Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacologic Therapy of Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is a multifaceted disorder that affects between 5% and 8% of women. As a syndrome, PCOS is comprised of reproductive, metabolic, and cardiovascular components. Hyperandrogenemia and hyperinsulinemia are central to the pathogenesis of PCOS and thus typically serve as the targets for treatment. The spectrum of therapeutic options is broad and ranges from lifestyle intervention to specific pharmacologic agents. This chapter details current pharmacologic treatments for women with PCOS using a symptom-specific approach with a special focus on the metabolic effects of each treatment. Generally, oligomenorrhea mandates regulation of menstrual cyclicity and protection of the endometrium against the development of dysplasia and carcinoma. Progestins, either alone or in combination with estrogen (in the form of an oral contraceptive) are the mainstay of treatment of oligomenorrhea. Insulin lowering therapies also improve menstrual regularity. When androgen excess is the main target for therapy, an antiandrogen and/or oral contraceptives is typically chosen. Metabolic concerns of PCOS include excess body weight and insulin resistance. Metformin and thiazolidenediones both improve hyperinsulinemia but their differential effects on body weight must be considered.
Phase-Sensitive Inversion Recovery (PSIR) Single-Shot TrueFISP for Assessment of Myocardial Infarction at 3 Tesla

Purpose:The aim of the current study was to show if contrast-to-noise ratio (CNR) could be improved without loss of diagnostic accuracy if a phase-sensitive inversion recovery (PSIR) single-shot TrueFISP sequence is used at 3.0 T instead of 1.5 T. Material and Methods:Ten patients with myocardial infarction were examined on a 1.5 T magnetic resonance (MR) system (Avanto, Siemens Medical Systems) and at a 3.0 T MR system. Imaging delayed contrast enhancement was started 10 minutes after application of contrast material. A phase-sensitive inversion recovery (PSIR) single-shot TrueFISP sequence was used at 1.5 and 3.0 T and compared with a segmented IR turboFLASH sequence at 1.5 T, which served as the reference method. Infarct volumes and CNR of infarction and normal myocardium were compared with the reference method. Results:The PSIR Single-Shot TrueFISP technique allows for imaging nine slices during a single breathhold without adaptation of the inversion time. The mean value of CNR between infarction and normal myocardium was 5.9 at 1.5 T and 12.2 at 3.0 T (magnitude images). The CNR mean value of the reference method was 8.4. The CNR mean value at 3.0 T was significantly (P = 0.03) higher than the mean value of the reference method. The correlation coefficients of the infarct volumes, determined with the PSIR single-shot TrueFISP technique at 1.5 T and at 3.0 T and compared with the reference method, were r = 0.96 (P = 0.001) and r = 0.99 (P = 0.0001). Conclusion:The use of PSIR single-shot TrueFISP at 3.0 T allows for accurate detection and assessment of myocardial infarction. CNR is significantly higher at 3.0 T compared with 1.5 T. The PSIR single-shot technique at 3.0 T provides a higher CNR than the segmented reference technique at 1.5 T.
Neuroprotective effect of activity‐dependent neurotrophic factor against toxicity from familial amyotrophic lateral sclerosis‐linked mutant SOD1 in vitro and in vivo

Amyotrophic lateral sclerosis (ALS) is the most common fatal motor neuron disease, affecting mostly middle‐aged people. There are no curative therapies for ALS. Several lines of evidence have supported the notion that the proapoptotic property of familial ALS (FALS)‐linked mutant Cu/Zn‐superoxide dismutase‐1 (SOD1) genes may play an important role in the pathogenesis of some FALS cases. Here we found that activity‐dependent neurotrophic factor (ADNF), a neurotrophic factor originally identified to have the anti‐Alzheimer's disease (AD) activity, protected against neuronal cell death caused by FALS‐linked A4T‐, G85R‐ and G93R‐SOD1 in a dose‐responsive fashion. Notably, ADNF‐mediated complete suppression of SOD1 mutant‐induced neuronal cell death occurs at concentrations as low as 100 fM. ADNF maintains the neuroprotective activity even at concentrations of more than 1 nM. This is in clear contrast to the previous finding that ADNF loses its protective activity against neurotoxicity induced by AD‐relevant insults, including some familial AD genes and amyloid β peptide at concentrations of more than 1 nM. Characterization of the neuroprotective activity of ADNF against cell death caused by SOD1 mutants revealed that CaMKIV and certain tyrosine kinases are involved in ADNF‐mediated neuroprotection. Moreover, in vivo studies showed that intracerebroventricularly administered ADNF significantly improved motor performance of G93A‐SOD1 transgenic mice, a widely used model of FALS, although survival was extended only marginally. Thus, the neuroprotective activity of ADNF provides a novel insight into the development of curative drugs for ALS. © 2004 Wiley‐Liss, Inc.
PHYLOGENY AND BIOGEOGRAPHY OF THE AMAZONA OCHROCEPHALA (AVES: PSITTACIDAE) COMPLEX

