bluuebunny/crossref_metadata_2025 huggingface dataset:
Next‐generation sequencing of urine specimens: A novel platform for genomic analysis in patients with non–muscle‐invasive urothelial carcinoma treated with bacille Calmette‐Guérin
Authors: Scott Sasinya N. , Ostrovnaya Irina , Lin Caroline M. , Bouvier Nancy , Bochner Bernard H. , Iyer Gopakumar , Solit David , Berger Michael F. , Lin Oscar
Published: March 2017

BACKGROUND

Biopsies from patients with high‐risk (HR) non–muscle‐invasive urothelial carcinoma (NMIUC), especially flat urothelial carcinoma in situ, frequently contain scant diagnostic material or denuded mucosa only, and this precludes further extensive genomic analysis. This study evaluated the use of next‐generation sequencing (NGS) analysis of urine cytology material from patients with HR NMIUC in an attempt to identify genetic alterations that might correlate with clinical features and responses to bacille Calmette‐Guérin (BCG) treatment.

METHODS

Forty‐one cytology slides from patients with HR NMIUC treated with intravesical BCG were selected for this study. Histological confirmation was available for all cases. The specimens were subjected to NGS analysis with a customized targeted exome capture assay composed of 341 genes.

RESULTS

In this cohort, genomic alterations were successfully identified in all cytology samples. Mutations were detected down to a 2% allele frequency and chromosomal rearrangements including copy number alterations and gene fusions were identified. The most frequently altered genes included telomerase reverse transcriptase (TERT), tumor protein 53 (TP53), Erb‐B2 receptor tyrosine kinase 2 (ERBB2), and chromatin remodeling genes such as lysine demethylase 6A (KDM6A) and AT‐rich interaction domain 1A (ARID1A). For patients with matched tumor tissue, cytology specimens revealed all mutations detected in tissue as well as additional mutations, and this suggested that urine might more effectively capture the full genetic heterogeneity of disease than an individual cystectomy. Alterations in multiple genes correlated with clinical and histopathological features, including responses to BCG treatment, flat architecture versus papillary architecture, and smoking history.

CONCLUSIONS

Urine specimens can replace tissue as a substrate for NGS analysis of HR NMIUC. Several genomic alterations identified in urine specimens might be associated with histological features and clinical characteristics. Cancer Cytopathol 2017;125:416–26. © 2017 American Cancer Society.
Barrington's nucleus: Neuroanatomic landscape of the mouse “pontine micturition center”
Authors: Verstegen Anne M. J. , Vanderhorst Veronique , Gray Paul A. , Zeidel Mark L. , Geerling Joel C.
Published: March 2017

Barrington's nucleus (Bar) is thought to contain neurons that trigger voiding and thereby function as the “pontine micturition center.” Lacking detailed information on this region in mice, we examined gene and protein markers to characterize Bar and the neurons surrounding it. Like rats and cats, mice have an ovoid core of medium‐sized Bar neurons located medial to the locus coeruleus (LC). Bar neurons express a GFP reporter for Vglut2, develop from a Math1/Atoh1 lineage, and exhibit immunoreactivity for NeuN. Many neurons in and around this core cluster express a reporter for corticotrophin‐releasing hormone (BarCRH). Axons from BarCRH neurons project to the lumbosacral spinal cord and ramify extensively in two regions: the dorsal gray commissural and intermediolateral nuclei. BarCRH neurons have unexpectedly long dendrites, which may receive synaptic input from the cerebral cortex and other brain regions beyond the core afferents identified previously. Finally, at least five populations of neurons surround Bar: rostral‐dorsomedial cholinergic neurons in the laterodorsal tegmental nucleus; lateral noradrenergic neurons in the LC; medial GABAergic neurons in the pontine central gray; ventromedial, small GABAergic neurons that express FoxP2; and dorsolateral glutamatergic neurons that express FoxP2 in the pLC and form a wedge dividing Bar from the dorsal LC. We discuss the implications of this new information for interpreting existing data and future experiments targeting BarCRH neurons and their synaptic afferents to study micturition and other pelvic functions.
Quantitative mapping reveals age and sex differences in vasopressin, but not oxytocin, immunoreactivity in the rat social behavior neural network
Authors: DiBenedictis Brett T. , Nussbaum Elizabeth R. , Cheung Harry K. , Veenema Alexa H.
Published: March 2017

The neuropeptides vasopressin (AVP) and oxytocin (OT) have been implicated in the regulation of numerous social behaviors in adult and juvenile animals. AVP and OT signaling predominantly occur within a circuit of interconnected brain regions known collectively as the “social behavior neural network” (SBNN). Importantly, AVP and OT signaling within the SBNN has been shown to differentially regulate diverse social behaviors, depending on the age and/or sex of the animal. We hypothesized that variation in the display of these behaviors is due in part to age and sex differences in AVP and OT synthesis within the SBNN. However, a thorough characterization of AVP and OT‐immunoreactive (ir) fibers and cell bodies across age and sex within the SBNN has been lacking in rats. We therefore quantified AVP‐ and OT‐ir fibers and cell bodies in 22 subregions of the forebrain SBNN in juvenile and adult, male and female rats. We found numerous age (16 subregions) and sex (10 subregions) differences in AVP‐ir fiber fractional areas, and AVP‐ir cell body numbers, which were mainly observed in the medial amygdala/bed nucleus of the stria terminalis to lateral septum circuit. In contrast to AVP, we observed no age or sex differences in OT‐ir fiber fractional areas or cell bodies in any of the 22 subregions of the forebrain SBNN. Thus, unlike the static pattern observed for OT, AVP innervation of the forebrain SBNN appears to undergo developmental changes, and is highly sexually dimorphic, which likely has significant functional consequences for the regulation of social behavior.
Effect of Food Intake on the Pharmacodynamics of Tenapanor: A Phase 1 Study
Authors: Johansson Susanne A. , Knutsson Mikael , Leonsson‐Zachrisson Maria , Rosenbaum David P.
Published: March 2017

