Miracle-dz/UniFAR-FTUs huggingface dataset:
Diabetes Mellitus Reduces the Antiarrhythmic Effect of Ion Channel Blockers

We designed the present study to examine whether diabetes mellitus affects the antiarrhythmic effect of flecainide, a sodium channel blocker, E-4031, a potassium channel blocker, and verapamil, a calcium channel blocker, in diabetic rats. The experiments were performed in intact and diabetic rats 2, 4, and 6 wk after administration of streptozotocin. Rats were anesthetized with halothane and monitored continuously for arterial blood pressure and premature ventricular contractions. The arrhythmogenic dose of epinephrine was defined as the smallest dose producing 3 or more premature ventricular contractions within a 15-s period. The arrhythmogenic doses of epinephrine in the presence of flecainide were 8.2 ± 2.2 (mean ± sd), 7.4 ± 6.1, 5.5 ± 2.8, and 2.0 ± 0.5 &mgr;g/kg in intact and diabetic rats 2, 4, and 6 wk after streptozotocin administration, respectively. Similarly, the arrhythmogenic doses of epinephrine in the presence of E-4031 were 7.7 ± 2.6, 2.3 ± 0.7, 2.0 ± 0.7, and 1.2 ± 0.5 &mgr;g/kg, and those in the presence of verapamil were 8.2 ± 2.1, 3.1 ± 1.2, 2.3 ± 0.9, and 1.5 ± 0.5 &mgr;g/kg. Insulin partially recovered the antiarrhythmic effect of the blockers. We concluded that diabetes mellitus reduces the antiarrhythmic effects of flecainide, E-4031, and verapamil.
Timing of X-chromosome inactivation in postimplantation mouse embryos.

SUMMARY The onset of X-chromosome inactivation was investigated cytologically in postimplanta- tion female mouse embryos of age 5£, 6\ and 1\ days post-coitum (d.p.c.) and in the isolated epiblasts of 6 d.p.c. embryos before primitive streak formation using a heat/hypotonic technique to reveal the inactive X chromosome by differentially dark staining with Giemsa. The results indicate that X inactivation has taken place in all the cells of the so-called ' un- differentiated' epiblast by 6 d.p.c. before primitive streak formation. Further evidence is presented to suggest that X inactivation is complete in all cells of the mouse embryo by 5i d.p.c.
What do attending physicians contribute in a house officer-based ambulatory continuity clinic?

OBJECTIVE: To study the educational contributions of attending physicians in an internal medicine house staff ambulatory clinic.DESIGN: Cross-sectional, self-administered survey.SETTING: University-affiliated general internal medicine practice.PATIENTS/PARTICIPANTS: Internal medicine residents and attendings.MEASUREMENTS AND MAIN RESULTS: Attending and resident perceptions of whether attendings made contributions to teaching points, diagnosis (DX), therapy (RX), and health care maintenance (HCM) were assessed in 428 patient encounters. Resident assessments significantly exceeded attending self-assessments of contributions to teaching points (82% vs 74%, P=.001), DX (44% vs 34%, P=.001), RX (61% vs 55%, P=.02), and HCM (19% vs 15%, P=.04). Both residents and attendings perceived that contributions declined progressively with increasing resident year (P<.05). Primary care and categorical residents assessed attending contributions comparably. However, attendings perceived contributing more to RX and HCM for categorical residents than primary care (P<.05). Male and female residents assessed attending contributions comparably. However, attendings perceived contributing generally more to DX in male residents than female (P=.003). In 8% of encounters, either residents or attendings felt that patient evaluation by the attending was needed. In these encounters with personal patient evaluation by attendings, both residents and attendings felt that attendings made more contributions to DX (P=.001) and teaching points than in other encounters.CONCLUSIONS: Attending physicians consistently underestimate their perceived contributions to house officer ambulatory teaching. Their personal patient evaluation increases assistance with DX and teaching points. Given perceived declining contributions by training year, attendings may need to identify other teaching strategies for interactions with senior residents.
The Associations of Naturalistic Classic Psychedelic Use, Mystical Experience, and Creative Problem Solving

