Miracle-dz/UniFAR-FTUs huggingface dataset:
Subjected to Parliament

In `Sacrifice and the Transformation of the Animal Body into a Scientific Object' Michael Lynch (1988) explores how the animal body is transformed into a scientific object in the laboratory. How did the laboratory become a (relatively) closed space in which scientists, the experts, were delegated the task of negotiating and transforming the interpretative sense of the animal — from sentient beings to analytic objects — as tools in a scientific machinery? By exploring a parliamentary controversy on experimental medicine at the turn of the 20th century I argue that this depended on a reworking of the status of the animal body, as well as the status of the laboratory. Crucial to this was social theory; specifically, utilitarian reasoning. Thus, what we need to study — this paper argues — is not simply the ways in which the practices of annual experimentation were met with opposition and critiques, but also how these practices came to be culturally and politically accepted, and what this implied for science - society relations. In analysing this controversy, the author attends to recent turn to politics in STS and argue for the significance of studying conventional political sites such as `Parliament' and the role that social theory plays in renegotiating and remaking sites and objects.
Students Completing a Pediatric Clinical Clerkship in a Regional Center Perform as Well as Their Peers Training at a University Teaching Hospital … And They Liked It Better?

Background: Medical school size in Ontario is increasing. As some institutions cannot accommodate all medical students in the university-affiliated hospital, some students are completing the majority of their clinical rotations in a regional setting. Purpose: To determine whether the regional experience is equivalent to the more traditional tertiary care experience. Methods: Students' examination results and rotation evaluation forms were collected after completing a pediatrics rotation. Results from students completing most of the rotation in a regional setting were compared to those who remained in a tertiary care setting. Results: There was no difference between the two groups on their final examination. Students in the rural setting rated the rotation higher than the students in the university setting. Conclusion: A regional rotation eases the challenges of an increasing medical class size and provides an educationally appropriate rotation for a clinical clerk.
Scaring and Bullying People into Security Won't Work

Users will pay attention to reliable and credible indicators of risks they want to avoid. Security mechanisms with a high false positive rate undermine the credibility of security and train users to ignore them. We need more accurate detection and better security tools if we are to regain users' attention and respect, rather than scare, trick, and bully them into complying with security measures that obstruct human endeavors.
The Calculated Genetic Barrier for Antiretroviral Drug Resistance Substitutions Is Largely Similar for Different HIV-1 Subtypes

Background: The genetic barrier, defined as the number of mutations required to overcome drug-selective pressure, is an important factor for the development of HIV drug resistance. Because of high variability between subtypes, particular HIV-1 subtypes could have different genetic barriers for drug resistance substitutions. This study compared the genetic barrier between subtypes using some 2000 HIV-1 sequences (>600 of non-B subtype) isolated from anti-retroviral-naive patients in Europe. Methods: The genetic barrier was calculated as the sum of transitions (scored as 1) and/or transversions (2.5) required for evolution to any major drug resistance substitution. In addition, the number of minor protease substitutions was determined for every subtype. Results: Few dissimilarities were found. An increased genetic barrier was calculated for I82A (subtypes C and G), V108I (subtype G), V118I (subtype G), Q151M (subtypes D and F), L210W (subtypes C, F, G, and CRF02_AG), and P225H (subtype A) (P < 0.001 compared with subtype B). A decreased genetic barrier was found for I82T (subtypes C and G) and V106M (subtype C) (P < 0.001 vs subtype B). Conversely, minor protease substitutions differed extensively between subtypes. Conclusions: Based on the calculated genetic barrier, the rate of drug resistance development may be similar for different HIV-1 subtypes. Because of differences in minor protease substitutions, protease inhibitor resistance could be enhanced in particular subtypes once the relevant major substitutions are selected.
Protective effects of dietary chamomile tea on diabetic complications.