Tenapanor (RDX5791/AZD1722) is a minimally systemic small‐molecule inhibitor of the sodium/hydrogen exchanger NHE3. Tenapanor acts in the gut to reduce absorption of sodium and phosphate. This phase 1 open‐label, 3‐way crossover study (NCT02226783) evaluated the effect of food on the pharmacodynamics of tenapanor. Eighteen volunteers completed a randomized sequence of three 4‐day treatments with tenapanor hydrochloride 15 mg twice daily: before food, after food, and while fasting. Participants received a diet standardized for sodium content. Stool sodium was significantly higher with tenapanor administration before versus after food (difference, +8.8 mmol/day, P = .006) or while fasting (+11.8 mmol/day, P = .0004). Differences in urinary sodium were not significant. Stool phosphorus was not significantly different with tenapanor before versus after food and significantly higher before food versus while fasting (+4.9 mmol/day, P = .006). Urinary phosphorus was significantly lower when tenapanor was administered before (−3.9 mmol/day, P = .0005) or after food (−3.7 mmol/day, P = .0009) versus while fasting. No serious adverse events were reported. These data suggest the effect of tenapanor on sodium absorption is most pronounced when administered before meals, whereas the effect on phosphate is similar whether administered before or after meals. This may support different timings of tenapanor administration with respect to food for sodium‐ and phosphate‐related indications.
The utility of pap cell block preparations with liqui‐PREP™ cell pellets to clarify the cytological diagnosis of atypical squamous cells of undetermined significance and atypical glandular cells
Authors: George Nicholas B. , Baldassari Jashua Haddad , Pérez Taveras Digno A. , José Fernández María , Concepción Robledo María
Published: March 2017

Objective

Atypical squamous cells of undetermined significance (ASCUS) and atypical glandular cells (AGC) reflect cellular abnormalities insufficient for clear diagnosis. We used cell pellets obtained from liquid‐based cytology (LBC) to prepare cell blocks (CB) and clarify the initial diagnosis of ASCUS and AGC.

Study Design

A total of 393 CBs with initial diagnosis of ASCUS or AGC were processed. Of those, 305 of the ASCUS and 20 of the AGC had adequate specimens. We compared results of CBs prepared from ASCUS and AGC to determine which had higher frequencies of higher‐grade lesions.

Results

A majority of specimens (83%) were adequate for evaluation. Compared with the initial diagnosis, 14% (42/305) of ASCUS were diagnosed with low‐grade squamous intraepithelial lesion (LSIL) in CB, while 10% (2/20) of AGC were diagnosed with LSIL or adenocarcinoma. No statistical relationship between the initial diagnosis of ASCUS and AGC and results of higher‐grade lesions in CB is evident as determined by p value greater than 0.05 (p = 0.228).

Conclusions

CBs prepared from Liqui‐PREP cell pellets are, in most cases, assessable and can be useful as an adjunctive test to help clarify the initial diagnosis of ASCUS and AGC. Diagn. Cytopathol. 2017;45:520–525. © 2017 Wiley Periodicals, Inc.
Metabolism of the tryptamine‐derived new psychoactive substances 5‐MeO‐2‐Me‐DALT, 5‐MeO‐2‐Me‐ALCHT, and 5‐MeO‐2‐Me‐DIPT and their detectability in urine studied by GC–MS, LC–MSn, and LC‐HR‐MS/MS
Authors: Caspar Achim T. , Gaab Jonas B. , Michely Julian A. , Brandt Simon D. , Meyer Markus R. , Maurer Hans H.
Published: March 2017

Many N,N‐dialkylated tryptamines show psychoactive properties and were encountered as new psychoactive substances. The aims of the presented work were to study the phase I and II metabolism and the detectability in standard urine screening approaches (SUSA) of 5‐methoxy‐2‐methyl‐N,N‐diallyltryptamine (5‐MeO‐2‐Me‐DALT), 5‐methoxy‐2‐methyl‐N‐allyl‐N‐cyclohexyltryptamine (5‐MeO‐2‐Me‐ALCHT), and 5‐methoxy‐2‐methyl‐N,N‐diisopropyltryptamine (5‐MeO‐2‐Me‐DIPT) using gas chromatography–mass spectrometry (GC–MS), liquid chromatography coupled with multistage accurate mass spectrometry (LC–MSn), and liquid chromatography‐high‐resolution tandem mass spectrometry (LC‐HR‐MS/MS). For metabolism studies, urine was collected over a 24 h period after administration of the compounds to male Wistar rats at 20 mg/kg body weight (BW). Phase I and II metabolites were identified after urine precipitation with acetonitrile by LC‐HR‐MS/MS. 5‐MeO‐2‐Me‐DALT (24 phase I and 12 phase II metabolites), 5‐MeO‐2‐Me‐ALCHT (24 phase I and 14 phase II metabolites), and 5‐MeO‐2‐Me‐DIPT (20 phase I and 11 phase II metabolites) were mainly metabolized by O‐demethylation, hydroxylation, N‐dealkylation, and combinations of them as well as by glucuronidation and sulfation of phase I metabolites. Incubations with mixtures of pooled human liver microsomes and cytosols (pHLM and pHLC) confirmed that the main metabolic reactions in humans and rats might be identical. Furthermore, initial CYP activity screenings revealed that CYP1A2, CYP2C19, CYP2D6, and CYP3A4 were involved in hydroxylation, CYP2C19 and CYP2D6 in O‐demethylation, and CYP2C19, CYP2D6, and CYP3A4 in N‐dealkylation. For SUSAs, GC–MS, LC‐MSn, and LC‐HR‐MS/MS were applied to rat urine samples after 1 or 0.1 mg/kg BW doses, respectively. In contrast to the GC–MS SUSA, both LC–MS SUSAs were able to detect an intake of 5‐MeO‐2‐Me‐ALCHT and 5‐MeO‐2‐Me‐DIPT via their metabolites following 1 mg/kg BW administrations and 5‐MeO‐2‐Me‐DALT following 0.1 mg/kg BW dosage. Copyright © 2017 John Wiley & Sons, Ltd.
An ecosystem services approach to the ecological effects of salvage logging: valuation of seed dispersal
Authors: Leverkus Alexandro B. , Castro Jorge
Published: March 2017

