Miracle-dz/UniFAR-FTUs huggingface dataset:
BDCA3 expression is associated with high IFN‐λ production by CD34+‐derived dendritic cells generated in the presence of GM‐CSF, IL‐4, and/or TGF‐β

High BDCA3 expression is associated with a specific human IFN‐λ‐producing dendritic cell (DC) subset. However, BDCA3 has also been detected on other DC subsets. Thus far, development and function of BDCA3 expression on DCs remains poorly understood. Human Langerhans cells (LCs) and interstitial DCs (intDCs) can be generated in vitro by differentiation of CD34+ hematopoietic progenitors via distinct precursor DCs (preDCs), CD1a+ preDCs, and CD14+ preDCs, respectively. Here, we identified BDCA3 expression in this well‐known GM‐CSF/TNF‐α‐driven culture system and described the effect of IL‐4 and/or TGF‐β on induction of BDCA3 expression. In control or TGF‐β cultures, BDCA3 was only detected on CD14+ preDC‐derived intDCs. IL‐4 induced BDCA3 expression in both CD14+‐derived and CD1a+‐derived cultures. TGF‐β and IL‐4 together further increased CD14+‐derived and CD1a+‐derived BDCA3+ DC frequencies, which partly expressed CLEC9A, but were not identical to the BDCA3highCLEC9A+ DC subset in vivo. Importantly, BDCA3+ cells, but not BDCA3− cells, in this system produced high IFN‐λ levels upon polyinosinic:polycytidylic acid (polyI:C) stimulation. This culture system, in which BDCA3 expression is preferentially associated with the intDC lineage and IFN‐λ‐producing capacity, will greatly contribute to further research on the function and regulation of BDCA3 expression and IFN‐λ production by DCs.
Does poor early metabolic control predict subsequent poor control in young children with Type 1 diabetes: An exploratory study

Background: We sought to determine whether poor metabolic control during the early stages of Type 1 diabetes mellitus predicts control during subsequent years. We hypothesized that poor control in the first year after diagnosis would predict poor control in the following year, and that poor control in the second year after diagnosis would predict poor metabolic control in subsequent years.
Characterization of a nicotinamide–adenine dinucleotide‐dependent cation channel in the CRI‐G1 rat insulinoma cell line

1 Cell‐free excised membrane patches were used to examine the properties of a novel nicotinamide–adenine dinucleotide (β‐NAD+)‐activated ion channel in the rat insulin‐secreting cell line, CRI‐G1. 2 In inside‐out recordings, β‐NAD+ (0.05–1.0 mm) induced the appearance of a channel characterized by extremely slow kinetics, with mean open times in the range of seconds. The estimated EC50 for activation was 114 μm. Channel activity declined with time (run‐down) following activation by β‐NAD+ in excised patches and this was not prevented by intra‐cellular application of trypsin. 3 The single channel current–voltage relationship was linear with a conductance of 74 pS in symmetrical NaCl. The channel appears equally permeable to Na+, K+ and Cs+, exhibits an appreciable permeability to Ca2+, Mg2+ and Ba2+, but excludes anions. 4 The channel displays an unusual voltage sensitivity, with an abrupt increase in open‐state probability at depolarized voltages. 5 Channel opening, in the presence of β‐NAD+, required both Ca2+ and Mg2+ to be present at the internal side of the membrane. Activation by Ca2+ required a concentration of at least 10 μm and was maximal at 0.1 mm. Ba2+ did not substitute for Ca2+ in inducing channel activity nor did it inhibit activation by Ca2+. Increasing the concentration of intracellular Mg2+ stabilized the open state of NAD+‐activated channels. 6 The non‐selective cation channel reported here differs in its gating and modulatory characteristics from non‐selective cation channels described in other tissues. This channel may play a role in the pathophysiological reponses of β‐cells to oxidative stress.
Body temperature and endocrine interactions before and after calving in beef cows.

