bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current view on regulation of voltage‐gated sodium channels by calcium and auxiliary proteins
Authors: Pitt Geoffrey S. , Lee Seok‐Yong 
Published: June 2016

AbstractIn cardiac and skeletal myocytes, and in most neurons, the opening of voltage‐gated Na+ channels (NaV channels) triggers action potentials, a process that is regulated via the interactions of the channels’ intercellular C‐termini with auxiliary proteins and/or Ca2+. The molecular and structural details for how Ca2+ and/or auxiliary proteins modulate NaV channel function, however, have eluded a concise mechanistic explanation and details have been shrouded for the last decade behind controversy about whether Ca2+ acts directly upon the NaV channel or through interacting proteins, such as the Ca2+ binding protein calmodulin (CaM). Here, we review recent advances in defining the structure of NaV intracellular C‐termini and associated proteins such as CaM or fibroblast growth factor homologous factors (FHFs) to reveal new insights into how Ca2+ affects NaV function, and how altered Ca2+‐dependent or FHF‐mediated regulation of NaV channels is perturbed in various disease states through mutations that disrupt CaM or FHF interaction.
Differential expression of postsynaptic NMDA and AMPA receptor subunits in the hippocampus and prefrontal cortex of the flinders sensitive line rat model of depression
Authors: Treccani Giulia , Gaarn du Jardin Kristian , Wegener Gregers , Müller Heidi Kaastrup 
Published: June 2016

AbstractGlutamatergic abnormalities have recently been implicated in the pathophysiology of depression, and the ionotropic glutamate receptors in particular have been suggested as possible underlying molecular determinants. The Flinders Sensitive Line (FSL) rats constitute a validated model of depression with dysfunctional regulation of glutamate transmission relatively to their control strain Flinders Resistant Line (FRL). To gain insight into how signaling through glutamate receptors may be altered in the FSL rats, we investigated the expression and phosphorylation of AMPA and NMDA receptor subunits in an enriched postsynaptic fraction of the hippocampus and prefrontal cortex. Compared to the hippocampal postsynaptic fractions of FRL rats, FSL rats exhibited decreased and increased levels of the NMDA receptor subunits GluN2A and GluN2B, respectively, causing a lower ratio of GluN2A/GluN2B. The GluA2/GluA3 AMPA receptor subunit ratio was significantly decreased while the expression of the individual GluA1, GluA2, and GluA3 subunits were unaltered including phosphorylation levels of GluA1 at S831 and S845. There were no changes in the prefrontal cortex. These results support altered expression of postsynaptic glutamate receptors in the hippocampus of FSL rats, which may contribute to the depressive‐like phenotype of these rats.
Folivory with leaf folding by giant flying squirrels: its patterns and possible function
Authors: Ito Mutsumi , Seto Nickie , Rico Brianna , Shigeta Mayumi , Tamura Noriko , Hayashi Fumio 
Published: June 2016

AbstractJapanese giant flying squirrels, Petaurista leucogenys, are entirely arboreal folivores. From spring to summer, their principal food source consists of leaves of the deciduous oak Quercus acutissima in western Tokyo, Japan. Before consuming the central part of each leaf, the squirrels fold the leaf two or more times with their forelegs. In the wild, leaf folding is a very rare behavior, even in primates. In our study, this peculiar feeding behavior was not observed across all study sites or even in some local populations. Herbivores generally try to maximize their intake of nutritious foods (e.g., sugars) containing low levels of plant defensive chemicals (e.g., phenols). We found that total phenolic contents in individual leaves of Q. acutissima were lower in the center than at the margins, whereas sugar (glucose) was homogenously distributed. Consequently, consumption of only leaf centers appears to be an adaptation by Japanese giant flying squirrels to avoid leaf margin defensive chemicals and structures. These leaf margin characteristics, which may have developed as defenses against herbivorous insects that generally feed from the margins, have contributed to the skillful and complex feeding behavior of this generalist folivore.
Effects and biological limitations of +Gz acceleration on the autonomic functions-related circulation in rats
Authors: Nishida Yasuhiro , Maruyama Satoshi , Shouji Ichiro , Kemuriyama Takehito , Tashiro Akimasa , Ohta Hiroyuki , Hagisawa Kohsue , Hiruma Megumi , Yokoe Hidetake 
Published: June 2016

