bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of the doubly labeled water method using off-axis integrated cavity output spectroscopy and isotope ratio mass spectrometry
Authors: Melanson Edward L. , Swibas Tracy , Kohrt Wendy M. , Catenacci Vicki A. , Creasy Seth A. , Plasqui Guy , Wouters Loek , Speakman John R. , Berman Elena S. F.
Published: October 2017

When the doubly labeled water (DLW) method is used to measure total daily energy expenditure (TDEE), isotope measurements are typically performed using isotope ratio mass spectrometry (IRMS). New technologies, such as off-axis integrated cavity output spectroscopy (OA-ICOS) provide comparable isotopic measurements of standard waters and human urine samples, but the accuracy of carbon dioxide production (V̇co2) determined with OA-ICOS has not been demonstrated. We compared simultaneous measurement V̇co2 obtained using whole-room indirect calorimetry (IC) with DLW-based measurements from IRMS and OA-ICOS. Seventeen subjects (10 female; 22 to 63 yr) were studied for 7 consecutive days in the IC. Subjects consumed a dose of 0.25 g H218O (98% APE) and 0.14 g 2H2O (99.8% APE) per kilogram of total body water, and urine samples were obtained on days 1 and 8 to measure average daily V̇co2 using OA-ICOS and IRMS. V̇co2 was calculated using both the plateau and intercept methods. There were no differences in V̇co2 measured by OA-ICOS or IRMS compared with IC when the plateau method was used. When the intercept method was used, V̇co2 using OA-ICOS did not differ from IC, but V̇co2 measured using IRMS was significantly lower than IC. Accuracy (~1–5%), precision (~8%), intraclass correlation coefficients ( R = 0.87–90), and root mean squared error (30–40 liters/day) of V̇co2 measured by OA-ICOS and IRMS were similar. Both OA-ICOS and IRMS produced measurements of V̇co2 with comparable accuracy and precision compared with IC.
Late-gestation maternal dietary methyl donor and cofactor supplementation in sheep partially reverses protection against allergic sensitization by IUGR
Authors: Wooldridge Amy L. , Bischof Robert J. , Liu Hong , Heinemann Gary K. , Hunter Damien S. , Giles Lynne C. , Simmons Rebecca A. , Lien Yu-Chin , Lu Wenyun , Rabinowitz Joshua D. , Kind Karen L. , Owens Julie A. , Clifton Vicki L. , Gatford Kathryn L.
Published: October 2017

Perinatal exposures are associated with altered risks of childhood allergy. Human studies and our previous work suggest that restricted growth in utero (IUGR) is protective against allergic disease. The mechanisms are not clearly defined, but reduced fetal abundance and altered metabolism of methyl donors are hypothesized as possible underlying mechanisms. Therefore, we examined whether late-gestation maternal dietary methyl donor and cofactor supplementation of the placentally restricted (PR) sheep pregnancy would reverse allergic protection in progeny. Allergic outcomes were compared between progeny from control pregnancies (CON; n = 49), from PR pregnancies without intervention (PR; n = 28), and from PR pregnancies where the dam was fed a methyl donor plus cofactor supplement from day 120 of pregnancy until delivery (PR + Methyl; n = 25). Both PR and PR + Methyl progeny were smaller than CON; supplementation did not alter birth size. PR was protective against cutaneous hypersensitivity responses to ovalbumin (OVA; P < 0.01 in singletons). Cutaneous hypersensitivity responses to OVA in PR + Methyl progeny were intermediate to and not different from the responses of CON and PR sheep. Cutaneous hypersensitivity responses to house dust mites did not differ between treatments. In singleton progeny, upper dermal mast cell density was greater in PR + Methyl than in PR or CON (each P < 0.05). The differences in the cutaneous allergic response were not explained by treatment effects on circulating immune cells or antibodies. Our results suggest that mechanisms underlying in utero programming of allergic susceptibility by IUGR and methyl donor availability may differ and imply that late-gestation methyl donor supplementation may increase allergy risk.
Role of TLR4 signaling in the nephrotoxicity of heme and heme proteins
Authors: Nath Karl A. , Belcher John D. , Nath Meryl C. , Grande Joseph P. , Croatt Anthony J. , Ackerman Allan W. , Katusic Zvonimir S. , Vercellotti Gregory M.
Published: October 2017

Destabilized heme proteins release heme, and free heme is toxic. Heme is now recognized as an agonist for the Toll-like receptor-4 (TLR4) receptor. This study examined whether the TLR4 receptor mediates the nephrotoxicity of heme, specifically, the effects of heme on renal blood flow and inflammatory responses. We blocked TLR4 signaling by the specific antagonist TAK-242. Intravenous administration of heme to mice promptly reduced renal blood flow, an effect attenuated by TAK-242. In vitro, TAK-242 reduced heme-elicited activation of NF-κB and its downstream gene monocyte chemoattractant protein-1(MCP-1); in contrast, TAK-242 failed to reduce heme-induced activation of the anti-inflammatory transcription factor Nrf2 and its downstream gene heme oxygenase-1 (HO-1). TAK-242 did not reduce heme-induced renal MCP-1 upregulation in vivo. TAK-242 did not reduce dysfunction and histological injury in the glycerol model of heme protein-induced acute kidney injury (AKI), findings corroborated by studies in TLR4+/+ and TLR4−/− mice. We conclude that 1) acute heme-mediated renal vasoconstriction occurs through TLR4 signaling; 2) proinflammatory effects of heme in renal epithelial cells involve TLR4 signaling, whereas the anti-inflammatory effects of heme do not; 3) TLR4 signaling does not mediate the proinflammatory effects of heme in the kidney; and 4) major mechanisms underlying glycerol-induced, heme protein-mediated AKI do not involve TLR4 signaling. These findings in the glycerol model are in stark contrast with findings in virtually all other AKI models studied to date and emphasize the importance of TLR4-independent pathways of heme protein-mediated injury in this model. Finally, these studies urge caution when using observations derived in vitro to predict what occurs in vivo.
ACh-induced hyperpolarization and decreased resistance in mammalian type II vestibular hair cells
Authors: Poppi Lauren A. , Tabatabaee Hessam , Drury Hannah R. , Jobling Phillip , Callister Robert J. , Migliaccio Americo A. , Jordan Paivi M. , Holt Joseph C. , Rabbitt Richard D. , Lim Rebecca , Brichta Alan M.
Published: October 2017