Abstract We present a phylogenetic analysis of relationships among members of the Amazona ochrocephala species complex of parrots, a broadly distributed group in Middle and South America that has been a “taxonomic headache. ” Mitochondrial DNA sequence data are used to infer phylogenetic relationships among most of the named subspecies in the complex. Sequence-based phylogenies show that Middle American subspecies included in the analysis are reciprocally monophyletic, but subspecies described for South America do not reflect patterns of genetic variation. Samples from the lower Amazon cluster with samples collected in western Amazonia—not with samples from Colombia and Venezuela, as was predicted by subspecies classification. All subspecies of the complex are more closely related to one another than to other Amazona species, and division of the complex into three species (A. ochrocephala, A. auropalliata, and A. oratrix) is not supported by our data. Divergence-date estimates suggest that these parrots arrived in Middle America after the Panama land-bridge formed, and then expanded and diversified rapidly. As in Middle America, diversification of the group in South America occurred during the Pleistocene, possibly driven by changes in distribution of forest habitat.
Role of Clara cells and type II cells in the development of pulmonary tumors in rats and mice following exposure to a tobacco-specific nitrosamine.

The role of the Clara and type II cell in the development of pulmonary tumors in the A/J mouse and Fischer rat was investigated by determining the relationship of DNA methylation and repair in pulmonary cells to oncogene activation and by characterizing the morphology of pulmonary tumors induced by treatment with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Marked differences in the formation of the promutagenic adduct O6-methylguanine (O6MG) were observed in pulmonary cells following treatment of rats with NNK. Concentrations of this adduct in Clara cells greatly exceeded (3- to 30-fold) those detected in type II cells and whole lung with doses of NNK ranging from 0.1 to 50 mg/kg. In addition, very low rates of repair of this adduct were detected in Clara cells, whereas efficient adduct removal occurred in type II cells. The importance of this adduct and the role of cell specificity was suggested by the fact that a strong correlation was observed between the concentration of O6MG in Clara cells and tumor incidence in the Fischer rat with doses of NNK ranging from 0.03-50 mg/kg. In contrast, no differences in adduct concentration between type II and Clara cells from A/J mice were observed under conditions resulting in pulmonary tumor formation. Activation of the K-ras gene was detected in lung tumors from A/J mice. This gene was activated by a mutation in codon 12 involving a GC to AT transition (GGT to GAT) and is consistent with base mispairing produced by the formation of O6MG. Activation of this gene was not associated with lung tumor formation in the Fischer rat. DNA from rat lung tumors did induce tumors in the nude mouse carcinogenicity assay. In addition, rat repetitive sequences were detected in DNA isolated from these nude mouse tumors. In spite of the cell selectivity for DNA methylation in Clara cells from rat and the relationship between O6MG formation and tumorigenicity, early proliferative lesions observed in both mice and rats involved the alveolar areas. Ultrastructural examination of these lesions and adenomas revealed morphologic features characteristic of the type II cell. Thus the lack of agreement between biochemical and morphological findings makes it difficult to hypothesize a cell of origin for the pulmonary neoplasms induced by NNK. However, these studies indicate that the concentration of O6MG in Clara cells is an excellent indicator of the carcinogenic potency of NNK in the rat. (ABSTRACT TRUNCATED AT 400 WORDS)
Apoptosis resistance in endometriosis.