Forest disturbances diminish ecosystem services and boost disservices. Because post‐disturbance management intends to recover the greatest possible value, selling timber often prevails over other considerations. Ecological research has shown diverse effects of salvage logging, yet such research has focused on the biophysical component of post‐disturbance ecosystems and lacks the link with human well‐being. Here we bridge that gap under the ecosystem services framework by assessing the impact of post‐fire management on a non‐timber value. By employing the replacement cost method, we calculated the value of the post‐fire natural regeneration of Holm oaks in southern Spain under three post‐fire management options by considering the cost of planting instead. The value of this ecosystem service in non‐intervention areas doubled that of salvage‐logged stands due to the preference for standing dead trees by the main seed disperser. Still, most of the value resulted from the resprouting capacity of oaks. The value of this and other ecosystem services should be added to traditional cost/benefit analyses of post‐disturbance management. We thus call for a more holistic approach to salvage logging research, one that explicitly links ecological processes with human well‐being through ecosystem services, to better inform decision‐makers on the outcomes of post‐disturbance management.
Impact of hydropeaking on downstream fish habitat at the Goesan Dam in Korea
Authors: Choi Sung‐Uk , Kim Seung Ki , Choi Byungwoong , Kim Yeonjoo
Published: March 2017

The impact of hydropeaking on downstream fish habitat was investigated. The study area is a 2.3‐km long reach of the Dal River, located downstream from the Goesan Dam, Korea. Such short‐term effects of hydropeaking as flow unsteadiness, down‐ramping rate, transport of benthic macro‐invertebrate, and changes in composite suitability index (CSI) and weighted usable area (WUA) were examined. To assess the change in CSI and WUA, physical habitat simulations were carried out. The 2D unsteady flow model and the habitat suitability index model were used for hydraulic and habitat simulations, respectively. Zacco platypus was selected as a target species of the study area. Hydraulic simulations showed that flow depth changes rapidly with time at the rising and falling stages of discharge due to hydropeaking, and this impact propagates with time. The down‐ramping rate was found to decrease gradually in the downstream direction, implying that the fish can be stranded in the 1.5‐km upstream reach. In addition, simulation results indicate that the transport of macro‐invertebrate may occur in the riffle, and the hydropeaking flows increase slightly the area of possible transport of macro‐invertebrate compared with the normal flow. However, catastrophic drift will not occur due to hydropeaking flows. The results of physical habitat simulations revealed that the hydropeaking flows decrease the CSI, although the river morphology affects the CSI to some extent. Regarding the WUA, the overall habitat quality in the entire study reach was found to decrease due to hydropeaking.
Contemporary patterns of fire extent and severity in forests of the Pacific Northwest, USA (1985–2010)
Authors: Reilly Matthew J. , Dunn Christopher J. , Meigs Garrett W. , Spies Thomas A. , Kennedy Robert E. , Bailey John D. , Briggs Kevin
Published: March 2017

Fire is an important disturbance in many forest landscapes, but there is heightened concern regarding recent wildfire activity in western North America. Several regional‐scale studies focus on high‐severity fire, but a comprehensive examination at all levels of burn severity (i.e., low, moderate, and high) is needed to inform our understanding of the ecological effects of contemporary fires and how they vary among vegetation zones at sub‐regional scales. We integrate Landsat time series data with field measurements of tree mortality to map burn severity in forests of the Pacific Northwest, USA, from 1985 to 2010. We then examine temporal trends in fire extent and spatial patterns of burn severity in relation to drought and annual fire extent. Finally, we compare results among vegetation zones and with expectations based on studies of historical landscape dynamics and fire regimes. Small increases in fire extent over time were associated with drought in all vegetation zones, but fire cumulatively affected <3% of wet vegetation zones, and most dry vegetation zones experienced less fire than expectations from fire history studies. Although the proportion of fire at any level of severity did not increase over time, temporal trends toward larger patches of high‐severity fire were related to drought and annual fire extent, depending on vegetation zone. In vegetation zones with historically high‐severity regimes, high‐severity fire accounted for a large proportion of recent fire extent (43–48%) and occurred primarily in patches ≥100 ha. In vegetation zones with historically low‐ and mixed‐severity regimes, low (45–54%)‐ and moderate‐severity (24–36%) fires were prevalent, but proportions of high‐severity fire (23–26%), almost half of which occurred in patches ≥100 ha, were much greater than expectations from most fire history studies. Our results support concerns about large patches of high‐severity fire in some dry forests but also suggest that spatial patterns of burn severity across much of the extent burned are generally consistent with current understanding of historical landscape dynamics in the region. This study highlights the importance of considering the ecological effects of fire at all levels of severity in management and policy initiatives intended to promote forest biodiversity and resilience to future fire activity.
Waveform Comparison and Difference Factors in Discharge Currents for Air Discharges from Different ESD Generators
Authors: TAKA YOSHINORI , ISHIDA TAKESHI , FUJIWARA OSAMU
Published: March 2017

