Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutant Presenilin 2 Transgenic Mouse: Effect on an Age‐Dependent Increase of Amyloid β‐Protein 42 in the Brain

Abstract: The N141I missense mutation in presenilin (PS) 2 is tightly linked with a form of autosomal dominant familial Alzheimer's disease (AD) in the Volga German families. We have generated transgenic mouse lines overexpressing human wild‐type or mutant PS2 under transcriptional control of the chicken β‐actin promoter. In the brains of transgenic mice, the levels of human PS2 mRNA were found to be five‐ to 15‐fold higher than that of endogenous mouse PS2 mRNA. The amyloid β‐protein (Aβ) 42 levels in the brains of mutant PS2 transgenic mice were higher than those in wild‐type PS2 transgenic mice at the age of 2, 5, or 8 months. In addition, the Aβ42 levels appeared to increase steadily in the mutant PS2 transgenic mouse brains from 2 to 8 months of age, whereas there was only a small increase in wild‐type transgenic mice between the ages of 5 and 8 months. There was no definite difference in the levels of N‐terminal and C‐terminal fragments between wild‐type and mutant PS2 transgenic mice at the age of 2, 5, or 8 months. These data show a definite effect of the PS2 mutation on an age‐dependent increase of Aβ42 content in the brain.
Efficacy of Hypertonic Saline and Normal Saline in the Treatment of Chronic Sinusitis

Introduction: Chronic sinusitis affects all age groups and is a cause for significant morbidity. Recent realization that noninfectious inflammatory causes can predispose to infectious sinusitis has evoked renewed interest in developing and documenting efficacious ancillary therapies that could supplement antibiotic use. Hypertonic saline solution has been shown to increase mucociliary clearance and ciliary beat frequency. Objectives: A double blinded randomized comparative study was undertaken to evaluate the effect of hypertonic saline (3.5%) nasal drops and normal saline (0.9%) nasal drops, to assess the tolerance of hypertonic saline nasal drops and to know if hypertonic nasal drops improve the “quality of life” in patients with chronic sinusitis. Methods: Fifty patients diagnosed as chronic sinusitis in the age group of 18-45 years were randomized into two groups; Group A was treated with normal saline and Group B with 3.5% hypertonic saline for a period of 4 weeks. Pre and Post treatment x-rays of the paranasal sinuses (Water’s view) were graded and radiological scores were given accordingly. The symptoms were evaluated before and after treatment using visual analogue score. Patients were queried about tolerance to the nasal solution and scores were given. Conclusion: Hypertonic saline nasal solution is more efficacious than normal saline solution in the treatment of patients with chronic sinusitis. Hypertonic saline nasal solution was well tolerated and it improved quality of life in these patients.
Nonsteroidal Anti-Inflammatory Drugs and Cardiovascular Outcomes in Women: Results From the Women’s Health Initiative

Background—Conclusive data about cardiovascular toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs) are sparse. We hypothesized that regular NSAID use is associated with increased risk for cardiovascular events in postmenopausal women, and that this association is stronger with greater cyclooxygenase (cox)-2 when compared with cox-1 inhibition. Methods and Results—Postmenopausal women enrolled in the Women’s Health Initiative were classified as regular users or nonusers of nonaspirin NSAIDs. Cox regression examined NSAID use as a time-varying covariate and its association with the primary outcome of total cardiovascular disease defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Secondary analyses considered the association of selective cox-2 inhibitors (eg, celecoxib), nonselective agents with cox-2>cox-1 inhibition (eg, naproxen), and nonselective agents with cox-1>cox-2 inhibition (eg, ibuprofen) with the primary outcome. Overall, 160 801 participants were available for analysis (mean follow-up, 11.2 years). Regular NSAID use at some point in time was reported by 53 142 participants. Regular NSAID use was associated with an increased hazard for cardiovascular events versus no NSAID use (hazard ratio [HR], 1.10; 95% confidence interval, 1.06–1.15; P<0.001). Selective cox-2 inhibitors were associated with a modest increased hazard for cardiovascular events (hazard ratio, 1.13; 1.04–1.23; P=0.004 and celecoxib only: HR, 1.13; 1.01–1.27; P=0.031). Among aspirin users, concomitant selective cox-2 inhibitor use was no longer associated with increased hazard for cardiovascular events. There was an increased risk for agents with cox-2>cox-1 inhibition (HR, 1.17; 1.10–1.24; P<0.001 and naproxen only: HR, 1.22; 1.12–1.34; P<0.001). This harmful association remained among concomitant aspirin users. We did not observe a risk elevation for agents with cox-1>cox-2 inhibition (HR, 1.01; 0.95–1.07; P=0.884 and ibuprofen only: HR, 1.00; 0.93–1.07; P=0.996). Conclusions—Regular use of selective cox-2 inhibitors and nonselective NSAIDs with cox-2>cox-1 inhibition showed a modestly increased hazard for cardiovascular events. Nonselective agents with cox-1>cox-2 inhibition were not associated with increased cardiovascular risk. Clinical Trial Registration—URL: www.clinicaltrials. gov. Unique identifier: NCT00000611.
Relation of smoking to breast cancer by estrogen receptor status

