bluuebunny/crossref_metadata_2025 huggingface dataset:
Intrathecal melanin-concentrating hormone reduces sympathetic tone and blocks cardiovascular reflexes
Authors: Egwuenu Eyitemi J. , Fong Angelina Y. , Pilowsky Paul M.
Published: July 2012

Melanin-concentrating hormone (MCH) is a neuropeptide that acts to increase feeding behavior and decrease energy expenditure. The role of MCH in central cardiorespiratory regulation is still poorly understood. Experiments were conducted on urethane-anesthetized, vagotomized, and artificially ventilated male Sprague-Dawley rats ( n = 22) to ascertain whether MCH modulates sympathetic vasomotor tone, as well as barosympathetic, chemosympathetic, and somatosympathetic reflexes at the level of the spinal cord. Intrathecal injection of 10 μl of MCH produced a dose-dependent hypotension, bradycardia, and sympathoinhibition. Peak response was observed following administration of 1 mM MCH, causing a decrease in mean arterial pressure of 39 ± 2 mmHg ( P < 0.001), splanchnic sympathetic nerve activity of 78 ± 11% ( P < 0.001), and heart rate of 87 ± 11 beats per minute (bpm) ( P < 0.01). The two peaks of the somatosympathetic reflex were decreased by intrathecal MCH, 7 ± 3% ( P < 0.01) and 31 ± 6% ( P < 0.01), respectively, and the spinal component of the reflex was accentuated 96 ± 23% ( P < 0.05), with respect to the baseline for MCH, compared with the two peaks and spinal component of the somatosympathetic reflex elicited following saline injection with respect to the baseline for saline. MCH decreased the sympathetic gain to 120 s of hyperoxic hypercapnea (10% CO2 in 90% O2) and to 10–12 s poikilocapneic anoxia (100% N2) from 0.74 ± 0.14%/s to 0.23 ± 0.04%/s ( P < 0.05) and 16.47 ± 3.2% to 4.35 ± 1.56% ( P < 0.05), respectively. There was a 34% decrease in gain and a 62% decrease in range of the sympathetic baroreflex with intrathecal MCH. These data demonstrate that spinal MCH blunts the central regulation of sympathetic tone and adaptive sympathetic reflexes.
Placental and vascular adaptations to exercise training before and during pregnancy in the rat
Authors: Gilbert Jeffrey S. , Banek Christopher T. , Bauer Ashley J. , Gingery Anne , Dreyer Hans C.
Published: July 2012

Although exercise during pregnancy is generally recommended and thought to be beneficial to mother and fetus, the nature of the adaptations to exercise during pregnancy and how they may be beneficial remain poorly understood. Recent studies suggest that exercise may stimulate expression of several cytoprotective and pro-angiogenic molecules such as heat shock proteins (HSP) and vascular endothelial growth factors (VEGF). We hypothesized that exercise training during pregnancy improves angiogenic balance, increases HSP expression, and improves endothelial function. Female rats were given access to an exercise wheel for 6 wk before and during pregnancy. On day 19 of pregnancy tissues were collected and snap frozen for later analysis. Western blots were performed in skeletal muscle and placenta. HSP 27 (3.7 ± 0.36 vs. 2.2 ± 0.38; P < 0.05), HSP 60 (2.2 ± 0.73 vs. 0.49 ± 0.08; P < 0.05), and HSP 90 (0.33 ± 0.09 vs. 0.11 ± 0.02; P < 0.05) were increased in the placentas of exercise-trained rats compared with sedentary controls. In addition, exercise training increased ( P < 0.05) plasma free VEGF and augmented ( P < 0.05) endothelium-dependent vascular relaxation compared with nonexercise control rats. The present data indicates chronic exercise training stimulates HSP expression in the placenta and that regular exercise training increases circulating VEGF in pregnant but not in nonpregnant rats. Although the present findings suggest that exercise before and during pregnancy may promote the expression of molecules that could attenuate placental and vascular dysfunction in complicated pregnancies, further studies are needed to determine the safety and effectiveness of exercise training as a therapeutic modality in pregnancy.
Inspiratory-resistive loading increases the ventilatory response to arousal but does not reduce genioglossus muscle activity on the return to sleep
Authors: Cori Jennifer M. , Nicholas Christian L. , Baptista Shaira , Huynh Ivan , Rochford Peter D. , O'Donoghue Fergal J. , Trinder John A. , Jordan Amy S.
Published: July 2012

