bluuebunny/crossref_metadata_2025 huggingface dataset:
Challenges in Compression Testing of 3D Angle-Interlocked Woven-Glass Fabric-Reinforced Polymeric Composites
Authors: Shah S. Z. H. , Choudhry R. S. , Khan L. A.
Published: October 2016

In this paper, the challenges are described in determination of compressive strength for three-dimensional (3D) angle-interlocked glass fabric-reinforced polymeric composites (3D-FRPCs). It makes use of both experimental investigation and finite-element analysis. The experimental investigation involved testing both two dimensional (2D) and 3D-FRPC using ASTM D6641/D6641M-14 and subsequent scanning electron microscopic (SEM) imaging of failed specimens to reveal the stress state at failure. This was further evaluated using laminate level finite-element (FE) analysis. The FE analysis required input of effective orthotropic elastic material properties of 3D-FRPC, which were determined by customizing a recently developed micro-mechanical model. The paper sheds new light on compressive failure of 3D angle-interlocked glass fabric composites, as only scarce data is available in literature about this class of materials. It showed that although the tests produce acceptable strength values the internal failure mechanisms change significantly and the standard deviation (SD) and coefficient of variance (COV) of 3D-FRPC ends up being much higher than that of 2D-FRPC. Moreover, while reporting and using the test data, some additional information about the 3D-fabric architecture, such as the direction of angle interlocking fabric, needs to be specified. This was because, for 3D angle interlocking of fabric along the warp direction, the strength values obtained in the warp and weft direction were significantly different from each other. The study also highlights that, because of complex weave architecture, it is not possible to achieve comparable volume fractions with 2D and 3D fabric-reinforced composites using similar manufacturing parameters for the vacuum-assisted resin-infusion process. Thus, the normalized compressive strength values (normalized with respect to volume fraction) are the highest for 3D-FRPC when measured along the warp direction, they are at an intermediate level for 2D-FRPC and the lowest for 3D-FRPC, when measured in the weft direction.
Evaluating Robust Product Design in Production Line: An Exploratory Investigation on Response Surface Methodology
Authors: Eslamipoor R. , Hosseini-Nasab H.
Published: October 2016

Inadequate control of a production line can result in catastrophic ramifications, which may lead to low-quality products. For this reason, enhancing the quality of product in the first stages of development requires considerable attention. In this regard, robust parameter design for product has emerged as an outstanding tool. This article presents a robust parameter design in one product, into which the concept of response surface methodology has been infused. Through this, by encompassing the variance and mean of response variable, an integrated approach is presented to combine three phases of product development: system design, parameter design, and tolerance design. Moreover, to survive in a competitive market, companies must produce appealing products. Therefore, we resorted to a feasible scheme to enhance customer satisfaction in the production process through the implementation of the desirability function concept. To approve the suitability of the presented method, it has been executed in an actual case study. Research results emphasize that the demonstrated model is more effective than dual-response and mean-square error techniques.
Formation of Bainite in Advanced High-Strength Steels During Isothermal Transformation
Authors: Kish L. B. , Haezebrouck D. M. , Tan S. , Garcia C. I.
Published: October 2016

The isothermal transformation of bainite in an advanced high-strength steel (AHSS) in the temperature range of 422°C to 482°C for transformation times of 10–6000 s has been examined using light optical microscopy (LOM), and orientation imaging microscopy (OIM). Thermodynamic calculations were done using equilibrium thermodynamic simulation software to produce a theoretical time-temperature-transformation (TTT) diagram, to which the experimental results of this study were compared. Advanced microstructural techniques, such as orientation-imaging-microscopy–electron-backscatter-diffraction (OIM-EBSD), image quality (IQ) phase identification, and polarized light microscopy, were used to observe and quantify the progress of the bainitic transformation during isothermal transformation. Orientation imaging microscopy using electron backscatter diffraction image quality (EBSD-IQ) was used with each sample to quantify the amount of bainite transformed. Results showed that the isothermal transformation at 422°C had 80.1 % bainite, whereas the isothermal transformation at 482°C had 85.5 % bainite transformed after 1200 s; while, after 6000 s, the amount of bainite increased to 90.1 % and 93.4 % respectively. As a result the chemical composition of the steel investigated and the microstructural characteristics of the bainite observed, it was not possible to discern the type of bainite formed at higher and lower temperatures because of the absence of carbides. The kinetics of transformation from the experimental results clearly indicated that the isothermal transformation is slower than that predicted by the theoretical thermodynamic program. The results of this study are presented and discussed.
Dilatometric Study of Phase Transformations in Steels: Some Issues
Authors: Catteau S. D. , Sourmail T. , Moine A.
Published: October 2016

Dilatometry is widely used in the investigation of phase transformation in steels, not only by research laboratories but also by most steel makers. Its application includes the determination of CCT and TTT diagrams, and more generally the investigation of phase transformation kinetics under controlled temperature conditions. A basic and often undiscussed assumption in the exploitation of dilatation measurements as a function of temperature is that of a constant and uniform temperature distribution in the specimen, and of a homogeneous material. In the present paper, various issues encountered with a widely used quenching dilatometer were discussed, including longitudinal temperature gradients, deformation anisotropy, or vacuum evaporation of some chemical species.
Subsecond Sensory Modulation of Serotonin Levels in a Primary Sensory Area and Its Relation to Ongoing Communication Behavior in a Weakly Electric Fish
Authors: Fotowat Haleh , Harvey-Girard Erik , Cheer Joseph F. , Krahe Rüdiger , Maler Leonard
Published: October 2016