In the mammalian vestibular periphery, electrical activation of the efferent vestibular system (EVS) has two effects on afferent activity: 1) it increases background afferent discharge and 2) decreases afferent sensitivity to rotational stimuli. Although the cellular mechanisms underlying these two contrasting afferent responses remain obscure, we postulated that the reduction in afferent sensitivity was attributed, in part, to the activation of α9- containing nicotinic acetylcholine (ACh) receptors (α9*nAChRs) and small-conductance potassium channels (SK) in vestibular type II hair cells, as demonstrated in the peripheral vestibular system of other vertebrates. To test this hypothesis, we examined the effects of the predominant EVS neurotransmitter ACh on vestibular type II hair cells from wild-type (wt) and α9-subunit nAChR knockout (α9−/−) mice. Immunostaining for choline acetyltransferase revealed there were no obvious gross morphological differences in the peripheral EVS innervation among any of these strains. ACh application onto wt type II hair cells, at resting potentials, produced a fast inward current followed by a slower outward current, resulting in membrane hyperpolarization and decreased membrane resistance. Hyperpolarization and decreased resistance were due to gating of SK channels. Consistent with activation of α9*nAChRs and SK channels, these ACh-sensitive currents were antagonized by the α9*nAChR blocker strychnine and SK blockers apamin and tamapin. Type II hair cells from α9−/− mice, however, failed to respond to ACh at all. These results confirm the critical importance of α9nAChRs in efferent modulation of mammalian type II vestibular hair cells. Application of exogenous ACh reduces electrical impedance, thereby decreasing type II hair cell sensitivity.

NEW & NOTEWORTHY Expression of α9 nicotinic subunit was crucial for fast cholinergic modulation of mammalian vestibular type II hair cells. These findings show a multifaceted efferent mechanism for altering hair cell membrane potential and decreasing membrane resistance that should reduce sensitivity to hair bundle displacements.
Figure-ground organization in the visual cortex: does meaning matter?
Authors: Ko Hee-kyoung , von der Heydt Rüdiger
Published: October 2017

Figure-ground organization in the visual cortex is generally assumed to be based partly on general rules and partly on specific influences of object recognition in higher centers as found in the temporal lobe. To see if shape familiarity influences figure-ground organization, we tested border ownership-selective neurons in monkey V1/V2 with silhouettes of human and monkey face profiles and “nonsense” silhouettes constructed by mirror-reversing the front part of the profile. We found no superiority of face silhouettes compared with nonsense shapes in eliciting border-ownership signals overall. However, in some neurons, border-ownership signals differed strongly between the two categories consistently across many different profile shapes. Surprisingly, this category selectivity appeared as early as 70 ms after stimulus onset, which is earlier than the typical latency of shape-selective responses but compatible with the earliest face-selective responses in the inferior temporal lobe. Although our results provide no evidence for a delayed top-down influence from object recognition centers, they indicate sophisticated shape categorization mechanisms that are much faster than generally assumed.

NEW & NOTEWORTHY A long-standing question is whether low-level sensory representations in cortex are influenced by cognitive “top-down” signals. We studied figure-ground organization in the visual cortex by comparing border-ownership signals for face profiles and matched nonsense shapes. We found no sign of “face superiority” in the population border-ownership signal. However, some neurons consistently differentiated between the face and nonsense categories early on, indicating the presence of shape classification mechanisms that are much faster than previously assumed.
Layer- and subregion-specific differences in the neurophysiological properties of rat medial prefrontal cortex pyramidal neurons
Authors: Song Chenghui , Moyer James R.
Published: October 2017

Medial prefrontal cortex (mPFC) is critical for the expression of long-term conditioned fear. However, the neural circuits involving fear memory acquisition and retrieval are still unclear. Two subregions within mPFC that have received a lot of attention are the prelimbic (PL) and infralimbic (IL) cortices (e.g., Santini E, Quirk GJ, Porter JT. J Neurosci 28: 4028–4036, 2008; Song C, Ehlers VL, Moyer JR Jr. J Neurosci 35: 13511–13524, 2015). Interestingly, PL and IL may play distinct roles during fear memory acquisition and retrieval but the underlying mechanism is poorly understood. One possibility is that the intrinsic membrane properties differ between these subregions. Thus, the current study was carried out to characterize the basic membrane properties of mPFC neurons in different layers and subregions. We found that pyramidal neurons in L2/3 were more hyperpolarized and less excitable than in L5. This was observed in both IL and PL and was associated with an enhanced h-current in L5 neurons. Within L2/3, IL neurons were more excitable than those in PL, which may be due to a lower spike threshold and higher input resistance in IL neurons. Within L5, the intrinsic excitability was comparable between neurons obtained in IL and PL. Thus, the heterogeneity in physiological properties of mPFC neurons may underlie the observed subregion-specific contribution of mPFC in cognitive function and emotional control, such as fear memory expression.

