Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of chronic administration of valproic acid to epileptic patients on coagulation tests and primary hemostasis

Valproic acid (VPA) is an antiepileptic drug that has been associated with impaired hemostasis and increased risk for postsurgical bleeding. However, the published reports provide controversial results. We measured parameters of primary hemostasis in VPA‐treated patients with epilepsy, focusing on adenosine nucleotide–dependent platelet responses, which play a central role in primary hemostasis. We enrolled 20 cases (epileptic patients receiving treatment with VPA) and 20 controls (12 epileptic patients receiving treatment with drugs different from VPA and 8 healthy subjects). Measurements included prothrombin time (PT), activated partial thromboplastin time (APTT), platelet count, platelet function analyzer (PFA)‐100 closure times, plasma von Willebrand factor levels, platelet content of ADP, ATP, and serotonin (all stored in platelet dense granules), and platelet shape change and aggregation induced by ADP and other platelet agonists, including the ATP analog α,β‐methylene‐ATP. The plasma concentration of VPA was in the therapeutic range in 17 patients and slightly above the upper limit in 3 patients. There were no statistically significant differences in any of the studied parameters in cases versus controls. Our thorough controlled study failed to show that chronic treatment with VPA induces significant abnormalities of coagulation and primary hemostasis. Therefore, VPA, when present in the circulation in the therapeutic range, does not impair hemostasis.
Service‐to‐service marketing: relationships between law firms and hospitals

Purpose – This paper aims to examine the key factors that facilitate the service to service (S2S) marketing relationships. Specifically, it aims to focus on the relationship between external counsels (law firms) and hospitals.Design/methodology/approach – The study uses exploratory research that comprised a series of interviews with the relevant parties.Findings – Reputation and word‐of‐word play roles in soliciting a firm to submit a proposal; advertisements seem to play no role. Furthermore, S2S marketing relationships occur over distinct and different phases and require a different set of facilitating factors.Research limitations/implications – As this was exploratory research conducted in the US, the results are not generalizable, nevertheless, they offer a unique insight into a kind of S2S marketing relationship, specifically between hospitals and law firms.Practical implications – Service providers who seek S2S marketing relationships should invest more in building and shoring‐up their reputation in.
Comparative Circulatory Effects of Isoproterenol and Dopamine in Lambs with Experimental Cyanotic Heart Disease

ABSTRACT: To determine whether the hemodynamic responses to adrenergic agonists are altered during chronic hypoxemia secondary to an intracardiac right to left shunt, we studied seven lambs with surgically created pulmonic stenosis and atrial septal defect and nine controls during infusions of isoproterenol at 0.1 and 0.5 μ/kg/min and dopamine at 5 and 20 μ/kg/min. Isoproterenol increased heart rate by 89 ± 17% in control but only 46 ± 6% in experimental lambs (p < 0.05). However, because resting heart rate was higher in experimental lambs (213 ± 7 versus 177 ± 12 beats/min, p < 0.05), maximal heart rates were similar (310 ± 7 versus 326 ± 6 beats/min; NS). Cardiac output increased during isoproterenol from 219 ± 20 to 425 ± 54 mL/min/kg in experimental lambs (p < 0.05) and, similarly, from 180 ± 20 to 425 ± 71 in controls (p < 0.05) (experimental versus control; NS). Dopamine also increased cardiac output similarly in both groups, at both doses, but without changing heart rate. Isoproterenol did not alter aortic oxygen saturation and increased systemic oxygen transport more than oxygean consumption. In contrast, dopamine at both doses decreased aortic oxygen saturation in experimental lambs (rest, 71 ± 2% versus dopamine, 59 ± 2%; p < 0.05). With dopamine, the increase in systemic oxygen transport was equalled by an increase in oxygen consumption. Thus, circulatory responses to isoproterenol are similar in lambs with experimental cyanotic heart disease and controls, although higher resting heart rate in the experimental lambs reduces chronotropic reserve. Circulatory responses to dopamine are different, mainly due to the decrease is oxygen saturation in the experimental lambs. Inasmuch as the oxygen cost/benefit ratio of adrenergk agonists may be altered by chronic hypoxemia and associated hemodynamic abnormalities, further evaluation of this ratio in hypoxemic human infants receiving these agents is indicated.
Vibroacoustic Analysis of Radial and Tangential Air-Gap Magnetic Forces in Permanent Magnet Synchronous Machines

