bluuebunny/crossref_metadata_2025 huggingface dataset:
Intravenous immune globulin and thromboembolic adverse events: A systematic review and meta‐analysis of RCTs
Authors: Ammann Eric M. , Haskins Cole B. , Fillman Kelsey M. , Ritter Rebecca L. , Gu Xiaomei , Winiecki Scott K. , Carnahan Ryan M. , Torner James C. , Fireman Bruce H. , Jones Michael P. , Chrischilles Elizabeth A.
Published: March 2016

Prior case reports and observational studies indicate that intravenous immune globulin (IVIg) products may cause thromboembolic events (TEEs), leading the FDA to require a boxed warning in 2013. The effect of IVIg treatment on the risk of serious TEEs (acute myocardial infarction, ischemic stroke, or venous thromboembolism) was assessed using adverse event data reported in randomized controlled trials (RCTs) of IVIg. RCTs of IVIg in adult patients from 1995 to 2015 were identified from Pubmed, Embase, ClinicalTrials.Gov, and two large prior reviews of IVIg's therapeutic applications. Trials at high risk of detection or reporting bias for serious adverse events were excluded. 31 RCTs with a total of 4,129 participants (2,318 IVIg‐treated, 1,811 control) were eligible for quantitative synthesis. No evidence was found of increased TEE risk among IVIg‐treated patients compared with control patients (odds ratio = 1.10, 95% CI: 0.44, 2.88; risk difference = 0.0%, 95% CI: −0.7%, 0.7%, I2 = 0%). No significant increase in risk was found when arterial and venous TEEs were analyzed as separate endpoints. Trial publications provided little specific information concerning the methods used to ascertain potential adverse events. Care should be taken in extrapolating the results to patients with higher baseline risks of TEE. Am. J. Hematol. 91:594–605, 2016. © 2016 Wiley Periodicals, Inc.
Should any genetic defect affecting α‐granules in platelets be classified as gray platelet syndrome?
Authors: Nurden Alan T. , Nurden Paquita
Published: March 2016

There is much current interest in the role of the platelet storage pool of α‐granule proteins both in hemostasis and non‐hemostatic events. As well as in the arrest of bleeding, the secreted proteins participate in wound healing, inflammation, and innate immunity while in pathology they may be actors in arterial thrombosis and atherosclerosis as well as cancer and metastasis. For a long time, gray platelet syndrome (GPS) has been regarded as the classic inherited platelet disorder caused by an absence of α‐granules and their contents. While NBEAL2 is the major source of mutations in GPS, other gene variants may give rise to significant α‐granule deficiencies in platelets. These include GATA1, VPS33B, or VIPAS39 in the arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome and now GFI1B. Nevertheless, many phenotypic differences are associated with mutations in these genes. This critical review was aimed to assess genotype/phenotype variability in disorders of platelet α‐granule biogenesis and to urge caution in grouping all genetic defects of α‐granules as GPS. Am. J. Hematol. 91:714–718, 2016. © 2016 Wiley Periodicals, Inc.
Rotation of nilotinib and imatinib for first‐line treatment of chronic phase chronic myeloid leukemia
Authors: Gugliotta Gabriele , Castagnetti Fausto , Breccia Massimo , Gozzini Antonella , Usala Emilio , Carella Angelo M. , Rege‐Cambrin Giovanna , Martino Bruno , Abruzzese Elisabetta , Albano Francesco , Stagno Fabio , Luciano Luigia , D'Adda Mariella , Bocchia Monica , Cavazzini Francesco , Tiribelli Mario , Lunghi Monia , Pia Falcone Antonietta , Musolino Caterina , Levato Luciano , Venturi Claudia , Soverini Simona , Cavo Michele , Alimena Giuliana , Pane Fabrizio , Martinelli Giovanni , Saglio Giuseppe , Rosti Gianantonio , Baccarani Michele ,   on behalf of the GIMEMA CML Working Party
Published: March 2016

The introduction of second‐generation tyrosine‐kinase inhibitors (TKIs) has generated a lively debate on the choice of first‐line TKI in chronic phase, chronic myeloid leukemia (CML). Despite the TKIs have different efficacy and toxicity profiles, the planned use of two TKIs has never been investigated. We report on a phase 2 study that was designed to evaluate efficacy and safety of a treatment alternating nilotinib and imatinib, in newly diagnosed BCR‐ABL1 positive, chronic phase, CML patients. One hundred twenty‐three patients were enrolled. Median age was 56 years. The probabilities of achieving a complete cytogenetic response, a major molecular response, and a deep molecular response (MR 4.0) by 2 years were 93%, 87%, and 61%, respectively. The 5‐year overall survival and progression‐free survival were 89%. Response rates and survival are in the range of those reported with nilotinib alone. Moreover, we observed a relatively low rate of cardiovascular adverse events (5%). These data show that the different efficacy and toxicity profiles of TKIs could be favorably exploited by alternating their use. Am. J. Hematol. 91:617–622, 2016. © 2016 Wiley Periodicals, Inc.
Cerebro–costo–mandibular syndrome: Clinical, radiological, and genetic findings
Authors: Tooley Madeleine , Lynch Danielle , Bernier Francois , Parboosingh Jillian , Bhoj Elizabeth , Zackai Elaine , Calder Alistair , Itasaki Nobue , Wakeling Emma , Scott Richard , Lees Melissa , Clayton‐Smith Jill , Blyth Moira , Morton Jenny , Shears Debbie , Kini Usha , Homfray Tessa , Clarke Angus , Barnicoat Angela , Wallis Colin , Hewitson Rebecca , Offiah Amaka , Saunders Michael , Langton‐Hewer Simon , Hilliard Tom , Davis Peter , Smithson Sarah
Published: March 2016