Electrostatic discharge (ESD) generators must be calibrated for contact discharges with the current waveform specified in International Electro‐technical Commission (IEC)61000‐4‐2; however, there are no requirements in current waveforms due to their bad reproducibility for air discharges in the IEC standard. Nevertheless, the air discharge immunity testing is under obligation in the present standard. This implies that different ESD generators are likely to provide significantly different test results for air discharge testing. In this study, two types of different ESD generators were used to measure discharge currents both for contact and air discharges with respect to charge voltages from 2 kV to 8 kV under the same conditions of experimental environment. As a result, we confirmed that the measured waveforms were almost identical for contact discharges regardless of charge voltages, while we found that they are quite different for air discharges with the same approaching speed when the charge voltages are increased. The latter result is because the generator has different impedance characteristics deriving from its structure, and because the spark lengths from the generators with the same charge voltage are different. A formula for calculating the discharge current from an ESD generator through an ideal switch in lieu of a spark, which was previously derived by us, was also employed to obtain the current waveform peculiar to the generator, in order to reveal that the formula provides the different upper limit of air discharge current peaks according to the generator.
Relation Between Power Transfer and Magnetic Flux in Magnetic Coupling Circuit Using Resonance
Authors: IMURA TAKEHIRO
Published: March 2017

Magnetic resonant coupling is one of the conditions for electromagnetic induction using a circuit topology. On the other hand, the relation between the main magnetic flux and the near magnetic field has not been sufficiently discussed in the discussion of the circuit topology, even though the main magnetic flux is used for energy transfer in wireless power transfer. The full explanation of the contribution of the main magnetic flux was not proposed with regard to a comparison between the magnetic resonant coupling and the other topologies. Therefore, in this paper, a series of explanations from the main magnetic flux to circuit topologies is presented, and the mechanism of magnetic resonant coupling is proposed with regard to circuit theory and electromagnetism. The proposed theory is validated through an electromagnetic field analysis and experiment.
Room‐Temperature Crystallization of CuS Nanostructures for Photothermal Applications through a Nanoreactor Approach
Authors: Morgese Giulia , Dolcet Paolo , Feis Alessandro , Gellini Cristina , Gialanella Stefano , Speghini Adolfo , Badocco Denis , Pastore Paolo , Casarin Maurizio , Gross Silvia
Published: March 2017

An inverse (water in oil) miniemulsion technique was successfully implemented for the first time for the synthesis of crystalline pure and doped CuS nanostructures for applications in photothermal therapy. Different copper and sulfur sources were tested for the preparation of the targeted compounds. The successful formation at room temperature of the covellite crystalline phase was determined by means of X‐ray diffraction crystallography, selected‐area electron diffraction, and X‐ray absorption spectroscopy. The morphology of the nanostructures was assessed by scanning and transmission electron microscopy, while the surface composition was determined by X‐ray photoelectron spectroscopy. Further investigations, aimed at obtaining a characterization as detailed as possible, were performed by combining the outcomes of complementary techniques. Droplet‐size variations, as a function of sonication time and/or mode, were studied using dynamic light‐scattering measurements. A high microscopic photothermal conversion efficiency – a relevant property for photothermal therapy and photoacoustic imaging – was determined by calibrated optoacoustic measurements. The photothermal efficiency of diluted aqueous dispersions of the CuS nanostructures is ≥ 0.72, as determined by laser excitation at 1064 nm.
Easy Access to SCF2‐Containing Molecules through a Versatile Reagent
Authors: Ismalaj Ermal , Glenadel Quentin , Billard Thierry
Published: March 2017

A new fluoroalkylmethanesulfenamide reagent was developed to synthesize various molecules bearing the SCF2CO2Me group. Furthermore, the carboxyl function was successfully post‐transformed, through C–C coupling, for easy access to molecules containing the –SCF2– functionality.
Synthesis of a Chiral Borate Counteranion, Its Trityl Salt, and Application Thereof in Lewis‐Acid Catalysis
Authors: Pommerening Phillip , Mohr Jens , Friebel Jonas , Oestreich Martin
Published: March 2017

The preparation of a chiral derivative of [B(C6F5)4]– in which the fluorine atom in the para position of each of the C6F5 groups is replaced by a 1,1′‐binaphthalen‐2‐yl group is described. The new counteranion was isolated as its lithium, sodium, and trityl salts. The chiral trityl salt was then used as a catalyst in selected counteranion‐directed Diels–Alder reactions and a Mukaiyama aldol addition, but no asymmetric induction was achieved. Application of the chiral trityl salt to the generation of silicon cations by silicon‐to‐carbon hydride transfer from hydrosilanes failed, presumably as a result of the incompatibility of the relatively electron‐rich naphthyl groups in the borate and the cationic silicon electrophiles.
Nucleus accumbens dopamine receptors mediate hypothalamus‐induced antinociception in the rat formalin test
Authors: Siahposht‐Khachaki A. , Pourreza P. , Ezzatpanah S. , Haghparast A.
Published: March 2017

Background

Lateral hypothalamus (LH) involves in modulation of tonic pain. Regarding the direct and indirect neural connections between the LH and nucleus accumbens (NAc), we aimed to examine the pain modulatory role of NAc dopamine receptors in modulation of LH‐induced analgesia in the formalin test.

