Miracle-dz/UniFAR-FTUs huggingface dataset:
Ranitidine‐acetaminophen interaction: Effects on acetaminophen‐induced hepatotoxicity in fischer 344 rats

Cimetidine has been shown to protect against acetaminophen‐mediated hepatotoxicity in both rats and mice. In contrast to cimetidine, ranitidine recently has been determined to potentiate the hepatotoxic action of acetaminophen in Fischer 344 rats. The present studies were designed to characterize this ranitidine‐acetaminophen interaction. Acetaminophen administration (750 mg per kg, p.o.) to F344 rats produced maximal hepatic necrosis, 24 hr after treatment, as assessed by SGPT activity and histopathology. Ranitidine pretreatment 30 min prior to acetaminophen treatment increased the toxicity but did not alter its course. Ranitidine administration (50 mg per kg) enhanced acetaminophen hepatotoxicity throughout the toxic dose range of acetaminophen (600 to 1,000 mg per kg) and potentiation of acetaminophen hepatotoxicity by ranitidine was dose‐dependent. Maximal increases were observed at 50 mg per kg ranitidine whereas, doses of ranitidine greater than 100 mg per kg inhibited acetaminophen toxicity. SGPT data were corroborated by histopathologic evaluation. Ranitidine was not intrinsically hepatotoxic when administered alone (500 mg per kg), or following glutathione depletion, or after induction of hepatic mixed‐function oxidase activity. The results obtained in these studies support the suggestion that, at high doses (>100 mg per kg), ranitidine reduces acetaminophen hepatotoxicity by reducing metabolic activation, while at lower doses ranitidine potentiates acetaminophen hepatotoxicity. Inhibition by ranitidine of acetaminophen conjugation is proposed as a possible mechanism of this potentiation.
Understanding (insect) species distributions across spatial scales

J. Hortal (j.hortal@imperial.ac.uk), NERC Centre for Population Biology, Div. of Biology, Imperial College London, Silwood Park Campus,Ascot, Berkshire SL5 7PY, UK. N. Roura-Pascual, A`rea de Biodiversitat, Centre Tecnolo`gic Forestal de Catalunya, Ctra. de St. Llorenc¸ deMorunys Km 2, ES-25280 Solsona, Catalonia, Spain. N. J. Sanders, Dept of Ecology and Evolutionary Biology, Univ. of Tennessee, Knoxville,TN 37996, USA. C. Rahbek, Center for Macroecology, Evolution, and Climate, Dept of Biology, Univ. of Copenhagen, Universitetsparken15, DK-2100 Copenhagen O, Denmark.
Influences on the Mantel-Haenszel Chi-Square in Detection of Differential Item Functioning under Rasch Conditions

The Mantel-Haenszel chi-square (χ2MH) is widely used to detect differential item functioning (item bias) between ethnic and gender-based subgroups on educational and psychological tests. The empirical behavior of χ2MH has been incompletely understood; previous research is inconclusive. The present simulation study explored the effects of sample size, number of items, and trait distributions on the power of χ2MH to detect modeled differential item functioning. A significant effect was obtained for sample size with unacceptably low power for 250 subjects each in the focal and reference groups. The discussion supports the 1990 recommendations of Swaminathan and Rogers, opposes the 1993 view of Zieky that a sample size of 250 for each group is adequate.
Therapy‐related acute promyelocytic leukemia: observations relating to APL pathogenesis and therapy *

