, Ricardo; Ramírez, Óscar; Vélez, Juan D.; Epstein, Judith E.; Richie, Thomas L.; Arévalo-Herrera, Myriam

2011-01-01

A safe and reproducible Plasmodium vivax infectious challenge method is required to evaluate the efficacy of malaria vaccine candidates. Seventeen healthy Duffy (+) and five Duffy (−) subjects were randomly allocated into three (A–C) groups and were exposed to the bites of 2–4 Anopheles albimanus mosquitoes infected with Plasmodium vivax derived from three donors. Duffy (−) subjects were included as controls for each group. Clinical manifestations of malaria and parasitemia were monitored beginning 7 days post-challenge. All Duffy (+) volunteers developed patent malaria infection within 16 days after challenge. Prepatent period determined by thick smear, was longer for Group A (median 14.5 d) than for Groups B and C (median 10 d/each). Infected volunteers recovered rapidly after treatment with no serious adverse events. The bite of as low as two P. vivax-infected mosquitoes provides safe and reliable infections in malaria-naive volunteers, suitable for assessing antimalarial and vaccine efficacy trials. PMID:21292872

Identification of rare and novel deletions that cause (δβ)0-thalassaemia and hereditary persistence of foetal haemoglobin in Indian population.

PubMed

Mayuranathan, Thiyagaraj; Rayabaram, Janakiram; Das, Reena; Arora, Neeraj; Edison, Eunice S; Chandy, Mammen; Srivastava, Alok; Velayudhan, Shaji R

2014-06-01

Hereditary persistence of foetal haemoglobin (HPFH) and (δβ)(0) -thalassaemia are conditions caused by large deletions that involve δ- and β-globin genes in the β-globin cluster, and they are characterized by increased haemoglobin (HbF) levels in adults. Significant phenotypic diversity is observed between the different mutations that cause these conditions. Molecular characterization of these deletions is important for accurate molecular diagnosis, and they will also provide the information on the cis-acting genetic regulatory elements present in the β-globin cluster. We performed gap-PCR, multiplex ligation-dependent probe amplification (MLPA), quantitative fluorescent multiplex PCR (QF-MPCR) and DNA sequencing to detect and characterize the deletions in the β-globin cluster. We characterized six different deletions resulting in (δβ)(0) -thalassaemia or HPFH in 51 unrelated families. With the help of multiple genetic tools, we performed comprehensive genetic analysis of HPFH and (δβ)(0) -thalassaemia in Indian population and could define the molecular basis of these conditions in this population. We also identified two novel HPFH mutations, 49.98 kb (HPFH-9) and 86.7 kb (HPFH-10) deletions, in this population. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Identification of intestinal ion transport defects in microvillus inclusion disease.

PubMed

Kravtsov, Dmitri V; Ahsan, Md Kaimul; Kumari, Vandana; van Ijzendoorn, Sven C D; Reyes-Mugica, Miguel; Kumar, Anoop; Gujral, Tarunmeet; Dudeja, Pradeep K; Ameen, Nadia A

2016-07-01

Loss of function mutations in the actin motor myosin Vb (Myo5b) lead to microvillus inclusion disease (MVID) and death in newborns and children. MVID results in secretory diarrhea, brush border (BB) defects, villus atrophy, and microvillus inclusions (MVIs) in enterocytes. How loss of Myo5b results in increased stool loss of chloride (Cl(-)) and sodium (Na(+)) is unknown. The present study used Myo5b loss-of-function human MVID intestine, polarized intestinal cell models of secretory crypt (T84) and villus resembling (CaCo2BBe, C2BBe) enterocytes lacking Myo5b in conjunction with immunofluorescence confocal stimulated emission depletion (gSTED) imaging, immunohistochemical staining, transmission electron microscopy, shRNA silencing, immunoblots, and electrophysiological approaches to examine the distribution, expression, and function of the major BB ion transporters NHE3 (Na(+)), CFTR (Cl(-)), and SLC26A3 (DRA) (Cl(-)/HCO3 (-)) that control intestinal fluid transport. We hypothesized that enterocyte maturation defects lead villus atrophy with immature secretory cryptlike enterocytes in the MVID epithelium. We investigated the role of Myo5b in enterocyte maturation. NHE3 and DRA localization and function were markedly reduced on the BB membrane of human MVID enterocytes and Myo5bKD C2BBe cells, while CFTR localization was preserved. Forskolin-stimulated CFTR ion transport in Myo5bKD T84 cells resembled that of control. Loss of Myo5b led to YAP1 nuclear retention, retarded enterocyte maturation, and a cryptlike phenotype. We conclude that preservation of functional CFTR in immature enterocytes, reduced functional expression of NHE3, and DRA contribute to Cl(-) and Na(+) stool loss in MVID diarrhea.

