bluuebunny/crossref_metadata_2025 huggingface dataset:
Static and dynamic postural control in long-term microgravity: evidence of a dual adaptation
Authors: Baroni Guido , Pedrocchi Alessandra , Ferrigno Giancarlo , Massion Jean , Pedotti Antonio
Published: December 2017

The adaptation of dynamic movement-posture coordination during forward trunk bending was investigated in long-term weightlessness. Three-dimensional movement analysis was carried out in two astronauts during a 4-mo microgravity exposure. The principal component analysis was applied to joint-angle kinematics for the assessment of angular synergies. The anteroposterior center of mass (CM) displacement accompanying trunk flexion was also quantified. The results reveal that subjects kept typically terrestrial strategies of movement-posture coordination. The temporary disruption of joint-angular synergies observed at subjects' first in-flight session was promptly recovered when repetitive sessions in flight were analyzed. The CM anteroposterior shift was consistently <3–4 cm, suggesting that subjects could dynamically control the CM position throughout the whole flight. This is in contrast to the observed profound microgravity-induced disruption of the quasi-static body orientation and initial CM positioning. Although this study was based on only two subjects, evidence is provided that static and dynamic postural control might be under two separate mechanisms, adapting with their specific time course to the constraints of microgravity.
PAF increases vascular permeability without increasing pulmonary arterial pressure in the rat
Authors: Clavijo Leonardo C. , Carter Mary B. , Matheson Paul J. , Wilson Mark A. , Wead William B. , Garrison R. Neal
Published: December 2017

In vivo pulmonary arterial catheterization was used to determine the mechanism by which platelet-activating factor (PAF) produces pulmonary edema in rats. PAF induces pulmonary edema by increasing pulmonary microvascular permeability (PMP) without changing the pulmonary pressure gradient. Rats were cannulated for measurement of pulmonary arterial pressure (Ppa) and mean arterial pressure. PMP was determined by using either in vivo fluorescent videomicroscopy or the ex vivo Evans blue dye technique. WEB 2086 was administered intravenously (IV) to antagonize specific PAF effects. Three experiments were performed: 1) IV PAF, 2) topical PAF, and 3) Escherichia coli bacteremia. IV PAF induced systemic hypotension with a decrease in Ppa. PMP increased after IV PAF in a dose-related manner. Topical PAF increased PMP but decreased Ppa only at high doses. Both PMP (88 ± 5%) and Ppa (50 ± 3%) increased during E. coli bacteremia. PAF-receptor blockade prevents changes in Ppa and PMP after both topical PAF and E. coli bacteremia. PAF, which has been shown to mediate pulmonary edema in prior studies, appears to act in the lung by primarily increasing microvascular permeability. The presence of PAF might be prerequisite for pulmonary vascular constriction during gram-negative bacteremia.
Nucleus raphé obscurus modulates hypoglossal output of neonatal rat in vitro transverse brain stem slices
Authors: Peever John H. , Necakov Aleksandar , Duffin James
Published: December 2017

Nucleus raphéobscurus (NRo) modulates hypoglossal (XII) nerve motor output in the in vitro transverse brain stem slice of neonatal rats (1–5 days old); chemical ablation of NRo and its focal CO2 acidification modulated the bursting rhythm of XII nerves. We microinjected a 4.5 mM solution of kainic acid into the NRo to disrupt cellular activity and observed that XII nerve activity was temporarily abolished ( n = 10). We also microinjected CO2-acidified (pH = 6.00 ± 0.01) artificial cerebrospinal fluid (aCSF) into the NRo ( n = 6), the pre-Bötzinger complex (PBC) ( n = 6), as well as a control region in the lateral tegmental field equidistant to NRo, PBC, and the XII motor nuclei ( n = 12). CO2acidification of the control region had no effect on XII motor output. CO2 acidification of the NRo significantly ( P < 0.05) increased the burst discharge frequency of XII nerves by 77%; integrated burst amplitude and burst duration increased by 64% and 52%, respectively. CO2 acidification of the PBC significantly ( P < 0.05) increased the burst discharge frequency of XII nerves by 65%, but neither integrated burst amplitude nor burst duration changed. These results demonstrate that chemical ablation of the NRo can abolish XII nerve bursting rhythm and that stimulation of the NRo with CO2-acidified aCSF can excite XII nerve bursting activity. From these observations, we conclude that, in transverse brain stem slices, the NRo contains pH/CO2-sensitive cells that modulate XII motor output.
Invited Review: Effects of different activity and inactivity paradigms on myosin heavy chain gene expression in striated muscle
Authors: Baldwin Kenneth M. , Haddad Fadia
Published: December 2017

