bluuebunny/crossref_metadata_2025_split huggingface dataset:
β-Blocker therapy for cirrhotic cardiomyopathy: a randomized-controlled trial
Authors: Silvestre Odilson M. , Farias Alberto Q. , Ramos Danusa S. , Furtado Meive S. , Rodrigues Ana C. , Ximenes Rafael O. , de Campos Mazo Daniel F. , Yoshimura Zitelli Patricia M. , Diniz Marcio A. , Andrade José L. , Strunz Celia , Friedmann Antônio A. , Lee Samuel S. , Carrilho Flair J. , D’Albuquerque Luiz A.C. , Bacal Fernando 
Published: April 2018

Background
Cirrhotic cardiomyopathy is characterized by an attenuated contractile response to stress. Long-term exposure of β-adrenergic receptors to persistently high levels of catecholamines has been implicated in its pathogenesis. We hypothesized that β-blockade with metoprolol could reverse the changes in heart function and morphology in cirrhotic cardiomyopathy.

Patients and methods
In this prospective randomized trial, we included 78 patients aged between 18 and 60 years with abnormal cardiac output response under dobutamine stress echocardiography, without primary cardiac disease or a history of alcohol intake. Patients were assigned randomly to receive metoprolol or placebo for 6 months. The primary endpoint was the improvement in cardiac output response to stress, measured by an increase in the left ventricle stroke volume more than 30%.

Results
Three (7.3%) patients in the metoprolol group and nine (24.3%) patients in the placebo group showed improved stroke volume (P=0.057). Diastolic dysfunction was found in two (4.8%) patients before and in five (15.6%) patients after therapy in the metoprolol group, and in 10 (27%) patients before and nine (31%) patients after therapy in the placebo group (P=0.67). After treatment, no echocardiography parameter of morphology was significantly different between metoprolol or placebo groups. No significant differences were observed in noradrenaline, plasma renin activity, and troponin levels between groups. Cirrhosis-related clinical events, including hospitalizations and mortality, were not significantly different between the two groups. Six months of therapy with β-blocker did not ameliorate heart function and morphology in patients with cirrhotic cardiomyopathy.
Linking opioid-induced hyperalgesia and withdrawal-associated injury site pain: a case report
Authors: Rieb Launette Marie , Norman Wendy V. , Martin Ruth Elwood , Berkowitz Jonathan , Wood Evan , Milloy Michael John , McNeil Ryan 
Published: April 2018

Abstract

Introduction and objectives:
Understanding the details of one individual's experience with pain, opioid use and withdrawal may generate insights into possible relationships between opioid-induced hyperalgesia and withdrawal-associated injury site pain (WISP).

Methods:
This case study was extracted from a mixed methods study that characterized WISP. In 2014, the individual was recruited from a primary care clinic that prescribes opioid agonist therapy. In an interview, she completed a 35-item survey and elaborated on her own experience. Follow-up contact was made in June of 2017.

Results:
This 34-year-old white woman had several twisting injuries of her right knee between ages 13 and 15. The pain resolved each time in a few days, and she was pain free for 15 years. Around age 30, she initiated illicit oxycodone recreationally (not for pain) and developed an opioid use disorder. On detoxification, she experienced severe knee pain for 6 weeks that resolved postdetoxification but returned after subsequent oxycodone use and withdrawal episodes along with generalized skin sensitivity. This experience of WISP became a barrier to opioid cessation. Although nonsteroidal anti-inflammatories and gabapentin relieved WISP and methadone therapy assisted her opioid use disorder, an eventual change to sublingual buprenorphine/naloxone provided superior control of both.

Conclusion:
This case report illustrates that both opioid use and withdrawal can reactivate injury site pain, which can increase with dose escalation and repeated withdrawal events. The timing, trajectory, and neuropathic features of WISP reported here are consistent with those previously reported for the development of opioid-induced hyperalgesia, possibly linking these phenomena.
Intense, Instantaneous, and Shooting Pain During Local Anesthesia for Implant Surgery
Authors: Scarano Antonio , Sinjari Bruna , Lorusso Felice , Mortellaro Carmen , D’Ovidio Cristian , Carinci Francesco 
Published: April 2018