ABSTRACT Developing methods for improving creativity is of broad interest. Classic psychedelics may enhance creativity; however, the underlying mechanisms of action are unknown. This study was designed to assess whether a relationship exists between naturalistic classic psychedelic use and heightened creative problem-solving ability and if so, whether this is mediated by lifetime mystical experience. Participants (N = 68) completed a survey battery assessing lifetime mystical experience and circumstances surrounding the most memorable experience. They were then administered a functional fixedness task in which faster completion times indicate greater creative problem-solving ability. Participants reporting classic psychedelic use concurrent with mystical experience (n = 11) exhibited significantly faster times on the functional fixedness task (Cohen’s d = –.87; large effect) and significantly greater lifetime mystical experience (Cohen’s d = .93; large effect) than participants not reporting classic psychedelic use concurrent with mystical experience. However, lifetime mystical experience was unrelated to completion times on the functional fixedness task (standardized β = –.06), and was therefore not a significant mediator. Classic psychedelic use may increase creativity independent of its effects on mystical experience. Maximizing the likelihood of mystical experience may need not be a goal of psychedelic interventions designed to boost creativity.
High-Affinity Interactions between Peptides and Heat Shock Protein 70 Augment CD8+ T Lymphocyte Immune Responses

Exogenously delivered antigenic peptides complexed to heat shock proteins (HSPs) are able to enter the endogenous Ag-processing pathway and prime CD8+ CTL. It was determined previously that a hybrid peptide containing a MHC class I-binding epitope and HSP70-binding sequence Javelin (J0) in complex with HSP70 could induce cytotoxic T cell responses in vivo that were more robust than those induced by the minimal epitope complexed with HSP70. The present study introduces a novel, higher-affinity HSP70-binding sequence (J1) that significantly enhances binding of various antigenic peptides to HSP70. A competition binding assay revealed a dissociation constant that was 15-fold lower for the H2-Kb OVA epitope SIINFEKL-J1 compared with SIINFEKL-J0, indicating a substantially higher affinity for HSP70. Further, modifying the orientation of the hybrid epitope and introducing a cleavable linker sequence between the Javelin and the epitope results in even greater immunogenicity, presumably by greater efficiency of epitope processing. The enhanced immunogenicity associated with Javelin J1 and the cleavable linker is consistently observed with multiple mouse and human epitopes. Thus, by creating a series of epitopes with uniform, high-affinity binding to HSP70, successful multiple epitope immunizations are possible, with equal delivery of each antigenic epitope to the immune system via HSP70. These modified epitopes have the potential for creating successful multivalent vaccines for immunotherapy of both infectious disease and cancer.
Effects of gamma‐aminobutyric acid on isolated cone photoreceptors of the turtle retina.

Isolated cones dissociated from the retina of the freshwater turtle were voltage clamped using a single 'patch' pipette electrode. gamma‐Aminobutyric acid (GABA) applied ionophoretically to the axon terminal evoked an inward current in cells held at ‐66 mV when they were recorded with patch pipettes filled with the 'control' pipette solution containing 120 mM‐Cl‐. Polarity of the GABA‐induced current reversed near 0 mV when examined with the pipette filled with the control pipette solution. The reversal potential depended strongly on both external and intrapipette Cl‐ concentrations ([Cl‐]o, and [Cl‐]p). The reversal potential agreed with the equilibrium potential for Cl‐ calculated by the Nernst equation with given [Cl‐]o and [Cl‐]p. The reversal potential was not affected by concentrations of either external Na or K ions. Voltage responses evoked by GABA were hyperpolarizing from its resting level of about ‐50 mV immediately after the rupture of the patch membrane. The response polarity reversed into depolarization in a few seconds when [Cl‐]p was greater than 24 mM, while hyperpolarizing responses persisted when [Cl‐]p was less than 12 mM. Thus, the intracellular Cl‐ concentration of undisturbed isolated cones was estimated to be between 12 and 24 mM. Cones were desensitized to GABA in the presence of GABA (greater than 100 nM) in the medium, or by a prolonged ionophoretic application. The maximum reduction in response amplitude was about 70% in both experiments. Muscimol was as potent as GABA, while beta‐p‐chlorophenyl‐GABA (baclofen) was ineffective even at 100 microM. GABA was antagonized by bicuculline competitively, and by picrotoxin non‐competitively. These observations suggest that turtle cones have GABAA receptors which associate with chloride channels. The present results suggest that GABA, presumably released continuously from monophasic horizontal cells in the dark, would exert a tonic hyperpolarization in red‐sensitive and green‐sensitive cones. Suppression by light of tonic GABA release would depolarize these types of cones by disinhibition. Disinhibitory depolarization in cones may contribute to the centre surround antagonism in retinal neurones, and to the biphasic colour responses recorded in a subtype of horizontal cells.
A new species of Margaromantis Piza, 1982 (Insecta: Mantodea) from Brazil