NEW & NOTEWORTHY This is the first study to demonstrate that medial prefrontal cortical (mPFC) neurons are heterogeneous in both a layer- and a subregion-specific manner. Specifically, L5 neurons are more depolarized and more excitable than those neurons in L2/3, which is likely due to variations in h-current. Also, infralimbic neurons are more excitable than those of prelimbic neurons in layer 2/3, which may be due to differences in certain intrinsic properties, including input resistance and spike threshold.
Calcium dynamics control K-ATP channel-mediated bursting in substantia nigra dopamine neurons: a combined experimental and modeling study
Authors: Knowlton Christopher , Kutterer Sylvie , Roeper Jochen , Canavier Carmen C.
Published: October 2017

Burst firing in medial substantia nigra (mSN) dopamine (DA) neurons has been selectively linked to novelty-induced exploration behavior in mice. Burst firing in mSN DA neurons, in contrast to lateral SN DA neurons, requires functional ATP-sensitive potassium (K-ATP) channels both in vitro and in vivo. However, the precise role of K-ATP channels in promoting burst firing is unknown. We show experimentally that L-type calcium channel activity in mSN DA neurons enhances open probability of K-ATP channels. We then generate a mathematical model to study the role of Ca2+ dynamics driving K-ATP channel function in mSN DA neurons during bursting. In our model, Ca2+ influx leads to local accumulation of ADP due to Ca-ATPase activity, which in turn activates K-ATP channels. If K-ATP channel activation reaches levels sufficient to terminate spiking, rhythmic bursting occurs. The model explains the experimental observation that, in vitro, coapplication of NMDA and a selective K-ATP channel opener, NN414, is required to elicit bursting as follows. Simulated NMDA receptor activation increases the firing rate and the rate of Ca2+ influx, which increases the activation of K-ATP. The model suggests that additional sources of hyperpolarization, such as GABAergic synaptic input, are recruited in vivo for burst termination or rebound burst discharge. The model predicts that NN414 increases the sensitivity of the K-ATP channel to ADP, promoting burst firing in vitro, and that that high levels of Ca2+ buffering, as might be expected in the calbindin-positive SN DA neuron subpopulation, promote rhythmic bursting pattern, consistent with experimental observations in vivo.

NEW & NOTEWORTHY Recently identified distinct subpopulations of midbrain dopamine neurons exhibit differences in their two primary activity patterns in vivo: tonic (single spike) firing and phasic bursting. This study elucidates the biophysical basis of bursts specific to dopamine neurons in the medial substantia nigra, enabled by ATP-sensitive K+ channels and necessary for novelty-induced exploration. A better understanding of how dopaminergic signaling differs between subpopulations may lead to therapeutic strategies selectively targeted to specific subpopulations.
State-dependent rhythmogenesis and frequency control in a half-center locomotor CPG
Authors: Ausborn Jessica , Snyder Abigail C. , Shevtsova Natalia A. , Rybak Ilya A. , Rubin Jonathan E.
Published: October 2017

The spinal locomotor central pattern generator (CPG) generates rhythmic activity with alternating flexion and extension phases. This rhythmic pattern is likely to result from inhibitory interactions between neural populations representing flexor and extensor half-centers. However, it is unclear whether the flexor-extensor CPG has a quasi-symmetric organization with both half-centers critically involved in rhythm generation, features an asymmetric organization with flexor-driven rhythmogenesis, or comprises a pair of intrinsically rhythmic half-centers. There are experimental data that support each of the above concepts but appear to be inconsistent with the others. In this theoretical/modeling study, we present and analyze a CPG model architecture that can operate in different regimes consistent with the above three concepts depending on conditions, which are defined by external excitatory drives to CPG half-centers. We show that control of frequency and phase durations within each regime depends on network dynamics, defined by the regime-dependent expression of the half-centers' intrinsic rhythmic capabilities and the operating phase transition mechanisms (escape vs. release). Our study suggests state dependency in locomotor CPG operation and proposes explanations for seemingly contradictory experimental data.

NEW & NOTEWORTHY Our theoretical/modeling study focuses on the analysis of locomotor central pattern generators (CPGs) composed of conditionally bursting half-centers coupled with reciprocal inhibition and receiving independent external drives. We show that this CPG framework can operate in several regimes consistent with seemingly contradictory experimental data. In each regime, we study how intrinsic dynamics and phase-switching mechanisms control oscillation frequency and phase durations. Our results provide insights into the organization of spinal circuits controlling locomotion.
Associations of Salivary BPIFA1 Protein in Chronic Periodontitis Patients with Type 2 Diabetes Mellitus
Authors: Guo Yue , Guo Lin-Na , Zhu Jun-Fei , Tang Chen-Yi , Feng Yun-Zhi , Zhou Hou-De
Published: October 2017

Aims. To explore the differences in salivary BPI fold containing family A, member 1 (BPIFA1) concentration among type 2 diabetes mellitus (T2DM) subjects with various severities of chronic periodontitis and to determine whether BPIFA1 in saliva can be used as a potential biomarker of T2DM.Methods. Unstimulated saliva samples were collected from 44 subjects with T2DM and 44 without T2DM (NDM). Additionally, demographic data and general health parameters, including fasting blood glucose (FBG) and body mass index (BMI), were collected. We also detected full-mouth clinical periodontal parameters including probing pocket depth (PPD), clinical attachment level (CAL), bleeding index (BI), and plaque index (PLI). Salivary BPIFA1, tumor necrosis factor-α(TNF-α), and interleukin-6 (IL-6) concentrations were also detected.Results. BPIFA1 in saliva was detected at relatively high levels. T2DM subjects had decreased salivary BPIFA1 concentrations (P=0.031). In T2DM subjects with nonperiodontitis or severe periodontitis, the level of BPIFA1 was significantly lower compared with that of NDM. Salivary TNF-αconcentration displayed a similar trend to BPIFA1 in the NDM group.Conclusions. BPIFA1 protein is rich in saliva and might be used as a potential predictive biomarker of T2DM, especially in patients with severe periodontitis and nonperiodontitis. This trial is registered withChiCTR-ROC-17010310.
On Some Relations between Accretive, Positive, and Pseudocontractive Operators and Passivity Results in Hilbert Spaces and Nonlinear Dynamic Systems
Authors: De la Sen M.
Published: October 2017

