Miracle-dz/UniFAR-FTUs huggingface dataset:
Integration of in vitro neurotoxicity data with biokinetic modelling for the estimation of in vivo neurotoxicity

Risk assessment of neurotoxicity is mainly based on in vivo exposure, followed by tests on behaviour, physiology and pathology. In this study, an attempt to estimate lowest observed neurotoxic doses after single or repeated dose exposure was performed. Differentiated human neuroblastoma SH-SY5Y cells were exposed to acrylamide, lindane, parathion, paraoxon, phenytoin, diazepam or caffeine for 72 hours. The effects on protein synthesis and intracellular free Ca2 + concentration were studied as physiological endpoints. Voltage operated Ca2 + channel function, acetylcholine receptor function and neurite degenerative effects were investigated as neurospecific endpoints for excitability, cholinergic signal transduction and axonopathy, respectively. The general cytotoxicity, determined as the total cellular protein levels after the 72 hours exposure period, was used for comparison to the specific endpoints and for estimation of acute lethality. The lowest concentration that induced 20% effect (EC 20) obtained for each compound, was used as a surrogate for the lowest neurotoxic level (LOEL) at the target site in vivo. The LOELs were integrated with data on adsorption, distribution, metabolism and excretion of the compounds in physiologically-based biokinetic (PBBK) models of the rat and the lowest observed effective doses (LOEDs) were estimated for the test compounds. A good correlation was observed between the estimated LOEDs and experimental LOEDs found in literature for rat for all test compounds, except for diazepam. However, when using in vitro data from the literature on diazepam's effect on gamma-amino butyric acid (GABA)A receptor function for the estimation of LOED, the correlation between the estimated and experimental LOEDs was improved from a 10 000-fold to a 10-fold difference. Our results indicate that it is possible to estimate LOEDs by integrating in vitro toxicity data as surrogates for lowest observed target tissue levels with PBBK models, provided that some knowledge about toxic mechanisms is known. Human & Experimental Toxicology (2007) 26, 333—338
Accessing External Technological Knowledge for Technological Development: When Technological Knowledge Distance Meets Slack Resources

This study elucidates how a firm accesses external technological knowledge (TK) and utilizes such TK, facilitated by slack resources, to determine the scope of technological development. We examine data from 947 cooperative technology agreements among 248 electronics and information technology firms in Taiwan. The results demonstrate that there is an inverted U-shaped relationship between TK distance and the scope of technological development. Furthermore, we find that the moderating effect of unabsorbed slack can extend the inverted U-shaped relationship in the direction of higher levels of technological diversification and greater TK distance. Additionally, unabsorbed and absorbed slack, respectively, moderate the linear relationship between TK distance and a firm's scope of technological development toward two striking favorable contrasts: technological diversification and specialization. Unabsorbed slack plays a positive catalytic role in the creation of technological diversification; however, absorbed slack does not serve such a role.
Cigarette smoking and the risk of development of lens opacities. The Framingham studies.

OBJECTIVE To examine the association between cigarette smoking and the incidence of nuclear and non-nuclear lens opacities in members of the Framingham Eye Study Cohort. PARTICIPANTS AND METHODS Eye examinations were conducted on surviving members of the Framingham Heart Study Cohort from 1973 to 1975 (Framingham Eye Study I) and again from 1986 to 1989 (Framingham Eye Study II). Smoking data, collected biennially since 1948 in the Heart Study, were used to examine the relationship between cigarette smoking and the incidence of lens opacities. Two thousand six hundred seventy-five persons were examined in the Framingham Eye Study I. Our analysis included 660 persons, aged 52 to 80 years, who were free of lens opacities at the first eye examination. RESULTS During the approximately 12.5 years between eye examinations, lens opacities developed in a total of 381 persons, with nuclear opacities constituting the most frequent type. In logistic regression analyses that controlled for age, sex, education, and diabetes, a significant positive association with increasing duration of smoking and number of cigarettes smoked daily was found for nuclear lens opacities, alone or in combination (test for trend, P < or = .002), but not for nonnuclear opacities (test for trend, P = .62). Among the heavier smokers (persons who smoked > or = 20 cigarettes per day according to 6 or more biennial Framingham Heart Study examinations), 77% were still smoking at the time of the first eye examination. Persons who smoked 20 or more cigarettes per day at the time of the first eye examination were at substantially increased risk for the development of nuclear opacities than nonsmokers (odds ratio, 2.84; 95% confidence interval, 1.46-5.51). There was no apparent excess risk for persons with nonnuclear lens opacities (odds ratio, 1.42; 95% confidence interval, 0.65-3.07). CONCLUSION This study provides further evidence that cigarette smokers have an increased risk of developing nuclear lens opacities. The risk was greatest for heavier smokers, who tended to be current smokers and who smoked more cigarettes and for a longer duration.
Characteristics of a nontreatment-seeking sample of over-the-counter codeine users: implications for intervention and prevention.