Therapy‐related acute promyelocytic leukemia (t‐APL) is a well‐recognized form of APL for which the underlying etiology has been well characterized. The pathogenesis of de novo (dn‐APL) remains unknown; but epidemiologic studies have consistently identified increased body mass index (BMI), younger age, and ethnicity as possible risk factors. We analyzed demographics, clinical features, and treatment responses in a contemporary series of 64 patients treated with all‐trans‐retinoic acid and anthracycline‐based therapy to assess for differences in these two etiologically distinct patient groups. Compared with patients with t‐APL (n = 11), those with dn‐APL (n = 53) had a greater median BMI (31.33 vs. 28.48), incidence of obesity (60.4% vs. 27.3%) (P = 0.04), and history of hyperlipidemia (45.3% vs. 18.2%) (P = 0.01). Fewer t‐APL than dn‐APL patients achieved complete remission at 63.6% vs. 92.5% respectively (P = 0.008). This was the result of a higher induction mortality rate of 36.4% vs. 7.5% respectively (P = 0.008). No cases of leukemic resistance were seen in either group. Overall survival (OS) was inferior in t‐APL compared with dn‐APL at 51% vs. 84%, respectively (P < 0.005), primarily as a result of higher induction mortality. Relapse occurred in nine patients (16.1%) overall, but no relapses occurred in the t‐APL cohort. Our observations provide further support for the hypothesis that abnormalities in lipid homeostasis may in some way be of pathogenic importance in dn‐APL. Therapy‐related APL is sensitive to standard therapy with no cases of resistance or relapse seen. The inferior OS of the t‐APL was due to induction mortality, possibly reflecting prior therapy.
Nuclear reprogramming: what has been done and potential avenues for improvements

A major challenge for reproductive biologists is the development of novel strategies to improve cloning efficiency. Even in species for which cloning is relatively successful, like cattle, the efficiency is still unacceptably low. In this review article we critically analyse all approaches that have been suggested by different laboratories in the field so far. As will be discussed below, so far none of these gives rise to a dramatic increase in cloning efficiency. Possibly, a multi-step approach including a pre-treatment of donor cells to modify their chromatin, along with improved culture system for cloned embryos would be the most promising.
A Content Analysis of Nonprofit Hospital Community Health Needs Assessments and Community Benefit Implementation Strategies in Philadelphia

Context: Nonprofit hospitals are mandated to perform a community health needs assessment, develop an implementation strategy to address community needs, and invest in improving community health through community benefit investments in order to maintain the tax exemptions afforded nonprofit hospitals. Objective: We sought to describe the regional health needs identified across community health needs assessments and the portfolio of implementation strategies reported to address those needs. Design: The study provides a content analysis of community health needs assessments and implementation strategies for nonprofit hospitals in one urban region. Setting: The study focused on nonprofit hospitals in Philadelphia, Pennsylvania. Main Outcome Measures: Community benefit documents were coded to characterize health needs and intervention activities using the 4 health factor categories of the County Health Rankings framework: clinical care, health behaviors, social and economic factors, and physical environment. Results: Hospitals predominantly identified health needs related to access to care, especially mental health and dental care, and insurance coverage and costs of care. In many instances, there is little alignment between needs identified through the community health needs assessments and the reported implementation strategies. Specifically, dental care, behavioral health, substance abuse, social factors, and health care and prescription drug costs were all cited as important community needs but were infrequently targeted by implementation strategies. Conclusions: Nonprofit hospital community health needs assessments in Philadelphia predominantly identify needs related to access to care and to some extent health behaviors. There is incomplete alignment between the needs identified in hospital assessments and the needs targeted in implementation strategies, underscoring a need for regional coordination in community benefit investments. Improved regional coordination between hospitals serving the region may offer the opportunity to eliminate duplicative efforts and increase the amount of funds available to address unmet needs.
Zn2+ Inhibits Mitochondrial Movement in Neurons by Phosphatidylinositol 3-Kinase Activation

Mitochondria have been identified as targets of the neurotoxic actions of zinc, possibly through decreased mitochondrial energy production and increased reactive oxygen species accumulation. It has been hypothesized that impairment of mitochondrial trafficking may be a mechanism of neuronal injury. Here, we report that elevated intraneuronal zinc impairs mitochondrial trafficking. At concentrations just sufficient to cause injury, zinc rapidly inhibited mitochondrial movement without altering morphology. Zinc chelation initially restored movement, but the actions of zinc became insensitive to chelator in <10 min. A search for downstream signaling events revealed that inhibitors of phosphatidylinositol (PI) 3-kinase prevented this zinc effect on movement. Moreover, transient inhibition of PI 3-kinase afforded neuroprotection against zinc-mediated toxicity. These data illustrate a novel mechanism that regulates mitochondrial trafficking in neurons and also suggest that mitochondrial trafficking may be closely coupled to neuronal viability.
Modulated expression of c‐Fos in the spinal cord following noxious thermal stimulation of monoarthritic rats