Matricaria chamomilla L. , known as "chamomile", has been used as an herbal tea or supplementary food all over the world. We investigated the effects of chamomile hot water extract and its major components on the prevention of hyperglycemia and the protection or improvement of diabetic complications in diabetes mellitus. Hot water extract, esculetin (3) and quercetin (7) have been found to show moderate inhibition of sucrase with IC50 values of 0.9 mg/mL and 72 and 71 microM, respectively. In a sucrose-loading test, the administration of esculetin (50 mg/kg body weight) fully suppressed hyperglycemia after 15 and 30 min, but the extract (500 mg/kg body weight) and quercetin (50 mg/kg body weight) were less effective. On the other hand, a long-term feed test (21 days) using a streptozotocin-induced rat diabetes model revealed that the same doses of extract and quercetin showed significant suppression of blood glucose levels. It was also found that these samples increased the liver glycogen levels. Moreover, chamomile extract showed potent inhibition against aldose reductase (ALR2), with an IC50 value of 16.9 microg/mL, and its components, umbelliferone (1), esculetin (3), luteolin (6), and quercetin (7), could significantly inhibit the accumulation of sorbitol in human erythrocytes. These results clearly suggested that daily consumption of chamomile tea with meals could contribute to the prevention of the progress of hyperglycemia and diabetic complications.
Regional‐ and Age‐Specific Neurochemical Alterations in Rats Rendered Microencephalic by Differentially Timed Gestational Methylazoxymethanol Treatment

Rats with different degrees of microencephaly were obtained by injecting pregnant mothers with methylazoxymethanol acetate (MAM) at gestational days 13.5 or 16.5. Specific markers for cholinergic (choline acetyltransferase, ChAT), GABAergic (glutamate decarboxylase, GAD), and glutamatergic (D‐3H aspartate high affinity uptake) neurons, were measured in several brain regions (cortex, hippocampus, anterior and posterior striatum, medial septum plus nucleus of the diagonal band, globus pallidus) in young and adult microencephalic rats. In adult rats born to mothers injected with MAM at gestational day 16.5 (G 16.5) ChAT level was increased in the cortex, hippocampus and striatum but decreased in the septal complex; GAD was decreased in the globus pallidus and, to a little extent, in the hippocampus while D‐3H aspartate uptake was decreased in the striatum. One month old rats belonging to the same group showed comparable differences with the exception of larger increase of ChAT in the cortex and striatum. In adult rats born from mothers injected with MAM at gestational day 13.5 (G13.5) differences in the cholinergic marker were in general less pronounced; GAD was not decreased in the globus pallidus and D‐3H aspartate uptake was unchanged in the striatum but significantly decreased in the hippocampus. The results are correlated with morphological brain alterations caused by differentially timed MAM treatment and with available information on the generation time of various neuronal populations. They show that the balance between different neurotransmitter systems can be experimentally altered and suggest that MAM treatment may provide an experimental tool for studying the development of this balance.
Sulfolobus acidocaldarius inorganic pyrophosphatase: Structure, thermostability, and effect of metal ion in an archael pyrophosphatase

The first crystal structure of an inorganic pyrophosphatase (S‐PPase) from an archaebacterium, the thermophile Sulfolobus acidocaldarius, has been solved by molecular replacement and refined to an R‐factor of 19.7% at 2.7 Å. S‐PPase is a D3 homohexameric protein with one Mg2+ per active site in a position similar to, but not identical with, the first activating metal in mesophilic pyrophosphatases (PPase). In mesophilic PPases, Asp65, Asp70, and Asp102 coordinate the Mg2+ while only Asp65 and Asp102 do in S‐PPase, and the Mg2+ moves by 0.7 Å. S‐PPase may therefore be deactivated at low temperature by mispositioning a key metal ion.
Variation of membrane properties in hair cells isolated from the turtle cochlea.