The goal of this mini-review is to summarize findings concerning the role that different models of muscular activity and inactivity play in altering gene expression of the myosin heavy chain (MHC) family of motor proteins in mammalian cardiac and skeletal muscle. This was done in the context of examining parallel findings concerning the role that thyroid hormone (T3, 3,5,3′-triiodothyronine) plays in MHC expression. Findings show that both cardiac and skeletal muscles of experimental animals are initially undifferentiated at birth and then undergo a marked level of growth and differentiation in attaining the adult MHC phenotype in a T3/activity level-dependent fashion. Cardiac MHC expression in small mammals is highly sensitive to thyroid deficiency, diabetes, energy deprivation, and hypertension; each of these interventions induces upregulation of the β-MHC isoform, which functions to economize circulatory function in the face of altered energy demand. In skeletal muscle, hyperthyroidism, as well as interventions that unload or reduce the weight-bearing activity of the muscle, causes slow to fast MHC conversions. Fast to slow conversions, however, are seen under hypothyroidism or when the muscles either become chronically overloaded or subjected to intermittent loading as occurs during resistance training and endurance exercise. The regulation of MHC gene expression by T3or mechanical stimuli appears to be strongly regulated by transcriptional events, based on recent findings on transgenic models and animals transfected with promoter-reporter constructs. However, the mechanisms by which T3and mechanical stimuli exert their control on transcriptional processes appear to be different. Additional findings show that individual skeletal muscle fibers have the genetic machinery to express simultaneously all of the adult MHCs, e.g., slow type I and fast IIa, IIx, and IIb, in unique combinations under certain experimental conditions. This degree of heterogeneity among the individual fibers would ensure a large functional diversity in performing complex movement patterns. Future studies must now focus on 1) the signaling pathways and the underlying mechanisms governing the transcriptional/translational machinery that control this marked degree of plasticity and 2) the morphological organization and functional implications of the muscle fiber's capacity to express such a diversity of motor proteins.
Lung mechanics in individuals with spinal cord injury: effects of injury level and posture
Authors: Baydur Ahmet , Adkins Rodney H. , Milic-Emili Joseph
Published: December 2017

Individuals with spinal cord injury (SCI) exhibit reduced lung volumes and flow rates as a result of respiratory muscle weakness. These features have not, however, been investigated in relation to the combined effects of injury level and posture. Changes in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, forced expiratory flow at 50% vital capacity (FEF50), inspiratory capacity (IC), and expiratory reserve volume (ERV) were assessed by injury level in the seated and supine positions in 74 individuals with SCI. The main findings were 1) FVC, FEV1, and IC increased with descending SCI level down to T10, below which they tended to level off; 2) supine values of FVC and FEV1tended to be larger in the supine compared with the seated posture down to injury level T1, caudad to which they were less than when seated; 3) IC increased proportionately more down to injury level L1, below which it declined slightly and plateaued; 4) ERV was measurable even at high cervical injuries, was generally smaller in the supine position, reached peak values in both positions at T10injury level, and then rapidly declined at lower levels; 5) when subjects were separated according to current, former, and never smokers, only formerly smoking paraplegic individuals demonstrated spirometric values significantly less than paraplegic individuals who never smoked. Changes in spirometric measurements in SCI are dependent on injury level and posture. These findings support the concept that the increase in vital capacity in supine position is related to the effect of gravity on abdominal contents and increase in IC.
Differential effects of exercise on insulin-signaling gene expression in human skeletal muscle
Authors: Wadley G. D. , Tunstall R. J. , Sanigorski A. , Collier G. R. , Hargreaves M. , Cameron-Smith D.
Published: December 2017

Skeletal muscle insulin sensitivity is enhanced after acute exercise and short-term endurance training. We investigated the impact of exercise on the gene expression of key insulin-signaling proteins in humans. Seven untrained subjects (4 women and 3 men) completed 9 days of cycling at 63 ± 2% of peak O2 uptake for 60 min/day. Muscle biopsies were taken before, immediately after, and 3 h after the exercise bouts (on days 1 and 9). The gene expression of insulin receptor substrate-2 and the p85α subunit of phosphatidylinositol 3-kinase was significantly higher 3 h after a single exercise bout, although short-term training ameliorated this effect. Gene expression of insulin receptor and insulin receptor substrate-1 was not significantly altered at any time point. These results suggest that exercise may have a transitory impact on the expression of insulin receptor substrate-2 and phosphatidylinositol 3-kinase; however, the predominant actions of exercise on insulin sensitivity appear not to reside in the transcriptional activation of the genes encoding major insulin-signaling proteins.
Effect of high transcapillary pressures on capillary ultrastructure and permeability coefficients in dog lung
Authors: Maron Michael B. , Fu Zhenxing , Mathieu-Costello Odile , West John B.
Published: December 2017

To determine the correlation between ultrastructural and physiological changes in blood-gas barrier function in lungs transiently exposed to very high vascular pressures, we increased capillary transmural pressure (Ptm) of 6 canine isolated perfused left lower lung lobe preparations (high-pressure group) to 80.3 Torr for 3.8 min and then determined the capillary filtration ( Kfc) and osmotic reflection (ςd) coefficients at a Ptm of 19.1 Torr in the ventilated lung lobes. This was followed by perfusion fixation of the lobes at a Ptm of 20.5 Torr for ultrastructural analysis. These data were compared with those obtained in six lobes in which Ptm was not transiently elevated before Kfc, ςd, and ultrastructural evaluation. Kfcwas higher [0.249 ± 0.042 (SE) vs. 0.054 ± 0.009 g · min−1· Torr−1· 100 g−1; P < 0.01] and ςdwas lower (0.52 ± 0.07 vs. 0.85 ± 0.08; P < 0.01) in the high-pressure group. In contrast, although endothelial and epithelial breaks were occasionally observed in some experiments, their incidence was not increased in the high-pressure group. These data suggest that the increased transvascular water and protein flux occurred through pathways of a size not resolvable by electron microscopy after vascular perfusion-fixation at a Ptm of 20.5 Torr.
Developmental study of cytochrome oxidase activity in the brain stem respiratory nuclei of postnatal rats
Authors: Liu Ying-Ying , Wong-Riley Margaret T. T.
Published: December 2017

