bluuebunny/crossref_metadata_2025 huggingface dataset:
Spontaneous Hemorrhage Precipitated by an Emotional Stress Drug in Anticoagulant-Treated Rats
Authors: Lucas O. N , Jaques L. B
Published: June 2018

L.S.D. was used as an emotional stress agent in rats in an attempt to evaluate the influence of the central nervous system in triggering spontaneous hemorrhage in rats treated with anticoagulants. L.A. was used to evaluate whether the hemorrhagic activity of L.S.D. was through the pituitary-adrenal axis. A high percentage of spontaneous hemorrhage was found when the emotional stress agent was combined with the anticoagulant. There was no mortality or hemorrhagic manifestation with anticoagulant alone or in the groups where the treatments were given alone as a control.
Das »Stauungsthromhelastogramm« (Klinische und experimentelle Bedeutung)
Authors: Stacher A
Published: June 2018

1. Es wird die Halbwertszeitberechnung der fallenden Amplitude des TEG als Maß für die Thrombolyse eingeführt. Beim normalen TEG beträgt die Halbwertszeit der Thrombolyse (LA/2) im Mittel 12 Stunden, mit einem Maximum von 17 Stunden und einem Minimum von 6 Stunden.

2. Durch Hypoxie infolge Stauung eines Armes kommt es zu Veränderungen des TEG, die von Stauungsdruck und -zeit abhängig sind. Um reproduzierbare Werte zu erlangen, beträgt die günstigste Stauungszeit 30 Minuten bei einem Druck von 80 mm Hg.

3. Das TEG nach 30 Minuten Stauung mit einem Druck von 80 mm Hg wird als »Stauungsthrombelastogramm« (St-TEG) bezeichnet. Normalerweise beträgt seine globale Gerinnungskonstante »r + k« 14 min 15 sec im Mittel (Streuung von 12–16 Minuten). Die maximale Amplitude ist geringer als beim Normal-TEG. Sie beträgt im Mittel 51 mm mit einer Streuung von 47–60 mm.

4. Die fibrinolytische Potenz findet beim St-TEG ihren Ausdruck in der Abnahme der Halbwertszeit in Prozenten gegenüber dem Normal-TEG. Eine Abnahme um mehr als 75% entspricht einer erhöhten, eine Abnahme um weniger als 18% des Ausgangswertes oder gar eine Zunahme einer verminderten fibrinolytischen Potenz.

5. Bei Untersuchungen von Patienten mit Thrombopenien, Leberzirrhosen, Blutungen aus dem Urogenitaltrakt, verschiedenen Karzinomen, einer Hämophilie A und bei Patienten unter Heparintherapie fand sich im St-TEG häufig eine erhöhte, bei Thrombosen, Fällen unter Marcoumar- und Kortikoidbehand-lung überwiegend eine verminderte fibrinolytische Potenz.

6. Es wurde die Wirkung von ε - Amino capronsäure, ρ - Aminomethylcy cio -hexancarbonsäure (Amicapron) und Trypsininhibitor (Trasylol) auf die Halbwertszeit im St-TEG untersucht. Sie war ausnahmslos verlängert. Bei Gabe von Stryphnon wurde sie immer verkürzt, während Premarin keine einheitlichen Werte ergab.

7. Vergleichende Untersuchungen von Blutbild, Thrombozyten, Fibrinogen ergaben einen leichten Anstieg der Werte, aber keine eindeutige Erklärung für das Auftreten der lytischen Aktivität. Vergleiche zwischen der Abnahme der La/2 nach der Stauung und dem Landis-Test ergaben keine Korrelation. Daraus, aus früheren und laufenden Untersuchungen wird geschlossen, daß die Aktivität eines Plasminogenaktivators nicht unmittelbar die Gefäßpermeabilität steigert.

8. Die sich aus dem Vorstehenden ergebenden diagnostischen Schlüsse und experimentellen Möglichkeiten des St auungsthr o mb elast ogr amm s (St-TEG) werden besprochen.
The Ullrastructure of Platelet Participation in Hemostasis
Authors: Johnson Shirley A. , Balboa Ronaldo S. , Pederson Harlan J. , Buckley Monica
Published: June 2018

The ultrastructure of platelet aggregation in vivo in response to bleeding brought about by transection of small mesenteric vessels in rats and guinea pigs has been studied. Platelets aggregate, degranulate and separating membranes disappear in parallel with fibrin appearance which is first seen at several loci after 30 seconds of bleeding. About 40 per cent of the electron opaque granules, some of which contain platelet factor 3 have disappeared after one minute of bleeding while the electron lucent granules increase by 70 per cent suggesting that some of them may be empty vesicles. Most of the platelet aggregates of the random type disappear leaving clumped red blood cells entrapped by a network of fibrin fibers which emanate from the remains of platelet aggregates of the rosette type to maintain hemostasis.
Enzymatic Characteristics of In-Vitro Incorporation of P32 Orthophosphate into Human Platelet Phosphatide
Authors: Grossman C. M , Kohn R
Published: June 2018

The incorporation of P32 orthophosphate into phosphatide by isolated human platelets in an artificial medium was studied. The addition of homologous plasma increased the incorporation and the formation of labelled phosphatide was significantly reduced in the absence of oxygen or in the presence of cyanide, and by varying the pH from 7.4 to 5.6 and 8.6. The enzymatic character of the incorporation and the role of platelet respiration are briefly discussed.
The Value of a Specialized Program for the Management of Oral Anticoagulation
Authors: Ansell Jack
Published: June 2018

Oral anticoagulation has proven to be an effective and useful therapy for over 50 years for patients at risk for thromboembolism, but recent evidence suggests that many patients are not only poorly managed, but therapy is withheld from a significant number of individuals because of the fear of complications and the labor intensiveness of treatment.

