Miracle-dz/UniFAR-FTUs huggingface dataset:
Hepatitis C Virus (HCV) Genotypes in the Caribbean Island of Martinique: Evidence for a Large Radiation of HCV-2 and for a Recent Introduction from Europe of HCV-4

ABSTRACT Molecular epidemiological studies of hepatitis C virus (HCV) in the Caribbean may help to specify the origin and spread of HCV infection. Indeed, the Caribbean population is intermixed from European and African origins and geographically close to the American continent. We characterized HCV genotypes in the Caribbean island of Martinique. HCV genotypes were analyzed by sequencing or reverse hybridization in the 5′ noncoding region (5′NC) in 250 HCV-monoinfected and 85 HCV-human immunodeficiency virus (HIV)-coinfected patients. In addition, sequencing in the nonstructural 5B (NS5B) gene was required to determine the subtype or to perform phylogenetic analysis in selected samples. Genotypes 1 to 6 were found, respectively, in 84.4, 6.8, 5.2, 2.8, 0.4, and 0.4% of 250 HCV-monoinfected patients and in 71.7, 7.1, 15.3, 5.9, 0, and 0% of 85 HCV-HIV-coinfected patients. HCV-1b was found in 66.4% of the HCV-monoinfected patients and was associated with blood transfusion, whereas HCV-1a was detected in 41.2% of the HCV-HIV-coinfected patients and was associated with intravenous drug use (IVDU). The HCV-3 strains belonged to subtype 3a and were linked to IVDU. Phylogenetic analyses were focused on HCV-2 and HCV-4, which are common in Africa. Two opposite patterns were evidenced. NS5B sequences from 19 HCV-2 isolates were affiliated with many different subtypes described either in Europe or in West Africa, suggesting an ancient radiation. In contrast, seven of the nine HCV-4 NS5B sequences ranged within HCV-4a and HCV-4d clusters spreading in continental France by the IVDU route. Epidemiological data demonstrate the recent introduction of HCV-4a and -4d subtypes into the Caribbean.
Lecithin/sphingomyelin Ratio versus Rapid Surfactant Test in Normal and Diabetic Pregnancies

Lecithin/sphingomyelin (L/S) ratio was measured and rapid surfactant test (RST) was performed on amniotic fluid samples drawn from 60 normal and 18 diabetic pregnancies, for determination of fetal lung maturity. The results were compared to the neonatal outcome. Comparison of L/S ratio and RST demonstrates a good correlation (95%) between the two tests in normal pregnancies. In diabetic pregnancies, however, correlation is notably lower (54%). Respiratory distress syndrome (RDS) was predicted in both L/S ratio and RST in 35–40% of normal pregnancies, with 60–65% of false negative results. In diabetic pregnancies the L/S ratio was as reliable as in normal pregnancies, but the RST was less reliable, with an RDS prediction rate of 18 %. The assumption is made that increased amniotic fluid volume in diabetic pregnancies, results in dilution of the surfactant giving more false negative results in RST than are seen with L/S ratio, as in the latter, by measuring the ratio between the two constituents of amniotic fluid, the dilution factor is abolished. In diabetic pregnancies, a positive RST is reliable, but with negative results, L/S ratio must be determined for correct assessment of fetal lung maturity.
Assessment of the influence of dietary vitamin E on sows and offspring in three parities: reproductive performance, tissue tocopherol, and effects on progeny.

Sixty crossbred (Yorkshire-Hampshire X Duroc) gilts were fed one of four corn-soybean meal diets fortified with . 3 ppm Se and 0, 16, 33, or 66 IU of DL-alpha-tocopheryl acetate/kg. The study was conducted over a three-parity period to evaluate sow reproductive performance and the vitamin E tissue status of both sows and progeny at various time periods postcoitum and(or) postpartum. The basal diet averaged 8.4 mg of alpha-tocopherol/kg and . 38 ppm of Se. Although litter size at birth was lowest (P less than .15) when sows were fed the basal diet, a higher incidence of agalactia when sows were fed the lower dietary vitamin E levels resulted in an increased (P less than .05) litter size at 7 d postpartum as dietary vitamin E increased. Sow serum alpha-tocopherol increased (P less than .01) at each measurement period as dietary vitamin E level increased. Colostrum and milk alpha-tocopherol concentrations increased (P less than .01) as dietary vitamin E level increased, and colostrum values were three to five times higher than at later milks. Colostrum alpha-tocopherol declined by parity from sows fed less than or equal to 16 IU/kg but was similar at each parity for sows fed greater than or equal to 33 IU/kg, resulting in a dietary vitamin E x parity interaction (P less than .01). The Se content of sow milk declined with parity but was not affected by dietary vitamin E level. Sow liver tocopherol at weaning (28 d postpartum) increased (P less than .01) as dietary vitamin E increased and increased with parity (P less than .05). Pig serum and liver alpha-tocopherol concentrations were elevated at birth and 7 and 28 d of age as sow dietary level of vitamin E increased. Upon weaning, pigs were fed a torula yeast-dextrose diet that contained 3.0 mg of alpha-tocopherol/kg and . 32 ppm Se for a 28-d postweaning period. Liver and serum alpha-tocopherol concentrations declined during the postweaning period. Evidence of the vitamin E deficiency occurred at 28 d postweaning in the progeny from sows fed the basal diet or 16 IU of vitamin E; the incidence was more prevalent in the pigs from Parities II and III. These results suggest that a supplemental level of 16 IU of vitamin E/kg of diet was inadequate for the reproducing sow; higher levels are justified, particularly when females are retained in the herd for several parities.
Protective effect of melatonin against homocysteine-induced vasoconstriction of human umbilical artery.