This paper analyzes Maxwell tensor tangential and radial magnetic forces in permanent magnet synchronous machines in the no-load case. Using matrix notation in the complex domain, a simple expression of the Fourier harmonics of both radial and tangential forces is derived, including all space and time harmonics. These expressions prove that both the frequency content of cogging torque and zeroth-order radial forces are linked to the least common multiple between the stator slot number and the rotor poles number, and that the optimal pole arc to pole pitch ratio to reduce cogging torque is also optimal for the reduction of average radial magnetic forces. It is also shown that both the smallest non-zero spatial order of tangential and radial force harmonics are given by the greatest common divider of the number of slots and the number of poles. These results can be used during the design stage when choosing the pole and slot numbers combination. These analytical results are then compared with calculations using MANATEE vibroacoustic and electromagnetic simulation software. Finally, some variable speed acoustic noise simulations are carried out on three different designs to analyze the efficiency of different vibroacoustic design rules on the slot and pole numbers combination. An attempt to formulate a new vibroacoustic design rule choice is detailed. It is concluded that no simple analytical design rule can be used to evaluate noise and vibrations induced by magnetic forces, and that numerical simulation is necessary.
Identification of Yeasts Isolated from Poultry Meat

In an assessment of the potential role of yeasts in the spoilage of poultry meat, the population and species diversity of yeasts were determined on 50 commercial raw and processed chicken and turkey product samples. Initial populations (log_10 cfu/g) ranged from less than 0.1 to 2.9, and increased by the expiration date to 0.4 to 5.1, respectively. 145 of 152 isolates were identified as belonging to 12 species. Yarrowia lipolytica and Candida zeylanoides were predominant, accounting for 39% and 26% of the isolates, respectively. Six different species of basidiomycetous yeasts were determined representing 24% of the isolates. The ability of the predominant yeast species to grow at refrigeration temperatures and their proteolytic and lipolytic activies suggest that yeasts may play a more significant role than previously recognised in the spoilage of poultry products.
Reproducibility of Optic Disk Topographic Measurements with the Topcon ImageNet and the Heidelberg Retina Tomograph

Objective: To compare the reproducibility of optic disk measurements provided by an image analyzer and a scanning laser tomograph. Methods: Ten images of the same eye of 10 normal volunteers were taken with the Heidelberg Retina Tomograph and with the Topcon ImageNet. Intraclass correlation coefficient (ICC) and coefficient of variation (CV) were used to evaluate the reproducibility of the measurements. Results: Eleven parameters were analyzed with the Topcon ImageNet. Six parameters (55%) had ICC greater than 90%. Four parameters (36%) had CV less than 10%. Twelve parameters were evaluated with the Heidelberg Retina Tomograph. Nine parameters (75%) had ICC over 90%. Nine parameters (75%) had CV less than 10%. Conclusion: Both systems provided reproducible data. The optic disk parameters provided by the Heidelberg Retina Tomograph had a better reproducibility than those obtained from the Topcon ImageNet.
Trait Anger and the Metabolic Syndrome Predict Progression of Carotid Atherosclerosis in Healthy Middle-Aged Women