INTRODUCTION In a cytological analysis of endometriotic lesions neither granulocytes nor cytotoxic T-cells appear in an appreciable number. Based on this observation we aimed to know, whether programmed cell death plays an essential role in the destruction of dystopic endometrium. Disturbances of the physiological mechanisms of apoptosis, a persistence of endometrial tissue could explain the disease. Another aspect of this consideration is the proliferation competence of the dystopic mucous membrane. METHODS Endometriotic lesions of 15 patients were examined through a combined measurement of apoptosis activity with the TUNEL technique (terminal deoxyribosyltransferase mediated dUTP Nick End Labeling) and the proliferation activity (with the help of the Ki-67-Antigens using the monoclonal antibody Ki-S5). RESULTS Twelve out of 15 women studied showed a positive apoptotic activity of 3-47% with a proliferation activity of 2-25% of epithelial cells. Therefore we concluded that the persistence of dystopic endometrium requires proliferative epithelial cells from middle to lower endometrial layers. CONCLUSION A dystopia misalignment of the epithelia of the upper layers of the functionalism can be rapidly eliminated by apoptotic procedures.
Plasma fibrinogen levels in healthy postmenopausal women: physical activity and hormone replacement status.

BACKGROUND Fibrinogen is a major component of the coagulation system and a powerful independent risk factor for cardiovascular disease in postmenopausal women. Regular physical activity has been recommended as an effective clinical approach to lowering plasma fibrinogen levels; currently, however, there are little or no data to support a relationship between habitual exercise status and plasma fibrinogen levels in healthy postmenopausal women who either use or do not use hormone replacement therapy (HRT). METHODS Plasma fibrinogen levels were measured in 20 physically active (56 +/- 1 yr) and 31 sedentary (58 +/- 1 yr) healthy postmenopausal women. Nine (45%) physically active and 15 (48%) sedentary women had been using HRT for > 1 year; the others were nonusers of HRT. RESULTS Plasma fibrinogen levels were approximately 15% lower (p = .001) in the physically active women (2.48 +/- .08 g/L) than the sedentary controls (2.92 +/- .06 g/L) and approximately 7% lower (p = .04) in the users (2.65 +/- .08 g/L) versus nonusers (2.84 +/- .08 g/L) of HRT. Moreover, the lower (0.4 g/L) plasma fibrinogen levels associated with regular physical activity were evident in both the users (2.39 +/- .11 vs 2.80 +/- .08 g/L, p = .001) and nonusers (2.56 +/- .11 vs 3.03 +/- .08 g/L, p = .006) of HRT. Stepwise multiple regression analysis revealed that percent body fat was the primary determinant of plasma fibrinogen levels, accounting for 30% of the variability. CONCLUSIONS Regular physical activity is associated with lower plasma fibrinogen levels in postmenopausal women; the lower plasma fibrinogen levels associated with regular physical activity are evident in both users and nonusers of HRT; and plasma fibrinogen levels are positively related to percent body fat in postmenopausal women differing in physical activity and HRT status. Lower plasma fibrinogen levels in physically active postmenopausal women may contribute to their lower risk of cardiovascular disease.
Lipid profiles are associated with lesion formation over 24 months in interferon-β treated patients following the first demyelinating event

Objectives To investigate the associations of serum lipid profile with disease progression in high-risk clinically isolated syndromes (CIS) after the first demyelinating event. Methods High density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) were obtained in pretreatment serum from 135 high risk patients with CIS (≥2 brain MRI lesions and ≥2 oligoclonal bands) enrolled in the Observational Study of Early Interferon β-1a Treatment in High Risk Subjects after CIS study (SET study), which prospectively evaluated the effect of intramuscular interferon β-1a treatment following the first demyelinating event. Thyroid stimulating hormone, free thyroxine, 25-hydroxy vitamin D3, active smoking status and body mass index were also obtained. Clinical and MRI assessments were obtained within 4 months of the initial demyelinating event and at 6, 12 and 24 months. Results The time to first relapse and number of relapses were not associated with any of the lipid profile variables. Higher LDL-C (p=0.006) and TC (p=0.001) levels were associated with increased cumulative number of new T2 lesions over 2 years. Higher free thyroxine levels were associated with lower cumulative number of contrast-enhancing lesions (p=0.008). Higher TC was associated as a trend with lower baseline whole brain volume (p=0.020). Higher high density lipoprotein was associated with higher deseasonalised 1,25-dihydroxy vitamin D3 (p=0.003) levels and a trend was found for deseasonalised 25-hydroxy vitamin D3 (p=0.014). Conclusions In early multiple sclerosis, lipid profile variables particularly LDL-C and TC levels are associated with inflammatory MRI activity measures.
Regional Variation in the Inversion Effect for Faces: Differential Effects for Feature Shape, Feature Configuration, and External Contour