Multiparous beef cows (n = 7) were used to evaluate peripartum changes and interactions among body temperature (BT) and circulating progesterone (P4), estradiol-17beta (E2), triiodothyronine (T3), cortisol, thyroxine (T4), and 13,14-dihydro-15-keto-prostaglandin F2alpha (PGFM) concentrations. Electronic temperature monitors were placed under the obliquus abdominis internus muscle of the left flank, and BT was measured using radiotelemetry every 3 min for 10-s periods from 144 h before to 24 h after calving. Environmental temperatures (ET) were recorded hourly. Body and environmental temperatures were averaged, separately, within 8-h periods. Blood samples were collected every 8 h, and hormone concentrations were measured. Time of day affected BT (P < .01), at 0300 cows had the lowest BT, at 1900 the highest, and at 1100 values were intermediate. Body temperature remained relatively constant (P > .10) from 144 to 56 h before calving and from 8 to 24 h after calving but decreased (P < .01) from 48 to 8 h before calving. Precalving BT was affected (P < .01) by ET, but hour-before-calving (time) had the greatest effect on BT during the 48 to 8 h immediately preceding parturition (b' = .41, P < .01) and was independent of ET effects. Before the BT decrease, cows gestating heifers had lower (P < .01) BT than cows gestating bulls. Plasma E2, PGFM, T3, and T4 concentrations before the precalving decrease in body temperature were greater (P < .03) in cows gestating bull rather than heifer calves. Approximately 30% of the variation (R2) during the temperature decrease was explained by plasma hormone concentrations; PGFM (b' = -.30, P < .05) and T3 (b' = -.22, P < .10) had the most significant effects. In conclusion, BT of the cow before the precalving decrease was affected by ET and sex of calf. However, the prepartum BT decrease was independent of these variables, and seemed partially endocrine-induced.
Use of C-banding for identifying radiation induced micronuclei

Abstract Differentiation of micronuclei (MN) caused by ionizing radiation from those caused by chemicals is a crucial step for managing treatment of individuals exposed to radiation. MN in binucleated lymphocytes in peripheral blood are widely used as biomarkers for estimating dose of radiation, but they are not specific for ionizing radiation. MN induced by ionizing radiation originate predominantly as a result of chromosome breaks (clastogenic action), whereas MN caused by chemical agents are derived from the loss of entire chromosomes (aneugenic action). C-banding highlights centromeres, which might make it possible to distinguish radiation induced MN, i.e., as a byproduct of acentric fragments, from those caused by the loss of entire chromosomes. To test the use of C-banding for identifying radiation induced MN, a blood sample from a healthy donor was irradiated with 3 Gy of Co-60 gamma rays and cultured. Cells were harvested and dropped onto slides, divided into a group stained directly with Giemsa and another processed for C banding, then stained with Giemsa. The frequency of MN in 500 binucleated cells was scored for each method. In preparations stained with Giemsa directly, the MN appeared as uniformly stained structures, whereas after C banding, some MN exhibited darker regions corresponding to centromeres that indicated that they were not derived from acentric fragments. The C-banding technique enables differentiation of MN from acentric chromosomal material. This distinction is useful for improving the specificity of the MN assay as a biomarker for ionizing radiation.
Immunoglobulin G antibodies against deamidated‐gliadin‐peptides outperform anti‐endomysium and tissue transglutaminase antibodies in children <2 years age

Mubarak A, Gmelig‐Meyling FHJ, Wolters VM, Ten Kate FJW, Houwen RHJ. Immunoglobulin G antibodies against deamidated‐gliadin‐peptides outperform anti‐endomysium and tissue transglutaminase antibodies in children <2 years. APMIS 2011; 119: 894–900.
SINGLE SESSION OF PASCAL VERSUS MULTIPLE SESSIONS OF CONVENTIONAL LASER FOR PANRETINAL PHOTOCOAGULATION IN PROLIFERATIVE DIABETIC RETINOPATHY: A Comparitive Study

Background: Panretinal photocoagulation remains the gold standard for treatment of proliferative diabetic retinopathy, which can be done in a single session or in multiple sessions. However, because of different reasons, single session is less frequently practiced. We describe the results of a single session of pattern scan laser versus multiple sessions of conventional laser in cases of proliferative diabetic retinopathy. Methods: A prospective study was performed on 50 patients (100 eyes), in whom proliferative diabetic retinopathy was diagnosed recently. Two eyes of an individual patient were randomly assigned, one for a single session of panretinal photocoagulation using pattern scan laser and the other for multiple sessions of conventional laser. Results: Our study confirms that single session is effective and even better than conventional laser in relation to the effect of treatment. Conclusion: Complications and the associated pain are less; thus, the patient's acceptance of PASCAL was high, and a single session was well tolerated with topical anesthesia alone.
Brain and Blood Concentrations of Propofol after Rapid Intravenous Injection in Sheep, and Their Relationships to Cerebral Effects

