The Association of Neuromuscular Attributes with Performance-based Mobility among Community-dwelling Older Adults with Symptomatic Lumbar Spinal Stenosis

Publication date: Available online 2 April 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Catherine T. Schmidt, Rachel E. Ward, Pradeep Suri, Dan K. Kiely, Ni Pensheng, Dennis E. Anderson, Jonathan F. Bean
ObjectiveTo identify differences in health factors, neuromuscular attributes and performance-based mobility among community-dwelling older adults with symptomatic lumbar spinal stenosis (SLSS); and to determine which neuromuscular attributes are associated with performance-based measures of mobility. We hypothesized that: (1) community-dwelling older adults with SLSS would have poorer health, greater neuromuscular impairment and worse mobility; and (2) greater impairment in trunk extensor muscle endurance, leg strength, leg speed and knee flexion range of motion (ROM) would be associated with performance-based mobility. Design: Cross-sectional; secondary data analysis of a cohort studySettingoutpatient rehabilitation centerParticipantsCommunity-dwelling adults > 65 years with self-reported mobility limitations and SLSSInterventionsN/AMain Outcome MeasuresShort Physical Performance Battery Score, Habitual Gait Speed, and Chair Stand TestResultsSLSS was classified using self-reported symptoms of neurogenic claudication and imaging. Among 430 community-dwelling older adults 54(13%) met criteria for SLSS. Compared to participants without SLSS, those with SLSS had more comorbidities, higher BMI, greater pain and less balance confidence. Participants with SLSS had greater impairment in trunk extensor muscle endurance, leg strength, leg strength asymmetry, knee flexion range of motion (ROM), knee extension ROM, and ankle ROM compared to participants without SLSS. Five neuromuscular attributes were associated with performance-based mobility among participants with SLSS: trunk extensor muscle endurance, leg strength, leg strength asymmetry, knee flexion ROM, and knee extension ROM asymmetry.ConclusionsCommunity-dwelling older adults with self-reported mobility limitations with SLSS exhibit poorer health characteristics, greater neuromuscular impairment and worse mobility when compared to those without SLSS. Poorer trunk extensor muscle endurance, leg strength, leg strength asymmetry, knee flexion ROM, and knee extension ROM asymmetry were associated with performance-based mobility among participants with SLSS.



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Effect of natural and semi-synthetic cadinanes from Heterotheca inuloides on NF-κB, Nrf2 and STAT3 signaling pathways and evaluation of their in vitro cytotoxicity in human cancer cell lines

Publication date: Available online 2 April 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Verónica Egas, Estrella Millán, Juan A. Collado, Teresa Ramírez-Apan, Carlos A. Méndez-Cuesta, Eduardo Muñoz, Guillermo Delgado
The effects of ten natural cadinane sesquiterpenoids isolated from Heterotheca inuloides on the pathways of the NF-κB, Nrf2 and STAT3 transcription factors were studied for the first time. The main constituent in this species, 7-hydroxy-3,4-dihydrocadalene (1), showed anti-NF-κB activity and activated the antioxidant Nrf2 pathway, which may explain the properties reported for the traditional use of the plant. In addition to the main metabolite, a structurally similar compound, 7-hydroxy-cadalene (2), also displayed anti-NF-κB activity. Thus, both natural compounds were used as templates for the preparation of a novel semi-synthetic derivative set, including esters and carbamates, which were evaluated for their potential in vitro antiproliferative activities against six human cancer cell lines. Carbamate derivatives 32 and 33 were found to exhibit potent activity against human colorectal adenocarcinoma and showed important selectivity in cancer cells. Among ester derivatives, compound 13 was determined to be a more potent NF-κB inhibitor and Nrf2 activator than its parent, 7-hydroxy-3,4-dihydrocadalene (1). Furthermore, this compound decreases levels of phospho-IκBα, a protein complex involved in the NF-κB activation pathway. Molecular simulations suggest that all active compounds interact with the activation loop of the IKKβ subunit in the IKK complex, which is the responsible of IκBα phosphorylation. Thus, we identified two natural, and one semi-synthetic, NF-κB and Nrf2 modulators and two new promising cytotoxic compounds.