Arousals from sleep are thought to predispose to obstructive sleep apnea by causing hyperventilation and hypocapnia, which reduce airway dilator muscle activity on the return to sleep. However, prior studies of auditory arousals have not resulted in reduced genioglossus muscle activity [GG-electromyogram (EMG)], potentially because airway resistance prior to arousal was low, leading to a small ventilatory response to arousal and minimal hypocapnia. Thus we aimed to increase the ventilatory response to arousal by resistive loading prior to auditory arousal and determine whether reduced GG-EMG occurred on the return to sleep. Eighteen healthy young men and women were recruited. Subjects were instrumented with a nasal mask with a pneumotachograph, an epiglottic pressure catheter, and intramuscular GG-EMG electrodes. Mask CO2levels were monitored. Three- to 15-s arousals from sleep were induced with auditory tones after resting breathing (No-Load) or inspiratory-resistive loading (Load; average 8.4 cmH2O·l−1·s−1). Peak minute ventilation following arousal was greater after Load than No-Load (mean ± SE; 8.0 ± 0.6 vs. 7.4 ± 0.6 l/min, respectively). However, the nadir end tidal partial pressure of CO2did not differ between Load conditions (43.1 ± 0.6 and 42.8 ± 0.5 mmHg, respectively), and no period of reduced GG activity occurred following the return to sleep (GG-EMG baseline, minimum after Load and No-Load = 2.9 ± 1.2%, 3.1 ± 1.3%, and 3.0 ± 1.3% max, respectively). These findings indicate that the hyperventilation, which occurs following tone-induced arousal, is appropriate for the prevailing level of respiratory drive, because loading did not induce marked hypocapnia or lower GG muscle activity on the return to sleep. Whether similar findings occur following obstructive events in patients remains to be determined.
Effects of contrast and contrast adaptation on static receptive field features in macaque area V1
Authors: Durand Jean-Baptiste , Girard Pascal , Barone Pascal , Bullier Jean , Nowak Lionel G.
Published: July 2012

The spatiotemporal features of the “static” receptive field (RF), as revealed with flashing bars or spots, determine other RF properties. We examined how some of these static RF features vary with contrast and contrast adaptation in area V1 of the anesthetized macaque monkey. RFs were mapped with light and dark flashing bars presented at three different contrasts, with the low and medium contrasts eliciting approximately 1/3 and 2/3 of the high-contrast response amplitude. The main results are as follows: 1) RF widths decreased when contrast decreased; however, the amount of decrease was less than that expected from an iceberg model and closer to the expectation of a contrast invariance of the RF width. 2) Area tuning experiments with drifting gratings showed an opposite effect of contrast: an increase in preferred stimulus diameter when contrast decreased. This implies that the effect of contrast on preferred stimulus size is not predictable from the static RF. 3) Contrast adaptation attenuated the effect of contrast on RF amplitude but did not significantly modify RF width. 4) RF subregion overlap was only marginally affected by changes in contrast and contrast adaptation; the classification of cells as simple and complex, when established from subregion overlap, appears to be robust with respect to changes in contrast and adaptation state. Previous studies have shown that the spatiotemporal features of the RF depend largely on the stimuli used to map the RF. This study shows that contrast is one elemental feature that contributes to the dynamics of the RF.
Alternative Reproductive Tactics in the Shell-Brooding Lake Tanganyika CichlidNeolamprologus brevis
Authors: Ota Kazutaka , Aibara Mitsuto , Morita Masaya , Awata Satoshi , Hori Michio , Kohda Masanori
Published: July 2012

Alternative reproductive tactics (ARTs) are found in several Lake Tanganyika shell-brooding cichlids. Field studies were conducted in the Wonzye population to examine reproductive ecology and ARTs in the Lake Tanganyika shell-brooding cichlidNeolamprologus brevis. We discovered that this fish occurred in both rocky- and sandy-bottom habitats, but in rocky habitats, brood-caring females exclusively occurred in shell-patches that another cichlid species created. AllN. brevisof both sexes in the patches were sexually mature, whereas immature males and females with unripe eggs were found frequently in sandy-bottom habitats. Males in sandy-bottom habitats were smaller, but fed more frequently and were in better somatic condition than males in the patches. Similar tendency was found in females. This indicates thatN. brevisuses different habitats depending on the stage of its life history, with migration from sandy-bottom habitats to the shell-patches for reproduction. Males in the patches exhibited different behavior patterns: floating above the patches and lying in the patches. The former was larger, more aggressive, and invested less in gonads (relative to body size) than the latter. These results accord with those of other shell-brooding Lake Tanganyika cichlids with ARTs, and they therefore suggest the presence of ARTs inN. brevis.
Skeletal Muscle Mitochondria and Aging: A Review
Authors: Peterson Courtney M. , Johannsen Darcy L. , Ravussin Eric
Published: July 2012

Aging is characterized by a progressive loss of muscle mass and muscle strength. Declines in skeletal muscle mitochondria are thought to play a primary role in this process. Mitochondria are the major producers of reactive oxygen species, which damage DNA, proteins, and lipids if not rapidly quenched. Animal and human studies typically show that skeletal muscle mitochondria are altered with aging, including increased mutations in mitochondrial DNA, decreased activity of some mitochondrial enzymes, altered respiration with reduced maximal capacity at least in sedentary individuals, and reduced total mitochondrial content with increased morphological changes. However, there has been much controversy over measurements of mitochondrial energy production, which may largely be explained by differences in approach and by whether physical activity is controlled for. These changes may in turn alter mitochondrial dynamics, such as fusion and fission rates, and mitochondrially induced apoptosis, which may also lead to net muscle fiber loss and age-related sarcopenia. Fortunately, strategies such as exercise and caloric restriction that reduce oxidative damage also improve mitochondrial function. While these strategies may not completely prevent the primary effects of aging, they may help to attenuate the rate of decline.
Final State Interaction Effects on theB+→J/ψρ+Decay
Authors: Mohammadi Behnam , Mehraban Hossein
Published: July 2012