Abstract A second species of the Neotropical mantid genus Margaromantis Piza, 1982, Margaromantis nigrolineata sp. n. is described from Bahia, Brazil. This new species can be recognized by the presence of a transverse black strip between compound eyes in the vertex; fore femora exhibiting black calluses on the inner face; lacking yellowish strips over the transverse veins on the metathoracic wings; left dorsal phallomere with rectangular ventral lamina, elongated and grooved lateral process, and a flattened, but not twisted apical process that is upwardly recurved.
Mouse Vα14i natural killer T cells are resistant to cytokine polarization in vivo

Under different circumstances, natural killer T (NKT) cells can cause a T helper (Th) 1 or a Th2 polarization of immune responses. We show here, however, that mouse NKT cells with an invariant Vα14 rearrangement (Vα14i NKT cells) rapidly produce both IL-4 and IFN-γ, and this pattern could not be altered by methods that polarize naive CD4+ T cells. Surprisingly, although cytokine protein was detected only after activation, resting Vα14i NKT cells contained IL-4 and IFN-γ mRNAs. Despite this finding, in vivo priming of mice with the glycolipid antigen recognized by Vα14i NKT cells resulted in a more Th2-oriented response upon antigen re-exposure. The Vα14i NKT cells from primed mice retain the ability to produce IL-4 and IFN-γ, but they are less effective at activating NK cells to produce IFN-γ. Our data therefore indicate that Vα14i NKT cells have a relatively inflexible immediate cytokine response, but that changes in their ability to induce IFN-γ secretion by NK cells may determine the extent to which they promote Th1 responses.
Peripartum cardiomyopathy in Turkey: Experience of three tertiary centres

We conducted this study to determine demographic details, and clinical presentations in patients with peripartum cardiomyopathy (PPCMP) of Turkish origin. The study population consisted of 58 patients with PPCMP treated at 3 major hospitals in Turkey, retrospectively. In this study, demographic details and initial echocardiographic data were recorded and long-term clinical status was evaluated. The mean age for the patient cohort was 31.47 ± 6.31 years. Thirty-eight patients (73.1%) were multigravida and seven patients had multifetal pregnancy (13.7%). The mean follow-up left ventricular (LV) ejection fraction increased from 31 ± 7 to 38 ± 19. A minority of patients were defined as improvers according to our pre-specified criteria. The average survival period after diagnosis of PPCMP was 20.66 ± 14.44 months. Initial values for LV end-diastolic diameter and urea were higher in the deceased patients compared with the surviving patients, respectively. Twenty-eight (48%) patients with PPCMP showed improvement in the follow-up period. Of the 58 PPCMP patients, 9 (15%) died during a mean follow-up of 32 ± 22 months.
The gastro‐œsophageal ‘sphincter’ and the mechanism of regurgitation

