Miracle-dz/UniFAR-FTUs huggingface dataset:
Binding of 4(5)-[2-(4-Azido-2-nitroanilino)ethyl]imidazole to Histamine Receptors in Guinea Pig Cerebral Cortical Membranes 1

Abstract The interaction of 4(5)-[2-(4-azido-2-nitroanilino)ethyl]imidazole (AAH), a photolabile histamine receptor antagonist, with the binding of histamine, mepyramine, and tiotidine to guinea pig cerebral cortical membranes was examined to evaluate the specificity of AAH for histamine H1 and H2 receptors. Saturable, specific binding of [3H]histamine, [3H]mepyramine, and [3H]tiotidine to the membranes was observed. Competition assays were used to assess the relative affinity of AAH for H1- and H2-receptors. The rank order of IC50 values obtained was (most to least potent) (i) for competing with [3H]histamine binding: histamine > AAH ≫ mepyramine ≃ tiotidine; (ii) for competing with [3H]mepyramine binding: mepyramine ≫ AAH ≃ histamine > tiotidine; and (iii) for competing with [3H]tiotidine binding: tiotidine ≫ mepyramine > histamine ≃ AAH. The affinity of AAH for H1 receptors was ca. 14-fold greater than for H2 receptors. These findings support previous evidence obtained in isolated smooth muscle preparations that AAH shows H1-receptor selectivity as an antagonist.
Role of loose feathers on the development of feather pecking in laying hens

1. The effect of the presence of loose feathers (on the floor) on the behaviour and plumage condition of laying hens (Lohmann Silver, LS) was studied during the rearing and laying periods. 2. From one day old, 60 birds in each of 4 straw-bedded pens (n = 240 in total) with 6·5 birds/m2 were either kept under conventional rearing and management conditions (CT: control group with feathers on the floor; n = 120) or in pens from which the feathers were collected from the floor 4 times/week (FR: feathers removed; n = 120). Fifty birds from each of these 4 groups (n = 200 in total) were randomly selected at the age of 16 weeks and allocated to 4 identical pens in a poultry layer house (PH; with perches and 1/3 slatted floor) with access to an outside area (winter garden, WG) at a stocking density of 6 birds/m2 in both PH and WG. 3. Observations on feather pecking and other behaviours (feeding, drinking, preening, standing, sitting, foraging, moving and dust bathing) were carried out at 8 ages: 6, 10, 15 (rearing period), 20, 25, 30, 35 and 40 weeks (laying period). Feather scoring was carried out at 15, 32 and 39 weeks of age. 4. There were no differences in feather pecking rates, forms (gentle, severe and aggressive pecks) as well as in the plumage condition between groups at the end of the rearing period. 5. Birds in the FR group exhibited lower rates and less severe feather pecking during the laying period. Accordingly, birds in the control group had worse feather condition at 32 and 39 weeks of age. Feather pecking rates within groups were, in general, greater in the afternoon compared to the morning periods. Birds in the control group were more active in walking. 6. Wings, rump, tail and back were the main targets for feather pecking. The majority of feather pecking occurred on the floor (66%) followed by feeding area (26%), perches (4%) and slats (4%). 7. Our results suggest that loose feathers on the floor may play an important role in the development and severity of feather pecking behaviour in laying hens and support the hypothesis (McKeegan and Savory, 1999) that feather pecking can be viewed as redirected foraging behaviour.
The hemodynamic response to interictal epileptic discharges localizes the seizure‐onset zone

Intracranial electroencephalography (EEG), performed presurgically in patients with drug‐resistant and difficult‐to‐localize focal epilepsy, samples only a small fraction of brain tissue and thus requires strong hypotheses regarding the possible localization of the epileptogenic zone. EEG/fMRI (functional magnetic resonance imaging), a noninvasive tool resulting in hemodynamic responses, could contribute to the generation of these hypotheses. This study assessed how these responses, despite their interictal origin, predict the seizure‐onset zone (SOZ).
Isoflurane induces cognitive deficits in the Morris water maze task in rats