Graphical abstract

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Editorial board

Publication date: 1 May 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 9





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Erratum to “Synthesis, biological evaluation, and physicochemical property assessment of 4-substituted 2-phenylaminoquinazolines as Mer tyrosine kinase inhibitors” [Bioorg. Med. Chem. 24 (2016) 3083–3092]

Publication date: 1 May 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 9
Author(s): Sheng-Biao Wang, Mu-Tian Cui, Xiao-Feng Wang, Emika Ohkoshi, Masuo Goto, De-Xuan Yang, Linna Li, Shoujun Yuan, Susan L. Morris-Natschke, Kuo-Hsiung Lee, Lan Xie




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Computational Refinement of Spectroscopic FRET Measurements

Publication date: Available online 2 April 2017
Source:Data in Brief
Author(s): Alexander Kyrychenko, Mykola V. Rodnin, Chiranjib Ghatak, Alexey S. Ladokhin
This article supplies raw data related to a research article entitled "Joint refinement of FRET measurements using spectroscopic and computational tools" (A. Kyrychenko, M. V.Rodnin, C. Ghatak, A. S. Ladokhin, 2017) [1], in which we demonstrate the use of molecular dynamics simulations to estimate FRET orientational factors in a benchmark donor-linker-acceptor system of enhanced cyan (ECFP) and enhanced yellow (EYFP) fluorescent proteins. This can improve the recalculation of donor-acceptor distance information from single-molecule FRET measurements.



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Multi-targeted protection of acetaminophen-induced hepatotoxicity in mice by tannic acid

Publication date: June 2017
Source:International Immunopharmacology, Volume 47
Author(s): Jianping Zhang, Qiongtao Song, Xue Han, Yuanyuan Zhang, Ying Zhang, Xuan Zhang, Xi Chu, Fenghua Zhang, Li Chu
Tannic acid (TA) is the polyphenol that has beneficial health effects against oxidative stress. However, the hepatoprotective effects of TA are still relatively unknown. In the present study, we evaluated the effects of TA on an acetaminophen (APAP)-induced hepatotoxicity model, which was established by administration of 400mg/kg of APAP. The levels of alanine transferase (ALT), aspartate transferase (AST), dendothelin-1 (ET-1), nitric oxide (NO) and malondialdehyde (MDA) in the APAP-induced hepatotoxicity mice were significantly increased (up to ~200%), while their levels were reduced by pretreatment with TA (25 and 50mg/kg) (P<0.05). The activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in the APAP-induced hepatotoxicity mice were significantly reduced (lower to ~65%), while their activities were increased by pretreatment with TA (25 and 50mg/kg) (P<0.05). In addition, pretreatment with oral TA (25 and 50mg/kg) for 3days before the APAP administration dose-dependently ameliorated changes in hepatic histopathology, suppressed overexpression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), c-fos, c-jun, NF-κB (p65) and caspase-3 (all P<0.05), downregulated bax and upregulated bcl-2, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) (all P<0.05) in the liver. These results indicate that TA exhibits significant hepatoprotective effects against APAP-induced hepatotoxicity and suggest that the hepatoprotective mechanisms of TA may be related to anti-oxidation, anti-inflammation and anti-apoptosis.



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Injured Brains and Adaptive Networks: The Benefits and Costs of Hyperconnectivity

Publication date: Available online 1 April 2017
Source:Trends in Cognitive Sciences
Author(s): Frank G. Hillary, Jordan H. Grafman
A common finding in human functional brain-imaging studies is that damage to neural systems paradoxically results in enhanced functional connectivity between network regions, a phenomenon commonly referred to as 'hyperconnectivity'. Here, we describe the various ways that hyperconnectivity operates to benefit a neural network following injury while simultaneously negotiating the trade-off between metabolic cost and communication efficiency. Hyperconnectivity may be optimally expressed by increasing connections through the most central and metabolically efficient regions (i.e., hubs). While adaptive in the short term, we propose that chronic hyperconnectivity may leave network hubs vulnerable to secondary pathological processes over the life span due to chronically elevated metabolic stress. We conclude by offering novel, testable hypotheses for advancing our understanding of the role of hyperconnectivity in systems-level brain plasticity in neurological disorders.