Cerebro–Costo–Mandibular syndrome (CCMS) is a rare autosomal dominant condition comprising branchial arch‐derivative malformations with striking rib‐gaps. Affected patients often have respiratory difficulties, associated with upper airway obstruction, reduced thoracic capacity, and scoliosis. We describe a series of 12 sporadic and 4 familial patients including 13 infants/children and 3 adults. Severe micrognathia and reduced numbers of ribs with gaps are consistent findings. Cleft palate, feeding difficulties, respiratory distress, tracheostomy requirement, and scoliosis are common. Additional malformations such as horseshoe kidney, hypospadias, and septal heart defect may occur. Microcephaly and significant developmental delay are present in a small minority of patients. Key radiological findings are of a narrow thorax, multiple posterior rib gaps and abnormal costo‐transverse articulation. A novel finding in 2 patients is bilateral accessory ossicles arising from the hyoid bone. Recently, specific mutations in SNRPB, which encodes components of the major spliceosome, have been found to cause CCMS. These mutations cluster in an alternatively spliced regulatory exon and result in altered SNRPB expression. DNA was available from 14 patients and SNRPB mutations were identified in 12 (4 previously reported). Eleven had recurrent mutations previously described in patients with CCMS and one had a novel mutation in the alternative exon. These results confirm the specificity of SNRPB mutations in CCMS and provide further evidence for the role of spliceosomal proteins in craniofacial and thoracic development. © 2016 Wiley Periodicals, Inc.
Survey of 2014 behavioral management programs for laboratory primates in the United States
Authors: Baker Kate C.
Published: March 2016

The behavioral management of laboratory nonhuman primates in the United States has not been thoroughly characterized since 2003. This article presents the results of a survey behavioral management programs at 27 facilities and covering a total of 59,636 primates, 27,916 housed in indoor cages and 31,720 in group enclosures. The survey included questions regarding program structure, implementation, and methodology associated with social housing, positive reinforcement training, positive human interaction, exercise enclosures, and several categories of inanimate enrichment. The vast majority of laboratory primates are housed socially (83%). Since 2003, the proportion of indoor‐housed primates reported to be housed singly has fallen considerably, from 59% to 35% in the facilities surveyed. The use of social housing remains significantly constrained by: 1) research protocol requirements, highlighting the value of closely involved IACUCs for harmonizing research and behavioral management; and 2) the unavailability of compatible social partners, underscoring the necessity of objective analysis of the methods used to foster and maintain compatibility. Positive reinforcement training appears to have expanded and is now used at all facilities responding to the survey. The use of enrichment devices has also increased in the participating facilities. For most behavioral management techniques, concerns over the possibility of negative consequences to animals are expressed most frequently for social housing and destructible enrichment, while skepticism regarding efficacy is limited almost exclusively to sensory enrichment. Behavioral management program staffing has expanded over time in the facilities surveyed, due not only to increased numbers of dedicated behavioral management technicians but also to greater involvement of animal care technicians, suggesting an increase in the integration of behavioral care into animal husbandry. Broad awareness of common practice may assist facilities with program evaluation and assessment of progress in the field can generate recommendations for continuing the advancement of primate behavioral management programs. Am. J. Primatol. 78:780–796, 2016. © 2016 Wiley Periodicals, Inc.
Neandertals' large lower thorax may represent adaptation to high protein diet
Authors: Ben‐Dor Miki , Gopher Avi , Barkai Ran
Published: March 2016

Humans are limited in their capacity to convert protein into energy. We present a hypothesis that a “bell” shaped thorax and a wide pelvis evolved in Neandertals, at least in part, as an adaptation to a high protein diet. A high protein diet created a need to house an enlarged liver and urinary system in a wider lower trunk. To test the hypothesis, we applied a model developed to identify points of nutritional stress. A ratio of obligatory dietary fat to total animal fat and protein sourced calories is calculated based on various known and estimated parameters. Stress is identified when the obligatory dietary fat ratio is higher than fat content ratios in available prey. The model predicts that during glacial winters, when carbohydrates weren't available, 74%−85% of Neandertals' caloric intake would have had to come from animal fat. Large animals contain around 50% fat calories, and their fat content is diminished during winter, so a significant stressful dietary fat deficit was identified by the model. This deficit could potentially be ameliorated by an increased capability to convert protein into energy. Given that high protein consumption is associated with larger liver and kidneys in animal models, it appears likely that the enlarged inferior section of the Neandertals thorax and possibly, in part, also his wide pelvis, represented an adaptation to provide encasement for those enlarged organs. Behavioral and evolutionary implications of the hypothesis are also discussed. Am J Phys Anthropol 160:367–378, 2016. © 2016 Wiley Periodicals, Inc.
Puromycin Analogues Capable of Multiplexed Imaging and Profiling of Protein Synthesis and Dynamics in Live Cells and Neurons
Authors: Ge Jingyan , Zhang Cheng‐Wu , Ng Xue Wen , Peng Bo , Pan Sijun , Du Shubo , Wang Danyang , Li Lin , Lim Kah‐Leong , Wohland Thorsten , Yao Shao Q.
Published: March 2016