Over the last decade several developments have occurred that may increase and improve the use of oral anticoagulation by effectively lowering the risk/benefit profile. Among these have been the standardization of the prothrombin time using the International Normalized Ratio leading to more appropriate and standardized therapy, and a number of consensus conferences in the United States and throughout the world focusing on indications for anticoagulation. Less has occurred in a coordinated fashion to substantially improve the management of oral anticoagulation until very recently. There is now accumulating evidence showing that a coordinated and focused approach to the management of therapy by specialized programs significantly improves clinical outcomes by improving therapeutic control, lessening the frequency of hemorrhage or thrombosis and decreasing the use of medical resources leading to more cost-effective therapy. Furthermore, with the development of new technologies for the measurement of prothrombin times (capillary whole blood PTs or point-of-care testing) allows for novel models of management including patient self-testing and patient self-management. These latter concepts are beginning to be popularized in several regions, especially Germany, Canada and the United States.

The focus of the presentation will be to comment on the barriers to more effective and widespread use of anticoagulation and to summarize advances in the management of therapy including the concept of anticoagulation management services, patient self-testing and patient self-management.
Rekombinantes Hirudin zur weiteren Antikoagulation bei Patienten mit Heparin-induzierter Thrombozytopenie
Authors: Greinacher A
Published: June 2018

Hirudin ist ein spezifischer Thrombininhibitor, der unabhängig von Kofaktoren wie Antithrombin und Heparin-Kofaktor II wirkt. Im Gegensatz zu Heparin wird r-Hirudin durch PF4 nicht inaktiviert. Hirudin bewirkt auch eine Hemmung von Thrombus-gebundenem Thrombin und von an Fibrinabbauprodukte gebundenem Thrombin, das vor einer Hemmung durch Heparin geschützt ist. Bei der Heparin-induzierten Thrombozytopenie (HIT) führt eine verstärkte Iη-vivo-Thrombozyten-aktivierung zur Freisetzung großer Mengen von PF4 und zur exzessiven Thrombinbildung. Betroffene Patienten müssen weiter parenteral antikoaguliert werden. Zur Beurteilung des klinischen Potentials von Hirudin bei dieser Indikation führten wir zwei prospektive Multizenterstudien mit 82 und 112 Patienten durch. In diesen Studien ermöglichte das Hirudin Lepirudin eine effektive parenterale Antikoagulation von HIT-Patienten. Durch Lepirudin kann die Inzidenz schwerwiegender Folgen der HIT reduziert werden. Blutungskomplikationen und die Induktion von Anti-Hirudin-Antikörper sind die wichtigsten unerwünschten Wirkungen der Therapie mit Hirudin.
Immunantwort auf rekombinantes Hirudin
Authors: Hoffmann Ursula , Song X. H. , Heene D. L. , Harenberg J. , Huhle G.
Published: June 2018

Rekombinantes Hirudin ist ein potentes, spezifisches Antithrombin-Agens, das in Hefezellen exprimiert wird. Die verschiedenen rekombinanten Hirudine befinden sich nun in der klinischen Prüfung bezüglich einer Anzahl von Indikationen. Die Ergebnisse vorliegender Studien versprechen eine hohe Effektivität und Sicherheit in der Vorbeugung von tiefen Beinvenenthrombosen und Lungenembolien bei Patienten mit elektiver Hüftchirurgie, bei Patienten mit akutem Myokardinfarkt, akutem koronaren Syndrom und der instabilen Angina mit nachfolgender Angioplastie. In diesen Studien waren unter der Therapie mit rekombinantem Hirudin allergische Reaktionen nicht aufgetreten. Rekombinantes Hirudin wurde ebenfalls hinsichtlich seiner Effektivität und Sicherheit bei Patienten mit heparin-induzierter Thrombozytopenie Typ II untersucht. Hier zeigte sich eine Inzidenz von Heparin-Antikörpern in bis zu 50% aller mit Hirudin langzeitbehandelten Patienten. Eine Immunantwort gegen rekombinantes Hirudin konnte ebenfalls in Tierversuchen zur Herstellung von monoklonalen Hirudinantikörpern produziert werden. Die vorliegenden Daten zeigen, daß die Hirudinantikörper teils hirudin-neutralisierende, teils halbwertszeitverlängernde Eigenschaften aufweisen. Die biologische Relevanz der Hirudin-Antikörper bleibt weiteren Studien vorbehalten.
Pharmacological Properties of Abciximab
Authors: Nakada Marian , Mascelli Mary Ann
Published: June 2018