1. Hair cells were enzymatically isolated from identified regions of the turtle basilar papilla and studied with the patch‐electrode technique. The experimental aim was to relate the resonance properties seen during current injection to the membrane currents measured in the same cell under whole‐cell voltage clamp. 2. Solitary hair cells had resting potentials of about ‐50 mV, and produced a damped oscillation in membrane potential at the onset and termination of a small current step; the resonant frequency varied from 9 to 350 Hz between cells, and was correlated with the region of papilla from which a cell had been isolated. The inferred frequency map was consistent with the tonotopic arrangement described previously in the intact papilla. 3. Depolarizations from the resting potential under voltage clamp activated a large net outward current with a steep voltage dependence, and the steady‐state current‐voltage relationship was strongly rectified about the resting potential. Input resistances tended to be smaller in cells with higher resonant frequencies, although there was no concurrent variation in membrane area as inferred from the cell capacitance. 4. The kinetics of the outward current evoked by a small depolarizing step depended upon the resonant frequency, fo, of the hair cell, and were slower in low‐frequency cells. On repolarization to the resting potential the current decayed exponentially with a time constant that changed from 150 ms in the lowest‐frequency cell to less than 1 ms in the highest‐frequency one. The time constant was approximately proportional to 1/f0(2). 5. Following repolarization to different membrane potentials, the tail current was found to reverse around ‐80 mV, indicating that the outward current was due mainly to K+. 6. The outward current was abolished by extracellular application of 25 mM‐tetraethylammonium chloride (TEA), or on exchange of Cs+ for K+ in the intracellular medium filling the recording electrode, each experiment supporting the contention that K+ is the major current carrier. Such treatments also removed the oscillations in membrane potential evoked by imposed current steps. 7. Addition of TEA or intracellular perfusion with Cs+ also revealed a fast inward current with an ionic sensitivity consistent with its being carried by Ca2+. Like the K+ current, the Ca2+ current was activated by small depolarization from the resting potential, and over this voltage range it was about five to ten times smaller than the K+ current. Its activation was more rapid than the fastest outward currents in high‐frequency cells. (ABSTRACT TRUNCATED AT 400 WORDS)
Increased level of platelet microparticles in survivors of myocardial infarction

Platelet microparticles (PMPs) are highly procoagulant and might therefore be important in the pathogenesis of arterial thrombotic diseases. The aim of this study was to determine plasma levels of PMPs in survivors of myocardial infarction (MI) and their relation to activation of primary (sCD40L) and secondary (thrombin‐antithrombin (TAT) complexes) haemostasis. An observational, population‐based case control study was conducted in 61 MI patients 1–4 years after the MI and 61 age‐matched and sex‐matched healthy controls. PMPs were quantified using an immunoassay that discriminates between small and large PMPs. MI patients had significantly higher total PMPs (314.3 µg/L, 273.1–361.4 µg/L versus 225.8 µg/L, 168.8–273.1 µg/L, p = 0.009) (geometric mean and 95% CI) and larger PMPs (181.3 µg/L, 160.7–204.3 µg/L versus 134.3 µg/L, 104.6–174.9 µg/L) than controls. The differences between groups remained significant after adjustments for use of cardiovascular drugs, body mass index, blood pressure and serum lipids, but were weakened when smoking was included in the analysis. Multiple regression analysis revealed a significant independent association between large PMPs and plasma TAT and soluble CD40 ligand (sCD40L) in MI patients, but not in healthy controls. The independent association between large PMPs and thrombin generation supports the concept that formation of PMPs is important for increased coagulation activation in MI patients.
Reduced iC3b‐mediated phagocytotic capacity of pulmonary neutrophils in cystic fibrosis

Cystic fibrosis (CF) is characterized by a neutrophil‐dominated chronic inflammation of the airways with persistent infections. In order to investigate whether neutrophils contribute to an inadequacy in the pulmonary defence mechanism, the phagocytic activity of pulmonary and peripheral blood neutrophils from CF and non‐CF respiratory patients were compared. Neutrophils were isolated from both the blood and bronchoalveolar lavage fluid of 21 patients with CF (12 male, 9 female; mean age 7·5 years, range 0·25–16·4 years) and 17 non‐CF subjects (9 male, 8 female; mean age 5·4 years, range 0·2–13·1 years). The ex vivo phagocytic rate of normal pulmonary neutrophils to internalize zymosan particles opsonized with iC3b was faster than that of circulating neutrophils (P < 0·05), but the maximum capacity (9 particles/cell) was similar. In contrast, pulmonary neutrophils from patients with CF had a lower phagocytic capacity than circulating neutrophils either from the same patients or from normal subjects. This deficiency could not be attributed to (i) the cell surface density of CR3 (CD18/CD11b) receptors, which were not significantly different between the other groups (ii) the signalling ability of the CR3 receptors, using cytosolic free Ca2+ signalling as the receptor activity read‐out or (iii) a decrease in cellular ATP concentration. As CFTR was not detectable on neutrophils from any source by either histochemistry or Western blotting, it was concluded that the reduced phagocytic capacity was not the direct result of a CFTR mutation, but was attributed to a failure of neutrophil phagocytic priming during translocation into the CF lung.
Neurosurgery 1992-98 December 1994, Volume 35, Number 6 1104 Postmortem Magnetic Resonance Imaging of Experimental Spinal Cord Injury: Magnetic Resonance Findings versus In Vivo Functional Deficit