Newly synthesized proteins constitute an important subset of the proteome involved in every cellular process, yet existing chemical tools used to study them have major shortcomings. Herein we report a suite of cell‐permeable puromycin analogues capable of being metabolically incorporated into newly synthesized proteins in different mammalian cells, including neuronal cells. Subsequent labeling with suitable bioorthogonal reporters, in both fixed and live cells, enabled direct imaging and enrichment of these proteins. By taking advantage of the mutually orthogonal reactivity of these analogues, we showed multiplexed labeling of different protein populations, as well as quantitative measurements of protein dynamics by fluorescence correlation spectroscopy, could be achieved in live‐cell environments.
Small Peptides Derived from Penetratin as Antibacterial Agents
Authors: Parravicini Oscar , Somlai Csaba , Andujar Sebastián A. , Garro Adriana D. , Lima Beatriz , Tapia Alejandro , Feresin Gabriela , Perczel Andras , Tóth Gabor , Cascales Javier López , Rodríguez Ana M. , Enriz Ricardo D.
Published: March 2016

The synthesis, in vitro evaluation and conformational study of several small‐size peptides acting as antibacterial agents are reported. Among the compounds evaluated, the peptides Arg‐Gln‐Ile‐Lys‐Ile‐Trp‐Arg‐Arg‐Met‐Lys‐Trp‐Lys‐Lys‐NH2, Arg‐Gln‐Ile‐Lys‐Ile‐Arg‐Arg‐Met‐Lys‐Trp‐Arg‐NH2, and Arg‐Gln‐Ile‐Trp‐Trp‐Trp‐Trp‐Gln‐Arg‐NH2 exhibited significant antibacterial activity. These were found to be very active antibacterial compounds, considering their small molecular size. In order to better understand the antibacterial activity obtained for these peptides, an exhaustive conformational analysis was performed, using both theoretical calculations and experimental measurements. Molecular dynamics simulations using two different media (water and trifluoroethanol/water) were employed. The results of these theoretical calculations were corroborated by experimental circular dichroism measurements. A brief discussion on the possible mechanism of action of these peptides at molecular level is also presented. Some of the peptides reported here constitute very interesting structures to be used as starting compounds for the design of new small‐size peptides possessing antibacterial activity.
History of chickenpox in glioma risk: a report from the glioma international case–control study (GICC)
Authors: Amirian E. Susan , Scheurer Michael E. , Zhou Renke , Wrensch Margaret R. , Armstrong Georgina N. , Lachance Daniel , Olson Sara H. , Lau Ching C. , Claus Elizabeth B. , Barnholtz‐Sloan Jill S. , Il'yasova Dora , Schildkraut Joellen , Ali‐Osman Francis , Sadetzki Siegal , Jenkins Robert B. , Bernstein Jonine L. , Merrell Ryan T. , Davis Faith G. , Lai Rose , Shete Sanjay , Amos Christopher I. , Melin Beatrice S. , Bondy Melissa L.
Published: March 2016

Varicella zoster virus (VZV) is a neurotropic α‐herpesvirus that causes chickenpox and establishes life‐long latency in the cranial nerve and dorsal root ganglia of the host. To date, VZV is the only virus consistently reported to have an inverse association with glioma. The Glioma International Case‐Control Study (GICC) is a large, multisite consortium with data on 4533 cases and 4171 controls collected across five countries. Here, we utilized the GICC data to confirm the previously reported associations between history of chickenpox and glioma risk in one of the largest studies to date on this topic. Using two‐stage random‐effects restricted maximum likelihood modeling, we found that a positive history of chickenpox was associated with a 21% lower glioma risk, adjusting for age and sex (95% confidence intervals (CI): 0.65–0.96). Furthermore, the protective effect of chickenpox was stronger for high‐grade gliomas. Our study provides additional evidence that the observed protective effect of chickenpox against glioma is unlikely to be coincidental. Future studies, including meta‐analyses of the literature and investigations of the potential biological mechanism, are warranted.
A Rationally Designed Connector for Assembly of Protein‐Functionalized DNA Nanostructures
Authors: Koßmann Katja J. , Ziegler Cornelia , Angelin Alessandro , Meyer Rebecca , Skoupi Marc , Rabe Kersten S. , Niemeyer Christof M.
Published: March 2016

We report on the rational engineering of the binding interface of the self‐ligating HaloTag protein to generate an optimized linker for DNA nanostructures. Five amino acids positioned around the active‐site entry channel for the chlorohexyl ligand (CH) of the HaloTag protein were exchanged for positively charged lysine amino acids to produce the HOB (halo‐based oligonucleotide binder) protein. HOB was genetically fused with the enzyme cytochrome P450 BM3, as well as with BMR, the separated reductase domain of BM3. The resulting HOB‐fusion proteins revealed significantly improved rates in ligation with CH‐modified oligonucleotides and DNA origami nanostructures. These results suggest that the efficient self‐assembly of protein‐decorated DNA structures can be greatly improved by fine‐tuning of the electrostatic interactions between proteins and the negatively charged nucleic acid nanostructures.
Biosynthesis of LL‐Z1272β: Discovery of a New Member of NRPS‐like Enzymes for Aryl‐Aldehyde Formation
Authors: Li Chang , Matsuda Yudai , Gao Hao , Hu Dan , Yao Xin Sheng , Abe Ikuro
Published: March 2016