Peripheral noxious stimulation evokes functional and biochemical changes in the spinal cord which results in central sensitization and hyperalgesia, but at the same time also induces the activation of inhibitory control systems. The purpose of the present study was to investigate whether the adaptive changes induced by ongoing peripheral inflammation influence the spinal cord expression of c‐Fos (a commonly used marker of neuronal activity) following an additional acute noxious stimulus. Therefore, the spinal expression of c‐Fos was immunohistochemically investigated following noxious thermal stimulation of a rat monoarthritic hindpaw at various time points (1, 4, 8, 21 days) after induction of monoarthritis. Compared to normal rats, c‐Fos expression following ipsilateral noxious thermal stimulation of monoarthritic rats was strongly modified in the deep laminae of the dorsal horn depending on the time course of inflammation. At 1 day of monoarthritis, an enhanced ipsilateral expression (135% and 208% of normal rats in laminae III–VI and VII, respectively) and at 3 weeks a reduced expression (38% and 23% of normal rats in laminae III–VI and VII, respectively) was detected. The amount of c‐Fos‐positive neurons in the ipsilateral superficial laminae I and II was unchanged at all time points investigated. To assess excitability changes on the contralateral side at an early stage of inflammation, a group of monoarthritic rats received a contralateral noxious stimulus at day 1 of monoarthritis. This resulted in a potentiated expression of c‐Fos ipsilateral to the acute noxious stimulus (i.e., contralateral to the monoarthritic hindpaw) restricted to lamina II (137% of normal rats) of the dorsal horn. The data showed that changes in c‐Fos expression depended on the time point of noxious heat stimulation (NHS) of monoarthritic rats, and differed in the ipsi‐ and contralateral side of the spinal cord. In addition to a possible habituation of c‐Fos expression, it may be speculated that the time course‐dependent changes reflect laminae‐specific modulations of excitatory and inhibitory mechanisms during monoarthritis. Further studies are necessary in order to provide more insights into the contribution of these mechanisms on noxious stimulus‐evoked c‐Fos expression. J. Neurosci. Res. 53:203–213, 1998. © 1998 Wiley‐Liss, Inc.
Growth of alveoli during postnatal development in humans based on stereological 1 estimation 2 3 Authors :

24 Rationale: Alveolarization in humans and nonhuman primates begins during prenatal 25 development. Advances in stereological counting techniques allow accurate assessment 26 of alveolar number; however, these techniques have not been applied to the developing 27 human lung. 28 Methods: Based on the recent ATS guidelines for stereology, lungs from human 29 autopsies, ages 2 months to 15 years, were fractionated and isometric uniform randomly 30 sampled to count the number of alveoli. The number of alveoli was compared to age, 31 weight, and height as well as growth between right and left lungs. 32 Results: The number of alveoli in the human lung increased exponentially during the 33 first two years of life but continued to increase albeit at a reduced rate through 34 adolescence. Alveolar numbers also correlated with the indirect radial alveolar count 35 technique. Growth curves for human alveolarization were compared using historical data 36 of nonhuman primates and rats. The alveolar growth rate in nonhuman primates was 37 nearly identical to the human growth curve. Rats were significantly different showing a 38 more pronounced exponential growth during the first 20 days of life. 39 Conclusions: This evidence indicates that the human lung may be more plastic than 40 originally thought with alveolarization occurring well into adolescence. The first 20 days 41 of life in rats implies a growth curve that may relate more to prenatal growth in humans. 42 The data suggests that nonhuman primates are a better laboratory model for studies of 43 human postnatal lung growth than rats. 44 Word Count: 235 45
Elevated mast cell tryptase in cerebrospinal fluid of multiple sclerosis patients

Multiple sclerosis (MS) lesions are associated with infiltration of T lymphocytes and macrophages that appear to mediate myelin destruction and gliosis (scarring). Mast cells are located perivascularly in the brain, are juxtaposed to neurons, and have been shown to secrete vasoactive and inflammatory mediators in response to neuropeptides and direct nerve stimulation. Mast cells have been previously identified in MS lesions, are activated by myelin basic protein, and can participate in the regulation of blood–brain barrier permeability, as well as in myelin destruction. Here, cerebrospinal fluid from MS patients and controls with other neurologic diseases was assayed for histamine, its major metabolite methylhistamine, and the specific mast cell marker tryptase. Histamine and methylhistamine were not elevated in MS. However, the mast cell specific proteolytic enzyme tryptase was significantly elevated in MS, suggesting that mast cell activation may be involved in the pathophysiology of this disease.
Genomic Models of Short-Term Exposure Accurately Predict Long-Term Chemical Carcinogenicity and Identify Putative Mechanisms of Action