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1/(2+Rc): A simple predictive formula for laboratory shrinkage-stress measurement

Publication date: Available online 1 April 2017
Source:Dental Materials
Author(s): Wondwosen A. Aregawi, Alex S.L. Fok
ObjectiveThis paper presents and verifies a simple predictive formula for laboratory shrinkage-stress measurement in dental composites that can account for the combined effect of material properties, sample geometry and instrument compliance.MethodsA mathematical model for laboratory shrinkage-stress measurement that includes the composite's elastic modulus, shrinkage strain, and their interaction with the sample's dimensions and the instrument's compliance has previously been developed. The model contains a dimensionless parameter, Rc, which represents the compliance of the instrument relative to that of the cured composite sample. A simplified formula, 1/(2+Rc), is proposed here for the normalized shrinkage stress to approximate the original model. The accuracy of the simplified formula is examined by comparing its shrinkage-stress predictions with those given by the exact formula for different cases. These include shrinkage stress measured using instruments with different compliances, samples with different thicknesses and composites with different filler fractions.ResultsThe simplified formula produces shrinkage-stress predictions that are very similar to those given by the full formula. In addition, it correctly predicts the decrease in shrinkage stress with an increasing configuration factor for compliant instruments. It also correctly predicts the value of the so-called flow factor of composites despite the fact that creep is not considered in the model.SignificanceThe new simple formula significantly simplifies the prediction of shrinkage stress for disc specimens used in laboratory experiments without much loss in precision. Its explicit analytical form shows clearly all the important parameters that control the level of shrinkage stress in such measurements. It also helps to resolve much of the confusion caused by the seemingly contradictory results reported in the literature. Further, the formula can be used as a guide for the design of dental composite materials or restorations to minimize their shrinkage stress.



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Lexical influence on stress processing in a fixed-stress language

Publication date: Available online 2 April 2017
Source:International Journal of Psychophysiology
Author(s): Linda Garami, Anett Ragó, Ferenc Honbolygó, Valéria Csépe
In the present study, we investigate how lexicality affects the processing of suprasegmental features at the word level. In contrast to earlier studies which analyzed the role of either segmental or suprasegmental feature in language processing our aim was to investigate the effect of the lexical status on the processing of violated stress pattern defined by linguistic rules. We have conducted a passive oddball ERP experiment, presenting a frequent CVCV word with legal (familiar) and illegal (unfamiliar) stress patterns. Former results obtained with pseudo-words in a similar paradigm enabled to assess the influence of lexical information on stress processing.The presence of lexically relevant information resulted in different ERP patterns compared to those obtained with pseudo-words. We obtained two consecutive MMN responses to the illegally stressed words while violating the illegal stress pattern with a legal one the deviant stimulus elicited two consecutive MMN responses as well. In the latter condition lexicality clearly enhanced the comparison of prosodic information between standard and deviant stimuli, as these components very completely missing when presenting pseudo-words.We interpret the results that lexicality acts as a filter since in the absence of lexical familiarity unfamiliar stress patterns are discriminated better.Our results highlight that even when stress is fully predictable, it is taken into account during pre-attentive processing of linguistic input.



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Diversity in AMPAR complexes in the brain

Publication date: August 2017
Source:Current Opinion in Neurobiology, Volume 45
Author(s): Eric Jacobi, Jakob von Engelhardt
AMPA receptor (AMPAR) complexes comprise four of the AMPAR subunits GluA1-4 and several additional interacting proteins. Subunit composition determines AMPAR function. However, AMPAR function depends to a large extent also on interacting proteins, which influence trafficking to the cell surface, activity-dependent subcellular localization and gating of AMPARs. In this review we report about recent findings on the diversity of AMPAR complexes that allow us to better understand functional properties of native receptors in the brain.



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Risk factors and state-of-the-art indications for boost irradiation in invasive breast carcinoma