LL‐Z1272β (1) is a prenylated aryl‐aldehyde produced by several fungi; it also serves as a key pathway intermediate for many fungal meroterpenoids. Despite its importance in the biosynthesis of natural products, the molecular basis for the biosynthesis of 1 has yet to be elucidated. Here we identified the biosynthetic gene cluster for 1 from Stachybotrys bisbyi PYH05‐7, and elucidated the biosynthetic route to 1. The biosynthesis involves a polyketide synthase, a prenyltransferase, and a nonribosomal peptide synthetase (NRPS)‐like enzyme, which is responsible for the generation of the aldehyde functionality. Interestingly, the NRPS‐like enzyme only accepts the farnesylated substrate to catalyze the carboxylate reduction; this represents a new example of a substrate for adenylation domains.
Four of the six Drosophila rhodopsin‐expressing photoreceptors can mediate circadian entrainment in low light
Authors: Saint‐Charles Alexandra , Michard‐Vanhée Christine , Alejevski Faredin , Chélot Elisabeth , Boivin Antoine , Rouyer François
Published: March 2016

Light is the major stimulus for the synchronization of circadian clocks with day–night cycles. The light‐driven entrainment of the clock that controls rest–activity rhythms in Drosophila relies on different photoreceptive molecules. Cryptochrome (CRY) is expressed in most brain clock neurons, whereas six different rhodopsins (RH) are present in the light‐sensing organs. The compound eye includes outer photoreceptors that express RH1 and inner photoreceptors that each express one of the four rhodopsins RH3–RH6. RH6 is also expressed in the extraretinal Hofbauer–Buchner eyelet, whereas RH2 is only found in the ocelli. In low light, the synchronization of behavioral rhythms relies on either CRY or the canonical rhodopsin phototransduction pathway, which requires the phospholipase C‐β encoded by norpA (no receptor potential A). We used norpAP24 cry02 double mutants that are circadianly blind in low light and restored NORPA function in each of the six types of photoreceptors, defined as expressing a particular rhodopsin. We first show that the NORPA pathway is less efficient than CRY for synchronizing rest–activity rhythms with delayed light–dark cycles but is important for proper phasing, whereas the two light‐sensing pathways can mediate efficient adjustments to phase advances. Four of the six rhodopsin‐expressing photoreceptors can mediate circadian entrainment, and all are more efficient for advancing than for delaying the behavioral clock. In contrast, neither RH5‐expressing retinal photoreceptors nor RH2‐expressing ocellar photoreceptors are sufficient to mediate synchronization through the NORPA pathway. Our results thus reveal different contributions of rhodopsin‐expressing photoreceptors and suggest the existence of several circuits for rhodopsin‐dependent circadian entrainment. J. Comp. Neurol. 524:2828–2844, 2016. © 2016 Wiley Periodicals, Inc.
Evolutionary loss of cone photoreception in balaenid whales reveals circuit stability in the mammalian retina
Authors: Schweikert Lorian E. , Fasick Jeffry I. , Grace Michael S.
Published: March 2016

The classical understanding of mammalian vision is that it occurs through “duplex” retinae containing both rod and cone photoreceptors, the signals from which are processed through rod‐ and/or cone‐specific signaling pathways. The recent discovery of rod monochromacy in some cetacean lineages provides a novel opportunity to investigate the effects of an evolutionary loss of cone photoreception on retinal organization. Sequence analysis of right whale (Eubalaena glacialis; family Balaenidae) cDNA derived from long‐wavelength sensitive (LWS) cone opsin mRNA identified several mutations in the opsin coding sequence, suggesting the loss of cone cell function, but maintenance of non‐photosensitive, cone opsin mRNA‐expressing cells in the retina. Subsequently, we investigated the retina of the closely related bowhead whale (Balaena mysticetus; family Balaenidae) to determine how the loss of cone‐mediated photoreception affects light signaling pathways in the retina. Anti‐opsin immunofluorescence demonstrated the total loss of cone opsin expression in B. mysticetus, whereas light microscopy, transmission electron microscopy, and bipolar cell (protein kinase C‐α [PKC‐α] and recoverin) immunofluorescence revealed the maintenance of cone soma, putative cone pedicles, and both rod and cone bipolar cell types. These findings represent the first immunological and anatomical evidence of a naturally occurring rod‐monochromatic mammalian retina, and suggest that despite the loss of cone‐mediated photoreception, the associated cone signaling structures (i.e., cone synapses and cone bipolar cells) may be maintained for multichannel rod‐based signaling in balaenid whales. J. Comp. Neurol. 524:2873–2885, 2016. © 2016 Wiley Periodicals, Inc.
Neuroprotective Effects of rhGLP‐1 in Diabetic Rats with Cerebral Ischemia/Reperfusion Injury
Authors: Jiang Daoli , Wang Yitong , Zang Yannan , Liu Xiaofang , Zhao Libo , Wang Qian , Liu Chang , Feng Wanyu , Yin Xiaoxing , Fang Yi
Published: March 2016

Preclinical Research

The aim of the present study was to evaluate the neuroprotective benefits of rhGLP‐1 in diabetic rats subjected to acute cerebral ischemia/reperfusion injury induced by middle cerebral artery occlusion/reperfusion (MCAO/R). Streptozotocin (STZ)‐induced diabetic rats were pretreated with rhGLP‐1 (10, 20, or 40 μg/kg ip, tid) for 14 days. During this time, body weight and fasting blood glucose levels were assessed. Rats were then subjected to MCAO 90 min/R 24 h. At 2 and 24 h of reperfusion, rats were evaluated for neurological deficits and blood samples were collected to analyze markers of brain injury. Rats were then sacrificed to assess the infarction volume. rhGLP‐1 pretreatment lowered blood glucose levels, improved neurological scores, attenuated infarct volumes, and reduced the blood levels of S100 calcium‐binding protein B (S100B), neuron‐specific enolase (NSE), and myelin basic protein (MBP). rhGLP‐1 has neuroprotective benefits in diabetic rats with cerebral ischemia/reperfusion injury and could potentially be used as a prophylatic neuroprotectant in diabetic patients at high risk of ischemic stroke. Drug Dev Res 77 : 124–133, 2016.   © 2016 Wiley Periodicals, Inc.
Pdgfra and Pdgfrb genetically interact during craniofacial development
Authors: McCarthy Neil , Liu Jocelyn S. , Richarte Alicia M. , Eskiocak Banu , Lovely C. Ben , Tallquist Michelle D. , Eberhart Johann K.
Published: March 2016