Background Despite an overall decrease in incidence of and mortality from cancer, about 40% of Americans will be diagnosed with the disease in their lifetime, and around 20% will die of it. Current approaches to test carcinogenic chemicals adopt the 2-year rodent bioassay, which is costly and time-consuming. As a result, fewer than 2% of the chemicals on the market have actually been tested. However, evidence accumulated to date suggests that gene expression profiles from model organisms exposed to chemical compounds reflect underlying mechanisms of action, and that these toxicogenomic models could be used in the prediction of chemical carcinogenicity. Results In this study, we used a rat-based microarray dataset from the NTP DrugMatrix Database to test the ability of toxicogenomics to model carcinogenicity. We analyzed 1,221 gene-expression profiles obtained from rats treated with 127 well-characterized compounds, including genotoxic and non-genotoxic carcinogens. We built a classifier that predicts a chemical's carcinogenic potential with an AUC of 0.78, and validated it on an independent dataset from the Japanese Toxicogenomics Project consisting of 2,065 profiles from 72 compounds. Finally, we identified differentially expressed genes associated with chemical carcinogenesis, and developed novel data-driven approaches for the molecular characterization of the response to chemical stressors. Conclusion Here, we validate a toxicogenomic approach to predict carcinogenicity and provide strong evidence that, with a larger set of compounds, we should be able to improve the sensitivity and specificity of the predictions. We found that the prediction of carcinogenicity is tissue-dependent and that the results also confirm and expand upon previous studies implicating DNA damage, the peroxisome proliferator-activated receptor, the aryl hydrocarbon receptor, and regenerative pathology in the response to carcinogen exposure.
White Epidermal Nevi at Birth in a Patient with Tuberous Sclerosis

We report a neonate who presented at birth with multiple, scattered, white macerated plaques. Punch biopsy confirmed epidermal nevi. At 3 months of age the patient presented with infantile spasms and, after full evaluation, was diagnosed with tuberous sclerosis complex (TSC). We suggest that physicians consider TSC in a neonate with epidermal nevi inconsistent with any described epidermal nevus syndrome.
Comparison of Goldmann and Schiotz tonometry in a community.

The Goldmann applanation tonometer, among clinical instruments presently available, may provide the most valid estimate of intraocular pressure in humans. Examination with this tonometer offers a promising method of collecting descriptive data on the frequency distribution of intraocular pressure. Accordingly, it is important to compare the field performance of Goldmann applanation tonometry with Schiotz indentation tonometry, since the Schiotz instrument has been used in most population studies. Such a comparison might also provide information of clinical interest. Since changes in posture are known to influence the level of ocular pressure, 1,2 a comparison of the Goldmann tonometer with the Schiotz tonometer should be made on subjects remaining in the same position. The Schiotz instrument performs properly only when oriented vertically, and accordingly, the supine-recumbent posture is an appropriate common position for a comparative study. One comparison of these instruments has been reported 1 in which both examinations were performed in
Low-loss sapphire waveguides for 75-110 GHz frequency range

Low-loss dielectric waveguides are promising for use instead of metal ones, but problems in transitions have to be overcome. A simple and effective structure made of a monocrystalline sapphire waveguide has been designed. Experimental results at 75-110 GHz indicate good matching with metal waveguides (VSWR /spl les/1.13) and low insertion loss (0.05-0.35 dB for 47 mm dielectric section).
High prevalence of metabolic syndrome and its correlates in two tribal populations of India and the impact of urbanization.