Hyperhomocysteinemia is a major and independent risk factor for vascular disease. Oxidative stress is a possible mechanism for homocysteine (Hcy)-induced endothelial dysfunction. Herein, we evaluated the antioxidant property of melatonin (MLT) in relation to the vasoconstrictive effect of Hcy on the human umbilical artery. In an initial experiment in a cell-free system, a micromolar concentration of iron was found to catalyze oxygen-dependent oxidation of Hcy. MLT (10 or 100 microM) did not affect oxygen-dependent oxidation of Hcy. Next, smooth muscle contraction induced by prostaglandin F(2alpha) (10 microM) was measured in arterial strips. Hcy (10 to 500 microM) increased this vascular tension in a concentration-dependent manner (P < 0.0001). Addition of Fe(2+) (10 microM) significantly potentiated the Hcy effect. Removal of endothelium (P < 0.05), pretreatment with a nitric oxide (NO) synthesis inhibitor (l-N(G)-monomethylarginine, 200 microM, P < 0.001), or pretreatment with a hydroxyl radical ((*)OH) scavenger (mannitol, 10 mM, P < 0.001) significantly attenuated contraction potentiated by Hcy plus Fe(2+). At a much lower concentration than mannitol, MLT (1 to 100 microM) significantly reduced the contractile effect of Hcy and Fe(2+) in a concentration-dependent manner. Hcy plus Fe(2+) significantly impaired calcium ionophore A 23187-induced relaxation (P < 0.0001), while MLT restored this relaxation in a concentration-dependent manner. These findings suggest that Hcy potentiates vascular tension in human umbilical artery, possibly by suppressing bioavailable NO. MLT protects against the vasoconstrictive effect of Hcy, most likely by scavenging (*)OH arising from Hcy autooxidation.
Donor‐Derived Infection: Old Problem, New Solutions?

Reports of the transmission of infection to organ transplantation recipients remain uncommon but occur with sufficient frequency to suggest that current approaches to screening of donors are inadequate. Recent transmissions of unusual viral infections have illustrated the vulnerability of immunosuppressed recipients to infections due to organisms of modest virulence for normal individuals. This theme was sustained in a recent report by Palacios et al. from Australia of the transmission of a novel arenavirus related to lymphocytic choriomeningitis virus (LCMV) to three organ recipients from a common donor (1). The donor was a 57-year-old male who died from cerebral hemorrhage 10 days after returning from a trip to rural Yugoslavia. Liver and kidneys were transplanted into three recipients respectively. All three recipients developed a febrile illness accompanied by encephalopathy and varying degrees of organ involvement. Extensive microbiological work-up for suspected pathogens was negative and all three recipients died. Previous reports of two similar clusters, in which seven out of eight recipients died from LCMV, were notable for the lack of symptoms in the deceased donor (who died of acute CNS hemorrhage) and the inability to detect LCMV in tissues from the organ donor even using specific primers derived from the recipients’ viral strain (2). Other recent clusters have been due to rabies, West Nile virus (WNV) and HIV.
Sleeping Problems and Suicide in 75,000 Norwegian Adults: A 20 Year Follow-up of the HUNT i Study