Background Postoperative cognitive dysfunction has been reported in young, middle-aged and elderly patients with greater incidence with increasing age. Neurocognitive deficits are associated with anaesthetic exposure in aged rodents but in younger adult animals the findings are inconsistent and in middle-aged animals they are unknown. We aimed to compare the effects of moderate duration isoflurane anaesthesia in 100% oxygen on Morris water maze performance in young adult and middle-aged rats. We hypothesised that isoflurane would have greater effects on learning and memory in middle-aged compared with young rats. Materials and methods Young adult (3 months, n = 25) and middle-aged (12 months, n = 20) male Sprague Dawley rats were assigned randomly to isoflurane exposure (1 minimum alveolar concentration, 4 h) or control conditions. Spatial learning (acquisition phase) and memory (probe trial) were tested in the Morris water maze 1 week after exposure. Middle-aged rats were retested in the probe trial 4 weeks after exposure for long-term memory retention. Latency to locate the hidden platform and time spent in the platform quadrant were compared between ages and treatments. Results Isoflurane did not affect acquisition of the water maze task in either age group. Isoflurane exposure induced a significant deficit in memory retention in young rats, but not middle-aged rats, in the probe trial 24 h after acquisition. Irrespective of treatment, middle-aged rats took longer to acquire the task than young rats. Four weeks after exposure, isoflurane-treated middle-aged rats showed no preference for target location, compared with sham-exposed rats which retained memory for previous platform location. Conclusion Isoflurane exposure impaired retention memory for platform location 1 week after exposure in young adult rats and resulted in a delayed although weak impairment at 4 weeks in middle-aged rats. The great variation in reported effects of isoflurane suggests a complex effect of this agent on memory which warrants further investigation.
Effects of Instructional Focus on Learning a Classical Ballet Movement, the Pirouette

This study investigated how changes in the focus of instruction might affect the learning by individuals who are not trained dancers of a complex classical ballet movement, the pirouette. Seventy-two volunteer college students were divided into six groups according to the focus of instruction: 1. head, 2. arms, 3. trunk, 4. knees, 5. feet, and 6. controls. In the acquisition phase, all groups performed 160 trials, over 2 consecutive days. At the beginning of each day, they received verbal instruction regarding some of the general principles involved in performance of the pirouette and viewed a video that illustrated those principles. Each group (head, arms, etc., exclusive of controls) was then given specific directions for controlling focus on its body part while performing the movement. After a week, all participants were asked to complete a retention test, with no additional instruction. The trials were videotaped with two cameras (frontally and laterally), and the results were analyzed by 10 specially trained examiners, utilizing Movement Pattern and Error of Performance measures. They revealed that all groups improved in the acquisition phase, and the improvement was maintained in the retention test. No differences were revealed between groups. It was concluded that generalized instruction in basic principles of the movement was more effective than focus on specific body parts in the teaching and learning of the pirouette.
Microalbuminuria three years after recovery from Escherichia coli O157 hemolytic uremic syndrome due to municipal water contamination.

BACKGROUND Knowledge of the long-term renal prognosis of diarrhea associated hemolytic uremic syndrome (HUS) is important for patient counseling and follow-up. However, estimates of long-term risk are highly variable, with previous studies not using a healthy control group. METHODS A municipal water system in the small rural town of Walkerton, Ontario, became contaminated with Escherichia coli O157:H7 in 2000. A cohort of 19 children who recovered from HUS was randomly age- and sex-matched to 38 children with no symptoms at the time of the outbreak. Both groups had detailed renal function testing 3 years after the outbreak, including a random urine albumin to creatinine, glomerular filtration rate estimated by Schwartz formula, and automated and manual blood pressure measurements. RESULTS There were no baseline differences between the groups with respect to age (mean 4.8 years, range 1 to 15), sex, or birth weight (mean 3.4 kg). In follow-up there were no differences between the groups in body surface area (mean 1.0 m(2)), or in the methods by which renal function was assessed. Compared to the group with no symptoms, patients with HUS demonstrated more microalbuminuria [32% vs. 5%, relative risk 4.8 (95% CI 1.1 to 22.0)], a nonsignificant trend toward lower GFR (124 vs. 134 mL/min per 1.73 m(2)), and no difference in blood pressure. CONCLUSION Children may demonstrate microalbuminuria 3 years after recovering from HUS. Longer follow-up is needed to determine if this finding has clinical relevance and utility.
In Vitro Permeation Screening of a New Formulation of Thiocolchicoside Containing Various Enhancers

