Miracle-dz/UniFAR-FTUs huggingface dataset:
Propofol and Etomidate Depress Cortical, Thalamic, and Reticular Formation Neurons During Anesthetic-Induced Unconsciousness

BACKGROUND: The sites where anesthetics produce unconsciousness are not well understood. Likely sites include the cerebral cortex, thalamus, and reticular formation. We examined the effects of propofol and etomidate on neuronal function in the cortex, thalamus, and reticular formation in intact animals. METHODS: Five cats had a recording well and electroencephalogram screws placed under anesthesia. After a 5-day recovery period, the cats were repeatedly studied 3 to 4 times per week. Neuronal (single-unit) activity in the cerebral cortex (areas 7, 18 and 19), thalamus (ventral posterolateral and ventral posteromedial nuclei and medial geniculate body), and reticular formation (mesencephalic reticular nucleus and central tegmental field) was recorded before, during, and after infusion of either propofol or etomidate. Cortical neuronal action potentials were analyzed separately as either regular spiking neurons or fast spiking neurons. RESULTS: Propofol and etomidate decreased the spontaneous firing rate of cortical neurons by 37% to 41%; fast spiking neurons and regular spiking neurons were similarly affected by the anesthetics. The neuronal firing rate in the thalamus and reticular formation decreased 30% to 49% by propofol and etomidate. The electroencephalogram shifted from a low-amplitude, high-frequency pattern to a high-amplitude, low-frequency pattern during drug infusion suggesting an anesthetic effect; peak power occurred at 12 to 13 Hz during propofol infusion. There were 2 major peaks during etomidate anesthesia: one at 12 to 14 Hz and another at 7 to 8 Hz. The cats were heavily sedated, with depressed corneal and whisker reflexes; withdrawal to noxious stimulation remained intact. CONCLUSION: These data show that neurons in the cortex, thalamus, and reticular formation are similarly depressed by propofol and etomidate. Although anesthetic depression of neuronal activity likely contributes to anesthetic-induced unconsciousness, further work is needed to determine how anesthetic effects at these sites interact to produce unconsciousness.
Determination of lipoic acid, Trolox methyl ether and tocopherols in human plasma by liquid-chromatography and ion-trap tandem mass spectrometry.

A method for the simultaneous determination of lipoic acid and/or Trolox methyl ether, along with α-, γ- and δ-tocopherol was developed using liquid chromatography-tandem mass spectrometry with negative electrospray ionization (HPLC-ESI-MS/MS) in an ion-trap mass spectrometer. Detection and quantification were accomplished by a multiple reaction monitoring method, using specific transitions from precursor ion to product ion for each analyte. Chromatographic separation was achieved in a 12 min run using a C(18) -bonded phase and methanol-aqueous ammonium acetate elution gradient. Linear correlations of the chromatographic peak area (r.u. × s(-1) ) to the injected amount (ng) gave the slope values (r.u. × s(-1) × ng(-1) ) 2.34 × 10(4) for α-tocopherol, 5.05 × 10(4) for γ-tocopherol, 1.27 × 10(5) for δ-tocopherol, 8.86 × 10(5) for lipoic acid and 1.23 × 10(5) for Trolox methyl ether. The lower limit of quantification ranged between 0.02 and 1.22 ng for Trolox methyl ether and lipoic acid. MS(3) experiments of γ- and δ-tocopherol suggest ion-radical reactions and dependence of the tocopherol fragmentation pattern on the phenolic ring methylation degree. The method is shown to be applicable to measurement of these metabolites in human serum after extraction.
The Need for More Workshops in Laparoscopic Surgery and Surgical Anatomy for European Gynaecological Oncology Trainees: A Survey by the European Network of Young Gynaecological Oncologists

