bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Performance Testing for Power and Return to Sports
Authors: Manske Robert , Reiman Michael
Published: March 2013

Context:

Functional performance testing of athletes can determine physical limitations that may affect sporting activities. Optimal functional performance testing simulates the athlete’s activity.

Evidence Acquisition:

A Medline search from 1960 to 2012 was implemented with the keywords functional testing, functional impairment testing, and functional performance testing in the English language. Each author also undertook independent searches of article references.

Conclusion:

Functional performance tests can bridge the gap between general physical tests and full, unrestricted athletic activity.
Efficient production of methane from artificial garbage waste by a cylindrical bioelectrochemical reactor containing carbon fiber textiles
Authors: Sasaki Daisuke , Sasaki Kengo , Watanabe Atsushi , Morita Masahiko , Igarashi Yasuo , Ohmura Naoya
Published: March 2013

A cylindrical bioelectrochemical reactor (BER) containing carbon fiber textiles (CFT; BER + CFT) has characteristics of bioelectrochemical and packed-bed systems. In this study, utility of a cylindrical BER + CFT for degradation of a garbage slurry and recovery of biogas was investigated by applying 10% dog food slurry. The working electrode potential was electrochemically regulated at −0.8 V (vs. Ag/AgCl). Stable methane production of 9.37 L-CH4 · L−1 · day−1 and dichromate chemical oxygen demand (CODcr) removal of 62.5% were observed, even at a high organic loading rate (OLR) of 89.3 g-CODcr · L−1 · day−1. Given energy as methane (372.6 kJ · L−1 · day−1) was much higher than input electric energy to the working electrode (0.6 kJ · L−1 · day−1) at this OLR. Methanogens were highly retained in CFT by direct attachment to the cathodic working electrodes (52.3%; ratio of methanogens to prokaryotes), compared with the suspended fraction (31.2%), probably contributing to the acceleration of organic material degradation and removal of organic acids. These results provide insight into the application of cylindrical BER + CFT in efficient methane production from garbage waste including a high percentage of solid fraction.
Complex adaptive systems modeling with Repast Simphony
Authors: North Michael J , Collier Nicholson T , Ozik Jonathan , Tatara Eric R , Macal Charles M , Bragen Mark , Sydelko Pam
Published: March 2013

Purpose

This paper is to describe development of the features and functions of Repast Simphony, the widely used, free, and open source agent-based modeling environment that builds on the Repast 3 library. Repast Simphony was designed from the ground up with a focus on well-factored abstractions. The resulting code has a modular architecture that allows individual components such as networks, logging, and time scheduling to be replaced as needed. The Repast family of agent-based modeling software has collectively been under continuous development for more than 10 years.

Method

Includes reviewing other free and open-source modeling libraries and environments as well as describing the architecture of Repast Simphony. The architectural description includes a discussion of the Simphony application framework, the core module, ReLogo, data collection, the geographical information system, visualization, freeze drying, and third party application integration.

Results

Include a review of several Repast Simphony applications and brief tutorial on how to use Repast Simphony to model a simple complex adaptive system.

Conclusions

We discuss opportunities for future work, including plans to provide support for increasingly large-scale modeling efforts.
The ‘39 steps’: an algorithm for performing statistical analysis of data on energy intake and expenditure
Authors: Speakman John R. , Fletcher Quinn , Vaanholt Lobke
Published: March 2013

The epidemics of obesity and diabetes have aroused great interest in the analysis of energy balance, with the use of organisms ranging from nematode worms to humans. Although generating energy-intake or -expenditure data is relatively straightforward, the most appropriate way to analyse the data has been an issue of contention for many decades. In the last few years, a consensus has been reached regarding the best methods for analysing such data. To facilitate using these best-practice methods, we present here an algorithm that provides a step-by-step guide for analysing energy-intake or -expenditure data. The algorithm can be used to analyse data from either humans or experimental animals, such as small mammals or invertebrates. It can be used in combination with any commercial statistics package; however, to assist with analysis, we have included detailed instructions for performing each step for three popular statistics packages (SPSS, MINITAB and R). We also provide interpretations of the results obtained at each step. We hope that this algorithm will assist in the statistically appropriate analysis of such data, a field in which there has been much confusion and some controversy.
Experimental tests of mate choice in nonhuman mammals: the need for an integrative approach
Authors: Charlton Benjamin D.
Published: March 2013

Experimental studies of mate choice have normally focused on non-mammal animal species, in which female mating preferences are based on clearly defined male traits. Because mammals are invariably larger and behaviourally more complex, they are less suited to this type of experimentation. Nevertheless, numerous studies on nonhuman mammals have shown that females appear to actively choose their mates. In this Commentary, I review the current literature to reveal that most experimental tests of mate choice in mammals are unable to reveal the actual male phenotypic trait(s) of female preference, which is crucial for identifying male characteristics under sexual selection. In addition, very few studies take into account female oestrous stage, or quantify the fitness benefits to discriminating females. Future work should concentrate on demonstrating female preferences for specific male traits that are shown by genetic paternity analysis to be correlated with male reproductive success, using setups that control for the effects of male and female mating strategies and in which the actual experiments are performed during the female's peak oestrous period.
Variation in temperature tolerance among families of Atlantic salmon (Salmo salar) is associated with hypoxia tolerance, ventricle size and myoglobin level
Authors: Anttila Katja , Dhillon Rashpal S. , Boulding Elizabeth G. , Farrell Anthony P. , Glebe Brian D. , Elliott Jake A. K. , Wolters William R. , Schulte Patricia M.
Published: March 2013