OBJECTIVES Recently, there has been considerable policy and public interest in the availability of over-the-counter (OTC) codeine. Case reports demonstrating severe harm from OTC codeine have been published. However, few studies have examined how people use these products and who develops dependence. The aim of this study was to better understand who develops problematic use of OTC codeine. DESIGN AND SETTING The authors conducted a web-based survey with people who self-reported OTC codeine use. Eight hundred participants completed the survey that examined codeine use and dependence, pain, and general physical and mental health. RESULTS Codeine-dependent people differed from nondependent codeine users on a range of characteristics. They were younger, had lower levels of employment and education, and were more likely to report family history of substance dependence. They were more likely to have taken well above recommended doses of OTC codeine and have taken codeine for considerably longer periods of time than recommended. Codeine-dependent people in this study differed markedly from other populations of opioid-dependent people recruited to research in Australia and were more similar to the general population, suggesting that a web-based survey may have reached an under-researched population of opioid-dependent people. CONCLUSIONS How best to use these findings to identify at-risk OTC codeine users requires consideration. Approaches aimed at reducing harm from prescription opioids may be difficult to implement in pharmacy settings. Implications for pharmacists and other health professionals are discussed.
Alzheimer’s Disease And Inflammation: A Review Of Cellular And Therapeutic Mechanisms

1. Of the neurodegenerative diseases that cause dementia, Alzheimer’s disease (AD) is the most common. Three major pathologies characterize the disease: senile plaques, neurofibrillary tangles and inflammation. We review the literature on events contributing to the inflammation and the treatments thought to target this pathology.
[Occupational exposure to glutaraldehyde during its use in chemical disinfection of endoscopes].

BACKGROUND To evaluate the air pollution experimentally produced by different solutions of glutaraldehyde due to the activity of chemical disinfection in a flexible endoscopy unit. METHODS The glutaraldehyde environment concentrations due to the use of 3 solutions (2% solution and its 1:5 and 1:20 dilutions) were measured by liquid chromatography after sampling on specific cartridges and by fotoacoustic method. RESULTS Only after the use of the most concentrated solution it was possible to detect glutaraldehyde in the environment air, with values between 0.2 and 0.3 mg/m3 and during specific activities such as after shaking the disinfecting solutions. CONCLUSIONS When the usual preventive recommendations are respected, the use of 1:5 and 1:20 solution of 2% glutaraldehyde products does not produce air concentrations of the aldehyde exceeding the current, even restrictive, limits proposed by industrial hygienists.
Event-related potentials (ERP) and SGIP1 gene polymorphisms in alcoholics: relation to family history of alcoholism and drug usage.

OBJECTIVE The electrophysiological characteristics may serve as valuable biomarkers for the genetic vulnerability underlying alcoholism. The purpose of this study was to evaluate the potential associations between single nucleotide polymorphisms (SNPs) located in the SGIP1 gene and the theta ERP quantitative traits. METHOD The theta band (4-7 Hz) visual ERP occurring in the P300 response in the resting EEG were examined to explore the electrophysiological effects of alcohol on the brain in five regions: frontal, central, parietal, temporal and occipital in patients with alcohol addiction. In addition, we tested the potential associations between single nucleotide polymorphisms (SNPs) located in the SGIP1 gene and ERP quantitative traits. RESULTS We found that the amplitude of the auditory P300 response differed considerably among groups of alcoholics in the frontal, central and temporal areas of the brain and it was lower in the studied brain regions in alcoholics in comparison to non-alcoholics. However, among subjects in the young adult group (GR-1) there was no statistical difference in amplitude of P300 response with control subjects in all studied brain regions in comparison with non-alcoholics. Moreover, we revealed that SNP rs10889635 had a significant effect on P300 amplitude in the central and temporal regions. The reduced P300 amplitude was in AA carriers in comparison to both carriers of GG and GA alleles. CONCLUSION The present study demonstrated a possible association of target P300 evoked theta and of alcohol dependence with SNPs from the gene SGIP1 in the region of rs10889635, but further studies are required.
Gastric regurgitation during general anaesthesia in different positions with the laryngeal mask airway

Ninety patients, divided into three groups of 30, were investigated to determine the incidence of gastric regurgitation during general anaesthesia administered via the laryngeal mask airway in the supine, Trendelenburg and lithotomy positions. Fifteen minutes before induction of anaesthesia each patient swallowed a 75mg methylene blue capsule. At the end of surgery, the LMA and the oropharynx were inspected for bluish discoloration which was considered to be a sign of gastric regurgitation. No blue dye was detected in the supine group but it was observed in one patient in each of the other two groups.
Task-Technology Fit and Individual Performance