The exclusive decay ofB+→J/ψρ+is studied in the framework of the QCD factorization (QCDF) method and final state interaction (FSI). A directB+→J/ψρ+decay is only occurred via a tree and a penguin based on the quark diagram analysis. The result that is found by using the QCDF method is less than the experimental result, so, the role of FSI is considered. The intermediate statesD+D̅0,D+*D̅0*,D+*D̅0, andD+D̅0*via the exchange ofD-andD-*are contributed to theB+→J/ψρ+decay. The above intermediate states is calculated by using the QCDF method. In the FSI effects the results of our calculations depend on “η” as the phenomenological parameter. The range of this parameter are selected from 1 to 2. For the exchanged particlesD-andD-*, it is found that ifη=1.58~1.83is selected the numbers of the branching ratio are placed in the experimental range. The experimental branching ratio ofB+→J/ψρ+decay is(5±0.8)×10-5, and our prediction number is(1.42±0.36)×10-5in the absence of FSI effects, and it becomes(4.2~5.8)×10-5when FSI contributions are taken into account.
Cytoreductive Surgery Plus Hyperthermic Perioperative Chemotherapy for Selected Patients with Peritoneal Metastases from Colorectal Cancer: A New Standard of Care or an Experimental Approach?
Authors: Sugarbaker Paul H.
Published: July 2012

Peritoneal metastases (PM) are a common presentation for patients with metastatic colorectal cancer (CRC), and the median survival of patients with PM is approximately one year. In a majority of patients, the disease remains limited to the peritoneal cavity. Therefore, investigators have applied cytoreductive surgery (CRS) and heated perioperative chemotherapy (HIPEC) as a standard approach for selected patients with PM from CRC. These investigators have demonstrated a very promising long-term survival in a subset of patients with a limited amount of isolated peritoneal metastatic disease. This paper presents the data that supports CRS and HIPEC as a treatment option for CRC patients with PM. These results of treatment are compared and contrasted to the results that can be expected with systemic chemotherapy alone.
Reproducing Kernel Method for Solving Nonlinear Differential‐Difference Equations
Authors: Mokhtari Reza , Toutian Isfahani Fereshteh , Mohammadi Maryam
Published: July 2012

On the basis of reproducing kernel Hilbert spaces theory, an iterative algorithm for solving some nonlinear differential‐difference equations (NDDEs) is presented. The analytical solution is shown in a series form in a reproducing kernel space, and the approximate solution un,m
is constructed by truncating the series to m terms. The convergence of un,m
to the analytical solution is also proved. Results obtained by the proposed method imply that it can be considered as a simple and accurate method for solving such differential‐difference problems.
The Impact of the Geologic History and Paleoclimate on the Diversification of East African Cichlids
Authors: Danley Patrick D. , Husemann Martin , Ding Baoqing , DiPietro Lyndsay M. , Beverly Emily J. , Peppe Daniel J.
Published: July 2012

The cichlid fishes of the East African Great Lakes are the largest extant vertebrate radiation identified to date. These lakes and their surrounding waters support over 2,000 species of cichlid fish, many of which are descended from a single common ancestor within the past 10 Ma. The extraordinary East African cichlid diversity is intricately linked to the highly variable geologic and paleoclimatic history of this region. Greater than 10 Ma, the western arm of the East African rift system began to separate, thereby creating a series of rift basins that would come to contain several water bodies, including the extremely deep Lakes Tanganyika and Malawi. Uplifting associated with this rifting backponded many rivers and created the extremely large, but shallow Lake Victoria. Since their creation, the size, shape, and existence of these lakes have changed dramatically which has, in turn, significantly influenced the evolutionary history of the lakes' cichlids. This paper reviews the geologic history and paleoclimate of the East African Great Lakes and the impact of these forces on the region's endemic cichlid flocks.
Frequency Modulation and Spatiotemporal Stability of the sCPG in Preterm Infants with RDS
Authors: Barlow Steven M. , Burch Mimi , Venkatesan Lalit , Harold Meredith , Zimmerman Emily
Published: July 2012

The nonnutritive suck (NNS) is an observable and accessible motor behavior which is often used to make inference about brain development and pre-feeding skill in preterm and term infants. The purpose of this study was to model NNS burst compression pressure dynamics in the frequency and time domain among two groups of preterm infants, including those with respiratory distress syndrome (RDS,N=15) and 17 healthy controls. Digitized samples of NNS compression pressure waveforms recorded at a 1-week interval were collected 15 minutes prior to a scheduled feed. Regression analysis and ANOVA revealed that healthy preterm infants produced longer NNS bursts and the mean burst initiation cycle frequencies were higher when compared to the RDS group. Moreover, the initial 5 cycles of the NNS burst manifest a frequency modulated (FM) segment which is a significant feature of the suck central pattern generator (sCPG), and differentially expressed in healthy and RDS infants. The NNS burst structure revealed significantly lower spatiotemporal index values for control versus RDS preterm infants during FM, and provides additional information on the microstructure of the sCPG which may be used to gauge the developmental status and progression of oromotor control systems among these fragile infants.
Evaluating User Response to In-Car Haptic Feedback Touchscreens Using the Lane Change Test
Authors: Pitts Matthew J. , Skrypchuk Lee , Wellings Tom , Attridge Alex , Williams Mark A.
Published: July 2012