It has been suggested that smoking is associated with estrogen‐negative breast cancer but not with estrogen‐positive breast cancer. A population‐based case‐control study was conducted in Geneva, Switzerland, to determine the relation of passive and active smoking to breast cancer when the referent unexposed category consisted of women unexposed to active and passive smoke. The 242 patients with breast cancer (cases), in whom estrogen receptor (ER) status was determined on biopsy material, were compared with 1,059 women free of breast cancer (controls). Lifetime history of active and passive smoking was recorded year by year, between age 10 and the date of interview. Prevalence rates of ER+ tumors were 74.7% in pre‐menopausal women and 74.2% in post‐menopausal women. Post‐menopausal active smokers had a lower prevalence of ER+ tumors (70.0%, p = ns). Among pre‐menopausal women, the age‐adjusted ORs of breast cancer with having smoked an average of ≥20 cigarettes per day (cpd) during lifetime were 2.7 for ER− tumors and 2.6 for ER+ tumors. Among post‐menopausal women, corresponding ORs were 5.7 for ER− tumors and 2.4 for ER+ tumors. Smoking was related to both ER− and ER+ breast cancer in pre‐ and post‐menopausal women, but the strength of the association appeared to be greater for ER− tumors among post‐menopausal women. Int. J. Cancer 75:339–342, 1998. © 1998 Wiley‐Liss, Inc.
Inhaled Epoprostenol for the Treatment of Pulmonary Arterial Hypertension in Critically Ill Adults

Pulmonary arterial hypertension (PAH) is a progressive disease without a cure. The primary treatment goal for patients with this disease is improving pulmonary blood flow through vasodilation of the pulmonary arteries. Several drugs are available that ameliorate walk distance and hemodynamics, but their maximum tolerated doses are limited in critically ill patients with PAH because of systemic vasodilation resulting in hypotension. The ideal vasodilator would be cost‐effective, safe, and selective to the pulmonary vasculature; no such agent currently exists. Inhaled nitric oxide selectively reduces pulmonary pressures without systemic hypotension. However, it is expensive, potentially toxic, and requires complex technology for monitoring and administration. Inhaled epoprostenol may be an alternative therapy to minimize systemic hypotension, which often accompanies rapid intravenous titration. To evaluate the safety and efficacy of inhaled epoprostenol in critically ill patients with PAH, we conducted a literature search by using the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases (1966‐August 2009) for relevant studies. Case reports and in vitro studies were excluded. Overall, 11 studies met the inclusion criteria. The PAH population included patients requiring cardiac surgery, lung or heart transplantation, or nonspecific intensive care. All trials showed that inhaled epoprostenol significantly decreased pulmonary pressures without lowering systemic blood pressure. The duration of therapy in most studies was 10–15 minutes, with one study evaluating its effects up to an average of 45.6 hours. Pulmonary pressures returned to baseline soon after drug discontinuation. Minimal adverse events were reported. Thus, inhaled epoprostenol in various subgroups of critically ill patients was effective in reducing pulmonary pressures. However, the significance of these effects on improving clinical outcomes remains unknown. Further studies are needed to determine the role of inhaled epoprostenol in critically ill patients with PAH.
A review article on phytochemistry and pharmacological profiles of Nardostachys jatamansi DC-medicinal herb

Nardostachys jatamansi [Family Valerianaceae] is a perennial herb found in Alpine Himalayas. N. jatamansi used for long period in various chronic diseases therapeutically. It is a reputed Ayurvedic herb and used in various multiple formulations. jatamansi has been used in the treatment of many disease and has several activities including anticonvulsant activity, antiparkinson’s activity, tranquillizing activity, hepatoprotective, neuroprotective, hypotensive, anti-diabetic activity. The objective of current review is to search literature for the pharmacological properties, safety/toxicity studies, phytochemical investigation and pharmacognostic studies of N. jatamansi. Complete information about the plant has been collected from various books, journals etc.
Mortality after a cholecystectomy: a population-based study.

