Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of Insertions in the HIV-1 P6 Ptapp Region on the Virological Response to Amprenavir

We evaluated the impact of genetic changes within p6Gag gene on the virological response (VR, mean decrease in plasma viral load at week 12) to unboosted amprenavir (APV). Gag-protease fragments, including gag p2, p7, p1, p6 regions and whole protease (PR) were sequenced from baseline plasma specimens of 84 highly pre-treated but APV-naive patients included in the NARVAL (ANRS 088) trial. The correlation between baseline p6Gag polymorphism, PR mutations, baseline characteristics and VR to APV was analysed in univariate analysis. Insertions (P459Ins) within p6 protein, leading to partial or complete duplication of the PTAPP motif, were significantly associated with a decreased VR (P459Ins versus wild-type; –0.3 ±0.8 vs –1.1 ±1.2 log copies/ml, P=0.007) and were more frequent when the V82A/F/T/S PR mutation was present (P=0.020). In multivariate analysis, after adjustment on the predictive factors of the VR in the NARVAL trial and on the PR mutations linked with response, there was a strong trend to an association (P=0.058) between the presence of P459Ins and an altered VR. In conclusion, these results suggest that insertions in the p6 region of HIV-1 gag gene may affect the VR, in highly pre-treated patients receiving an unboosted APV-containing regimen.
Functional or Fantasy? Examining the Implications of Subjective Temporal Perspective “Trajectories” for Life Satisfaction

In a 5-year longitudinal study of young community adults, the authors examined subjective temporal perspective (STP) “trajectories” derived from ratings of past, present, and anticipated future life satisfaction (LS) collected at two time points. Upward STP trajectories (past < present < future LS) were normative at both time points. Opposing hypotheses were derived from the literature concerning the potential positive versus negative implications of upward STP trajectories. Using latent trajectory modeling, individual differences in STP trajectories were examined in relation to mental, physical, and interpersonal functioning as well as future satisfaction bias (over- vs. underestimation of future LS). Steeper upward STP trajectories were associated with less positive functioning, both concurrently and prospectively, as well as greater future satisfaction bias. Therefore, rather than representing a realistic, adaptive form of self-enhancement, steep upward STP trajectories for LS appeared to be a form of fantasizing and wishful thinking, associated with distress, dissatisfaction, and dysfunction.
Xanthine oxidase and cardiovascular risk in obese children.

BACKGROUND Pathological mechanisms of how childhood obesity leads to increased risk of cardiovascular disease (CVD) are not fully characterized. Oxidative-stress-related enzymes, such as xanthine oxidase (XO), have been linked to obesity, endothelial dysfunction, and CVD in adults, but little is known about this pathway in children. The aim of this study was to determine whether differential XO activity is associated with endothelial dysfunction, CVD risk factors, or cytokine levels. METHODS Fasting plasma samples were obtained from obese (BMI ≥ 95th percentile; n = 20) and age- and gender-matched healthy weight (BMI > 5th and < 85th percentile; n = 22) children and adolescents (mean age, 12 ± 3 years) to quantify XO activity. In addition, fasting cholesterol, insulin, glucose, blood pressure, endothelial function, and cytokine levels were assessed. RESULTS We observed a 3.8-fold increase in plasma XO activity in obese, compared to healthy weight, children (118 ± 21 vs. 31 ± 9 nU/mg of protein; p < 0.001). Plasma XO activity was correlated with BMI z-score (r = 0.41), waist circumference (r = 0.41), high-density lipoprotein cholesterol (r = -0.32), oxidized low-density lipoprotein (r = 0.57), adiponectin (r = -0.53), and monocyte chemotactic protein-1 (r = -0.59). CONCLUSION XO activity is highly elevated in obese children and correlates with CVD risk factors, suggesting that XO may play a role in increasing cardiovascular risk early in life in the context of obesity.
Informed Consent Practices and its Implication for Emergency Obstetrics Care in Azare, North-Eastern Nigeria