This paper investigates some parallel relations between the operators I-G and G in Hilbert spaces in such a way that the pseudocontractivity, asymptotic pseudocontractivity, and asymptotic pseudocontractivity in the intermediate sense of one of them are equivalent to the accretivity, asymptotic accretivity, and asymptotic accretivity in the intermediate sense of the other operator. If the operators are self-adjoint then the obtained accretivity-type properties are also passivity-type properties. Such properties are very relevant in stability theory since they refer to global stability properties of passive feed-forward, in general, nonlinear, and time-varying controlled systems controlled via feedback by elements in a very general class of passive, in general, nonlinear, and time-varying controllers. These results allow the direct generalization of passivity results in controlled dynamic systems to wide classes of tandems of controlled systems and their controllers, described by G-operators, and their parallel interpretations as pseudocontractive properties of their counterpart I-G-operators. Some of the obtained results are also directly related to input-passivity, output-passivity, and hyperstability properties in controlled dynamic systems. Some illustrative examples are also given in the framework of dynamic systems described by extended square-integrable input and output signals.
EGHB010, a Standardized Extract of Paeoniae Radix and Glycyrrhizae Radix, Inhibits VEGF‐Induced Tube Formation In Vitro and Retinal Vascular Leakage and Choroidal Neovascularization In Vivo
Authors: Jung Eunsoo , Jung Wookwon , Park Su-Bin , Kim Chan-Sik , Kim Jin Sook , Kim Junghyun
Published: October 2017

EGHB010 is a hot water extract of the rhizome mixture of Paeonia lactiflora Pallas and Glycyrrhiza uralensis Fisch. Choroidal neovascularization (CNV) and vascular leakage are the common pathophysiologies of age‐related macular degeneration. In this study, we aimed to evaluate the effect of EGHB010 on retinal vascular leakage and laser‐induced CNV in a rat model. Vascular endothelial growth factor‐ (VEGF‐) induced tube formation was assayed in human retinal microvascular endothelial cells. Intravitreal VEGF‐induced blood‐retinal barrier breakdown was assayed in Sprague‐Dawley rats. Experimental CNV was induced by laser photocoagulation in Brown Norway rats. EGHB010 (50 and 100 mg/kg/day) was administered orally for 10 days after laser photocoagulation. Choroidal flat mounts were prepared to measure the lesion size of CNV. Incubation of retinal vascular endothelial cells with EGHB010 (12.5 and 25 μg/mL) resulted in the inhibition of VEGF‐induced tube formation in a dose‐dependent manner. VEGF‐mediated retinal vascular leakage was blocked by the oral administration of EGHB010. The CNV area was significantly lower in EGHB010‐treated rats than in vehicle‐treated rats. These results suggest that EGHB010 is a potent antiangiogenic agent. Thus, the oral administration of EGHB010 may have a beneficial effect in the treatment of vascular leakage and CNV in patients with age‐related macular degeneration.
Wind Tunnel Tests on Aerodynamic Characteristics of Ice‐Coated 4‐Bundled Conductors
Authors: Xin-min Li , Xiao-chun Nie , Yong-kun Zhu , Yi You , Zhi-tao Yan
Published: October 2017

Wind tunnel tests were carried out to obtain the static aerodynamic characteristics of crescent iced 4‐bundled conductors with different ice thicknesses, initial ice accretion angles, bundle spaces, and wind attack angles. The test models were made of the actual conductors and have a real rough surface. Test results show that the influence of wake interference on the drag coefficients of leeward subconductors is obvious. The interference angle range is larger than 20° and the drag coefficient curves of leeward subconductors have a sudden decrease phenomenon at some certain wind attack angles. The absolute value of the lift and moment coefficient increases with the increase of the ice thickness. In addition, the galloping of the iced subconductor may occur at the angle of wind attack near ±20° and the wake increases the moment coefficient. The variation of initial ice accretion angle has a significant influence on the aerodynamic coefficients. The aerodynamic coefficient curves exhibit a “moving” phenomenon at different initial ice accretion angles. The bundle spaces have a great influence on the moment coefficient of leeward thin ice‐coated conductors. With the increase of ice thickness, the bundle spaces generally have little influence on the aerodynamic coefficients.
Submicrosecond Q-Switching Er-Doped All-Fiber Ring Laser Based on Black Phosphorus
Authors: Cai Yao , He Yanliang , Zhang Xiaoke , Jiang Rui , Su Chenliang , Li Ying
Published: October 2017

Black phosphorus (BP), a new two-dimensional (2D) material, has been deeply developed for extensive applications in electronics and optoelectronics due to its similar physical structure to graphene and thickness dependent direct band gap. Here, we demonstrated a submicrosecond passive Q-switching Er-doped fiber laser with BP as saturable absorber (SA). The BP saturable absorber was fabricated by mechanical exfoliation method. By taking full advantage of the ultrafast relaxation time of BP-SA and careful design of compact ring cavity, we obtained stable Q-switching pulses output with a shortest duration as narrow as 742 ns. With increasing the pump power, the pulse repetition rate accreted gradually almost linearly from 9.78 to 61.25 kHz, and the pulse duration declined rapidly at lower pump power regime and retained approximate stationary at higher pump power regime from 3.05 to 0.742 μs. The experimental results indicate that BP-SA can be an effective SA for nanosecond Q-switching pulse generation.
Explaining Continuance Intention of Fruit and Vegetable Consumption among the Rural Elderly: An Application of the Expectancy Confirmation Model
Authors: Jafari Mohamad Reza , Ahmadi Angali Kambiz , Mohamadian Hashem
Published: October 2017

