Miracle-dz/UniFAR-FTUs huggingface dataset:
Meat‐related mutagens/carcinogens in the etiology of colorectal cancer

Diets containing substantial amounts of red or preserved meats may increase the risk of various cancers, including colorectal cancer. This association may be due to a combination of factors such as the content of fat, protein, iron, and/or meat preparation (e.g., cooking or preserving methods). Red meat may be associated with colorectal cancer by contributing to N‐nitroso compound (NOC) exposure. Humans can be exposed to NOCs by exogenous routes (from processed meats in particular) and by endogenous routes. Endogenous exposure to NOCs is dose‐dependently related to the amount of red meat in the diet. Laboratory results have shown that meats cooked at high temperatures contain other potential mutagens in the form of heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). To investigate the role of these compounds, we have created separate databases for HCAs and PAHs, which we have used in conjunction with a validated meat‐cooking food frequency questionnaire. The role of meat type, cooking methods, doneness levels, and meat‐cooking mutagens has been examined in both case‐control studies and prospective cohort studies, with mixed results. Here, we review the current epidemiologic knowledge of meat‐related mutagens, and evaluate the types of studies that may be required in the future to clarify the association between meat consumption and colorectal cancer. Environ. Mol. Mutagen. 44:44–55, 2004. Published 2004 Wiley‐Liss, Inc.
CYP3A4 expressed by insect cells infected with a recombinant baculovirus containing both CYP3A4 and human NADPH-cytochrome P450 reductase is catalytically similar to human liver microsomal CYP3A4.

Human cytochrome CYP3A4 is the most abundant of all the P450s in human liver and is involved in the metabolism of many environmental toxicants and drugs. Kinetic studies with CYP3A4 have been hampered due to low activity of this enzyme obtained from recombinant gene expression systems or difficulty in reconstituting activity with the native enzyme purified from human liver. To overcome these obstacles, we have expressed high levels of catalytically active CYP3A4 and human NADPH-cytochrome P450 reductase (CYPOR) together in two insect cell lines, Spodoptera frugiperda (Sf9) and Trichoplusia ni (T.ni), via a single recombinant baculovirus carrying both cDNAs (CYP3A4-OR). Microsomes containing recombinant CYP3A4-OR from these cell lines were up to 50-times more active in testosterone 6 beta-hydroxylase activity than recombinant CYP3A4 expressed alone and supplemented with purified rabbit CYPOR. The spectral P450 content of CYP3A4-OR T.ni microsomes was 107 pmol/mg microsomal protein and the cytochrome c reductase activity was 3904 units/mg. Recombinant CYP3A4-OR was catalytically similar to human liver CYP3A4 based on similarities in the testosterone metabolite profile, time course of metabolite formation, Vmax and Km values (for CYP3A4-OR, Vmax was 8.8 nmol/min/mg microsomal protein [70 nmol/min/nmol CYP3A4] and Km was 33 microM), the extent of inhibition by 100 microM troleandomycin (> 75%) in the presence of 25 microM testosterone, and the degree of P450 activation in the presence of 20 microM 7,8-benzoflavone. The coexpression of recombinant cytochrome b5 with CYP3A4-OR did not result in an additional increase in CYP3A4-OR activity.
Depressive Disorders During Pregnancy: Prevalence and Risk Factors in a Large Urban Sample