Background: Consent practices can affect the institution of emergency obstetrics care in the health facility, and may indeed, determine the degree of maternal mortality and morbidity. Objectives: This study was aimed at determining informed consent practices and its implication for Emergency Obstetrics Care (EOC). Methods: A cross-sectional study involving 787 women who presented with obstetric emergencies at the FMC Azare from 1st January 2008 to 31st December 2009 was done. The sociodemographic characteristics and birth outcome were compared between those that gave early consent (EC) and those that gave delayed consent (DC). Data was analysed using SPSS version 11. Morbidities and mortalities were compared in the two groups and P < 0.05 was considered statistically significant. Results: EC for obstetric intervention was obtained in 260 (33.0%) of the cases, while 527 (66.0%) gave DC. The mean length of time for DC was 4.5 ± 3.5 hours (Range 1.25 to 72 hours). In 62.9% of cases the consent was given by the husband while the patient consented in 5.6%. In-laws, relatives and others were responsible for 13.8%, 8.5%, 5.7% and 3.5% respectively. Consent was significantly delayed when given by the husbands, in-laws and relatives. Patients that gave consents for their own treatment were more likely to be gainfully employed (P=0.019), educated (P=0.004) and booked (P=0.001). Maternal mortality, intrauterine fetal death, low Apgar scores and early neonatal death were significantly increased in the DC group with P values of 0.016, 0.032 and 0.026 respectively. Conclusion: Delay in giving Consent contributes significantly to maternal and fetal morbidity and mortality in our environment because it increases the 3rd level of delay.
No role of the dopamine transporter in acute ethanol effects on striatal dopamine dynamics

The acute effects of ethanol on dopamine (DA) release and clearance in the caudate–putamen were evaluated in wild‐type and dopamine transporter (DAT) knockout (DAT‐KO) mice, using microdialysis and voltammetry. Dialysate DA levels were elevated, ∼80% above baseline levels, after administration of 2 g/kg ethanol in both wild‐type and DAT‐KO mice. In brain slices containing the caudate–putamen, a low (20 mM) concentration of ethanol produced no change in electrically stimulated DA release in either wild‐type or DAT‐KO mice. A high concentration (200 mM) of ethanol caused a similar decrease in DA release in slices from both types of mice. DA clearance was unaltered across the genotypes at low and high concentrations of ethanol. The fact that ethanol had similar effects in wild‐type and DAT‐KO mice, measured by in vivo microdialysis or brain slice voltammetry, supports the idea that acute ethanol does not interact with the DAT to produce its effects on the DA system. Synapse 60:288–294, 2006. © 2006 Wiley‐Liss, Inc.
Identification and characterization of Aspergillus flavus and aflatoxins

Aspergillus flavus is the main producer of the well known carcinogenic aflatoxins. The presence of this fungus and aflatoxins is of huge concern in terms of food safety. The identification of A. flavus is not straightforward due to similarities with closely related species (e.g. A. parasiticus and A. nomius). Also, from the biochemical point of view the closely-related species are able to produce different mycotoxins. In order to clarify the differentiation between species the identification schemes is revisited. Selective media, data from mycotoxins production and molecular biology tools are discussed in order to clarify the concept of A. flavus species.
Prevention of Intra-abdominal Adhesions Using the Antiangiogenic COX-2 Inhibitor Celecoxib

Objective:To determine the effects of COX-2 specific inhibitors on postoperative adhesion formation. Summary and Background Data:Intra-abdominal adhesions are the major cause of intestinal obstruction and secondary infertility after surgical procedures. Because adhesion synthesis requires angiogenesis, and cyclooxygenase-2 enzyme (COX-2) inhibitors have antiendothelial activity, we tested COX-2 inhibitors in a murine model of intra-abdominal adhesion formation. Methods:A silicone patch was secured to the lateral abdominal wall of groups of C57BL/6 mice, followed by cecal abrasion to promote adhesion formation. Beginning on the day of surgery, mice were treated with the selective COX-2 agents, celecoxib or rofecoxib, and the nonspecific COX inhibitors, aspirin, naproxen, ibuprofen, or indomethacin. Animals were treated for 10 days and killed. A second group (celecoxib, rofecoxib, aspirin) was treated for 10 days and observed for an additional 25 days. After treatment, intra-abdominal adhesions were scored using a standard method. The patch was subjected to immunohistochemistry with the endothelial-specific marker, CD31. Results:Animals treated with selective and nonselective COX-2 inhibitors, except aspirin, had significantly fewer adhesions than control animals. Celecoxib produced a maximal reduction in adhesion formation compared with rofecoxib and the nonselective COX-2 inhibitors at 10 days. After 25 days, celecoxib and rofecoxib, but not aspirin, had fewer adhesions than control mice. Adhesions from mice treated with celecoxib had reduced microvessel density compared with rofecoxib, the nonselective COX inhibitors, and control animals. Conclusions:Selective COX-2 inhibitors, in particular celecoxib, provide durable inhibition of intra-abdominal adhesions through an antiangiogenic mechanism.
EFFECT OF ULTRAVIOLET IRRADIATION ON EGGS AND LARVAE OF THE NORTHERN ANCHOVY, ENGRAULIS MORDAX, AND THE PACIFIC MACKEREL, SCOMBER JAPONlCUS, DURING THE EMBRYONIC STAGE *