Serotonergic neurons of the raphe nuclei of vertebrates project to most regions of the brain and are known to significantly affect sensory processing. The subsecond dynamics of sensory modulation of serotonin levels and its relation to behavior, however, remain unknown. We used fast-scan cyclic voltammetry to measure serotonin release in the electrosensory system of weakly electric fish,Apteronotus leptorhynchus. These fish use an electric organ to generate a quasi-sinusoidal electric field for communicating with conspecifics. In response to conspecific signals, they frequently produce signal modulations called chirps. We measured changes in serotonin concentration in the hindbrain electrosensory lobe (ELL) with a resolution of 0.1 s concurrently with chirping behavior evoked by mimics of conspecific electric signals. We show that serotonin release can occur phase locked to stimulus onset as well as spontaneously in the ELL region responsible for processing these signals. Intense auditory stimuli, on the other hand, do not modulate serotonin levels in this region, suggesting modality specificity. We found no significant correlation between serotonin release and chirp production on a trial-by-trial basis. However, on average, in the trials where the fish chirped, there was a reduction in serotonin release in response to stimuli mimicking similar-sized same-sex conspecifics. We hypothesize that the serotonergic system is part of an intricate sensory–motor loop: serotonin release in a sensory area is triggered by sensory input, giving rise to motor output, which can in turn affect serotonin release at the timescale of the ongoing sensory experience and in a context-dependent manner.
Synaptic Contributions to Receptive Field Structure and Response Properties in the Rodent Lateral Geniculate Nucleus of the Thalamus
Authors: Suresh Vandana , Çiftçioğlu Ulaş M. , Wang Xin , Lala Brittany M. , Ding Kimberly R. , Smith William A. , Sommer Friedrich T. , Hirsch Judith A.
Published: October 2016

Comparative physiological and anatomical studies have greatly advanced our understanding of sensory systems. Many lines of evidence show that the murine lateral geniculate nucleus (LGN) has unique attributes, compared with other species such as cat and monkey. For example, in rodent, thalamic receptive field structure is markedly diverse, and many cells are sensitive to stimulus orientation and direction. To explore shared and different strategies of synaptic integration across species, we made whole-cell recordingsin vivofrom the murine LGN during the presentation of visual stimuli, analyzed the results with different computational approaches, and compared our findings with those from cat. As for carnivores, murine cells with classical center-surround receptive fields had a “push-pull” structure of excitation and inhibition within a given On or Off subregion. These cells compose the largest single population in the murine LGN (∼40%), indicating that push-pull is key in the form vision pathway across species. For two cell types with overlapping On and Off responses, which recalled either W3 or suppressed-by-contrast ganglion cells in murine retina, inhibition took a different form and was most pronounced for spatially extensive stimuli. Other On-Off cells were selective for stimulus orientation and direction. In these cases, retinal inputs were tuned and, for oriented cells, the second-order subunit of the receptive field predicted the preferred angle. By contrast, suppression was not tuned and appeared to sharpen stimulus selectivity. Together, our results provide new perspectives on the role of excitation and inhibition in retinothalamic processing.

SIGNIFICANCE STATEMENTWe explored the murine lateral geniculate nucleus from a comparative physiological perspective. In cat, most retinal cells have center-surround receptive fields and push-pull excitation and inhibition, including neurons with the smallest (highest acuity) receptive fields. The same is true for thalamic relay cells. In mouse retina, the most numerous cell type has the smallest receptive fields but lacks push-pull. The most common receptive field in rodent thalamus, however, is center-surround with push-pull. Thus, receptive field structure supersedes size per se for form vision. Further, for many orientation-selective cells, the second-order component of the receptive field aligned with stimulus preference, whereas suppression was untuned. Thus, inhibition may improve spatial resolution and sharpen other forms of selectivity in rodent lateral geniculate nucleus.
Molecular Identity of the Mechanotransduction Channel in Hair Cells: Not Quiet There Yet
Authors: Wu Zizhen , Müller Ulrich
Published: October 2016

Hair cells in the mammalian cochlea are specialized mechanosensory cells that convert sound-induced vibrations into electrochemical signals. The molecular composition of the mechanotransduction channel underlying auditory perception has been difficult to define. The study of genes that are linked to inherited forms of deafness has recently provided tantalizing clues. Current findings indicate that the mechanotransduction channel in hair cells is a complex molecular machine. Four different proteins (TMHS/LHFPL5, TMIE, TMC1, and TMC2) have so far been linked to the transduction channel, but which proteins contribute to the channel pore still needs to be determined. Current evidence also suggests that the channel complex may contain additional, yet to be identified components.
TREM2/DAP12 Signal Elicits Proinflammatory Response in Microglia and Exacerbates Neuropathic Pain
Authors: Kobayashi Masaaki , Konishi Hiroyuki , Sayo Akira , Takai Toshiyuki , Kiyama Hiroshi
Published: October 2016

Neuropathic pain afflicts millions of people, and the development of an effective treatment for this intractable pain is an urgent issue. Recent evidence has implicated microglia in neuropathic pain. The present study showed that the DNAX-activating protein of 12 kDa (DAP12) and its associated “triggering receptor expressed on myeloid cells 2” (TREM2) were predominantly expressed by microglia in the dorsal horn after spinal nerve injury, revealing a role for TREM2/DAP12 signaling in neuropathic pain. Nerve injury-induced proinflammatory cytokine expression in microglia and pain behaviors were significantly suppressed inDap12-deficient mice. Furthermore, intrathecal administration of TREM2 agonistic antibody induced proinflammatory cytokine expression, as well as neuropathic pain, in mice without nerve injury. The agonistic antibody induced proinflammatory responses and neuropathic pain was not observed inDap12-deficient mice. Together, these results suggest that TREM2/DAP12-mediated signals in microglia exacerbate nerve injury-induced neuropathic pain by inducing proinflammatory cytokine secretion from microglia. Suppression of DAP12-mediated signals could be a therapeutic target for neuropathic pain.