We utilized cytochrome oxidase (CO) as a marker of neuronal functional activity to examine metabolic changes in brain stem respiratory nuclei of rats from newborn to 21 day of age. The pre-Bötzinger complex (PBC), upper airway motoneurons of nucleus ambiguus (NAUAM), ventrolateral nucleus of solitary tract (NTSVL), and medial and lateral parabrachial nuclei (PBM and PBL, respectively) were examined at postnatal days (P) 0, 1, 2, 3, 4, 5, 7, 14, and 21. CO histochemistry was performed, and the intensity of CO reaction product was quantitatively analyzed by optical densitometry. In addition, CO histochemistry was combined with neurokinin-1 receptor (NK1R) immunogold-silver staining to doubly label neurons of PBC in P14 animals. The results showed that levels of CO activity generally increased with age in all of the nuclei examined. However, a significant decrease was found in NAUAM at P3 ( P < 0.01), and a distinct plateau of CO activity was noted at P3 in PBC and at P3 and P4 in NTSVL, PBM, and PBL. Of the neurons examined in PBC, 83% were doubly labeled with CO and NK1R. Of these, CO activity was high in 33.9%, moderate in 27.3%, and light in 38.8% of neurons, suggesting different energy demands in these metabolic groups that may be related to their physiological or synaptic properties. The transient decrease or plateau in CO activity at P3 and P4 implies a period of synaptic adjustment or reorganization during development, when there may be decreased excitatory synaptic drive or increased inhibitory synaptic drive, or both, in these brain stem respiratory nuclei. The adjustment, in turn, may render the system less responsive to respiratory insults. This may bear some relevance to our understanding of pathological events during postnatal development, such as occurs in sudden infant death syndrome.
Effect of number of stimuli and timing of twitch application on variability in interpolated twitch torque
Authors: Suter Esther , Herzog Walter
Published: December 2017

Application of a supramaximal electrical twitch to the voluntarily contracted muscle is used to assess the level of muscle activation. Large variability in the interpolated twitch torque (ITT) has been observed when repeated stimulations are performed. It is hypothesized that this variability in ITT is caused by the stochastic nature of the timing of twitch application relative to pulses of voluntary excitation trains. Two experiments were performed on 12 subjects each to test this hypothesis. For the first experiment, a single twitch was superimposed on a train stimulation at different time intervals relative to the train pulses. For the second experiment, single, double, triple, or quadruple twitches were applied on a voluntarily contracted muscle. The ITT critically depended on the time point of twitch application: a single pulse applied 5 ms before a train pulse consistently evoked higher ITTs than all other stimulation conditions. Furthermore, variability of the ITT decreased as the number of applied twitches increased. The results support the hypothesis that a large part of the variability in the ITT may be caused by the timing of the superimposed twitch relative to the motor unit trains. The variability may be reduced by increasing the number of superimposed twitches.
Effect of short-term exercise training on angiogenic growth factor gene responses in rats
Authors: Gavin Timothy P. , Wagner Peter D.
Published: December 2017

We investigated whether 1) 5 days of exercise training would reduce the acute exercise-induced increase in skeletal muscle growth factor gene expression; and 2) reductions in the increase in growth factor gene expression in response to short-term exercise training would be coincident with increases in skeletal muscle oxidative potential. Female Wistar rats were used. Six groups (rest; exercise for 1–5 consecutive days) were used to measure the growth factor response through the early phases of an exercise training program. Vascular endothelial growth factor (VEGF), transforming growth factor-β1(TGF-β1), and basic fibroblast growth factor (bFGF) mRNA were analyzed from the left gastrocnemius by quantitative Northern blot. Citrate synthase activity was analyzed from the right gastrocnemius. VEGF and TGF-β1mRNA increased after each of 5 days of exercise training, whereas exercise on any day did not increase bFGF mRNA. On day 1, the VEGF mRNA response was significantly greater than on days 2–5. However, the reduced increase in VEGF mRNA observed on days 2–5 was not coincident with increases in citrate synthase activity. These findings suggest that, in skeletal muscle, 1) VEGF and TGF-β1mRNA are increased through 5 days of exercise training and 2) the reduced exercise-induced increase in VEGF mRNA responses on days 2–5 does not result from increases in oxidative potential.
In vivo pressure-flow curve in unilateral rat lung ischemia-reperfusion injury
Authors: Yu C.-C. , Lai Y.-L.
Published: December 2017

The pressure-flow (P-Q˙) curve has been widely used in many studies to describe the effects of various factors on vascular hemodynamics. It is not clear, however, whether unilateral ischemia-reperfusion (IR) alters the P-Q˙ curve of the rat lung. In this study, we developed an in vivo P-Q˙ curve using the unilateral (left) rat lung before and after IR. Animals were divided into two groups: sham and IR. The protocol of the IR group consisted of three periods: baseline, ischemia, and reperfusion. P-Q˙ curves were obtained by altering blood flow of the left lung during the baseline and the reperfusion periods. The sham group received the same operation without IR procedure. An additional group was used to compare pulmonary blood flow measured by the microsphere and the ultrasonic methods. IR treatment rotated the P-Q˙ curve toward the left, indicating an increase in resistance in the left lung. However, this rotation was not found in the sham group. A significant correlation ( r = 0.87, P < 0.01) between percentages of blood flow obtained by the microsphere and ultrasonic methods in both right and left lungs was demonstrated. Therefore, we demonstrated a simple and useful technique to evaluate changes in the P-Q˙ curves caused by IR in the unilateral rat lung model.
Genes differentially expressed in medulloblastoma and fetal brain
Authors: MICHIELS E. M. C. , OUSSOREN E. , VAN GROENIGEN M. , PAUWS E. , BOSSUYT P. M. M. , VOÛTE P. A. , BAAS F.
Published: December 2017