Abciximab is the first of a new class of therapeutic agents that specifically block the function of the platelet cell adhesion receptor, glycoprotein (GP) IIb/IIIa and the subsequent platelet aggregation that contributes to thrombosis. Abciximab displays high avidity for the GPIIb/IIIa receptor, which results in a prolonged platelet-bound half-life, and a sustained duration of platelet inhibition resulting from the redistribution and equilibration of abciximab molecules among circulating platelets at gradually diminishing levels of GPIIb/IIIa receptor occupancy. In contrast to its extended platelet bound life-span, unbound abciximab is cleared rapidly (half-life <10 min) after an intravenous bolus dose. Nevertheless, a subsequent continuous infusion that maintains relatively low concentrations of free abciximab (50 to 100 ng/ml) sustains the pharmacologic GPIIb/IIIa receptor blockade throughout the duration of treatment. In addition, abciximab also interacts with other potentially important biological targets. The agent binds with equal affinity to the other β3 containing integrin, the vitronectin (αvβ3) receptor, and more weakly to the leukocyte Mac-1 receptor. The high avidity and multi-receptor specificity of abciximab are consistent both short- and long-term therapeutic benefits in patients with acute coronary syndromes.
Research on the wireless power transmission technology based on maximum energy efficiency tracking under dynamic distance
Authors: Zhuang Peihong , Yang Yan , Yu Zhiyuan , Hou Jing , Gao Tian
Published: June 2018

Focusing on the maximum efficiency of magnetic resonant coupling wireless power transmission, this paper analyzes circuits by use of lumped parameter models, deduces the relationship between the maximum energy efficiency and the duty cycle of the inverter at the transmitting terminal, and proposes a self-adaptive control technique to ensure that the wireless power transmission system maintains the maximum energy efficiency when the transmission distance changes; the effectiveness and feasibility of this method is verified with a hardware platform.
Inhomogeneous initial-boundary value problem for the 2D nonlinear Schrödinger equation
Authors: Kaikina Elena I.
Published: June 2018

We consider the inhomogeneous Dirichlet initial-boundary value problem for the nonlinear multidimensional Schrödinger equation, formulated on an upper right-quarter plane. We study traditionally important problems of the theory of nonlinear partial differential equations, such as global in time existence of solutions to the initial-boundary value problem and the asymptotic behavior of solutions for large time. Also we are interested in the study of the influence of the Dirichlet boundary data on the asymptotic behavior of solutions. Our approach to get well-posedness of nonlinear problems is based on studying a linear theory and then using the fixed point argument. To get a linear theory for the multidimensional model, we proposed a general method based on the Riemann–Hilbert approach and theory Cauchy type integral equations. To get smooth solutions in L∞, we modify a method based on the factorization for the free Schrödinger evolution group.
Protein phosphatase 2A is crucial for sarcomere organization inCaenorhabditis elegansstriated muscle
Authors: Qadota Hiroshi , Matsunaga Yohei , Bagchi Pritha , Lange Karen I. , Carrier Karma J. , Pols William Vander , Swartzbaugh Emily , Wilson Kristy J. , Srayko Martin , Pallas David C. , Benian Guy M.
Published: June 2018

Protein phosphatase 2A (PP2A) is a heterotrimer composed of single catalytic and scaffolding subunits and one of several possible regulatory subunits. We identified PPTR-2, a regulatory subunit of PP2A, as a binding partner for the giant muscle protein UNC-89 (obscurin) in Caenorhabditis elegans. PPTR-2 is required for sarcomere organization when its paralogue, PPTR-1, is deficient. PPTR-2 localizes to the sarcomere at dense bodies and M-lines, colocalizing with UNC-89 at M-lines. PP2A components in C. elegans include one catalytic subunit LET-92, one scaffolding subunit (PAA-1), and five regulatory subunits (SUR-6, PPTR-1, PPTR-2, RSA-1, and CASH-1). In adult muscle, loss of function in any of these subunits results in sarcomere disorganization. rsa-1 mutants show an interesting phenotype: one of the two myosin heavy chains, MHC A, localizes as closely spaced double lines rather than single lines. This “double line” phenotype is found in rare missense mutants of the head domain of MHC B myosin, such as unc-54(s74). Analysis of phosphoproteins in the unc-54(s74) mutant revealed two additional phosphoserines in the nonhelical tailpiece of MHC A. Antibodies localize PPTR-1, PAA-1, and SUR-6 to I-bands and RSA-1 to M-lines and I-bands. Therefore, PP2A localizes to sarcomeres and functions in the assembly or maintenance of sarcomeres.
Hybrid correction of highly noisy long reads using a variable-order de Bruijn graph
Authors: Morisse Pierre , Lecroq Thierry , Lefebvre Arnaud
Published: June 2018

Motivation

The recent rise of long read sequencing technologies such as Pacific Biosciences and Oxford Nanopore allows to solve assembly problems for larger and more complex genomes than what allowed short reads technologies. However, these long reads are very noisy, reaching an error rate of around 10–15% for Pacific Biosciences, and up to 30% for Oxford Nanopore. The error correction problem has been tackled by either self-correcting the long reads, or using complementary short reads in a hybrid approach. However, even though sequencing technologies promise to lower the error rate of the long reads below 10%, it is still higher in practice, and correcting such noisy long reads remains an issue.

Results

We present HG-CoLoR, a hybrid error correction method that focuses on a seed-and-extend approach based on the alignment of the short reads to the long reads, followed by the traversal of a variable-order de Bruijn graph, built from the short reads. Our experiments show that HG-CoLoR manages to efficiently correct highly noisy long reads that display an error rate as high as 44%. When compared to other state-of-the-art long read error correction methods, our experiments also show that HG-CoLoR provides the best trade-off between runtime and quality of the results, and is the only method able to efficiently scale to eukaryotic genomes.