SIGNIFICANCE STATEMENTRecent studies have revealed that activated microglia in the spinal dorsal horn exacerbate neuropathic pain, which has suggested that suppression of microglial activity should be considered as a therapeutic target. However, only a few molecules have been identified as regulators of microglial activity. In this study, we focused on a receptor complex of TREM2 and DAP12, both of which are expressed by microglia and have been implicated in the pathogenesis of Alzheimer's disease, and demonstrated that TREM2/DAP12 signaling promoted proinflammatory responses in microglia and exacerbates neuropathic pain. The present results revealed the functional significance of TREM2/DAP12 signaling in microglial activation after neuronal injury, and could help in the development of treatments for neuropathic pain and neurodegenerative diseases.
Ablation of Newly Generated Hippocampal Granule Cells Has Disease-Modifying Effects in Epilepsy
Authors: Hosford Bethany E. , Liska John P. , Danzer Steve C.
Published: October 2016

Hippocampal granule cells generated in the weeks before and after an epileptogenic brain injury can integrate abnormally into the dentate gyrus, potentially mediating temporal lobe epileptogenesis. Previous studies have demonstrated that inhibiting granule cell production before an epileptogenic brain insult can mitigate epileptogenesis. Here, we extend upon these findings by ablating newly generated cells after the epileptogenic insult using a conditional, inducible diphtheria-toxin receptor expression strategy in mice. Diphtheria-toxin receptor expression was induced among granule cells born up to 5 weeks before pilocarpine-induced status epilepticus and these cells were then eliminated beginning 3 d after the epileptogenic injury. This treatment produced a 50% reduction in seizure frequency, but also a 20% increase in seizure duration, when the animals were examined 2 months later. These findings provide the first proof-of-concept data demonstrating that granule cell ablation therapy applied at a clinically relevant time point after injury can have disease-modifying effects in epilepsy.

SIGNIFICANCE STATEMENTThese findings support the long-standing hypothesis that newly generated dentate granule cells are pro-epileptogenic and contribute to the occurrence of seizures. This work also provides the first evidence that ablation of newly generated granule cells can be an effective therapy when begun at a clinically relevant time point after an epileptogenic insult. The present study also demonstrates that granule cell ablation, while reducing seizure frequency, paradoxically increases seizure duration. This paradoxical effect may reflect a disruption of homeostatic mechanisms that normally act to reduce seizure duration, but only when seizures occur frequently.
Uric Acid Induces Cognitive Dysfunction through Hippocampal Inflammation in Rodents and Humans
Authors: Shao Xiaoni , Lu Wenjie , Gao Fabao , Li Dandan , Hu Jing , Li Yan , Zuo Zeping , Jie Hui , Zhao Yinglan , Cen Xiaobo
Published: October 2016

Uric acid (UA) is a purine metabolite that in most mammals is degraded by the hepatic enzyme uricase to allantoin. Epidemiological studies have shown that an elevated UA level predicts the development of cognition and memory deficits; however, there is no direct evidence of this relationship, and the underlying mechanism is largely undefined. Here, we show that a high-UA diet triggers the expression of proinflammatory cytokines, activates the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB pathway, and increases gliosis in the hippocampus of Wistar rats. We, subsequently, identify a specific inhibitor of NF-κB, BAY11-7085, and show that stereotactic injections of the inhibitor markedly ameliorate UA-induced hippocampal inflammation and memory deficits in C57BL/6 mice. We also found that NF-κB is activated in the primary cultured hippocampal cells after UA administration. Additionally, C57BL/6 mice that lack TLR4 are substantially protected against UA-induced cognitive dysfunction, possibly due to a decrease in inflammatory gene expression in the hippocampus. Importantly, magnetic resonance imaging confirms that hyperuricemia in rats and humans is associated with gliosis in the hippocampus. Together, these results suggest that UA can cause hippocampal inflammation via the TLR4/NF-κB pathway, resulting in cognitive dysfunction. Our findings provide a potential therapeutic strategy for counteracting UA-induced neurodegeneration.