Publication date: Available online 1 April 2017
Source:Brachytherapy
Author(s): Alfredo Polo, Csaba Polgár, Jean-Michel Hannoun-Levi, Jose-Luis Guinot, Cristina Gutierrez, Razvan Galalae, Erik van Limbergen, Vratislav Strnad
PurposeThe aim of the study was to give recommendations on patient selection criteria for the administration of boost doses after whole-breast irradiation (WBI) in invasive breast cancer based on available clinical evidence complemented by expert opinion.Methods and MaterialsA systematic search of the PubMed database was conducted to identify factors associated with increased risk for local failure that can define risk groups, and to provide evidence for an adequate guidance to the use of the boost as a function of the risk of local recurrence in breast-conserving therapy. The authors reviewed the published clinical evidence for the use of boost after WBI, complemented by other relevant studies and, through a series of formal meetings communications, formulated the recommendations presented in this article.ResultsThe GEC-ESTRO Breast Cancer Working Group recommends three categories guiding patient selection for the use of a boost after WBI: (1) a low-risk group for whom boost adds little benefit, including patients aging at least 50 years with unicentric, unifocal, and clear surgical margins of at least 2 mm and no axillary lymph nodes invasion. In this group, a boost of 10–16 Gy EQD2 after WBI (25fr × 2 Gy or 15 fr × 2.67 Gy) is optional and not mandatory, (2) a high-risk group, for whom boost is considered mandatory and where dose escalation above 16 Gy EQD2 should be considered; including patients aging ≤40 years with close margins, extensive intraductal component or triple-negative phenotype, or patients with positive resection margins regardless of patient age, and (3) an intermediate-risk group, for whom the boost (10–16 Gy EQD2) is considered mandatory, includes patients below 40 years without major risk criteria, patients >40 years and <50 years regardless of any risk factors, or patients >50 years with any risk factor (close margins, tumor size >3 cm, extensive intraductal component, lymphovascular invasion, lymph node invasion, multicentric or multifocal tumors, triple-negative phenotype, or after neoadjuvant chemotherapy in case of residual tumor).ConclusionsThese recommendations may provide a clinical guidance regarding the use of boost after WBI in invasive breast cancer and holds for standard and hypofractionated WBI. Furthermore they should promote further clinical research focusing on controversial issues in the treatment of early-stage breast carcinoma.



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Temporal changes in radiocesium contamination derived from the Fukushima Dai-ichi Nuclear Power Plant accident in oceanic zooplankton in the western North Pacific

Publication date: June 2017
Source:Journal of Environmental Radioactivity, Volume 172
Author(s): Minoru Kitamura, Makio C. Honda, Yasunori Hamajima, Yuichiro Kumamoto, Michio Aoyama, Hajime Kawakami, Tatsuo Aono, Miho Fukuda, Yoshihisa Mino
We investigated temporal changes of the contamination of oceanic zooplankton with radiocesium (¹³⁴Cs and ¹³⁷Cs) derived from the Fukushima Dai-ichi Nuclear Power Plant accident one month to three years after the accident at subarctic and subtropical stations (1900 and 900–1000 km from the plant, respectively) in the western North Pacific. The maximum activity concentrations of ¹³⁷Cs in zooplankton were two orders of magnitude higher than the pre-accident level. In the first four months after the accident, the activity concentrations of radiocesium in subtropical zooplankton decreased rapidly, but no similar change was observed at the subarctic station. The radiocesium derived from atmospheric deposition rapidly decreased as a result of seawater mixing. Thus, most of the subtropical zooplankton (with short lifespans) that had taken up radiocesium just after the accident were probably replaced by newly hatched zooplankton within four months of the accident, whereas subarctic zooplankton (with long lifespans) that were highly contaminated with radiocesium were still alive four months after the accident. By the end of the study, ¹³⁷Cs activity concentrations in subtropical zooplankton were still high, whereas the activity concentrations in subarctic zooplankton had decreased to nearly the pre-accident level. The former concentrations were probably influenced by a secondary supply of radiocesium via advection of subtropical mode water that was highly contaminated with Fukushima-derived radiocesium. Unexpectedly, at the subarctic station, the radiocesium activity concentrations in surface zooplankton were lower than those in subsurface zooplankton, whereas the opposite relationship was observed in surface and subsurface seawater. Because carnivores predominated in the subsurface zooplankton community, we hypothesize that the higher radiocesium activity concentrations in subsurface zooplankton were influenced by bioaccumulation. We conclude that radiocesium activity concentrations in zooplankton are influenced not only by the supply of radiocesium to the environment but also by the characteristics of the zooplankton community.



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Editorial Board

Publication date: May 2017
Source:Brain and Development, Volume 39, Issue 5





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Treatment of intractable seizure in Wolf–Hirschhorn syndrome with bromide

Publication date: Available online 1 April 2017
Source:Brain and Development
Author(s): Inn-Chi Lee, Syuan-Yu Hong




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Announcements and reports

Publication date: May 2017
Source:Brain and Development, Volume 39, Issue 5





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Cover

Publication date: May 2017
Source:Brain and Development, Volume 39, Issue 5





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Contents

Publication date: May 2017
Source:Brain and Development, Volume 39, Issue 5





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Developmental changes in autonomic responses are associated with future reward/punishment expectations: A study of sympathetic skin responses in the Markov decision task