In fishes, performance failure at high temperature is thought to be due to a limitation on oxygen delivery (the theory of oxygen and capacity limited thermal tolerance, OCLTT), which suggests that thermal tolerance and hypoxia tolerance might be functionally associated. Here we examined variation in temperature and hypoxia tolerance among 41 families of Atlantic salmon (Salmo salar), which allowed us to evaluate the association between these two traits. Both temperature and hypoxia tolerance varied significantly among families and there was a significant positive correlation between critical maximum temperature (CTmax) and hypoxia tolerance, supporting the OCLTT concept. At the organ and cellular levels, we also discovered support for the OCLTT concept as relative ventricle mass (RVM) and cardiac myoglobin (Mb) levels both correlated positively with CTmax (R2=0.21, P<0.001 and R2=0.17, P=0.003, respectively). A large RVM has previously been shown to be associated with high cardiac output, which might facilitate tissue oxygen supply during elevated oxygen demand at high temperatures, while Mb facilitates the oxygen transfer from the blood to tissues, especially during hypoxia. The data presented here demonstrate for the first time that RVM and Mb are correlated with increased upper temperature tolerance in fish. High phenotypic variation between families and greater similarity among full- and half-siblings suggests that there is substantial standing genetic variation in thermal and hypoxia tolerance, which could respond to selection either in aquaculture or in response to anthropogenic stressors such as global climate change.
Design of Survivable Networks Using Three- and Four-Partition Facets
Authors: Agarwal Yogesh
Published: March 2013

This paper considers the problem of designing a multicommodity network with single facility type subject to the requirement that under failure of any single edge, the network should permit a feasible flow of all traffic. We study the polyhedral structure of the problem by considering the multigraph obtained by shrinking the nodes, but not the edges, in a k-partition of the original graph. A key theorem is proved according to which a facet of the k-node problem defined on the multigraph resulting from a k-partition is also facet defining for the larger problem under a mild condition. After reviewing the prior work on two-partition inequalities, we develop two classes of three-partition inequalities and a large number of inequality classes based on four-partitions. Proofs of facet-defining status for some of these are provided, while the rest are stated without proof. Computational results show that the addition of three- and four-partition inequalities results in substantial increase in the bound values compared to those possible with two-partition inequalities alone. Problems of 35 nodes and 80 edges with fully dense traffic matrices have been solved optimally within a few minutes of computer time.
Drug Monographs: Bosutinib and Regorafenib
Authors: Solimando Dominic A. , Waddell J. Aubrey
Published: March 2013

The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases.
Ensuring the Safety of Sterile Admixtures Prepared outside of the Institution
Authors: Eberts Matthew W. , Cecere David A. , Mark Scott
Published: March 2013

Director's Forum is designed to guide pharmacy leaders in establishing patient-centered services in hospitals and health systems. This article provides an overview of outsourcing sterile products and discusses tools that pharmacy leaders can use to ensure the safety of the medications dispensed in their institution.
Phentermine/Topiramate for the Treatment of Obesity
Authors: Smith Steven M , Meyer Melissa , Trinkley Katy E
Published: March 2013

OBJECTIVE

To review the pharmacology, efficacy, and safety of phentermine/topiramate (PHEN/TPM) in the management of obese patients.

DATA SOURCES

MEDLINE (1966-July 2012) was searched using the terms weight loss, obesity, phentermine and topiramate, phentermine, topiramate, Qnexa, Qsymia, and VI-0521. Additionally, the new drug application and prescribing information for PHEN/TPM were retrieved.

STUDY SELECTION/DATA EXTRACTION

All studies considering the pharmacology, efficacy, and safety of PHEN/TPM were reviewed with a focus on efficacy and safety data from Phase 3 trials.

DATA SYNTHESIS

In 3 Phase 3 trials (EQUIP, CONQUER, and SEQUEL), treatment with PHEN/TPM consistently demonstrated statistically significant weight loss compared with placebo. After 56 weeks of treatment, percent weight loss achieved with PHEN/TPM was 10.6%, 8.4%, and 5.1% with 15/92 mg, 7.5/46 mg, and 3.75/23 mg, respectively (p < 0.0001). The 52-week extension study (SEQUEL) showed maintained weight loss over 2 years with 9.3% and 10.5% weight loss from baseline for 7.5/46 mg and 15/92 mg PHEN/TPM (p < 0.0001). A significantly higher proportion of patients achieved greater than 5%, 10%, or 15% weight loss with PHEN/TPM compared with placebo. Significant reductions in waist circumference, fasting triglycerides, and fasting glucoses were also attributable to PHEN/TPM. The drug was generally well tolerated in clinical trials. Adverse reactions occurring in 5% or more of study subjects included paresthesia, dizziness, dysgeusia, insomnia, constipation, and dry mouth.