SIGNIFICANCE STATEMENTThis work demonstrates that a high-uric acid (UA) diet triggers the expression of proinflammatory cytokines, activates the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB pathway, and increases gliosis in the hippocampus of Wistar rats. Inhibition of the NF-κB signaling pathway markedly ameliorates UA-induced hippocampal inflammation and cognitive dysfunction in C57BL/6 mice. TLR4-knock-out mice are substantially protected against UA-induced cognitive dysfunction, possibly due to a decrease in inflammatory gene expression in the hippocampus. Moreover, magnetic resonance imaging confirms that hyperuricemia in rats and humans are associated with gliosis in the hippocampus. Together, this study suggests that there is an important link between UA-induced cognitive dysfunction and hippocampal inflammation in rodents and humans, which may have remarkable implications in the treatment of UA-induced neurodegeneration.
Light-Driven Processes Control Both Rhodopsin Maturation and Recycling in Mosquito Photoreceptors
Authors: Metoxen Alexander J. , Leming Matthew T. , Hu Xiaobang , Whaley Michelle A. , O'Tousa Joseph E.
Published: October 2016

Many invertebrates carry out a daily cycle of shedding and rebuilding of the photoreceptor's photosensitive rhabdomeric membranes. The mosquitoAedes aegyptishows a robust response, losing nearly all Aaop1 rhodopsin from the rhabdomeric membranes during the shedding process at dawn. Here, we made use of Aaop1 antibodies capable of distinguishing newly synthesized, glycosylated rhodopsin from mature nonglycosylated rhodopsin to characterize the fate of Aaop1 during the shedding and rebuilding processes. The rhabdomeric rhodopsin is moved into large cytoplasmic vesicles at dawn and is subsequently degraded during the standard 12 h daytime period. The endocytosed rhodopsin is trafficked back to the photosensitive membranes if animals are shifted back to dark conditions during the morning hours. During the daytime period, small vesicles containing newly synthesized and glycosylated Aaop1 rhodopsin accumulate within the cytoplasm. At dusk, these vesicles are lost as the newly synthesized Aaop1 is converted to the nonglycosylated form and deposited in the rhabdomeres. We demonstrate that light acts though a novel signaling pathway to block rhodopsin maturation, thus inhibiting the deglycosylation and rhabdomeric targeting of newly synthesized Aaop1 rhodopsin. Therefore, light controls two cellular processes responsible for the daily renewal of rhodopsin: rhodopsin endocytosis at dawn and inhibition of rhodopsin maturation until dusk.

SIGNIFICANCE STATEMENTOrganisms use multiple strategies to maximize visual capabilities in different light conditions. Many invertebrates show a daily cycle of shedding the photoreceptor's rhabdomeric membranes at dawn and rebuilding these during the following night. We show here that theAedes aegyptimosquito possesses two distinct light-driven cellular signaling processes for modulating rhodopsin content during this cycle. One of these, endocytosis of rhabdomeric rhodopsin, has been described previously. The second, a light-activated cellular pathway acting to inhibit the anterograde movement of newly synthesized rhodopsin, is revealed here for the first time. The discovery of this cellular signaling pathway controlling a G-protein-coupled receptor is of broad interest due to the prominent role of this receptor family across all areas of neuroscience.
Differential Expression of Munc13-2 Produces Unique Synaptic Phenotypes in the Basolateral Amygdala of C57BL/6J and DBA/2J Mice
Authors: Gioia Dominic A. , Alexander Nancy J. , McCool Brian A.
Published: October 2016

C57BL/6J (B6) and DBA/2J (D2) mice are well known to differentially express a number of behavioral phenotypes, including anxiety-like behavior, fear conditioning, and drug self-administration. However, the cellular mechanisms contributing to these differences remain unclear. Given the basolateral amygdala (BLA) contributes to these behaviors, we characterized strain-dependent differences in presynaptic and postsynaptic function in BLA neurons by integrating electrophysiological, biochemical, and genetic approaches to identify specific molecular mechanisms. We found that D2 glutamatergic synapses expressed enhanced release probability and lower sensitivity to both the inhibitory effects of low extracellular calcium and facilitation by phorbol esters. Furthermore, repetitive stimulation of BLA afferents at low (2 Hz) or high (40 Hz) frequencies revealed that B6 terminals, relative to D2 terminals, were more sensitive to synaptic fatigue principally because of reduced vesicle recycling rates. Additionally, B6 synapses exhibited more robust augmentation of spontaneous release after repetitive stimulation relative to the D2 strain.In silicoanalysis of the inheritance of synaptic physiology from an array of BXD recombinant inbred strains (Jansen et al., 2011) identified a segment on chromosome 4 containing the gene encoding Munc13-2, which has calcium-/phorbol ester-binding domains and controls presynaptic function. We subsequently found that B6 mice express substantially higher levels of Munc13-2 compared with the D2 strain whereas expression of several release-related proteins, including Munc13-1, was equivalent. We then knocked down the expression of Munc13-2 in B6 mice using a short hairpin RNA and found this recapitulated the presynaptic phenotype of D2 BLA synapses.

SIGNIFICANCE STATEMENTDBA/2J and C57BL/6J mice have been used to understand the genetic mechanisms controlling behaviors related to a number of psychiatric illnesses. However, the fundamental neurobiological mechanisms producing these behavioral characteristics remain unresolved. Here we identify a critical family of presynaptic proteins differentially expressed by these strains that control strain-dependent synaptic physiology. This family of proteins regulates excitation/secretion coupling, vesicle recycling, and short-term plasticity throughout the CNS. Thus, differential inheritance of proteins like Munc13-2 has broad implications for genetic control over a wide variety of pathological behaviors. Importantly, these proteins also contain a large number of modulatory sites, making them attractive potential targets for the development of novel neuropharmaceutical treatments.
Oxidation of KCNB1 Potassium Channels Causes Neurotoxicity and Cognitive Impairment in a Mouse Model of Traumatic Brain Injury
Authors: Yu Wei , Parakramaweera Randika , Teng Shavonne , Gowda Manasa , Sharad Yashsavi , Thakker-Varia Smita , Alder Janet , Sesti Federico
Published: October 2016