Background: One of the most prevalent congenital birth defects is cleft palate. The palatal skeleton is derived from the cranial neural crest and platelet‐derived growth factors (Pdgf) are critical in palatogenesis. Of the two Pdgf receptors, pdgfra is required for neural crest migration and palatogenesis. However, the role pdgfrb plays in the neural crest, or whether pdgfra and pdgfrb interact during palatogenesis is unclear. Results: We find that pdgfrb is dispensable for craniofacial development in zebrafish. However, the palatal defect in pdgfra;pdgfrb double mutants is significantly more severe than in pdgfra single mutants. Data in mouse suggest this interaction is conserved and that neural crest requires both genes. In zebrafish, pdgfra and pdgfrb are both expressed by neural crest within the pharyngeal arches, and pharmacological analyses demonstrate Pdgf signaling is required at these times. While neither proliferation nor cell death appears affected, time‐lapsed confocal analysis of pdgfra;pdgfrb mutants shows a failure of proper neural crest condensation during palatogenesis. Conclusions: We provide data showing that pdgfra and pdgfrb interact during palatogenesis in both zebrafish and mouse. In zebrafish, this interaction affects proper condensation of maxillary neural crest cells, revealing a previously unknown interaction between Pdgfra and Pdgfrb during palate formation. Developmental Dynamics 245:641–652, 2016. © 2016 Wiley Periodicals, Inc.
Assessing spatial covariance among time series of abundance
Authors: Jorgensen Jeffrey C. , Ward Eric J. , Scheuerell Mark D. , Zabel Richard W.
Published: March 2016

For species of conservation concern, an essential part of the recovery planning process is identifying discrete population units and their location with respect to one another. A common feature among geographically proximate populations is that the number of organisms tends to covary through time as a consequence of similar responses to exogenous influences. In turn, high covariation among populations can threaten the persistence of the larger metapopulation. Historically, explorations of the covariance in population size of species with many (>10) time series have been computationally difficult. Here, we illustrate how dynamic factor analysis (DFA) can be used to characterize diversity among time series of population abundances and the degree to which all populations can be represented by a few common signals. Our application focuses on anadromous Chinook salmon (Oncorhynchus tshawytscha), a species listed under the US Endangered Species Act, that is impacted by a variety of natural and anthropogenic factors. Specifically, we fit DFA models to 24 time series of population abundance and used model selection to identify the minimum number of latent variables that explained the most temporal variation after accounting for the effects of environmental covariates. We found support for grouping the time series according to 5 common latent variables. The top model included two covariates: the Pacific Decadal Oscillation in spring and summer. The assignment of populations to the latent variables matched the currently established population structure at a broad spatial scale. At a finer scale, there was more population grouping complexity. Some relatively distant populations were grouped together, and some relatively close populations – considered to be more aligned with each other – were more associated with populations further away. These coarse‐ and fine‐grained examinations of spatial structure are important because they reveal different structural patterns not evident in other analyses.
Increased Variability and Asymmetric Expansion of the Hippocampal Spatial Representation in a Distal Cue‐Dependent Memory Task
Authors: Park Seong‐Beom , Lee Inah
Published: March 2016

Place cells in the hippocampus fire at specific positions in space, and distal cues in the environment play critical roles in determining the spatial firing patterns of place cells. Many studies have shown that place fields are influenced by distal cues in foraging animals. However, it is largely unknown whether distal‐cue‐dependent changes in place fields appear in different ways in a memory task if distal cues bear direct significance to achieving goals. We investigated this possibility in this study. Rats were trained to choose different spatial positions in a radial arm in association with distal cue configurations formed by visual cue sets attached to movable curtains around the apparatus. The animals were initially trained to associate readily discernible distal cue configurations (0° vs. 80° angular separation between distal cue sets) with different food‐well positions and then later experienced ambiguous cue configurations (14° and 66°) intermixed with the original cue configurations. Rats showed no difficulty in transferring the associated memory formed for the original cue configurations when similar cue configurations were presented. Place field positions remained at the same locations across different cue configurations, whereas stability and coherence of spatial firing patterns were significantly disrupted when ambiguous cue configurations were introduced. Furthermore, the spatial representation was extended backward and skewed more negatively at the population level when processing ambiguous cue configurations, compared with when processing the original cue configurations only. This effect was more salient for large cue‐separation conditions than for small cue‐separation conditions. No significant rate remapping was observed across distal cue configurations. These findings suggest that place cells in the hippocampus dynamically change their detailed firing characteristics in response to a modified cue environment and that some of the firing properties previously reported in a foraging task might carry more functional weight than others when tested in a distal‐cue‐dependent memory task. © 2016 Wiley Periodicals, Inc.
Breathing maneuvers as a coronary vasodilator for myocardial perfusion imaging
Authors: Teixeira Tiago , Nadeshalingam Gobinath , Fischer Kady , Marcotte François , Friedrich Matthias G.
Published: March 2016

Purpose

A combined breathing maneuver of hyperventilation, followed by a long voluntary breathhold leads to coronary vasodilation. We investigated the impact of breathing maneuvers on MR first‐pass cardiac perfusion imaging and its potential clinical utility.