OBJECTIVE: To estimate the prevalence of major and minor depression, panic disorder, and suicidal ideation during pregnancy while also identifying factors independently associated with antenatal depressive disorders. METHODS: In this prospective study, participants were 1,888 women receiving ongoing prenatal care at a university obstetric clinic from January 2004 through January 2009. Prevalence of psychiatric disorders was measured using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria based on the Patient Health Questionnaire. Multiple logistic regression identified factors associated with probable major depressive disorder and any depressive disorder. RESULTS: Antenatal depressive disorders were present in 9.9% with 5.1% (97) meeting criteria for probable major depression and 4.8% (90) meeting criteria for probable minor depression. Panic disorder was present in 3.2% (61), and current suicidal ideation was reported by 2.6% (49). Among patients with probable major depression, 29.5% (28) reported current suicidal ideation. Psychosocial stress (odds ratio [OR], 1.29; 95% confidence interval [CI], 1.21–1.36), domestic violence (OR 3.45; 95% CI 1.46–8.12), chronic medical conditions (OR 3.05; 95% CI 1.63–5.69), and race (Asian: OR 5.81; 95% CI 2.55–13.23; or African American: OR 2.98; 95% CI 1.24–7.18) each significantly increased the odds of probable antepartum major depressive disorder, whereas older age (OR 0.92; 95% CI 0.88–0.97) decreased the odds. Factors associated with odds of any depression were similar overall except that Hispanic ethnicity (OR 2.50; 95% CI 1.09–5.72) also independently increased the odds of any depression. CONCLUSION: Antenatal major and minor depressive disorders are common and significantly associated with clinically relevant and identifiable risk factors. By understanding the high point prevalence and associated factors, clinicians can potentially improve the diagnosis and treatment rates of serious depressive disorders in pregnant women. LEVEL OF EVIDENCE: II
Genotyping of the polymorphic N‐acetyltransferase (NAT2) and loss of heterozygosity in bladder cancer patients

Acetylation is one of the major routes in metabolism and detoxification of a large number of drugs, chemicals and carcinogens. Slow acetylators are said to be more susceptible to developing bladder cancer and because of investigations about tumor risk based on phenotyping procedures, it was our aim to study the distribution of allelic constellations of the N‐acetyltransferase (NAT2) by genotyping patients with bladder cancer. We analysed NAT2 gene of blood and tumor DNA from 60 patients with primary bladder cancer and DNA of blood samples from 154 healthy individuals. Using ASO‐PCR/RFLP techniques we identified 70% of patients with bladder cancer (n = 42) to be slow acetylators while genotyping of controls resulted in 61% with slow acetylators (n = 94). In addition, dividing bladder cancer patients in males and females the genotype NAT2 * 5B/NAT2 * 6A occured with much higher frequencies in males (OR = 4, 95%; CI = 1.8–8.9).
Exercise training reduces severity of atherosclerosis in apolipoprotein E knockout mice via nitric oxide.

BACKGROUND Exercise training may protect against the development of atherosclerosis, although the precise mechanisms are still unknown. The present study assessed the hypothesis that exercise training would reduce the severity of experimental atherosclerosis in apolipoprotein-E (apoE)-deficient mice via nitric oxide (NO). METHODS AND RESULTS ApoE-deficient mice fed a high-fat diet underwent exercise training (30 min swimming) 3 times per week for 8 weeks. The exercise group were also given oral N(G)-nitro-L-arginine methylester (L-NAME; 25 mg x kg (-1) x day(-1)), an inhibitor of NO synthase. Fatty streak plaque lesions developed in ApoE-deficient mice fed the high-fat diet, and were suppressed in the mice that underwent swimming training. In contrast, atherosclerotic lesions were not ameliorated in mice that had exercise training plus oral L-NAME treatment. Immunohistochemical analysis revealed that the expression of endothelial NO increased in mice undergoing exercise compared with the mice that did not exercise, and that the expression was suppressed in the mice having exercise plus oral L-NAME treatment. Differences in lesion area did not correlate with any significant alterations in serum lipid levels. CONCLUSION Exercise training suppressed atherosclerosis via the NO system.
Prevalence of permanent childhood hearing impairment in the United Kingdom and implications for universal neonatal hearing screening: questionnaire based ascertainment study.