Michiels, E. M. C., E. Oussoren, M. van Groenigen, E. Pauws, P. M. M. Bossuyt, P. A. Voûte, and F. Baas. Genes differentially expressed in medulloblastoma and fetal brain. Physiol. Genomics 1: 83–91, 1999.—Serial analysis of gene expression (SAGE) was used to identify genes that might be involved in the development or growth of medulloblastoma, a childhood brain tumor. Sequence tags from medulloblastoma (10229) and fetal brain (10692) were determined. The distributions of sequence tags in each population were compared, and for each sequence tag, pairwise χ2 test statistics were calculated. Northern blot was used to confirm some of the results obtained by SAGE. For 16 tags, the χ2 test statistic was associated with a P value < 10−4. Among those transcripts with a higher expression in medulloblastoma were the genes for ZIC1 protein and the OTX2 gene, both of which are expressed in the cerebellar germinal layers. The high expression of these two genes strongly supports the hypothesis that medulloblastoma arises from the germinal layer of the cerebellum. This analysis shows that SAGE can be used as a rapid differential screening procedure.
A novel mutation in FGFR-3 disrupts a putative N-glycosylation site and results in hypochondroplasia
Authors: WINTERPACHT ANDREAS , HILBERT KATJA , STELZER CHRISTIANE , SCHWEIKARDT THORSTEN , DECKER HEINZ , SEGERER HUGO , SPRANGER JÜRGEN , ZABEL BERNHARD
Published: December 2017

Winterpacht, Andreas, Katja Hilbert, Christiane Stelzer, Thorsten Schweikardt, Heinz Decker, Hugo Segerer, Jürgen Spranger, and Bernhard Zabel. A novel mutation in FGFR-3 disrupts a putative N-glycosylation site and results in hypochondroplasia. Physiol. Genomics 2: 9–12, 2000.—Fibroblast growth factor receptor 3 (FGFR3) is a glycoprotein that belongs to the family of tyrosine kinase receptors. Specific mutations in the FGFR3 gene are associated with autosomal dominant human skeletal disorders such as hypochondroplasia, achondroplasia, and thanatophoric dysplasia. Hypochondroplasia (HCH), the mildest form of this group of short-limbed dwarfism disorders, results in ∼60% of cases from a mutation in the intracellular FGFR3-tyrosine kinase domain. The remaining cases may either be caused by defects in other FGFR gene regions or other yet unidentified genes. We describe a novel HCH mutation, the first found outside the common mutation hot spot of this condition. This point mutation, an N328I exchange in the extracellular Ig domain III of the receptor, seems to be unique as it affects a putative N-glycosylation site that is conserved between different FGFRs and species. The amino acid exchange itself most probably has no impact on the three-dimensional structure of the receptor domain, suggesting that the phenotype is the result of altered receptor glycosylation and its pathophysiological consequences.
Circadian rhythms in a nutshell
Authors: EDERY ISAAC
Published: December 2017

Edery, Isaac. Circadian rhythms in a nutshell. Physiol Genomics 3: 59–74, 2000.—Living organisms on this planet have adapted to the daily rotation of the earth on its axis. By means of endogenous circadian clocks that can be synchronized to the daily and seasonal changes in external time cues, most notably light and temperature, life forms anticipate environmental transitions, perform activities at biologically advantageous times during the day, and undergo characteristic seasonal responses. The effects of transmeridian flight and shift work are stark reminders that although modern technologies can create “cities that never sleep” we cannot escape the recalcitrance of endogenous clocks that regulate much of our physiology and behavior. Moreover, malfunctions in the human circadian timing system are implicated in several disorders, including chronic sleep disorders in the elderly, manic-depression, and seasonal affective disorders (SAD or winter depression). Recent progress in understanding the molecular mechanisms underlying circadian rhythms has been remarkable. In its most basic form, circadian clocks are comprised of a set of proteins that, by virtue of the design principles involved, generate a self-sustaining transcriptional-translational feedback loop with a free-running period of about 24 h. One or more of the clock components is acutely sensitive to light, resulting in an oscillator that can be synchronized to local time. This review provides an overview of the roles circadian clocks play in nature, how they might have arisen, human health concerns related to clock dysfunction, and mainly focuses on the clockworks found in Drosophila and mice, the two best studied animal model systems for understanding the biochemical and cellular bases of circadian rhythms.
Role of intracellular calcium in human adipocyte differentiation
Authors: SHI HANG , HALVORSEN YUAN-DI , ELLIS PAMELA N. , WILKISON WILLIAM O. , ZEMEL MICHAEL B.
Published: December 2017

Shi, Hang, Yuan-Di Halvorsen, Pamela N. Ellis, William O. Wilkison, and Michael B. Zemel. Role of intracellular calcium in human adipocyte differentiation. Physiol Genomics 3: 75–82, 2000.—Intracellular calcium ([Ca2+]i) modulates adipocyte lipid metabolism and inhibits the early stages of murine adipogenesis. Consequently, we evaluated effects of increasing [Ca2+]iin early and late stages of human adipocyte differentiation. Increasing [Ca2+]iwith either thapsigargin or A23187 at 0–1 h of differentiation markedly suppressed differentiation, with a 40–70% decrease in triglyceride accumulation and glycerol-3 phosphate dehydrogenase (GPDH) activity ( P < 0.005). However, a 1-h pulse of either agent at 47–48 h only modestly inhibited differentiation. Sustained, mild stimulation of Ca2+influx with either agouti protein or 10 mM KCl-induced depolarization during 0–48 h of differentiation inhibited triglyceride accumulation and GPDH activity by 20–70% ( P < 0.05) and markedly suppressed peroxisome proliferator-activated receptor gamma (PPARγ) expression. These effects were reversed by Ca2+channel antagonism. In contrast, Ca2+pulses late in differentiation (71–72 h or 48–72 h) markedly increased these markers of differentiation. Thus increasing [Ca2+]iappears to exert a biphasic regulatory role in human adipocyte differentiation, inhibiting the early stages while promoting the late stage of differentiation and lipid filling.
Transcriptional regulation of the adipocyte fatty acid synthase gene by agouti: interaction with insulin
Authors: CLAYCOMBE KATE J. , WANG YANXIN , JONES BRYNN H. , KIM SUYEON , WILKISON WILLIAM O. , ZEMEL MICHAEL B. , CHUN JOSEPH , MOUSTAID-MOUSSA NAIMA
Published: December 2017