Objective: Hostility may predict coronary heart disease morbidity and mortality, as well as the metabolic syndrome. We tested to see if high levels of the attitudinal and emotional aspects of hostility lead to progression of carotid atherosclerosis in women and if the metabolic syndrome is a mediator of the association. Methods: Two hundred nine healthy women were followed during the perimenopausal and postmenopausal periods. Carotid artery ultrasound scans measured intima-media thickness (IMT) an average 7.4 (SD = 0.9, range 4.2–10.8) and 10.5 years (SD = 1.1, range = 6.9–13.0) after baseline. Hostility was measured at baseline and at the first carotid scan with Spielberger Trait Anger (being angry frequently) and Anger In (suppressing angry feelings) scales, and the Cook-Medley Hostility Inventory (hostile, cynical attitudes toward others). Metabolic syndrome was measured at the study entry and through the second carotid scan. Results: Baseline Trait Anger scores predicted an increase in IMT across 3 years (p < .05) and predicted the risk for developing the metabolic syndrome (p < .05). The risk for developing the metabolic syndrome, in turn, predicted an increase in IMT across 3 years (p < .05). Anger suppression and cynical attitudes were not associated with progression of carotid atherosclerosis. Conclusion: Anger predicts progression of carotid atherosclerosis, and the metabolic syndrome may mediate this association. Women who experience angry feelings frequently may benefit from interventions aimed at reducing anger and reducing the metabolic syndrome components early in the natural history of atherosclerosis. CHD = coronary heart disease; IMT = intima-media thickness; HWS = healthy women study; BP = blood pressure; DBP = diastolic blood pressure; SBP = systolic blood pressure; HDL-C = high-density lipoprotein cholesterol; ANCOVA = univariate analysis of covariance; RMSEA = root mean square error of approximation.
A new type of signal peptide: central role of a twin‐arginine motif in transfer signals for the delta pH‐dependent thylakoidal protein translocase.

The delta pH‐driven and Sec‐related thylakoidal protein translocases recognise distinct types of thylakoid transfer signal, yet all transfer signals resemble bacterial signal peptides in structural terms. Comparison of known transfer signals reveals a single concrete difference: signals for the delta pH‐dependent system contain a common twin‐arginine motif immediately before the hydrophobic region. We show that this motif is critical for the delta pH‐driven translocation process; substitution of the arg‐arg by gln‐gln or even arg‐lys totally blocks translocation across the thylakoid membrane, and replacement by lys‐arg reduces the rate of translocation by > 100‐fold. The targeting information in this type of signal thus differs fundamentally from that of bacterial signal peptides, where the required positive charge can be supplied by any basic amino acid. Insertion of a twin‐arg motif into a Sec‐dependent substrate does not alter the pathway followed but reduces translocation efficiency, suggesting that the motif may also repel the Sec‐type system. Other information must help to specify the choice of translocation mechanism, but this information is unlikely to reside in the hydrophobic region because substitution by a hydrophobic section from an integral membrane protein does not affect the translocation pathway.
Impaired protein synthesis induced by acute alcohol intoxication is associated with changes in eIF4E in muscle and eIF2B in liver.

BACKGROUND Acute alcohol intoxication in rats decreases protein synthesis in skeletal muscle and, to a lesser extent, in liver. The purpose of the present study was to examine potential mechanisms for the inhibitory effect of acute ethanol exposure. METHODS Rats were injected intraperitoneally with either ethanol (75 mmol/kg) or saline, and tissues were examined 2.5 hr later. Rates of protein synthesis in vivo were determined by [3H]phenylalanine incorporation into protein, and various eukaryotic initiation factors (eIFs) were quantitated by Western blot analysis to identify possible mechanisms for regulating translation. RESULTS Protein synthesis in gastrocnemius and liver was decreased (39% and 21%, respectively) after alcohol administration, compared with saline-injected control animals. Alcohol administration did not alter tissue RNA content but diminished translational efficiency in muscle (43%) and liver (24%). Hepatic eIF2B activity was decreased 24% in alcohol-treated rats, and this was associated with a 95% increase in eIF2alpha phosphorylation. However, alcohol did not alter the amount of 4E-binding protein 1 (4E-BP1) bound to eIF4E, cIF4E bound to eIF4G, or the phosphorylation state of either 4E-BP1 or eIF4E. In contrast to liver, neither eIF2B activity nor the phosphorylation of eIF2alpha was affected in muscle of alcohol-treated rats. However, acute alcohol intoxication increased binding of 4E-BP1 to eIF4E (113%), decreased the amount of cIF4E bound to cIF4G (81%), and decreased the amount of 4E-BP1 in the phosphorylated gamma-form (77%). The plasma concentrations of insulin and insulin-like growth factor-I were unchanged by alcohol, but muscle insulin-like growth factor-I messenger ribonucleic acid abundance was decreased 35%. CONCLUSIONS These data suggest that acute alcohol intoxication decreases translation initiation and protein synthesis in liver and muscle via different mechanisms. Changes in eIF2B appear to predominate in liver, whereas alterations in eIF4E availability appear more critical in skeletal muscle for controlling translation initiation.
Win 55212-2, a cannabinoid receptor agonist, attenuates leukocyte/endothelial interactions in an experimental autoimmune encephalomyelitis model