BACKGROUND The trade-off between the benefits of surgery for gallstone disease for a large population and the risk of lethal outcome in a small minority requires knowledge of the overall mortality. METHODS Between 2007 and 2010, 47 912 cholecystectomies for gallstone disease were registered in the Swedish Register for Cholecystectomy and endoscopic retrograde cholangiopancreatography (ERCP) (GallRiks). By linkage to the Swedish Death Register, the 30-day mortality after surgery was determined. The age- and sex-standardized mortality ratio (SMR) was estimated by dividing the observed mortality with the expected mortality rate in the Swedish general population 2007. The Charlson Comorbidity Index (CCI) was estimated by International Classification of Diseases (ICD) codes retrieved from the National Patient Register. RESULTS Within 30 days after surgery, 72 (0.15%) patients died. The 30-day mortality was close [SMR = 2.58; 95% confidence interval (CI): 2.02-3.25] to that of the Swedish general population. In multivariable logistic regression analysis, predictors of 30-day mortality were age >70 years [odds ratio (OR) 7.04, CI: 2.23-22.26], CCI > 2 (OR 1.93, CI: 1.06-3.51), American Society of Anesthesiologists (ASA) > 2 (OR 13.28, CI: 4.64-38.02), acute surgery (OR 10.05, CI:2.41-41.95), open surgical approach (OR 2.20, CI: 1.55-4.69) and peri-operative complications (OR 3.27, CI: 1.74-6.15). DISCUSSION Mortality after cholecystectomy is low. Co-morbidity and peri-operative complications may, however, increase mortality substantially. The increased mortality risk associated with open cholecystectomy could be explained by confounding factors influencing the decision to perform open surgery.
Furfural reduction mechanism of a zinc‐dependent alcohol dehydrogenase from Cupriavidus necator JMP134

FurX is a tetrameric Zn‐dependent alcohol dehydrogenase (ADH) from Cupriavidus necator JMP134. The enzyme rapidly reduces furfural with NADH as the reducing power. For the first time among characterized ADHs, the high‐resolution structures of all reaction steps were obtained in a time‐resolved manner, thereby illustrating the complete catalytic events of NADH‐dependent reduction of furfural and the dynamic Zn2+ coordination among Glu66, water, substrate and product. In the fully closed conformation of the NADH complex, the catalytic turnover proved faster than observed for the partially closed conformation due to an effective proton transfer network. The domain motion triggered by NAD(H) association/dissociation appeared to facilitate dynamic interchanges in Zn2+ coordination with substrate and product molecules, ultimately increasing the enzymatic turnover rate. NAD+ dissociation appeared to be a slow process, involving multiple steps in concert with a domain opening and reconfiguration of Glu66. This agrees with the report that the cofactor is not dissociated from FurX during ethanol‐dependent reduction of furfural, in which ethanol reduces NAD+ to NADH that is subsequently used for furfural reduction.
Subsequent Epilepsy in Very‐Low‐Birthweight Infants: A Long‐Term Follow‐up Study from Birth

Summary: We studied 197 survivors of 290 very‐low‐birthweight (VLBW, <1,500g) infants admitted to our neonatal intensive care unit from 1977 through 1982. The children were all followed until at least age 6 years (mean 10 years 6 months). Eight children (4.1%) had epilepsy: 5 had generalized, 2 had unilateral, and 1 had partial seizures. Two (1.0%) had active and poorly controlled epilepsy. Three had a history of epileptic seizures, but none for ≥ 6 years, and 3 were no longer receiving antiepileptic drug (AED) treatment. Most (5 of 8) were severely multiply handicapped. As compared with VLBW children without epileptic seizures and neurodevelopmental abnormalities, VLBW children with epileptic seizures had a gestational age <27 weeks, a weight <1,000 g, severe perinatal complications as indicated by an Apgar score of <4 at 5 min, and the need for long‐term oxygen administration.
Can Manipulation of Orthokeratology Lens Parameters Modify Peripheral Refraction?