Touchscreen interfaces are widely used in modern technology, from mobile devices to in-car infotainment systems. However, touchscreens impose significant visual workload demands on the user which have safety implications for use in cars. Previous studies indicate that the application of haptic feedback can improve both performance of and affective response to user interfaces. This paper reports on and extends the findings of a 2009 study conducted to evaluate the effects of different combinations of touchscreen visual, audible, and haptic feedback on driving and task performance, affective response, and subjective workload; the initial findings of which were originally published in (M. J. Pitts et al., 2009). A total of 48 non-expert users completed the study. A dual-task approach was applied, using the Lane Change Test as the driving task and realistic automotive use case touchscreen tasks. Results indicated that, while feedback type had no effect on driving or task performance, preference was expressed for multimodal feedback over visual alone. Issues relating to workload and cross-modal interaction were also identified.
Hallucination in a Seizure Patient Using Levetiracetam: A Case Report
Authors: Shakya D. R. , Dutta A. , Gautam R.
Published: July 2012

Levetiracetam, a relatively new antiepileptic drug (AED), is used mainly as adjuvant and less as monotherapy of seizure. Though rare, Levetiracetam is reported to induce hallucination. To highlight the potential of this adverse drug event, we report a seizure-case that had auditory hallucination with Levetiracetam. A 32-year lady had 7-year history of unresponsive spells which increased in the last year, also occurred while asleep and were diagnosed as “generalized seizure” with video-EEG. With gradual optimization of Levetiracetam to 2250 mg, she continuously heard distressing sound of saw cutting wooden blocks. After 3-day continuous auditory hallucination, Levetiracetam had to be changed to sodium valproate.
Dynamics of Foraging and Recruitment Behavior in the Asian Subterranean TermiteCoptotermes gestroi(Rhinotermitidae)
Authors: Arab Alberto , carollo Blanco Yara , Costa-Leonardo Ana Maria
Published: July 2012

The present study investigated the trail-following behavior of the subterranean termiteCoptotermes gestroi(Wasmann Rhinotermitidae) under laboratory conditions. The results showed that workers were the first to initiate the exploration to the food source. When food was discovered they returned to the nest laying a trail for recruiting nestmates to the food source. In this situation, workers always traveled significantly faster when returning from the arenas. Both workers and soldiers were recruited to the food source; however, the soldier/worker proportion was higher during the first phase of the recruitment. When no food was available, the number of recruited nestmates and the speed on their way back to the nest were significantly lower. The results also showed that scout foragers always laid trail pheromones when entering into unknown territories, and that chemical signals found in the food could induce workers ofC. gestroito increase their travel speed.
PV Power-Generation System with a Phase-Shift PWM Technique for High Step-Up Voltage Applications
Authors: Tsai Cheng-Tao , Chen Sin-Hua
Published: July 2012

A PV power-generation system with a phase-shift pulse-width modulation (PWM) technique for high step-up voltage applications is proposed. The proposed power-generation system consists of two stages. In the input stage, all power switches of the full-bridge converter with phase-shift technique can be operated with zero-current switching (ZCS) at turn-on or turn-off transition. Hence, the switching losses of the power switches can be reduced. Then, in the DC output stage, a voltage-doubler circuit is used to boost a high dc-link bus voltage. To supply a utility power, a dc/ac inverter is connected to induce a sinusoidal source. In order to draw a maximum power from PV arrays source, a microcontroller is incorporated with the perturbation and observation method to implement maximum power point tracking (MPPT) algorithm and power regulating scheme. In this study, a full load power of 300 W prototype has been built. Experimental results are presented to verify the performance and feasibility of the proposed PV power-generation system.
HELLP Syndrome Complicated with Postpartum Subcapsular Ruptured Liver Hematoma and Purtscher-Like Retinopathy
Authors: Cernea Daniela , Dragoescu Alice , Novac Marius
Published: July 2012

Purtscher's retinopathy is usually associated with trauma, acute pancreatitis, vasculitis, lupus, and bone fractures. It was rarely described postpartum in patients with preeclampsia as well as associated with HELLP syndrome. We present a case of a multiparous patient aged 44 with severe preeclampsia and postpartum HELLP syndrome complicated with Purtscher-like retinopathy and large ruptured subcapsular liver hematoma that required emergency abdominal surgery after premature delivery of a dead fetus. Postsurgical outcome was favorable regarding both liver function and visual acuity.
Effect of Intervention in Subjects with High Risk of Diabetes Mellitus in Pakistan
Authors: Iqbal Hydrie Muhammad Zafar , Basit Abdul , Shera A. Samad , Hussain Akhtar
Published: July 2012