A key concern in Information Systems (IS) research has been to better understand the linkage between information systems and individual performance. The research reported in this study has two primary objectives: (1) to propose a comprehensive theoretical model that incorporates valuable insights from two complementary streams of research, and (2) to empirically test the core of the model. At the heart of the new model is the assertion that for an information technology to have a positive impact on individual performance, the technology: (1) must be utilized and (2) must be a good fit with the tasks it supports. This new model is moderately supported by an analysis of data from over 600 individuals in two companies. This research highlights the importance of the fit between technologies and users' tasks in achieving individual performance impacts from information technology. It also suggests that task-technology fit when decomposed into its more detailed components, could be the basis for a strong diagnostic tool to evaluate whether information systems and services in a given organization are meeting user needs.
Hyperthyroidism and Hepatic Dysfunction: A Case Series Analysis

Liver dysfunction in hyperthyroid patients has not been well characterized. We analyzed the clinical records of 43 patients with hyperthyroidism to define the spectrum of clinical and liver test abnormalities. The patients were divided into three categories: (a) 18 patients with uncomplicated hyperthyroidism (HT) (b) 19 with hyperthyroidism and congestive heart failure (HT/CHF), and (c) 6 with hyperthyroidism and concomitant unrelated liver disease (HT/ULD). Hepatomegaly and/or spenomegaly were noted in 15 of 19 (79%) patients with HT/CHF as compared to 6 of 18 (33%) patients with HT and 3 of 6 (50%) patients with HT/ULD. Four patients with HT/CHF had ascites. Serum aminotransferase levels > 250 IU/L were noted in only 1 of 37 (3%) patients without unrelated liver disease. Patients with HT/ULD or HT/CHF had markedly low prothrombin time. Serum bilirubin levels as high as 323 $mUM were noted in patients with HT. No characteristic liver histology due to hyperthyroidism was noted. Severe liver test abnormalities, including deep jaundice and prolonged prothrombin time, can occur in patients with hyperthyroidism alone or with HT/CHF. This makes the diagnosis of concomitant, unrelated liver disease difficult until the hyperthyroidism has been controlled.
Diverse Basis of β-Catenin Activation in Human Hepatocellular Carcinoma: Implications in Biology and Prognosis

Aim β-catenin signaling is a major oncogenic pathway in hepatocellular carcinoma (HCC). Since β-catenin phosphorylation by glycogen synthase kinase 3β (GSK3β) and casein kinase 1ε (CK1ε) results in its degradation, mutations affecting these phosphorylation sites cause β-catenin stabilization. However, the relevance of missense mutations in non-phosphorylation sites in exon 3 remains unclear. The current study explores significance of such mutations in addition to addressing the clinical and biological implications of β-catenin activation in human HCC. Methods Gene alteration in exon3 of CTNNB1, gene expression of β-catenin targets such as glutamate synthetase (GS), axin2, lect2 and regucalcin (RGN), and protein expression of β-catenin were examined in 125 human HCC tissues. Results Sixteen patients (12.8%) showed conventional missense mutations affecting codons 33, 37, 41, and 45. Fifteen additional patients (12.0%) had other missense mutations in codon 32, 34, and 35. Induction of exon3 mutation caused described β-catenin target gene upregulation in HCC cell line. Interestingly, conventional and non-phosphorylation site mutations were equally associated with upregulation of β-catenin target genes. Nuclear localization of β-catenin was associated with poor overall survival (p = 0.0461). Of these patients with nuclear β-catenin localization, loss of described β-catenin target gene upregulation showed significant poorer overall survival than others (p = 0.0001). Conclusion This study suggests that both conventional and other missense mutations in exon 3 of CTNNB1 lead to β-catenin activation in human HCC. Additionally, the mechanism of nuclear β-catenin localization without upregulation of described β-catenin target genes might be of clinical importance depending on distinct mechanism.
Prevalence of Escherichia coli O157:H7 in White-tailed Deer from Louisiana

Escherichia coli O157:H7 (EC O157) is an important zoonosis. White-tailed deer (Odocoileus virginianus) have been implicated in transmission of this bacterium to humans and have been suggested as reservoirs that might affect carriage in cattle populations. Our study objectives were to estimate prevalence of EC O157 in feces of hunter-harvested deer and to describe fecal shedding patterns in a captive herd sampled over 1 yr. Prevalence of EC O157 in hunter-harvested deer was 0.3% (n=338). In August 2001, EC O157 was detected in one of 55 deer (1.8%) from the captive herd. Prevalence over the 1-yr period was 0.4% (n=226). Escherichia coli O157:H7 was rarely isolated from hunter-harvested deer during the winter. We could not describe a seasonal shedding pattern based on one positive sample in the captive herd. These data do not support a prominent role of deer as a reservoir for EC O157 for cattle or humans.
beta-Lactamase detection in nine staphylococcal species

Detection of beta-lactamase by four different techniques (two acidometric, one chromogenic cephalosporin, and one iodometric) was evaluated with 79 isolates of nine different species of staphylococci. Overall, each technique detected more positive isolates when beta-lactamase production had been induced with oxacillin before testing, and each technique performed equally well when organisms were tested after induction.
Serum selenium and the risk of cancer, by specific sites: case-control analysis of prospective data.