Abstract Objective: To estimate the prevalence of confirmed permanent childhood hearing impairment and its profile across age and degree of impairment in the United Kingdom. Design: Retrospective total ascertainment through sources in the health and education sectors by postal questionnaire. Setting: Hospital based otology and audiology departments, community health clinics, education services for hearing impaired children. Participants: Children born from 1980 to 1995, resident in United Kingdom in 1998, with permanent childhood hearing impairment (hearing level in the better ear >40 dB averaged over 0.5, 1, 2, and 4 kHz). Main outcome measures: Numbers of cases with date of birth and severity of impairment converted to prevalences for each annual birth cohort (cases/1000 live births) and adjusted for underascertainment. Results: 26 000 notifications ascertained 17 160 individual children. Prevalence rose from 0.91 (95% confidence interval 0.85 to 0.98) for 3 year olds to 1.65 (1.62 to 1.68) for children aged 9-16 years. Adjustment for underascertainment increased estimates to 1.07 (1.03 to 1.12) and 2.05 (2.02 to 2.08). Comparison with previous studies showed that prevalence increases with age, rather than declining with year of birth. Conclusions: Prevalence of confirmed permanent childhood hearing impairment increases until the age of 9 years to a level higher than previously estimated. Relative to current yields of universal neonatal hearing screening in the United Kingdom, which are close to 1/1000 live births, 50-90% more children are diagnosed with permanent childhood hearing impairment by the age of 9 years. Paediatric audiology services must have the capacity to achieve early identification and confirmation of these additional cases. What is already known on this topic The prevalence of confirmed permanent childhood hearing impairment (>40 dB HL) in the United Kingdom has been estimated to rise with age to 1.33/1000 live births among children aged 5 years and older It has been predicted that only an additional 16% of children will remain to be detected in the postnatal years, given current yields from universal neonatal hearing screening What this study adds The prevalence of confirmed permanent childhood hearing impairment (>40 dB HL) in the United Kingdom has risen with age to at least 1.65/1000 live births (and may be as high as 2.05/1000 live births) among children 9 years of age and older If the current yield from screening is sustained, then an additional 50-90% of children will remain to be detected in the postnatal years
Increasing titers and changing specificities of antinuclear antibodies in patients with chronic liver disease who develop hepatocellular carcinoma

Background. Patients with liver cirrhosis and chronic hepatitis are at high risk for development of hepatocellular carcinoma (HCC). In HCC and other malignant neoplasms, antinuclear antibodies (ANA) have been detected, but the clinical and biologic significance of these autoantibodies has not been established. This study documents changing ANA manifested as seroconversion from a negative to positive ANA status, increasing titers, and changing antibody specificities in patients in whom chronic liver disease has progressed to HCC.
Tools, harmonization and standardization procedures of the impact and outcome evaluation indices obtained during a kindergarten‐based, family‐involved intervention to prevent obesity in early childhood: the ToyBox‐study

The ToyBox‐intervention is a kindergarten‐based, family‐involved intervention targeting multiple lifestyle behaviours in preschool children, their teachers and their families. This intervention was conducted in six European countries, namely Belgium, Bulgaria, Germany, Greece, Poland and Spain. The aim of this paper is to provide a descriptive overview of the harmonization and standardization procedures of the baseline and follow‐up evaluation of the study (and substudies). Steps related to the study's operational, standardization and harmonization procedures as well as the impact and outcome evaluation assessment tools used are presented. Experiences from the project highlight the importance of safeguarding the measurement process to minimize data heterogeneity derived from potential measurement error and country‐by‐country differences. In addition, it was made clear that continuing quality control and support is an important component of such studies. For this reason, well‐supported communication channels, such as regular email updates and teleconferences, and regular internal and external meetings to ensure smooth and accurate implementation were in place during the study. The ToyBox‐intervention and its harmonized and standardized procedures can serve as a successful case study for future studies evaluating the efficacy of similar interventions.
Regulation of Cell Surface Tissue Transglutaminase: Effects on Matrix Storage of Latent Transforming Growth Factor-β Binding Protein-1

Using a cytochemical approach, we examined the role of tissue transglutaminase (tTgase, Type II) in the incorporation of latent TGF-β binding protein-1 (LTBP-1) in the extracellular matrix of Swiss 3T3 fibroblasts in which tTgase expression can be modulated through a tetracycline-controlled promoter. Increased tTgase expression led to an increased rate of LTBP-1 deposition in the matrix, which was accompanied by an increased pool of deoxycholate-insoluble fibronectin. Matrix deposition of LTBP-1 could also be reduced by the competitive amine substrate putrescine. Immunolocalization at the fluorescence and electron microscopic level showed that extracellular tTgase is located at the basal and apical surfaces of cells and at cell-cell contacts, and that LTBP-1 is co-distributed with cell surface tTgase, suggesting an early contribution of tTgase to the binding of LTBP-1 to matrix proteins. LTPB-1 was also found to co-localize with both intracellular and extracellular fibronectin, and increased immunoreactivity for LTBP-1 and fibronectin was found in large molecular weight polymers in the deoxycholate-insoluble matrix of fibroblasts overexpressing tTgase. We conclude that regulation of tTgase expression is important for controlling matrix storage of latent TGF-β1 complexes and that fibronectin may be one extracellular component to which LTBP-1 is crosslinked when LTBP-1 and tTgase interact at the cell surface.
Dietary genistein intake and cognitive performance in a multiethnic cohort of midlife women