Objectives: To investigate the association of sleeping problems with suicide risk. Design: Prospective cohort study linking health survey information on sleep problems to Norway’s national mortality registry. Participants were followed up from 1984-6 until december 31, 2004. Setting: Residents of Nord-Trøndelag Norway, aged 20 years or older in 1984-6. Participants: Altogether 87,285 people were eligible for the survey and 74,977 (86%) took part in one or more aspects of the study. Interventions: Measurements and Results: Three percent of participants experienced sleeping problems every night, 5% experienced problems “often” and 31% reported problems “sometimes. ” There were 188 suicides during follow-up. Sleeping problems at baseline were strongly associated with subsequent suicide risk. Compared to participants who reported no sleeping problems the age- and sex- adjusted hazard ratios for suicide were 1.9 (Ci 1.3-2.6), 2.7 (Ci 1.4-5.0), and 4.3 (Ci 2.3-8.3) for reporting sleeping problems sometimes, often, or almost every night, respectively. Associations were stronger in younger (< 50 years) participants, but we found no statistical evidence for gender differences. Adjusting for measures of common mental disorder and alcohol use at baseline weakened the associations, but the 3% of subjects with the worst sleep patterns remained at two fold increased risk of suicide. Conclusions: Sleeping problems are a marker of suicide risk, mainly due to the presence of both sleeping problems and mixed anxiety and depression. Physicians should be aware of the possible vulnerability for people affected by sleeping problems.
MLP/BP-based soft DFEs with bit-interleaved TCM for distorted 16-QAM signal recovery in severe ISI channels

In this work, we base on multi-layered perceptron neural networks with backpropagation algorithm (MLP/BP) to construct soft decision feedback equalizers (DFEs). The proposal is used to recover distorted 16-point quadrature amplitude modulation (16-QAM) signal. For better performance, error control codes (ECC) are applied to enhance the accuracy of the transmitted data. From the simulations, we note that the MLP/BP-based soft DFEs with bit-interleaved TCM can recover severe distorted 16-QAM data as well as suppress intersymbol interference (ISI) and background additive white Gaussian noise (AWGN). As compared with the LMS DFE, the proposed scheme can provide better bit-error-rate (BER) and packet-error-rate (PER) performance.
Staging of Colon Carcinoma Using Water Enema CT

Objective To determine the accuracy of water enema CT (WECT) for staging colon carcinoma. Materials and Methods Thirty patients with colon cancer, diagnosed by barium enema and/or colonoscopy, underwent preoperative WECT. Dynamic contrast enhanced CT studies were performed after rectal administration of 2 L lukewarm tap water. Images were prospectively analyzed for depth of tumor invasion, nodal involvement, and distant metastases by investigators blinded to the results of barium enema and colonoscopy. Surgical/pathologic proof was obtained in all cases Results Using WECT, 23 of 30 patients were correctly staged. Correct staging occurred in 2 of 2 patients with Stage A, 3 of 3 patients with Stage B1, 6 of 9 patients with Stage B2, 1 of 2 patients with Stage C1, 5 of 8 patients with Stage C2, and 6 of 6 patients with Stage D tumors. Of the patients incorrectly staged, 4 were understaged and 3 were overstaged; all were due to errors in predicting lymph node involvement. Sensitivity and specificity for evaluating nodal involvement were 60 and 79%. respectively. Conclusions Water enema CT allows for accurate depiction and staging of colon carcinoma. Aqueous distention of the colon avoids artifacts seen with positive contrast agents yet allows accurate evaluation of the bowel wall and pericolonic structures.
Melanocytes in Clear Cell Acanthoma

The presence of melanocytes in 11 clear cell acanthoma cases was investigated by silver impregnation. Melanocytes were always present, their density showing great variability from case to case and within each individual neoplasm. The possible existence of a pigmented counterpart to clear cell acanthoma is discussed.
A prospective study to optimize insulin treatment by switching to insulin glargine in type 2 diabetic patients previously uncontrolled on premixed insulin: the optimization study

Abstract Objective: To evaluate the efficacy, safety and treatment satisfaction of insulin glargine plus oral antidiabetic drugs (OADs) in Chinese individuals with Type 2 diabetes inadequately controlled with premixed insulin plus OADs. Methods: In this open-label, single-arm, 16-week, phase IV study, 313 subjects with Type 2 diabetes inadequately controlled with premixed insulin plus OADs were switched to insulin glargine plus OADs. Changes in glycaemic control, incidence of hypoglycaemia and treatment satisfaction using the Diabetes Treatment Satisfaction Questionnaire (DTSQ) were evaluated. Results: Switching to insulin glargine was associated with significant reductions in levels of glycosylated haemoglobin (HbA1c; 8.4 ± 0.6 to 7.9 ± 1.0%; p < 0.001) and fasting plasma glucose (FPG; 9.50 ± 2.10 to 6.58 ± 2.07 mmol/L; p < 0.001). A total of 32.9% of subjects experienced hypoglycaemia, including two cases of severe hypoglycaemia. Treatment satisfaction was improved with insulin glargine (DTSQ 8-item scores, all p < 0.001). Logistic regression analysis showed a significant association between baseline HbA1c, disease duration, endpoint FPG and HbA1c < 7%. Conclusion: This single-arm study suggested that switching to insulin glargine plus OADs significantly improved glycaemic control, with a low incidence of hypoglycaemia, in patients with Type 2 diabetes uncontrolled on premixed insulin plus OADs. Switching to insulin glargine was also associated with better patient treatment satisfaction compared with previous treatment. The main limitations to this study are the open-label design and the lack of a control arm.
Peroxisome Proliferator-activated Receptor α Negatively Regulates the Vascular Inflammatory Gene Response by Negative Cross-talk with Transcription Factors NF-κB and AP-1*