Objective The objective of this study was to highlight the relative preference of European gynecologic oncology trainees for workshops that could support and supplement their training needs. Methods A Web-based survey was sent to 900 trainees on the European Network of Young Gynaecological Oncologists database in November 2011. Respondents were asked to rate a 13-item questionnaire (using a 1- to 5-point Likert scale) on workshop topics they felt would most benefit their training requirements. Free text space for additional topics was also provided. Descriptive analysis was used to describe the mean scores reported for different items. A complete linkage hierarchical cluster analysis with Dendron plot was used to assess any clustering of data, and Cronbach &agr; was used to assess the internal reliability of the questionnaire. Results One hundred ninety trainees from 37 countries responded to the survey, giving a 21% response rate. The 3 most important topics reported were laparoscopic surgery; surgical anatomy, and imaging techniques in gynecologic oncology. The Dendron plot indicated 4 different clusters of workshops (research related skills, supportive ancillary skills, related nonsurgical subspecialties, and core surgical skills) reflecting different competencies trainees need to meet. There was no significant association between individual country of training and workshop preference. The mean duration of the workshop preferred by 71% of respondents was 2 days. Cronbach &agr; of the 13-item questionnaire was 0.78, which suggests good internal consistency/reliability. Conclusions This report for the first time highlights the relative importance and significance European trainees attach to some of their training needs in gynecologic oncology. Laparoscopic surgery, surgical anatomy, and imaging appear to be the 3 areas of greatest need. The European Society of Gynaecological Oncology, other national specialist societies, and institutions should direct additional training efforts at these areas.
rhEPO treatment of postpartum anemia

Postpartum hemorrhage is a continuing problem occurring in 5-10% of all deliveries. Due to recent problems with blood transfusion, heterologous blood is nowadays restricted to life-threatening indications. As a consequence the clinician is faced with many patients suffering from overt symptoms of anemia. We therefore investigated the effect of recombinant human erythropoietin (rhEPO) in combination with adequate iron supplementation as an alternative for blood transfusion in postpartum anemia. In a pilot study we could show that rhEPO can enhance the effect of endogenous erythropoietin on erythropoiesis. These data could be confirmed in a larger randomized trial. In another study we could show that rhEPO given s.c. is as effective as i.v. Measurement of the iron stores, however, demonstrated low values at the end of pregnancy indicating that iron is a limiting factor for erythropoiesis in postpartum anemia. In a next study i.v. iron combined with rhEPO showed a greater increase in Hb compared to i.v. iron alone. The chosen dose of i.v. iron, however, was too small as shown by the low ferritin levels. We concluded from these previous studies that rhEPO enhances endogenous erythropoiesis, but so far the effect was only slight (ca 1 g/dl within 14 days); all treated patients developed overt iron deficiency in terms of low ferritin levels despite oral and i.v. iron supplementation; no major side-effects were seen. A further study in healthy non pregnant volunteers demonstrated an effect on erythropoiesis lasting for 3-4 days after a single dose of 300 U/kg rhEPO. (ABSTRACT TRUNCATED AT 250 WORDS)
Fast neural networks for sub-matrix (object/face) detection

In recent years, fast neural networks for sub-matrix (object/face) detection have been introduced based on cross correlation in frequency domain between the input image and the weights of neural networks. In H. M. El-Bakry (2003), it has been proved that for those fast neural networks, either the weights of neural networks or the input image must be symmetric. In case of converting the input image into a symmetric one, those fast neural networks become slower than conventional neural networks. In this paper, a new form of symmetry for he input image to fast the operation of neural nets is presented. Simulation results using Matlab confirm the theoretical computations.
Impact of intracranial pressure monitoring on mortality in patients with traumatic brain injury: a systematic review and meta-analysis.