Faces are perceived via an orientation-dependent expert mechanism. We previously showed that inversion impaired perception of the spatial relations of features more in the lower face than in the (more salient) upper face, suggests a failure to rapidly process this type of structural data from the entire face. In this study we wished to determine if this interaction between inversion and regional salience, which we consider a marker for efficient whole-face processing, was specific to second-order (coordinate) spatial relations or also affected other types of structural information in faces. We used an oddity paradigm to test the ability of seventeen subjects to discriminate changes in feature size, feature spatial relations, and external contour in both the upper and lower face. We also tested fourteen subjects on perception of two different types of spatial relations: second-order changes that create plausible alternative faces, and illegal spatial changes that transgress normal rules of facial geometry. In both experiments we examined for asymmetries between upper-face and lower-face perceptual accuracy with brief stimulus presentations. While all structural changes were less easily discerned in inverted faces, only changes to spatial relations showed a marked asymmetry between the upper and lower face, with far worse performance in the mouth region. Furthermore, this asymmetry was found only for second-order spatial relations and not illegal spatial changes. These results suggest that the orientation-dependent face mechanism has a rapid whole-face processing capacity specific to the internal second-order (coordinate) spatial relations of facial features.
Optimization of RNA 3D structure prediction using evolutionary restraints of nucleotide–nucleotide interactions from direct coupling analysis

Abstract Direct coupling analysis of nucleotide coevolution provides a novel approach to identify which nucleotides in an RNA molecule are likely in direct contact, and this information obtained from sequence only can be used to predict RNA 3D structures with much improved accuracy. Here we present an efficient method that incorporates this information into current RNA 3D structure prediction methods, specifically 3dRNA. Our method makes much more accurate RNA 3D structure prediction than the original 3dRNA as well as other existing prediction methods that used the direct coupling analysis. In particular our method demonstrates a significant improvement in predicting multi-branch junction conformations, a major bottleneck for RNA 3D structure prediction. We also show that our method can be used to optimize the predictions by other methods. These results indicate that optimization of RNA 3D structure prediction using evolutionary restraints of nucleotide–nucleotide interactions from direct coupling analysis offers an efficient way for accurate RNA tertiary structure predictions.
Morphometric and Psychometric Comparisons between Non-Substance-Abusing Patients with Posttraumatic Stress Disorder and Normal Controls

Background: Hippocampal decrease in size in response to posttraumatic stress disorder (PTSD) is still a subject of controversy. The aims of this study were to: (1) confirm previous hippocampus findings in PTSD patients compared to controls, using ethnically similar study groups where alcohol and drug abuse were non-existent; (2) test influence of disease duration as well as depression scores on possible morphological changes; (3) test whether the voxel-based morphometry (VBM) data confirm the group differences seen in the region of interest (ROI) analysis, and (4) test the associations between the cognitive test scores and the morphological changes. Methods: VBM and ROI-based analysis were applied in 23 patients and 17 healthy controls. Culture-neutral cognitive tests were used. Results: The ROI-based method showed significantly decreased gray matter volumes for global hippocampal volume, as in a separate analysis of left and right sides in the PTSD group. Total volume of the hippocampus was significantly decreased on the left side, as in the global assessment. A multiple regression VBM model showed significant voxel clusters for group affiliation in the right hippocampus, modelling lowering of gray matter associated with the PTSD group. Disease duration was shown to be negatively correlated to bilateral hippocampal volume and high depression score to bilateral gray matter parahippocampal volume. No significant correlations were found between hippocampal or parahippocampal volumes and cognitive functions. Conclusion: The present and previous studies showed that morphologic differences do not appear to be due to drug or alcohol abuse. The VBM data partially confirm the group differences seen in the ROI-based method in the medial temporal lobe. The fact that the significantly lower score on the short-term memory test in the PTSD group is not correlated to hippocampal volume may suggest a more general basis for such memory impairment.
Blended Learning: How Teachers Balance the Blend of Online and Classroom Components