Materials and Methods

We studied 24 healthy volunteers (37 ± 12 years; 62.5% men) on a clinical 3 Tesla MRI system and performed first‐pass perfusion MR at rest, during a short breathhold (S‐HVBH) following 60 s of hyperventilation, and at the end of a long breathhold (L‐HVBH) following the hyperventilation, performed in random order. A blinded reader analyzed signal intensity upslope, upslope index, and time between 20 and 80% of maximal signal.

Results

All volunteers tolerated the breathing maneuvers well and completed the study protocol. The upslope of the signal‐intensity‐over‐time curve was increased during S‐HVBH (1.86 ± 0.70 units/s, P < 0.05) and at the end of L‐LVBH (1.77 ± 0.82 units/s), when compared with baseline results (1.34 ± 0.58 units/s). Corrected for the arterial input, the upslope was higher at the end of the L‐HVBH (0.095 ± 0.019 units/s versus 0.077 ± 0.016 units/s at rest, P < 0.01) as was the myocardial perfusion reserve index (1.25 ± 0.22 versus 1.09 ± 0.17; P < 0.001). In a multiple regression model, only gender, rate‐pressure product, and breathhold time were independently and significantly related to the upslope (R = 0.771; P < 0.001).

Conclusion

In conclusion, a voluntary long breathhold after hyperventilation leads to an increase of the myocardial perfusion reserve index. This may impact findings from current practice of first‐pass perfusion imaging. The clinical utility of breathing maneuvers as a vasodilatory stimulus for first‐pass perfusion imaging may warrant further research. J. MAGN. RESON. IMAGING 2016;44:947–955.
Interactions of subglottal pressure and neuromuscular activation on fundamental frequency and intensity
Authors: Chhetri Dinesh K. , Park Soo Jin
Published: March 2016

Objectives/Hypothesis

Fundamental frequency (F0) and intensity sound pressure level (SPL) of voice are controlled by intrinsic laryngeal muscle (ILM) activation and subglottal pressure (Psub). Their interactions were investigated.

Methods

In an in vivo canine model, the thyroarytenoid (TA), lateral cricoarytenoid/interarytenoid (LCA/IA), and cricothyroid (CT) muscles were independently activated from threshold to maximal contraction by neuromuscular stimulation in various combinations, whereas airflow was increased to phonation onset pressure and beyond. The resultant acoustic output was analyzed for effects of Psub on vibratory stability, F0, and SPL. Muscle activation plots and vocal range profiles by individual ILM activation states were analyzed.

Results

Cricothyroid activation increased phonation onset F0, but vibration was less stable in high CT conditions and displayed vibratory mode change. In addition, a decrease in F0 with increased Psub was observed in high CT conditions. Intensity increased with Psub in all conditions, but the slope was greater at high CT, low TA/LCA/IA activations. Lateral cricoarytenoid/interarytenoid activation improved vocal efficiency. To maintain same F0 with increasing SPL (messa di voce), TA activation was decreased and LCA/IA activation was increased. The same F0 and SPL could be achieved with a variety of ILM activation combinations.

Conclusion

Cricothyroid is primarily required for increasing F0, whereas TA can increase or decrease F0 and SPL. Lateral cricoarytenoid/interarytenoid activation likely maintains vocal fold adduction during increased Psub and improves vocal efficiency. This study also demonstrates laryngeal motor equivalence, the ability of the larynx to achieve the same target F0 and SPL with multiple combinations of ILM activation.

Level of Evidence

N/A. Laryngoscope, 126:1123–1130, 2016
The efficacy of combination therapy for idiopathic sudden sensorineural hearing loss
Authors: Jung Da Jung , Park Ji Hye , Jang Jeong Hun , Lee Kyu‐Yup
Published: March 2016

Objectives/Hypothesis

The aim of this study was to compare the hearing results of patients with idiopathic sudden sensorineural hearing loss (ISSNHL) who initially were treated with either a combination therapy of systemic steroids (SS) and intratympanic steroid injection (IT‐S) or SS only.

Methods

The study followed a retrospective case‐control design. One‐hundred five patients who were diagnosed with ISSNHL and required treatment via admission were enrolled in this study. The control group (n = 53) was treated with SS, and the study group (n = 52) received SS as well as IT‐S. We divided the patients according to pretreatment hearing levels. The outcome measured was improvement after the treatment audiology data at pretreatment were compared with those at day 10 and > 90 days after the treatment. Outcome data were analyzed using the t test, Pearson's χ2 test, Fisher's exact test, and multivariate analyses of covariance with adjustment for pretreatment hearing levels.

Results

After more than 90 days, the average pure tone audiometry (PTA) in the control and study groups were 54.8 ± 31.4 dB and 43 ± 31.2 dB, respectively (P = 0.013). Hearing recovery rate was 57.7% in the control group and 69.8% in the study group. The hearing gain of the study group was higher than that of the control group at high frequencies within the 10 days of the treatment period. Analysis between subgroups, divided according to the severity of pretreatment hearing level, showed that the recovery rate was higher at all frequencies in the study group than in the control group in patients with mild to moderate hearing loss (pretreatment PTA < 70 dB). However, in patients with severe to profound hearing loss (pretreatment PTA ≥ 70 dB), the hearing outcomes of the study and control groups were not significantly different, except at a low frequency.