Purpose To investigate changes in peripheral refraction, corneal topography, and aberrations induced by changes in orthokeratology (OK) lens parameters in myopes. Methods Subjects were fitted with standard OK lenses that were worn overnight for 2 weeks. Peripheral refraction, corneal topography, and corneal surface aberrations were measured at baseline and after 14 nights of OK lens wear. Subsequent to a 2-week washout period, subjects were refitted with another set of lenses where one eye was randomly assigned to wear an OK lens with a smaller optic zone diameter (OZD) and the other eye with a steeper peripheral tangent. Measurements were taken again at a second baseline and after 14 days of overnight wear of the second OK lens set. Results Standard OK lenses with a 6-mm OZD and 1/4 peripheral tangent caused significant changes in both peripheral refraction and corneal topography. Significant hyperopic shift occurred in the central visual field (VF) while a myopic shift was found at 35 degrees in the nasal VF. OK induced significant reductions in corneal power at all positions along the horizontal corneal chord except at 2.4 mm nasal where there was no significant change and at 2.8 mm nasal where there was an increase in corneal refractive power. A positive shift in spherical aberration was induced for all investigated lens designs except for the 1/2 tangent design when calculated over a 4-mm pupil. Reducing OZD and steepening the peripheral tangent did not cause significant changes in peripheral refraction or corneal topography profiles across the horizontal meridian. Conclusions OK lenses caused significant changes in peripheral refraction, corneal topography, and corneal surface aberrations. Modifying OZD and peripheral tangent made no significant difference to the peripheral refraction or corneal topography profile. Attempting to customize refraction and topography changes through manipulation of OK lens parameters appears to be a difficult task.
Neuroanatomical correlates of behavioral rating versus performance measures of working memory in typically developing children and adolescents.

OBJECTIVE The frequent lack of correspondence between performance and observational measures of executive functioning, including working memory, has raised questions about the validity of the observational measures. This study was conducted to investigate sources of this discrepancy through correlation of volumetric and cortical thickness (CT) neuroimaging values with performance and questionnaire measures of working memory (WM). METHODS Using longitudinal data from the NIH MRI Study of Normal Brain Development (Volumes, N= 347, 54.3% female; CT, N= 350, 54.6% female; age range: 6 to 16.9 years), scores on the Behavioral Rating Inventory of Executive Function (BRIEF) WM, Emotional Control (EC) and Inhibition (INH) scales; Wechsler Scale of Intelligence for Children-III Digit Span; and Cambridge Neuropsychological Test Battery Spatial Working Memory (CANTAB SWM) were correlated with each other and with morphometric measurements using mixed effects linear regression models. RESULTS BRIEF WM was correlated with CANTAB SWM (p < .001). With whole brain correction, BRIEF WM and EC were both correlated with CT of the posterior parahippocampal gyrus (PHG), EC on the right side only. Performance measures of WM were unrelated to lobar volumes or CT, but were associated with volumes of hippocampus and amygdala. CONCLUSIONS The known role of PHG in contextual learning suggests that the BRIEF WM assesses contextualized learning/memory, potentially explaining its loose correspondence to the decontextualized performance measures. Observational measures can be useful and valid functional metrics, complementing performance measures. Labels used to characterize scales should be interpreted with caution, however.
NG2‐expressing cells in the nervous system revealed by the NG2‐EYFP‐knockin mouse

The NG2 glycoprotein is a type I membrane protein expressed by immature cells in the developing and adult mouse. NG2+ cells of the embryonic and adult brain have been principally viewed as oligodendrocyte precursor cells but have additionally been considered a fourth glial class. They are likely to be a heterogeneous population. In order to facilitate studies on the function of NG2+ cells and to characterize these cells in situ, we generated an enhanced yellow fluorescent protein (EYFP) “knockin mouse. ” EYFP‐expressing cells in heterozygous knockin mice expressed the NG2 protein in all regions and at all ages studied. The EYFP+ cells did not express markers of mature glia, developing or mature neurons or microglia, but expressed markers typical for immature oligodendrocyte‐lineage cells. Examination of the hippocampus showed heterogeneity in the population with regard to expression of S100ß and glutamine synthetase. Furthermore, different subpopulations of NG2+ cells in the hippocampus could be recognized by their electrophysiological properties. genesis 46:743–757, 2008. © 2008 Wiley‐Liss, Inc.
MicroRNA-140 is expressed in differentiated human articular chondrocytes and modulates interleukin-1 responses.