Claycombe, Kate J., Yanxin Wang, Brynn H. Jones, Suyeon Kim, William O. Wilkison, Michael B. Zemel, Joseph Chun, and Naima Moustaid-Moussa. Transcriptional regulation of the adipocyte fatty acid synthase gene by agouti: interaction with insulin. Physiol Genomics 3: 157–162, 2000.—Mice carrying dominant mutations at the agouti locus exhibit ectopic expression of agouti gene transcripts, obesity, and type II diabetes through unknown mechanisms. To gain insight into the role of agouti protein in modulating adiposity, we investigated regulation of a key lipogenic gene, fatty acid synthase (FAS) by agouti alone and in combination with insulin. Both agouti and insulin increase FAS activity in 3T3-L1 and in human adipocytes. Agouti and insulin independently and additively increase FAS activity in 3T3-L1 adipocytes. We further investigated the mechanism responsible for the agouti-induced FAS expression in these cells and demonstrated that both insulin (3-fold increase) and agouti (2-fold) increased FAS gene expression at the transcriptional level. Furthermore, insulin and agouti together exerted additive effects (5-fold increase) on FAS gene transcription. Transfection assays of FAS promoter-luciferase fusion gene constructs into 3T3-L1 adipocytes indicated that the agouti response element(s) is (are) located in the −435 to −415 region (−435/−415) of the FAS promoter. Nuclear proteins binding to this novel sequence are adipocyte specific. Thus the agouti response sequences mapped to a region upstream of the insulin-responsive element (which we previously reported to be located at −67/−52), consistent with additive effects of these two factors on FAS gene transcription.
Quantitative trait loci mapping for cholesterol gallstones in AKR/J and C57L/J strains of mice
Authors: PAIGEN BEVERLY , SCHORK NICHOLAS J. , SVENSON KAREN L. , CHEAH YIN-CHAI , MU JIAN-LONG , LAMMERT FRANK , WANG DAVID Q.-H. , BOUCHARD GUYLAINE , CAREY MARTIN C.
Published: December 2017

Quantitative trait locus (QTL) mapping was used to locate genes that determine the difference in cholesterol gallstone disease between the gallstone-susceptible strain C57L/J and the gallstone-resistant strain AKR/J. Gallstone weight was determined in 231 male (AKR × C57L) F1× AKR backcross mice fed a lithogenic diet containing 1% cholesterol, 0.5% cholic acid, and 15% butterfat for 8 wk. Mice having no stones and mice having the largest stones were genotyped at ∼20-cM intervals to find the loci determining cholesterol gallstone formation. The major locus, Lith1, mapped near D2Mit56 and was confirmed by constructing a congenic strain, AK.L- Lith1s. Another locus, Lith2, mapped near D19Mit58 and was also confirmed by constructing a congenic strain AK.L- Lith2s. Other suggestive, but not statistically significant, loci mapped to chromosomes 6, 7, 8, 10, and X. The identification of these Lith genes will elucidate the pathophysiology of cholesterol gallstone formation.
APO E gene and gene-environment effects on plasma lipoprotein-lipid levels
Authors: HAGBERG JAMES M. , WILUND KENNETH R. , FERRELL ROBERT E.
Published: December 2017

Apolipoprotein E (apo E) is important in plasma lipid metabolism and is a component of several plasma lipoprotein-lipid particles. Three major apo E isoforms are encoded by three common alleles at the APO E locus. The E2 allele is associated with lower and the E4 allele with higher total plasma cholesterol and LDL cholesterol levels compared with the E3 allele. Available data generally indicate that APO E2, and possibly E3, genotype individuals reduce plasma total and low-density lipoprotein (LDL) cholesterol levels more than APO E4 individuals with statin therapy. Some evidence also indicates that APO E2 individuals are more likely to respond favorably to gemfibrozil and cholestyramine. On the other hand, it appears that with probucol, APO E4 genotype individuals may improve plasma lipoprotein-lipid profiles more than APO E3 individuals. APO E2 and E3 genotype perimenopausal women appear to improve plasma lipoprotein-lipid profiles more with hormone replacement therapy than APO E4 women. On the other hand, low-fat diet interventions tend to reduce plasma LDL cholesterol and, perhaps, plasma total cholesterol levels more in APO E4 than in APO E2 or E3 individuals. Both cross-sectional and longitudinal studies generally indicate that APO E2 and E3 individuals improve plasma lipoprotein-lipid profiles more with exercise training than APO E4 individuals. Although these data are hardly definitive, they lend strong support for the possibility that in the near future individuals will be directed to what might be their optimal therapy for improving plasma lipoprotein-lipid profiles and cardiovascular disease risk based partially on APO E genotype.
VHL tumor suppressor regulates Cl−/HCO3−exchange and Na+/H+exchange activities in renal carcinoma cells
Authors: KARUMANCHI S. ANANTH , JIANG LIANWEI , KNEBELMANN BERTRAND , STUART-TILLEY ALAN K. , ALPER SETH L. , SUKHATME VIKAS P.
Published: December 2017