Despite teacher resistance to the use of technology in education, blended learning has increased rapidly, driven by evidence of its advantages over either online or classroom teaching alone. However, blended learning courses still fail to maximize the benefits this format offers. Much research has been conducted on various aspects of this problem, but only one other study has examined teaching practice in a blended course. Teachers using blended learning were interviewed about their use of online and classroom components and the reasons for their decisions. The online and classroom aspects of their course were analysed against a pedagogical framework of engagement strategies. Classroom components were found to be more highly valued by teachers than those online, an attitude largely driven by their perceptions that specific learning functions were best suited to particular formats. The courses themselves reflect these values. Most teachers used well-developed engagement strategies in their classroom teaching, compared to a minimal use of strategies online. Further, with one exception there was a lack of integration between online and classroom components. Blended learning will not fulfill its promise of better learning unless teachers can be encouraged to re-think and redesign courses that afford students more, and different learning experiences than those offered by either online or classroom alone. This paper adds to a small literature base examining what teachers actually do in blended learning, and signals steps that teachers and their institutions might take to build on the opportunities presented by blended learning.
The relationship between coronary calcification and the metabolic markers of osteopontin, fetuin-A, and visfatin.

OBJECTIVES We investigated whether coronary calcification detected by multislice computed tomography (MSCT) was correlated with plasma osteopontin, serum fetuin-A, and visfatin levels. STUDY DESIGN The study included 64 consecutive patients (51 males, 13 females; mean age 49.5+/-10.9 years; range 33 to 78 years) who underwent MSCT for suspected coronary artery disease. Coronary artery calcification (CAC) scores of the patients were calculated using the Agatston scoring method. Plasma osteopontin, serum fetuin-A, and visfatin levels were measured from fasting blood samples and correlations were sought with calcium scores. RESULTS Coronary calcification was detected in 32 patients (50%). The mean CAC score was 146.5+/-333.7 Agatston units (AU), indicating an intermediate risk for coronary artery disease. In 10 patients (15.6%), the CAC score exceeded 400 AU. The mean fetuin-A, visfatin, and osteopontin levels were 25.6+/-6.4 ng/ml, 19.7+/-47.2 ng/ml, and 20.4+/-16.1 ng/ml, respectively. Serum visfatin (r=0.15, p=0.37) and fetuin-A (r=0.17, p=0.22) were not correlated with the CAC score, whereas plasma osteopontin level showed a moderate correlation with the CAC score (r=0.35; p=0.008). In ROC analysis, the area under the curve for identification of CAC was greatest for osteopontin (0.741; p=0.004), followed by fetuin-A (0.574; p=0.31), and visfatin (0.580; p=0.27). The cut-off value was 18.45 ng/ml for osteopontin, with a sensitivity of 72% and specificity of 73%. CONCLUSION Our results suggest that there might be an association between CAC and plasma osteopontin levels. Research should continue to find out a metabolic parameter that will strongly indicate coronary calcification.
Formation and control of emerging C‐ and N‐DBPs in drinking water

A survey of 16 US drinking water treatment plants was conducted regarding the occurrence, formation, and control of emerging disinfection by‐products (DBPs), with a focus on drinking waters that were impacted by treated wastewater and/or algae. The formation and control trends of certain emerging carbonaceous (haloacetaldehyde) and nitrogenous (haloacetonitrile, halonitromethane, cyanogen halide, nitrosamine) DBPs were different from those of the regulated trihalomethanes (THMs). This was due to differences in the sources of precursors (e.g., humic substances versus proteinaceous materials) plus differences in the effect of disinfection processes on these DBPs. For example, ozone increased the formation potential (FP) of chloropicrin (median = 226%), whereas biofiltration typically decreased the FP of the ozonated water (median = 48%), which—together with coagulation or softening—resulted (in general) in a net decrease (median = 33%) in FP through the ozone plants. Alternatively, coagulation with the polymer polyDADMAC (a source of N‐nitrosodimethylamine [NDMA] precursor) increased the FP of NDMA (43‐82%), whereas ozonation often destroyed NDMAFP (median to maximum = 10‐87%). This article discusses how utilities can minimize and balance the formation of THMs and haloacetic acids with that of certain emerging DBPs.