Background and Aim. Healthy aging is the permanent right of all people. Thus, the purpose of this work was to investigate the expectation confirmation model constructs on intention of continuing to consume fruit and vegetables among the rural elderly.Materials and Methods. This cross-sectional study was conducted on 332 elderly. The expectation confirmation model served as a theoretical framework. A random sampling was recruited. Data were collected through face-to-face visit in the second 6 months of 2016. The data were then analyzed using LISREL 8.5 and SPSS 16 software.Results. This model could explain 79% of intention to continue fruit and vegetable consumption. The usefulness and satisfaction had the most effect on the intention to continue the consumption of fruit and vegetables.Conclusion. Expectation confirmation model depicted a proper application in explaining the intention to continue the consumption of fruit and vegetables in the elderly. Since perceived benefits were the most important factor in determining the intention to continue F&V consumption in this study, it is required that policymakers utilize suitable efficient strategies to promote the perception of benefits of F&V consumption in the elderly by means of campaigns in the society, organizations, and families.
Hawthorn Leaf Flavonoids Protect against Diabetes‐Induced Cardiomyopathy in Rats via PKC‐α Signaling Pathway
Authors: Min Qing , Bai Yuting , Zhang Yuchen , Yu Wei , Zhang Minli , Liu Dongyang , Diao Tingting , Lv Wei
Published: October 2017

Objectives. DCM has become one of the main reasons of death in diabetic patients. In this study, we aimed to explore the hawthorn leaf flavonoids (HLF) protective effect against diabetes‐induced cardiac injury and the underlying mechanisms in experimental rats. Methods. Experimental diabetic model was induced by intraperitoneal injection of streptozotocin (STZ, 40 mg/kg) in rats after feeding with high‐fat diet for 8 weeks. The diabetic rats received a 16‐week treatment of different doses of HLF (50, 100, and 200). The morphological changes of myocardial cells were observed by light microscope; the concentration of antioxidant indicator and TNF‐α and the expression of PKC‐α mRNA, PKC‐α, and NF‐κB proteins were assessed as well. Results. STZ‐induced diabetes mellitus prompted blood glucose, cardiac injury, oxidative stress, and inflammation, accompanied with suppressed body weight. On the contrary, HLF administration improved body weight and blood glucose and attenuated myocardial structural abnormalities in diabetic rats. In addition, HLF decreased MDA level and enhanced SOD activities, inhibited TNF‐α expression, and downregulated PKC‐α mRNA, PKC‐α, and NF‐κB which were induced by diabetes. Conclusions. HLF has a protective effect against diabetic cardiomyopathy in rats. The mechanism may be involved in reducing oxidative stress and inflammation via inactivation of the PKC‐α signaling pathway.
Natural Remission of Major Periprosthetic Osteolysis following Total Hip Arthroplasty with Metal-on-Metal Bearings
Authors: Tamaki Tatsuya , Oinuma Kazuhiro
Published: October 2017

The natural course of adverse events following the use of metal-on-metal (MoM) bearings in total hip arthroplasty (THA) is not well known. In this article, we report the case of a patient with asymptomatic major acetabular osteolysis following MoM THA that diminished gradually without any surgical intervention. A 58-year-old male underwent one-stage bilateral MoM THA for bilateral osteoarthritis. Four years after THA, major acetabular osteolysis developed in his right hip without any local or systemic symptoms. The patient underwent a careful radiographic and clinical observation without any surgical intervention because he did not want to undergo revision surgery. The lesion gradually diminished after 7 years, and most of the osteolytic area was replaced by newly formed bone at 10 years. He continues to be followed with no evidence of cup loosening or migration. Our observation suggests that a periprosthetic osteolytic change related to the use of MoM bearings has the potential for natural remission.
Correlation between Choroidal Neovascularization Shown by OCT Angiography and Choroidal Thickness in Patients with Chronic Central Serous Chorioretinopathy
Authors: Gołębiewska Joanna , Brydak-Godowska Joanna , Moneta-Wielgoś Joanna , Turczyńska Monika , Kęcik Dariusz , Hautz Wojciech
Published: October 2017

Purpose. To assess the occurrence of choroidal neovascularization (CNV) secondary to chronic central serous chorioretinopathy (CSCR) using optical coherence tomography angiography (OCTA) and correlate these findings with choroidal thickness (CT). Materials and Methods. This retrospective study included 25 consecutive patients (43 eyes), mean age 48.12 ± 7.8 years, diagnosed with persistent CSCR. All patients underwent a complete ophthalmic examination, fluorescein angiography (FA), indocyanine green angiography (ICGA), optical coherence tomography, and OCTA. Results. CNV was confirmed in 18.6% of eyes using FA and ICGA and in 25.6% of eyes using OCTA. All cases of CNV were associated with irregular retinal pigment epithelial detachment. CT was increased in the affected eyes (mean 491.05 ± 91.98), but there were no statistically significant correlations between CT and CNV and PED occurrence (p=0.661 and p=0.614, resp.) and between CT and duration of the disease (p=0.940). Conclusions. OCTA detected CNV more frequently than other imaging modalities. CNV coexisted with irregular PED in all cases. CT was increased in eyes with chronic CSCR, but without any correlation with CNV occurrence; therefore, CT cannot be considered as a predictor of CNV occurrence. Further studies with a larger number of patients are needed to confirm these findings.
Bilateral Neck Pyomyositis Caused byStaphylococcus capitisandStaphylococcus saccharolyticusin a Diabetic Adult
Authors: Young Nicholas , Bhally Hasan
Published: October 2017