Abstract
The effects of gravitational loading (G load) on humans have been studied ever since the early 20th century. After the dangers of G load in the vertical head-to-leg direction (+Gz load) became evident, many animal experiments were performed between 1920 and 1945 in an effort to identify the origins of high G-force-induced loss of consciousness (G-LOC), which led to development of the anti-G suit. The establishment of norms and training for G-LOC prevention resulted in a gradual decline in reports of animal experiments on G load, a decline that steepened with the establishment of anti-G techniques in humans, such as special breathing methods and skeletal muscle contraction, called an anti-G straining maneuver, which are voluntary physiological functions. Because the issue involves humans during flight, the effects on humans themselves are clearly of great importance, but ethical considerations largely preclude any research on the human body that probes to any depth the endogenous physiological states and functions. The decline in reports on animal experiments may therefore signify a general decline in research into the changes seen in the various involuntary, autonomic functions. The declining number of related reports on investigations of physiological autonomic systems other than the circulatory system seems to bear this out. In this review, we therefore describe our findings on the effects of G load on the autonomic nervous system, cardiac function, cerebral blood flow, tissue oxygen level, and other physiological autonomic functions as measured in animal experiments, including denervation or pharmacological blocking, in an effort to present the limits and the mechanisms of G-load response extending physiologically. We demonstrate previously unrecognized risks due to G load, and also describe fundamental research aimed at countering these effects and development of a scientific training measure devised for actively enhancing +Gz tolerance in involuntary, autonomic system functions. The research described here is rough and incomplete, but it is offered as a beginning, in the hope that researchers may find it of reference and carry the effort toward completion. The advances described here include (1) a finding that cerebral arterial perfusion pressure decreases to nearly zero under +5.0 Gz loads, (2) indications that G load may cause myocardial microinjuries, (3) detection of differences between cerebral regions in tissue-oxygen level under +3.0 Gz load, (4) discovery that hypotension is deeper under decreasing +Gz loads than increasing +Gz loads with use of an anti-G system, due in part to suppression of baroreceptor reflex, and (5) revelations and efforts investigating new measures to reduce cerebral hypotension, namely the “teeth-clenching pressor response” and preconditioning with slight but repeated G loads.
Undergraduate Training in Human Sexuality—Evaluation of the Impact on Medical Doctors' Practice Ten Years After Graduation
Authors: Clegg Mary , Pye Joanne , Wylie Kevan R. 
Published: June 2016

Abstract

Introduction
It has been suggested that an indicator of a doctor's ability to assess patients' sexual function relates to the level of earlier training. The amount and quality of training the doctor receives at the undergraduate level and beyond could contribute to the doctor's confidence and competence.

Aims
To evaluate whether doctors found that the teaching in human sexuality received at medical school was sufficient for their future practice and whether their chosen medical specialty and exposure to issues related to sexual health affected this opinion.

Methods
One hundred seventy doctors maintaining contact with the University of Sheffield Medical School Alumni Office after qualifying in 2004 were sent self-completion postal questionnaires. Space was allocated for supplementary comments to their answers.

Main Outcome Measures
Self-completion postal questionnaire.

Results
Although the response rate was low, there appeared to be an impact of the teaching of human sexuality on the clinical practice of doctors. More than two-thirds of respondents rated the teaching as useful and more than 70% felt more confident in diagnosing and managing male and female sexual issues.