Availability and implementation

HG-CoLoR is implemented is C++, supported on Linux platforms and freely available at https://github.com/morispi/HG-CoLoR.

Supplementary information

Supplementary data are available at Bioinformatics online.
LncmiRSRN: identification and analysis of long non-coding RNA related miRNA sponge regulatory network in human cancer
Authors: Zhang Junpeng , Liu Lin , Li Jiuyong , Le Thuc Duy
Published: June 2018

Motivation

MicroRNAs (miRNAs) are small non-coding RNAs with the length of ∼22 nucleotides. miRNAs are involved in many biological processes including cancers. Recent studies show that long non-coding RNAs (lncRNAs) are emerging as miRNA sponges, playing important roles in cancer physiology and development. Despite accumulating appreciation of the importance of lncRNAs, the study of their complex functions is still in its preliminary stage. Based on the hypothesis of competing endogenous RNAs (ceRNAs), several computational methods have been proposed for investigating the competitive relationships between lncRNAs and miRNA target messenger RNAs (mRNAs). However, when the mRNAs are released from the control of miRNAs, it remains largely unknown as to how the sponge lncRNAs influence the expression levels of the endogenous miRNA targets.

Results

We propose a novel method to construct lncRNA related miRNA sponge regulatory networks (LncmiRSRNs) by integrating matched lncRNA and mRNA expression profiles with clinical information and putative miRNA-target interactions. Using the method, we have constructed the LncmiRSRNs for four human cancers (glioblastoma multiforme, lung cancer, ovarian cancer and prostate cancer). Based on the networks, we discover that after being released from miRNA control, the target mRNAs are normally up-regulated by the sponge lncRNAs, and only a fraction of sponge lncRNA-mRNA regulatory relationships and hub lncRNAs are shared by the four cancers. Moreover, most sponge lncRNA-mRNA regulatory relationships show a rewired mode between different cancers, and a minority of sponge lncRNA-mRNA regulatory relationships conserved (appearing) in different cancers may act as a common pivot across cancers. Besides, differential and conserved hub lncRNAs may act as potential cancer drivers to influence the cancerous state in cancers. Functional enrichment and survival analysis indicate that the identified differential and conserved LncmiRSRN network modules work as functional units in biological processes, and can distinguish metastasis risks of cancers. Our analysis demonstrates the potential of integrating expression profiles, clinical information and miRNA-target interactions for investigating lncRNA regulatory mechanism.

Availability and implementation

LncmiRSRN is freely available (https://github.com/zhangjunpeng411/LncmiRSRN).

Supplementary information

Supplementary data are available at Bioinformatics online.
A network-based zoning for parallel whole-cell simulation
Authors: Das Barnali , Patil Abhijeet Rajendra , Mitra Pralay
Published: June 2018

Motivation

In Computational Cell Biology, whole-cell modeling and simulation is an absolute requirement to analyze and explore the cell of an organism. Despite few individual efforts on modeling, the prime obstacle hindering its development and progress is its compute-intensive nature. Towards this end, little knowledge is available on how to reduce the enormous computational overhead and which computational systems will be of use.

Results

In this article, we present a network-based zoning approach that could potentially be utilized in the parallelization of whole-cell simulations. Firstly, we construct the protein–protein interaction graph of the whole-cell of an organism using experimental data from various sources. Based on protein interaction information, we predict protein locality and allocate confidence score to the interactions accordingly. We then identify the modules of strictly localized interacting proteins by performing interaction graph clustering based on the confidence score of the interactions. By applying this method to Escherichia coli K12, we identified 188 spatially localized clusters. After a thorough Gene Ontology-based analysis, we proved that the clusters are also in functional proximity. We then conducted Principal Coordinates Analysis to predict the spatial distribution of the clusters in the simulation space. Our automated computational techniques can partition the entire simulation space (cell) into simulation sub-cells. Each of these sub-cells can be simulated on separate computing units of the High-Performance Computing (HPC) systems. We benchmarked our method using proteins. However, our method can be extended easily to add other cellular components like DNA, RNA and metabolites.

Availability and implementation

 

Supplementary information

Supplementary data are available at Bioinformatics online.
Database of evidence for precision oncology portal
Authors: Sun Sam Q , Mashl R Jay , Sengupta Sohini , Scott Adam D , Wang Weihua , Batra Prag , Wang Liang-Bo , Wyczalkowski Matthew A , Ding Li
Published: June 2018

A database of curated genomic variants with clinically supported drug therapies and other oncological annotations is described. The accompanying web portal provides a search engine with two modes: one that allows users to query gene, cancer type, variant type or position for druggable mutations, and another to search for and to visualize, on three-dimensional protein structures, putative druggable sites that cluster with known druggable mutations.