The delayed rectifier potassium (K+) channel KCNB1 (Kv2.1), which conducts a major somatodendritic current in cortex and hippocampus, is known to undergo oxidation in the brain, but whether this can cause neurodegeneration and cognitive impairment is not known. Here, we used transgenic mice harboring human KCNB1 wild-type (Tg-WT) or a nonoxidable C73A mutant (Tg-C73A) in cortex and hippocampus to determine whether oxidized KCNB1 channels affect brain function. Animals were subjected to moderate traumatic brain injury (TBI), a condition characterized by extensive oxidative stress. Dasatinib, a Food and Drug Administration–approved inhibitor of Src tyrosine kinases, was used to impinge on the proapoptotic signaling pathway activated by oxidized KCNB1 channels. Thus, typical lesions of brain injury, namely, inflammation (astrocytosis), neurodegeneration, and cell death, were markedly reduced in Tg-C73A and dasatinib-treated non-Tg animals. Accordingly, Tg-C73A mice and non-Tg mice treated with dasatinib exhibited improved behavioral outcomes in motor (rotarod) and cognitive (Morris water maze) assays compared to controls. Moreover, the activity of Src kinases, along with oxidative stress, were significantly diminished in Tg-C73A brains. Together, these data demonstrate that oxidation of KCNB1 channels is a contributing mechanism to cellular and behavioral deficits in vertebrates and suggest a new therapeutic approach to TBI.

SIGNIFICANCE STATEMENTThis study provides the first experimental evidence that oxidation of a K+channel constitutes a mechanism of neuronal and cognitive impairment in vertebrates. Specifically, the interaction of KCNB1 channels with reactive oxygen species plays a major role in the etiology of mouse model of traumatic brain injury (TBI), a condition associated with extensive oxidative stress. In addition, a Food and Drug Administration–approved drug ameliorates the outcome of TBI in mouse, by directly impinging on the toxic pathway activated in response to oxidation of the KCNB1 channel. These findings elucidate a basic mechanism of neurotoxicity in vertebrates and might lead to a new therapeutic approach to TBI in humans, which, despite significant efforts, is a condition that remains without effective pharmacological treatments.
The Rubber Tail Illusion as Evidence of Body Ownership in Mice
Authors: Wada Makoto , Takano Kouji , Ora Hiroki , Ide Masakazu , Kansaku Kenji
Published: October 2016

The ownership of one's body parts represents a fundamental aspect of self-consciousness. Accumulating empirical evidence supports the existence of this concept in humans and nonhuman primates, but it is unclear whether nonprimate mammals experience similar feelings. Therefore, the present study used rubber tails to investigate body ownership in rodents. When the real tails and rubber tails were synchronously stroked, the mice responded as if their own tails were touched when the rubber tails were grasped. In contrast, when the stimuli were delivered asynchronously, there was a significantly lower mean response rate when the rubber tail was grasped. These findings suggest that mice may experience body ownership of their tails, suggestive of the rubber hand illusion in humans.

SIGNIFICANCE STATEMENTTo explore the manner in which the ownership of body parts is experienced, this study specifically used the rubber hand illusion (RHI), in which self-consciousness can be extended out of one's own body. Accumulating empirical evidence supports the existence of this concept in humans and nonhuman primates, but it remains unclear whether nonprimate mammals experience similar feelings. This study demonstrated for the first time that mice may experience body ownership of their tails, which is suggestive of the RHI in humans and provides evidence that may highlight how humans experience the ownership of body parts.
CD8+T Cells and Endogenous IL-10 Are Required for Resolution of Chemotherapy-Induced Neuropathic Pain
Authors: Krukowski Karen , Eijkelkamp Niels , Laumet Geoffroy , Hack C. Erik , Li Yan , Dougherty Patrick M. , Heijnen Cobi J. , Kavelaars Annemieke
Published: October 2016

Chemotherapy-induced peripheral neuropathy (CIPN), characterized by pain and numbness in hands and feet, is a common side effect of cancer treatment. In most patients, symptoms of CIPN subside after treatment completion. However, in a substantial subgroup, CIPN persists long into survivorship. Impairment in pain resolution pathways may explain persistent CIPN. We investigated the contribution of T cells and endogenous interleukin (IL)-10 to resolution of CIPN. Paclitaxel-induced mechanical allodynia was prolonged in T-cell-deficient (Rag1−/−) mice compared with wild-type (WT) mice. There were no differences between WT and Rag1−/−mice in severity of paclitaxel-induced mechanical allodynia. Adoptive transfer of either CD3+or CD8+, but not CD4+, T cells to Rag1−/−mice normalized resolution of CIPN. Paclitaxel treatment increased the number of T cells in lumbar dorsal root ganglia (DRG), where CD8+T cells were the major subset. Inhibition of endogenous IL-10 signaling by intrathecal injection of anti-IL-10 to WT mice or Rag1−/−mice reconstituted with CD8+T cells delayed recovery from paclitaxel-induced mechanical allodynia. Recovery was also delayed in IL-10 knock-out mice. Conversely, administration of exogenous IL-10 attenuated paclitaxel-induced allodynia.In vitro, IL-10 suppressed abnormal paclitaxel-induced spontaneous discharges in DRG neurons. Paclitaxel increased DRG IL-10 receptor expression and this effect requires CD8+T cells. In conclusion, we identified a novel mechanism for resolution of CIPN that requires CD8+T cells and endogenous IL-10. We propose that CD8+T cells increase DRG IL-10 receptor expression and that IL-10 suppresses the abnormal paclitaxel-induced spontaneous discharges by DRG neurons to promote recovery from CIPN.