Mutations in the von Hippel-Lindau (VHL) tumor suppressor gene are thought to play a critical role in the pathogenesis of both sporadic and VHL disease-associated clear-cell renal carcinomas (RCC). Differential display-PCR identified the AE2 anion exchanger as a candidate VHL target gene. AE2 mRNA and polypeptide levels were approximately threefold higher in 786-O VHL cells than in 786-O Neo cells. In contrast, Cl−/HCO3−exchange activity in 786-O VHL cells was 50% lower than in 786-O Neo cells. Since resting intracellular pH (pHi) values were indistinguishable, we postulated that Na+/H+exchange activity (NHE) might be similarly reduced in 786-O VHL cells. NHE-mediated pHirecovery from acid load was less than 50% that in 786-O Neo cells, whereas hypertonicity-stimulated, amiloride-sensitive NHE was indistinguishable in the two cell lines. The NHE3 mRNA level was higher in 786-O VHL than 786-O Neo cells, but NHE1 mRNA levels did not differ. AE2 and NHE3 are the first transcripts reported to be upregulated by pVHL. Elucidation of mechanisms responsible for downregulation of both ion exchange activities will require further investigation.
Uterine Rupture after Laparoscopic Myomectomy in Two Cases: Real Complication or Malpractice?
Authors: Vimercati Antonella , Del Vecchio Vittoria , Chincoli Annarosa , Malvasi Antonio , Cicinelli Ettore
Published: December 2017

We describe two cases of uterine rupture in pregnancy after laparoscopic myomectomy and analyze all the aetiological factors involved in this circumstance according to the recent literature, focusing above all on the surgical procedures and the characteristics of the excised myomas. The two cases of uterine rupture in pregnancy following laparoscopic myomectomy occurred at 36 and 18 weeks of gestation, respectively. Both women had undergone laparoscopic multiple myomectomy and uterine rupture occurred along the isthmic myomectomy scars, despite the fact that compliance with all the recent technical surgical recommendations for the previous laparoscopic multiple myomectomy had been fully observed. In our cases we identified the isthmic localization, size of the excised myomas (≥4 cm), and individual characteristics of the healing process as possible risk factors for “a real complication.” Larger studies and robust case-control analyses are needed to draw reliable conclusions; special care should be paid when performing laparoscopic myomectomy in women planning a later pregnancy.
RBF Nonsmooth Control Method for Vibration of Building Structure with Actuator Failure
Authors: Wang Jianhui , Zhang Chunliang , Zhu Houyao , Huang Xiaofang , Zhang Li
Published: December 2017

In order to accommodate the actuator failure, the finite-time stable nonsmooth control method with RBF neural network is used to suppress the structural vibration. The traditional designed control methods neglect influence of actuator failure in structural vibration. By Lyapunov stable theory, the designed control method is demonstrated to suppress the building structural vibration with actuator failure. Finally, there are some examples to numerically simulate the three-layer building structure which is affected by El Centro seismic wave. Control effect of nonsmooth control is compared with no control and LQR control. The simulation results demonstrate that the designed control method is great for vibration of building structure with actuator failure and great antiseismic effect.
Resistance Training and Stroke: A Critical Analysis of Different Training Programs
Authors: Gambassi Bruno Bavaresco , Coelho-Junior Hélio José , Schwingel Paulo Adriano , Almeida Fabiano de Jesus Furtado , Gaspar Novais Tânia Maria , Lauande Oliveira Paula de Lourdes , Sauaia Bismarck Ascar , Melo Cristiane Dominice , Uchida Marco Carlos , Rodrigues Bruno
Published: December 2017

The aim of this study was to carry out a literature review on the overall benefits of resistance training (RT) after stroke and undertake a critical analysis of the resistance exercise programs surveyed (rest interval between sets and exercises, number of sets, number of repetitions, intensity, duration of training, and weekly frequency). To obtain articles for the review, we searched PubMed, Google Scholar, and Physiotherapy Evidence Database (PEDro). Inclusion criteria were considered using the PICO (population, intervention, control/comparison, and outcome variables) model. The following characteristics were recorded for all articles: type of study, author, year of publication, participants (time after stroke, sample size, and age), benefits of RT, and structured resistance exercise programs. Positive effects of training were found on anxiety status, quality of life, muscle hypertrophy, cognitive function, strength, and muscle power. Only 5 studies described the main variables of RT in detail. Lack of control of some variables of RT may negatively affect the results of this practice. The findings of the present study may further inform health and physical conditioning professionals on the importance and necessity of using the main variables in the search for benefits for individuals with stroke.
Multiple Tophaceous Gout of Hand with Extensor Tendon Rupture
Authors: Tobimatsu Haruki , Nakayama Masanori , Sakuma Yu , Imamura Hitoshi , Yano Koichiro , Itagaki Hiroko , Ikari Katsunori
Published: December 2017