Thiocolchicoside, a muscle relaxant agent with anti-inflammatory and analgesic actions, also is used topically for the treatment of muscular spasms and for rheumatologic, orthopedic, and traumatologic disorders. In this study, thiocolchicoside was formulated to use as foam to avoid contact with the afflicted area during the spreading phase. To enhance drug penetration, various enhancers were added to the base formulation. The tested enhancers were ethoxyethylendiglycol (Transcutol ®), highly purified phosphatidylcholine (Lipoid S20), capsaicin, propylene glycol dipelargonate (DPPG), and glycolysed ethoxylated glycerides (Labrafil M1944 CS). The transdermal absorption of the tested formulations containing enhancers, in comparison with base formulation, was evaluated in vitro through rat skin using standard Franz diffusion cells. Base formulation was found to have a higher permeation profile than the simple aqueous and hydroalcoholic solutions of the drug, meaning that the base formulation by itself enhances the drug permeation. Among the tested formulations, only the formulation containing DPPG/ethanol was found to be statistically different, showing an enhancement factor of 3.58. In the same experimental session, Muscoril ® ointment, the commercially available pharmaceutical product containing the same thiocolchicoside concentration (0.25%), also was tested. The formulation containing DPPG/ ethanol showed a 4.86 times increase of permeability constant in comparison with Muscoril ® ointment. The formulation containing DPPG/ethanol as an enhancer could be a good candidate for a new topical foam, considering its good characteristics of permeability and compliance.
Blood pressure-dependent and independent effects of agents that inhibit the renin–angiotensin system

Objectives To evaluate the blood pressure-dependent and independent effects of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) on major cardiovascular events. Methods Using data from 26 large-scale trials comparing an ACEI or an ARB with placebo or another drug class, meta-regression analyses were conducted in which treatment-specific relative risks for major cause-specific outcomes [stroke, major coronary heart disease (CHD) events and heart failure] were regressed against follow-up blood pressure differences. Results From a total of 146 838 individuals with high blood pressure or an elevated risk of cardiovascular disease, 22 666 major cardiovascular events were documented during follow-up. The analyses showed comparable blood pressure-dependent reductions in risk with ACEI and ARB (P ≥ 0.3 for all three outcomes). The analyses also showed that ACEI produced a blood pressure-independent reduction in the relative risk of CHD of approximately 9% (95% confidence interval 3–14%). No similar effect was detected for ARB, and there was some evidence of a difference between ACEI and ARB in this regard (P = 0.002). For both stroke and heart failure there was no evidence of any blood pressure-independent effects of either ACEI or ARB. Conclusion There are similar blood pressure-dependent effects of ACEI and ARB for the risks of stroke, CHD and heart failure. For ACEI, but not ARB, there is evidence of blood pressure-independent effects on the risk of major coronary disease events.
Gene-Based Pathogen Detection: Can We Use qPCR to Predict the Outcome of Diagnostic Metagenomics?

In microbial food safety, molecular methods such as quantitative PCR (qPCR) and next-generation sequencing (NGS) of bacterial isolates can potentially be replaced by diagnostic shotgun metagenomics. However, the methods for pre-analytical sample preparation are often optimized for qPCR, and do not necessarily perform equally well for qPCR and sequencing. The present study investigates, through screening of methods, whether qPCR can be used as an indicator for the optimization of sample preparation for NGS-based shotgun metagenomics with a diagnostic focus. This was used on human fecal samples spiked with 103 or 106 colony-forming units (CFU)/g Campylobacter jejuni, as well as porcine fecal samples spiked with 103 or 106 CFU/g Salmonella typhimurium. DNA was extracted from the samples using variations of two widely used kits. The following quality parameters were measured: DNA concentration, qPCR, DNA fragmentation during library preparation, amount of DNA available for sequencing, amount of sequencing data, distribution of data between samples in a batch, and data insert size; none showed any correlation with the target ratio of the spiking organism detected in sequencing data. Surprisingly, diagnostic metagenomics can have better detection sensitivity than qPCR for samples spiked with 103 CFU/g C. jejuni. The study also showed that qPCR and sequencing results may be different due to inhibition in one of the methods. In conclusion, qPCR cannot uncritically be used as an indicator for the optimization of sample preparation for diagnostic metagenomics.
United Kingdom Prospective Diabetes Study, 30: diabetic retinopathy at diagnosis of non-insulin-dependent diabetes mellitus and associated risk factors.