Antigen presenting cells (APCs) from thermally injured and/or septic rats modulate CD4+ T cell responses of naive rat.

PubMed

Fazal, Nadeem; Raziuddin, Syed; Khan, Mehdi; Al-Ghoul, Walid M

2006-01-01

Regulation of immune response is marked by complex interactions among the cells that recognize and present antigens. Antigen presenting cells (APCs), the antigen presenting cell component of the innate immune response plays an important role in effector CD4+ T cell response. Thermal injury and/or superimposed sepsis in rats' leads to suppressed CD4+ T cell functions. We investigated modulations of CD4+ T cell function by APCs (purified non-T cells) from thermally injured and/or septic rats. Rats were subjected to 30% total body surface area scald burn or exposed to 37 degrees C water (Sham burn) and sepsis was induced by cecal-ligation and puncture (CLP) method. At day 3 post-injury animals were sacrificed and CD4+ T cells and APCs from mesenteric lymph nodes (MLN) were obtained using magnetic microbead isolation procedure. APCs from injured rats were co-cultured with sham rat MLN CD4+ T cells and proliferative responses (thymidine incorporation), phenotypic changes (Flow cytometry), IL-2 production (ELISA) and CTLA-4 mRNA (RT-PCR) were determined in naive rat CD4+ T cells. The data indicate that APCs from thermally injured and/or septic rats when co-cultured with CD4+ T cells suppressed CD4+ T cell effector functions. This lack of CD4+ T cell activation was accompanied with altered co-stimulatory molecules, i.e., CD28 and/or CTLA-4 (CD152). In conclusion, our studies indicated that defective APCs from thermally injured and/or septic rats modulate CD4+ T cell functions via changes in co-stimulatory molecules expressed on naive CD4+ T cells. This altered APC: CD4+ T cell interaction leads to suppressed CD4+ T cell activation of healthy animals.

Support vector inductive logic programming outperforms the naive Bayes classifier and inductive logic programming for the classification of bioactive chemical compounds.

PubMed

Cannon, Edward O; Amini, Ata; Bender, Andreas; Sternberg, Michael J E; Muggleton, Stephen H; Glen, Robert C; Mitchell, John B O

2007-05-01

We investigate the classification performance of circular fingerprints in combination with the Naive Bayes Classifier (MP2D), Inductive Logic Programming (ILP) and Support Vector Inductive Logic Programming (SVILP) on a standard molecular benchmark dataset comprising 11 activity classes and about 102,000 structures. The Naive Bayes Classifier treats features independently while ILP combines structural fragments, and then creates new features with higher predictive power. SVILP is a very recently presented method which adds a support vector machine after common ILP procedures. The performance of the methods is evaluated via a number of statistical measures, namely recall, specificity, precision, F-measure, Matthews Correlation Coefficient, area under the Receiver Operating Characteristic (ROC) curve and enrichment factor (EF). According to the F-measure, which takes both recall and precision into account, SVILP is for seven out of the 11 classes the superior method. The results show that the Bayes Classifier gives the best recall performance for eight of the 11 targets, but has a much lower precision, specificity and F-measure. The SVILP model on the other hand has the highest recall for only three of the 11 classes, but generally far superior specificity and precision. To evaluate the statistical significance of the SVILP superiority, we employ McNemar's test which shows that SVILP performs significantly (p < 5%) better than both other methods for six out of 11 activity classes, while being superior with less significance for three of the remaining classes. While previously the Bayes Classifier was shown to perform very well in molecular classification studies, these results suggest that SVILP is able to extract additional knowledge from the data, thus improving classification results further.

R57K Polymorphism in the Human Immunodeficiency Virus Type 1 Protease as Predictor of Early Virological Failure in a Cohort of Antiretroviral-Naive Patients Treated Mostly with a Nelfinavir-Containing Regimen

PubMed Central

Masquelier, Bernard; Droz, Cecile; Dary, Martin; Perronne, Christian; Ferré, Virginie; Spire, Bruno; Descamps, Diane; Raffi, François; Brun-Vézinet, Françoise; Chêne, Geneviève

2003-01-01

In 243 antiretroviral-naive human immunodeficiency-infected patients starting a first-line-protease inhibitor (mainly nelfinavir)-containing therapy, the presence of the polymorphism R57K in the protease at the inception of therapy was independently associated with a higher rate of virological failure. PMID:14576131