CONCLUSIONS

PHEN/TPM is a new, once-daily, controlled-release, combination weight-loss product approved as an adjunct to diet and exercise for chronic weight management of obese or overweight patients with weight-related comorbidities. PHEN/TPM is modestly effective and a viable option for patients interested in losing weight, although long-term safety data are lacking.
Alternative Monitoring of Argatroban Using Plasma-Diluted Thrombin Time
Authors: Wanat Matthew A , Hart Sara R , Putney David , Liebl Michael G , Chandler Wayne
Published: March 2013

OBJECTIVE

To report a case of heparin-induced thrombocytopenia (HIT) in a patient with concurrent liver dysfunction and a prolonged baseline activated partial thromboplastin time (aPTT) in whom argatroban therapy was monitored with aPTT and a novel plasma-diluted thrombin assay.

CASE SUMMARY

An 80-year-old man with HIT and liver dysfunction was treated with argatroban, which was initiated at a dose of 0.5 μg/kg/min and gradually decreased to 0.09 μg/kg/min. The patient had a mildly prolonged aPTT at baseline (37.5 seconds). He was concurrently monitored with aPTT, per institution protocol, and plasma-diluted thrombin time. Plasma-diluted thrombin times were consistently lower than aPTTs, but mirrored the trend of the aPTTs. Eleven hours after argatroban was stopped, the aPTT remained elevated (53.9 seconds), while the plasma-diluted thrombin time returned to normal range (26.4 seconds). The patient's therapy was transitioned to warfarin and he had a hospital course with no thrombotic or bleeding complications.

DISCUSSION

Plasma-diluted thrombin time is a novel laboratory test consisting of 1 part patient plasma diluted with 3 parts normal plasma. Plasma-diluted thrombin time has been shown to blunt the sensitivity of the thrombin time and may be more accurate for drug monitoring. A MEDLINE search revealed 2 studies using the plasma-diluted thrombin time assay. The first study compared aPTT and plasma-diluted thrombin times in blood samples mixed with argatroban, bivalirudin, or lepirudin at 3 different concentrations. Blood samples contained lupus inhibitors, vitamin k deficiency, or normal baseline aPTTs. The aPTT overestimated drug concentrations in all samples with lupus anticoagulant and vitamin k deficiency, while the plasma-diluted thrombin time correctly estimated drug concentrations in nearly all samples. The second study looked at monitoring dabigatran with plasma-diluted thrombin time and found a linear relationship between the plasma-diluted thrombin time and the dabigatran dose-response curve.

CONCLUSIONS

Plasma-diluted thrombin time may be an alternative for direct thrombin inhibitor monitoring in patients with elevated aPTT values at baseline. Further randomized control trials are needed to determine its applicability in clinical practice.
Tissue- and Cell-Specific Co-localization of Intracellular Gelatinolytic Activity and Matrix Metalloproteinase 2
Authors: Solli Ann Iren , Fadnes Bodil , Winberg Jan-Olof , Uhlin-Hansen Lars , Hadler-Olsen Elin
Published: March 2013

Matrix metalloproteinase 2 (MMP-2) is a proteolytic enzyme that degrades extracellular matrix proteins. Recent studies indicate that MMP-2 also has a role in intracellular proteolysis during various pathological conditions, such as ischemic injuries in heart and brain and in tumor growth. The present study was performed to map the distribution of intracellular MMP-2 activity in various mouse tissues and cells under physiological conditions. Samples from normal brain, heart, lung, liver, spleen, pancreas, kidney, adrenal gland, thyroid gland, gonads, oral mucosa, salivary glands, esophagus, intestines, and skin were subjected to high-resolution in situ gelatin zymography and immunohistochemical staining. In hepatocytes, cardiac myocytes, kidney tubuli cells, epithelial cells in the oral mucosa as well as in excretory ducts of salivary glands, and adrenal cortical cells, we found strong intracellular gelatinolytic activity that was significantly reduced by the metalloprotease inhibitor EDTA but not by the cysteine protease inhibitor E-64. Furthermore, the gelatinolytic activity was co-localized with MMP-2. Western blotting and electron microscopy combined with immunogold labeling revealed the presence of MMP-2 in different intracellular compartments of isolated hepatocytes. Our results indicate that MMP-2 takes part in intracellular proteolysis in specific tissues and cells during physiological conditions.
Resting-State Functional Connectivity Predicts Impulsivity in Economic Decision-Making
Authors: Li Nan , Ma Ning , Liu Ying , He Xiao-Song , Sun De-Lin , Fu Xian-Ming , Zhang Xiaochu , Han Shihui , Zhang Da-Ren
Published: March 2013

Increasing neuroimaging evidence suggests an association between impulsive decision-making behavior and task-related brain activity. However, the relationship between impulsivity in decision-making and resting-state brain activity remains unknown. To address this issue, we used functional MRI to record brain activity from human adults during a resting state and during a delay discounting task (DDT) that requires choosing between an immediate smaller reward and a larger delayed reward. In experiment I, we identified four DDT-related brain networks. The money network (the striatum, posterior cingulate cortex, etc.) and the time network (the medial and dorsolateral prefrontal cortices, etc.) were associated with the valuation process; the frontoparietal network and the dorsal anterior cingulate cortex–anterior insular cortex network were related to the choice process. Moreover, we found that the resting-state functional connectivity of the brain regions in these networks was significantly correlated with participants' discounting rate, a behavioral index of impulsivity during the DDT. In experiment II, we tested an independent group of subjects and demonstrated that this resting-state functional connectivity was able to predict individuals' discounting rates. Together, these findings suggest that resting-state functional organization of the human brain may be a biomarker of impulsivity and can predict economic decision-making behavior.
Strength of Coupling within a Mnemonic Control Network Differentiates Those Who Can and Cannot Suppress Memory Retrieval
Authors: Paz-Alonso Pedro M. , Bunge Silvia A. , Anderson Michael C. , Ghetti Simona
Published: March 2013