The time-course of propofol concentrations in the blood and brain following rapid administration of three doses were examined using a sheep preparation and regional pharmacokinetic techniques. These were compared to the time-course of cerebral effects of propofol reported previously. There were marked differences between the time-course of propofol concentrations in arterial blood and the brain, with a close relationship between the time-course of brain concentrations and effects on depth of anaesthesia and CBF. There was evidence that the effect of propofol on cerebral blood flow altered its own rate of elution from the brain. Hysteresis between arterial propofol concentrations and cerebral effects following rapid IV administration therefore appears to have a pharmacokinetic basis, and conventional compartmental pharmacokinetic analysis using blood concentrations alone may fail to accurately predict the time-course of both brain propofol concentrations and depth of anaesthesia.
Food Insecurity and Associated Factors in the Portuguese Population

Background The burden of food insecurity in Portugal, and the socioeconomic and demographic factors that are related to this condition, are unknown. Objective To evaluate the frequency of food insecurity and to identify its associated characteristics in the Portuguese population. Methods Data from 3,552 heads of family respondents of the 2005/06 Portuguese National Health Survey were analyzed in a cross-sectional study. Food insecurity was evaluated with the use of the US Department of Agriculture Household Food Security Survey Module 6-Item Short Form. Chi-square tests and multivariate logistic regression models were conducted. Significance was indicated at p < . 05. Results Among the respondents, 16.5% were food insecure and 3.5% had very low food security. The odds of being food insecure were highest for women (OR, 1.51; 95% CI, 1.20 to 1.91), smokers (OR, 1.56; 95% CI, 1.20 to 2.02), younger people (OR, 2.54; 95% CI, 1.69 to 3.80), unemployed people (OR, 3.04; 95% CI, 2.01 to 4.60), those with lower education (OR, 7.98; 95% CI, 4.73 to 13.49), and those with lower income (OR, 6.27; 95% CI, 4.23 to 9.30). Conclusions The present study explored for the first time the burden of food insecurity in Portugal, revealing that it was highly prevalent, affecting one in six Portuguese citizens. Low education and low income were the main factors associated with food insecurity.
INFLUENCE OF INTRACRANIAL ANEURYSM‐TO‐PARENT VESSEL SIZE RATIO ON HEMODYNAMICS AND IMPLICATION FOR RUPTURE: RESULTS FROM A VIRTUAL EXPERIMENTAL STUDY

OBJECTIVEThe effectiveness of intracranial aneurysm (IA) size as a predictor for rupture has been debated. We recently performed a retrospective analysis of IA morphology and found that a new index, namely, aneurysm-to-parent vessel size ratio (SR), was strongly correlated with IA rupture, with 77% of ruptured IAs showing an SR of more than 2, and 83% of unruptured IAs showing an SR of 2 or less. As hemodynamics have been implicated in both IA development and rupture, we examine how varying SR influences intra-aneurysmal hemodynamics. METHODSOne sidewall and 1 terminal IA were virtually reconstructed from patient 3-dimensional angiographic images. In 2 independent in silico experiments, the SR was varied from 1.0 to 3.5 by virtually changing either aneurysm size or vessel diameter while keeping the other parameter constant. Pulsatile computational fluid dynamics simulations were performed on each model for hemodynamics analysis. RESULTSLow SR (≤2) aneurysm morphology consistently demonstrated simple flow patterns with a single intra-aneurysmal vortex, whereas higher SR (>2) aneurysm morphology presented multiple vortices and complex flow patterns. The aneurysm luminal area that was exposed to low wall shear stress increased with increasing SR. Complex flow, multiple vortices, and low aneurysmal wall shear stress have been associated with ruptured IAs in previous studies. CONCLUSIONHigher SR, irrespective of aneurysm type and absolute aneurysm or vessel size, gives rise to flow patterns typically observed in ruptured IAs. These results provide hemodynamic support for the existing correlation of SR with rupture risk.
Attitude of women towards family planning methods and its use--study from a slum of Delhi.