Conclusion
The results show a link between the undergraduate teaching of sexual medicine and education and a subsequent proactive approach to sexuality issues; unfortunately, the study does not provide any information about the level of skills or ability in this field of medicine. We have confirmed that the Sheffield model might be suitable for teaching sexual medicine issues in the United Kingdom but cannot confirm that the current format is suitable for international undergraduate audiences. Future study could include other medical schools and a comparison of sexual medicine practice among physicians who received undergraduate medical education and overall numbers could be increased to compare current practice with the number of hours of sexual medicine education as a key parameter.
Retrospective case series examining the clinical significance of subjective fetal cardiac ventricular disproportion
Authors: Gabbay‐Benziv Rinat , Cetinkaya Demir Bilge , Crimmins Sarah , Esin Sertac , Turan Ozhan M. , Turan Sifa 
Published: June 2016

AbstractObjectiveTo evaluate fetal cardiac ventricular disproportion as a marker of cardiac anomalies.MethodsA retrospective case series included data from all patients who had a fetus diagnosed subjectively with ventricular disproportion by routine obstetric ultrasonography between January 1, 2007 and December 31, 2013 at a single tertiary center in the USA. Fetal and neonatal echocardiography, and neonatal outcome data were retrieved. Outcomes were described for all fetuses with subjective ventricular disproportion. Then, the objective right‐to‐left ventricular ratio (RLVR) was calculated as a continuous (after transformation to gestational age specific z‐scores) or categorical value (> 2SD for gestational week), based on previously published reference values. Subsequently, correlations between the objective RLVR and neonatal outcomes were evaluated.ResultsRecords from 60 fetuses diagnosed with ventricular disproportion at 16–38 weeks of gestation were included. These pregnancies resulted in 54 live deliveries; postnatally, 20 (37%) of these neonates were diagnosed with aortic coarctation and 39 (72%) were diagnosed with other cardiac anomalies, with or without aortic coarctation. No significant differences in objective prenatal diagnostic findings (RLVR) were demonstrated between neonates who were diagnosed postnatally with aortic coarctation or any cardiac anomaly and those not.ConclusionSubjective ventricular disproportion, regardless of objective diagnosis, was associated with cardiac defects. The use of fetal and neonatal echocardiography following diagnosis of fetal ventricular disproportion appears justified.
Evaluación de reactivos de opción múltiple en medicina. Evidencia de validez de un instrumento
Authors: Rivera Jiménez Jesús , Flores Hernández Fernando , Alpuche Hernández Amilcar , Martínez González Adrián 
Published: June 2016

Introducción: La adecuada elaboración de los reactivos de un examen constituye una evidencia de validez del mismo. A pesar de existir un consenso general sobre las recomendaciones en la elaboración de un buen reactivo, hay diferentes estudios publicados que reportan una alta incidencia de fallas en el apego a las mismas. Se propone un instrumento para evaluar la calidad en la elaboración de reactivos de opción múltiple y se describe el proceso de obtención de evidencias de validez.
Método: Se obtuvo evidencia de validez de un instrumento diseñado ex profeso para evaluar las características de los reactivos de opción múltiple, de acuerdo con las fuentes propuestas por los Standards for Educational and Psychological Testing, atendiendo a aquellas fuentes relacionadas con el contenido, el proceso de respuesta y la estructura interna. Se calculó el índice Kappa (por el modelo propuesto por Fleiss) y la correlación punto-biserial de Pearson para medir la concordancia en los diferentes criterios que evalúa el instrumento. Se realizó un análisis factorial exploratorio para identificar las dimensiones del instrumento y se calculó el alfa de Cronbach como estadístico de consistencia interna.
Resultados: La concordancia entre múltiples jueces tuvo un valor mayor de 0.8 (acuerdo casi perfecto) para 12 de los 21 criterios, y de 0.19 para el nivel taxonómico. El análisis factorial definió 4 dimensiones con un KMO = 0.666, (p < .01), una varianza total explicada de 49.979%, y un α de Cronbach de 0.627.
Conclusión: Este instrumento puede ser aplicado para la evaluación de reactivos de opción múltiple, ya que cuenta con evidencia de validez relacionada con el contenido, el proceso de respuesta y estructura interna y los indicadores psicométricos son adecuados para su instrumentación.
La importancia del preámbulo sobre la pregunta de investigación
Authors: Ortega-Marlasca Manuel-María 
Published: June 2016