A 45-year-old man presented with painless subcutaneous masses bilaterally on his hands and loss of motion or contracture of the fingers. Initially, drug therapy to reduce the serum uric acid was administered and was expected to reduce the tophi. However, during observation at the clinic, spontaneous rupture of an extensor tendon occurred, and surgical repair of the tendon and resection of the masses were performed. Surgical exploration of the right hand showed hypertrophic white-colored crystal deposits that both surrounded and invaded the extensor digitorum communis of the index finger, which was ruptured. Histopathologic examination of the specimen demonstrated findings consistent with gouty tophi. Tophaceous gout can induce a rupture of tendons during clinical observation, and surgical resection of the tophi might be needed to prevent ruptures.
Opium Use and Risk of Pancreatic Cancer: A Prospective Cohort Study
Authors: Moossavi Shirin , Mohamadnejad Mehdi , Pourshams Akram , Poustchi Hossein , Islami Farhad , Sharafkhah Maryam , Mirminachi Babak , Nasseri-Moghaddam Siavosh , Semnani Shahryar , Shakeri Ramin , Etemadi Arash , Merat Shahin , Khoshnia Masoud , Dawsey Sanford M. , Pharoah Paul D. , Brennan Paul , Abnet Christian C. , Boffetta Paolo , Kamangar Farin , Malekzadeh Reza
Published: December 2017

Background: We examined the association between opium consumption and pancreatic cancer incidence in a large-scale prospective cohort of the general population in northeastern Iran.

Methods: A total of 50,045 adults were systematically followed up (median of 7.4 years), and incident cases of pancreatic cancer were identified. Self-reported data on opium consumption was collected at baseline. Cumulative use (-year) was defined as number of nokhods (a local unit, approximately 0.2 g) of opium consumed per day multiplied by number of years consuming. Adjusted HRs and 95% confidence intervals (CIs) for the association between opium consumption and pancreatic cancer were calculated using Cox proportional hazards regression models.

Results: Overall, 54 confirmed cases of pancreatic cancer were identified. Opium use of more than 81 nokhod-years (high cumulative use), compared with never use, was strongly associated with pancreatic cancer even after adjustments for multiple potential confounding factors [HR = 3.01; 95% CI, 1.25–7.26]. High cumulative consumption of opium was significantly associated with risk of pancreatic cancer after adjusting for cumulative dose of cigarette smoking [HR = 3.56; 95% CI, 1.49–8.50]. In a sensitivity analysis, we excluded participants (including 2 pancreatic cancer cases) who were recruited within the first 5 years of starting opium consumption; high cumulative use of opium was still associated with pancreatic cancer risk [HR = 2.75; 95% CI, 1.14–6.64].

Conclusions: Our results showed a positive association between opium consumption and pancreatic cancer.

Impact: This is the first prospective large-scale study to show the association of opium consumption with pancreatic cancer as a risk factor. Cancer Epidemiol Biomarkers Prev; 27(3); 268–73. ©2017 AACR.
Antibiotic and Analgesic Prescription Patterns among Dentists or Management of Dental Pain and Infection during Endodontic Treatment
Authors: Maslamani Manal , Sedeqi Faraj
Published: December 2017

Objective: The aim of this study was to determine prescription patterns of antibiotics and analgesics among dentists in the management of dental pain and infection for medically healthy patients undergoing endodontic management. Materials and Methods: This descriptive cross-sectional survey was based on a structured questionnaire. The questionnaire collected data on age, gender, years of experience, and the qualifications of dentists. Feedback on prescription patterns for antibiotics and analgesics was collected for a number of clinical scenarios. Participants' choices regarding the type, dose, and duration of antibiotics/analgesics were recorded. Completed questionnaires were analyzed using the Statistical Package for Social Sciences (SPSS; version 24) to determine relationships between prescription patterns, age, gender, and educational qualification. Results: Of the 227 participants surveyed, 190 (83.7%) did not prescribe antibiotics for patients complaining of severe pain. There were significant associations between age and years of experience and antibiotic prescription for pain management (p = 0.035 and 0.04, respectively). Of the participants, 199 (87.7%) never prescribed antibiotics for reversible pulpitis with normal periapical area; there was a statistical significance in relation to gender (p = 0.044). Amoxicillin 500 mg was prescribed most of the time (51.5%). Diclofenac K (50 mg) was prescribed by 41% of the participants, while 39.2% of the participants very often prescribed ibuprofen (600 mg). Conclusion: Most dentists prescribed analgesics and antibiotics as recommended, but more education on the proper use of these medicines is needed for dentists and patients.
Una poética del resentimiento: memoria y moral en la obra de Louise Bourgeois
Authors: Peralta Cristina
Published: December 2017

El propósito de este artículo es mostrar el resentimiento como una forma eminentemente moderna de sensibilidad con la que situarse en el mundo y elaborar un proyecto de subjetivación personal. Utilizaré la obra de Louise Bourgeois porque su forma de entender el proceso creativo es un ejemplo paradigmático de cómo el resentimiento se vuelve creador dando lugar a dichos procesos de subjetivación. Desarrollaré la idea de que Bourgeois hace un arte resentido porque a través de este afecto trata con el motivo más existencial de su producción, es decir, cómo convertir lo accidental en necesario. Elaboraré mi argumento basándome en el texto de Judith Butler, Dar cuenta de uno mismo.
Ensaio visual
Authors: Ramos Nuno
Published: December 2017

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Caminhabilidade, paisagem e ambiência no centro histórico de Goiás-GO
Authors: Cardoso Carina Folena , Fonseca Thalita Pereira , Gonçalves Pedro Henrique
Published: December 2017