OBJECTIVES To report on the prevalence of retinopathy in patients with newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) and to evaluate the relationship of retinopathy to clinical and biochemical variables. DESIGN A multicenter, randomized, controlled clinical study of therapy in patients with NIDDM. SETTING AND PATIENTS Patients were part of the United Kingdom Prospective Diabetes Study, a 23-center study of 2964 white patients who had both eyes photographed and assessed. OUTCOME MEASURES The presence and severity of diabetic retinopathy were evaluated by sex, and the relationship of retinopathy to medical and biochemical parameters was assessed. RESULTS Retinopathy, defined as microaneurysms or worse lesions in at least 1 eye, was present in 39% of men and 35% of women. Marked retinopathy with cotton wool spots or intraretinal microvascular abnormalities was present in 8% of men and 4% of women. The severity of retinopathy was related in both sexes to higher fasting plasma glucose levels, higher systolic and diastolic blood pressure, lower serum insulin levels, and reduced beta-cell function. In addition, in men, increased alcohol consumption was related to increased severity of retinopathy, while leaner women had more severe eye lesions. Visual acuity was normal in most patients, but in men there was a trend for those with more severe retinal lesions to have worse visual acuity. CONCLUSIONS Diabetic retinopathy is common in patients with newly diagnosed NIDDM. Careful ophthalmic assessment at diagnosis is important.
Cortisol and Heart Rate Changes in First‐ and Fourth‐Time Donors

It is well‐known that during blood donation some subjects experience mild, moderate, or severe stress reactions. The frequency of these reactions is higher in first‐time donors than in experienced ones. However, hormonal variations might nevertheless be present in subjects who show no clinical reaction. Cortisol is the hormone classically involved in response to stress. The aim of this study was to evaluate cortisol behavior in blood donors who did not manifest clinical reaction. Cortisol was studied before and after the first and fourth blood donation in 20 blood donors, aged 25–45 years. Blood pressure and heart rate were also evaluated. Plasma cortisol concentrations decreased during the first (from 202.6±9.2 ng/ml at ‐15 min, to 147.5±8.0 ng/ml, at +30 min; p<0.001), but not during the fourth (142.5±7 ng/ml vs. 153.0±10.1 ng/ml) blood donation; blood pressure remained stable throughout donations, while the heart rate significantly decreased (from 78 to 68 beats/min; p<0.001) only during the first experience. The increased cortisol levels observed before the first donation are apparently due to emotional components, since they were not observed in experienced donors. We may conclude that blood donation per se is not a stressful event and that moderate stress, as suggested by the increased cortisol levels and heart rate at the first donation, is secondary to emotional rather than to physical factors and occurs during a never‐experienced‐before event.
Trends in door-to-balloon time and mortality in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.

BACKGROUND In patients with acute ST-elevation myocardial infarction (STEMI) who are undergoing percutaneous coronary intervention, current guidelines for reperfusion therapy recommend a door-to-balloon (DTB) time of less than 90 minutes. Considerable effort has focused on reducing DTB time with the assumption that a reduction in DTB time translates into a significant reduction in mortality; however, the clinical impact of this effort has not been evaluated. Therefore, our objective was to determine whether a decline in DTB time in patients with STEMI was associated with an improvement in clinical outcomes. METHODS We assessed the yearly trend in DTB time for 8771 patients with STEMI who were undergoing primary percutaneous coronary intervention from 2003 to 2008 as part of the Blue Cross Blue Shield of Michigan Cardiovascular Consortium and correlated it with trends in in-hospital mortality. Patients were stratified according to risk of death using a mortality model to evaluate whether patient risk factors affect the relationship between DTB time and mortality. RESULTS Median DTB time decreased each year from 113 minutes in 2003 to 76 minutes in 2008 (P < .001), and the percentage of patients who were revascularized with a DTB time of less than 90 minutes increased from 28.5% in 2003 to 67.2% in 2008 (P < .001). In-hospital mortality remained unchanged at 4.10% in 2003, 4.02% in 2004, 4.40% in 2005, 4.42% in 2006, 4.73% in 2007, and 3.62% in 2008 (P = .69). After the differences in baseline characteristics were adjusted for, there was no difference in the standardized mortality ratios (SMRs) across the study period (SMR, 1.00; 95% confidence interval [CI], 0.74-1.26 in 2003 compared with SMR, 0.95; 95% CI, 0.77-1.13 in 2008). CONCLUSIONS There has been a dramatic reduction in median DTB time and increased compliance with the related national guideline. Despite these improvements, in-hospital mortality was unchanged over the study period. Our results suggest that a successful implementation of efforts to reduce DTB time has not resulted in the expected survival benefit.
Crucial role of the sarcoplasmic reticulum in the developmental regulation of Ca2+ transients and contraction in cardiomyocytes derived from embryonic stem cells

