bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analgesic Effects of Hydromorphone versus Buprenorphine in Buprenorphine-maintained Individuals
Authors: Huhn Andrew S. , Strain Eric C. , Bigelow George E. , Smith Michael T. , Edwards Robert R. , Tompkins D. Andrew 
Published: November 2018

Abstract

EDITOR’S PERSPECTIVE

What We Already Know about This Topic
The prevalence of patients prescribed buprenorphine for treatment of opioid use disorder is increasing
Managing acute pain in buprenorphine-maintained individuals can be challenging

What This Article Tells Us That Is New
Large doses of intravenous hydromorphone can provide analgesia in buprenorphine-maintained individuals
However, the use of hydromorphone for analgesia in buprenorphine-maintained individuals confers greater abuse liability and side effects than does supplemental intravenous buprenorphine

Background
Managing acute pain in buprenorphine-maintained individuals in emergency or perioperative settings is a significant challenge. This study compared analgesic and abuse liability effects of adjunct hydromorphone and buprenorphine using quantitative sensory testing, a model of acute clinical pain, in persons maintained on 12 to 16 mg sublingual buprenorphine/naloxone.

Methods
Participants (N = 13) were enrolled in a randomized within-subject, double-blind, placebo-controlled three-session experiment. Each session used a cumulative dosing design with four IV injections (4, 4, 8, and 16 mg of hydromorphone or 4, 4, 8, and 16 mg of buprenorphine); quantitative sensory testing and abuse liability assessments were measured at baseline and after each injection. The primary analgesia outcome was change from baseline cold pressor testing; secondary outcomes included thermal and pressure pain testing, as well as subjective drug effects and adverse events.

Results
A significant two-way interaction between study drug condition and dose was exhibited in cold pressor threshold (F10,110 = 2.14, P = 0.027) and tolerance (F10,110 = 2.69, P = 0.006). Compared to after placebo, participants displayed increased cold pressor threshold from baseline after cumulative doses of 32 mg of IV hydromorphone (means ± SD) (10 ± 14 s, P = 0.035) and 32 mg of buprenorphine (3 ± 5 s, P = 0.0.39) and in cold pressor tolerance after cumulative doses of 16 mg (18 ± 24 s, P = 0.018) and 32 mg (48 ± 73 s, P = 0.041) IV hydromorphone; cold pressor tolerance scores were not significant for 16 mg (1 ± 15 s, P = 0.619) or 32 mg (7 ± 16 s, P = 0.066) buprenorphine. Hydromorphone and buprenorphine compared with placebo showed greater ratings on subjective measures of high, any drug effects, good effects, and drug liking. Adverse events were more frequent during the hydromorphone compared with buprenorphine and placebo conditions for nausea, pruritus, sedation, and vomiting.

Conclusions
In this acute clinical pain model, high doses of IV hydromorphone (16 to 32 mg) were most effective in achieving analgesia but also displayed higher abuse liability and more frequent adverse events. Cold pressor testing was the most consistent measure of opioid-related analgesia.
Contribution of Baroreceptor Function to Pain Perception and Perioperative Outcomes
Authors: Suarez-Roca Heberto , Klinger Rebecca Y. , Podgoreanu Mihai V. , Ji Ru-Rong , Sigurdsson Martin I. , Waldron Nathan , Mathew Joseph P. , Maixner William 
Published: November 2018

Abstract
Baroreceptors are mechanosensitive elements of the peripheral nervous system that maintain homeostasis by coordinating physiologic responses to external and internal stimuli. While it is recognized that carotid and cardiopulmonary baroreceptor reflexes modulate autonomic output to mitigate excessive fluctuations in arterial blood pressure and to maintain intravascular volume, increasing evidence suggests that baroreflex pathways also project to key regions of the central nervous system that regulate somatosensory, somatomotor, and central nervous system arousal. In addition to maintaining autonomic homeostasis, baroreceptor activity modulates the perception of pain, as well as neuroimmune, neuroendocrine, and cognitive responses to physical and psychologic stressors. This review summarizes the role that baroreceptor pathways play in modulating acute and chronic pain perception. The contribution of baroreceptor function to postoperative outcomes is also presented. Finally, methods that enhance baroreceptor function, which hold promise in improving postoperative and pain management outcomes, are presented.
Excess Mortality Among Adults Hospitalized With Traumatic Brain Injury in Australia: A Population-Based Matched Cohort Study
Authors: Lystad Reidar P. , Cameron Cate M. , Mitchell Rebecca J. 
Published: November 2018

Objective:
To quantify and describe excess mortality attributable to traumatic brain injury (TBI) during the 12 months after hospitalization.