THE RELATIONSHIP BETWEEN the severity of the posttraumatic functional deficit and findings on magnetic resonance imaging (MRI) was investigated in a rat model of experimental spinal cord trauma. Thirty Sprague-Dawley rats were subjected to an identical, moderate, contusion injury of the spinal cord. Control animals underwent laminectomy without cord injury. The severity of the functional deficit was assessed with the Combined Behavioral Score (CBS). Animals were killed at 3, 7, 14, 21, or 28 days after injury, and the fixed, excised spinal cords were studied with MRI at 1.9 T. The lesion length was measured on sagittal spin-echo MRI. The lesion length measured on MRI was highly correlated with the CBS functional score ( = 0.56, P = 0.002). There were significant correlations between lesion length as determined by MRI and by histological morphometry ( r = 0.44, P = 0.02), between histological morphometric lesion length and CBS functional deficit ( r = 0.76, P < 0.001), and between the area of residual white matter at the lesion epicenter, determined by histological techniques, and the severity of functional deficit ( r = -0.59, P = 0.001). A qualitative estimate of the area of preserved white matter, derived from MRI, was significantly correlated with the severity of functional deficit ( r = 0.56, P = 0.006). A multiple regression of MRIdetermined lesion length and MRI estimate of residual white matter versus CBS explained more than 42% of the variability of the functional deficit among these animals subjected to the same weight drop injury. We conclude that MRI parameters are reliable predictors of the severity of neurological deficit in experimental spinal cord trauma.
Dual Nucleoside Reverse Transcriptase Inhibitor Therapy in the Combination Antiretroviral Therapy Era and Predictors of Discontinuation or Switch to Combination Antiretroviral Therapy

Background:Contrary to current HIV/AIDS management guidelines, and despite the arrival of potent combination antiretroviral therapy (cART) many years ago, some patients are still treated with dual nucleoside reverse transcriptase inhibitor (NRTI) regimens. Methods:We selected 5222 patients who received dual NRTI therapy for at least 6 months during 1998 to 2002, representing 9.9% of the 52,981 ARV-treated patients recorded in the French Hospital Database on HIV. Factors associated with switching to cART or with ARV discontinuation were identified by using Cox models. Results:The 3-year probabilities of switching to cART and of antiretroviral (ARV) drug discontinuation were 55.2% (95% confidence interval [CI]: 53.8 to 56.7) and 10.9% (95% CI: 10.1 to 11.8), respectively, whereas 1591 patients (30.5%) kept the dual NRTI therapy during all the study period. Place of birth and region of care did not influence the choice of treatment strategy. After adjustment, the likelihood of switching to cART was lower among women, intravenous drug users, and patients with an undetectable plasma viral load (pVL) on at least 1 occasion during follow-up; in contrast, it was higher among patients with AIDS and those with a low CD4 cell count at enrollment or at the last follow-up visit. The likelihood of ARV discontinuation was higher among women and intravenous drug users and lower among patients with a low CD4 cell count at inclusion or at the last follow-up visit and among patients with an undetectable pVL on at least 1 occasion during follow-up. The likelihood of switching to cART or discontinuing ARV drugs was higher among patients receiving zidovudine/zalcitabine or didanosine/stavudine than among those receiving zidovudine/lamivudine. Conclusions:In France, until recent years, some patients (mainly women and intravenous drug users) were still receiving dual NRTI therapy despite free access to care and to highly effective ARV regimens. Dual NRTI therapy is gradually being replaced by cART, although some patients with satisfactory immunovirologic status are discontinuing all ARV drugs.
Age, gender, and voided volume dependency of peak urinary flow rate and uroflowmetry nomogram in the Indian population