Abstract
Administration of local anesthetics is daily routine for most dental practitioners. Normally, the effect is achieved, and no adverse effects are seen. In this article, the authors describe the complications of immediate, intense and shooting pain, numbness, and marked pallor of the cheek, which occurred during infiltration of a local anesthetic in buccal vestibule infiltration. The patients moved suddenly because of pain and marked pallor of the cheek near the root of the nose and lower eyelid pallor was observed. The pain was very short and the injection was performed again after a few minutes. Two patients also reported an alteration of vision or paralysis of the extra-ocular muscles and drooping eyelid due to paralysis of the levator palpebrae superioris muscle and signs of numbness in the infraorbital area on the same side as the anesthesia. While 3 patients were also apprehensive and started to scare with heart palpitations, as they did not understand what was happening. Probably the anesthetic solutions were injected into an intravascular artery and passed from the extraosseous branch of posterior superior alveolar artery through to the infraorbital artery, which could produce the clinical signs observed in the present study. At the same time, the inoculation of anesthetic in the artery could be grounds for legal disputes for the dentist. In fact, in the absence of vascular disease, anomalies documented by the dentist, they would, however, respond to professional liability and be liable for damages caused to the patient. In conclusion, despite the fact that this condition requires no treatment, it could lead to the recognition of clinical signs in patient with injection of local anesthesia into the artery. At the same time, the inoculation of anesthetic in the artery could be grounds for legal disputes for the dentist.
Superficial Fascia in the Cheek and the Superficial Musculoaponeurotic System
Authors: Hwang Kun , Choi Jung Ho 
Published: April 2018

Abstract
The origins and validity of the term “superficial musculoaponeurotic system” (SMAS) is reviewed. Gray stated the superficial fascia connects the skin with the deep or aponeurotic fascia and consists of fibro-areolar tissue. Hollinshead wrote superficial fascia exists throughout the body and contains a variable amount of fat. In the head and neck, it encloses voluntary muscles in its deep portion. Skoog found superficial fascia was fixed to the dense, deep fascia by fibrous adhesions in the temporal, preauricular, and parotid area. Mitz stated “There is a ‘superficial muscular and aponeurotic system’ (SMAS) in the parotid and cheek areas.” SMAS has an intimate relationship with the entire superficial fascia of the head and neck and divides the subcutaneous fat into 2 layers. Wassef found a continuous fibromuscular layer at the deep limit of the “subcutis,” which corresponded to the “superficial fascia.” Nakajima reported the subcutaneous adipofascial tissue was made up of 2 adipofascial layers. Macchi found 2 different fibroadipose connective layers bounded to the laminar connective tissue layer (SMAS). In the cheek, Hwang found horizontal fibrous connective tissues (membranous layer of superficial fascia) divided the superficial fascia into the superficial fatty layer and the deep fatty layer. Recently, Mitz explained the reason for the term SMAS. The “musculo+aponeurotic” component is based on histology of muscle cells, including the risorius, in the same structure to be surgically consistent. The aponeurotic cells belong to the same surgical layer. SMAS is not sufficient to replace the old term “superficial fascia” of the cheek area.
Cerebral Multimodal Monitoring in Sepsis: An Experimental Study
Authors: Kurtz Pedro , d’Avila Joana C. , Prado Darwin , Madeira Caroline , Vargas-Lopes Charles , Panizzutti Rogerio , Azevedo Luciano C.P. , Bozza Fernando A. 
Published: April 2018

ABSTRACT
Acute brain dysfunction is a complication of sepsis, and its pathophysiology remains poorly understood. We studied the brain metabolism in a resuscitated animal model of sepsis. Twelve anesthetized, mechanically ventilated, and invasively monitored pigs were allocated to a sham procedure (N = 5) or sepsis (N = 7). Sepsis was induced through fecal inoculation in the peritoneum. Fluid resuscitation was maintained during the entire study period. Animals were observed until spontaneous death or for a maximum of 24 h. In addition to global hemodynamic and laboratory assessment, intracranial pressure and cerebral microdialysis (MD) were evaluated at baseline, 6, 12, 18, and 24 h after sepsis induction. After euthanasia, the brain was rapidly removed and a fragment from the frontal cortex was analyzed for markers of neuroinflammation, metabolism, and neurotransmission. Septic animals developed a hyperdynamic state associated with increased arterial lactate. Cerebral microdialysis showed unchanged levels of lactate/pyruvate ratios and brain glucose between the groups. Brain/serum glucose ratios were increased in the septic animals during the study period despite a progressive decrease in serum glucose. Moreover, extracellular glutamine levels were elevated starting at 6 h after sepsis. Tissue analysis showed elevated glutamate, glutamine, and glutamine synthetase in the sepsis group. However, C-Fos, a marker of neuronal activity, was unchanged between groups. In this animal model of resuscitated sepsis, we found increased oxidative stress and alterations in neuroenergetics characterized by exacerbated activity of the glutamate/glutamine cycle and increased glucose utilization by the brain, however without any evidence of decompensated energy metabolism.
Role of Emergency Laparoscopic Colectomy for Colorectal Cancer
Authors: Vallance Abigail E. , Keller Deborah S. , Hill James , Braun Michael , Kuryba Angela , van der Meulen Jan , Walker Kate , Chand Manish 
Published: April 2018