Design:
Population-based matched cohort study using linked hospital and mortality data.

Setting:
Australia.

Participants:
Individuals 18 years and older who were hospitalized with a principal diagnosis of TBI in 2009 (n = 6929) and matched noninjured individuals randomly selected from the electoral roll (n = 6929).

Main Measures:
Survival distributions were compared using a Kaplan-Meier plot with a log-rank test. Mortality rate ratios (MRRs) were computed using Cox proportional hazard regression with and without controlling for demographic characteristics and preexisting health status.

Results:
Individuals with TBI experienced significantly worse survival during the 12 months after hospitalization (χ2 = 640.9, df = 1, P < .001), and were more than 7.5 times more likely to die compared with their noninjured counterparts (adjusted MRR, 7.76; 95% confidence interval, 6.07–9.93). TBI was likely to be a contributory factor in 87% of deaths in the TBI cohort. Excess mortality was higher among males, younger age groups, and those with more severe TBI.

Conclusion:
Excess mortality is high among individuals hospitalized with TBI and most deaths are attributable to the TBI. Increased primary and secondary preventive efforts are warranted to reduce the mortality burden of TBI.
Clinical Magnetic Resonance Imaging of the Knee at 7 T
Authors: Wyss Michael , Manoliu Andrei , Marcon Magda , Spinner Georg , Luechinger Roger , Pruessmann Klaas P. , Andreisek Gustav 
Published: November 2018

Purpose
The aim of this study was to evaluate the efficiency and performance of different fat suppression techniques for clinical 7 T knee magnetic resonance imaging including the slice-selective gradient reversal (SSGR) technique.

Materials and Methods
This article is an ethical board–approved prospective study with written informed consent from 8 volunteers (mean, 31 ± 4 years). It included fat phantom and knee magnetic resonance imaging at 3 T (Magnetom Skyra; Siemens Healthcare) and at 7 T (Achieva, Philips Healthcare). At 3 T, an axial proton density-weighted turbo spin echo sequence with spectral adiabatic inversion recovery (SPAIR) was acquired. At 7 T, a series of 5 proton density-weighted turbo spin echo sequences was acquired: (a) without fat suppression, (b) with spectral presaturation with inversion recovery (SPIR), (c) with SPAIR, (d) with SSGR, and (e) with the combination of SSGR + SPIR. Additional noise scans allowed pixelwise calculation of signal-to-noise ratio and contrast-to-noise ratio maps. Quantitative data at 7 T were compared with each other but not to 3 T. Two independent radiologists evaluated overall image quality, homogeneity and grade of fat suppression, and the delineation between 2 adjacent structures. Results were compared using Wilcoxon signed rank and paired sample t tests.

Results
Relative signal-to-noise ratios of fat demonstrated that the SPIR technique reduced the fat signal to 45% ± 5.4%; SPAIR, 18% ± 1.2%; SSGR, 14% ± 1.1%; and SSGR + SPIR, 11% ± 0.3%. Contrast-to-noise ratio showed superior contrast between muscle-fat (P < 0.001) and fluid-fat (P ≤ 0.001) for SSGR and SSGR + SPIR. The radiologists rated the overall image quality higher at 7 T than 3 T. The homogeneity and grade of fat suppression as well as the delineation between 2 different (adjacent) structures were rated best for SSGR + SPIR.

Conclusions
At 7 T, fat saturation for clinical knee imaging using SSGR and the combination of SSGR + SPIR was superior compared with standard methods based on spectrally selective radiofrequency pulses.
Association of MRI T2 Signal Intensity With Desmoid Tumor Progression During Active Observation
Authors: Cassidy Michael R. , Lefkowitz Robert A. , Long Niamh , Qin Li-Xuan , Kirane Amanda , Sbaity Eman , Hameed Meera , Coit Daniel G. , Brennan Murray F. , Singer Samuel , Crago Aimeé M. 
Published: November 2018