Objectives: The objective of this study was measurement of urine flow parameters by a non invasive urodynamic test. Variation of flow rates based on voided volume, age, and gender are described. Different nomograms are available for different populations and racial differences of urethral physiology are described. Currently, there has been no study from the Indian population on uroflow parameters. So the purpose of this study was to establish normal reference ranges of maximum and average flow rates, to see the influence of age, gender, and voided volume on flow rates, and to chart these values in the form of a nomogram. Methods: We evaluated 1,011 uroflowmetry tests in different age groups in a healthy population (healthy relatives of our patients) 16-50 year old males, >50 year old males, 5-15 year old children, and >15 year pre-menopausal and post-menopausal females. The uroflowmetry was done using the gravitimetric method. Flow chart parameters were analyzed and statistical calculations were used for drawing uroflow nomograms. Results: Qmax values in adult males were significantly higher than in the elderly and Qmax values in young females were significantly higher than in young males. Qmax values in males increased with age until 15 years old; followed by a slow decline until reaching 50 years old followed by a rapid decline after 50 years old even after correcting voided volume. Qmax values in females increased with age until they reached age 15 followed by decline in flow rate until a pre-menopausal age followed by no significant decline in post-menopausal females. Qmax values increased with voided volume until 700 cc followed by a plateau and decline. Conclusions: Qmax values more significantly correlated with age and voided volume than Qavg. Nomograms were drawn in centile form to provide normal reference ranges. Qmax values in our population were lower than described in literature. Patients with voided volume up to 50 ml could be evaluated with a nomogram.
Some neurochemical effects of amphetamine, methylamphetamine and p‐bromomethylamphetamine in the rat

1 Low doses of d‐amphetamine increased brain noradrenaline concentrations in the rat; doses greater than 5 mg/kg, however, caused a decrease. Methylamphetamine also showed this dual effect, but a reduction in brain noradrenaline concentration only occurred when doses greater than 10 mg/kg were administered. p‐Bromomethylamphetamine did not significantly reduce brain noradrenaline concentrations even at a dose of 60 mg/kg. The order of potency in reducing the concentration of noradrenaline correlated with the central stimulant effects; d‐amphetamine produced the greatest and p‐bromomethylamphetamine the least increase in motor activity. 2 d‐Amphetamine and d‐methylamphetamine potentiated the action of 4,α‐dimethyl‐m‐tyramine (H77/77) in depleting brain noradrenaline; the greatest potentiation was produced by d‐amphetamine. This suggests that the phenylethylamines may affect brain noradrenaline concentrations by acting on the reserpine resistant uptake mechanism. 3 Differences were found in the effect of the three drugs on brain dopamine concentrations; d‐amphetamine caused a decrease while p‐bromomethylamphetamine caused an increase. Methylamphetamine had no effect on the concentration of dopamine. Only p‐bromomethylamphetamine significantly reduced the depletion of brain dopamine concentrations caused by H77/77. 4 Methylamphetamine and p‐bromomethylamphetamine reduced the concentration of 5‐hydroxytryptamine (5‐HT) in the brain; administration of the same dose of d‐amphetamine did not change the concentration of 5‐HT. 5 Changes in the blood and brain concentrations of tyrosine and tryptophan, and in the concentration of γ‐amino‐n‐butyric acid in the brain could not be correlated with the changes observed in the concentrations of biogenic amines in the brain.
Disability Trends in Hong Kong Community-Dwelling Chinese Older Adults

Objective: This article examines the trends of disability in six activities of daily living (ADLs) among Hong Kong community-dwelling older adults during the period from 1996 to 2004 by using three independent cross-sectional surveys of representative samples. Method: Logistic regression was performed to assess the association between the year of survey and the presence of any ADL limitation with a wide range of covariates. Results: We found that older adults in 2004 were more likely to report ADL disability than their counterparts in 1996, and the results would remain valid after considering the prevalence of ADL disability in nursing home residents. In addition, we found that age, education, the use of proxy, and the presence of six medical conditions were significantly related to ADL limitation. Discussion: In general, public health efforts to prevent ADL limitation should be supported to reduce the demand for long-term care services in the coming decades.