Availability and implementation

http://dinglab.wustl.edu/depo
A guide to policy analysis as a research method
Authors: Browne Jennifer , Coffey Brian , Cook Kay , Meiklejohn Sarah , Palermo Claire
Published: June 2018

Policy analysis provides a way for understanding how and why governments enact certain policies, and their effects. Public health policy research is limited and lacks theoretical underpinnings. This article aims to describe and critique different approaches to policy analysis thus providing direction for undertaking policy analysis in the field of health promotion. Through the use of an illustrative example in nutrition it aims to illustrate the different approaches. Three broad orientations to policy analysis are outlined: (i) Traditional approaches aim to identify the ‘best’ solution, through undertaking objective analyses of possible solutions. (ii) Mainstream approaches focus on the interaction of policy actors in policymaking. (iii) Interpretive approaches examine the framing and representation of problems and how policies reflect the social construction of ‘problems’. Policy analysis may assist understanding of how and why policies to improve nutrition are enacted (or rejected) and may inform practitioners in their advocacy. As such, policy analysis provides researchers with a powerful tool to understand the use of research evidence in policymaking and generate a heightened understanding of the values, interests and political contexts underpinning policy decisions. Such methods may enable more effective advocacy for policies that can lead to improvements in health.
Learning optimal opioid prescribing and monitoring: a simulation study of medical residents
Authors: Kannampallil Thomas G , McNutt Robert , Falck Suzanne , Galanter William L , Patterson Dave , Darabi Houshang , Sharabiani Ashkan , Schiff Gordon , Odwazny Richard , Vaida Allen J , Wilkie Diana J , Lambert Bruce L
Published: June 2018

Objective

Hospitalized patients often receive opioids. There is a lack of consensus regarding evidence-based guidelines or training programs for effective management of pain in the hospital. We investigated the viability of using an Internet-based opioid dosing simulator to teach residents appropriate use of opioids to treat and manage acute pain.

Materials and methods

We used a prospective, longitudinal design to evaluate the effects of simulator training. In face-to-face didactic sessions, we taught 120 (108 internal medicine and 12 family medicine) residents principles of pain management and how to use the simulator. Each trainee completed 10 training and, subsequently, 5 testing trials on the simulator. For each trial, we collected medications, doses, routes and times of administration, pain scores, and a summary score. We used mixed-effects regression models to assess the impact of simulation training on simulation performance scores, variability in pain score trajectories, appropriate use of short- and long-acting opioids, and use of naloxone.

Results

Trainees completed 1582 simulation trials (M = 13.2, SD = 6.8), with sustained improvements in their simulated pain management practices. Over time, trainees improved their overall simulated pain management scores (b = 0.05, P < .01), generated lower pain score trajectories with less variability (b = −0.02, P < .01), switched more rapidly from short-acting to long-acting agents (b = −0.50, P < .01), and used naloxone less often (b = −0.10, P < .01).

Discussion and conclusions

Trainees translated their understanding of didactically presented principles of pain management to their performance on simulated patient cases. Simulation-based training presents an opportunity for improving opioid-based inpatient acute pain management.
Inspiring Curiosity and Restoring Humility: The Evolution of Competency-Based Continuing Medical Education
Authors: McMahon Graham T.
Published: June 2018

Dr. David Price and his colleagues, in their article in this issue of Academic Medicine, summarize the findings from recent studies regarding the association of Maintenance of Certification and physicians’ learning and improvements in care. Their evaluation demonstrates that physicians often changed their practice because of these educational interventions. In this Invited Commentary, the author argues that, although this finding is reassuring, it may be the right answer to the wrong question. The critical questions the profession faces are whether physicians have the humility to routinely submit themselves to the judgment of their peers, whether they will accept responsibility for managing their professional competence and that of their colleagues, and whether they are willing to create a process for identifying and remediating underperforming clinicians.

If certifying boards assume responsibility for this system of accountability, then each would need to set the competency expectations for physicians in its specialty areas, allow clinicians to self-identify their core scope of practice, assume responsibility for summative assessment, provide formative feedback to participants, and link physicians to recommended professional development activities. Continuing certification must be sensitive to the burdens it puts on physicians and recognize engagement in a spectrum of learning activities that are integrated with daily practice, including continuing medical education. By assuming responsibility for their own continuing competency and that of their colleagues, physicians can manifest their commitment to their patients and their profession.
Incisional Nociceptive Input Impairs Attention-related Behavior and Is Associated with Reduced Neuronal Activity in the Prefrontal Cortex in Rats
Authors: Ririe Douglas G. , Boada M. Danilo , MacGregor Megan K. , Martin Salem J. , Strassburg Tracy J. , Kim Susy A. , Eisenach James C. , Martin Thomas J.
Published: June 2018

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background

Cognitive capacity may be reduced from inflammation, surgery, anesthesia, and pain. In this study, we hypothesized that incision-induced nociceptive input impairs attentional performance and alters neuronal activity in the prefrontal cortex.

Methods

Attentional performance was measured in rats by using the titration variant of the 5-choice serial reaction time to determine the effect of surgical incision and anesthesia in a visual attention task. Neuronal activity (single spike and local field potentials) was measured in the medial prefrontal cortex in animals during the task.

Results

Incision significantly impaired attention postoperatively (area under curve of median cue duration-time 97.2 ± 56.8 [n = 9] vs. anesthesia control 25.5 ± 14.5 s-days [n = 9], P = 0.002; effect size, η2 = 0.456). Morphine (1 mg/kg) reduced impairment after incision (area under curve of median cue duration-time 31.6 ± 36.7 [n = 11] vs. saline 110 ± 64.7 s-days [n = 10], P < 0.001; η2 = 0.378). Incision also decreased cell activity (n = 24; 1.48 ± 0.58 vs. control, 2.93 ± 2.02 bursts/min; P = 0.002; η2 = 0.098) and local field potentials (n = 28; η2 = 0.111) in the medial prefrontal cortex.