Multiple sclerosis (MS) is the most common of the immune demyelinating disorders of the central nervous system (C NS). Leukocyte/endothelial interactions are important steps in the progression of the disease and substances that interfere with these activities have been evaluated as potential therapeutic agents. C annabinoid receptor agonists have been shown to downregulate immune responses and there is preliminary evidence that they may slow the progress of MS. The purpo se of this investigation was to determine how cannabinoid recepto r agonists interfere with leukocyte rolling and adhesion. This was investigated in an experimental autoimmune encephalo myelitis (EAE) model using six to eight week old C 57BL/6 mice. Mouse myelin oligodendrocyte protein and pertussis toxin were used to induce EAE. WIN 55212-2, C B1 and C B2 antagonist were given. By use of in vivo intravital microscopy, leukocyte/endothelial interactio ns were evaluated via a cranial window implanted two days before. The results demonstrated that EAE increases leukocyte rolling and firm adhesion in the brain, and that this increased leukocyte/endothelial interactio n can be attenuated by administration of WIN 55212-2. Furthermore, use of the selective antagonists for the C B1 recepto r (SR 141716A) and the C B2 receptor (SR144528) in this study demonstrated that the cannabinoid’s inhibitory effects on leukocyte/endothelial interactions can be mediated by activating C B2 receptor.
The Impact of Group Music Therapy on Depression and Cognition in Elderly Persons With Dementia

Objective: The aims of this study were to determine the effectiveness of group music therapy for improving depression and delaying the deterioration of cognitive functions in elderly persons with dementia. Method: The study had a prospective, parallel-group design with permuted-block randomization. Older persons with dementia (N = 104) were randomly assigned to the experimental or control group. The experimental group received 12 sessions of group music therapy (two 30-min sessions per week for 6 weeks), and the control group received usual care. Data were collected 4 times: (1) 1 week before the intervention, (2) the 6th session of the intervention, (3) the 12th session of the intervention, and (4) 1 month after the final session. Results: Group music therapy reduced depression in persons with dementia. Improvements in depression occurred immediately after music therapy and were apparent throughout the course of therapy. The cortisol level did not significantly decrease after the group music therapy. Cognitive function significantly improved slightly at the 6th session, the 12th session, and 1 month after the sessions ended; in particular, short-term recall function improved. The group music therapy intervention had the greatest impact in subjects with mild and moderate dementia. Conclusion: The group music intervention is a noninvasive and inexpensive therapy that appeared to reduce elders’ depression. It also delayed the deterioration of cognitive functions, particularly short-term recall function. Group music therapy may be an appropriate intervention among elderly persons with mild and moderate dementia.
[Rosuvastatin improves myocardial function and arteriosclerosis plaque in patients with ST-segment elevation after acute myocardial infarction and percutaneous coronary intervention].

OBJECTIVE To evaluate the effect of rosuvastatin on the functions of the surviving myocardium and arteriosclerosis plaque in patients with ST-segment elevation after acute myocardial infarction (STEMI) and percutaneous coronary intervention (PCI). METHODS Sixty-five STEMI patients were randomized to receive 40 mg simvastatin (n=32) or 10 mg rosuvastatin (n=33) before sleep in addition to conventional medications. Before PCI and after the 12-month medications, the plasma levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) were measured, and echocardiography and (99)Tc(m)-MIBI single-photon emission computed tomography (SPECT) were performed to assess the therapeutic effects. RESULTS At the end of 12 months, the patients in simvastatin group showed significantly reduced total cholesterol, LDL-C, CRP, TNF-α, and (99)Tc(m)-MIBI uptake fraction. In rosuvastatin group, these reductions were even more obvious; the intima media thickness (IMT) of the common carotid artery was reduced significantly after a 12-month rosuvastatin therapy, but almost remained unchanged after simvastatin therapy. CONCLUSION Rosuvastatin therapy in addition to conventional medications can significantly reduce IMT and improve the functions of the surviving myocardium in patients with STEMI after PCI.
Multiple Transporters Affect the Disposition of Atorvastatin and Its Two Active Hydroxy Metabolites: Application of in Vitro and ex Situ Systems