The ability to direct our thought processes influences not only what we do, but also what we remember later. Here we sought to identify the brain network that supports the ability to control memory retrieval and to understand the neural basis of age-related changes and individual differences in the capacity for mnemonic control. To this end, we collected functional MRI data from 43 children and young adults while they attempted to retrieve or suppress retrieval of previously learned associations. Seed-based functional connectivity analyses revealed a largely right-lateralized dorsolateral prefrontal cortex-cingulate-parietal-hippocampal network that exhibited strongly correlated activity during retrieval suppression. Regardless of age, individuals who were able to suppress memory retrieval exhibited tighter coupling between key nodes in this dorsolateral prefrontal cortex-cingulate-parietal-hippocampal network than individuals who did not. Further, only those capable of mnemonic control exhibited tighter coupling during successful retrieval suppression (intentional forgetting) than during unsuccessful retrieval (unintentional forgetting). Across both children and adults, individual differences in retrieval suppression were best explained by the strength of these network interactions.
The Balance of Striatal Feedback Transmission Is Disrupted in a Model of Parkinsonism
Authors: López-Huerta Violeta G. , Carrillo-Reid Luis , Galarraga Elvira , Tapia Dagoberto , Fiordelisio Tatiana , Drucker-Colin Rene , Bargas Jose
Published: March 2013

Inhibitory connections among striatal projection neurons (SPNs) called “feedback inhibition,” have been proposed to endow the striatal microcircuit with computational capabilities, such as motor sequence selection, filtering, and the emergence of alternating network states. These properties are disrupted in models of Parkinsonism. However, the impact of feedback inhibition in the striatal network has remained under debate. Here, we test this inhibition at the microcircuit level. We used optical and electrophysiological recordings in mice and rats to demonstrate the action of striatal feedback transmission in normal and pathological conditions. Dynamic calcium imaging with single-cell resolution revealed the synchronous activation of a pool of identified SPNs by antidromic stimulation. Using bacterial artificial chromosome-transgenic mice, we demonstrate that the activated neuron pool equally possessed cells from the direct and indirect basal ganglia pathways. This pool inhibits itself because of its own GABA release when stimuli are frequent enough, demonstrating functional and significant inhibition. Blockade of GABAAreceptors doubled the number of responsive neurons to the same stimulus, revealing a second postsynaptic neuron pool whose firing was being arrested by the first pool. Stronger connections arise from indirect SPNs. Dopamine deprivation impaired striatal feedback transmission disrupting the ability of a neuronal pool to arrest the firing of another neuronal pool. We demonstrate that feedback inhibition among SPNs is strong enough to control the firing of cell ensembles in the striatal microcircuit. However, to be effective, feedback inhibition should arise from synchronized pools of SPNs whose targets are other SPNs pools.
Structure, Function, and Cortical Representation of the Rat Submandibular Whisker Trident
Authors: Thé Lydia , Wallace Michael L. , Chen Christopher H. , Chorev Edith , Brecht Michael
Published: March 2013

Although the neurobiology of rodent facial whiskers has been studied intensively, little is known about sensing in other vibrissae. Here we describe the under-investigated submandibular “whisker trident” on the rat's chin. In this three-whisker array, a unique unpaired midline whisker is laterally flanked by two slightly shorter whiskers. All three whiskers point to the ground and are curved backwards. Unlike other whiskers, the trident is not located on an exposed body part. Trident vibrissae are not whisked and do not touch anything over long stretches of time. However, trident whiskers engage in sustained ground contact during head-down running while the animal is exploring or foraging. In biomechanical experiments, trident whiskers follow caudal ground movement more smoothly than facial whiskers. Remarkably, deflection angles decrease with increasing ground velocity. We identified one putative trident barrel in the left somatosensory cortex and two barrels in the right somatosensory cortex. The elongated putative trident-midline barrel is the longest and largest whisker barrel, suggesting that the midline trident whisker is of great functional significance. Cortical postsynaptic air-puff responses in the trident representation show much less temporal precision than facial whisker responses. Trident whiskers do not provide as much high-resolution information about object contacts as facial whiskers. Instead, our observations suggest an idiothetic function: their biomechanics allow trident whiskers to derive continuous measurements about ego motion from ground contacts. The midline position offers unique advantages in sensing heading direction in a laterally symmetric manner. The changes in trident deflection angle with velocity suggest that trident whiskers might function as a tactile speedometer.
Neural Injury Alters Proliferation and Integration of Adult-Generated Neurons in the Dentate Gyrus
Authors: Perederiy Julia V. , Luikart Bryan W. , Washburn Eric K. , Schnell Eric , Westbrook Gary L.
Published: March 2013