Objective:
To evaluate factors associated with the use of laparoscopic surgery and the associated postoperative outcomes for urgent or emergency resection of colorectal cancer in the English National Health Service.

Summary of Background Data:
Laparoscopy is increasingly used for elective colorectal cancer surgery, but uptake has been limited in the emergency setting.

Methods:
Patients recorded in the National Bowel Cancer Audit who underwent urgent or emergency colorectal cancer resection between April 2010 and March 2016 were included. A multivariable multilevel logistic regression model was used to estimate odds ratios (ORs) of undergoing laparoscopic resection and postoperative outcome according to approach.

Results:
There were 15,516 patients included. Laparoscopy use doubled from 15.1% in 2010 to 30.2% in 2016. Laparoscopy was less common in patients with poorer physical status [American Society of Anaesthesiologists (ASA) 4/5 vs 1, OR 0.29 (95% confidence interval, 95% CI 0.23–0.37), P < 0.001] and more advanced T-stage [T4 vs T0-T2, OR 0.28 (0.23–0.34), P < 0.001] and M-stage [M1 vs M0, OR 0.85 (0.75–0.96), P < 0.001]. Age, socioeconomic deprivation, nodal stage, hospital volume, and a dedicated colorectal emergency service were not associated with laparoscopy. Laparoscopic patients had a shorter length of stay [median 8 days (interquartile range (IQR) 5 to 15) vs 12 (IQR 8 to 21), adjusted mean difference −3.67 (−4.60 to 2.74), P < 0.001], and lower 90-day mortality [8.1% vs 13.0%; adjusted OR 0.78 (0.66–0.91), P = 0.004] than patients undergoing open resection. There was no significant difference in rates of readmission or reoperation by approach.

Conclusion:
The use of laparoscopic approach in the emergency resection of colorectal cancer is linked to a shorter length of hospital stay and reduced postoperative mortality.
Transvaginal Trigger Point Injections Improve Pain Scores in Women with Pelvic Floor Hypertonicity and Pelvic Pain Conditions
Authors: Bartley Jamie , Han Esther , Gupta Priyanka , Gaines Natalie , Killinger Kim A. , Boura Judith A. , Farrah Morgan , Gilleran Jason , Sirls Larry T. , Peters Kenneth M. 
Published: April 2018

Objectives
Chronic pelvic pain in women often requires multimodal treatment regimens. We describe our method of transvaginal trigger point injections (TPIs) and report outcomes using change in pain scores.

Methods
This was a retrospective review of women treated with in-office pelvic floor muscle injections from January 2012 to August 2015. Lidocaine 1% and 2%, bupivacaine 0.5%, or ropivacaine 0.5% with or without the addition of triamcinolone 40 mg was used for the injections. Pain was reported on a 0- to 10-point numerical rating scale before and after injection. Differences in pretreatment and posttreatment pain scores were analyzed after the first injection and after subsequent injections. Repeated-measures analysis was used to determine if any variable affected treatment response.

Results
One hundred one women with a mean age of 44 years had a total of 257 separate visits for pelvic floor muscle injections. Triamcinolone was used at 90.2% (230/255) of the TPI visits. After the initial TPI visit, there was significant decrease in total levator numerical rating scale score (maximum score, 20; mean, −6.21 ± 4.7; P < 0.0001), and 77% (70/91) of patients had improved. These significant improvements were noted at all visits 1 through 4 and whether bilateral or unilateral injections were done. Only the total amount of local anesthestic used had a significant effect on the change in total levator pain scores (P = 0.002). Minor adverse effects including leg numbness, dizziness, nausea, bleeding, and headache occurred at 10% of visits.