Objective: To examine the relationship between food frequency questionnaire estimated isoflavone intakes and cognitive performance. Design: The Study of Women's Health Across the Nation (SWAN), is a multiethnic, community based, longitudinal study of women aged 42 to 52 years at entry. Dietary isoflavone intakes were estimated from an interviewer-administered food frequency questionnaire at baseline. Intakes of genistein and daidzein were highly correlated (r = 0.98); therefore, analyses were conducted using genistein only. The SWAN includes white, African American, Hispanic, Chinese, and Japanese women; this analysis was performed only in the latter two ethnic groups because the others had minimal genistein intake (median, <4 &mgr;g/day). Cognitive function tests were measured at the fourth annual follow-up visit using the East Boston Memory Test (Immediate and Delayed), Symbol Digit Modalities Test, and Digit Span Backward Test. Ethnicity-specific general linear models were used to examine the relationship between each of these cognitive tests and energy-adjusted genistein intake controlling for age, menopause stage, ever-use of any hormones, and current use of any hormones. Results: Among 195 Japanese and women and 185 Chinese women, median intakes of genistein (&mgr;g/day) were 6,788 and 3,534, respectively. No associations between genistein intake and measures of cognitive performance were found in either ethnic group. Conclusions: Our results did not support the hypothesis that genistein intake, at the levels consumed by the study sample, benefits cognitive performance. It also possible that the bioavailability of genistein in food sources is insufficient to exert a neurophysiological effect or that the potential effect of genistein is only manifest in low-estrogen states; the current study is not able to address these possibilities.
Cost-effectiveness of enoxaparin as thromboprophylaxis in acutelly ill medical patients from the Italian NHS perspective.

OBJECTIVE To determine the cost-effectiveness of thromboprophylaxis with enoxaparin versus no thromboprophlaxis in patients with acute medical illness in Italy from the NHS perspective. METHODS Markov process analysis techniques were used to model the health economic outcomes. Clinical data were derived mainly from the MEDENOX trial, while health care utilization was derived from Delphi panels. RESULTS An analysis over the MEDENOX trial period shows that the cost per event avoided is [symbol: see text] 2450.99, while the cost per life saved is [symbol: see text] 8395.89. The lifetime model, which assumes no higher risk for recurrence of VTE and mortality in asymptomatic patients, shows that the use of enoxaparin leads a cost per event avoided of [symbol: see text] 2243.20, and cost per life year gained of [symbol: see text] 605.38. The lifetime model, which assumes a higher risk for recurrence of VTE in asymptomatic patients, shows that enoxaparin is dominant over no thromboprophylaxis. CONCLUSION The results showed that the favourable clinical benefit of enoxaparin as thromboprophylaxis in patients with acute medical illness, which was observed in the MEDENOX trial, results in a positive health economic benefit on the short-term and long-term in the health care setting of Italy.
Oncogenous Osteomalacia and Myopericytoma of the Thoracic Spine: A Case Report