Neural plasticity following brain injury illustrates the potential for regeneration in the central nervous system. Lesioning of the perforant path, which innervates the outer two-thirds of the molecular layer of the dentate gyrus, was one of the first models to demonstrate structural plasticity of mature granule cells (Parnavelas et al., 1974; Caceres and Steward, 1983; Diekmann et al., 1996). The dentate gyrus also harbors a continuously proliferating population of neuronal precursors that can integrate into functional circuits and show enhanced short-term plasticity (Schmidt-Hieber et al., 2004; Abrous et al., 2005). To examine the response of adult-generated granule cells to unilateral complete transection of the perforant pathin vivo, we tracked these cells using transgenic POMC-EGFP mice or by retroviral expression of GFP. Lesioning triggered a marked proliferation of newborn neurons. Subsequently, the dendrites of newborn neurons showed reduced complexity within the denervated zone, but dendritic spines still formed in the absence of glutamatergic nerve terminals. Electron micrographs confirmed the lack of intact presynaptic terminals apposing spines on mature cells and on newborn neurons. Newborn neurons, but not mature granule cells, had a higher density of dendritic spines in the inner molecular layer postlesion accompanied by an increase in miniature EPSC amplitudes and rise times. Our results indicate that injury causes an increase in newborn neurons and lamina-specific synaptic reorganization indicative of enhanced plasticity. The presence ofde novodendritic spines in the denervated zone suggests that the postlesion environment provides the necessary signals for spine formation.
Electrophysiological Characterization of Spino-Sciatic and Cortico-Sciatic Associative Plasticity: Modulation by Trans-Spinal Direct Current and Effects on Recovery after Spinal Cord Injury in Mice
Authors: Ahmed Zaghloul
Published: March 2013

Associative stimulation causes enduring changes in the nervous system based on the Hebbian concept of spike-timing-dependent plasticity. The present study aimed to characterize the immediate and long-term electrophysiological effects of associative stimulation at the level of spinal cord and to test how trans-spinal direct current stimulation (tsDC) modulates associative plasticity. The effect of combined associative stimulation and tsDC on locomotor recovery was tested in a unilateral model of spinal cord injury (SCI). Two associative protocols were tested: (1) spino-sciatic associative (SSA) protocol, in which the first stimulus originated from the sciatic nerve and the second from the spinal cord; and (2) cortico-sciatic associative (CSA) protocol, in which the first stimulus originated from the sciatic nerve and the second from the motor cortex. In addition, those two protocols were repeated in combination with cathodal tsDC application. SSA and CSA stimulation produced immediate enhancement of spinal and cortical outputs, respectively, depending on the duration of the interstimulus interval. Repetitive SSA or CSA stimulation produced long-term potentiation of spinal and cortical outputs, respectively. Applying tsDC during SSA or CSA stimulation markedly enhanced their immediate and long-term effects. In behaving mice with unilateral SCI, four consecutive 20 min sessions of CSA + tsDC markedly reduced error rate in a horizontal ladder-walking test. Thus, this form of artificially enhanced associative connection can be translated into a form of motor relearning that does not depend on practice or experience.
Precise Lamination of Retinal Axons Generates Multiple Parallel Input Pathways in the Tectum
Authors: Robles Estuardo , Filosa Alessandro , Baier Herwig
Published: March 2013

The axons of retinal ganglion cells (RGCs) form topographic connections in the optic tectum, recreating a two-dimensional map of the visual field in the midbrain. RGC axons are also targeted to specific positions along the laminar axis of the tectum. Understanding the sensory transformations performed by the tectum requires identification of the rules that control the formation of synaptic laminae by RGC axons. However, there is little information regarding the spatial relationships between multiple axons as they establish laminar and retinotopic arborization fields within the same region of neuropil. Moreover, the contribution of RGC axon lamination to the processing of visual information is unknown. We used Brainbow genetic labeling to visualize groups of individually identifiable axons during the assembly of a precise laminar map in the larval zebrafish tectum. Live imaging of multiple RGCs revealed that axons target specific sublaminar positions during initial innervation and maintain their relative laminar positions throughout early larval development, ruling out a model for lamina selection based on iterative refinements. During this period of laminar stability, RGC arbors undergo structural rearrangements that shift their relative retinotopic positions. Analysis of cell-type-specific lamination patterns revealed that distinct combinations of RGCs converge to form each sublamina, and this input heterogeneity correlates with different functional responses to visual stimuli. These findings suggest that lamina-specific sorting of retinal inputs provides an anatomical blueprint for the integration of visual features in the tectum.
Association with Reward Negatively Modulates Short Latency Phasic Conditioned Responses of Dorsal Raphe Nucleus Neurons in Freely Moving Rats
Authors: Li Yuhong , Dalphin Neil , Hyland Brian I.
Published: March 2013