Objective:The aim of this study was to identify predictors of desmoid progression during observation.Summary of Background Data:Untreated desmoids can grow, remain stable, or regress, but reliable predictors of behavior have not been identified.Methods:Primary or recurrent desmoid patients were identified retrospectively from an institutional database. In those managed with active observation who underwent serial magnetic resonance imaging (MRIs) with T2-weighted sequences, baseline tumor size was recorded, and 2 radiologists independently estimated the percentage of tumor volume showing hyperintense T2 signal at baseline. Associations of clinical or radiographic characteristics with progression-free survival (PFS; by RECIST) were evaluated by Cox regression and Kaplan-Meier statistics.Results:Among 160 patients with desmoids, 72 were managed with observation, and 37 of these had serial MRI available for review. Among these 37 patients, median age was 35 years and median tumor size was 4.7 cm; all tumors were extra-abdominal (41% in abdominal wall). Although PFS was not associated with size, site, or age, it was strongly associated with hyperintense T2 signal in ≥90% versus <90% of baseline tumor volume (as defined by the “test” radiologist; hazard ratio = 11.3,P= 0.003). For patients in the ≥90% group (n = 20), 1-year PFS was 55%, compared with 94% in the <90% group (n = 17). The percentage of baseline tumor volume with hyperintense T2 signal defined by a validation radiologist correlated with results of the test radiologist (ρ = 0.75).Conclusion:The percent tumor volume characterized by hyperintense T2 signal is associated with desmoid progression during observation and may help distinguish patients who would benefit from early intervention from those who may be reliably observed.
Pretransplant Cancer in Kidney Recipients in Relation to Recurrent and De Novo Cancer Incidence Posttransplantation and Implications for Graft and Patient Survival
Authors: Unterrainer Christian , Opelz Gerhard , Döhler Bernd , Süsal Caner 
Published: November 2018

Background.
Whether kidney transplant recipients who were treated for a malignant tumor before transplantation are at an increased risk of developing a tumor posttransplantation has not been adequately quantified and characterized.

Methods.
We studied more than 270 000 patients on whom pretransplant and posttransplant malignancy data were reported to the Collaborative Transplant Study. More than 4000 of these patients were treated for pretransplant malignancy. The posttransplant tumor incidence in these patients was compared to that in recipients without a pretransplant tumor. Cox regression, considering multiple confounders, was applied.

Results.
Significant increases in posttransplant tumor incidence with hazard ratio ranging from 2.10 to 5.47 (all P < 0.001) were observed for tumors in the site-specific pretransplant locations, suggesting tumor recurrences. There were also significantly increased de novo tumors in new locations with hazard ratio ranging from 1.28 to 1.89. Pretransplant basal cell carcinoma of the skin and male genital cancer were associated with significantly increased death-censored graft survival, suggesting impaired immune responsiveness against transplanted kidneys. Time interval from pretransplant tumor occurrence to transplantation and posttransplant mammalian target of rapamycin inhibitor treatment was not found to be of significant relevance in this study.

Conclusions.
Patients who experienced a pretransplant tumor are at significant risk of tumor recurrence, regardless of the length of interval between tumor treatment and transplantation. There is also some increased risk for de novo tumors, suggesting impaired immune surveillance. Impaired tumor immunity appears to extend to a lower rate of transplant rejection because patients with pretransplant tumors tended to show improved death-censored graft survival.
Red muscle activity in bluegill sunfishLepomis macrochirusduring forward accelerations
Authors: Schwalbe Margot A. B. , Boden Alexandra L. , Wise Tyler N. , Tytell Eric D. 
Published: November 2018

AbstractFishes generate force to swim by activating muscles on either side of their flexible bodies. To accelerate, they must produce higher muscle forces, which leads to higher reaction forces back on their bodies from the environment. If their bodies are too flexible, the forces during acceleration cannot be transmitted effectively to the environment. Here, we investigate whether fish can use their red muscle to stiffen their bodies during acceleration. We used high-speed video, electromyographic recordings, and a new digital inertial measurement unit to quantify body kinematics, red muscle activity, and 3D orientation and centre of mass acceleration during forward accelerations and steady swimming over several speeds. During acceleration, fish co-activated anterior muscle on the left and right side, and activated all muscle sooner and kept it active for a larger fraction of the tail beat cycle. These activity patterns are consistent with our hypothesis that fish use their red muscle to stiffen their bodies during acceleration. We suggest that during impulsive movements, flexible organisms like fishes can use their muscles not only to generate propulsive power but to tune the effective mechanical properties of their bodies, increasing performance during rapid movements and maintaining flexibility for slow, steady movements.
The discovery of three new hare lagoviruses reveals unexplored viral diversity in this genus
Authors: Mahar Jackie E. , Hall Robyn N. , Shi Mang , Mourant Roslyn , Huang Nina , Strive Tanja , Holmes Edward C. 
Published: November 2018

