bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuroprotective Effects of Increased Extracellular Ca2+ During Aglycemia in White Matter
Authors: Brown Angus M. , Ransom Bruce R.
Published: December 2017

We investigated the effects of extracellular [Ca2+] ([Ca2+]o) on aglycemia-induced dysfunction and injury in adult rat optic nerves. Compound action potentials (CAPs) from adult rat optic nerve were recorded in vitro, and the area under the CAP was used to monitor nerve function before and after 1 h periods of aglycemia. In control artificial cerebrospinal fluid (ACSF) containing 2 mM Ca2+, CAP function fell after 29.9 ± 1.5 (SE) min and recovered to 48.8 ± 3.9% following aglycemia. Reducing bath [Ca2+] during aglycemia progressively improved recovery. For example, in Ca2+-free ACSF, the CAP recovered to 99.1 ± 3.8%. Paradoxically, increasing bath [Ca2+] also improved recovery from aglycemia. In 5 or 10 mM bath [Ca2+], CAP recovered to 78.8 ± 9.2 or 91.6 ± 5.2%, respectively. The latency to CAP failure during aglycemia increased as a function of bath [Ca2+] from 0 to 10 mM. Increasing bath [Mg2+] from 2 to 5 or 10 mM, with bath [Ca2+] held at 2 mM, increased latency to CAP failure with aglycemia and improved recovery from this insult. [Ca2+]o recorded with calcium-sensitive microelectrodes in control ACSF, dropped reversibly during aglycemia from 1.54 ± 0.03 to 0.45 ± 0.04 mM. In the presence of higher ambient levels of bath [Ca2+] (i.e., 5 or 10 mM), the aglycemia-induced decrease in [Ca2+]o declined, indicating that less Ca2+ left the extracellular space to enter an intracellular compartment. These results indicate that the role of [Ca2+], and divalent cations in general, during aglycemia is complex. While extracellular Ca2+ was required for irreversible aglycemic injury to occur, higher levels of [Ca2+] or [Mg2+] increased the latency to CAP failure and improved the extent of recovery, apparently by limiting Ca2+ influx. These effects are theorized to be mediated by divalent cation screening.
Increased Sensitivity of Sensory Neurons to Tumor Necrosis Factor α in Rats With Chronic Compression of the Lumbar Ganglia
Authors: Liu Baogang , Li Huiqing , Brull Sorin J. , Zhang Jun-Ming
Published: December 2017

Proinflammatory cytokines may sensitize primary sensory neurons and facilitate development of neuropathic pain processes after peripheral nerve injury. The goal of this study was to determine whether responses of dorsal root ganglion (DRG) neurons to exogenous tumor necrosis factor α (TNF-α) are altered in a chronically compressed DRG (CCD) injury model. Extracellular recordings from teased dorsal root microfilaments demonstrated that acute topical application of TNF-α to the DRG for 15 min evoked C- and Aβ-fiber responses in both normal and CCD rats. However, the response latency was significantly shorter, and the peak discharge rate was higher, in CCD fibers than in normal fibers. Intracellular recordings from small- and large-sized neurons showed that TNF-α induced greater depolarization and greater decrease in rheobase in CCD neurons than in normal neurons. The proportion of both small- and large-sized neurons that were responsive to TNF-α increased significantly after CCD injury. Furthermore, TNF-α altered the discharge patterns of large, spontaneously active neurons in addition to enhancing their discharge rates. However, the depolarization caused by TNF-α in such neurons was minor (<2 mV). Inflammatory cytokines such as TNF-α increased the sensitivity of sensory neurons in normal and CCD rats. The CCD injury itself, on the other hand, increased neuronal responses to inflammatory cytokines.
Sound Repetition Rate in the Human Auditory Pathway: Representations in the Waveshape and Amplitude of fMRI Activation
Authors: Harms Michael P. , Melcher Jennifer R.
Published: December 2017

Sound repetition rate plays an important role in stream segregation, temporal pattern recognition, and the perception of successive sounds as either distinct or fused. This study was aimed at elucidating the neural coding of repetition rate and its perceptual correlates. We investigated the representations of rate in the auditory pathway of human listeners using functional magnetic resonance imaging (fMRI), an indicator of population neural activity. Stimuli were trains of noise bursts presented at rates ranging from low (1–2/s; each burst is perceptually distinct) to high (35/s; individual bursts are not distinguishable). There was a systematic change in the form of fMRI response rate-dependencies from midbrain to thalamus to cortex. In the inferior colliculus, response amplitude increased with increasing rate while response waveshape remained unchanged and sustained. In the medial geniculate body, increasing rate produced an increase in amplitude and a moderate change in waveshape at higher rates (from sustained to one showing a moderate peak just after train onset). In auditory cortex (Heschl's gyrus and the superior temporal gyrus), amplitude changed somewhat with rate, but a far more striking change occurred in response waveshape—low rates elicited a sustained response, whereas high rates elicited an unusual phasic response that included prominent peaks just after train onset and offset. The shift in cortical response waveshape from sustained to phasic with increasing rate corresponds to a perceptual shift from individually resolved bursts to fused bursts forming a continuous (but modulated) percept. Thus at high rates, a train forms a single perceptual “event,” the onset and offset of which are delimited by the on and off peaks of phasic cortical responses. While auditory cortex showed a clear, qualitative correlation between perception and response waveshape, the medial geniculate body showed less correlation (since there was less change in waveshape with rate), and the inferior colliculus showed no correlation at all. Overall, our results suggest a population neural representation of the beginning and the end of distinct perceptual events that is weak or absent in the inferior colliculus, begins to emerge in the medial geniculate body, and is robust in auditory cortex.
Sources of Signal-Dependent Noise During Isometric Force Production
Authors: Jones Kelvin E. , Hamilton Antonia F. de C. , Wolpert Daniel M.
Published: December 2017