The dorsal raphe nucleus (DRN) is implicated in mood regulation, control of impulsive behavior, and in processing aversive and reward-related signals. DRN neurons show phasic responses to sensory stimuli, but whether association with reward modulates these responses is unknown. We recorded DRN neurons from rats in a contextual conditioned approach paradigm in which an auditory cue was either followed or not followed by reward, depending on a global context signal. Conditioned approach (licking) occurred after cues in the reward context, but was suppressed in the no-reward context. Many DRN neurons showed short-latency phasic activations in response to the cues. There was striking contextual bias, with more and stronger excitations in the no-reward context than in the reward context. Therefore, DRN activity scaled inversely with cue salience and with the probability of subsequent conditioned approach. Tonic changes were similarly discriminatory, with increases being dominant after cues in the no-reward context, when licking was suppressed, and tonic decreases in rate dominant after reward-predictive cues during expression of conditioned licking. Phasic and tonic DRN responses thus provide signals of consistent valence but over different timescales. The tonic changes in activity are consistent with previous data and hypotheses relating DRN activity to response suppression and impulse control. Phasic responses could contribute to this via online modulation of attention allocation through projections to sensory-processing regions.
Locomotor Sensitization to Ethanol Impairs NMDA Receptor-Dependent Synaptic Plasticity in the Nucleus Accumbens and Increases Ethanol Self-Administration
Authors: Abrahao Karina Possa , Ariwodola Olusegun J. , Butler Tracy R. , Rau Andrew R. , Skelly Mary Jane , Carter Eugenia , Alexander Nancy P. , McCool Brian A. , Souza-Formigoni Maria Lucia O. , Weiner Jeffrey L.
Published: March 2013

Although alcoholism is a worldwide problem resulting in millions of deaths, only a small percentage of alcohol users become addicted. The specific neural substrates responsible for individual differences in vulnerability to alcohol addiction are not known. In this study, we used rodent models to study behavioral and synaptic correlates related to individual differences in the development of ethanol locomotor sensitization, a form of drug-dependent behavioral plasticity associated with addiction vulnerability. Male Swiss Webster mice were treated daily with saline or 1.8 g/kg ethanol for 21 d. Locomotor activity tests were performed once a week for 15 min immediately after saline or ethanol injections. After at least 11 d of withdrawal, cohorts of saline- or ethanol-treated mice were used to characterize the relationships between locomotor sensitization, ethanol drinking, and glutamatergic synaptic transmission in the nucleus accumbens. Ethanol-treated mice that expressed locomotor sensitization to ethanol drank significantly more ethanol than saline-treated subjects and ethanol-treated animals resilient to this form of behavioral plasticity. Moreover, ethanol-sensitized mice also had reduced accumbal NMDA receptor function and expression, as well as deficits in NMDA receptor-dependent long-term depression in the nucleus accumbens core after a protracted withdrawal. These findings suggest that disruption of accumbal core NMDA receptor-dependent plasticity may represent a synaptic correlate associated with ethanol-induced locomotor sensitization and increased propensity to consume ethanol.
Compensation for Research-Related Injury in NIH-Sponsored HIV/AIDS Clinical Trials in Africa
Authors: Mamotte Nicole , Wassenaar Douglas , Singh Nivedhna
Published: March 2013

Concern has been voiced in the research ethics literature that under U.S. federal regulations U.S. sponsors, particularly the NIH, are not required to provide compensation for the treatment of research-related injury for trial participants or to allow grant funds to be used by investigators for appropriate insurance. This is problematic in developing country contexts because most participants are unlikely to have health insurance, resulting in overburdened and under-resourced health systems in many developing countries being responsible for providing care and treatment for research-related injury. This study provides preliminary insight into how respondent principal investigators of NIH-sponsored HIV/AIDS clinical trials in Africa and African research ethics committees deal with compensation for research-related injury. The majority of PIs surveyed provided free treatment for research-related injury, but few provided other forms of financial reparation to participants. The study also found that half of the PIs surveyed indicated that NIH funds were used for compensation, highlighting a contradiction between literature and practice. The majority of REC chairs surveyed indicated that their RECs routinely reviewed compensation plans for research-related injury and that their ethics application forms specifically requested information on compensation. Findings from one southern African country revealed that NIH funds were not used to provide treatment and/or financial reparation for research-related injury. Instead, PIs from this country relied on the government or the individual research participant (and/or their medical aid/health insurer) to cover the costs of research-related injury. The findings are discussed in the light of the recent (December 2011) U.S. Presidential Commission for the Study of Bioethics report which recommends that research participants are morally entitled to compensation for research-related injury.
How IRBs View and Make Decisions about Consent Forms
Authors: Klitzman Robert L.
Published: March 2013

IRBs have been criticized for long and complicated consent forms, but how IRBs make decisions about these issues hasn't been examined. I contacted leaders of 60 IRBs, and interviewed Irb leaders from 34 (response rate = 55%), and 13 members and administrators. IRBs confront challenges and dilemmas regarding these documents: What and how much these forms should include (e.g., how “perfect” forms should be). While IRBs generally seek to decrease the length and complexity, institutions and industry funders often want these forms to be legal documents. IRBs may also “nitpick” these documents without realizing the costs. This study, the first to explore how IRBs view and make decisions about consent forms, suggests underlying tensions, ambiguities, and subjectivities that have important implications for future policy, practice, education, and research.
Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis
Authors: Corona Giovanni , Rastrelli Giulia , Monami Matteo , Saad Farid , Luconi Michaela , Lucchese Marcello , Facchiano Enrico , Sforza Alessandra , Forti Gianni , Mannucci Edoardo , Maggi Mario
Published: March 2013

Objective

Few randomized clinical studies have evaluated the impact of diet and physical activity on testosterone levels in obese men with conflicting results. Conversely, studies on bariatric surgery in men generally have shown an increase in testosterone levels. The aim of this study is to perform a systematic review and meta-analysis of available trials on the effect of body weight loss on sex hormones levels.