OBJECTIVE MicroRNA (miRNA) are a class of noncoding small RNAs that act as negative regulators of gene expression. MiRNA exhibit tissue-specific expression patterns, and changes in their expression may contribute to pathogenesis. The objectives of this study were to identify miRNA expressed in articular chondrocytes, to determine changes in osteoarthritic (OA) cartilage, and to address the function of miRNA-140 (miR-140). METHODS To identify miRNA specifically expressed in chondrocytes, we performed gene expression profiling using miRNA microarrays and quantitative polymerase chain reaction with human articular chondrocytes compared with human mesenchymal stem cells (MSCs). The expression pattern of miR-140 was monitored during chondrogenic differentiation of human MSCs in pellet cultures and in human articular cartilage from normal and OA knee joints. We tested the effects of interleukin-1beta (IL-1beta) on miR-140 expression. Double-stranded miR-140 (ds-miR-140) was transfected into chondrocytes to analyze changes in the expression of genes associated with OA. RESULTS Microarray analysis showed that miR-140 had the largest difference in expression between chondrocytes and MSCs. During chondrogenesis, miR-140 expression in MSC cultures increased in parallel with the expression of SOX9 and COL2A1. Normal human articular cartilage expressed miR-140, and this expression was significantly reduced in OA tissue. In vitro treatment of chondrocytes with IL-1beta suppressed miR-140 expression. Transfection of chondrocytes with ds-miR-140 down-regulated IL-1beta-induced ADAMTS5 expression and rescued the IL-1beta-dependent repression of AGGRECAN gene expression. CONCLUSION This study shows that miR-140 has a chondrocyte differentiation-related expression pattern. The reduction in miR-140 expression in OA cartilage and in response to IL-1beta may contribute to the abnormal gene expression pattern characteristic of OA.
Rat bone marrow‐derived mast cells co‐cultured with 3T3 fibroblasts in the absence of T‐cell derived cytokines require stem cell factor for their survival and maintain their mucosal mast cell‐like phenotype

When cultured without fibroblasts, rat bone marrow‐derived mast cells (BMMC) contain abundant rat mast cell proteinase type II (RMCP‐II), and exhibit survival and proliferation when maintained in mesenteric lymph node conditioned medium (CM). When BMMC were co‐cultured with 3T3 fibroblasts in the absence of CM, BMMC numbers increased for 7 days and the BMMC survived for up to 23 days. There was a gradual loss of stored RMCP‐II in BMMC that were co‐cultured with 3T3 cells, but the fibroblast microenvironment did not induce a detectable increase in the low levels of the connective tissue mast cell (CTMC)‐associated proteinase, RMCP‐I, in the BMMC. Nor did 3T3 cell co‐culture induce significant heparin synthesis in BMMC as judged by the cells' reactivity with the fluorescent heparin‐binding dye, berberine sulphate. These results suggest that rat BMMC, unlike murine BMMC, do not have the potential to develop multiple CTMC‐like characteristics upon co‐culture with 3T3 cells. However, when BMMC and fibroblast co‐cultures were treated with an antibody to recombinant rat stem cell factor (rrSCF), mast cell survival was completely abrogated. This result suggests that endogenous, fibroblast‐derived SCF is essential for the maintenance of rat BMMC viability in the absence of CM. On the other hand, prior treatment of the fibroblasts with the anti‐rrSCF antibody did not affect the adherence of BMMC to the monolayer, implying that (an)other molecule(s) is(are) involved in the attachment process. The demonstration that rat BMMC survival on fibroblasts in vitro is dependent upon SCF may indicate an important mechanism by which tissue mucosal cells can be maintained in vivo in the absence of T‐cell derived factors.
The decline of non-marital fertility in Europe, 1880-1940.

Abstract Between 1880 and 1940, to take approximate dates, illegitimate fertility rates in Europe dropped precipitously, falling in most countries by 50% or more. The rates used throughout this paper relate extra-marital births to the number of unmarried (i.e. single, widowed and divorced) women; we use a standardized index, I ({ih}) to be discussed later. In Fig. 1 we present most of the European series of I ( h )'s that can be computed from existing census and vital registration data. Although there are interesting exceptions the general picture is clear: a decline in illegitimate fertility commenced in most countries in the last quarter of the nineteenth century, and was arrested in the 1920's and 1930's. Once it had begun in a country, the downward course was swift and uninterrupted, until non-marital fertility had been cut in half.