SIGNIFICANCE STATEMENTChemotherapy-induced peripheral neuropathy persists after completion of cancer treatment in a significant subset of patients, whereas others recover. Persistent neuropathy after completion of cancer treatment severely affects quality of life. We propose that understanding how neuropathy resolves will identify novel avenues for treatment. We identified a novel and critical role for CD8+T cells and for endogenous IL-10 in recovery from paclitaxel-induced neuropathy in mice. Enhancing the capacity of CD8+T cells to promote resolution or increasing IL-10 signaling are promising targets for novel interventions. Clinically, peripheral blood CD8+T-cell function and/or the capacity of individuals to produce IL-10 may represent biomarkers of risk for developing persistent peripheral neuropathy after completion of cancer treatment.
Are Care Plans Suitable for the Management of Multiple Conditions?
Authors: Young Charlotte E. , Boyle Frances M. , Mutch Allyson J.
Published: October 2016

Background

Care plans have been part of the primary care landscape in Australia for almost two decades. With an increasing number of patients presenting with multiple chronic conditions, it is timely to consider whether care plans meet the needs of patients and clinicians.

Objectives

To review and benchmark existing care plan templates that include recommendations for comorbid conditions, against four key criteria: (i) patient preferences, (ii) setting priorities, (iii) identifying conflicts and synergies between conditions, and (iv) setting dates for reviewing the care plan.

Design

Document analysis of Australian care plan templates published from 2006 to 2014 that incorporated recommendations for managing comorbid conditions in primary care.

Results

Sixteen templates were reviewed. All of the care plan templates addressed patient preference, but this was not done comprehensively. Only three templates included setting priorities. None assisted in identifying conflicts and synergies between conditions. Fifteen templates included setting a date for reviewing the care plan.

Conclusions

Care plans are a well-used tool in primary care practice, but their current format perpetuates a single-disease approach to care, which works contrary to their intended purpose. Restructuring care plans to incorporate shared decision-making and attention to patient preferences may assist in shifting the focus back to the patient and their care needs.
Adipose tissue in control of metabolism
Authors: Luo Liping , Liu Meilian
Published: October 2016

Adipose tissue plays a central role in regulating whole-body energy and glucose homeostasis through its subtle functions at both organ and systemic levels. On one hand, adipose tissue stores energy in the form of lipid and controls the lipid mobilization and distribution in the body. On the other hand, adipose tissue acts as an endocrine organ and produces numerous bioactive factors such as adipokines that communicate with other organs and modulate a range of metabolic pathways. Moreover, brown and beige adipose tissue burn lipid by dissipating energy in the form of heat to maintain euthermia, and have been considered as a new way to counteract obesity. Therefore, adipose tissue dysfunction plays a prominent role in the development of obesity and its related disorders such as insulin resistance, cardiovascular disease, diabetes, depression and cancer. In this review, we will summarize the recent findings of adipose tissue in the control of metabolism, focusing on its endocrine and thermogenic function.
Human umbilical perivascular cells (HUCPVCs): a novel source of mesenchymal stromal-like (MSC) cells to support the regeneration of the testicular niche
Authors: Maghen Leila , Shlush Ekaterina , Gat Itai , Filice Melissa , Barretto Tanya A , Jarvi Keith , Lo Kirk , Gauthier-Fisher Andrée , Librach Clifford L
Published: October 2016

The expansion of functional testicular biopsy-derived human spermatogonial stem cells (hSSC)ex vivomay enable the restoration of fertility in pre-pubertal males having undergone gonadotoxic therapies or men with severe male factor infertility. Various somatic cells are known to regulate SSC homeostasis and spermatogenesis in the developing and adult testis. Prior attempts to recapitulate this niche demonstrated the requirement of feeder cells, such as endogenous testicular somatic cells, for germ cell expansionex vivo. However, this strategy has limitations in the expansion of hSSCs from tissue biopsies for which spermatogenesis is absent or defective. Our aim was to evaluate the first trimester human umbilical cord perivascular cells (FTM HUCPVCs), a novel source of mesenchymal stromal-like cells (MSCs), as potential human feeder cells for standardized hSSC expansionex vivo.Targeted RNA sequencing analysis demonstrated that CD90+ve FTM HUCPVCs expandedin vitrounder germ cell culture conditions express a profile of targeted testicular-associated transcripts that is similar to cultured human CD90+ve testicular adherent cells (hTACs) and secrete LIF, FGF2 and BMP4, key growth factors known to regulate spermatogenesis. We also demonstrated that mitotically inactivated FTM HUCPVCs support the expansion of mouse germ cells and putative SSCsex vivoand that FTM HUCPVC transplantation promotesin vivogerm cell regeneration after mono-2-ethylhexyl phthalate (MEHP)-induced seminiferous tubule damage in a murine model, including a partial reconstitution of tubular cellular architecture and reestablishment of DAZL and acrosin+ve germ cell layers. Together, these data suggest that FTM HUCPVCs have phenotypical and functional properties that may support repair of the human testicular niche.
New record of Sturnira bakeri Velazco & Patterson, 2014 (Chiroptera: Phyllostomidae) from northwestern Peru
Authors: Sánchez Pamela , Pacheco Victor
Published: October 2016