Conclusions
Pelvic floor muscle injections decrease pain levels in women with pelvic floor dysfunction.
VenomKB v2.0: A knowledge repository for computational toxinology
Authors: Romano Joseph D. , Nwankwo Victor , Tatonetti Nicholas P. 
Published: April 2018

AbstractMotivationVenom peptides comprise one of the richest sources of bioactive compounds available for drug discovery. However, venom data and knowledge are fragmentary and poorly structured, and fail to capitalize on the important characteristics of venoms that make them so interesting to the biomedical community.ResultsWe present VenomKB v2.0, a new open-access resource for knowledge representation and retrieval of venom bioactivities, sequences, structures, and classifications. VenomKB provides a complete infrastructure for computational toxinology, with a focus on drug discovery and effects that venoms have on the human body. VenomKB is accompanied by a suite of tools for programmatic access, and, in this article, we highlight scenarios demonstrating its usefulness and novel contributions to toxinology, pharmacology, and informatics.AvailabilityVenomKB can be accessed online at http://venomkb.org/, and the code can be found at https://github.com/tatonetti-lab/venomkb/. All code and data are available under open-source and open-access licenses.
Bivariate genome-wide association analysis strengthens the role of bitter receptor clusters on chromosomes 7 and 12 in human bitter taste
Authors: Hwang Liang-Dar , Gharahkhani Puya , Breslin Paul A. S. , Gordon Scott D. , Zhu Gu , Martin Nicholas G. , Martin Nicholas G. , Reed Danielle R. , Wright Margaret J. 
Published: April 2018

AbstractHuman perception of bitter substances is partially genetically determined. Previously we discovered a single nucleotide polymorphism (SNP) within the bitter taste receptor gene TAS2R19 on chromosome 12 that accounts for 5.8% of the variance in the perceived intensity rating of quinine, and we strengthened the classic association between TAS2R38 genotype and the bitterness of propylthiouracil (PROP). Here we performed a genome-wide association study (GWAS) using a 40% larger sample (n = 1999) together with a bivariate approach to detect previously unidentified common variants with small effects on bitter perception. We identified two signals, both with small effects (< 2%), within the bitter taste receptor clusters on chromosomes 7 and 12, which influence the perceived bitterness of denatonium benzoate and sucrose octaacetate respectively. We also provided the first independent replication for an association of caffeine bitterness on chromosome 12. Furthermore, we provided evidence for pleiotropic effects on quinine, caffeine, sucrose octaacetate and denatonium benzoate for the three SNPs on chromosome 12 and the functional importance of the SNPs for denatonium benzoate bitterness. These findings provide new insights into the genetic architecture of bitter taste and offer a useful starting point for determining the biological pathways linking perception of bitter substances.
Identification of Miro as a mitochondrial receptor for myosin XIX
Authors: Oeding Stefanie J. , Majstrowicz Katarzyna , Hu Xiao-Ping , Schwarz Vera , Freitag Angelika , Honnert Ulrike , Nikolaus Petra , Bähler Martin 
Published: April 2018

ABSTRACTMitochondrial distribution in cells is critical for cellular function and proper inheritance during cell division. In mammalian cells, mitochondria are transported predominantly along microtubules by kinesin and dynein and along actin filaments by myosin. Myosin XIX (Myo19) associates with the outer mitochondrial membrane, but no specific receptor has been identified. Using proximity BioID labeling, we identified Miro-1 and Miro-2 as potential binding partners of Myo19. Interaction studies show that Miro-1 binds to a C-terminal fragment of the Myo19 tail region and that Miro recruits the Myo19 tail in vivo. This recruitment is regulated by the nucleotide-state of the N-terminal Rho-like GTPase domain of Miro. Notably, Myo19 protein stability in cells depends on its association with Miro. Finally, Myo19 regulates the subcellular distribution of mitochondria. Downregulation, as well as overexpression, of Myo19 induces perinuclear collapse of mitochondria, phenocopying the loss of kinesin KIF5 or its mitochondrial receptor Miro. These results suggest that Miro coordinates microtubule- and actin-based mitochondrial movement.
Progressive Alignment of Inhibitory and Excitatory Delay May Drive a Rapid Developmental Switch in Cortical Network Dynamics
Authors: Romagnoni Alberto , Colonnese Matthew T. , Touboul Jonathan D. , Gutkin Boris 
Published: April 2018