AbstractOur knowledge of mammalian viruses has been strongly skewed toward those that cause disease in humans and animals. However, recent metagenomic studies indicate that most apparently healthy organisms carry viruses, and that these seemingly benign viruses may comprise the bulk of virus diversity. The bias toward studying viruses associated with overt disease is apparent in the lagoviruses (familyCaliciviridae) that infect rabbits and hares: although most attention has been directed toward the highly pathogenic members of this genus - the rabbit haemorrhagic disease virus and European brown hare syndrome virus - a number of benign lagoviruses have also been identified. To determine whether wild European brown hares in Australia might also carry undetected benign viruses, we used a meta-transcriptomics approach to explore the gut and liver RNA viromes of these invasive animals. This led to the discovery of three new lagoviruses. While one of the three viruses was only detected in a single hare, the other two viruses were detected in 20% of all hares tested. All three viruses were most closely related to other hare lagoviruses, but were highly distinct from both known viruses and each other. We also found evidence for complex recombination events in these viruses, which, combined with their phylogenetic distribution, suggests that there is likely extensive unsampled diversity in this genus. Additional metagenomic studies of hares and other species are clearly needed to fill gaps in the lagovirus phylogeny and hence better understand the evolutionary history of this important group of mammalian viruses.
Dynamics of age-related catastrophic mitotic failures and recovery in yeast
Authors: Crane Matthew M. , Russell Adam E. , Schafer Brent J. , Hong Mung Gi , Goings Joslyn E. , Chen Kenneth L. , Blue Ben W. , Kaeberlein Matt 
Published: November 2018

AbstractGenome instability is a hallmark of aging and contributes to age-related disorders such as progeria, cancer, and Alzheimer’s disease. In particular, nuclear quality control mechanisms and cell cycle checkpoints have generally been studied in young cells and animals where they function optimally, and where genomic instability is low. Here, we use single cell imaging to study the consequences of increased genomic instability during aging, and identify striking age-associated genome missegregation events. During these events the majority of mother cell chromatin, and often both spindle poles, are mistakenly sent to the daughter cell. This breakdown in mitotic fidelity is accompanied by a transient cell cycle arrest that can persist for many hours, as cells engage a retrograde transport mechanism to return chromosomes to the mother cell. The repetitive ribosomal DNA (rDNA) has been previously identified as being highly vulnerable to age-related replication stress and genomic instability, and we present several lines of evidence supporting a model whereby expansion of rDNA during aging results in nucleolar breakdown and competition for limited nucleosomes, thereby increasing risk of catastrophic genome missegregation.
Chromosome-wide evolution and sex determination in a nematode with three sexes
Authors: Tandonnet Sophie , Koutsovoulos Georgios D. , Adams Sally , Cloarec Delphine , Parihar Manish , Blaxter Mark L. , Pires-daSilva Andre 
Published: November 2018

AbstractThe free-living nematode Auanema rhodensis is a rare example of a species with three sexes, in which males, females and hermaphrodites coexist. A. rhodensis males have only one X chromosome (XO), whereas females and hermaphrodites have two (XX). The A. rhodensis X chromosome is unusual: it does not recombine in hermaphrodites and is transmitted from father to son. The mechanism that controls the production of females versus hermaphrodites is unknown but is dependent on maternal and larval environmental factors. Here we report the genome sequence and genetic map of A. rhodensis, placing over 95% of the sequence in seven linkage groups. Comparison of the seven A. rhodensis chromosomes to chromosomal assemblies of Caenorhabditis elegans and three other rhabditine nematodes identified deeply conserved linkage groups we call Nigon units, some of which have been maintained in all species analysed. Others have undergone breakage and fusion, and the A. rhodensis karyotype is the product of a unique set of rearrangements involving three Nigon units. The A. rhodensis X chromosome is much smaller than the autosomes, is less gene dense and is 3 to 4 times more polymorphic, reflecting its unique transmission history. Differential expression analyses comparing females and hermaphrodites, identified several candidate genes, including orthologues of C. elegans gld-1, tra-1 and dmd-10/11, that are potentially involved in the female-hermaphrodite sexual decision.
Memory trace superimposition impairs recall in a mouse model of AD
Authors: Poll Stefanie , Schmid Lena C. , Steffen Julia , Wagner Jens , Schmidt Boris , Jackson Walker S. , Schoch Susanne , Ehninger Dan , Fuhrmann Martin 
Published: November 2018