Abstract— Anchovy and mackerel eggs and yolk‐sac larvae were exposed to UV radiation in the bioactive band of wavelengths between 280 and 320 nm. the UV‐B region of the spectrum. Irradiation levels were based upon predicted UV‐B increases that would result from anthropogenic diminution of Earth's protective ozone shell. Dose‐response relationships for mortality and histological and morphological effects were determined for two different spectral energy compositions, using FS‐40 sunlamps and two filter combinations. Anchovy were more sensitive than mackerel to UV‐B. Data for anchovy were analyzed in terms of DNA‐effective doses, i.e. the integrated spectral thence (in J/m2/nm) with the energy at each nm weighted by its effectiveness relative to the Setlow generalized DNA action spectrum. Fifty per cent of anchovy survived a cumulative DNA effective dose of 1150J'm‐2 over a 4‐day period. In the surviving larvae. irradiation induced lesions in the brain and eye. caused marked dispersion of pigment within melanophores and retarded growth and development. At the lowest dosage used. 760 (J. m‐2)DNA, growth was retarded and brain lesions occurred in anchovy. Calculations of Smith and Baker (in this issue) indicate that in clear ocean water a significant incidence of lesions and retardation of growth in anchovy could occur at the surface at a 25%, reduction in ozone and down to 3.5 m at a 50% reduction. Eggs and larvae of anchovy occur at these depths.
Clinical utility of postmortem microcomputed tomography of the fetal heart: diagnostic imaging vs macroscopic dissection

Congenital cardiac malformations are commonly identified at perinatal autopsy, which can be challenging in fetuses of early gestation and in macerated fetuses. Our objective was to examine fetal complex congenital heart disease by microcomputed tomography (micro‐CT), using standard autopsy as the gold standard.
Critical Parameters in the Quantitation of the Stages of Initiation, Promotion, and Progression in One Model of Hepatocarcinogenesis in the Rat∗

Critical parameters in the quantitation of altered hepatic foci (AHF) developing during multistage hepatocarcinogenesis in the rat include: 1) the enumeration of AHF induced by test agents as well as those AHF occurring spontaneously in livers of untreated animals; 2) the volume percentage or fraction of the liver occupied by all AHF as a reflection of the total number of altered cells within the liver and the degree of tumor promotion which has occurred; and 3) the phenotype of individual AHF as determined by multiple markers with serial sections. These parameters, especially the number of AHF, should be corrected by the presence of spontaneous AHF which increase with the age of the animal, more so in males than females. While accurate estimation of the background level of spontaneous AHF can be important in demonstrating that a carcinogenic agent does not possess the ability to increase the numbers of AHF above the background level, a better method to distinguish the effectiveness and relative potencies of agents as initiators or promoters is reviewed. The relative effectiveness of four different markers–γ-glutamyltranspeptidase (GGT), a placental form of glutathione S-transferase (GST), canalicular ATPase, and glucose 6-phosphatase (G6Pase)–was described for the chemicals C.I. Solvent Yellow 14 and chlorendic acid as promoting agents in males and females. C.I. Solvent Yellow 14 is a more effective promoting agent in females than males, and AHF exhibit extremely low numbers scored by GGT. On the other hand, the numbers of AHF present in livers of male rats promoted by this agent are more than twice those seen in livers of female animals, possibly owing to the effectiveness of this agent as an initiator in the male but not the female. Very few AHF, especially in the male, are scored by GGT during chlorendic acid promotion. The distribution of phenotypes with these markers also differs in the spontaneous AHF appearing in the livers of animals fed 0.05% phenobarbital on either a crude NIH-07 or AIN-76 purified diet. Such studies emphasize the extreme dependence of the promoting stage of hepatocarcinogenesis on environmental factors of sex, diet, and the molecular nature of the promoting agent itself. The hallmark of the final stage of progression in the development of hepatocellular carcinomas is aneuploidy, which may be reflected by phenotypic heterogeneity within individual AHF, termed foci-in-foci. The implications of such quantitative analyses during hepatocarcinogenesis induced by specific agents in relation to the specific action of the agent at one or more of the stages of hepatocarcinogenesis are discussed.
Prevalence of dental fluorosis & dental caries in association with high levels of drinking water fluoride content in a district of Gujarat, India