OBJECT Some studies have demonstrated that intracranial pressure (ICP) monitoring reduces the mortality of traumatic brain injury (TBI). But other studies have shown that ICP monitoring is associated with increased mortality. Thus, the authors performed a meta-analysis of studies comparing ICP monitoring with no ICP monitoring in patients who have suffered a TBI to determine if differences exist between these strategies with respect to mortality, intensive care unit (ICU) length of stay (LOS), and hospital LOS. METHODS The authors systematically searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (Central) from their inception to October 2013 for relevant studies. Randomized clinical trials and prospective cohort, retrospective observational cohort, and case-control studies that compared ICP monitoring with no ICP monitoring for the treatment of TBI were included in the analysis. Studies included had to report at least one point of mortality in an ICP monitoring group and a no-ICP monitoring group. Data were extracted for study characteristics, patient demographics, baseline characteristics, treatment details, and study outcomes. RESULTS A total of 14 studies including 24,792 patients were analyzed. The meta-analysis provides no evidence that ICP monitoring decreased the risk of death (pooled OR 0.93 [95% CI 0.77-1.11], p = 0.40). However, 7 of the studies including 12,944 patients were published after 2012 (January 2012 to October 2013), and they revealed that ICP monitoring was significantly associated with a greater decrease in mortality than no ICP monitoring (pooled OR 0.56 [95% CI 0.41-0.78], p = 0.0006). In addition, 7 of the studies conducted in North America showed no evidence that ICP monitoring decreased the risk of death, similar to the studies conducted in other regions. ICU LOSs were significantly longer for the group subjected to ICP monitoring (mean difference [MD] 0.29 [95% CI 0.21-0.37]; p < 0.00001). In the pooled data, the hospital LOS with ICP monitoring was also significantly longer than with no ICP monitoring (MD 0.21 [95% CI 0.04-0.37]; p = 0.01). CONCLUSIONS In this systematic review and meta-analysis of ICP monitoring studies, the authors found that the current clinical evidence does not indicate that ICP monitoring overall is significantly superior to no ICP monitoring in terms of the mortality of TBI patients. However, studies published after 2012 indicated a lower mortality in patients who underwent ICP monitoring.
Role of the intrinsic transglutaminase in the Ca2+-mediated crosslinking of erythrocyte proteins.

Transamidase (i.e., "transglutaminase") activity of human erythrocytes, lysed by a single freezing and thawing to 37 degrees, was measured by a method of incorporating [14C]putrescine into N,N'-dimethylcasein. In the absence of added calcium ions, virtually no enzyme activity could be detected. An increase in concentration of the cation to about 0.5 mM, however, turned on the enzyme to appreciable levels of activity. Simultaneously, Ca2+ produced formation of high molecular weight, nondisulfied bonded protein polymers either directly in the lysate or in fresh cells when the cation was added together with the A23187 ionophore. The polymers could be readily identified in the isolated cell ghosts by means of disc gel electrophoresis. If the Ca2+-promoted formation of polymers was allowed to take place in the presence of 14C-putrescine, then this tracer became incorporated into the polymeric material. The incorporation indicated that polymerization occurred through gamma-glutamyl-epsilon-lysine bridtes. It is suggested that the intrinsic transamidase mediates protein crosslinking of the erythrocyte membrane whenever there is an increase in intracellular Ca2+ concentration. The presence of suitable transglutaminase substrates, e.g. histamine, inhibited crosslinking when the cells were incubated with Ca2+ and ionophore.
Association between ALDH2 rs671 G>A polymorphism and gastric cancer susceptibility in Eastern Asia

To date, the relationship between the aldehyde dehydrogenases-2 (ALDH2) rs671 G>A (Glu504Lys) polymorphism and gastric cancer (GC) risk has not been thoroughly elucidated. To derive a more precise estimation of the effect of the ALDH2 rs671 G>A polymorphism on GC, we conducted this meta-analysis. We searched for qualified studies in the Embase, PubMed, Wang Fan and China National Knowledge Infrastructure databases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the association. A total of 6,421 GC patients and 8,832 control subjects were included in the present study. The pooled results indicated no significant relationship between the ALDH2 rs671 G>A polymorphism and GC susceptibility in all genetic models. A stratified analysis by country showed that the ALDH2 rs671 G>A polymorphism might be a risk factor for GC in Japan (Allele model: P unadjusted = 0.034; Dominant model: P unadjusted = 0.040); however, the result was nonsignificant when the Bonferroni correction and false discovery rate (FDR) were applied. In subgroup analyses by drinking status in the dominant model, our study revealed that the ALDH2 rs671 G>A polymorphism significantly increased the risk of GC for drinkers (dominant model: P < 0.001). No relationship between the ALDH2 rs671 G>A polymorphism and GC risk was observed in any other subgroup. Our present study indicated no association between the ALDH2 rs671 G>A polymorphism and GC risk in Eastern Asian populations. However, the ALDH2 rs671 G>A polymorphism can significantly increase GC risk for drinkers.
The relationship between shift work and mental health among electronics workers in South Korea: A cross-sectional study