Conclusion

The results of this study suggest that the treatment of ISSNHL with combination therapy results in higher hearing recovery rates when compared to treatment with SS alone, even in patients with severe hearing loss.

Level of Evidence

3b. Laryngoscope, 126:1871–1876, 2016
Sialendoscopy‐assisted surgery and the chronic obstructive sialadenitis symptoms questionnaire: A prospective study
Authors: Aubin‐Pouliot Annick , Delagnes Elise A. , Chang Jolie L. , Ryan William R.
Published: March 2016

Objectives/Hypothesis

To prospectively assess symptoms of obstructive sialadenitis before and after sialendoscopy‐assisted salivary duct surgery (SASDS) using the chronic obstructive sialadenitis symptoms (COSS) questionnaire to determine and predict impact of interventions.

Study Design

Prospective cohort study.

Methods

Adult patients with chronic obstructive sialadenitis who underwent SASDS were asked to complete the COSS questionnaire and the Short‐Form‐8 (SF‐8) quality‐of‐life (QOL) survey prior to surgery and 3 months postoperatively. Chronic obstructive sialadenitis symptoms surveys were scored on a scale from 0 to 100.

Results

Forty patients undergoing SASDS, including 54 glands, completed preoperative and postoperative surveys. Overall, the mean COSS score improved from 36.1 (standard error of the mean [SEM] 2.6) preoperatively to 13.5 (SEM 2.4) 3 months postoperatively (p < 0.001). Submandibular gland cases had a significant mean score reduction of 27.8 (from 38.1 to 10.3; p < 0.005). Parotid gland cases had a significant mean score reduction of 13.6 (from 32.6 to 19.0; p < 0.0001). Patients with sialolithiasis‐related sialadenitis had greater COSS score improvement after surgery than those with radioactive iodine‐ or inflammatory‐related disease. An improvement in symptoms was seen for 100% and 47% of patients with sialolithiasis and inflammatory etiologies, respectively. The pre‐ and post‐SASDS SF‐8 QOL scores were not significantly different.

Conclusions

Obstructive sialadenitis‐related symptoms significantly declined 3 months after SASDS. The COSS questionnaire was able to measure changes in sialadenitis symptoms not captured in the SF‐8 QOL survey. This is the first study to prospectively survey sialadenitis‐specific symptoms to determine impact of surgical interventions.

Level of Evidence

4. Laryngoscope, 126:1343–1348, 2016
Practice variations in voice treatment selection following vocal fold mucosal resection
Authors: Moore Jaime E. , Rathouz Paul J. , Havlena Jeffrey A. , Zhao Qianqian , Dailey Seth H. , Smith Maureen A. , Greenberg Caprice C. , Welham Nathan V.
Published: March 2016

Objectives/Hypothesis

To characterize initial voice treatment selection following vocal fold mucosal resection in a Medicare population.

Study Design

Retrospective analysis of a large, nationally representative Medicare claims database.

Methods

Patients with > 12 months of continuous Medicare coverage who underwent a leukoplakia‐ or cancer‐related vocal fold mucosal resection (index) procedure during calendar years 2004 to 2009 were studied. The primary outcome of interest was receipt of initial voice treatment (thyroplasty, vocal fold injection, or speech therapy) following the index procedure. We evaluated the cumulative incidence of each postindex treatment type, treating the other treatment types as competing risks, and further evaluated postindex treatment utilization using the proportional hazards model for the subdistribution of a competing risk. Patient age, sex, and Medicaid eligibility were used as predictors.

Results

A total of 2,041 patients underwent 2,427 index procedures during the study period. In 14% of cases, an initial voice treatment event was identified. Women were significantly less likely to receive surgical or behavioral treatment compared to men. From age 65 to 75 years, the likelihood of undergoing surgical treatment increased significantly with each 5‐year age increase; after age 75 years, the likelihood of undergoing either surgical or behavioral treatment decreased significantly every 5 years. Patients with low socioeconomic status were significantly less likely to undergo speech therapy.

Conclusion

The majority of Medicare patients do not undergo voice treatment following vocal fold mucosal resection. Further, the treatments analyzed here appear disproportionally utilized based on patient sex, age, and socioeconomic status. Additional research is needed to determine whether these observations reflect clinically explainable differences or disparities in care.

Level of Evidence

2c. Laryngoscope, 126:2505–2512, 2016
Value of septoturbinal flap in the frontal sinus drill‐out type IIb according to draf
Authors: Fiorini Francesca Romana , Nogueira Claudia , Verillaud Benjamin , Sama Anshul , Herman Philippe
Published: March 2016

Objectives/Hypothesis

The Draf IIb aims at widening the frontal sinus drainage in a minimally invasive fashion. However, this technique is associated with a high stenosis rate. Hence, local nasal flaps have been recently introduced or designed to speed up mucosal healing and prevent scarring.

Study Design

The objective of this study was to present the septoturbinal flap (STF), its use in a Draf IIb, and to examine postoperative outcomes of this procedure.

Methods

From an initial pool of 48 patients with frontal sinus disease to be treated with a Draf IIb, we prospectively selected 46 (95.84%) patients, submitted to a Draf IIb with STF in two Institutions, from November 2010 to November 2014. We excluded two cases (4.16%) for which a flap could not be performed for anatomic restrictions. We present the STF technique and describe demographic data, indication for surgery, and surgery type.