Conclusions

These results show that acute postoperative nociceptive input from incision reduces attention-related task performance and decreases neuronal activity in the medial prefrontal cortex. Decreased neuronal activity suggests nociceptive input is more than just a distraction because neuronal activity increases during audiovisual distraction with similar behavioral impairment. This suggests that nociceptive input and the medial prefrontal cortex may contribute to attentional impairment and mild cognitive dysfunction postoperatively. In this regard, pain may affect postoperative recovery and return to normal activities through attentional impairment by contributing to lapses in concentration for routine and complex tasks.
Reduced Cerebral Blood Flow in the Visual Cortex and Its Correlation With Glaucomatous Structural Damage to the Retina in Patients With Mild to Moderate Primary Open-angle Glaucoma
Authors: Wang Qian , Chen Weiwei , Qu Xiaoxia , Wang Huaizhou , Wang Ying , Zhang Xun , Li Ting , Wang Ningli , Xian Junfang
Published: June 2018

Purpose:

Altered ocular and cerebral vascular autoregulation and vasoreactivity have been demonstrated in patients with primary open-angle glaucoma (POAG). In the present study, we investigated the correlations between reduced cerebral blood flow (CBF) in early and higher-tier visual cortical areas and glaucomatous changes in the retinas of patients with mild to moderate POAG.

Patients and Methods:

3-dimensional pseudocontinuous arterial spin labelling magnetic resonance imaging at 3 T was performed in 20 normal controls and 15 mild to moderate POAG patients. Regions of interest were selected based on the Population-Average, Landmark- and Surface-based (PALS) atlas of the human cerebral cortex. Arterial spin labelling–measured CBF values were extracted in the early and higher-tier visual cortical areas and were compared between patients and controls using a 2-sample t test. Pearson correlation analyses were used to assess the correlations between reduced CBF and cup-to-disc ratio, retinal nerve fiber layer thickness, and ganglion cell complex thickness.

Results:

Reduced CBF in early visual cortical areas (V1, V2, and ventral posterior area) and in the higher-tier visual left lateral occipital cortex was presented in mild to moderate POAG patients compared with controls. Furthermore, reduced CBF of the right areas V2 and ventral posterior area was correlated with cup-to-disc ratio, total ganglion cell complex thickness, and average retinal nerve fiber layer thickness.

Conclusions:

In conclusion, the complex pathologic progress of POAG includes abnormal cerebral perfusion within the visual cortex since the mild to moderate disease stages. The association of cerebral perfusion changes with alterations of the optic disc and the retina may contribute to the early diagnosis of POAG.
Shear-Mediated Platelet Activation Enhances Thrombotic Complications in Patients With LVADs and Is Reversed After Heart Transplantation
Authors: Consolo Filippo , Sferrazza Giulia , Motolone Giulia , Pieri Marina , De Bonis Michele , Zangrillo Alberto , Redaelli Alberto , Slepian Marvin J. , Pappalardo Federico
Published: June 2018

We present a time-series analysis of shear-mediated platelet activation (SMPA) in a patient supported by a Left Ventricular Assist Device (LVAD) who developed recurrent thromboembolic events over the course of support. The patient showed marked alterations of SMPA as quantified via the Platelet Activity State (PAS) assay. At the time of a first pump thrombosis, PAS was equal to 16.2 ± 2.1%, indicating a significant level of SMPA. A moderate decrease of PAS was observed 30 days after pump exchange (PAS = 9.5 ± 1.0%). A sudden PAS increase was recorded after 60 days (PAS = 60.5 ± 4.3%), and an ischemic stroke with hemorrhagic transformation was subsequently diagnosed at 120 days after pump exchange (PAS = 86.9 ± 7.5%); high PAS values did not recover over time likely because of sustained platelet activation from the inflammatory milieu caused by a driveline infection occurred at 240 days of support (PAS = 84.4 ± 7.3%). PAS values were completely reversed after heart transplantation (PAS = 0.6 ± 0.1%), demonstrating resolution of SMPA. This study provides further insight into our understanding of the pathogenesis of LVAD thrombosis, addressing SMPA as a relevant key factor associated with thrombotic complications. With the PAS assay, we have identified a reliable biomarker to promote tailored pharmacological therapy for the prevention of thromboembolic events in patients with LVADs.
Expanding the Spectrum of EBV-positive Marginal Zone Lymphomas
Authors: Gong Shunyou , Crane Genevieve M. , McCall Chad M. , Xiao Wenbin , Ganapathi Karthik A. , Cuka Nathan , Davies-Hill Theresa , Xi Liqiang , Raffeld Mark , Pittaluga Stefania , Duffield Amy S. , Jaffe Elaine S.
Published: June 2018

Traditionally low-grade B-cell lymphomas have been excluded from the category of monomorphic posttransplant lymphoproliferative disorders. However, recent reports identified Epstein-Barr virus-positive (EBV+) extranodal marginal zone lymphomas (MZL), almost exclusively seen in the posttransplant setting. Some reported cases responded to reduced immunosuppression, suggesting that they should be considered as a form of posttransplant lymphoproliferative disorders. We identified 10 cases of EBV+ MZL, 9 in extranodal sites and 1 presenting in lymph node. Two cases arose following solid organ transplantation, but other settings included iatrogenic immunosuppression for rheumatoid arthritis (2); prior chemotherapy (2); congenital immune deficiency (1); and increased age (3), as the only potential cause of immune dysfunction. There were 4 males and 6 females; age range 18 to 86. The atypical plasmacytoid and/or monocytoid B cells were positive for EBV in all cases, with either latency I or II in all cases tested. Monotypic light chain expression was shown in all with 6 cases positive for IgG, and 2 for IgM, undetermined in 2. Clonal immunoglobulin gene rearrangement was positive in all cases with successful amplification. MYD88 L265P was wild type in the 6 cases tested. We show that EBV+ MZLs can arise in a variety of clinical settings, and are most often extranodal. Treatment varied, but most patients had clinically indolent disease with response to reduction of immune suppression, or immunochemotherapy.
The new reckoning: The Combat Casualty Care Research Program responds to real and present challenges in military operational projections
Authors: Davis Michael R. , Rasmussen Todd E. , Holcomb Barbara R.
Published: June 2018