Methods

Vehicle‐control groups received saline or DMSO into the NAc and saline into the LH. Carbachol‐control groups received carbachol (250 nmol/L) into the LH, 5 min after saline or DMSO injection into the NAc. In treatment groups, intra‐NAc administration of SCH‐23390 or sulpiride (D1‐and D2‐like dopamine receptor antagonists, respectively) was performed 5 min before carbachol injection. Formalin test was done in all rats 5 min after the second injection.

Results

The blockade of NAc dopamine receptors reduced carbachol‐induced antinociception during both phases of formalin test and reduction in LH‐induced analgesia during the late phase was more than that during the early phase. Furthermore, contribution of D2‐like dopamine receptors to mediation of anti‐hyperalgesic effect of carbachol was greater than that of D1‐like dopamine receptors during the late phase.

Conclusions

The findings suggest that LH‐VTA‐NAc circuit is contributed to the modulation of formalin‐induced pain. These findings demonstrate that transmission at D1‐ and D2‐like dopamine receptors mediates the LH‐induced analgesia.

Significance

Blockade of accumbal dopamine receptors attenuated analgesia induced by carbachol injection into the lateral hypothalamus during both phases of formalin test. Effect of blockade of D1‐ and D2‐like dopamine receptors on reduction in antinociception was more during the late phase. Contribution of D2‐like dopamine receptors to mediation of antinociception during the late phase was greater than the early phase.
Remote ischaemic conditioning decreases blood flow and improves oxygen extraction in patients with early complex regional pain syndrome
Authors: Hegelmaier T. , Kumowski N. , Mainka T. , Vollert J. , Goertz O. , Lehnhardt M. , Zahn P.K. , Maier C. , Kolbenschlag J.
Published: March 2017

Background

Remote ischaemic conditioning (RIC) is the cyclic application of non‐damaging ischaemia leading to an increased tissue perfusion, among others triggered byNO(monoxide). Complex regional pain syndrome (CRPS) is known to have vascular alterations such as increased blood shunting and decreasedNOblood‐levels, which in turn lead to decreased tissue perfusion. We therefore hypothesized thatRICcould improve tissue perfusion inCRPS.

Method

In this proof‐of‐concept study,RICwas applied in the following groups: in 21 patients with earlyCRPSwith a clinical history less than a year, in 20 age/sex‐matched controls and in 12 patients with unilateral nerve lesions via a tourniquet on the unaffected/non‐dominant upper limb. Blood flow and tissue oxygen saturation (StO2) were assessed before, during and afterRICvia laser Doppler and tissue spectroscopy on the affected extremity. The oxygen extraction fraction was calculated.

Results

AfterRIC, blood flow declined inCRPS(p < 0.01). StO2decreased inCRPSand healthy controls (p < 0.01). Only inCRPS, the oxygen extraction fraction correlated negatively with the decreasing blood flow (p < 0.05).

Conclusion

Contrary to our expectations,RICinduced a decrease of blood flow inCRPS, which led to a revised hypothesis: the decrease of blood flow might be due to an anti‐inflammatory effect that attenuates vascular disturbances and reduces blood shunting, thus improving oxygen extraction. Further studies could determine whether a repeated application ofRICleads to a reduced hypoxia in chronicCRPS.

Significance

Remote ischaemic conditioning leads to a decrease of blood flow. This decrease inversely correlates with the oxygen extraction in patients withCRPS.
Implication of statistical design approach methodology for optimization of COD removal, effluent quality, and biosludge settling properties in aerobic bioreactors
Authors: Zeynali V. , Sargolzaei J. , Hedayati Moghaddam A. , Ali Masoudi Seyed Mohammad
Published: March 2017

Synthetic wastewater containing wheat starch and different carbon sources were treated using sequencing batch reactor (SBR) in pilot scale. First, the effects of number of impellers, input mixed liquor suspended solid (MLSS), carbon source, and temperature were investigated on treatment ability, effluent quality, and sludge settlement properties by fractional factorial design (FFD). Impeller diameter would not show considerable effect on reactor performance. Next, the most important parameters were investigated within a response surface methodology (RSM) context. Removal efficiency (COD removal), effluent total suspended solid (TSS), and sludge volume index (SVI) were assessed as outputs. The determination coefficient (R2) value for COD removal, effluent TSS, and SVI were 0.9679, 0.9638, and 0.9744, respectively. In optimum condition, COD removal of 88%, TSS of 62 mg/L, and SVI of 55 mL/g were obtained. © 2017 American Institute of Chemical Engineers Environ Prog, 36: 1428–1438, 2017
Onchocerciasis‐associated epilepsy: From recent epidemiological and clinical findings to policy implications
Authors: Colebunders Robert , Njamnshi Alfred K. , van Oijen Marieke , Mukendi Deby , Kashama Jean Marie , Mandro Michel , Gumisiriza Nolbert , Preux Pierre‐Marie , Suykerbuyk Patrick , Idro Richard
Published: March 2017

A high prevalence of epilepsy is reported in many onchocerciasis‐endemic regions. In this paper we discuss recent epidemiological and clinical aspects as well as public health implications of onchocerciasis‐associated epilepsy (OAE) and propose a strategy to reduce the burden of disease. OAE probably presents in a variety of clinical manifestations, including the nodding syndrome and the Nakalanga syndrome. The most common clinical presentation, however, is generalized (primarily tonic‐clonic) seizures. A characteristic of OAE is the onset of seizures between the ages of 3 and 18 years and clustering in certain families and villages close to rapid‐flowing black‐fly‐infested rivers. A strategy combining active surveillance for epilepsy with early treatment with antiepileptic drugs and prevention of onchocerciasis by increasing the geographical and therapeutic coverage of community‐directed treatment with ivermectin (CDTi) may considerably decrease the burden of disease.
Rodent age‐related impairments in discriminating perceptually similar objects parallel those observed in humans
Authors: Johnson Sarah A. , Turner Sean M. , Santacroce Lindsay A. , Carty Katelyn N. , Shafiq Leila , Bizon Jennifer L. , Maurer Andrew P. , Burke Sara N.
Published: March 2017