It has been proposed that the invariant kinematics observed during goal-directed movements result from reducing the consequences of signal-dependent noise (SDN) on motor output. The purpose of this study was to investigate the presence of SDN during isometric force production and determine how central and peripheral components contribute to this feature of motor control. Peripheral and central components were distinguished experimentally by comparing voluntary contractions to those elicited by electrical stimulation of the extensor pollicis longus muscle. To determine other factors of motor-unit physiology that may contribute to SDN, a model was constructed and its output compared with the empirical data. SDN was evident in voluntary isometric contractions as a linear scaling of force variability (SD) with respect to the mean force level. However, during electrically stimulated contractions to the same force levels, the variability remained constant over the same range of mean forces. When the subjects were asked to combine voluntary with stimulation-induced contractions, the linear scaling relationship between the SD and mean force returned. The modeling results highlight that much of the basic physiological organization of the motor-unit pool, such as range of twitch amplitudes and range of recruitment thresholds, biases force output to exhibit linearly scaled SDN. This is in contrast to the square root scaling of variability with mean force present in any individual motor-unit of the pool. Orderly recruitment by twitch amplitude was a necessary condition for producing linearly scaled SDN. Surprisingly, the scaling of SDN was independent of the variability of motoneuron firing and therefore by inference, independent of presynaptic noise in the motor command. We conclude that the linear scaling of SDN during voluntary isometric contractions is a natural by-product of the organization of the motor-unit pool that does not depend on signal-dependent noise in the motor command. Synaptic noise in the motor command and common drive, which give rise to the variability and synchronization of motoneuron spiking, determine the magnitude of the force variability at a given level of mean force output.
Concordant and Discordant Coding of Spatial Location in Populations of Hippocampal CA1 Pyramidal Cells
Authors: Brown Joel E. , Skaggs William E.
Published: December 2017

Pyramidal cells in the rat hippocampus commonly show place-related activity, but it has been difficult to understand the factors that govern them. A particularly important question is whether individual cells have identifiable correlates that can be manipulated independently of the correlates of other cells. Recently Tanila et al. examined the activity of small ensembles of hippocampal cells in rats running on a plus-maze with distinct intra- and extramaze cues. When the two sets of cues were rotated 90° in opposite directions, some cells followed the intramaze cues, others followed the extramaze cues, and others “remapped” unpredictably; moreover, all possible combinations were seen within simultaneously recorded ensembles. In the current study, CA1 pyramidal cell population activity was recorded from four rats in a similar paradigm, using a recording system that permitted the analysis of ensembles of 4–70 simultaneously recorded units. The results were consistent with the data from the earlier study in showing an increase in remapping over time and in showing some place fields following one of the defined sets of cues while others remapped. When the possibility of random remapping was controlled for, however, the analysis did not show significant numbers of place fields following both sets of cues simultaneously. Furthermore, all rats initially showed fully concordant responses with all place fields following the local cues. For two rats, this pattern continued until a new configuration was introduced at which time all fields switched to follow the distal cues. Taken together, the results are difficult to reconcile with the hypothesis that individual hippocampal cells encode information about different subsets of cues in the environment.
Functional Characterization of GABAA Receptors in Neonatal Hypothalamic Brain Slice
Authors: Huang Ren-Qi , Dillon Glenn H.
Published: December 2017

The hypothalamus influences a number of autonomic functions. The activity of hypothalamic neurons is modulated in part by release of the inhibitory neurotransmitter GABA onto these neurons. GABAA receptors are formed from a number of distinct subunits, designated α, β, γ, δ, ε, and θ, many of which have multiple isoforms. Little data exist, however, on the functional characteristics of the GABAA receptors present on hypothalamic neurons. To gain insight into which GABAA receptor subunits are functionally expressed in the hypothalamus, we used an array of pharmacologic assessments. Whole cell recordings were made from thin hypothalamic slices obtained from 1- to 14-day-old rats. GABAA receptor-mediated currents were detected in all neurons tested and had an average EC50 of 20 ± 1.6 μM. Hypothalamic GABAA receptors were modulated by diazepam (EC50 = 0.060 μM), zolpidem (EC50 = 0.19 μM), loreclezole (EC50 = 4.4 μM), methyl-6,7-dimethoxy-4-ethyl-β-carboline (EC50= 7.7 μM), and 5α-pregnan-3α-hydroxy-20-one (3α-OH-DHP). Conversely, these receptors were inhibited by Zn2+ (IC50 = 70.5 μM), dehydroepiandrosterone sulfate (IC50 = 16.7 μM), and picrotoxin (IC50 = 2.6 μM). The α4/6-selective antagonist furosemide (10–1,000 μM) was ineffective in all hypothalamic neurons tested. The results of our pharmacological analysis suggest that hypothalamic neurons express functional GABAA receptor subtypes that incorporate α1 and/or α2 subunits, β2 and/or β3 subunits, and the γ2 subunit. Our results suggest receptors expressing α3–α6, β1, γ1, and δ, if present, represent a minor component of functional hypothalamic GABAA receptors.
Organization of Corticostriatal Motor Inputs in Monkey Putamen
Authors: Nambu Atsushi , Kaneda Katsuyuki , Tokuno Hironobu , Takada Masahiko
Published: December 2017