Este trabalho relaciona os níveis de caminhabilidade do centro histórico da cidade de Goiás (GO) com a contemplação de sua paisagem cultural em percursos ordinários. A investigação se dá através de abordagens quantitativas e qualitativas a partir de três perspectivas: distâncias percorridas; qualidade dos ambientes contemplados nos percursos; paisagem. Como desdobramento dos procedimentos metodológicos e dos resultados encontrados, discute-se sobre a contribuição do estudo da qualidade paisagística e ambiental à análise da caminhabilidade, procurando superar uma avaliação segmentária desta. Os resultados apresentam índices abaixo da média para todos os percursos, o que dificilmente enquadraria a cidade de Goiás no rol das chamadas “cidades ativas” por suas deficiências no âmbito da caminhabilidade.
Espaços livres privados nas pequenas cidades
Authors: Maté Cláudia , Santiago Alina Gonçalves
Published: December 2017

As cidades pequenas são maioria no cenário nacional, no entanto ainda são poucas as pesquisas desenvolvidas acerca da realidade dessas cidades, principalmente a respeito de seu espaço urbano. Da mesma forma, os estudos desenvolvidos a respeito do sistema de espaços livres também têm se concentrado em grandes e médias cidades brasileiras. Nesse contexto, este artigo tem como objetivo analisar os espaços livres privados (ELPr) de uma pequena cidade, Pinhalzinho, no estado de Santa Catarina, identificando suas particularidades e também as similaridades e diferenças existentes com os resultados já encontrados nos estudos de cidades de maior porte. A metodologia adotada tem como referência principal os estudos dos sistemas de espaços livres desenvolvidos pela Rede Nacional de Pesquisa Quapá-SEL, com o uso da interface Sistemas de Informação Geográfica para identificação, categorização, quantificação e análise dos espaços livres privados. A análise destes resultou em altas taxas de espaço livre intraquadra e na predominância de espaços verdes e permeáveis, aspectos bem particulares à pequena cidade em estudo.
New‐Onset Atrial Fibrillation After Coronary Artery Bypass Graft and Long‐Term Risk of Stroke: A Meta‐Analysis
Authors: Megens Matthew R. , Churilov Leonid , Thijs Vincent
Published: December 2017

Background

New‐onset atrial fibrillation (
NOAF
) after coronary artery bypass graft is related to an increased short‐term risk of stroke and mortality. We investigated whether the long‐term risk of stroke is increased.

Methods and Results

We performed a systematic review and meta‐analysis of studies that included patients who had coronary artery bypass graft and who afterwards developed
NOAF
during their index admission; these patients did not have previous atrial fibrillation. The primary outcome was risk of stroke at 6 months or more in patients who developed
NOAF
compared with those who did not. Odds ratios, relative risk, and hazard ratios were considered equivalent; outcomes were pooled on the log‐ratio scale using a random‐effects model and reported as exponentiated effect‐sizes. We included 16 studies, comprising 108 711 participants with a median follow‐up period of 2.05 years. Average participant age was 66.8 years, with studies including an average of 74.8% males. There was an increased long‐term risk of stroke in the presence of
NOAF
(unadjusted studies effect‐sizes=1.36, 95% confidence interval, 1.12–1.65,
P
=0.001, adjusted studies effect‐sizes=1.25, 95% confidence interval, 1.09–1.42,
P
=0.001). There was evidence of moderate effect variation because of heterogeneity in studies reporting unadjusted (
P
=0.021, I
2
=49.8%) and adjusted data (
P
=0.081, I
2
=49.1%), and publication bias in the latter group (Egger's test,
P
=0.031). Sensitivity analysis on unadjusted data by study quality, design, and surgery did not alter the effect direction.

Conclusions

Presence of
NOAF
in patients post–coronary artery bypass graft is associated with increased long‐term risk of stroke compared with patients without
NOAF
. Further studies may show whether the increased risk is mediated by atrial fibrillation and whether anticoagulation reduces risk.
Feuer und göttliche Dialektik bei Heraklit
Authors: Vassallo Christian
Published: December 2017

This paper provides a new critical edition, with a short commentary, of col. 330 (olimfr. 17) ofP.Herc.1428, the ‘midollo’ of the roll containing Philodemus’On Piety. The autopsy of the original manuscript has allowed new readings and conjectures, which can shed new light on the doxographical context of this piece of evidence. In particular, new elements clarify the way in (and the purpose for) which Philodemus mixed the Heraclitean fragments on Fire (fr. 79 Marcovich = DK 22 B 64) and on the mixture of opposites in God (fr. 77 Marcovich = DK 22 B 67).1
Determined to Come Most Freely
Authors: Anderson James N. , Manata Paul
Published: December 2017

It is commonly held that Calvinism is committed to theological determinism, and therefore also to compatibilism insofar as Calvinism affirms human freedom and moral responsibility. Recent scholarship has challenged this view, opening up space for a form of Calvinism that allows for libertarian free will. In this article we critically assess two versions of ‘libertarian Calvinism’ recently proposed by Oliver Crisp. We contend that Calvinism (defined along the confessional lines adopted by Crisp) is implicitly committed to theological determinism, and even if it were not so committed, it would still rule out libertarian free will on other grounds.
The Dialogue between Herman Bavinck and Mou Zongsan on Human Nature and Its Quality
Authors: Xu Ximian
Published: December 2017

This article aims to make a comparison between Herman Bavinck, a leading neo-Calvinist theologian, and Mou Zongsan, arguably the most innovative New Confucian philosopher, on human nature and its quality, and to build a dialogue between them. Bavinck sets forth a theocentric explication on human nature, that is the imago Dei, which was created, is fallen and can only be restored in Jesus Christ who is the true imago Dei. In contrast, Mou anthropocentrically expounds human nature, which immanentizes the heavenly decree and is innately good. Despite their fundamental differences, a dialogue can still be articulated by differing Bavinck’s God from Kant’s God, the latter of which is critiqued by Mou.