Picturing neuroscience research through a human rights lens: Imaging first-episode schizophrenic treatment-naive individuals

PubMed Central

Eijkholt, Marleen; Anderson, James A.; Illes, Judy

2012-01-01

In this paper we examine imaging research involving first-episode schizophrenic treatment-naive individuals (FESTNIs) through a legal human rights lens; in particular, the lens of the Additional Protocol to the Convention on Human Rights and Biomedicine Concerning Biomedical Research. We identify a number of ethical and legal hot spots highlighted by the Protocol, and offer a series of recommendations designed to ensure the human rights compatibility of this research. Subsequently, we argue that the lack of reporting on design elements related to ethical concerns frustrates commitments at the heart of the human rights approach, namely, transparency and openness to international scrutiny. To redress this problem, we introduce two norms for the first time: ethical transparency, and ethical reproducibility. When concluding, we offer a set of reporting guidelines designed to operationalize these norms in the context of imaging research involving FESTNIs. Though we will not make this case here, we believe that parallel reporting guidelines should be incorporated into other areas of research involving human subjects. PMID:22304987

A Naive Bayes machine learning approach to risk prediction using censored, time-to-event data.

PubMed

Wolfson, Julian; Bandyopadhyay, Sunayan; Elidrisi, Mohamed; Vazquez-Benitez, Gabriela; Vock, David M; Musgrove, Donald; Adomavicius, Gediminas; Johnson, Paul E; O'Connor, Patrick J

2015-09-20

Predicting an individual's risk of experiencing a future clinical outcome is a statistical task with important consequences for both practicing clinicians and public health experts. Modern observational databases such as electronic health records provide an alternative to the longitudinal cohort studies traditionally used to construct risk models, bringing with them both opportunities and challenges. Large sample sizes and detailed covariate histories enable the use of sophisticated machine learning techniques to uncover complex associations and interactions, but observational databases are often 'messy', with high levels of missing data and incomplete patient follow-up. In this paper, we propose an adaptation of the well-known Naive Bayes machine learning approach to time-to-event outcomes subject to censoring. We compare the predictive performance of our method with the Cox proportional hazards model which is commonly used for risk prediction in healthcare populations, and illustrate its application to prediction of cardiovascular risk using an electronic health record dataset from a large Midwest integrated healthcare system. Copyright © 2015 John Wiley & Sons, Ltd.

Distinct expression patterns for type II topoisomerases IIA and IIB in the early foetal human telencephalon.

PubMed

Harkin, Lauren F; Gerrelli, Dianne; Gold Diaz, Diana C; Santos, Chloe; Alzu'bi, Ayman; Austin, Caroline A; Clowry, Gavin J

2016-03-01

TOP2A and TOP2B are type II topoisomerase enzymes that have important but distinct roles in DNA replication and RNA transcription. Recently, TOP2B has been implicated in the transcription of long genes in particular that play crucial roles in neural development and are susceptible to mutations contributing to neurodevelopmental conditions such as autism and schizophrenia. This study maps their expression in the early foetal human telencephalon between 9 and 12 post-conceptional weeks. TOP2A immunoreactivity was restricted to cell nuclei of the proliferative layers of the cortex and ganglionic eminences (GE), including the ventricular zone and subventricular zone (SVZ) closely matching expression of the proliferation marker KI67. Comparison with sections immunolabelled for NKX2.1, a medial GE (MGE) marker, and PAX6, a cortical progenitor cell and lateral GE (LGE) marker, revealed that TOP2A-expressing cells were more abundant in MGE than the LGE. In the cortex, TOP2B is expressed in cell nuclei in both proliferative (SVZ) and post-mitotic compartments (intermediate zone and cortical plate) as revealed by comparison with immunostaining for PAX6 and the post-mitotic neuron marker TBR1. However, co-expression with KI67 was rare. In the GE, TOP2B was also expressed by proliferative and post-mitotic compartments. In situ hybridisation studies confirmed these patterns of expression, except that TOP2A mRNA is restricted to cells in the G2/M phase of division. Thus, during early development, TOP2A is likely to have a role in cell proliferation, whereas TOP2B is expressed in post-mitotic cells and may be important in controlling expression of long genes even at this early stage. © 2015 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.

Dutch guideline for clinical foetal-neonatal and paediatric post-mortem radiology, including a review of literature.