Sturnira bakeri was recently described from southwestern Ecuador near the Peruvian border and was suggested to occur also in Peru. To confirm this hypothesis we present a morphological and morphometric revision of specimens of Sturnira collectedfrom northwestern Peru. As result, we report the presence of S. bakeri from Peru and extend its distribution range southwestward by at least 32.3 km from previous occurrences, and we suggest that S. luisi is apparently absent from Peru. We also found evidence of sexual size dimorphism in S. bakeri.
Hybrid Simulation in Teaching Clinical Breast Examination
Authors: Nassif Joseph , Sleiman Abdul-Karim , Nassar Anwar , Naamani Sima , Sharara-Chami Rana
Published: October 2016

This article was migrated. The article was not marked as recommended. Problem: Clinical Breast Examination (CBE) is traditionally taught to third year medical students using a lecture and a table-top breast model. The opportunity to clinically practice CBE depends on patient availability and willingness to be examined by students, especially in culturally sensitive environments. Intervention: We employed hybrid simulation of the breast and aimed to investigate its effectiveness as an educational tool for teaching CBE to medical students. The hybrid simulation model consists of a standardized patient (SP) wearing a silicone breast simulator jacket. Context: We compared the use of this tool to the traditional method using a blinded randomized controlled design. Medical students (N=82, 48.8% male) were randomized into teaching activities: hybrid simulation and control. Both groups received didactic teaching followed by a practical session. The control group practiced on the table-top model traditionally used while the intervention group practiced on the hybrid model (SP+breast jacket). Next, all students were assessed on their technical and communication skills in an Objective Structured Clinical Examination (OSCE) that included three SP stations. SPs were trained to act according to specified cultural roles: a liberal woman, a veiled woman and a moderately modest woman. Assessment employed a variety of simulated lesions. Outcomes: The hypothesized outcomes consisted of a more complete acquisition of CBE skills, improved lesion detection and better communication skills. CBE completeness scores did not differ between the two groups (p=0.889). Hybrid simulation improved lesion identification grades (p<0.001) without increasing false positives. Communication skills were worse in the hybrid simulation group as graded by the SP (p<0.001), but not as reported by the students (p=0.346). We commented on the students' comfort during OSCE. Hybrid simulation relieved the fear of missing a lesion on CBE (p=0.043) and increased satisfaction with the teaching method among students (p=0.002). Lessons Learned: As a novel educational tool, hybrid simulation improves the sensitivity of CBE done by medical students without affecting its specificity. Although it might not necessarily improve their communication or sensitivity to cultural aspects of CBE, hybrid simulation might have a role in increasing the self-confidence of medical students during CBE.
80 anos de Serviço Social no Brasil: organização política e direção social da profissão no processo de ruptura com o conservadorismo
Authors: Abramides Maria Beatriz Costa
Published: October 2016

Resumo: O presente artigo se refere à trajetória histórica do Serviço Social brasileiro, considerada a direção social da profissão e o processo de ruptura com o conservadorismo. As determinações e os caminhos da profissão serão analisados a partir do projeto ético-político profissional hegemônico em sua relação com as lutas sociais e os direitos dos trabalhadores.
Trajetória acadêmica de professoras aposentadas do Serviço Social
Authors: Mesquita Paula Fabrícia Brandão Aguiar
Published: October 2016

Resumo: A discussão deste texto originou-se de uma pesquisa de pós-doutoramento, no qual se investigam as docentes aposentadas do curso de Serviço Social da UECE. A curiosidade advém de compreender as trajetórias dessas professoras, pioneiras do curso, e perseguir o sentido que atribuíram à prática docente. Foram revelados a relevância da experiência profissional como condição para o magistério, a ausência de mestrado e doutorado na sua formação, além de fortes traços humanistas em seus discursos.
A Interlocução de Narrativas: Um Estudo sobre Papéis de Gênero
Authors: Fávero Maria Helena , Maracci Inara Linn
Published: October 2016

RESUMO Retomamos a distinção entre sexo e gênero e entre papéis sexuais e de gênero na psicologia feminista. Referimos as contraposições à naturalização e discutimos a influência das ideologias da feminilidade e da masculinidade na socialização. Descrevemos um estudo sobre as concepções de quatro mulheres sobre os papéis de gênero, considerando a subjetividade na coleta e análise de dados. Utilizamos a narrativa e o grupo focal, tomando a proposição e os atos da fala como unidades de análise. Evidenciamos seis proposições articuladas a dois eixos principais: (a) as condições de vida e o abandono e (b) o significado e a prática da maternidade. Discutimos a identificação e o apego na socialização de gênero, defendendo o papel dos estudos psicológicos de gênero para as transformações sociais.
Evaluación de la diversidad en comunidades de tardígrados (Ecdysozoa: Tardigrada) en hábitats urbano y rural de la ciudad de Salta (Argentina)
Authors: González-Reyes Andrea , Acosta X. , Corronca J. , Rocha M. , Doma I. , Repp E. Y.
Published: October 2016