Aims. To observe the rate of conversion from impaired glucose tolerance (IGT) to diabetes following lifestyle modification (LSM) or a combination of lifestyle and metformin compared to a control population with 18-month followup.Methods. Forty screening camps were organized, which 5000 people attended. Around 2300 persons filled the questionnaire and 1825 subjects were identified as high risk. Of 1739 subjects who took the oral glucose tolerance test, 317 subjects were identified as IGT. The 317 IGT subjects were randomized into three groups: control group was given standard medical advice, LSM group was given intensive lifestyle modification advice, while LSM + drug group was given intensive lifestyle advice and metformin 500 mg twice daily.Results. At the end, 273 subjects completed the study, giving a compliance rate of 86%. Total of 47 incident cases of diabetes were diagnosed (overall incidence was 4 cases per 1000 person-months with the incidence of 8.6 cases in control group, 2.5 cases in the LSM, and 2.3 cases in the LSM + drug groups).Conclusions. Study showed that lifestyle intervention had a major impact in preventing diabetes among IGT subjects in this region. Adding drug did not show any improved results. We recommend lifestyle advice and followup should be incorporated in primary health care.
Comparative Study of Endothelial Function and Uterine Artery Doppler Velocimetry between Pregnant Women with or without Preeclampsia Development
Authors: Brandão Augusto Henriques Fulgêncio , Pereira Ludmila Maria Guimarães , Gonçalves Alessandra Cristina de Oliveira , Reis Zilma Silveira Nogueira , Leite Henrique Vítor , Cabral Antônio Carlos Vieira
Published: July 2012

Background. Poor placentation and systemic endothelial dysfunction have been identified as main events in Preeclampsia (PE). The relationship and chronology of these phenomena are important if we are to understand the pathophysiological mechanisms underlying this major clinical problem.Objectives. To compare the evolution of placentation and endothelial function in normotensive and preeclamptic pregnancies.Patients and methods. In a prospective cohort study, 59 pregnant women with a high risk of developing PE were subjected to flow-mediated dilation (FMD) and to Doppler velocimetry of uterine arteries in order to obtain their Pulsatility Index (UtA-PI). The variations in the FMD and UtA-PI values, between 16+0and 19+6and 24+0and 27+6weeks of gestation, were compared, taking PE development into consideration.Results. Nine patients developed PE and the other 50 women remained normotensive. At 16+0to 19+6weeks of pregnancy, patients that developed PE presented higher values of UtA-PI than the normotensive group, but there was no difference in FMD results between them. At 24+0to 27+6weeks, the patients that developed PE presented higher values of UtA-PI and lower values of FMD than the women that remained normotensive.Conclusions. These results corroborate the evidence that endothelial injury is secondary to poor placentation.
A Hybrid Network Model to Extract Key Criteria and Its Application for Brand Equity Evaluation
Authors: Chen Chin-Yi , Li Chung-Wei
Published: July 2012

Making a decision implies that there are alternative choices to be considered, and a major challenge of decision‐making is to identify the adequate criteria for program planning or problem evaluation. The decision‐makers’ criteria consists of the characteristics or requirements each alternative must possess and the alternatives are rated on how well they possess each criterion. We often use criteria developed and used by different researchers and institutions, and these criteria have similar means and can be substituted for one another. Choosing from existing criteria offers a practical method to engineers hoping to derive a set of criteria for evaluating objects or programs. We have developed a hybrid model for extracting evaluation criteria which considers substitutions between the criteria. The model is developed based on Social Network Analysis and Maximum Mean De‐Entropy algorithms. In this paper, the introduced methodology will also be applied to analyze the criteria for assessing brand equity as an application example. The proposed model demonstrates that it is useful in planning feasibility criteria and has applications in other evaluation‐planning purposes.
HCV and Lymphoproliferation
Authors: Zignego Anna Linda , Giannini Carlo , Gragnani Laura
Published: July 2012

Hepatitis C virus (HCV) infection is a serious public health problem because of its worldwide diffusion and sequelae. It is not only a hepatotropic but also a lymphotropic agent and is responsible not only for liver injury—potentially evolving to cirrhosis and hepatocellular carcinoma—but also for a series of sometimes severely disabling extrahepatic diseases and, in particular, B-cell lymphoproliferative disorders. These latter range from benign, but prelymphomatous conditions, like mixed cryoglobulinemia, to frank lymphomas. Analogously withHelicobacter pylorirelated lymphomagenesis, the study of the effects of viral eradication confirmed the etiopathogenetic role of HCV and showed it is an ideal model for better understanding of the molecular mechanisms involved. Concerning these latter, several hypotheses have been proposed over the past two decades which are not mutually exclusive. These hypotheses have variously emphasized the important role played by sustained stimulation of the immune system by HCV, infection of the lymphatic cells, viral proteins, chromosomal aberrations, cytokines, or microRNA molecules. In this paper we describe the main hypotheses that have been proposed with the corresponding principal supporting data.
IDO Is a Nodal Pathogenic Driver of Lung Cancer and Metastasis Development
Authors: Smith Courtney , Chang Mee Young , Parker Katherine H. , Beury Daniel W. , DuHadaway James B. , Flick Hollie E. , Boulden Janette , Sutanto-Ward Erika , Soler Alejandro Peralta , Laury-Kleintop Lisa D. , Mandik-Nayak Laura , Metz Richard , Ostrand-Rosenberg Suzanne , Prendergast George C. , Muller Alexander J.
Published: July 2012