BACKGROUND AND OBJECTIVES Metabolic syndrome is one of the major causes of morbidity and mortality in the world. The prevalence of this syndrome is high among Asians, including Indians, and is rising, particularly with the adoption of a modernized life style. Whether traditional societies in India have a low prevalence and the extent to which a transition to a modern life style contributes to the increase in prevalence are unknown. To examine the role of environmental and genetic factors in metabolic syndrome we conducted a study in two sub-Himalayan tribal populations with shared ancestry (Toto and Bhutia). The Toto live exclusively in a rural area, whereas a section of the Bhutia has adopted a modern life style. METHODS Fasting (12 h) blood samples of Toto (n=258); rural Bhutia (n=75) and urban Bhutia (n=230) were collected, with written informed consent. Lipid profile, blood pressures, body fat and other anthropometric parameters were assessed. Criteria suggested by National Cholesterol Education Programme (NCEP) Adult Treatment Panel III (2001) were used for assessment of metabolic syndrome. RESULTS The prevalence of metabolic syndrome was high (about 30-50%) among the Bhutia, with no significant rural-urban difference. Among the Toto, though the prevalence of metabolic syndrome was low (about 4-9%), their lipid levels were alarmingly adverse (about 37-67% had low HDLcholesterol or high triglyceride levels). There was an additional adverse impact of adoption of urban life-styles (perhaps primarily mediated through dietary changes) on cardiovascular risk factors. INTERPRETATION AND CONCLUSION Our study suggested that metabolic syndrome and its correlates could be a major health problem even in traditional societies, indicating that this syndrome was not necessarily a result of modernization. Further, our study indicates that genetic factors that adversely affect the levels of such variables have long antiquities in Indian ethnic groups.
Synthetic Surfactant Based on Analogues of SP-B and SP-C Is Superior to Single-Peptide Surfactants in Ventilated Premature Rabbits

Background: Respiratory distress syndrome (RDS) is currently treated with surfactant preparations obtained from natural sources and attempts to develop equally active synthetic surfactants have been unsuccessful. One difference in composition is that naturally derived surfactants contain the two hydrophobic proteins SP-B and SP-C while synthetic preparations contain analogues of either SP-B or SP-C. It was recently shown that both SP-B and SP-C (or SP-C33, an SP-C analogue) are necessary to establish alveolar stability at end-expiration in a rabbit RDS model, as reflected by high lung gas volumes without application of positive end-expiratory pressure. Objectives: To study the efficacy of fully synthetic surfactants containing analogues of both SP-B and SP-C compared to surfactants with only one protein analogue. Methods: Premature newborn rabbits, treated with synthetic surfactants, were ventilated for 30 min without positive end-expiratory pressure. Tidal volumes as well as lung gas volumes at end-expiration were determined. Results: Treatment with 2% Mini-B (a short-cut version of SP-B) and 2% SP-C33, or its C-terminally truncated form SP-C30, in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol, 68:31 (w/w) resulted in median lung gas volumes of 8–9 ml/kg body weight, while animals treated with 2% Mini-B surfactant or 2% SP-C33/SP-C30 surfactant had lung gas volumes of 3–4 ml/kg, and those treated with Curosurf, a porcine surfactant, 15–17 ml/kg. In contrast, mixing SP-C33 with peptides with different distributions of positively charged and hydrophobic residues did not improve lung gas volumes. Conclusions: The data indicate that synthetic surfactants containing analogues of both SP-B and SP-C might be superior to single-peptide surfactants in the treatment of RDS.
Effects of Web‐based Career Identity Training for Stress Management among Japanese Nurses: A Randomized Control Trial

Job stress among hospital nurses is often high because of the high quantitative and qualitative nature of their workload. One of the main reasons is negative career identity (CI). Indeed, CI and the degree of role conflict in nurses has been found to be worse than in other occupations . CI is defined as the cognitive representation of self, derived from past work experiences, beliefs, values, attributes, and motives that define individuals in terms of their work roles . The reason for a relatively bad CI among Japanese nurses may be the low flexibility of the work style in Japanese hospitals. Many nurses desire to develop their professional skills and want their own careers to be compatible with their daily life-cycle . Methods reported for improving CI are similar to the methods used in career counseling, and should also be effective for use with Japanese nurses. Web-based training is comparatively low-cost and accessible compared to traditional classroom training. In fact, the effectiveness has been found to be the same as that of classroom training . In this study, to examine the effects of a web-based CI training program on nurses, changes in career identity and levels of job stress were examined among Japanese hospital nurses.