In adult myocardium, excitation‐contraction coupling is critically regulated by sarcoplasmic reticulum (SR) Ca2+ release via type 2 ryanodine receptor (RyR2), but generally, it is believed that SR‐function is rudimentary in the fetal heart and in embryonic stem (ES) cell‐derived cardiomyocytes (ESCMs), a possible source for cell replacement therapies. This study used wild‐type (RyR2+/+) and RyR2 null (RyR2−/−) ESCMs as an in vitro model of cardiomyogenesis, together with pharmacological approaches and expression profiles of genes relevant for SR function, to elucidate the functional importance of RyR2 and SR on the regulation of Ca2+ transients and contraction during early cardiomyocyte development. During differentiation of RyR2+/+ ESCMs, SR function developed progressively with increased basal cytosolic free Ca2+ concentration ([Ca2+]i), enhanced frequency and amplitude, and decreased duration of Ca2+ transients that were inhibited by ryanodine and thapsigargin. These functional traits correlated with SR Ca2+ load and the expression of RyR2, SERCA2a, and phospholamban. RyR2−/− ESCMs, comparatively, demonstrated a significantly prolonged time‐to‐peak and reduced frequency of Ca2+ transients and contractions. β‐adrenergic stimulation of RyR2+/+ ESCMs increased the frequency and amplitude of Ca2+ transients with differentiation but was much weaker in RyR2−/− ESCMs. We conclude that functional SR and control of RyR2‐mediated SR Ca2+ release directly contribute to the spontaneous and β‐adrenergic receptor‐stimulated contraction of ESCMs, even at very immature stages of development.
Results of a Placebo-Controlled Study of the Metabolic Effects of the Addition of Metformin to Sulfonylurea-Treated Patients: Evidence for a central role of adipose tissue

OBJECTIVE To define the metabolic effects of metformin in the treatment of NIDDM and to evaluate potential mechanisms for its ability to improve glycemic control. RESEARCH DESIGN AND METHODS Sulfonylurea-treated patients, with inadequate glycemic control, were treated with metformin in either a placebo-controlled or open fashion. Measurements were made of 1) fasting and postprandial plasma glucose, insulin, and free fatty acid (FFA) concentrations; 2) glucose appearance and disappearance rates measured overnight with 3-[3H]glucose; and 3) plasma FFA concentrations during a 45-min infusion period at relatively low (∼ 60 pmol/l) insulin concentrations. RESULTS Mean ± SE hourly plasma glucose, insulin, and FFA concentrations were similar before and after treatment in the placebo group. In contrast, mean hourly plasma glucose concentrations were significantly lower (P < 0.005) after metformin treatment in both the placebo-controlled and open-label groups (−3.9 ± 1.0 and −4.4 ± 0.8 mmol/l, respectively). Similarly, day-long hourly FFA levels were lower (P < 0.005) following metformin in the placebo-controlled and open-label groups (−87 ± 35 and −136 ± 31 μmol/l, respectively). Plasma insulin concentrations did not change with treatment in any group. Overnight glucose turnover studies indicated that neither the rate of glucose appearance (hepatic glucose production) or glucose disappearance changed significantly with treatment in the placebo or metformin groups. Because plasma glucose concentration was much lower after metformin treatment, overnight glucose metabolic clearance rate was significantly (P < 0.001) lower in this group. Finally, plasma FFA concentrations in response to a low-dosage insulin infusion (5 mU · m−2 · min−1) were significantly lower after metformin as compared with the placebo-treated group (P < 0.001). CONCLUSIONS Metformin treatment was associated with significantly lower day-long plasma glucose and FFA concentrations. Although overnight hepatic glucose production was unchanged following treatment with metformin, the overnight glucose metabolic clearance rate significantly increased. Given these findings, it is suggested that at least part of the antihyperglycemic effect of metformin is due to an increase in glucose uptake, secondary to a decrease in release of FFA from adipose tissue, and lower circulating FFA concentrations.