To analyze the organization of corticostriatal motor inputs, we examined the neuronal responses in the putamen (Put) to stimulation in the primary motor cortex (MI) and the supplementary motor area (SMA). Stimulating electrodes were chronically implanted in the distal and proximal parts of the forelimb representation of the MI and in the forelimb representation of the SMA in Japanese monkeys ( Macaca fuscata). Stimulation in the MI and SMA evoked orthodromic spike discharges in both phasically active and tonically active Put neurons. The latency of excitation evoked by MI stimulation was shorter than that of excitation evoked by SMA stimulation. Neurons responding exclusively to MI stimulation (MI-recipient neurons) and those responding exclusively to SMA stimulation (SMA-recipient neurons) were distributed predominantly in the ventrolateral and dorsomedial portion of the caudal aspect of the Put, respectively. About 20% of the recorded neurons responded concurrently to stimulation in both the MI and SMA (MI + SMA-recipient neurons). These neurons were located in the intermediate zone between the MI- and SMA-recipient zones. More than half of the Put neurons responded to sensorimotor stimulation. Movements of the forelimb were readily elicited by microstimulation in the MI-recipient zone, less frequently in the MI + SMA-recipient zone, and rarely in the SMA-recipient zone. More detailed analysis of the somatotopic arrangement based on cortical inputs, sensorimotor responses, and microstimulation-evoked movements revealed that within the MI- and MI + SMA-recipient zones of the Put, neurons representing the distal part of the forelimb were located more ventrally than those representing the proximal part. No such somatotopy was clearly detected in the SMA-recipient zone. The present results indicate that corticostriatal inputs from the forelimb regions of the MI and SMA are largely segregated. On the other hand, convergent inputs from the MI and SMA were noted on single neurons located at the junction between the two input zones. In addition, the corticostriatal inputs from the forelimb region of the MI exhibited a distal to proximal somatotopic organization along the ventrodorsal axis of the Put.
Short-Term Dynamics of Thalamocortical and Intracortical Synapses Onto Layer 6 Neurons in Neocortex
Authors: Beierlein Michael , Connors Barry W.
Published: December 2017

Layer 6 is the main source of neocortical connections back to specific thalamic nuclei. Corticothalamic (CT) systems play an important role in shaping sensory input, but little is known about the functional circuitry that generates CT activity. We recorded from the two main types of neurons in layer 6, regular-spiking (RS; pyramidal neurons) and fast-spiking (FS; inhibitory interneurons) cells and compared the physiological properties of different excitatory inputs. Thalamic stimulation evoked two monosynaptic inputs with distinct properties: suspected thalamocortical (TC) synaptic events had short latencies, short-term synaptic depression, and paired-pulse responses that suggested subnormal axonal conduction. A second group of synaptic responses likely originated from intracortical collaterals of CT cells that were antidromically activated from the thalamus. These intracortical responses had longer latencies, short-term synaptic facilitation, and were transmitted by axons with supernormal conduction. Suspected TC inputs to FS cells had significantly larger amplitudes than those onto RS cells. Dual recordings from neighboring neurons in layer 6 revealed both facilitating and depressing synaptic connections; the depressing synapses were probably formed by layer 6 cells that do not project to the thalamus, and thus were not sampled by thalamic stimulation. We conclude that layer 6 neurons integrate a variety of inputs with distinct temporal dynamics that are determined by the presynaptic cell type.
Response Selectivity for Species-Specific Calls in the Inferior Colliculus of Mexican Free-Tailed Bats is Generated by Inhibition
Authors: Klug Achim , Bauer Eric E. , Hanson Joshua T. , Hurley Laura , Meitzen John , Pollak George D.
Published: December 2017

Here we show that inhibition shapes diverse responses to species-specific calls in the inferior colliculus (IC) of Mexican free-tailed bats. We presented 10 calls to each neuron of which 8 were social communication and 2 were echolocation calls. We also measured excitatory response regions: the range of tone burst frequencies that evoked discharges at a fixed intensity. The calls evoked highly selective responses in that IC neurons responded to some calls but not others even though those calls swept through their excitatory response regions. By convolving activity in the response regions with the spectrogram of each call, we evaluated whether responses to tone bursts could predict discharge patterns evoked by species-specific calls. The convolutions often predicted responses to calls that evoked no responses and thus were inaccurate. Blocking inhibition at the IC reduced or eliminated selectivity and greatly improved the predictive accuracy of the convolutions. By comparing the responses evoked by two calls with similar spectra, we show that each call evoked a unique spatiotemporal pattern of activity distributed across and within isofrequency contours and that the disparity in the population response was greatly reduced by blocking inhibition. Thus the inhibition evoked by each call can shape a unique pattern of activity in the IC population and that pattern may be important for both the identification of a particular call and for discriminating it from other calls and other signals.
Spatial Attention and Memory Versus Motor Preparation: Premotor Cortex Involvement as Revealed by fMRI
Authors: Simon Stéphane R. , Meunier Martine , Piettre Loÿs , Berardi Anna M. , Segebarth Christoph M. , Boussaoud Driss
Published: December 2017