We report a case of pyomyositis of the paraspinal neck muscles caused by two coagulase-negative staphylococci:Staphylococcus capitisandStaphylococcus saccharolyticus.Inflammation in the spermatic cords was an additional feature of this infection. Treatment with six weeks of first-generation cephalosporin therapy resulted in complete clinical and radiological resolution.
A Case of Polyarteritis Nodosa Presenting as Rapidly Progressing Intermittent Claudication of Right Leg
Authors: Fonseka Chathuranga Lakmal , Galappaththi Sampath Rukshani , Abeyaratne Dayakshi , Tissera Nirmali , Wijayaratne Lalith
Published: October 2017

Background. Polyarteritis nodosa (PAN) is a medium vessel vasculitis which causes significant morbidity and mortality. Usually, it presents with constitutional symptoms with angiographic evidence of aneurysms or segmental stenosis of arteries of mesenteric or renal vasculature. It is exceedingly uncommon for PAN to present with symptomatic progressive intermittent claudication. Case Presentation. We describe a 60-year-old male who presented with rapidly progressive intermittent claudication of his right leg. He did not have any significant atherosclerotic risk factors. He had recent onset hypertension and loss of weight. He also had mononeuropathy of right common peroneal nerve and livedo reticularis rash. With negative autoimmune markers and suggestive histology in deep punch skin biopsy and angiographic evidence of segmental stenosis of femoral and renal arteries, we diagnosed PAN. We treated him with aggressive immunosuppressants and vascular bypass surgery of right femoral vessels; he showed a good response. Conclusion. Rapidly progressive unilateral intermittent claudication could be a very rare, but noteworthy presentation of PAN. With suggestive histology and exclusion of other comorbidities aggressive immunosuppressants should be instituted. Vascular bypass surgery for critical ischaemia of the limbs is an option that could be considered for limb-threatening disease.
Soluble Urokinase Plasminogen Activator Receptor and the Risk of Coronary Artery Disease in Young Chinese Patients
Authors: Huang Yuli , Zhou Haobin , Wu Yu , Yang You , Li Wensheng , Lu Jianhua , Hu Yunzhao
Published: October 2017

Background. Soluble urokinase plasminogen activator receptor (suPAR) is a novel marker of chronic inflammation and is considered to be a risk factor for coronary artery disease (CAD) in Caucasians. This study investigated the role of suPAR in young Chinese patients with CAD.Methods. The study involved a total of 196 consecutive young (age ≤ 55 years) patients with angiographically proven CAD and 188 age-matched non-CAD individuals as controls. Traditional risk factors were evaluated using conventional assays, and levels of suPAR were measured by sandwich enzyme-linked immunosorbent assays.Results. Levels of suPAR were significantly correlated with age (r=0.20,P=0.04), smoking (r=0.33,P=0.008), body mass index (r=0.21,P=0.03), and high-sensitivity C-reactive protein (hs-CRP;r=0.31,P=0.01). Multivariate logistic regression analysis showed that male sex (odds ratio (OR) = 3.12; 95% confidence interval (CI) = 1.18–8.25,P=0.02), smoking (OR = 3.41, 95% CI = 1.55–7.50,P=0.002), triglyceride (OR = 1.89, 95% CI = 1.10–3.25,P=0.02), high-sensitivity C-reactive protein (OR = 1.24, 95% CI = 1.02–0.03,P=0.03), and suPAR (OR = 1.37, 95% CI = 1.09–1.72,P=0.007) were independently associated with CAD risk in young patients.Conclusions. SuPAR is a novel independent risk factor for CAD in young Chinese patients. Further studies evaluating the effect of anti-inflammatory treatment on the suPAR levels and the risk of CAD are needed.
Synthesis of Adaptive Robust Controllers for a Class of Nonlinear Systems with Input Saturations
Authors: Oba Kenta , Oya Hidetoshi , Kubo Tomohiro , Matsuki Tsuyoshi
Published: October 2017

This paper deals with a design problem of an adaptive robust controller for a class of nonlinear systems with specified input saturations. For the nonlinear system under consideration, the nonlinearity means unknown perturbations and satisfies the matching condition. In this paper, we show that sufficient conditions for the existence of the proposed adaptive robust controller giving consideration to input saturations are given in terms of linear matrix inequalities (LMIs). Finally, simple illustrative examples are shown.
The Effect of PSE and Non-PSE Adductor and Semimembranosus Pig Muscles on the Occurrence of Destructured Zones in Cooked Hams
Authors: Eliášová Martina , Kameník Josef , Saláková Alena , Pavlík Zdeněk , Pospiech Matej , Tremlová Bohuslava
Published: October 2017

The aim of this study was to analyse pig muscles used in the production of cooked hams with a view to the occurrence of PSE-type defects and their potential effect on the frequency of destructured zones in finished products. One hundred and six samples of m. adductor (AD) and m. semimembranosus (SM) pig muscles were studied. The two kinds of muscle differed from each other in terms of their pH values and colour (L⁎: lightness, a⁎: redness, and b⁎: yellowness); these differences between the two categories were statistically significant (P<0.001). The AD muscles were divided into meat with PSE (pale, soft, and exudative) defects and non-PSE meat by sensory examination. A total of 44.3% of AD muscles showed PSE defects. Lightness L⁎ fell within a range of 50.68–55.23 in non-PSE meat (AD) and was statistically significantly lower (P<0.001) than in PSE meat (56.25–58.78). Drip loss (AD) was higher (P<0.001) in PSE meat (4.83–6.27%) than in non-PSE meat (3.53–5.0%). Cooked hams prepared from pig muscles showed evident destructured zones when sliced, the number and overall area of which were not affected by the occurrence of PSE defects in the raw meat used.
Influence Parameters on Nitriding Process of Ferromanganese Alloy
Authors: Ghali S. , El-Faramawy H. , Eissa M. , Ahmed A.
Published: October 2017