Background & objectives: Endemic fluorosis resulting from high fluoride concentration in groundwater is a major public health problem in India. This study was carried out to measure and compare the prevalence of dental fluorosis and dental caries in the population residing in high and normal level of fluoride in their drinking water in Vadodara district, Gujarat, India. Methods: A cross-sectional study was conducted in Vadodara district, six of the 261 villages with high fluoride level and five of 1490 with normal fluoride level in drinking water were selected. The data collection was made by house-to-house visits twice during the study period. Results: The dental fluorosis prevalence in high fluoride area was 59.31 per cent while in normal fluoride area it was 39.21 per cent. The prevalence of dental caries in high fluoride area was 39.53 per cent and in normal fluoride area was 48.21 per cent with CI 6.16 to 11.18. Dental fluorosis prevalence was more among males as compared to females. Highest prevalence of dental fluorosis was seen in 12-24 yr age group. Interpretation & conclusions: The risk of dental fluorosis was higher in the areas showing more fluoride content in drinking water and to a lesser degree of dental caries in the same area. High fluoride content is a risk factor for dental fluorosis and problem of dental fluorosis increased with passage of time suggesting that the fluoride content in the water has perhaps increased over time. Longitudinal studies should be conducted to confirm the findings.
Persistent endothelial abnormalities and blood–brain barrier leak in primary and secondary progressive multiple sclerosis

Epithelial and endothelial tight junctions are pathologically altered in infectious, inflammatory, neoplastic and other diseases. Previously, we described such abnormalities, associated with serum protein leak, in tight junctions of the blood–brain barrier endothelium, in lesional and normal‐appearing white matter (NAWM) in secondary progressive (SP) and acute multiple sclerosis (MS). This work is extended here to lesions and NAWM in primary progressive multiple sclerosis (PPMS) and to cortical grey matter in PPMS and SPMS. Immunocytochemistry and semiquantitative confocal microscopy for the tight junction protein zonula occludens 1 (ZO‐1) was performed on snap‐frozen sections from PPMS (n = 6) and controls (n = 5). Data on 2103 blood vessels were acquired from active lesions (n = 10), inactive lesions (n = 15), NAWM (n = 42) and controls (n = 20). Data on 1218 vessels were acquired from normal‐appearing grey matter (PPMS, 5; SPMS, 6; controls, 5). In PPMS abnormal ZO‐1 expression in active white matter lesions and NAWM, was found in 42% and 13% of blood vessels, respectively, comparable to previous data from acute and SPMS. In chronic white matter plaques, however, abnormalities were considerably more frequent (37%) in PPMS than in SPMS. Abnormality was also more frequent in normal‐appearing grey matter in SPMS (23%) than in PPMS (10%). In summary, abnormal tight junctions in both SPMS and PPMS are most frequent in active white matter lesions but persist in inactive lesions, particularly in PPMS. Abnormal tight junctions are also common in normal‐appearing grey matter in SPMS. Persistent endothelial abnormality with leak (PEAL) is therefore widespread but variably expressed in MS and may contribute to disease progression.
Hypsin, a novel thermostable ribosome-inactivating protein with antifungal and antiproliferative activities from fruiting bodies of the edible mushroom Hypsizigus marmoreus.

A novel ribosome-inactivating protein with a molecular weight of 20 kDa was isolated from fruiting bodies of the mushroom Hypsizigus marmoreus. The isolation procedure entailed ion exchange chromatography on CM-cellulose, affinity chromatography on Affi-gel Blue Gel and ion exchange chromatography on Mono Q. The protein designated hypsin demonstrated an inhibitory action against mycelial growth in various fungal species including Mycosphaerella arachidicola, Physalospora piricola, Fusarium oxysporum, and Botrytis cinerea with an IC50 of 2.7, 2.5, 14.2, and 0.06 microM, respectively. Translation in the rabbit reticulocyte lysate system was inhibited with an IC50 of 7 nM and HIV-1 reverse transcriptase activity was inhibited with an IC50 of 8 microM. Antiproliferative activity against mouse leukemia cells and human leukemia and hepatoma cells was observed. About 60% of the translation-inhibitory activity was retained after heating at 100 degrees C for 10 min. No loss of translation-inhibitory activity occurred after brief treatment with trypsin.
Cancer Therapy : Preclinical Metronomic Activity of CD 44-Targeted Hyaluronic Acid-Paclitaxel in Ovarian Carcinoma