Recent studies in both monkeys and humans indicate that the dorsal premotor cortex participates in spatial attention and working memory, in addition to its well known role in movement planning and execution. One important question is whether these functions overlap or are segregated within this frontal area. Single-cell recordings in monkeys suggest a relative specialization of the rostral portion of dorsal premotor cortex for attention and/or memory and of the caudal region for motor preparation. To test whether this possibility also holds true in humans, we used functional magnetic resonance imaging (fMRI) to compare, in the same set of subjects, brain activation related to strong spatial attention and memory demands to that elicited by long motor preparatory periods. The behavioral protocol was based on a task that had proved effective for dissociating neuronal properties related to these two functions in the monkey brain. The principle of the monkey task was that a first cue guided the focus of spatial attention and memory, whereas a second one instructed an arm movement. Based on this principle, two tasks were developed. One maximized spatial attention and memory demands by presenting long series of stimuli (4, 8, or 12) before the motor instructional cue, whereas the other extended the motor preparation phase by imposing long and variable delays (1–5.5 s) between the onset of the instructional cue and movement execution. The two tasks and their respective control conditions were arranged in two blocked-design sequences. The results indicate that the brain networks underlying the two functional domains overlap in the caudate nucleus and presupplementary motor area, and possibly in lateral prefrontal cortex as well, but involve different dorsal premotor fields. Motor preparation primarily recruited a dorsal premotor area located caudally, within the precentral gyrus (together with the supplementary motor area), whereas spatial attention and memory preferentially activated a more rostral site, in and anterior to the precentral sulcus (in addition to the posterior parietal cortex). These findings strengthen the idea that the primate dorsal premotor cortex contributes to both motor and nonmotor processes. Moreover, they corroborate emerging evidence from monkey physiology suggesting a relative functional segregation within this cortex, with attention to short-term storage of visuospatial information engaging a more rostral region than motor preparation.
Testicular Inflammatory Myofibroblastic Tumor: A Known Entity at a Very Rare Site
Authors: Voelker Hans-Ullrich , Kuehn Daniel , Strehl Annette , Kircher Stefan
Published: December 2017

Inflammatory myofibroblastic tumors (IMT) are distinctive lesions of unknown etiology, composed of myofibroblastic spindle cells with an associated inflammatory background. They can occur in a wide age range and at all anatomic sites, but most frequently they can be observed in the lung (especially in pediatric cases), abdomen, or retroperitoneum. The urinary bladder is one of the most common sites in urological cases. We present a very rare case of IMT of the testis. Clinically, a 40-year-old patient showed a palpable painless lesion of the right testis. Ultrasound examination showed two solid intratesticular foci. During surgical intervention, the intraoperative frozen section revealed mesenchymal tumors admixed with an uncommon inflammatory infiltrate, consistent with a reorganized abscess. Despite the benign result, orchiectomy was performed due to the multifocal presentation and the large size of 3 cm. The final diagnosis was IMT without ALK-rearrangement. Incomplete resection increases the risk of local relapses to 30%. In this case, a complete resection could be achieved and the patient is free of tumor 15 months later.
Approach to Hemoptysis in the Modern Era
Authors: Gagnon Sébastien , Quigley Nicholas , Dutau Hervé , Delage Antoine , Fortin Marc
Published: December 2017

Hemoptysis is a frequent manifestation of a wide variety of diseases, with mild to life-threatening presentations. The diagnostic workup and the management of severe hemoptysis are often challenging. Advances in endoscopic techniques have led to different new therapeutic approaches. Cold saline, vasoconstrictive and antifibrinolytic agents, oxidized regenerated cellulose, biocompatible glue, laser photocoagulation, argon plasma coagulation, and endobronchial stents and valves are amongst the tools available to the bronchoscopist. In this article, we review the evidence regarding the definition, etiology, diagnostic modalities, and treatment of severe hemoptysis in the modern era with emphasis on bronchoscopic techniques.
Corrosion Properties of 34CrMo4 Steel Modified by Shot Peening
Authors: Zheng Qiang , Li Kejian , Yin Xueguo , Li Bingbing , Li Chunhong , Ma Yilong , Sun Jianchun , Chen Dengming
Published: December 2017

A nanocrystalline layer was prepared on the surface of 34CrMo4 steel by time controlling shot peening (SP, i.e., 1, 5, 10, and 20 minutes). Field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD) analysis, and transmission electron microscope (TEM) were applied to analyze the surface, cross-sections, and grain size of the specimens before and after SP. The electrochemical corrosion behavior was used to simulate a liquid under the oil and gas wells environment. It was characterized by the potentiodynamic polarization test and electrochemical impedance spectroscopy (EIS). The analysis results show that the surfaces of the SP samples were very rough and had numerous cracks. A passive film on SP surface was formed by nanocrystalline grains. However, the passive film formed in the initial stage was not dense or uniform, and cracks occurred in the passive film during peening, resulting in a decrease in corrosion resistance.
Low-Frequency Repetitive Transcranial Magnetic Stimulation for Stroke-Induced Upper Limb Motor Deficit: A Meta-Analysis
Authors: Zhang Lan , Xing Guoqiang , Shuai Shiquan , Guo Zhiwei , Chen Huaping , McClure Morgan A. , Chen Xiaojuan , Mu Qiwen
Published: December 2017