BACKGROUND To predict the need of family planning methods, family planning managers often rely on unmet need derived from measure of contraceptive demand. However women's intention and her background knowledge of family planning methods not received as much attention as a measure of family planning methods demand. OBJECTIVE To know the attitude of women regarding use of family planning methods and to find out the factors that restricts its use, and the change in pattern of use over a period of one year. METHODS This was a prospective study. One (Block G) out of eight blocks was selected randomly. Using convenient sample method, families were selected starting from a point in the selected block (Block G). 40 women of childbearing age group (15- 49 years) were enrolled. All women were followed for a period of one year. RESULTS Weakness was narrated as the commonest side effect from all family planning methods. More than 70% women told that irregular menstruation from Oral Contraceptive pills and ill health from tubectomy as the other side effects. Demands for more children and for son preferences were the leading reason for not using any methods followed by afraid of side effects and health problems. There was negligible change in the use of family planning methods during the period of the study. CONCLUSION Effective family planning methods use should be advocated through adequate counseling about the correct use, side effects and their proper management and their benefit in the back ground of custom and belief.
Systemic thromboembolic adverse events in patients treated with intravitreal anti-VEGF drugs for neovascular age-related macular degeneration

Introduction: The consistent association between choroid neovascularization (CNV) and increased VEGF-A expression provides a strong reason for exploring the therapeutic potential of anti-VEGF agents in the treatment of neovascular age-related macular degeneration (AMD). The authors report the systemic side effects secondary to intravitreal administration of these compounds, that is, the main cardiovascular effects, as well as the less frequent cerebrovascular accidents, myocardial infarction, transient ischemic attacks, deep vein thrombosis, pulmonary embolism and thromboflebitis. Areas covered: The authors reviewed major Clinical Trials and publications concerning systemic adverse events of anti-VEGF drugs in order to identify the main thromboembolic events related to the use of these agents and their occurrence. Anti-VEGF efficacy, safety and tolerability are also discussed. Expert opinion: Three compounds (pegaptanib, ranibizumab and aflibercept) have been approved for the treatment of AMD; a fourth agent, bevacizumab, is used off-label. Anti-VEGF therapy has not shown the ability to fully eradicate the CNV, so that recurrences are common when the intravitreal injections are suspended. Although no evident rise in anti-VEGF-induced thromboembolic side effects was reported, more data are required to evaluate hemodynamic and pharmacokinetics of these compounds. Since only few studies have focused on these aspects, further researches are mandatory to determine distribution, effects and duration of these substances.
Single- and repeated-dose pharmacokinetics of eplerenone, a selective aldosterone receptor blocker, in rats

1. The pharmacokinetics of eplerenone (EP) were examined in rats following single or repeated dosing with 14 C-labelled or unlabelled EP to characterize absorption, metabolism and excretion. Rates of EP metabolism and cytochrome P450 activities were determined in vitro after repeated dose administration of EP. 2. Following a single i.v. dose (15 mg kg − 1), the elimination half-life of EP was 0.80 and 1.14 h in male and female rats, respectively. Plasma clearances (CL) of EP were 1.62 and 1.20 l kg − 1 h − 1 in males and females, respectively. Following a single oral dose (15 mg kg − 1), C max and T max of EP were 1.71 µg ml − 1 and 0.5 h in male rats. The corresponding values in female rats were 3.54 µg ml − 1 and 1.0 h. The systemic availability of EP was 25.6% in male rats and 66.4% in female rats, demonstrating sex differences in the pharmacokinetics of EP. 3. In the 8-day study, the AUC 0-24h 's of total EP (closed lactone ring form plus open form) following 100 and 200 mg kg − 1 oral doses were approximately half those on day 1 in male rats. After repeated dosing for 13 weeks, the pharmacokinetics of total EP did not change with study duration at the 20 mg kg − 1 dose in both males and females. However, at the 100 mg kg − 1 dose, AUC 0-24h 's were notably reduced on day 24 but progressively increased on subsequent days to approximate day 1 levels by day 86 in both sexes. At the 500 mg kg − 1 dose, the AUCs on day 86 remained lower than those on day 1. Reductions in AUCs on days 8 and 24 appeared to be the result of metabolism induction. 4. EP was extensively metabolized in male rats and most faecal and urinary radioactivity was in the form of metabolites. In female rats, the vast majority of urine and faecal radioactivity was associated with total EP. Thus, the sex difference in the pharmakokinetics of EP was due to more extensive metabolism in male rats. 5. The major metabolite in the rat was 6 β -OH EP. EP 6 β -hydroxylase activity was well correlated with testosterone 6 β -hydroxylase activity, indicating that EP metabolism to 6 β -OH EP was mediated primarily by CYP3A in the rat. 6. After repeated dose administration, EP increased 6 β -hydroxylase activities of testosterone and EP itself in a dose-dependent manner in both male and female rats, indicating that EP was a CYP3A inducer in the rat. There appeared to be no effects on activities of CYP1A1, 2B and 2E1.
PRL-3 promotes epithelial mesenchymal transition by regulating cadherin directly