SummaryLearning and memory processes depend on the hippocampus and are impaired in Alzheimer’s disease (AD). Active neuronal ensembles form an engram by encoding information during learning. Their reactivation is required for memory recall. However, it remains unresolved whether the engram in CA1 principal neurons is impaired under AD-like conditions. We used two-photon in vivo imaging to visualize the expression of the immediate early gene c-fos within CA1 neurons during contextual fear conditioning and retrieval. Surprisingly, we identified engrams in wild-type mice and in the mouse model of AD indicating intact memory formation. However, under AD-like conditions engrams were superimposed by a high number of newly recruited fosGFP+ neurons during memory recall. This superimposition resembled the network configuration of wild-type mice exposed to a novel context. Artificial superimposition of the memory trace during recall in wild-type mice was sufficient to induce memory impairment. Thus, we propose superimposition of the CA1 memory trace as a mechanism for memory impairment in a mouse model of AD.HighlightsDecreased fosGFP expression in direct vicinity to amyloid-β plaquesIntact engram in CA1 of APP/PS1 miceImpurity of the retrieval network in CA1 is sufficient to impair memory recallPoll et al. present a novel mechanism for memory impairment in a mouse model of AD. The potential memory trace was found intact in the CA1 region of the hippocampus. However, excessive neuronal activity during retrieval, was superimposing the memory trace in a mouse model of AD.
Meiotic MCM proteins promote and inhibit crossovers during meiotic recombination
Authors: Hartmann Michaelyn , Kohl Kathryn P. , Sekelsky Jeff , Hatkevich Talia 
Published: November 2018

AbstractCrossover formation as a result of meiotic recombination is vital for proper segregation of homologous chromosomes at the end of meiosis I. In many organisms, crossovers are generated through two crossover pathways: Class I and Class II. To ensure accurate crossover formation, meiosis-specific protein complexes regulate the degree in which each pathway is used. One such complex is the mei-MCM complex, which contains MCM (mini-chromosome maintenance) and MCM-like proteins REC (ortholog of Mcm8), MEI-217, and MEI-218, collectively called the mei-MCM complex. The mei-MCM complex genetically promotes Class I crossovers and inhibits Class II crossovers inDrosophila, but it is unclear how individual mei-MCM proteins contribute to crossover regulation. In this study, we perform genetic analyses to understand how specific regions and motifs of mei-MCM proteins contribute to Class I and II crossover formation and distribution. Our analyses show that the long, disordered N-terminus of MEI-218 is dispensable for crossover formation, and that mutations that disrupt REC’s Walker A and B motifs differentially affect Class I and Class II crossover formation. In Rec Walker A mutants, Class I crossovers exhibit no change, but Class II crossovers are increased. However, inrecWalker B mutants, Class I crossovers are severely impaired, and Class II crossovers are increased. These results suggest that REC may form multiple complexes that exhibit differential REC-dependent ATP binding and hydrolyzing requirements. These results provide genetic insight into the mechanisms through which mei-MCM proteins promote Class I crossovers and inhibit Class II crossovers.
Tamoxifen improves glucose tolerance in a delivery, sex, and strain-dependent manner in mice
Authors: Ceasrine Alexis M. , Lin Eugene E. , Lumelsky David N. , Ruiz-Otero Nelmari , Boehm Erica D. , Kuruvilla Rejji 
Published: November 2018

ABSTRACTTamoxifen, a selective estrogen receptor modulator, is widely used in mouse models to temporally control gene expression but is also known to affect body composition. Here, we report that tamoxifen has significant and sustained effects on glucose tolerance, independent of effects on insulin sensitivity, in mice. Intraperitoneal, but not oral, tamoxifen delivery improved glucose tolerance in three inbred mouse strains. The extent and persistence of tamoxifen-induced effects were sex- and strain-dependent. These findings highlight the need to revise commonly used tamoxifen-based protocols for gene manipulation in mice by including longer chase periods following injection, oral delivery, and the use of tamoxifen-treated littermate controls.