RESÚMEN Este trabajo se realizó bajo la hipótesis de que existe una pérdida creciente de diversidad en las comunidades de tardígrados, desde las áreas rurales hacia las urbanas, incrementando la homogenización de sus comunidades producto de la urbanización. Para la ciudad de Salta, se tomaron muestras en áreas con tránsito vehicular alto y muestras en áreas rurales circundantes. Se identificaron en total ocho especies/morfoespecies. El inventario tuvo una completitud mayor al 94%. La comunidad rural fue más diversa y estructuralmente más uniforme que la comunidad urbana. Macrobiotus hufelandi Schultze, 1834 resultó especie indicadora y Milnesium sp. como detectora para el hábitat urbano, mientras que Paramacrobiotus areolatus Murray, 1907 resultó indicadora para el hábitat rural.
Apostas de mudança na educação médica: trajetórias de uma escola de medicina
Authors: Teófilo Tiago José Silveira , Santos Nereida Lúcia Palko dos , Baduy Rossana Staevie
Published: October 2016

O objetivo do estudo foi conhecer práticas de ensino-aprendizagem, arranjos institucionais e a participação de diferentes atores em curso de graduação em medicina na cidade de Sobral-CE. Trata-se de estudo qualitativo descritivo, que utilizou-se da entrevista individual e em grupo para coleta de dados. Foram participantes do estudo: coordenadores, discentes e docentes de uma escola pública de medicina. A análise do discurso foi a técnica de análise do material empírico. Os resultados mostraram que os discursos elencaram três apostas de mudança: currículo em módulos como inovação pedagógica, a estratégia da aprendizagem baseada em problemas, e a Estratégia Saúde da Família como eixo estruturante para a mudança na formação. Concluiu-se que os discursos colocam as técnicas pedagógicas em si como o centro do debate. A atenção básica à saúde aparece como espaço por excelência para o acolhimento e responsabilização na produção do cuidado.
Espiral construtivista: uma metodologia ativa de ensino-aprendizagem
Authors: Lima Valéria Vernaschi
Published: October 2016

A partir da teoria sociointeracionista da educação e da trajetória das práticas pedagógicas nas sociedades ocidentais, o artigo apresenta a espiral construtivista como uma metodologia ativa de ensino-aprendizagem. Discute as origens e a utilização de metodologias ativas no ensino superior, focalizando: a aprendizagem baseada em problemas, a metodologia da problematização, o método científico e o uso de narrativas, simulações ou atuações em cenários reais de prática. A exploração da espiral construtivista, de acordo com os movimentos: “identificando problemas”; “formulando explicações”; “elaborando questões”; “construindo novos significados”; “avaliando processo e produtos”, destaca semelhanças e diferenças em relação às metodologias ativas focalizadas. Para além dos aspectos metodológicos envolvidos, a intencionalidade educacional na utilização da espiral construtivista é explicitada pela natureza dos disparadores de aprendizagem utilizados e pelo sentido transformador da realidade derivado da postura crítica e reflexiva na interação do “sujeito” e “objeto”.
Motivos da escolha do automóvel no acesso a megaeventos: caso da Copa das Confederações 2013, Rio de Janeiro
Authors: Escobar Nathaly , Flórez Josefina , Portugal Licinio da Silva
Published: October 2016

Resumo Realizar um megaevento implica em inúmeros e significativos impactos, em especial na mobilidade urbana, cujo tratamento e mitigação exigem adequadas estratégias e políticas, dentre as quais se destaca o incentivo ao uso dos modos de transporte mais sustentáveis. A efetividade das estratégias dependerá de diversos fatores que interferem no processo de escolha modal. Neste artigo, com base em consulta a mais de mil espectadores que assistiram aos jogos da Copa das Confederações 2013, realizados no Rio de Janeiro, pretende-se apresentar e analisar os principais motivos que influenciaram no uso do automóvel. Adicionalmente, a partir de uma revisão bibliográfica, identificam-se os motivos instrumentais que incidem na escolha do automóvel, confrontando-os com os obtidos na nossa pesquisa. Mesmo que tais motivos e sua hierarquização sejam suscetíveis a mudar no tempo e sensíveis às especificidades locais, parece que, no caso das cidades brasileiras, sistemas de transportes alternativos ao automóvel apresentam uma forte deficiência quanto a atributos como o conforto e a rapidez, o que ressalta a necessidade de não só restringir o acesso ao automóvel, mas de se investir na melhoria dos transportes públicos e não motorizados, tornando-os opções mais atraentes para os usuários de automóvel realizarem a transferência modal.
Território, territorialidade e fronteira: o problema dos limites municipais e seus desdobramentos em Belém/PA
Authors: Lima da Silva Marlon , Tourinho Helena Lúcia Zagury
Published: October 2016

Resumo O trabalho versa sobre o problema dos limites municipais à luz dos conceitos de território, territorialidade e fronteira. Mostra-se que imprecisões e inadequações nas leis, no que se refere ao estabelecimento dos limites fronteiriços de Belém, no Estado do Pará, com outros municípios, têm resultado em conflitos de mapas, de gestão pública, além da divisão de ocupações/conjuntos habitacionais, causando uma série de problemas aos gestores municipais e, principalmente, aos moradores das áreas em conflito. Ao analisar estudos realizados pelos poderes públicos com o objetivo de redefinir os limites, revela-se que tais pesquisas são incompletas e falham por não considerarem aspectos relativos às territorialidades dos grupos envolvidos na questão. Partindo-se do princípio que a definição de limites territoriais é muito mais do que uma questão de técnica de cartografia, embora esta seja importante, defende-se que a proposição de novos limites municipais deve considerar os conceitos de território, territorialidade e fronteira, além de ser apresentada a metodologia desenvolvida pelos autores deste artigo, que são técnicos da Companhia de Desenvolvimento e Administração da Área Metropolitana de Belém.