PRL-3 is a key gene associated with progression and metastasis of colorectal cancer. Recently PRL-3 was suggested to promote epithelial mesenchymal transition（EMT） by down-regulating E-cadhrin expression. But the mechanisms of EMT induced by PRL-3 remain largely unknown. Here we found that PRL-3 could also promote EMT in a colorectal cancer cell model SW480 with deficient E-cadherin expression in vivo and in vitro. PRL-3 stable overexpression or knockdown SW480 cells were injected subcutaneously into nude mice. Immunohistochemical analyses of tumor samples from nude mice showed that PRL-3 promoted up-regulation of mesenchymal marker vimentin and down-regulation of epithelial markers E-cadherin and cytokeratin. Glycogen synthase kinase-3β inactivated by PRL-3 as assessed by phosphospecific antibodies was a key event in EMT induced by PRL-3. Inhibition of glycogen synthase kinase-3β by lithium chloride, a highly selective inhibitor, leading to phosphorylation of glycogen synthase kinase-3β increased Snail expression. In order to identify the direct effects of PRL-3, we isolated CDH22, one member of cadherin family, as a new candidate of interacting proteins of PRL-3 in yeast two-hybrid systems, and the interaction was confirmed in vitro by GST pull-down assay or in exogenous cell systems and endogenous colorectal cancer cells by co-immunoprecipitation assay and co-localization analysis. We observed that PRL-3 promoted down-regulation of CDH22 expression. Interestingly, expression of E-cadherin was recovered in SW480 cells after PRL-3 was knocked-down. Our results first linked PRL-3 to cadherin directly. It provided new insights into the regulatory mechanisms of EMT induced by PRL-3.
Experimental Carotid Stenosis and Endothelial Injury in the Rabbit: An In Vivo Model to Study Intravascular Platelet Aggregation

Summary Previous studies have shown that experimental canine coronary artery stenosis associated with endothelial injury results in a typical pattern of coronary flow characterized by gradual decreases in coronary flow to almost zero values followed by restorations of flow to normal values. This pattern of flow, called cyclic flow reductions (CFRs), is the consequence of recurrent platelet aggregation at the site of the stenosis and endothelial injury and subsequent dislodgement of the thrombus. In the present study, platelet activation and aggregation in vivo was induced by placing an external constrictor around carotid arteries with endothelial injury in anesthetized rabbits. Carotid blood flow velocity was measured continuously with a Doppler flow probe positioned proximally to the constrictor. After placement of the constrictor, CFRs developed in 14 of 14 rabbits with a mean frequency of 16.5 ± 2.3 cycles/h. CFRs were observed for 30 min, and the animals were treated with either an i.v. bolus of aspirin (10 mg/kg) or R 68070 (20 mg/kg), a drug with simultaneous TxA2 synthase and TxA2/PGH2 receptor blocking properties. Aspirin completely inhibited CFRs in 4 of 7 rabbits, whereas R 68070 eliminated CFRs in 7 of 7 animals. In the 3 animals that did not respond to aspirin, administration of ketanserin (0.25 mg/ kg i.v.), a selective serotonin S2 receptor antagonist, completely abolished CFRs. Both aspirin and R 68070 resulted in a marked reduction in serum TxB2 formation and in a complete inhibition of ex vivo platelet aggregation in response to arachidonic acid, whereas aggregation in response to U46619, a TxA2 mimetic, was inhibited only in R 68070-treated rabbits. We conclude that 1) CFRs develop in rabbit carotid arteries at sites of experimental stenosis and endothelial injury; 2) this model can be usefully employed to study platelet aggregation and platelet-vessel wall interaction in vivo and to test the efficacy of antiplatelet interventions.