Background and Purpose. This meta-analysis aimed to evaluate the therapeutic potential of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) over the contralesional hemisphere on upper limb motor recovery and cortex plasticity after stroke.Methods. Databases of PubMed, Medline, ScienceDirect, Cochrane, and Embase were searched for randomized controlled trials published before Jun 31, 2017. The effect size was evaluated by using the standardized mean difference (SMD) and a 95% confidence interval (CI). Resting motor threshold (rMT) and motor-evoked potential (MEP) were also examined.Results. Twenty-two studies of 1 Hz LF-rTMS over the contralesional hemisphere were included. Significant efficacy was found on finger flexibility (SMD = 0.75), hand strength (SMD = 0.49), and activity dexterity (SMD = 0.32), but not on body function (SMD = 0.29). The positive changes of rMT (SMD = 0.38 for the affected hemisphere and SMD = −0.83 for the unaffected hemisphere) and MEP (SMD = −1.00 for the affected hemisphere and SMD = 0.57 for the unaffected hemisphere) were also significant.Conclusions. LF-rTMS as an add-on therapy significantly improved upper limb functional recovery especially the hand after stroke, probably through rebalanced cortical excitability of both hemispheres. Future studies should determine if LF-rTMS alone or in conjunction with practice/training would be more effective.Clinical Trial Registration Information. This trial is registered with unique identifierCRD42016042181.
Neonatal Pneumopericardium in a Nonventilated Term Infant: A Case Report and Review of the Literature
Authors: Roychoudhury Smita , Kaur Sharandeep , Soraisham Amuchou Singh
Published: December 2017

Neonatal pneumopericardium (PPC) is a rare form of neonatal air leak syndrome with high morbidity and mortality. Air leak syndrome in the newborn is usually associated with active resuscitation, respiratory distress syndrome, meconium aspiration syndrome, mechanical ventilation, or trauma associated with labour. Neonatal PPC can be associated with other air leak syndromes such as pneumomediastinum, pneumothorax, pneumoperitoneum, and subcutaneous and interstitial emphysema. Spontaneous PPC is a rare event in the neonatal period. We report a case of PPC in association with pneumothorax in a nonventilated term infant. The infant responded to thoracocentesis without the need for pericardiocentesis.
Anti‐Inflammatory Activity of Babassu Oil and Development of a Microemulsion System for Topical Delivery
Authors: Reis Mysrayn Y. F. A. , Santos Simone M. dos , Silva Danielle R. , Silva Márcia V. , Correia Maria Tereza S. , Navarro Daniela M. A. Ferraz , Santos Geanne K. N. , Hallwass Fernando , Bianchi Otávio , Silva Alexandre G. , Melo Janaína V. , Mattos Alessandra B. , Ximenes Rafael M. , Machado Giovanna , Saraiva Karina L. A.
Published: December 2017

Babassu oil extraction is the main income source in nut breakers communities in northeast of Brazil. Among these communities, babassu oil is used for cooking but also medically to treat skin wounds and inflammation, and vulvovaginitis. This study aimed to evaluate the anti‐inflammatory activity of babassu oil and develop a microemulsion system with babassu oil for topical delivery. Topical anti‐inflammatory activity was evaluated in mice ear edema using PMA, arachidonic acid, ethyl phenylpropiolate, phenol, and capsaicin as phlogistic agents. A microemulsion system was successfully developed using a Span® 80/Kolliphor® EL ratio of 6 : 4 as the surfactant system (S), propylene glycol and water (3 : 1) as the aqueous phase (A), and babassu oil as the oil phase (O), and analyzed through conductivity, SAXS, DSC, TEM, and rheological assays. Babassu oil and lauric acid showed anti‐inflammatory activity in mice ear edema, through inhibition of eicosanoid pathway and bioactive amines. The developed formulation (39% A, 12.2% O, and 48.8% S) was classified as a bicontinuous to o/w transition microemulsion that showed a Newtonian profile. The topical anti‐inflammatory activity of microemulsified babassu oil was markedly increased. A new delivery system of babassu microemulsion droplet clusters was designed to enhance the therapeutic efficacy of vegetable oil.
Multiobjective Optimization of a Rotman Lens through the QLWS Minimization
Authors: Pinchera Daniele , Perna Stefano , Migliore Marco Donald
Published: December 2017

We address the multiobjective optimization of a Rotman lens by means of a recently proposed method based on the minimization of a properly defined global cost function named Quantized Lexicographic Weighted Sum (QLWS). More specifically, we have considered three different objectives concurring during the optimal synthesis of the lens. First, the difference between actual and desired delay among the excitations of the array elements fed by the lens needs to be lower than a given threshold. Second, gain losses of the beams scanned by the array fed by the lens need to be lower than a given threshold. Third, lens insertion losses should be as low as possible. Exploitation of the QLWS based approach allowed us to obtain in a few minutes a Rotman lens fulfilling these three concurring objectives and to improve the starting result obtained by a commercial software.
A Simple Model for Inducing Optimal Increase of SDF-1 with Aminoglycoside Ototoxicity
Authors: Ju Hyun Mi , Lee Sun Hee , Choi Jin Sil , Seo Young Joon
Published: December 2017