Como especialista en Medicina Familiar y Comunitaria con vinculación en la educación pregrado en nuestra Facultad de Medicina, creo que se debería de haber hecho una referencia a la formación del estudiante de medicina en los centros de salud y/o en la atención primaria en general. Es algo que muchos valoramos y por lo que hemos luchado (y lo seguimos haciendo) por su presencia específica en la formación básica de todo estudiante de medicina.
Computational discovery and
in vivo
validation of
hnf4
as a regulatory gene in planarian regeneration
Authors: Lobo Daniel , Morokuma Junji , Levin Michael 
Published: June 2016

Abstract
Motivation: Automated computational methods can infer dynamic regulatory network models directly from temporal and spatial experimental data, such as genetic perturbations and their resultant morphologies. Recently, a computational method was able to reverse-engineer the first mechanistic model of planarian regeneration that can recapitulate the main anterior–posterior patterning experiments published in the literature. Validating this comprehensive regulatory model via novel experiments that had not yet been performed would add in our understanding of the remarkable regeneration capacity of planarian worms and demonstrate the power of this automated methodology.
Results: Using the Michigan Molecular Interactions and STRING databases and the MoCha software tool, we characterized as hnf4 an unknown regulatory gene predicted to exist by the reverse-engineered dynamic model of planarian regeneration. Then, we used the dynamic model to predict the morphological outcomes under different single and multiple knock-downs (RNA interference) of hnf4 and its predicted gene pathway interactors β -catenin and hh . Interestingly, the model predicted that RNAi of hnf4 would rescue the abnormal regenerated phenotype (tailless) of RNAi of hh in amputated trunk fragments. Finally, we validated these predictions in vivo by performing the same surgical and genetic experiments with planarian worms, obtaining the same phenotypic outcomes predicted by the reverse-engineered model.
Conclusion: These results suggest that hnf4 is a regulatory gene in planarian regeneration, validate the computational predictions of the reverse-engineered dynamic model, and demonstrate the automated methodology for the discovery of novel genes, pathways and experimental phenotypes.
Contact: michael.levin@tufts.edu
Intrathecal Catheterization and Drug Delivery in Guinea Pigs
Authors: Eddinger Kelly A. , Rondon Eric S. , Shubayev Veronica I. , Grafe Marjorie R. , Scadeng Miriam , Hildebrand Keith R. , Page Linda M. , Malkmus Shelle A. , Steinauer Joanne J. , Yaksh Tony L. 
Published: June 2016

Abstract

Background
Intrathecal infusion of opioids in dogs, sheep, and humans produces local space-occupying masses. To develop a small-animal model, the authors examined effects of intrathecal catheterization and morphine infusion in guinea pigs.

Methods
Under isoflurane, polyethylene or polyurethane catheters were advanced from the cisterna magna to the lumbar enlargement. Drugs were delivered as a bolus through the externalized catheter or continuously by subcutaneous minipumps. Hind paw withdrawal to a thermal stimulus was assessed. Spinal histopathology was systematically assessed in a blinded fashion. To assist in determining catheter placement, ex vivo images were obtained using magnetic resonance imaging in several animals. Canine spinal tissue from previous intrathecal morphine studies was analyzed in parallel.

Results
(1) Polyethylene (n = 30) and polyurethane (n = 25) catheters were implanted in the lumbar intrathecal space. (2) Bolus intrathecal morphine produced a dose-dependent (20 to 40 μg/10 μl) increase in thermal escape latencies. (3) Absent infusion, a catheter-associated distortion of the spinal cord and a fibrotic investment were noted along the catheter tract (polyethylene > polyurethane). (4) Intrathecal morphine infusion (25 mg/ml/0.5 μl/h for 14 days) resulted in intrathecal masses (fibroblasts, interspersed collagen, lymphocytes, and macrophages) arising from meninges proximal to the catheter tip in both polyethylene- and polyurethane-catheterized animals. This closely resembles mass histopathology from intrathecal morphine canine studies.