The ability to accurately remember distinct episodes is supported by high‐level sensory discrimination. Performance on mnemonic similarity tasks, which test high‐level discrimination, declines with advancing age in humans and these deficits have been linked to altered activity in hippocampal CA3 and dentate gyrus. Lesion studies in animal models, however, point to the perirhinal cortex as a brain region critical for sensory discriminations that serve memory. Reconciliation of the contributions of different regions within the cortical–hippocampal circuit requires the development of a discrimination paradigm comparable to the human mnemonic similarity task that can be used in rodents. In the present experiments, young and aged rats were cross‐characterized on a spatial water maze task and two variants of an object discrimination task: one in which rats incrementally learned which object of a pair was rewarded and different pairs varied in their similarity (Experiment 1), and a second in which rats were tested on their ability to discriminate a learned target object from multiple lure objects with an increasing degree of feature overlap (Experiment 2). In Experiment 1, aged rats required more training than young to correctly discriminate between similar objects. Comparably, in Experiment 2, aged rats were impaired in discriminating a target object from lures when the pair shared more features. Discrimination deficits across experiments were correlated within individual aged rats, though, for the cohort tested, aged rats were not impaired overall in spatial learning and memory. This could suggest discrimination deficits emerging with age precede declines in spatial or episodic memory, an observation that has been made in humans. Findings of robust impairments in object discrimination abilities in the aged rats parallel results from human studies, supporting use of the developed tasks for mechanistic investigation of cortical–hippocampal circuit dysfunction in aging and disease.
Recent developments in nanomedicine for melanoma treatment
Authors: Tang Jian‐Qin , Hou Xiao‐Yang , Yang Chun‐Sheng , Li Ya‐Xi , Xin Yong , Guo Wen‐Wen , Wei Zhi‐Ping , Liu Yan‐Qun , Jiang Guan
Published: March 2017

Melanoma is a most aggressive skin cancer with limited therapeutic options and its incidence is increasing rapidly in recent years. The discovery and application of new targeted therapy agents have shown significant benefits. However, adverse side‐effects and resistance to chemotherapy remain formidable challenges in the clinical treatment of malignant melanoma. Nanotherapeutics offers an important prospect of overcoming these drawbacks. The anti‐tumoral applications of nanomedicine are varied, including those in chemotherapy, RNA interference, photothermal therapy, and photodynamic therapy. Furthermore, nanomedicine allows delivery of the effector structures into the tumor site via passive or active targeting, thereby allowing increased therapeutic specificity and reduced side effects. In this review, we summarize the latest developments in the application of nanocarrier‐mediated targeted drug delivery to melanoma and nanomedicine‐related clinical trials in melanoma treatment. We also discuss existing problems and opportunities for future developments, providing direction and new thoughts for further studies.
Sulforaphene enhances radiosensitivity of hepatocellular carcinoma through suppression of the NF‐κB pathway
Authors: Ren Kewei , Li Zhen , Li Yahua , Zhang Wenzhe , Han Xinwei
Published: March 2017

Sulforaphene (SFE), a naturally occurring isothiocyanate found in cruciferous vegetables, has attracted increasing attention for its anti‐cancer effect in many cancers, including hepatocellular carcinoma (HCC). However, the precise role of SFE in the radiosensitivity of HCC is still unclear. Here, cell proliferation and apoptosis were detected by MTT and flow cytometry assay, respectively. The activity of NF‐κB was further evaluated by ELISA. We also observed the effect of SFE and/or radiation on tumor growth. The results showed that SFE inhibited cell proliferation and induced apoptosis in HCC cells. Radiation increased NF‐kB activity, while PDTC, a NF‐kB inhibitor, enhanced radiation‐induced cell death. SFE inhibited NF‐kB activity and the downstream gene expressions of the NF‐kB pathway in HCC cells. Moreover, SFE enhanced the inhibitory effect of radiation on tumor growth both in vitro and in vivo. This study indicated that SFE sensitized the radiosensitivity of HCC by blocking the NF‐kB pathway.
The ontogeny and population variability of human hepatic dihydronicotinamide riboside:quinone oxidoreductase (NQO2)
Authors: Riches Zoe , Liu Yuejian , Berman Jacob M. , Walia Gurinder , Collier Abby C.
Published: March 2017

Dihydronicotinamide riboside:quinone oxidoreductase (NQO2) is an enzyme that performs reduction reactions involved in antioxidant defense. We hypothesized that NQO2 hepatic drug clearance would develop in children over time, similar to NQO1. Using human liver cytosol (n = 117), the effects of age, sex, ethnicity, and weight on NQO2 expression and activity were probed. No significant correlations were observed. Biochemical activity of NQO2 was as high at birth as in adults (0.23 ± 0.04 nmol/min/mg protein, mean ± SEM, range 0–1.83). In contrast, modeled hepatic clearance through the NQO2 pathway was up to 10% of adult levels at birth, reaching predicted adult levels (0.3 ± 0.03 L/h) at 14 years of age. Comparisons between NQO1 and NQO2 in the same livers showed that neither protein (P = 0.32) nor activity (P = 0.23) correlated, confirming both orthologs are independently regulated. Because hepatic clearance through NQO2 does not mature until teenage years, compounds detoxified by this enzyme may be more deleterious in children.
Comparative Structural, Optical, and Photoluminescence Studies of YF3:Pr, YF3:Pr@LaF3, and YF3:Pr@LaF3@SiO2 Core–Shell Nanocrystals
Authors: Ansari Anees A.
Published: March 2017