This issue of the Journal of Trauma and Acute Care Surgery features topics from the 2017 Military Health System Research Symposium and starts a second decade of partnership between the Combat Casualty Care Research Program (CCCRP) and the journal. This publication comes at a time of significant change for the CCCRP, as it responds to military planning for the future multidomain battlefield (MDB). The projected MDB portends markedly different operational scenarios than those conducted over the past 17 years. Emerging threats around the globe have the Department of Defense preparing for more complex battlefields that are larger in size and scope and which pit the United States against better equipped and more sophisticated adversaries. As the CCCRP navigates this new reckoning associated with trauma care on the MDB, its research investments will need to be robust and enabled to plan, program, and budget for agile and closer-term solutions. To accomplish this, the program will need to expand on its strong foundation of lessons learned and assets developed over the past 20 years.
Incidence, Outcomes, and Long-term Immune Response to Tuberculosis in Organ Transplant Recipients
Authors: Natori Yoichiro , Ferreira Victor H. , Nellimarla Srinivas , Husain Shahid , Rotstein Coleman , Humar Atul , Kumar Deepali
Published: June 2018

Background

Tuberculosis (TB) is a significant opportunistic infection in solid organ transplant recipients (SOTR). There are limited data on TB incidence in transplantation from low prevalence countries as well as on long-term TB-specific immune responses.

Methods

We performed a single-center retrospective review of SOTR diagnosed with active TB between 2000 and 2015 and further contacted the available patients for a study of long-term T-cell responses using an interferon-gamma (IFN-γ) release assay and a flow cytometry-based assay.

Results

We identified 31 SOTR with active TB for an incidence of 62 cases/100 000 patient-years. Nineteen (61.3%) of 31 patients were diagnosed within the first year after transplant. Nineteen (61.3%) were born in countries with high TB prevalence and disseminated disease occurred in 22.6%. No patient had been screened for latent TB infection pretransplant. The majority of patients received isoniazid and a rifamycin as part of multidrug regimen. In addition, 13 (44.8%) of 29 patients received quinolones. One-year mortality in this population was 19.4%. Eight patients were available for long-term immune responses. Of these, all had detectable IFN-γ response by IFN-γ release assay testing and 7 of 8 had detectable TB-specific T cells, primarily central and effector T-cell responses in the CD4+ compartment and terminally differentiated T cells in the CD8+ compartment.

Conclusions

TB has high incidence in SOTR even in low-prevalence regions but especially targets patients who originated from TB-endemic countries. Long-term TB-specific T-cell responses were found in the majority of patients.
Separate block-based parameter estimation method for Hammerstein systems
Authors: Zhang Shuo , Wang Dongqing , Liu Feng
Published: June 2018

Different from the output–input representation-based identification methods of two-block Hammerstein systems, this paper concerns a separate block-based parameter estimation method for each block of a two-block Hammerstein CARMA system, without combining the parameters of two parts together. The idea is to consider each block as a subsystem and to estimate the parameters of the nonlinear block and the linear block separately (interactively), by using two least-squares algorithms in one recursive step. The internal variable between the two blocks (the output of the nonlinear block, and also the input of the linear block) is replaced by different estimates: when estimating the parameters of the nonlinear part, the internal variable between the two blocks is computed by the linear function; when estimating the parameters of the linear part, the internal variable is computed by the nonlinear function. The proposed parameter estimation method possesses property of the higher computational efficiency compared with the previous over-parametrization method in which many redundant parameters need to be computed. The simulation results show the effectiveness of the proposed algorithm.
Functional materials based on molecules with hydrogen-bonding ability: applications to drug co-crystals and polymer complexes
Authors: Hutchins Kristin M.
Published: June 2018

The design, synthesis and property characterization of new functional materials has garnered interest in a variety of fields. Materials that are capable of recognizing and binding with small molecules have applications in sensing, sequestration, delivery and property modification. Specifically, recognition of pharmaceutical compounds is of interest in each of the aforementioned application areas. Numerous pharmaceutical compounds comprise functional groups that are capable of engaging in hydrogen-bonding interactions; thus, materials that are able to act as hydrogen-bond receptors are of significant interest for these applications. In this review, we highlight some crystalline and polymeric materials that recognize and engage in hydrogen-bonding interactions with pharmaceuticals or small biomolecules. Moreover, as pharmaceuticals often exhibit multiple hydrogen-bonding sites, many donor/acceptor molecules have been specifically designed to interact with the drug via such multiple-point hydrogen bonds. The formation of multiple hydrogen bonds not only increases the strength of the interaction but also affords unique hydrogen-bonded architectures.
Inbred burying beetles suffer fitness costs from making poor decisions
Authors: Richardson Jon , Comin Pauline , Smiseth Per T.
Published: June 2018