IN 1719 Helvetius wrote a description of a morphological sphincter at the cardio-oesophageal junction and so started a controversy which has continued to the present day. The persisting division of modern anatomical opinion is illustrated by the reports of Lendrum (1937), who dissected 150 esophagi and denies that a sphincter exists, and of Lerche (1950) who studied roo specimens and is convinced that the structure described by Helvetius is an anatomical fact. Amongst those who believe in the presence of an inherent sphincter are Hurst ( I ~ I I ) , Farsell (1912)~ and Abel (1929), but even they do not agree on its exact site. Other workers, unimpressed by the evidence for an intrinsic sphincter, have looked elsewhere for a mechanism which would explain the sphincteric properties of the cardia. Chevalier Jackson (1922) claimed that the diaphragm exerts a pinch-cock effect on the esophagus and this view has been widely accepted. Dick and Hurst (1942) and Negus (1946) support the belief that the cesophagus enters the stomach in such a manner as to form a flap-valve between its left lip and the fundus. Finally, Payne and Poulton (1927) have suggested that the lower end of the oesophagus possesses sphincteric action even though no distinct morphological structure can be displayed. The controversy has arisen because of the need to account for the functions of the cardio-oesophageal junction in limiting regurgitation and delaying the entry of esophageal contents into the stomach. The problem also concerns the clinician who is interested because of the syndromes which result from disorder of these functions. In the early years of this century attention was particularly directed towards the disorder of emptying which resulted in dilatation and elongation of the gullet. The theories of spasm (cardiospasm) and failure of relaxation (achalasia) were expounded and these in turn started their controversies. During the past decade a great deal has been said and written about gastrocesophageal regurgitation. Arising largely from the influence of Allison, the importance of sliding hiatus hernia in causing esophagitis, through acidregurgitation, has become generally known and the clinical recognition of the condition is now commonplace. It is the purpose of this essay to report certain experimental and clinical observations which cast some light on the cardio-esophageal mechanism. True to the current trend, this work is chiefly concerned with regurgitation, particularly regurgitation in the absence of gross pathological abnormality.
Live Now ‐ Pay by Ageing: High Performance Mitochondrial Activity in Youth and its Age‐Related Side Effects

Radical oxygen species are a byproduct of normal energy metabolism in mitochondria. The short‐lived radicals cause damage to their immediate surrounding, i.e. the mitochondria. While most of this damage will be removed by normal mitochondrial turnover, damage to mitochondrial DNA (mtDNA) can persist and may accumulate with age. Recent evidence indicates that mutant mtDNA molecules can accumulate within individual cells, potentially hampering mitochondrial function.
Effects of antimetabolite induced cellular growth arrest on fibroblast-fibroblast interactions.

The use of single five-minute applications of antimetabolites during glaucoma filtration surgery has significantly reduced the occurrence of post-operative scarring and bleb failure. However, surgery for some patients is still unsuccessful, despite the use of antiproliferative agents, due to formation of scar tissue at the drainage site. It is not known if cells growth arrested in the treated area with a single application of antimetabolites influence the activity of adjacent non-treated cells. We hypothesise that the activity of non-treated cells recruited to the wound site may be involved in post-operative scarring. The aim of this study was to investigate the effects of antimetabolite induced cellular growth arrest on cell-cell interactions using in vitro techniques.Tenon's capsule fibroblast cultures were growth arrested by exposure for 5 minutes to mitomycin-C (0.001, 0.01 and 0.1 mg ml-1), 5-fluorouracil (0.25, 2.5 and 25 mg ml-1) or phosphate buffered saline (PBS). Following a period of serum-starvation, conditioned media (CM) were subsequently collected from the cells at intervals up to 29 days post-treatment. Correction for cell number was made prior to supplementation of serum-free medium with CM. CM were assessed for ability to support or inhibit normal non-treated fibroblast proliferation, migration and collagen contraction. Conditioned media collected from cells growth arrested with MMC or 5FU stimulated normal fibroblast proliferation, migration and collagen contraction in excess of non-conditioned serum-free medium. Peaks of fibroblast activity in CM differed according to which drug and concentration had originally been given to the treated cells. This study has demonstrated that CM collected from fibroblasts treated for 5 minutes with a range of concentrations of antimetabolites can differentially influence normal non-treated fibroblast activity. This in vitro data suggests that despite entering growth arrest, fibroblasts may still influence the behaviour of other cells via soluble mediators. They may have implications in the clinical setting, in that it may not be sufficient to suppress proliferation alone to prevent fibroblast behaviour associated with scarring after glaucoma filtration surgery.
Blood Pressure Trends in Patients With Seropositive Rheumatoid Arthritis Compared With Controls Without Rheumatoid Arthritis: A Retrospective Cohort Study