Objectives. As a homing factor of stem cell, stromal derived factor-1 (SDF-1) is important for the regenerative research in ototoxicity. Mice models with aminoglycoside ototoxicity have been widely used to study the regeneration capacity of MSCs in repair of cochlear injury. We developed a mouse model with maximal increase in SDF-1 levels in the inner ear, according to the “one-shot” doses of kanamycin and furosemide. Methods. C57BL/6 mice had kanamycin (420, 550, and 600 mg/kg) dissolved in PBS, followed by an intraperitoneal injection of furosemide (130 mg/kg). The injuries of inner ear were measured with hearing thresholds, histology, and outer hair cell counts at 0, 3, 5, 7, 10, and 14 days before the sacrifice. The levels of SDF-1 in the inner ear were tested by real-time RT-PCR and immunohistochemistry. Results. There were a significant reduction in hearing thresholds and a maximal increase of SDF-1 levels in the furosemide 130 mg/kg + kanamycin 550 mg/kg group, but severe hearing deterioration over time was observed in the furosemide 130 mg/kg + kanamycin 600 mg/kg group and four mice were dead. SDF-1 was detected mostly in the stria vascularis and organ of Corti showing the highest increase in expression. Conclusion. We observed optimal induction of the stem cell homing factor in the newly generated aminoglycoside-induced ototoxicity mouse model using a “one-shot” protocol. This study regarding high SDF-1 levels in our mouse model of ototoxicity would play a major role in the development of therapeutic agents using MSC homing.
Transvaginal Management of Vaginal Cuff Dehiscence with Bowel Evisceration following Delayed Diagnosis
Authors: Bleull Samantha , Smith Hunter , Shapiro Robert
Published: December 2017

One of the most serious complications that can arise from hysterectomy is vaginal cuff dehiscence with subsequent bowel evisceration. Treatment via vaginal approach has been utilized in early cases of vaginal cuff dehiscence where the need for bowel resection is less likely. Our case examines the treatment of vaginal cuff dehiscence through a vaginal approach approximately 36 hours after apparent vaginal dehiscence with subsequent bowel evisceration. In this case, we chose a vaginal approach even in the setting of possible bowel obstruction and a significant leukocytosis. We utilized CT scan findings to help guide our surgical approach. Although the subjective appearance of the bowel protruding through the vaginal cuff was reassuring, this played little role in guiding our decision with regard to surgical approach. Vaginal cuff dehiscence with evisceration can be managed successfully via a vaginal approach even with prolonged exposure of the bowel to vaginal flora. CT scan should be utilized to evaluate bowel integrity when considering a vaginal dehiscence repair. A high index of suspicion is warranted as these cases can present up to many years after hysterectomy.
Using Smartphones to Assist People with Down Syndrome in Their Labour Training and Integration: A Case Study
Authors: Gomez Javier , Torrado Juan Carlos , Montoro Germán
Published: December 2017

This article describes a proposal and case study based on mobile phones and QR Codes to assist individuals with cognitive disabilities in their labour training and integration. This proposal, named AssisT-Task, is a full functional mobile application for Android smartphones and offers step-by-step guidance, establishing a learning method through task sequencing. It has been tested with a group of 10 users and 2 types of labour tasks. Through 7 recorded sessions, we compared the performance and the learning progress with the tool against the traditional assisting method, based on paper instructions. The results show that people with cognitive disabilities learnt and performed better and faster when using AssisT-Task than the traditional method, particularly on tasks that require cognitive effort rather than manual skills. This learning has proved to be essential to obtain an adequate degree of personal autonomy for people with cognitive impairment.
Association of Paraoxonase-1 Q192R (rs662) Single Nucleotide Variation with Cardiovascular Risk in Coffee Harvesters of Central Colombia
Authors: Siller-López Fernando , Garzón-Castaño Sandra , Ramos-Márquez Martha E. , Hernández-Cañaveral Iván
Published: December 2017

Paraoxonase 1 (PON1), a high-density lipoprotein-associated antioxidant enzyme, hydrolyzes several organophosphate pesticides and oxidized lipids. The PON1 Q192R polymorphism affects the catalytic efficiency and is considered a risk factor for pesticide intoxication and cardiovascular disease (CVD) but the association is not consistent between individuals or populations. We aimed to study the association of PON1 Q192R polymorphism with CVD risk in coffee harvesters of central Colombia. Demographics were collected from 205 subjects via standardized questionnaires. Lipid profiles and serum butyrylcholinesterase (BChE) were measured by standard procedures. The calculated 10-year atherosclerotic CVD (ASCVD) risk was used as the cardiovascular risk estimate. Q192R genotype was determined by real-time PCR. Prevalence of hypertension, hypercholesterolemia, and the 10-year ASCVD risk was 33%, 62%, and 22%, respectively. BChE levels were no indicative of recent pesticide exposure, although a positive correlation was observed with BChE and hypercholesterolemia. The Q192R genotype frequencies were 38% (QQ), 44% (QR), and 18% (RR). We found an association of the 192Q genotype with hypertension. The results of this study signal the importance to evaluate the influence and potential interactions of BChE and PON1 192Q allele with known genetic and environmental factors implicated in the pathogenesis of CVD.
Mathematical Modeling of Biofilm Structures Using COMSTAT Data
Authors: Verotta Davide , Haagensen Janus , Spormann Alfred M. , Yang Katherine
Published: December 2017