Atorvastatin (ATV) is primarily metabolized by CYP3A in the liver to form two active hydroxy metabolites. Therefore, the sequential transport system governed by hepatic uptake and efflux transporters is important for the drug disposition and metabolism. Here, we assessed the interaction of ATV with hepatic uptake transporter organic anion transporting polypeptide (Oatp) and efflux transporter multidrug resistance associated protein 2 (MRP2/Mrp2) in vitro and ex situ using the isolated perfused rat liver (IPRL). Rifampicin (RIF) was chosen as an inhibitor for Oatp in both uptake and IPRL studies. Its inhibitory effects on MRP2 and metabolism were also tested using MRP2-overexpressing cells and rat microsomes, respectively. Our results indicate that RIF effectively inhibits the Oatp-mediated uptake of ATV and its metabolites. Inhibition on MRP2-mediated efflux of ATV was also observed at a high RIF concentration. Compared with ATV alone in the IPRL, the area under the curve(s) (AUC) of ATV was significantly increased by RIF, whereas the AUC of both metabolites were also increased in a concentration-dependent manner. However, the extent of metabolism was significantly reduced, as reflected by the reduced amounts of metabolites detected in RIF-treated livers. In conclusion, inhibition of Oatp-mediated uptake seems to be the major determinant for interaction between ATV and RIF. Metabolites of ATV were subject to Oatp-mediated uptake as well, suggesting that they undergo a similar disposition pathway as the parent drug. These data emphasize the relevance of uptake transporter as being one of the major players in hepatic drug elimination, even for substrates that undergo metabolism.
Spontaneous activity in the statoacoustic ganglion of the chicken embryo.

Statoacoustic ganglion cells in the mature bird include neurons that are responsive to sound (auditory) and those that are not (nonauditory). Those that are nonauditory have been shown to innervate an otolith organ, the macula lagena, whereas auditory neurons innervate the basilar papilla. In the present study, single-unit recordings of statoacoustic ganglion cells were made in embryonic (E19, mean = 19.2 days of incubation) and hatchling (P6-P14, mean = 8.6 days posthatch) chickens. Spontaneous activity from the two age groups was compared with developmental changes. Activity was evaluated for 47 auditory, 11 nonauditory, and 6 undefined eighth nerve neurons in embryos and 29 auditory, 26 nonauditory, and 1 undefined neurons in hatchlings. For auditory neurons, spontaneous activity displayed an irregular pattern [discharge interval coefficient of variation (CV) was >0.5, mean CV for embryos was 1.46 +/- 0.58 and for hatchlings was 1.02 +/- 0.25; means +/- SD]. Embryonic discharge rates ranged from 0.05 to 97.6 spikes per second (sp/s) for all neurons (mean 18.6 +/- 16.9 sp/s). Hatchling spontaneous rates ranged from 1.2 to 185.2 sp/s (mean 66.5 +/- 39.6 sp/s). Discharge rates were significantly higher for hatchlings (P < 0.001). Many embryonic auditory neurons displayed long silent periods between irregular bursts of neural activity, a feature not seen posthatch. All regular bursting discharge patterns were correlated with heart rate in both embryos and hatchlings. Preferred intervals were visible in the time interval histograms (TIHs) of only one embryonic neuron in contrast to 55% of the neurons in posthatch animals. Generally, the embryonic auditory TIH displayed a modified quasi-Poisson distribution. Nonauditory units generally displayed regular (CV <0.5) or irregular (CV >0.5) activity and Gaussian and modified-Gaussian TIHs. Long silent periods or bursting patterns were not a characteristic of embryonic nonauditory neurons. CV varied systematically as a function of discharge rate in nonauditory but not auditory primary afferents. Minimum spike intervals (dead time) and interval modes for auditory neurons were longer in embryos (dead time: embryos 2.88 +/- 6.85 ms; hatchlings 1.50 +/- 1.76 ms; modal intervals: embryo 10.09 +/- 22.50 ms, hatchling 3.54 +/- 3.29 ms). The results show that significant developmental changes occur in spontaneous activity between E19 and posthatch. It is likely that both presynaptic and postsynaptic changes in the neuroepithelium contribute to maturational refinements during this period of development.