Praseodymium (Pr3+)‐doped YF3
(core) and LaF3
‐covered YF3
:Pr (core–shell) nanocrystals (NCs) were prepared successfully by an ecofriendly, polyol‐based, co‐precipitation process, which were then coated with a silica shell by using a sol–gel‐based Stober method. X‐ray diffraction (XRD), transmission electron microscopy (TEM), thermal analysis, Fourier transform infrared (FTIR), UV/vis, energy bandgap, and photoluminescence studies were used to analyze the crystal structure, morphology, and optical properties of the nanomaterial. XRD and TEM results show that the grain size increases after sequential growth of crystalline LaF3
and the silica shell. The silica surface modification enhances the solubility and colloidal stability of the core–shell‐SiO2 NCs. The results indicate that the surface coating affects the optical properties because of the alteration in crystalline size of the materials. The emission intensity of silica‐modified NCs was significantly enhanced compared to that of core and core–shell NCs. These results are attributed to the formation of chemical bonds between core–shell and noncrystalline SiO2
shell via La–O–Si bridges, which activate the “dormant” Pr3+ ions on the surfaces of the nanoparticles. The luminescence efficiency of the as‐prepared core, core–shell, and core–shell‐SiO2 NCs are comparatively analyzed, and the observed differences are justified on the basis of the surface modification surrounding the luminescent seed core NCs.
UV Spectrum of the Simplest Deuterated Criegee Intermediate CD2OO
Authors: Ting Allen Wei‐Lun , Lin Jim Jr‐Min
Published: March 2017

The ultraviolet (UV) absorption spectrum of the simplest deuterated Criegee intermediate CD2OO has been measured and compared with that of CH2OO. While the UV spectra of CH2OO and CD2OO are similar in the overall shape, distinctive oscillatory structures at the long wavelength side of the absorption band show clear effect of isotopic substitution. The average spacing between the vibrational peaks decreases from 606 cm−1 for CH2OO to 528 cm−1 for CD2OO. This large isotope effect cannot be explained by one‐dimensional model along the dissociative O−O bond. Instead, vibrational modes involving motions of the H‐atoms are expected to be responsible for the observed oscillatory structure. This isotope effect offers a stringent test for theoretical investigations on the absorption spectrum and excited‐state dynamics of the simplest Criegee intermediate.
Lipocalin‐2 (NGAL) Attenuates Autophagy to Exacerbate Cardiac Apoptosis Induced by Myocardial Ischemia
Authors: Sung Hye Kyoung , Chan Yee Kwan , Han Meng , Jahng James Won Suk , Song Erfei , Danielson Eric , Berger Thorsten , Mak Tak W. , Sweeney Gary
Published: March 2017

Lipocalin‐2 (Lcn2; also termed neutrophil gelatinase‐associated lipocalin (NGAL)) levels correlate positively with heart failure (HF) yet mechanisms via which Lcn2 contributes to the pathogenesis of HF remain unclear. In this study, we used coronary artery ligation surgery to induce ischemia in wild‐type (wt) mice and this induced a significant increase in myocardial Lcn2. We then compared wt and Lcn2 knockout (KO) mice and observed that wt mice showed greater ischemia‐induced caspase‐3 activation and DNA damage measured by TUNEL than Lcn2KO mice. Analysis of autophagy by LC3 and p62 Western blotting, LC3 immunohistochemistry and transmission electron microscopy (TEM) indicated that Lcn2 KO mice had a greater ischemia‐induced increase in autophagy. Lcn2KO were protected against ischemia‐induced cardiac functional abnormalities measured by echocardiography. Upon treating a cardiomyocyte cell line (h9c2) with Lcn2 and examining AMPK and ULK1 phosphorylation, LC3 and p62 by Western blot as well as tandem fluorescent RFP/GFP‐LC3 puncta by immunofluorescence, MagicRed assay for lysosomal cathepsin activity and TEM we demonstrated that Lcn2 suppressed autophagic flux. Lcn2 also exacerbated hypoxia‐induced cytochromc c release from mitochondria and caspase‐3 activation. We generated an autophagy‐deficient H9c2 cell model by overexpressing dominant‐negative Atg5 and found significantly increased apoptosis after Lcn2 treatment. In summary, our data indicate that Lcn2 can suppress the beneficial cardiac autophagic response to ischemia and that this contributes to enhanced ischemia‐induced cell death and cardiac dysfunction. J. Cell. Physiol. 232: 2125–2134, 2017. © 2016 Wiley Periodicals, Inc.
Police officers' beliefs about, and use of, cues to deception
Authors: Wright Clea , Wheatcroft Jacqueline M.
Published: March 2017