Mathematical modeling holds great potential for quantitatively describing biofilm growth in presence or absence of chemical agents used to limit or promote biofilm growth. In this paper, we describe a general mathematical/statistical framework that allows for the characterization of complex data in terms of few parameters and the capability to (i) compare different experiments and exposures to different agents, (ii) test different hypotheses regarding biofilm growth and interaction with different agents, and (iii) simulate arbitrary administrations of agents. The mathematical framework is divided to submodels characterizing biofilm, including new models characterizing live biofilm growth and dead cell accumulation; the interaction with agents inhibiting or stimulating growth; the kinetics of the agents. The statistical framework can take into account measurement and interexperiment variation. We demonstrate the application of (some of) the models using confocal microscopy data obtained using the computer program COMSTAT.
The Anti‐Inflammatory Effects of a Yin Zhi Huang Soup in an Experimental Autoimmune Prostatitis Rat Model
Authors: Deng Longsheng , Zhang Xikui , Zhu Weikun , Lu Taikun , Chen Jinchun , Zou Qiang , Zheng Qizhong , Chen Junying , Jiang Changming , Jin Guanyu
Published: December 2017

The present study aimed to investigate the therapeutic effects of the Chinese herbal medicine Yin Zhi Huang soup (YZS) in an experimental autoimmune prostatitis (EAP) rat model. In total, 48 rats were randomly divided into the following four groups (n = 12/group): saline group, pathological model group, Qianlietai group, and YZS group. We determined the average wet weight of the prostate tissue, the ratio of the wet weight of the prostate tissue to body weight, tumor necrosis factor‐alpha (TNF‐α) levels in the blood serum, the expression of inducible nitric oxide synthase (iNOS) in the rats’ prostate tissues, and the pathological changes in the prostate tissue using light microscopy. YZS reduced the rats’ prostate wet weight, the ratio of the prostate wet weight to body weight, and TNF‐α levels in the blood serum and inhibited the expression of iNOS in the rats’ prostate tissues (P < 0.05). Following YZS treatment, the pathological changes in the rats’ prostates were improved compared with those in the model group (P < 0.05). Furthermore, YZS treatment reduced inflammatory changes in the prostate tissue. It also significantly suppressed proinflammatory cytokines, such as TNF‐α, and chemokines, such as iNOS, in the rat model of EAP.
IGF-1R and Leptin Expression Profile and the Effects of Metformin Treatment on Metabolic and Endocrine Parameters in PCOS Mice
Authors: Prado Correia Luis Eduardo , de Almeida Bruna Cristine , de Jesus Simões Manuel , Abi Haidar Mauro , Berguio Vidotti Daniela , Silva Ivaldo
Published: December 2017

We aim to assess the effects of metformin treatment on metabolic and endocrine parameters and genes expression related to the insulin-responsive pathway in polycystic ovary syndrome (PCOS). This study comprises twenty-eight obese mice divided into three metformin-treated groups for seven and twenty days and eight nonobese and nontreated ones. We found a significant decrease in glycemia after metformin treatment at days seven and twenty. However, we did not observe differences in body weight measurement. Histologically, after twenty days we observed follicular development with regression of androgenic effects. Levels of IGF-1R protein expression were low after twenty days of treatment, but LEP proteins showed an overexpression in the ovarian stroma. We assessed the IGF-1R and LEP mRNAs levels; data showed a significant overexpression of LEP after seven days of treatment, while the IGF-1R was downregulated. Metformin therapy seems to exert a beneficial effect on histological and anovulatory features, reducing follicular number and pyknosis formation, possibly involved in the reversion of androgenic stimulus. Expression of IGF-1 and LEPR indicates a relevant role in androgenic features reversion present in PCOS, hormonal equilibrium, body weight regulation, and glucose metabolism, therefore, under phenotype obesity and infertility regulation in this model.
LIF Drives Neural Remodeling in Pancreatic Cancer and Offers a New Candidate Biomarker
Authors: Bressy Christian , Lac Sophie , Nigri Jérémy , Leca Julie , Roques Julie , Lavaut Marie-Nöelle , Secq Véronique , Guillaumond Fabienne , Bui Thi-Thien , Pietrasz Daniel , Granjeaud Samuel , Bachet Jean-Baptiste , Ouaissi Mehdi , Iovanna Juan , Vasseur Sophie , Tomasini Richard
Published: December 2017

Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive stroma and pathogenic modifications to the peripheral nervous system that elevate metastatic capacity. In this study, we show that the IL6-related stem cell–promoting factor LIF supports PDAC-associated neural remodeling (PANR). LIF was overexpressed in tumor tissue compared with healthy pancreas, but its receptors LIFR and gp130 were expressed only in intratumoral nerves. Cancer cells and stromal cells in PDAC tissues both expressed LIF, but only stromal cells could secrete it. Biological investigations showed that LIF promoted the differentiation of glial nerve sheath Schwann cells and induced their migration by activating JAK/STAT3/AKT signaling. LIF also induced neuronal plasticity in dorsal root ganglia neurons by increasing the number of neurites and the soma area. Notably, injection of LIF-blocking antibody into PDAC-bearing mice reduced intratumoral nerve density, supporting a critical role for LIF function in PANR. In serum from human PDAC patients and mouse models of PDAC, we found that LIF titers positively correlated with intratumoral nerve density. Taken together, our findings suggest LIF as a candidate serum biomarker and diagnostic tool and a possible therapeutic target for limiting the impact of PANR in PDAC pathophysiology and metastatic progression.