A 24 factorial design technique was used to investigate the magnitude effect of temperature, time, carbon percent, and pressure of the nitriding process of gas solid reaction of ferromanganese. The design was based on experiments results obtained from nitriding of two grades of ferromanganese alloys containing 0.23% C and 7.1% C at temperatures 700°C and 950°C, during time of 2 hours and 6 hours and with nitrogen pressure of 1 and 8 bar. The required calculations were carried out by Matlab. It was found that the highest positive effect was temperature while the carbon content has the highest negative effect. Nitrogen pressure has more positive effect than time. The interaction combination between two parameters or more of temperature, nitrogen pressure, and time has positive influence with different extent. The interaction combination between carbon and one or more of parameters of time, temperature, or nitrogen pressure has negative effect on nitriding process. The driven models were found to be in good agreement with the experiments and published work of nitriding process of ferromanganese containing different carbon contents (0.23–7.1%) in temperature range 700°C–950°C, with nitrogen pressure up to 8 bar, and during time of 2–6 hours.
Usefulness of Sacral Sublaminar Wire for Low Transverse Sacral Fractures: Two Cases’ Report
Authors: Sasaji Tatsuro , Imaizumi Hideki , Murakami Taishi
Published: October 2017

Low transverse sacral fractures are rare, with only two published reports regarding their surgery. The complication associated with surgery for sacral fractures is the prominence of implants. In addition, screw fixation below S3 is impractical. We performed posterior sacral fixation using S2 alar iliac (S2AI) screws and sacral sublaminar wires for low transverse sacral fractures. Case 1 was 65-year-old male with an S2-3 transverse sacral fracture. We performed laminectomy (S2-3) and passed ultrahigh molecular weight polyethylene (UHMWPE) cables from laminectomy area to the third posterior sacral foramina. We inserted S2AI screws and connected rods. We also tightened the UHMWPE cables. The implants did not protrude into skin. One year after surgery, the sacral fracture healed without any displacement. Case 2 was a 42-year-old female with an S2 transverse sacral fracture. We performed laminectomy (S1–3) and passed UHMWPE cables from laminectomy area to the third and fourth posterior sacral foramina. We inserted S1 pedicular screws and S2AI screws and connected rods. We also tightened UHMWPE cables. The implants did not protrude into skin. One year after surgery, the sacral fracture healed without any displacement. We consider sacral sublaminar wires to be useful bone anchors in lower sacrum.
PAX5-Negative Classical Hodgkin Lymphoma: A Case Report of a Rare Entity and Review of the Literature
Authors: Vali Betts Elham , Dwyre Denis M. , Wang Huan-You , Rashidi Hooman H.
Published: October 2017

Classical Hodgkin lymphoma (CHL) is recognized as a B-cell neoplasm arising from germinal center or postgerminal center B-cells. The hallmark of CHL is the presence of CD30 (+) Hodgkin and Reed-Sternberg (HRS) cells with dim expression of PAX5. Nearly all of the HRS cells are positive for PAX5. However, a small minority of HRS cells may lack PAX5 expression, which can cause a diagnostic dilemma. Herein we describe two cases of PAX5-negative CHL and review of the English literature on this very rare entity. It is crucial to be aware of this phenomenon, which in some cases may lead to misdiagnosis and may ultimately adversely affect patient’s management.
Legionnaires’ Disease Complicated with Rhabdomyolysis and Acute Kidney Injury in an AIDS Patient
Authors: Seegobin Karan , Maharaj Satish , Baldeo Cherisse , Downes Julio Perez , Reddy Pramod
Published: October 2017

Objective. To present a case of an uncommon triad of Legionella pneumonia, rhabdomyolysis, and renal failure, with review of the relevant literature. Case. A 51-year-old with a history of human immunodeficiency virus (HIV), chronic obstructive pulmonary disease (COPD), and hypertension presented with fever, cough, and shortness of breath over four days. Chest X-ray showed consolidation in left lower lung field; urine was positive for Legionella antigen and myoglobin; creatine kinase was 51092U/L; creatine was 6.9 mg/dL, and his CD4 count was 41 cells/ul. He was managed with azithromycin and levofloxacin and further required dialysis and ventilatory support in the intensive care unit due to renal failure and respiratory failure. He responded well to the treatment and made a complete recovery. Legionella pneumophila infection is a recognized but rare cause of rhabdomyolysis with high morbidity and mortality when there is extrapulmonary involvement. Early diagnosis and appropriate treatment is essential to improve outcomes. Conclusion. Physicians should consider Legionella pneumonia in patients with rhabdomyolysis, renal failure, and respiratory symptoms. Early diagnosis and treatment have been shown to have good clinical response. Timely intensive care management, together with early and judicious use of dialysis in patients complicated with rhabdomyolysis and renal failure, may lead to good outcomes.
Comparative Study of Strength and Corrosion Resistant Properties of Plain and Blended Cement Concrete Types
Authors: Saraswathy Velu , Karthick Subbiah , Lee Han Seung , Kwon Seung-Jun , Yang Hyun-Min
Published: October 2017