Interleukin-6 (IL-6) is a pleiotropic cytokine, whose plasma levels are elevated in inflammatory diseases such as atherosclerosis. We have previously reported that peroxisome proliferator-activated receptor α (PPARα) ligands (fibrates) lower elevated plasma concentrations of IL-6 in patients with atherosclerosis and inhibit IL-1-stimulated IL-6 secretion by human aortic smooth muscle cells (SMC). Here, we show that aortic explants isolated from PPARα-null mice display an exacerbated response to inflammatory stimuli, such as lipopolysaccharide (LPS), as demonstrated by increased IL-6 secretion. Furthermore, fibrate treatment represses IL-6 mRNA levels in LPS-stimulated aortas of PPARα wild-type, but not of PPARα-null mice, demonstrating a role for PPARα in this fibrate action. In human aortic SMC, fibrates inhibit IL-1-induced IL-6 gene expression. Furthermore, activation of PPARα represses both c-Jun- and p65-induced transcription of the human IL-6 promoter. Transcriptional interference between PPARα and both c-Jun and p65 occurs reciprocally, since c-Jun and p65 also inhibit PPARα-mediated activation of a PPAR response element-driven promoter. This transcriptional interference occurs independent of the promoter context as demonstrated by cotransfection experiments using PPARα, p65, and c-Jun Gal4 chimeras. Overexpression of the transcriptional coactivator cAMP-responsive element-binding protein-binding protein (CBP) does not relieve PPARα-mediated transcriptional repression of p65 and c-Jun. Finally, glutathione S-transferase pull-down experiments demonstrate that PPARα physically interacts with c-Jun, p65, and CBP. Altogether these data indicate that fibrates inhibit the vascular inflammatory response via PPARα by interfering with the NF-κB and AP-1 transactivation capacity involving direct protein-protein interaction with p65 and c-Jun.
Phosphorylation and Activation of Heart 6-Phosphofructo-2-kinase by Protein Kinase B and Other Protein Kinases of the Insulin Signaling Cascades*

To understand the insulin-induced activation of 6-phosphofructo-2-kinase (PFK-2) of the bifunctional enzyme PFK-2/fructose-2,6-bisphosphatase in heart, the effect of phosphorylation by protein kinases of the insulin signaling pathways on PFK-2 activity was studied. Purified PFK-2/fructose-2,6-bisphosphatase from bovine heart is a mixture of two isoforms (M r 58,000 and 54,000 on SDS-polyacrylamide gels). The M r 54,000 protein is an alternatively spliced form, lacking phosphorylation sites for protein kinases. Recombinant enzymes corresponding to theM r 58,000 (BH1) and M r54,000 (BH3) forms were expressed and used as substrates for phosphorylation. The recombinant BH1 isoform was phosphorylated by p70 ribosomal S6 kinase (p70s6k), mitogen-activated protein kinase-activated protein kinase-1, and protein kinase B (PKB), whereas the recombinant BH3 isoform was a poor substrate for these protein kinases. Treatment with all protein kinases activated PFK-2 in the recombinant BH1 preparation. Phosphorylation of the recombinant BH1 isoform correlated with PFK-2 activation and was reversed by treatment with protein phosphatase 2A. All the protein kinases phosphorylated Ser-466 and Ser-483 in the BH1 isoform, but to different extents: p70s6k preferentially phosphorylated Ser-466, whereas mitogen-activated protein kinase-activated protein kinase-1 and PKB phosphorylated Ser-466 and Ser-483 to a similar extent. We propose that PKB is part of the insulin signaling cascade for PFK-2 activation in heart.
Soluble tumor necrosis factor receptors correlate with parasitemia and disease severity in human malaria.