Publication date: Available online 1 April 2017
Source:Brain and Development
Author(s): Hiromi Hosaka, Kakuro Aoyagi, Yoshimi Kaga, Hideaki Kanemura, Kanji Sugita, Masao Aihara
ObjectiveAutonomic nervous system activity is recognized as a major component of emotional responses. Future reward/punishment expectations depend upon the process of decision making in the frontal lobe, which is considered to play an important role in executive function. The aim of this study was to investigate the relationship between autonomic responses and decision making during reinforcement tasks using sympathetic skin responses (SSR).MethodsNine adult and 9 juvenile (mean age, 10.2years) volunteers were enrolled in this study. SSRs were measured during the Markov decision task (MDT), which is a reinforcement task. In this task, subjects must endure a small immediate loss to ultimately get a large reward. The subjects had to undergo three sets of tests and their scores in these tests were assessed and evaluated.ResultsAll adults showed gradually increasing scores for the MDT from the first to third set. As the trial progressed from the first to second set in adults, SSR appearance ratios remarkably increased for both punishment and reward expectations. In comparison with adults, children showed decreasing scores from the first to second set. There were no significant inter-target differences in the SSR appearance ratio in the first and second set in children. In the third set, the SSR appearance ratio for reward expectations was higher than that in the neutral condition.ConclusionsIn reinforcement tasks, such as MDT, autonomic responses play an important role in decision making. We assume that SSRs are elicited during efficient decision making tasks associated with future reward/punishment expectations, which demonstrates the importance of autonomic function. In contrast, in children around the age of 10years, the autonomic system does not react as an organized response specific to reward/punishment expectations. This suggests the immaturity of the future reward/punishment expectations process in children.



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Golgi trafficking defects in postnatal microcephaly: The evidence for “Golgipathies”

Publication date: Available online 2 April 2017
Source:Progress in Neurobiology
Author(s): Sandrine Passemard, Franck Perez, Emilie Colin-Lemesre, Sowmyalakshmi Rasika, Pierre Gressens, Vincent El Ghouzzi
The Golgi apparatus plays a central role in cell homeostasis, not only in processing and maturing newly synthesized proteins and lipids but also in orchestrating their sorting, packing, routing and recycling on the way to their final destination. These multiple secretory pathways require a complex ballet of vesicular and tubular carriers that continuously bud off from donor membranes and fuse to acceptor membranes. Membrane trafficking is particularly prominent in axons, where cargo molecules have a long way to travel before they reach the synapse, and in oligodendrocytes, which require an immense increase in membrane surface in order to sheathe axons in myelin. Interestingly, in recent years, genes encoding Golgi-associated proteins with a role in membrane trafficking have been found to be defective in an increasing number of inherited disorders whose clinical manifestations include postnatal-onset microcephaly (POM), white matter defects and intellectual disability. Several of these genes encode RAB GTPases, RAB-effectors or RAB-regulating proteins, linking POM and intellectual disability to RAB-dependent Golgi trafficking pathways and suggesting that their regulation is critical to postnatal brain maturation and function. Here, we review the key roles of the Golgi apparatus in post-mitotic neurons and the oligodendrocytes that myelinate them, and provide an overview of these Golgi-associated POM-causing genes, their function in Golgi organization and trafficking and the likely mechanisms that may link dysfunctions in RAB-dependent regulatory pathways with POM.



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Identification of transcription factors that may reprogram lung adenocarcinoma

Publication date: Available online 1 April 2017
Source:Artificial Intelligence in Medicine
Author(s): Chenglin Liu, Yu-Hang Zhang, Tao Huang, Yudong Cai
BackgroundLung adenocarcinoma is one of most threatening disease to human health. Although many efforts have been devoted to its genetic study, few researches have been focused on the transcription factors which regulate tumor initiation and progression by affecting multiple downstream gene transcription. It is proved that proper transcription factors may mediate the direct reprogramming of cancer cells, and reverse the tumorigenesis on the epigenetic and transcription levels.MethodsIn this paper, a computational method is proposed to identify the core transcription factors that can regulate as many as possible lung adenocarcinoma associated genes with as little as possible redundancy. A greedy strategy is applied to find the smallest collection of transcription factors that can cover the differentially expressed genes by its downstream targets. The optimal subset which is mostly enriched in the differentially expressed genes is then selected.ResultsSeven core transcription factors (MCM4, VWF, ECT2, RBMS3, LIMCH1, MYBL2 and FBXL7) are detected, and have been reported to contribute to tumorigenesis of lung adenocarcinoma. The identification of the transcription factors provides a new insight into its oncogenic role in tumor initiation and progression, and benefits the discovery of functional core set that may reverse malignant transformation and reprogram cancer cells.



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