PubMed

Sonnemans, L J P; Vester, M E M; Kolsteren, E E M; Erwich, J J H M; Nikkels, P G J; Kint, P A M; van Rijn, R R; Klein, W M

2018-06-01

Clinical post-mortem radiology is a relatively new field of expertise and not common practice in most hospitals yet. With the declining numbers of autopsies and increasing demand for quality control of clinical care, post-mortem radiology can offer a solution, or at least be complementary. A working group consisting of radiologists, pathologists and other clinical medical specialists reviewed and evaluated the literature on the diagnostic value of post-mortem conventional radiography (CR), ultrasonography, computed tomography (PMCT), magnetic resonance imaging (PMMRI), and minimally invasive autopsy (MIA). Evidence tables were built and subsequently a Dutch national evidence-based guideline for post-mortem radiology was developed. We present this evaluation of the radiological modalities in a clinical post-mortem setting, including MIA, as well as the recently published Dutch guidelines for post-mortem radiology in foetuses, neonates, and children. In general, for post-mortem radiology modalities, PMMRI is the modality of choice in foetuses, neonates, and infants, whereas PMCT is advised in older children. There is a limited role for post-mortem CR and ultrasonography. In most cases, conventional autopsy will remain the diagnostic method of choice. Based on a literature review and clinical expertise, an evidence-based guideline was developed for post-mortem radiology of foetal, neonatal, and paediatric patients. What is Known: • Post-mortem investigations serve as a quality check for the provided health care and are important for reliable epidemiological registration. • Post-mortem radiology, sometimes combined with minimally invasive techniques, is considered as an adjunct or alternative to autopsy. What is New: • We present the Dutch guidelines for post-mortem radiology in foetuses, neonates and children. • Autopsy remains the reference standard, however minimal invasive autopsy with a skeletal survey, post-mortem computed tomography, or post

The RNA Binding Protein CsrA Is a Pleiotropic Regulator of the Locus of Enterocyte Effacement Pathogenicity Island of Enteropathogenic Escherichia coli▿

PubMed Central

Bhatt, Shantanu; Edwards, Adrianne Nehrling; Nguyen, Hang Thi Thu; Merlin, Didier; Romeo, Tony; Kalman, Daniel

2009-01-01

The attaching and effacing (A/E) pathogen enteropathogenic Escherichia coli (EPEC) forms characteristic actin-filled membranous protrusions upon infection of host cells termed pedestals. Here we examine the role of the RNA binding protein CsrA in the expression of virulence genes and proteins that are necessary for pedestal formation. The csrA mutant was defective in forming actin pedestals on epithelial cells and in disrupting transepithelial resistance across polarized epithelial cells. Consistent with reduced pedestal formation, secretion of the translocators EspA, EspB, and EspD and the effector Tir was substantially reduced in the csrA mutant. Purified CsrA specifically bound to the sepL espADB mRNA leader, and the corresponding transcript levels were reduced in the csrA mutant. In contrast, Tir synthesis was unaffected in the csrA mutant. Reduced secretion of Tir appeared to be in part due to decreased synthesis of EscD, an inner membrane architectural protein of the type III secretion system (TTSS) and EscF, a protein that forms the protruding needle complex of the TTSS. These effects were not mediated through the locus of enterocyte effacement (LEE) transcriptional regulator GrlA or Ler. In contrast to the csrA mutant, multicopy expression of csrA repressed transcription from LEE1, grlRA, LEE2, LEE5, escD, and LEE4, an effect mediated by GrlA and Ler. Consistent with its role in other organisms, CsrA also regulated flagellar motility and glycogen levels. Our findings suggest that CsrA governs virulence factor expression in an A/E pathogen by regulating mRNAs encoding translocators, effectors, or transcription factors. PMID:19581394

Molecular characterization of locus of enterocyte effacement pathogenicity island in shigatoxic Escherichia coli isolated from human & cattle in West Bengal, India

PubMed Central

Das, Suresh Chandra; Ramamurthy, Thandavanaryanalu; Ghosh, Santanu; Pazhani, Gururaja Perumal; Sen, Tista; Singh, Raghubir