Meta‐analytic findings indicate that people, including police officers, are generally poor at detecting low‐stakes deception. Related to this, investigations of behaviours that people reportedly use to make truth or lie judgements tend to conclude that people rely on incorrect stereotypes. However, consistent findings suggest that police officers are able to detect high‐stakes deception; this implies that, at least in some contexts, police officers utilise reliable cues to deception. The research presented here was an investigation of cues to deception used by police officers (N = 69), when making veracity decisions about real world, high‐stakes communications. Data were collected on both free report cues, and also prescribed cues that were known (from previous research), to discriminate between liars and truth‐tellers in the communications that the police officers observed. Officers free reported using cues related to verbal content, emotion, body language, eyes, vocal cues, and external cues. Most prescribed cues were self‐reportedly used correctly by large majorities of the officers, suggesting that they may not rely on inaccurate stereotypes. Self‐report use of categories of free report cues, and prescribed cues, was not related to accuracy in detecting deception. As people may not always be aware of the behaviours on which their judgements are based, the relationships between some of the behaviours actually displayed in the communications, and group accuracy in detecting deception in those communications, were also investigated. Group accuracy was related to the presence of subjective, emotion‐related cues in the communications.
Wind and buoyancy driven horizontal exchange in shallow embayments of a tropical reservoir: Lake Argyle, Western Australia
Authors: Woodward B. L. , Marti C. L. , Imberger J. , Hipsey M. R. , Oldham C. E.
Published: March 2017

Many factors including depth, vegetation density, wind, and gyres may act to influence the littoral exchange in a water body but very few studies have investigated the interaction between more than two of these factors at any time. To investigate these controls on horizontal exchange in a large tropical reservoir, we conducted a 9‐d intensive field experiment in Lake Argyle, Western Australia. The experiment began with a 7‐d cooling period that generated water in the shallows of the reservoir embayments that was persistently cooler than the interior. This led to an underflow of dense water that moved from the lake boundary toward the center of the reservoir. A three‐dimensional hydrodynamic model (ELCOM) was able to adequately reproduce this thermal structure and was used to demonstrate its sensitivity to wind‐sheltering effects and submerged macrophyte presence. Further analysis of the predictions indicated that when the ratio of the shear and buoyancy force, averaged over 6 h (B6h) and 6‐h averaged wind speed in the direction of the embayment (U6h) was (1) greater than 0.5 ms−1 and 4.5 ms−1 respectively, the exchange was dominated by a topographic gyre formation, (2) when 0.1 < B6h < 0.5 and 2.4 ms−1 < U6h < 4.5 ms−1, the resulting circulation was a combination of differential cooling flows and a topographic gyre circulation, and (3) when U6h fell below 2.4 ms−1, purely buoyancy driven flow occurred but only if the buoyancy forces across the embayments were an order of magnitude greater than wind‐induced velocity shear.
Motor learning in animal models of Parkinson's disease: Aberrant synaptic plasticity in the motor cortex
Authors: Xu Tonghui , Wang Shaofang , Lalchandani Rupa R. , Ding Jun B
Published: March 2017

In Parkinson's disease (PD), dopamine depletion causes major changes in the brain, resulting in the typical cardinal motor features of the disease. PD neuropathology has been restricted to postmortem examinations, which are limited to only a single time of PD progression. Models of PD in which dopamine tone in the brain is chemically or physically disrupted are valuable tools in understanding the mechanisms of the disease. The basal ganglia have been well studied in the context of PD, and circuit changes in response to dopamine loss have been linked to the motor dysfunctions in PD. However, the etiology of the cognitive dysfunctions that are comorbid in PD patients has remained unclear until now. In this article, we review recent studies exploring how dopamine depletion affects the motor cortex at the synaptic level. In particular, we highlight our recent findings on abnormal spine dynamics in the motor cortex of PD mouse models through in vivo time‐lapse imaging and motor skill behavior assays. In combination with previous studies, a role of the motor cortex in skill learning and the impairment of this ability with the loss of dopamine are becoming more apparent. Taken together, we conclude with a discussion on the potential role for the motor cortex in PD, with the possibility of targeting the motor cortex for future PD therapeutics. © 2017 International Parkinson and Movement Disorder Society
High‐speed whole‐brain oximetry by golden‐angle radial MRI
Authors: Cao Wen , Chang Yulin V. , Englund Erin K. , Song Hee Kwon , Barhoum Suliman , Rodgers Zachary B. , Langham Michael C. , Wehrli Felix W.
Published: March 2017

Purpose

To determine whole‐brain cerebral metabolic rate of oxygen (CMRO2), an improved imaging approach, based on radial encoding, termed radial OxFlow (rOxFlow), was developed to simultaneously quantify draining vein venous oxygen saturation (SvO2) and total cerebral blood flow (tCBF).

Methods

To evaluate the efficiency and precision of the rOxFlow sequence, 10 subjects were studied during a paradigm of repeated breath‐holds with both rOxFlow and Cartesian OxFlow (cOxFlow) sequences. CMRO2 was calculated at baseline from OxFlow‐measured data assuming an arterial O2 saturation of 97%, and the SvO2 and tCBF breath‐hold responses were quantified.

Results

Average neurometabolic‐vascular parameters across the 10 subjects for cOxFlow and rOxFlow were, respectively: SvO2 (%) baseline: 64.6 ± 8.0 versus 64.2 ± 6.6; SvO2 peak: 70.5 ± 8.5 versus 72.6 ± 5.4; tCBF (mL/min/100 g) baseline: 39.2 ± 3.8 versus 40.6 ± 8.0; tCBF peak: 53.2 ± 5.1 versus 56.1 ± 11.7; CMRO2 (µmol O2/min/100 g) baseline: 111.5 ± 26.8 versus 120.1 ± 19.6. The above measures were not significantly different between sequences (P > 0.05).

Conclusion

There was good agreement between the two methods in terms of the physiological responses measured. Comparing the two, rOxFlow provided higher temporal resolution and greater flexibility for reconstruction while maintaining high SNR. Magn Reson Med 79:217–223, 2018. © 2017 International Society for Magnetic Resonance in Medicine.