Purpose: Most primary human ovarian tumors and peritoneal implants, as well as tumor vascular endothelial cells, express the CD44 family of cell surface proteoglycans, the natural ligand for which is hyaluronic acid. Metronomic dosing, the frequent administration of chemotherapeutics at substantially lower thanmaximum tolerated doses (MTD), has been shown to result in reducednormal tissue toxicity and to minimize "off-treatment" exposure resulting in an improved therapeutic ratio. Experimental Design:We tested the hypothesis that hyaluronic acid (HA) conjugates of paclitaxel (TXL; HA-TXL) would exert strong antitumor effects with metronomic (MET) dosing and induce antiangiogenic effects superior to those achieved with MTD administration or with free TXL. Female nude mice bearing SKOV3ip1orHeyA8ovarian cancer cellswere treated intraperitoneally (i.p.)withMETHA-TXL regimens (or MTD administration) to determine therapeutic and biologic effects. Results: All METHA-TXL–treatedmice and theMTD group revealed significantly reduced tumor weights and nodules compared with controls (all P values < 0.05) in the chemotherapy-sensitive models. However, the MTD HA-TXL–treated mice showed significant weight loss compared with control mice, whereas body weights were not affected in the metronomic groups in HeyA8-MDR model, reflecting reduced toxicity. In the taxane-resistantHeyA8-MDRmodel, significant reduction in tumorweight andnodule countswasnoted in themetronomic groups whereas the response of theMTD group did not achieve significance. While both MTD and metronomic regimens reduced proliferation (Ki-67) and increased apoptosis (TUNEL, terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling), only metronomic treatment resulted in significant reductions in angiogenesis (CD31, microvessel density). Moreover, metronomic treatment resulted in substantial increases in thrombospondin-1 (Tsp-1), an inhibitor of angiogenesis. Conclusions: This study showed that MET HA-TXL regimens have substantial antitumor activity in ovarian carcinoma, likely via apredominant antiangiogenicmechanism.ClinCancer Res; 1–8. 2012AACR.
Hyposmolarity evokes norepinephrine efflux from synaptosomes by a depolarization‐ and Ca2+‐dependent exocytotic mechanism

Osmolarity reduction (20%) elicited 3H‐norepinephrine (NE) efflux from rat cortical synaptosomes. The hyposmotic NE release resulted from the following events: (i) a Na+‐dependent and La3+‐, Gd3+‐ and ruthenium red‐sensitive depolarization; (ii) a cytosolic Ca2+ ([Ca2+]i) rise with contributions from external Ca2+ influx and internal Ca2+ release, probably through the mitochondrial Na+–Ca2+ exchanger; and (iii) activation of a [Ca2+]i‐evoked, tetanus toxin (TeTX)‐sensitive, PKC‐modulated NE efflux mechanism. This sequence was established from results showing a drop in the hyposmotic [Ca2+]i rise by preventing depolarization with La3+, and by the inhibitory effects of Ca2+‐free medium (EGTA; 50%), CGP37157 (the mitochondrial Na+–Ca2+ exchanger blocker; 48%), EGTA + CGP37157 or by EGTA‐AM (> 95% in both cases). In close correspondence with these effects, NE efflux was 92% decreased by Na+ omission, 75% by La3+, 47% by EGTA, 50% by CGP37157, 90% by EGTA + CGP37157 and 88% by EGTA‐AM. PKC influenced the intracellular Ca2+ release and, mainly through this action, modulated NE efflux. TeTX suppressed NE efflux. The K+‐stimulated NE release, studied in parallel, was unaffected by Na+ omission, or by La3+, Gd3+ or ruthenium red. It was fully dependent on external Ca2+, insensitive to CGP37157 and abolished by TeTX. These results suggest that the hyposmotic events, although different from the K+‐evoked depolarization and [Ca2+]i rise mechanisms, are able to trigger a depolarization‐dependent, Ca2+‐dependent and TeTX‐sensitive mechanism for neurotransmitter release.