Design

Meta-analysis.

Methods

An extensive Medline search was performed including the following words: ‘testosterone’, ‘diet’, ‘weight loss’, ‘bariatric surgery’, and ‘males’. The search was restricted to data from January 1, 1969 up to August 31, 2012.

Results

Out of 266 retrieved articles, 24 were included in the study. Of the latter, 22 evaluated the effect of diet or bariatric surgery, whereas two compared diet and bariatric surgery. Overall, both a low-calorie diet and bariatric surgery are associated with a significant (P<0.0001) increase in plasma sex hormone-binding globulin-bound and -unbound testosterone levels (total testosterone (TT)), with bariatric surgery being more effective in comparison with the low-calorie diet (TT increase: 8.73 (6.51–10.95) vs 2.87 (1.68–4.07) for bariatric surgery and the low-calorie diet, respectively; both P<0.0001 vs baseline). Androgen rise is greater in those patients who lose more weight as well as in younger, non-diabetic subjects with a greater degree of obesity. Body weight loss is also associated with a decrease in estradiol and an increase in gonadotropins levels. Multiple regression analysis shows that the degree of body weight loss is the best determinant of TT rise (B=2.50±0.98, P=0.029).

Conclusions

These data show that weight loss is associated with an increase in both bound and unbound testosterone levels. The normalization of sex hormones induced by body weight loss is a possible mechanism contributing to the beneficial effects of surgery in morbid obesity.
RAC1b overexpression in papillary thyroid carcinoma: a role to unravel
Authors: Silva Ana Luísa , Carmo Francisca , Bugalho Maria João
Published: March 2013

Context

TheBRAFV600E mutation is the most frequent genetic alteration in papillary thyroid carcinoma (PTC). In colorectal cancer,BRAFV600E was described to functionally cooperate with RAC1b, a hyperactive splice variant of the small GTPase RAC1, to sustain cell survival. This interplay has never been investigated in PTCs.

Objective

We aimed to analyze the expression of RAC1b in PTC and correlate its expression withBRAFV600E mutational status, histopathological features, and clinical outcome.

Patients and methods

Sixty-one patients and 87 samples (61 PTCs and 26 normal thyroid tissues) were included. Patients were divided into two groups based on longitudinal evolution and final outcome.RAC1bexpression levels were determined by quantitative RT-PCR and western blotting.

Results

RAC1bwas expressed in thyroid and overexpressed in 46% of PTCs. Neither RAC1b overexpression nor V600E mutation correlated with histopathological features classically associated with worse prognosis.RAC1boverexpression was significantly associated with both V600E mutation (P=0.0008) and poor clinical outcome (P=0.0029). WhereasBRAFV600E alone did not associate with patient outcome (P=0.2865), the association ofRAC1boverexpression withBRAFV600E was overrepresented in the group with poorer clinical outcome (P=0.0044).

Conclusions

Present results document, for the first time, expression of RAC1b in normal thyroid cells as well as overexpression in a subset of PTCs. Furthermore, they suggest a possible interplay betweenBRAFV600E and RAC1b contributing to poor clinical outcome. Future studies are needed to clarify the oncogenic potential of RAC1b in thyroid carcinogenesis.
The pharmacokinetics of acyl, des-acyl, and total ghrelin in healthy human subjects
Authors: Tong Jenny , Dave Nimita , Mugundu Ganesh M , Davis Harold W , Gaylinn Bruce D , Thorner Michael O , Tschöp Matthias H , D'Alessio David , Desai Pankaj B
Published: March 2013

Background

Ghrelin stimulates GH secretion and regulates energy and glucose metabolism. The two circulating isoforms, acyl (AG) and des-acyl (DAG) ghrelin, have distinct metabolic effects and are under active investigation for their therapeutic potentials. However, there is only limited data on the pharmacokinetics of AG and DAG.

Objectives

To evaluate key pharmacokinetic parameters of AG, DAG, and total ghrelin in healthy men and women.

Methods

In study 1, AG (1, 3, and 5 μg/kg per h) was infused over 65 min in 12 healthy (8 F/4 M) subjects in randomized order. In study 2, AG (1 μg/kg per h), DAG (4 μg/kg per h), or both were infused over 210 min in ten healthy individuals (5 F/5 M). Plasma AG and DAG were measured using specific two-site ELISAs (study 1 and 2), and total ghrelin with a commercial RIA (study 1). Pharmacokinetic parameters were estimated by non-compartmental analysis.

Results

After the 1, 3, and 5 μg/kg per h doses of AG, there was a dose-dependent increase in the maximum concentration (Cmax) and area under the curve (AUC(0–last)) of AG and total ghrelin. Among the different AG doses, there was no difference in the elimination half-life, systemic clearance (CL), and volume of distribution. DAG had decreased CL relative to AG. The plasma DAG:AG ratio was ∼2:1 during steady-state infusion of AG. Infusion of AG caused an increase in DAG, but DAG administration did not change plasma AG. Ghrelin administration did not affect plasma acylase activity.