AbstractNervous system maturation occurs on multiple levels, synaptic, circuit, and network, at divergent time scales. For example, many synaptic properties mature gradually, while emergent network dynamics, as data show, change abruptly. Here, we combine experimental and theoretical approaches to investigate a sudden transition in spontaneous thalamocortical activity necessary for the development of vision. Inspired by in vivo measurements of time-scales and amplitudes of synaptic currents, we extend the Wilson and Cowan model to take into account the relative onset timing and amplitudes of inhibitory and excitatory neural population responses. We study the dynamics of this system and identify the bifurcations as the onset timescales of excitation and inhibition are varied. We focus on the specific typical developmental changes in synaptic timescales consistent with the experimental observations. These findings argue that the inhibitory timing is a critical determinant of thalamocortical activity maturation; a gradual decay of the ratio of inhibitory to excitatory onset time below one drives the system through a bifurcation that leads to a sudden switch of the network spontaneous activity from high-amplitude oscillations to a non-oscillatory active state. This switch also drives a marked change to a linear network response to transient stimuli, agreeing to the in vivo observations. The switch observed in the model is representative of the sudden transition in the sensory cortical activity seen early in development.
New tools for evaluating protein tyrosine sulphation: Tyrosyl Protein Sulphotransferases (TPSTs) are novel targets for RAF protein kinase inhibitors
Authors: Byrne Dominic P , Li Yong , Ngamlert Pawin , Ramakrishnan Krithika , Eyers Claire E , Wells Carrow , Drewry David H , Zuercher William J , Berry Neil G , Fernig David G , Eyers Patrick A 
Published: April 2018

ABSTRACTProtein tyrosine sulphation is a post-translational modification (PTM) best known for regulating extracellular protein-protein interactions. Tyrosine sulphation is catalysed by two Golgi-resident enzymes termed Tyrosyl Protein Sulpho Transferases (TPSTs) 1 and 2, which transfer sulphate from the co-factor PAPS (3’-phosphoadenosine 5’-phosphosulphate) to a context-dependent tyrosine in a protein substrate. A lack of quantitative tyrosine sulphation assays has hampered the development of chemical biology approaches for the identification of small molecule inhibitors of tyrosine sulphation. In this paper, we describe the development of a non-radioactive mobility-based enzymatic assay for TPST1 and TPST2, through which the tyrosine sulphation of synthetic fluorescent peptides can be rapidly quantified. We exploit ligand binding and inhibitor screens to uncover a susceptibility of TPST1 and 2 to different classes of small molecules, including the anti-angiogenic compound suramin and the kinase inhibitor rottlerin. By screening the Published Kinase Inhibitor Set (PKIS), we identified oxindole-based inhibitors of the Ser/Thr kinase RAF as low micromolar inhibitors of TPST1/2. Interestingly, unrelated RAF inhibitors, exemplified by the dual BRAF/VEGFR2 inhibitor RAF265, were also TPST inhibitorsin vitro. We propose that target-validated protein kinase inhibitors could be repurposed, or redesigned, as more-specific TPST inhibitors to help evaluate the sulphotyrosyl proteome. Finally, we speculate that mechanistic inhibition of cellular tyrosine sulphation might be relevant to some of the phenotypes observed in cells exposed to anionic TPST ligands and RAF protein kinase inhibitors.SUMMARY STATEMENTWe develop new assays to quantify tyrosine sulphation by the human tyrosine sulphotransferases TPST1 and 2. TPST1 and 2 catalytic activities are inhibited by protein kinase inhibitors, suggesting new starting points to synthesise (or repurpose) small molecule compounds to evaluate biological TPST using chemical biology.
Differential DNA modification of an enhancer at the IGF2 locus affects dopamine synthesis in patients with major psychosis
Authors: Pai Shraddha , Li Peipei , Killinger Bryan , Marshall Lee , Jia Peixin , Liao Ji , Petronis Arturas , Szabo Piroska , Labrie Viviane 
Published: April 2018

AbstractDopamine dysregulation is central to the pathogenesis of diseases with major psychosis, but its molecular origins are unclear. In an epigenome-wide investigation in neurons, individuals with schizophrenia and bipolar disorder showed reduced DNA modifications at an enhancer in IGF2, which disrupted the regulation of the dopamine synthesis enzyme tyrosine hydroxylase and striatal dopamine levels in transgenic mice. Epigenetic control of this enhancer may be an important molecular determinant of psychosis.