Elevated serum or plasma concentration of immunoreactive tumor necrosis factor (TNF) is consistently detected in patients with malaria. TNF levels correlate with high parasitemia and clinical severity but not always with outcome. Since the effects of TNF may be neutralized by soluble TNF receptors, sera of 30 nonimmune patients with malaria were analyzed before and during antimalarial therapy. High concentrations of receptors R1 (55 kDa) and R2 (75 kDa) were detected immunologically in all sera of untreated patients. Levels of immunoreactive TNF correlated closely with levels of soluble TNF R1 and R2 (r = .75 and .59, respectively). In contrast, sera lacked cytotoxic activity against target cells in the TNF bioassays. Soluble TNF receptor levels remained elevated for days after treatment. These results suggest that excessive release of TNF induced by the asexual stage of malaria parasites is controlled by a subsequent shedding of soluble TNF receptors that may bind and deactivate biologically functional TNF.
Characterization and chromosome location of the gene GSTZ1 encoding the human Zeta class glutathione transferase and maleylacetoacetate isomerase

The Zeta class of cytosolic glutathione-S-transferases (GSTs) has recently been identified and spans a range of species from plants to humans. The cDNA and protein of a human member of this class have been previously characterised in our laboratory. This cDNA has also been described as maleylacetoacetate isomerase (MAAI), an enzyme of the phenylalanine catabolism pathway (Fernandez-Canon and Penalva, 1998). The present study has determined the structure and chromosome location of the gene encoding human GSTZ1/MAAI. The gene spans approximately 10.9 kb and is composed of 9 exons. Three intron positions of GSTZ1 were precisely conserved compared to the carnation and Caenorhabditis elegans Zeta GST genes. Fluorescent in situ hybridization mapped the gene to a single locus on chromosome 14q24.3, which is in agreement with an independent localization between the Genethon markers D14S263 and D14S67. The coding region of the gene differed from the GSTZ1 cDNA at two nucleotide positions in exon 3, resulting in Lys-32→Glu and Arg-42→ Gly substitutions. This gene structure information will allow analysis of the polymorphism in genomic DNA samples, and enables further investigations into genetic defects in this step of the phenylalanine catabolism pathway.
Role of mRNA Stability during Genome-wide Adaptation of Lactococcus lactis to Carbon Starvation*

The stability of mRNA was investigated for the first time at the genomic scale during carbon starvation adaptation of Lactococcus lactis IL1403. In exponential phase, mRNA half-lives were correlated positively to open reading frame length. A polypurine sequence, AGGAG, was identified as a putative 5′-stabilizer and inverted repeated sequences as a 3′-destabilizer. These original findings suggested that multiple pathways of mRNA degradation should coexist: internal cleavage, endonuclease cleavage initiated at the 5′-end, and exonuclease attack at the 3′-end. During carbon starvation adaptation, mRNA stability globally increased, but specific mechanisms allowing a wide range of stabilization factors between genes and differential kinetic evolution were involved. A formal method allowing the quantification of the relative influences of transcription and degradation on the mRNA pool control was developed and applied in L. lactis. Gene expression was mostly controlled by altered transcription prior to carbon source exhaustion, while the influence of mRNA stability increased during the starvation phase. This study highlighted that stability modulation in response to adverse growth conditions can govern gene regulation to the same extent as transcription in bacteria.
Distribution, levels, and activation of MEK1 in Alzheimer's disease

Extracellular‐signal‐regulated kinase (ERK) has been implicated in the pathogenesis of Alzheimer's disease (AD), but the upstream cascade leading to ERK activation has not been elucidated. In this study, we focused on one of the physiological activators of ERK, mitogen‐activated protein kinase (MAPK)/ERK kinase 1 (MEK1). Although there was no significant difference in the level and distribution of total MEK1 between AD and age‐matched control cases, increased levels of activated phospho‐MEK1 were specifically localized to neuronal intracytoplasmic granular structures in severe AD (Braak stage V–VI). The considerable overlap between MEK1 and its downstream effector, phospho‐ERK, suggests both a functional and mechanistic link. Nuclear localization of phospho‐MEK1 was a prominent feature in both mild AD cases (Braak stage III–IV) and control cases with limited pathology (Braak stage I–II). Since MEK1 is normally cytoplasmic due to the active export from nucleus because of the presence of nuclear export signal in its amino‐terminus, we suspect that the apparent nuclear accumulation of phospho‐MEK1 in AD patients at early stages suggests that abnormal nuclear trafficking may contribute to the pathogenesis of AD. By immunoblot analyses, phospho‐MEK1 was significantly increased in AD over control cases. Together, these findings lend further credence to the notion that the ERK pathway is dysregulated in AD and also indicate an active role for this pathway in disease pathogenesis.