Rheumatoid arthritis (RA) conveys an increased risk of cardiovascular disease (CVD), making it imperative that traditional CVD risk factors are well controlled. This study compared blood pressure (BP) trends over 13 years among patients with seropositive RA and patients without RA who received care within a large health care system in Minnesota.
The role of cinnamon as a modulator of the expression of genes related to antioxidant activity and lipid metabolism of laying quails

Since cinnamon has vitamins and minerals in addition to antioxidants compounds in its chemical composition studies have shown the potential of cinnamon supplementation on some important characteristics in the performance of birds. Thus, this study was conducted under the hypothesis that the inclusion of cinnamon in the laying quail diet could influence the performance of the birds through the expression of genes related to antioxidant activity and lipid metabolism. To test this hypothesis, 144 Japanese quail (Coturnix japonica) with an initial age of 18 weeks and average weight of 133g were distributed in a completely randomized design with two treatments: no cinnamon supplementation (NCS—control group) and with supplementation of 9g/kg of cinnamon powder (CPS). The experiment lasted for 84 days. At the end of the experimental period, six animals from each treatment were euthanized by cervical dislocation, blood was collected and organs weighed. Liver tissue was collected for gene expression and biochemical analyses. We observed a significant effect of cinnamon inclusion on the weight of the pancreas (P = 0.0418), intestine (P = 0.0209) and ovary (P = 0.0389). Lower weights of the pancreas and intestine, and a higher ovary weight was observed in birds receiving the CPS diet. Quails fed with cinnamon supplementation also had better feed conversion per egg mass (2.426 g /g, P = 0.0126), and higher triglyceride (1516.60 mg/dL, P = 0.0207), uric acid (7.40 mg/dL, P = 0.0003) and VLDL (300.40 mg/dL, P = 0.0252) contents. A decreased content of thiobarbituric acid reactive substances (TBARS) and lower catalase activity was observed in the liver of quails from the CPS diet (0.086 nmoles/mg PTN, and 2.304 H2O2/min/mg PTN, respectively). Quails from the CPS group presented significantly greater expression of FAS (fatty acid synthase, 36,03 AU), ACC (Acetyl-CoA Carboxylase, 31.33 AU), APOAI (apolipoprotein A-I, 803,9 AU), ESR2 (estrogen receptor 2, 0.73 AU) SOD (superoxide dismutase, 4,933.9 AU) and GPx7 (glutathione peroxidase 7, 9.756 AU) than quails from the control group. These results allow us to suggest that cinnamon powder supplementation in the diet of laying quails can promote balance in the metabolism and better performance through the modulation of antioxidant activity and the expression of genes related to lipid metabolism.
Numerical Study of the Effect of Corneal Layered Structure on Ocular Biomechanics

Purpose: The study aimed to improve the accuracy of corneal numerical simulation by adopting a better representation of the corneal layered structure. The study considered both the shear and tensile behavior of the interface surfaces between stromal lamellae, and assessed the effect of modeling the cornea's three main layers—the epithelium, stroma, and endothelium with their respective material properties. Methods: Twelve human donor corneas were tested to determine the behavior of the stroma under surface shear. Numerical models were then built to consider the stromal inter-lamellar adhesion, which included the shear behavior determined experimentally and the tensile behavior available in the literature. They also adopted the distinctive material properties of the epithelium, stroma, and endothelium. The numerical models simulated corneal behavior under intraocular pressure elevation, concentric anterior pressure, and the conditions under tonometry with the Goldmann applanation tonometer. Results: The stress-strain shear behavior of stromal tissue followed an exponential pattern, with an initial low stiffness increasing gradually under higher stresses. This behavior was adopted in the numerical simulation to set the level of adhesion between stromal layers. Considering that the stromal inter-lamellar adhesion and the distinctive material properties of corneal layers had a significant effect in simulating the response to concentrated anterior pressures, which cause bending of corneal tissue, this was almost unnecessary when predicting the effect of intraocular pressure, which put the cornea under membrane tension. Conclusions: The corneal layered structure affects the results of numerical simulations especially in problems where the cornea is subjected to bending effects.