Objective To determine the relationship between shift work and mental health, particularly insomnia, depression, and suicidal ideation, among electronics production workers. Methods A survey was conducted with 14,226 workers from an electronics manufacturer in South Korea. After excluding 112 individuals with incomplete responses, 14,114 respondents were analyzed. As part of a larger project, we collected data on respondents’ general characteristics, work-related characteristics, and health status; however, in this study, we focused on the data related to shift work and mental health. Insomnia, depression, and suicidal ideation were set as dependent variables and working schedule as set as the independent variable. We performed multiple logistic regression analysis with daytime workers as the reference group. The model was adjusted for age, gender, body mass index, workplace, educational level, and marital status with or without children under 6 years of age. Results Relative to daytime workers, shift workers had 2.35, 1.23, and 1.17 greater odds of insomnia, depression, and suicidal ideation, respectively. Within the shift worker group, we found that the odds of depression and suicidal ideation increased dramatically when respondents had insomnia. The ORs for depression and suicidal ideation were 4.899 and 7.934, respectively. Conclusions Our findings suggest that shift work is related to an increased risk of mental health problems in production workers, and the sleep disturbance related with shift work is a central mechanism for this relationship. Since these results suggest that proactive management of sleep problems might attenuate their detrimental effects on shift worker’s mental health.
Induction of Apoptosis and Inhibition of Cell Growth in Human Hepatocellular Carcinoma Cells by COX‐2 Inhibitors

Abstract: The aim of the present study was to examine the effects of nonselective (indomethacin) and selective cyclooxygenase‐2 (COX‐2) inhibitors (NS‐398, nimesulide, and CAY10404) on cell growth, cell cycle distribution, and apoptosis in three human hepatocellular carcinoma cell lines (HepG2, HuH‐6, and HA22T/VGH) with different characteristics of differentiation and biological behavior. The four COX inhibitors showed a dose‐dependent growth‐inhibitory effect in all the cell lines. No substantial arrests in the progression of the cells through the cell cycle were observed after treatment of HuH‐6 or HA22T/VGH for 48 h with the various inhibitors. On the other hand, there were significant increases in apoptosis, with the highest effect of cell kill being seen after treatment with indomethacin, especially in HuH‐6. Our findings support the suggestion that selective or, perhaps more efficiently, nonselective COX‐2 inhibitors may have potential therapeutic effects in hepatocellular carcinoma. Further studies must be carried out to better determine the possible mechanisms of these effects.
Solifenacin provides effective antimuscarinic therapy for the complete management of overactive bladder

Solifenacin is an antimuscarinic agent, administered once daily, which has been newly approved for the treatment of overactive bladder (OAB). Solifenacin administered at 5- and 10-mg once-daily doses shows efficacy for all the symptoms of OAB in both ‘wet’ and ‘dry’ patients, including improvements in patient quality of life and satisfaction. These improvements are observed as early as week 2 of treatment and are maintained over 12-week and 1-year time periods, without being compromised by the age or gender of the patient. Solifenacin demonstrates a favourable tolerability profile, with mild dry mouth as the most common adverse event associated with its use, both at the 5- and 10-mg doses; this allows for flexibility in the dosing regimen, in which physicians can administer solifenacin 5 mg, with the option to safely increase the dose to 10 mg if necessary based on the severity of patient’s symptoms. The favourable efficacy and safety profile of solifenacin, coupled with its dose flexibility, are consistent with solifenacin being a convenient treatment option for patients with OAB.
The Anti‐Ghrelin Spiegelmer NOX‐B11‐3 Blocks Ghrelin‐ but not Fasting‐Induced Neuronal Activation in the Hypothalamic Arcuate Nucleus