Study Design. A case report. Objective. To illustrate a rare case of oncogenous osteomalacia caused by a spinal thoracic myopericytoma. Summary of Background Data. Osteomalacia related to a tumor is well known. The cause of the disorder is usually a highly vascularized, benign tumor of mesenchymal origin. Location of the tumor in the spine is very rare. Removal of the tumor is followed by resolution of osteomalacia. Methods. Diagnosis of oseomalacia was established on the presence of cardinal clinical, biologic, and radiologic features of osteomalacia. Localization of the tumor at T5 and T6 levels was obtained by magnetic resonance imaging. Surgical treatment consisted in a circumferential correction-fusion with hemivertebrectomy of T5 and T6 and tumor removal. Results. Tumor removal was rapidly followed by disappearance of the clinical symptoms of osteomalacia, and by correction of hypophosphatemia. At 2-years follow-up, no recurrence of the tumor was detectable on imaging studies—the correction fusion remained stable. Histologically, the tumor was classified as a myopericytoma. There was no relapse of the clinical features of osteomalacia. However, secondary recurrence of the biologic markers due to an incomplete tumor removal was disclosed. Conclusion. Removal of the tumor was followed by healing of the clinical features of osteomalacia, demonstrating the causal connection between the myopericytoma and the osteopathy.
Dengue Virus Subverts the Interferon Induction Pathway via NS2B/3 Protease-IκB Kinase ε Interaction

ABSTRACT Dengue is the world's most common mosquito-borne viral infection and a leading cause of morbidity throughout the tropics and subtropics. Viruses are known to evade the establishment of an antiviral state by regulating the activation of interferon regulatory factor 3 (IRF3), a critical transcription factor in the alpha/beta interferon induction pathway. Here, we show that dengue virus (DENV) circumvents the induction of the retinoic acid-inducible gene I-like receptor (RLR) pathway during infection by blocking serine 386 phosphorylation and nuclear translocation of IRF3. This effect is associated with the expression of nonstructural 2B/3 protein (NS2B/3) protease in human cells. Using interaction assays, we found that NS2B/3 interacts with the cellular IκB kinase ε (IKKε). Docking computational analysis revealed that in this interaction, NS2B/3 masks the kinase domain of IKKε and potentially affects its functionality. This observation is supported by the DENV-associated inhibition of the kinase activity of IKKε. Our data identify IKKε as a novel target of DENV NS2B/3 protease.
The Tennessee Educational Improvement Act: A Beginning Discussion

Tennessee is no stranger to educa­ tional reform. In February of 1984, it enacted The Comprehensive Education Reform Act of 1984 (SBl) . The act ear­ marked more than $401 million in new revenues for kindergarten through higher education during the 1984-85 school year, and more than $1 billion for the following three years (School Reform in JO States, 1988) . The heart of the reform package was a five-step career ladder, the first comprehensive incentive pay system in America. In addition to the career ladder, the Ten­ nesseee reform act extended tenure from three years to four years, formu­ lated tougher standards for teacher training, extended the school year by five days, provided over � million for textbooks and supplies, purchased computers for school use, and pro­ vided money for first grade readiness among other reform provisions. Tennessee was not alone in passing major pieces of educational reform legislation . So many states enacted education laws in response to a deluge of reform reports, that consequently this period of activity has commonly been called the first wave of reform. As part of this wave, George Deukme­ j iian, Governor of California, signed into law in 1983 the omnibus education bill SB813. This major reform law made more than 80 changes in the
Association between socioeconomic status and adiposity in urban Cameroon.

BACKGROUND As the relation between socioeconomic status (SES) and obesity may depend on the stage of development of a country, this relation is assessed in adults from urban Cameroon. METHODS A sample comprising 1530 women and 1301 men aged 25 years and above, from 1897 households in the Biyem-Assi health area in the capital of Cameroon, Yaoundé, were interviewed about their household amenities, occupation, and education. Weight, height, and waist circumference were measured and subjects were classified as obese if their BMI>or=30 kg/m2 or overweight if BMI was between 25.0 and 29.9 kg/m2. Abdominal obesity was defined by a waist circumference>or=80 cm in women and>or=94 cm in men. RESULTS Of the sample studied 33% of women and 30% of men were overweight (P<0.08), whereas 22% of women and 7% of men were obese (P<0.001). Abdominal obesity was present in 67% of women and 18% of men (P<0.001). After adjusting for age, leisure time physical activity, alcohol consumption, and tobacco smoking, the prevalence of overweight+obesity, obesity, and abdominal obesity increased with quartiles of household amenities in both genders and with occupational level in men. CONCLUSION SES is positively associated with adiposity in urban Cameroon after adjusting for confounding factors.