Conclusions
Continuous intrathecal infusion of morphine leads to pericatheter masses that morphologically resemble those observed in dogs and humans. This small-animal model may be useful for studying spinal drug toxicology in general and the biology of intrathecal granuloma formation in particular.
Rapid Infusion of Hydroxyethyl Starch 70/0.5 but not Acetate Ringer’s Solution Decreases the Plasma Concentration of Propofol during Target-controlled Infusion
Authors: Itakura Sayako , Masui Kenichi , Kazama Tomiei 
Published: June 2016

Abstract

Background
Rapid fluid infusion resulting in increased hepatic blood flow may decrease the propofol plasma concentration (Cp) because propofol is a high hepatic extraction drug. The authors investigated the effects of rapid colloid and crystalloid infusions on the propofol Cp during target-controlled infusion.

Methods
Thirty-six patients were randomly assigned to 1 of 3 interventions (12 patients per group). At least 30 min after the start of propofol infusion, patients received either a 6% hydroxyethyl starch (HES) solution at 24 ml·kg−1·h−1 or acetated Ringer’s solution at 24 or 2 ml·kg−1·h−1 during the first 20 min. In all groups, acetated Ringer’s solution was infused at 2 ml·kg−1·h−1 during the next 20 min. The propofol Cp was measured every 2.5 min as the primary outcome. Cardiac output, blood volume, and indocyanine green disappearance rate were determined using a pulse dye densitogram analyzer before and after the start of fluid administration. Effective hepatic blood flow was calculated as the blood volume multiplied by the indocyanine green disappearance rate.

Results
The rapid HES infusion significantly decreased the propofol Cp by 22 to 37%, compared to the Cp at 0 min, whereas the rapid or maintenance infusion of acetate Ringer’s solution did not decrease the propofol Cp. Rapid HES infusion, but not acetate Ringer’s solution infusion, increased the effective hepatic blood flow.

Conclusions
Rapid HES infusion increased the effective hepatic blood flow, resulting in a decreased propofol Cp during target-controlled infusion. Rapid HES infusion should be used cautiously as it may decrease the depth of anesthesia.
Electronically Mediated Time-out Initiative to Reduce the Incidence of Wrong Surgery
Authors: Rothman Brian S. , Shotwell Matthew S. , Beebe Russ , Wanderer Jonathan P. , Ehrenfeld Jesse M. , Patel Nimesh , Sandberg Warren S. 
Published: June 2016

Abstract

Background
“Wrong surgery” is defined as wrong site, wrong operation, or wrong patient, with estimated incidence up to 1 per 5,000 cases. Responding to national attention on wrong surgery, our objective was to create a care redesign intervention to minimize the rate of wrong surgery.

Methods
The authors created an electronic system using existing intraoperative electronic documentation to present a time-out checklist on large in-room displays. Time-out was dynamically interposed as a forced-function documentation step between “patient-in-operating room” and “incision.” Time to complete documentation was obtained from audit logs. The authors measured the postimplementation wrong surgery rate and used Bayesian methods to compare the pre- and postimplementation rates at our institution. Previous probabilities were selected using wrong surgery rate estimates from the observed performance reported in the literature to generate previous probabilities (4.24 wrong surgeries per 100,000 cases).

Results
No documentation times exceeded 5 min; 97% of documentation tasks were completed within 2 min. The authors performed 243,939 operations over 5 yr using the system, with zero wrong surgeries, compared with 253,838 operations over 6 yr with two wrong surgeries before implementation. Bayesian analysis suggests an 84% probability that the postimplementation wrong rate is lower than baseline. However, given the rarity of wrong surgery in our sample, there is substantial uncertainty. The total system-development cost was $34,000, roughly half the published cost of one weighted median settlement for wrong surgery.

Conclusion
Implementation of a forced-completion electronically mediated time-out process before incision is feasible, but it is unclear whether true performance improvements occur.