Indoleamine 2,3-dioxygenase (IDO) enzyme inhibitors have entered clinical trials for cancer treatment based on preclinical studies, indicating that they can defeat immune escape and broadly enhance other therapeutic modalities. However, clear genetic evidence of the impact of IDO on tumorigenesis in physiologic models of primary or metastatic disease is lacking. Investigating the impact of Ido1 gene disruption in mouse models of oncogenic KRAS-induced lung carcinoma and breast carcinoma–derived pulmonary metastasis, we have found that IDO deficiency resulted in reduced lung tumor burden and improved survival in both models. Micro-computed tomographic (CT) imaging further revealed that the density of the underlying pulmonary blood vessels was significantly reduced in Ido1-nullizygous mice. During lung tumor and metastasis outgrowth, interleukin (IL)-6 induction was greatly attenuated in conjunction with the loss of IDO. Biologically, this resulted in a consequential impairment of protumorigenic myeloid-derived suppressor cells (MDSC), as restoration of IL-6 recovered both MDSC suppressor function and metastasis susceptibility in Ido1-nullizygous mice. Together, our findings define IDO as a prototypical integrative modifier that bridges inflammation, vascularization, and immune escape to license primary and metastatic tumor outgrowth.

Significance: This study provides preclinical, genetic proof-of-concept that the immunoregulatory enzyme IDO contributes to autochthonous carcinoma progression and to the creation of a metastatic niche. IDO deficiency in vivo negatively impacted both vascularization and IL-6–dependent, MDSC-driven immune escape, establishing IDO as an overarching factor directing the establishment of a protumorigenic environment. Cancer Discov; 2(8); 722–35. ©2012 AACR.

Read the Commentary on this article by Novitskiy et al., p. 673.

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Prenatal Immune Stress in Rats Dampens Fever during Adulthood
Authors: Abdeslam Mouihate
Published: July 2012

Fever is a major component of the host’s defense against infection. Inadequate febrile response can predispose an individual to the deleterious effects of infection. Neonatal exposure to infectious agents such as bacterial lipopolysaccharide (LPS) permanently dampens the adult febrile response. Whether prenatal immune challenge alters febrile response during adulthood is still not known. In the present study, LPS (100 µg/kg, i.p.) or pyrogen-free saline was administered to pregnant rats on either gestation day (GD) 12, 15 or 19 and the febrile response of their respective adult offspring was monitored. During adulthood (>70 days old), the rats born to LPS-injected dams on GD15 displayed a significantly attenuated febrile response to LPS (50 µg/kg, i.p.) compared to their control counterparts born to dams given saline on GD15. Immune challenge during either early (GD12) or late (GD19) pregnancy did not have a significant impact on fever in the adult offspring. Immune challenge on GD15, but not on GD12 or 19, heightened the plasma corticosterone response to a subsequent LPS injection to the adult offspring but did not have a significant effect on their basal plasma corticosterone levels. Finally, LPS-induced COX-2 in the fever-controlling regions of the hypothalamus was significantly reduced in the adult rats born to dams given LPS on GD15 compared to their counterparts born to dams given saline on GD15. Such COX-2 reduction was not observed in the adult offspring born to dams given LPS on either GD12 or 19. Taken together, these data suggest that a single immune challenge during a critical window of pregnancy alters the neuroimmune response in adult offspring.
Differentiation of Human Embryonic Stem Cells and Induced Pluripotent Stem Cells to Cardiomyocytes
Authors: Mummery Christine L. , Zhang Jianhua , Ng Elizabeth S. , Elliott David A. , Elefanty Andrew G. , Kamp Timothy J.
Published: July 2012

Since human embryonic stem cells were first differentiated to beating cardiomyocytes a decade ago, interest in their potential applications has increased exponentially. This has been further enhanced over recent years by the discovery of methods to induce pluripotency in somatic cells, including those derived from patients with hereditary cardiac diseases. Human pluripotent stem cells have been among the most challenging cell types to grow stably in culture, but advances in reagent development now mean that most laboratories can expand both embryonic and induced pluripotent stem cells robustly using commercially available products. However, differentiation protocols have lagged behind and in many cases only produce the cell types required with low efficiency. Cardiomyocyte differentiation techniques were also initially inefficient and not readily transferable across cell lines, but there are now a number of more robust protocols available. Here, we review the basic biology underlying the differentiation of pluripotent cells to cardiac lineages and describe current state-of-the-art protocols, as well as ongoing refinements. This should provide a useful entry for laboratories new to this area to start their research. Ultimately, efficient and reliable differentiation methodologies are essential to generate desired cardiac lineages to realize the full promise of human pluripotent stem cells for biomedical research, drug development, and clinical applications.
Microfluidic Single-Cell Analysis Shows That Porcine Induced Pluripotent Stem Cell–Derived Endothelial Cells Improve Myocardial Function by Paracrine Activation
Authors: Gu Mingxia , Nguyen Patricia K. , Lee Andrew S. , Xu Dan , Hu Shijun , Plews Jordan R. , Han Leng , Huber Bruno C. , Lee Won Hee , Gong Yongquan , de Almeida Patricia E. , Lyons Jennifer , Ikeno Fumi , Pacharinsak Cholawat , Connolly Andrew J. , Gambhir Sanjiv S. , Robbins Robert C. , Longaker Michael T. , Wu Joseph C.
Published: July 2012

Rationale:

Induced pluripotent stem cells (iPSCs) hold great promise for the development of patient-specific therapies for cardiovascular disease. However, clinical translation will require preclinical optimization and validation of large-animal iPSC models.

Objective:

To successfully derive endothelial cells from porcine iPSCs and demonstrate their potential utility for the treatment of myocardial ischemia.