There is growing interest in how environmental conditions, such as resource availability, can modify the severity of inbreeding depression. However, little is known about whether inbreeding depression is also associated with differences in individual decision-making. For example, decisions about how many offspring to produce are often based upon the prevailing environmental conditions, such as resource availability, and getting these decisions wrong may have important fitness consequences for both parents and offspring. We tested for effects of inbreeding on individual decision-making in the burying beetle
Nicrophorus vespilloides,
which uses the size of a carrion resource to make decisions about number of offspring. Both inbred and outbred females adjusted their initial decisions about number of eggs to lay based on carcass size. However, when we forced individuals to update this initial decision by providing them with a different-sized carcass partway through reproduction, inbred females failed to update their decision about how many larvae to cull. Consequently, inbred females reared too many larvae, resulting in negative fitness consequences in the form of smaller offspring and reduced female post-reproductive condition. Our study provides novel insights into the effects of inbreeding by showing that poor decision-making by inbred individuals can negatively affect fitness.
Muscles provide an internal water reserve for reproduction
Authors: Brusch George A. , Lourdais Olivier , Kaminsky Brittany , DeNardo Dale F.
Published: June 2018

The use of fat to support the energy needs of reproduction (i.e. capital breeding) has been studied in a diversity of taxa. However, despite reproductive output (i.e. young or eggs) being approximately 70% water, little is known about the availability of internal resources to accommodate the hydric demands of reproduction. Recent research suggests that dehydration increases the catabolism of muscle as a means of maintaining water balance. Accordingly, we investigated the interactive effects of reproductive investment and water deprivation on catabolism and reproductive output in female Children's pythons (
Antaresia childreni
). Both reproductive and non-reproductive females were either provided water ad libitum or were water-deprived for three weeks at the time when reproductive females were gravid. We found that water-deprived reproductive females had, in general, greater body mass loss, epaxial muscle loss, plasma osmolality and plasma uric acid concentrations relative to the other groups. Furthermore, water-deprived females had similar clutch sizes compared with females with access to water, but produced lighter eggs and lower total clutch masses. Our results provide the first evidence that selective protein catabolism can be used to support water demands during reproduction, and, as a result, these findings extend the capital breeding concept to non-energetic resources.
Little plant, big city: a test of adaptation to urban environments in common ragweed (
Ambrosia artemisiifolia
)
Authors: Gorton Amanda J. , Moeller David A. , Tiffin Peter
Published: June 2018

A full understanding of how cities shape adaptation requires characterizing genetically-based phenotypic and fitness differences between urban and rural populations under field conditions. We used a reciprocal transplant experiment with the native plant common ragweed, (
Ambrosia artemisiifolia
), and found that urban and rural populations have diverged in flowering time, a trait that strongly affects fitness. Although urban populations flowered earlier than rural populations, plants growing in urban field sites flowered later than plants in rural field sites. This counter-gradient variation is consistent adaptive divergence between urban and rural populations. Also consistent with local adaptation, both urban and rural genotypes experienced stronger net selection in the foreign than in the local habitat, but this pattern was not significant for male fitness. Despite the evidence for local adaptation, rural populations had higher lifetime fitness at all sites, suggesting that selection has been stronger or more uniform in rural than urban populations. We also found that inter-population differences in both flowering time and fitness tended to be greater among urban than rural populations, which is consistent with greater drift or spatial variation in selection within urban environments. In summary, our results are consistent with adaptive divergence of urban and rural populations, but also suggest there may be greater environmental heterogeneity in urban environments which also affects evolution in urban landscapes.
LCM-seq reveals unique transcriptional adaption mechanisms of resistant neurons in spinal muscular atrophy
Authors: Nichterwitz S , Storvall H , Nijssen J , Comley LH , Allodi I , van der Lee M , Schweingruber C , Deng Q , Sandberg R , Hedlund E
Published: June 2018

Somatic motor neurons are selectively vulnerable in spinal muscular atrophy (SMA), a lethal disease caused by a deficiency of the ubiquitously expressed survival of motor neuron (SMN) protein. However, some brainstem motor neuron groups, including oculomotor and trochlear (ocular), which innervate the muscles around the eyes, are for unknown reasons spared. Here, using laser capture microdissection coupled with RNA sequencing (LCM-seq), we investigate the transcriptional dynamics in discrete neuronal populations in health and SMA to reveal mechanisms of vulnerability and resistance. Using gene correlation network analysis, we reveal a p53-mediated stress response that is intrinsic to all somatic motor neurons independent of their vulnerability, but absent in resistant red nucleus and visceral motor neurons. However, our temporal and spatial differential expression analysis across neuron types clearly demonstrates that the majority of SMA-induced modulations are cell-type specific. Notably, using gene ontology and protein-network analyses we show that ocular motor neurons present unique disease-adaptation mechanisms that could explain their resilience. In particular, ocular motor neurons up-regulate; i) Syt1, Syt5 and Cplx2, which modulate neurotransmitter release; ii) the motor neuron survival factors Chl1 and Lif, iii) Aldh4, that can protect cells from oxidative stress and iv) the caspase inhibitor Pak4. In conclusion, our in-depth longitudinal analysis of gene expression changes in SMA reveal novel cell-type specific changes that present compelling targets for future gene therapy studies aimed towards preserving vulnerable motor neurons.