Results

Indications for surgery included 24 (52.17%) mucoceles or mucopyoceles, 12 (26.1%) chronic rhinosinusitis, four (8.7%) osteomas, two (4.35%) meningoencephaloceles, and four (8.7%) inverted papillomas. Difficult anatomic conditions were encountered in half of the patients.

Restenosis of the frontal sinus drainage pathway occurred in one (2.17%) patient. Far‐seated frontal mucoceles recurred in two cases (4.35%), with frontal drainage pathway remaining patent. Rescue treatment comprised a Draf III in two cases and one frontal sinus obliteration. Outcome was favorable for 43 (93.5%) patients.

Conclusion

The use of STF was associated with a high rate of success for a Draf IIb.

Level of Evidence

4. Laryngoscope, 126:2428–2432, 2016
Effect of vocal fold asymmetries on glottal flow
Authors: Oren Liran , Khosla Sid , Gutmark Ephraim
Published: March 2016

Objectives/Hypothesis

Voice disorders, such as unilateral vocal fold paralysis or paresis, and vocal fold scarring feature structural asymmetries of the vocal folds. Studies on how structural asymmetries affect voice has mostly been limited to computational simulations and experiments on mechanical models. The purpose of the current study is to examine the effects of asymmetries in left–right position, height, and length of the vocal folds on the intraglottal flow characteristics, as well as acoustics in the canine larynx model.

Study Design

Basic science.

Methods

Measurements of intraglottal flow velocity fields were taken in excised canine larynges using particle image velocimetry. Asymmetries of the vocal folds are induced by translating the vocal processes in space using a prong apparatus connected to a micrometer.

Results

Asymmetries in length height and abduction produced a reduction in the intraglottal vortices strength and subsequently the glottal efficiency.

Conclusion

Current findings can affect future recommendations for surgical interventions that are used to treat unilateral vocal fold paralysis.

Level of Evidence

NA Laryngoscope, 126:2534–2538, 2016
Computational vademecums for real‐time simulation of surgical cutting in haptic environments
Authors: Quesada Carlos , González David , Alfaro Iciar , Cueto Elías , Chinesta Francisco
Published: March 2016

A new method for the real‐time simulation of surgical cutting in haptic environments is presented. It is based on the intensive use of computational vademecums, that is, a sort of computational parametric meta‐model, which is computed offline and only evaluated online. Therefore, the necessary time savings are obtained, allowing for feedback responses on the order of kilohertz. Such a high‐dimensional, parametric solution of the problem is computed by employing proper generalized decomposition for the offline phase of the method, along with X‐FEM techniques for the incorporation of the discontinuities in the displacement field after cutting, in the online phase. A thorough description of the proposed method, along with examples of its performance in the simulation of corneal surgery, are provided. Copyright © 2016 John Wiley & Sons, Ltd.
Intermediate divergence levels maximize the strength of structure–sequence correlations in enzymes and viral proteins
Authors: Jackson Eleisha L. , Shahmoradi Amir , Spielman Stephanie J. , Jack Benjamin R. , Wilke Claus O.
Published: March 2016

Structural properties such as solvent accessibility and contact number predict site‐specific sequence variability in many proteins. However, the strength and significance of these structure–sequence relationships vary widely among different proteins, with absolute correlation strengths ranging from 0 to 0.8. In particular, two recent works have made contradictory observations. Yeh et al. (Mol. Biol. Evol. 31:135–139, 2014) found that both relative solvent accessibility (RSA) and weighted contact number (WCN) are good predictors of sitewise evolutionary rate in enzymes, with WCN clearly out‐performing RSA. Shahmoradi et al. (J. Mol. Evol. 79:130–142, 2014) considered these same predictors (as well as others) in viral proteins and found much weaker correlations and no clear advantage of WCN over RSA. Because these two studies had substantial methodological differences, however, a direct comparison of their results is not possible. Here, we reanalyze the datasets of the two studies with one uniform analysis pipeline, and we find that many apparent discrepancies between the two analyses can be attributed to the extent of sequence divergence in individual alignments. Specifically, the alignments of the enzyme dataset are much more diverged than those of the virus dataset, and proteins with higher divergence exhibit, on average, stronger structure–sequence correlations. However, the highest structure–sequence correlations are observed at intermediate divergence levels, where both highly conserved and highly variable sites are present in the same alignment.
Biodiversity, ecosystem functioning, and classical biological control
Authors: Evans Edward W.
Published: March 2016

Increasing concern over worldwide loss of biodiversity has led ecologists to focus intently on how ecosystem functioning may depend on diversity. In applied entomology, there is longstanding interest in the issue, especially as regards the importance of natural enemy diversity for pest control. Here I review parallels in interest, conceptual framework, and conclusions concerning biodiversity as it affects ecosystem functioning in general and classical biological control in particular. Whereas the former focuses on implications of loss of diversity, the latter focuses on implications of increase in diversity as additional species of natural enemies are introduced to novel communities in new geographic regions for insect pest and weed control. Many field studies now demonstrate that ecosystem functioning, e.g., as reflected in primary productivity, is enhanced and stabilized over time by high diversity as the community increases in its efficiency in exploiting available resources. Similarly, there is growing field support for the generalization that increasing species and functional diversity of natural enemies leads to increasing pest suppression. Nonetheless a central concern of classical biological control in particular, as it seeks to minimize non-target effects, remains as to whether one or a few species of natural enemies can provide sufficient pest control.