Methods and Results:

Porcine adipose stromal cells were reprogrammed to generate porcine iPSCs (piPSCs). Immunohistochemistry, quantitative PCR, microarray hybridization, and angiogenic assays confirmed that piPSC-derived endothelial cells (piPSC-ECs) shared similar morphological and functional properties as endothelial cells isolated from the autologous pig aorta. To demonstrate their therapeutic potential, piPSC-ECs were transplanted into mice with myocardial infarction. Compared with control, animals transplanted with piPSC-ECs showed significant functional improvement measured by echocardiography (fractional shortening at week 4: 27.2±1.3% versus 22.3±1.1%;
P
<0.001) and MRI (ejection fraction at week 4: 45.8±1.3% versus 42.3±0.9%;
P
<0.05). Quantitative protein assays and microfluidic single-cell PCR profiling showed that piPSC-ECs released proangiogenic and antiapoptotic factors in the ischemic microenvironment, which promoted neovascularization and cardiomyocyte survival, respectively. Release of paracrine factors varied significantly among subpopulations of transplanted cells, suggesting that transplantation of specific cell populations may result in greater functional recovery.

Conclusions:

In summary, this is the first study to successfully differentiate piPSCs-ECs from piPSCs and demonstrate that transplantation of piPSC-ECs improved cardiac function after myocardial infarction via paracrine activation. Further development of these large animal iPSC models will yield significant insights into their therapeutic potential and accelerate the clinical translation of autologous iPSC-based therapy.
Greater Exposure to Sexual Content in Popular Movies Predicts Earlier Sexual Debut and Increased Sexual Risk Taking
Authors: O’Hara Ross E. , Gibbons Frederick X. , Gerrard Meg , Li Zhigang , Sargent James D.
Published: July 2012

Early sexual debut is associated with risky sexual behavior and an increased risk of unplanned pregnancy and sexually transmitted infections later in life. The relations among early movie sexual exposure (MSE), sexual debut, and risky sexual behavior in adulthood (i.e., multiple sexual partners and inconsistent condom use) were examined in a longitudinal study of U.S. adolescents. MSE was measured using the Beach method, a comprehensive procedure for media content coding. Controlling for characteristics of adolescents and their families, analyses showed that MSE predicted age of sexual debut, both directly and indirectly through changes in sensation seeking. MSE also predicted engagement in risky sexual behaviors both directly and indirectly via early sexual debut. These results suggest that MSE may promote sexual risk taking both by modifying sexual behavior and by accelerating the normal rise in sensation seeking during adolescence.
Using Game Theory to Examine Incentives in Influenza Vaccination Behavior
Authors: Chapman Gretchen B. , Li Meng , Vietri Jeffrey , Ibuka Yoko , Thomas David , Yoon Haewon , Galvani Alison P.
Published: July 2012

The social good often depends on the altruistic behavior of specific individuals. For example, epidemiological studies of influenza indicate that elderly individuals, who face the highest mortality risk, are best protected by vaccination of young individuals, who contribute most to disease transmission. To examine the conditions under which young people would get vaccinated to protect elderly people, we conducted a game-theory experiment that mirrored real-world influenza transmission, with “young” players contributing more than “elderly” players to herd immunity. Participants could spend points to get vaccinated and reduce the risk of influenza. When players were paid according to individual point totals, more elderly than young players got vaccinated, a finding consistent with the Nash equilibrium predicting self-interested behavior. When players were paid according to group point totals, however, more young than elderly players got vaccinated—a finding consistent with the utilitarian equilibrium predicting group-optimal behavior—which resulted in higher point totals than when players were paid for their individual totals. Thus, payout structure affected whether individuals got vaccinated for self-interest or group benefit.
Migration of Health Workers in the Pacific Islands
Authors: Yamamoto T. S. , Sunguya B.F. , Shiao L. W. , Amiya R. M. , Saw Y. M. , Jimba M.
Published: July 2012

Human resources for health (HRH) are a crucial component of a well-functioning health system. Problems in the global HRH supply and distribution are an obstacle to achieving the health-related Millennium Development Goals and other health outcomes. The Pacific Island region, covering 20 000 to 30 000 islands in the South Pacific Ocean, is suffering a serious HRH crisis. Yet updated evidence and data are not available for the 22 Pacific Island Countries and Territories. The objective of this study was thus to explore the current HRH situation in the Pacific Island region, focusing particularly on the issue of health workforce migration. HRH trends and gaps differ by country, with some showing increases in HRH density over the past 20 years whereas others have made negligible progress. Currently, three Pacific Island countries are facing critical HRH shortages, a worsening of the situation from 2006, when HRH issues were first brought to widespread global attention. In this region, skilled personnel migration is a major issue contributing to the limited availability of HRH. Political commitment from source and destination countries to strengthen HRH would be a key factor toward increasing efforts to train new health personnel and to implement effective retention strategies.
EU social policy and the governance architecture of Europe 2020
Authors: Armstrong Kenneth A
Published: July 2012