Significance: This study suggests a target to limit neural remodeling in pancreatic cancer, which contributes to poorer quality of life and heightened metastatic progression in patients. Cancer Res; 78(4); 909–21. ©2017 AACR.
Molecular Predicators of Duodenal Familial Adenomatous Polyposis Chemoprevention: Do Chemopreventive Drugs Hit Their Presumed Molecular Targets?
Authors: Shureiqi Imad
Published: December 2017

Patients with familial adenomatous polyposis (FAP) have an increased risk of developing duodenal adenomas and adenocarcinomas. In previous trials, sulindac (a cyclooxygenase inhibitor) alone failed to significantly suppress duodenal tumorigenesis in FAP patients, but sulindac plus the tyrosine kinase inhibitor erlotinib significantly reduced duodenal polyp burden. Delker and colleagues report in this issue (beginning on page 4) on transcriptome analyses that aimed to identify the molecular targets mediating the response to sulindac–erlotinib. Their exploratory transcriptome analyses suggested that sulindac–erlotinib suppressed duodenal polyposis via inhibiting Wnt/β-catenin, EGFR, and cyclooxygenase pathways. This perspective discusses the significance and limitations of the study. Cancer Prev Res; 11(1); 1–3. ©2017 AACR.

See related article by Delker et al., p. 4
Gender-Specific Antenatal Growth Reference Charts in Monochorionic Twins
Authors: Torres Ximena , Bennasar Mar , Eixarch Elisenda , Rueda Claudia , Goncé Anna , Muñoz Miriam , Marimón Edda , Martínez Josep M. , Gratacós Eduard , Figueras Francesc
Published: December 2017

Objective: To create antenatal gender-specific reference growth charts in uncomplicated monochorionic diamniotic twins. Materials and Methods: This is a prospective longitudinal study in which uncomplicated monochorionic (MC) twin pregnancies were included from 23 + 4 weeks of gestation onwards. Estimated fetal weight (EFW) and biometric parameters (biparietal diameter, head circumference, abdominal circumference, and femur length) were evaluated in both fetuses every 2 weeks using standardized methodology. Maternal and fetal complications were excluded. Charts were fitted for each biometric parameter and EFW in relation to gestational age and fetal gender using multilevel mixed models. Results: The final analysis included a total of 456 ultrasound examinations in 62 MC twins, with a mean of 7 scans per pregnancy (range 5–8). The mean as well as 5th and 95th percentiles of each biometric parameter and EFW were adjusted in relation to gender and gestational age between 24 and 37 weeks of gestation. Male fetuses have higher reference values than females, and the disparity is larger in the upper centiles of the distribution. Discussion: We provide gender-specific reference growth charts for MC twins. We suggest that these charts will improve prenatal MC twin assessment and surveillance, with a more accurate classification of normal or growth-restricted fetuses adjusted per sex.
Systemic Venous Drainage Is Associated with an Unfavorable Prenatal Behavior in Fetal Bronchopulmonary Sequestration
Authors: Lin Mei-Fang , Xie Hong-Ning , Zhao Xiu-Hua , Peng Ruan , Zheng Ju , Peng Zhen-Peng
Published: December 2017

Objective: This study aimed to determine the significance of the venous drainage pattern of bronchopulmonary sequestration (BPS) in the prenatal course. Methods: The venous drainage pattern of fetuses with BPS was determined with high-definition flow and confirmed by postnatal three-dimensional computed tomography angiography scan or autopsy. The volume of BPS lesions during gestation was recorded by the three-dimensional ultrasonographic Virtual Organ Computer-Aided Analysis software. The relationship between venous drainage pattern and prenatal characteristics was determined. Results: Seventy-one fetuses were enrolled: 35 with systemic venous drainage (SVD) and 36 with pulmonary venous drainage (PVD). The volumes of BPS lesions significantly increased from the middle second trimester to the later second trimester in the SVD group. A marked decrease from the later second trimester to the third trimester was observed in the PVD group. The incidences of associated anomalies, hydrops, and polyhydramnios in the SVD group were 14.2, 23.3, and 33.3%, respectively, significantly higher than those in the PVD group (0, 0, and 5.6%, respectively). Conclusions: Our data indicate that SVD is correlated with a higher risk of associated anomalies and an unfavorable prenatal course in fetal BPS. Identification of the venous drainage pattern is of clinical significance in predicting the prenatal behavior of fetal BPS.
Intralenticular Ozurdex® – One Year Later
Authors: Regan Kathleen A. , Blake Charles R. , Lukowski Zachary L. , Iyer Siva S.R.
Published: December 2017

Reported here is a case of intralenticular sustained-release dexamethasone implant (Ozurdex®, Allergan, Irvine, CA, USA) present for 1 year with effective treatment of refractory diabetic macular edema without rapid cataract formation. The crystalline lens remained stable for 12 months on exam despite the presence of the steroid-secreting foreign body. The diabetic macular edema resolved on exam and on optical coherence tomography. After 1 year, cataract extraction was uneventfully performed by phacoemulsification for a mild decline in visual acuity. Macular edema remains resolved 2 months following cataract removal. This is the longest reported period of observation of intralenticular Ozurdex in the literature. Ozurdex remains effective despite intralenticular location, and it can have minimal effects on cataract progression.