Conclusions

The pharmacokinetics of AG and total ghrelin appears to be linear and proportional in the dose range tested. AG and DAG have very distinct metabolic fates in the circulation. There is deacylation of AG in the plasma but no evidence of acylation.
Wombat reproduction (Marsupialia; Vombatidae): an update and future directions for the development of artificial breeding technology
Authors: Hogan Lindsay A , Janssen Tina , Johnston Stephen D
Published: March 2013

This review provides an update on what is currently known about wombat reproductive biology and reports on attempts made to manipulate and/or enhance wombat reproduction as part of the development of artificial reproductive technology (ART) in this taxon. Over the last decade, the logistical difficulties associated with monitoring a nocturnal and semi-fossorial species have largely been overcome, enabling new features of wombat physiology and behaviour to be elucidated. Despite this progress, captive propagation rates are still poor and there are areas of wombat reproductive biology that still require attention, e.g. further characterisation of the oestrous cycle and oestrus. Numerous advances in the use of ART have also been recently developed in the Vombatidae but despite this research, practical methods of manipulating wombat reproduction for the purposes of obtaining research material or for artificial breeding are not yet available. Improvement of the propagation, genetic diversity and management of wombat populations requires a thorough understanding of Vombatidae reproduction. While semen collection and cryopreservation in wombats is fairly straightforward there is currently an inability to detect, induce or synchronise oestrus/ovulation and this is an impeding progress in the development of artificial insemination in this taxon.
Si Quantum Dot Structures and Some Aspects of Applications
Authors: Shcherbyna Lyudmula V. , Torchynska Tetyana V.
Published: March 2013

Papers in the Appendix were published in electronic format as Volume 1534
Exciton - Light coupling in SiC nanocrystals
Authors: Rodriguez Miguel Morales , Polupan Georgiy
Published: March 2013

Papers in the Appendix were published in electronic format as Volume 1534
Emission and Strain in InGaAs/GaAs structures with Embedded InAs
quantum dots
Authors: Tamayo Ricardo Cisneros , Polupan Georgiy , Vega Macotela Leonardo G.
Published: March 2013

Papers in the Appendix were published in electronic format as Volume 1534
Size Control of Cadmium Sulfide Nanoparticles in Polyvinyl Alcohol and Gelatin by Polyethyleneimine Addition
Authors: Rayevska Oleksandra E. , Grodzyuk Galyna Ya. , Stroyuk Oleksandr L. , Kuchmiy Stepan Ya. , Plyusnin Victor F.
Published: March 2013

Papers in the Appendix were published in electronic format as Volume 1534
Photoinduced Photoluminescence Enhancement in CdSe Quantum Dot – Polyvinyl Alcohol Composites
Authors: Borkovska L. , Korsunska N. , Stara T. , Bondarenko V. , Gudymenko O. , Stroyuk O. , Raevska O. , Kryshtab T.
Published: March 2013

Papers in the Appendix were published in electronic format as Volume 1534
Structural and Optical Properties of Porous III-V Semiconductors GaAs, InP Prepared by Electrochemical Etching
Authors: Dmitruk Nicholas L. , Berezovska Natalia I. , Dmitruk Igor M. , Naumenko Denis O. , Simkiene Irene , Snitka Valentinas
Published: March 2013

Papers in the Appendix were published in electronic format as Volume 1534
Design and implementation of a measurement system for automatically measurement of electrical parameters of thermoelectric generators
Authors: Petrov Dmitry , Assion Fabian , Hilleringmann Ulrich
Published: March 2013

The continues development of thermoelectric generators causes a permanent improvement of their characteristics. New types of thermoelectric generators can work at temperatures up to 1000 K. With this, special measurement equipment is needed to control the electrical parameters of the new developed specimens. The devices must be tested over the whole range of operating temperatures. For each temperature value a series of electrical measurements has to be performed. To establish the maximal output power of the thermoelectric generators, a load resistor with variable resistance has to be connected to the output of thermoelectric generator. The measurement system should measure the electrical current through the load resistor and the voltage over this resistor to determine the device parameters. A large amount of measurement data have to be collected and processed to evaluate the electrical characteristics of the specimen and to present them in graphical form, suitable for the comparison with others specimens.
Encapsulation of Stimuli-Responsive Fusion Proteins in Silica: Thermally Responsive Metal Ion-Sensitive Hybrid Membranes
Authors: Li Linying , Im Owen , Chilkoti Ashutosh , López Gabriel P.
Published: March 2013

In this study, we demonstrate the fabrication of hybrid membranes that exhibit discrete and reversible changes in permeability in response to changes in calcium ion (Ca2+) concentration and temperature. Fusion proteins comprising calmodulin (CAM) and elastin-like polypeptides (ELPs) were used as stimuli-responsive elements due to their ability to undergo a reversible lower critical solution temperature (LCST) phase transition, which is sensitive to Ca2+binding. The calmodulin elastin-like polypeptides fusions (CAM-ELPs) were incorporated into polymerizing silica networks using a simple sol-gel process and spin coating. Permeation experiments with solutions of crystal violet showed that the membranes are both Ca2+-responsive and thermally responsive. Under suitable pressure drop across the membranes, in the absence of Ca2+or below the LCST of the ELPs, the hybrid membranes are impermeable to water. After addition of Ca2+or above the LCSTs, they become permeable to water. The permeability can be toggled back and forth by sequential addition of calcium and ethylenediamine tetraacetic acid (EDTA). These results demonstrate that CAMELP/silica hybrid membranes can serve as tunable molecular filters whose permeability can be switched on and off in response to Ca2+and temperature.