The hypothalamic arcuate nucleus (Arc) is the presumed target site for the orexigenic hormone ghrelin, which is secreted from the stomach during fasting. Ghrelin directly activates Arc neurones. Similar to exogenous ghrelin, overnight food deprivation also induces c‐Fos expression in the Arc of mice. In the present study, we tested the role of endogenous ghrelin in the fasting‐induced c‐Fos expression in the Arc of mice. We used NOX‐B11‐3, the latest generation of the recently developed ghrelin‐binding compounds, so‐called RNA Spiegelmers (SPM) to block endogenous ghrelin action during food deprivation. The specificity and potency of this compound was also tested in electrophysiological and immunohistological experiments. In electrophysiological in vitro single cell recordings, NOX‐B11‐3 effectively blocked the excitatory effect of ghrelin in the medial Arc (ArcM) of rats whereas the biologically inactive control SPM had no effect. Furthermore, NOX‐B11‐3 (15 mg/kg i.p.) potently suppressed ghrelin‐induced (25 µg/kg s.c., 12 h after SPM injection) c‐Fos expression in the Arc. However, when injected at the beginning of a 14‐h fasting period, the same dose of NOX‐B11‐3 had no effect on the c‐Fos expression in the Arc of mice. These results demonstrate that NOX‐B11‐3 is a long‐acting compound, which effectively blocks the effect of exogenous ghrelin on neuronal activity in the Arc under in vitro and in vivo conditions. Furthermore, increased ghrelin signalling does not appear to be a necessary factor for the activation of Arc neurones during food deprivation or other fasting‐related signals might have masked or compensated for the loss of the ghrelin effect.
Estimation of competitive antagonist affinity from functional inhibition curves using the Gaddum, Schild and Cheng‐Prusoíf equations

1 The estimation of antagonist affinity from functional experiments in which the effect of a fixed agonist concentration is reduced by a range of antagonist concentrations (‘functional inhibition curves’) has been considered from both a theoretical and experimental viewpoint. 2 Theoretical predictions are compared with results obtained from the stimulation of [35S]‐GTPγS binding by acetylcholine to membranes of Chinese hamster ovary (CHO) cells stably transfected with human m1–m4 muscarinic receptors, and inhibition of the stimulated binding by pirenzepine and AQ‐RA 741. 3 The usual procedure of applying the Cheng‐Prusoff correction is shown to be theoretically invalid, and predictions are made of the size and distribution of errors associated with this procedure. 4 A different procedure for estimating antagonist affinity, using the principles of dose‐ratio analysis and analogous to use of the Gaddum equation, is found to be accurate and theoretically valid. 5 A novel method of analysis allows accurate estimation of both antagonist affinity and Schild slope, by fitting the combined data from an antagonist inhibition curve and an agonist activation curve directly to a form of the Schild equation (derived by Waud) using non‐linear regression analysis. 6 It is shown that the conventional Schild analysis can be enhanced by treating part of the data as a family of inhibition curves and including in the Schild plot dose‐ratios estimated from the inhibition curves.
Endothelin Release and Shift in Prostaglandin Balance Are Involved in the Modulation of Vascular Tone by Recombinant Erythropoietin

Summary: Hypertension is the main side effect developing in patients suffering from renal anemia who are treated with recombinant human erythropoietin (rhEPO). We investigated the effect of rhEPO on the vascular tone of rabbit aorta. rhEPO had no direct vasoconstrictor effect, but it enhanced norepinephrine (NE)‐induced contractions of rabbit aortic rings. Relaxations to acetylcholine (ACh, 1 μM) were unaltered in the presence or absence of rhEPO, indicating that the endothelium‐dependent NO pathway was not affected by rhEPO. In rings of human renal artery and rabbit aorta, rhEPO (200 U/ml) increased the synthesis of constrictor prostanoids. The cyclooxygenase inhibitors indomethacin and aspirin abolished the increase in prostanoid production. However, they did not completely suppress the rhEPO‐induced enhancement of NE contractions in rabbit aorta. We further investigated the effect of rhEPO on prostanoid and endothelin‐1 synthesis in cultured human endothelial cells. Endothelial cells from human umbilical veins (HUVEC) were isolated and cultured. After incubation with rhEPO, the formation of prostaglandin (PG) I2 (analyzed as its stable metabolite 6‐keto‐PGF1&agr;), PGF2&agr;, PGE2, thromboxane (Tx) B2, and of endothelin‐1 (ET‐1) was measured by radioimmunoassay (RIA). rhEPO (200 U/ml) increased the formation of PGF2&agr; and TxB2 and decreased the formation of PGI2 in HUVEC. The release of ET‐1 was increased by nearly 90% in the presence of rhEPO (200 U/ml). We conclude that a shift in the balance of constrictor and relaxing prostanoids as well as an increased synthesis of ET‐1 may contribute to the hypertensive side effect of rhEPO therapy. ET‐1 may at least in part be responsible for the unexpectedly low inhibitory effect of indomethacin on rhEPO‐enhanced contractions of rabbit aorta.