2017-01-01

Background & objectives: Shigatoxic Escherichia coli (STEC) recovered from dairy animals of Kolkata, India, harboured the putative virulence genes; however, the animals did not exhibit clinical symptoms. Similarly, human isolates in this locality also showed variations in degree of symptoms. Hence, this study was designed to know the presence of recognized gene(s) in the locus of enterocyte effacement (LEE) pathogenicity island in these STEC isolates and functional status of the cardinal gene (eae) related to pathogenicity. Methods: Genes were characterized using polymerase chain reaction (PCR) assays, and functional status of cardinal gene (eae) was evaluated by fluorescent actin staining (FAS) assay. Variation in eae gene was determined by intimin PCR. Results: Cattle STEC isolates carried 22 genes in LEE pathogenicity island in different frequencies ranging from 5.63 to 47.88 per cent of the isolates. In human isolates, the genes namely ler, escRSTU, orf2, escC, escV, orf3 and tir that are associated with secretory function, were found to be absent and rest of the genes were present in lower frequency. Further, the cardinal gene (eae) responsible for initiation of pathogenesis was in a very low frequency in human (n=2; 10.5%) and cattle (n=11; 15.5%) isolates. None of these eae+ STEC isolates from human and cattle revealed positivity in FAS assay. Interpretation & conclusions: Majority of human STEC isolates lacked the cardinal virulence gene (eae), and genes for secretory function that are essential for facilitating pathogenesis. This may partially be attributed to low occurrence of STEC in human clinical diarrhoea in this area. Although a few isolates (11 of 71) from cattle had eae gene, they did not express phenotypically. This could be one of the reasons for not appearing of clinical symptoms in the hosts. PMID:29205193

Effect of tibial bone resection on the development of fast- and slow-twitch skeletal muscles in foetal sheep.

PubMed

West, J M; Williams, N A; Luff, A R; Walker, D W

2000-04-01

To determine if longitudinal bone growth affects the differentiation of fast- and slow-twitch muscles, the tibial bone was sectioned at 90 days gestation in foetal sheep so that the lower leg was permanently without structural support. At 140 days (term is approximately 147 days) the contractile properties of whole muscles, activation profiles of single fibres and ultrastructure of fast- and slow-twitch muscles from the hindlimbs were studied. The contractile and activation profiles of the slow-twitch soleus muscles were significantly affected by tibial bone resection (TIBX). The soleus muscles from the TIBX hindlimbs showed: (1) a decrease in the time to peak of the twitch responses from 106.2 +/- 10.7 ms (control, n = 4) to 65.1 +/- 2.48 ms (TIBX, n = 5); (2) fatigue profiles more characteristic of those observed in the fast-twitch muscles: and (3) Ca2+ - and Sr2+ -activation profiles of skinned fibres similar to those from intact hindlimbs at earlier stages of gestation. In the FDL, TIBX did not significantly change whole muscle twitch contraction time, the fatigue profile or the Ca2+ - and Sr2+ -activation profiles of skinned fibres. Electron microscopy showed an increased deposition of glycogen in both soleus and FDL muscles. This study shows that the development of the slow-twitch phenotype is impeded in the absence of the physical support normally provided by the tibial bone. We suggest that longitudinal stretch is an important factor in allowing full expression of the slow-twitch phenotype.

Identification of intestinal ion transport defects in microvillus inclusion disease

PubMed Central

Kravtsov, Dmitri V.; Ahsan, Md Kaimul; Kumari, Vandana; van Ijzendoorn, Sven C. D.; Reyes-Mugica, Miguel; Kumar, Anoop; Gujral, Tarunmeet; Dudeja, Pradeep K.

2016-01-01

Loss of function mutations in the actin motor myosin Vb (Myo5b) lead to microvillus inclusion disease (MVID) and death in newborns and children. MVID results in secretory diarrhea, brush border (BB) defects, villus atrophy, and microvillus inclusions (MVIs) in enterocytes. How loss of Myo5b results in increased stool loss of chloride (Cl−) and sodium (Na+) is unknown. The present study used Myo5b loss-of-function human MVID intestine, polarized intestinal cell models of secretory crypt (T84) and villus resembling (CaCo2BBe, C2BBe) enterocytes lacking Myo5b in conjunction with immunofluorescence confocal stimulated emission depletion (gSTED) imaging, immunohistochemical staining, transmission electron microscopy, shRNA silencing, immunoblots, and electrophysiological approaches to examine the distribution, expression, and function of the major BB ion transporters NHE3 (Na+), CFTR (Cl−), and SLC26A3 (DRA) (Cl−/HCO3−) that control intestinal fluid transport. We hypothesized that enterocyte maturation defects lead villus atrophy with immature secretory cryptlike enterocytes in the MVID epithelium. We investigated the role of Myo5b in enterocyte maturation. NHE3 and DRA localization and function were markedly reduced on the BB membrane of human MVID enterocytes and Myo5bKD C2BBe cells, while CFTR localization was preserved. Forskolin-stimulated CFTR ion transport in Myo5bKD T84 cells resembled that of control. Loss of Myo5b led to YAP1 nuclear retention, retarded enterocyte maturation, and a cryptlike phenotype. We conclude that preservation of functional CFTR in immature enterocytes, reduced functional expression of NHE3, and DRA contribute to Cl− and Na+ stool loss in MVID diarrhea. PMID:27229121