As the successor to the decade-long Lisbon agenda, Europe 2020 is the European Union’s 10-year strategy for ‘smart’, ‘sustainable’ and ‘inclusive’ growth. This article analyses the ‘governance architecture’ of this new agenda, and, more particularly, its social dimension. Insofar as Europe 2020 has a social dimension it is located within a suite of thematic ‘flagship initiatives’, as well as within a policy coordination framework that, while building upon the Lisbon agenda’s governance architecture, now forms part of the European Semester framework. Whereas the flagship initiatives continue a long tradition of the deployment of non-legislative instruments and EU funds towards the EU’s social goals, the role to be played by the ‘open method of coordination’ as a ‘new’ post-Lisbon form of EU social governance remains unclear. Indeed, the risk is that political energy will be concentrated on policy coordination as a means of strengthening EU economic governance rather than as a vehicle for articulating a progressive social policy vision.
Freestanding Inpatient Rehabilitation Facility Performance Following the 60 Percent Rule
Authors: Shay Patrick D. , Ozcan Yasar A.
Published: July 2012

The 60 percent rule has served as a controversial policy change within the postacute care sector since its revision in 2004, requiring inpatient rehabilitation facilities (IRFs) to admit no less than 60% of patients according to 1 of 13 specific conditions or else risk the loss of IRF designation according to Medicare’s prospective payment system. Using a contingency theory framework, this study proposes that the 60 percent rule introduced considerable uncertainty into freestanding IRFs’ operational environment, and as a result, IRFs’ operational performance varied according to their “fit” between certain structural characteristics and the pervasive environmental uncertainty. The results suggest that operational performance, as measured by facility Malmquist Index scores, decreased on average for freestanding IRFs following the 60 percent rule’s enforcement in 2005. In contrast, organizations possessing structural characteristics that better “fit” the heightened environmental uncertainty exhibited improved performance on average during the study’s 6-year time period.
How effective are affective activities? Relative benefits of two types of structured input activities as part of a computer-delivered lesson on the Spanish subjunctive
Authors: Henshaw Florencia
Published: July 2012

Proponents of Processing Instruction (VanPatten, 2005) claim that learners benefit most when presented with both referential and affective structured input activities. Following a classic pretest–posttest design, the present study investigates the role of these two types of activities on the learning of the Spanish subjunctive. Groups differed only with respect to the types of activities completed during practice: (1) affective activities only, (2) referential activities only, or (3) referential activities followed by affective activities. All groups showed a significant improvement in performance on recognition and interpretation tasks, suggesting that both types of activities, either in isolation or combined, may be equally beneficial to learners. All practice conditions experienced a decline in performance over the span of two weeks, but delayed posttest scores were still significantly higher than pretest scores, indicating that some of the gains from instruction were maintained over time. Additionally, in the case of interpretation items, results revealed that the two groups that engaged in affective activities were able to better maintain learning gains over the span of two weeks than the group that completed only referential activities. Findings are discussed in relation to the role of task-essentialness in structured input practice.
Characterization of Neuronal Intrinsic Properties and Synaptic Transmission in Layer I of Anterior Cingulate Cortex from Adult Mice
Authors: Li Xiang-Yao , Chen Tao , Descalzi Giannina , Koga Kohei , Qiu Shuang , Zhuo Min
Published: July 2012

The neurons in neocortex layer I (LI) provide inhibition to the cortical networks. Despite increasing use of mice for the study of brain functions, few studies were reported about mouse LI neurons. In the present study, we characterized intrinsic properties of LI neurons of the anterior cingulate cortex (ACC), a key cortical area for sensory and cognitive functions, by using whole-cell patch clamp recording approach. Seventy one neurons in LI and 12 pyramidal neurons in LII/III were recorded. Although all of the LI neurons expressed continuous adapting firing characteristics, the unsupervised clustering results revealed five groups in the ACC, including: Spontaneous firing neurons; Delay-sAHP neurons, Delay-fAHP neurons, and two groups of neurons with ADP, named ADP1 and ADP2, respectively. Using pharmacological approaches, we found that LI neurons received both excitatory (mediated by AMPA, kainate and NMDA receptors), and inhibitory inputs (which were mediated by GABAA receptors). Our studies provide the first report characterizing the electrophysiological properties of neurons in LI of the ACC from adult mice.
More Active Mums in Stirling (MAMMiS): a physical activity intervention for postnatal women. Study protocol for a randomized controlled trial
Authors: Gilinsky Alyssa S , Hughes Adrienne R , McInnes Rhona J
Published: July 2012

Background

Many postnatal women are insufficiently physically active in the year after childbirth and could benefit from interventions to increase activity levels. However, there is limited information about the efficacy, feasibility and acceptability of motivational and behavioral interventions promoting postnatal physical activity in the UK.

Methods

The MAMMiS study is a randomized, controlled trial, conducted within a large National Health Service (NHS) region in Scotland. Up to 76 postnatal women will be recruited to test the impact of two physical activity consultations and a 10-week group pram-walking program on physical activity behavior change. The intervention uses evidence-based motivational and behavioral techniques and will be systematically evaluated using objective measures (accelerometers) at three months, with a maintenance measure taken at a six-month follow-up. Secondary health and well-being measures and psychological mediators of physical activity change are included.

Discussion

The (MAMMiS study will provide a test of a theoretical and evidence-based physical activity behavior change intervention for postnatal women and provide information to inform future intervention development and testing within this population.

Trial registration

Current Controlled Trials ISRCTN79011784