The relative performances of mechanical, permeability, and corrosion resistance properties of different concrete types were compared. Concrete types were made from ordinary Portland cement (OPC), Portland pozzolana cement (PPC), and Portland slag cement (PSC). Compressive strength test, effective porosity test, coefficient of water absorption, short-term accelerated impressed voltage test, and rapid chloride permeability test (RCPT) were conducted on M30 and M40 grades of concrete designed with OPC, PPC, and PSC cements for 28- and 90-day cured concrete types. Long-term studies such as microcell and electrochemical evaluation were carried out to understand the corrosion behaviour of rebar embedded in different concrete types. Better corrosion resistant properties were observed for PSC concrete by showing a minimum current flow, lowest free chloride contents, and lesser porosity. Besides, PSC concrete has shown less coefficient of water absorption, chloride diffusion coefficient (CDC), and lower corrosion rate and thereby the time taken for initiation of crack extended.
A Cycle Deep Belief Network Model for Multivariate Time Series Classification
Authors: Wang Shuqin , Hua Gang , Hao Guosheng , Xie Chunli
Published: October 2017

Multivariate time series (MTS) data is an important class of temporal data objects and it can be easily obtained. However, the MTS classification is a very difficult process because of the complexity of the data type. In this paper, we proposed a Cycle Deep Belief Network model to classify MTS and compared its performance with DBN and KNN. This model utilizes the presentation learning ability of DBN and the correlation between the time series data. The experimental results showed that this model outperforms other four algorithms: DBN, KNN_ED, KNN_DTW, and RNN.
Selective Androgen Receptor Modulator RAD140 Inhibits the Growth of Androgen/Estrogen Receptor–Positive Breast Cancer Models with a Distinct Mechanism of Action
Authors: Yu Ziyang , He Suqin , Wang Dannie , Patel Hitisha K. , Miller Chris P. , Brown Jeffrey L. , Hattersley Gary , Saeh Jamal C.
Published: October 2017

Purpose: Steroidal androgens suppress androgen receptor and estrogen receptor positive (AR/ER+) breast cancer cells and were used to treat breast cancer, eliciting favorable response. The current study evaluates the activity and efficacy of the oral selective AR modulator RAD140 in in vivo and in vitro models of AR/ER+ breast cancer.

Experimental Design: A series of in vitro assays were used to determine the affinity of RAD140 to 4 nuclear receptors and evaluate its tissue-selective AR activity. The efficacy and pharmacodynamics of RAD140 as monotherapy or in combination with palbociclib were evaluated in AR/ER+ breast cancer xenograft models.

Results: RAD140 bound AR with high affinity and specificity and activated AR in breast cancer but not prostate cancer cells. Oral administration of RAD140 substantially inhibited the growth of AR/ER+ breast cancer patient-derived xenografts (PDX). Activation of AR and suppression of ER pathway, including the ESR1 gene, were seen with RAD140 treatment. Coadministration of RAD140 and palbociclib showed improved efficacy in the AR/ER+ PDX models. In line with efficacy, a subset of AR-repressed genes associated with DNA replication was suppressed with RAD140 treatment, an effect apparently enhanced by concurrent administration of palbociclib.

Conclusions: RAD140 is a potent AR agonist in breast cancer cells with a distinct mechanism of action, including the AR-mediated repression of ESR1. It inhibits the growth of multiple AR/ER+ breast cancer PDX models as a single agent, and in combination with palbociclib. The preclinical data presented here support further clinical investigation of RAD140 in AR/ER+ breast cancer patients. Clin Cancer Res; 23(24); 7608–20. ©2017 AACR.
Modulation of Navitoclax Sensitivity by Dihydroartemisinin-Mediated MCL-1 Repression in BCR-ABL+ B-Lineage Acute Lymphoblastic Leukemia
Authors: Budhraja Amit , Turnis Meghan E. , Churchman Michelle L. , Kothari Anisha , Yang Xue , Xu Haiyan , Kaminska Ewa , Panetta John C. , Finkelstein David , Mullighan Charles G. , Opferman Joseph T.
Published: October 2017

Purpose: BCR-ABL+ B-ALL leukemic cells are highly dependent on the expression of endogenous antiapoptotic MCL-1 to promote viability and are resistant to BH3-mimetic agents such as navitoclax (ABT-263) that target BCL-2, BCL-XL, and BCL-W. However, the survival of most normal blood cells and other cell types is also dependent on Mcl-1. Despite the requirement for MCL-1 in these cell types, initial reports of MCL-1–specific BH3-mimetics have not described any overt toxicities associated with single-agent use, but these agents are still early in clinical development. Therefore, we sought to identify approved drugs that could sensitize leukemic cells to ABT-263.

Experimental Design: A screen identified dihydroartemisinin (DHA), a water-soluble metabolite of the antimalarial artemisinin. Using mouse and human leukemic cell lines, and primary patient-derived xenografts, the effect of DHA on survival was tested, and mechanistic studies were carried out to discover how DHA functions. We further tested in vitro and in vivo whether combining DHA with ABT-263 could enhance the response of leukemic cells to combination therapy.

Results: DHA causes the downmodulation of MCL-1 expression by triggering a cellular stress response that represses translation. The repression of MCL-1 renders leukemic cells highly sensitive to synergistic cell death induced by ABT-263 in a mouse model of BCR-ABL+ B-ALL both in vitro and in vivo. Furthermore, DHA synergizes with ABT-263 in human Ph+ ALL cell lines, and primary patient-derived xenografts of Ph+ ALL in culture.

Conclusions: Our findings suggest that combining DHA with ABT-263 can improve therapeutic response in BCR-ABL+ B-ALL. Clin Cancer Res; 23(24); 7558–68. ©2017 AACR.