From 1971 to 1975, serum specimens were obtained from 6,860 men of Japanese ancestry in Hawaii. Since then, the following numbers of newly diagnosed cases with epithelial cancer have been identified: 82 colon, 71 lung, 66 stomach, 32 rectum, and 29 urinary bladder. The stored sera of the 280 cases and of 293 randomly selected controls were tested to determine their levels of selenium. There was no association of serum selenium with lung, stomach, or rectal cancer. An increase in relative risk (RR) was noted only for subjects in the lowest quintile of selenium values, as compared to the RR for subjects in the highest quintile, for colon (RR = 1.8) and urinary bladder cancer (RR = 3.1), but neither of these RR estimates was statistically significant (P = .09 and P = .07, respectively). Further work is needed to determine whether the antioxidant properties of selenium protect against specific types of cancer.
The Measurement of Fatigue and Chronic Fatigue Syndrome

to poorer perception and judgement. Reduced channel capacity (limiting the amount of information which can be handled at one time) makes it increasingly difficult to perform complex manoeuvres such as efficient judging of entry into a busy roundabout and, at the same time, needing to be aware of warning and direction signs. O'Neil et al., in this issue (p 199), draw attention to the special problem ofpatients with signs of dementia continuing to drive in spite of getting lost, and having accidents. Concerned carers reported examples of impaired driving ability like driving the wrong way round roundabouts, up the wrong lane of a dual carriageway and through neighbour's front gardens. The effects of an accident in terms of the injury caused also change with age. For a given impact an older person will more commonly suffer a fracture or other serious trauma and a given injury is more likely to cause death; the curves for injuries and for fatalities thus rise with age even more steeply than for accident involvement. The Automobile Association (AA) recently sponsored a questionnaire study of the views of current elderly drivers. Many of them recognized increasing difficulty with coping with traffic. They were not, however, commonly aware of difficulty at junctions though this is a more frequent site for their accidents than for younger drivers. Many had made sensible modifications to driving habits-reducing night driving, for instance and planning journeys to avoid heavy traffic. Many recognized that at some time they would have to give up driving and to a large extent would rely on their family doctor to advise them when the time had come. The occasion of the routine health assessment of older patients could be a good opportunity for doctors to give such advice. Medical Aspects ofFitness to Drive, published by the Medical Commission on Accident Prevention (MCAP)l, contains useful advice in dealing with potentially difficult doctor/patient relationships which may arise. There remains, however, scope for advice from relatives and friends, as well as the family doctor, as described in the booklet Helping the Older Driver2 produced by the MCAP and the AA. It would be helpful to know more about the circumstances and reasons which cause people to give up driving. Drivers may recognize that they have lost their confidence, relatives may be concerned about safety, the doctor may give advice or the licence may be withdrawn following an accident. The …
Running head : CONCEPTUALIZATION AND TREATMENT 1 Depression Prevention , Conceptualization , and Treatment through Adlerian Psychotherapy

Numerous biographies and historical accounts describe Abraham Lincoln as a very somber, melancholy individual. Psychologists and historians postulate that Lincoln would have been diagnosed today with clinical depression. In the present study Lincoln’s history and symptoms are explained from the perspective of Adlerian therapy, which has been supported for the treatment of depression through previous studies. The current study also designs a treatment plan that could theoretically treat the symptoms of Lincoln by applying Adlerian techniques. From the information available about Lincoln’s life and mental health, Adlerian psychotherapy effectively describes the depression of Abraham Lincoln. In addition, depression prevention techniques are explored and applied to use in Abraham Lincoln’s case. Out of the options, CB intervention programs are very effective in preventing depression.
Regulatory Dependence and Scientific Advisory Boards

The Food and Drug Administration (FDA) uses scientific procedures to evaluate regulated firms' new product applications. Much of its basic intellectual resources, in the form of scientific advisory committee members, come from research institutions. Regulated firms may seek connections to the FDA advisory committee members to affect the regulatory approval process. However, individual linkages may fail. The use of Scientific Advisory Boards (SAB) with multiple members provides redundant ties to the regulator, which means that the failure of each tie becomes less material. This paper is principally concerned with the firm's motivation to rebalance power imbalances rather than any actual regulatory outcomes. Controlling for alternative explanations, I find that dependence on the regulator is positively associated with the probability of having a SAB. Selected network diagrams add credibility to the hypothesis.