bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intracellular and non-neuronal targets of voltage-gated potassium channel complex antibodies
Authors: Lang Bethan , Makuch Mateusz , Moloney Teresa , Dettmann Inga , Mindorf Swantje , Probst Christian , Stoecker Winfried , Buckley Camilla , Newton Charles R , Leite M Isabel , Maddison Paul , Komorowski Lars , Adcock Jane , Vincent Angela , Waters Patrick , Irani Sarosh R 
Published: January 2017

ObjectivesAutoantibodies against the extracellular domains of the voltage-gated potassium channel (VGKC) complex proteins, leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-2 (CASPR2), are found in patients with limbic encephalitis, faciobrachial dystonic seizures, Morvan's syndrome and neuromyotonia. However, in routine testing, VGKC complex antibodies without LGI1 or CASPR2 reactivities (double-negative) are more common than LGI1 or CASPR2 specificities. Therefore, the target(s) and clinical associations of double-negative antibodies need to be determined.MethodsSera (n=1131) from several clinically defined cohorts were tested for IgG radioimmunoprecipitation of radioiodinated α-dendrotoxin (125I-αDTX)-labelled VGKC complexes from mammalian brain extracts. Positive samples were systematically tested for live hippocampal neuron reactivity, IgG precipitation of125I-αDTX and125I-αDTX-labelled Kv1 subunits, and by cell-based assays which expressed Kv1 subunits, LGI1 and CASPR2.ResultsVGKC complex antibodies were found in 162 of 1131 (14%) sera. 90 of these (56%) had antibodies targeting the extracellular domains of LGI1 or CASPR2. Of the remaining 72 double-negative sera, 10 (14%) immunoprecipitated125I-αDTX itself, and 27 (38%) bound to solubilised co-expressed Kv1.1/1.2/1.6 subunits and/or Kv1.2 subunits alone, at levels proportionate to VGKC complex antibody levels (r=0.57, p=0.0017). The sera with LGI1 and CASPR2 antibodies immunoprecipitated neither preparation. None of the 27 Kv1-precipitating samples bound live hippocampal neurons or Kv1 extracellular domains, but 16 (59%) bound to permeabilised Kv1-expressing human embryonic kidney 293T cells. These intracellular Kv1 antibodies mainly associated with non-immune disease aetiologies, poor longitudinal clinical–serological correlations and a limited immunotherapy response.ConclusionsDouble-negative VGKC complex antibodies are often directed against cytosolic epitopes of Kv1 subunits and occasionally against non-mammalian αDTX. These antibodies should no longer be classified as neuronal-surface antibodies. They consequently lack pathogenic potential and do not in themselves support the use of immunotherapies.
Vertical Brand Extension at Vinamilk, Vietnam
Authors: Nguyen Quang Tri , Wongsurawat Winai , Beise-Zee Rian 
Published: January 2017

This case study illustrates the role of marketing instruments on the success of a vertical brand extension executed by a leading dairy company in Vietnam — Vinamilk. In 2011, the company launched a fortified liquid milk line as a step-down vertical brand extension from its previous and more premium line — 100% fresh milk. The key issue in the study is to understand how Vinamilk used marketing communication and distancing techniques (or differentiation tactics) to influence the performance of the vertical brand extension. The case findings show that despite quite serious cannibalization on the core brand, the vertical brand extension at Vinamilk was deemed a successful launch. The success was attributable to marketing communication that was rooted in profound consumer understanding — the right product offered to the right target at the right price supported with heavy consumer pull and trade push marketing. Vinamilk’s strong umbrella brand and wide distribution network also contributed to the successful launch. The most serious challenge was cannibalization on the previous premium product line — Vinamilk 100% fresh milk. As Vietnamese consumers grew wealthier and more sophisticated, non-reconstituted, fresh milk would likely become the biggest seller in the future, a sector Vinamilk could not afford to lose. Competition in this premium market was already heating up, requiring the company to strengthen this product line. For longer term strategy, Vinamilk had been forced to revisit its liquid milk product portfolio. A more clearly defined role for each product line along with effective differentiation would be required.
Genome-Wide Prioritization and Transcriptomics Reveal Novel Signatures Associated With Thiazide Diuretics Blood Pressure Response
Authors: Shahin Mohamed H. , Sá Ana C. , Webb Amy , Gong Yan , Langaee Taimour , McDonough Caitrin W. , Riva Alberto , Beitleshees Amber L. , Chapman Arlene B. , Gums John G. , Turner Stephen T. , Boerwinkle Eric , Scherer Steven E. , Sadee Wolfgang , Cooper-DeHoff Rhonda M. , Johnson Julie A. 
Published: January 2017

Background—
Thiazide diuretics are among the most commonly prescribed antihypertensives. However, <50% of thiazide-treated patients achieve blood pressure (BP) control. Herein, we used different omics (genomics and transcriptomics) to identify novel biomarkers of thiazide diuretics BP response.

Methods and Results—

Genome-wide analysis included 228 white hypertensives with BP determined at baseline and after 9 weeks of hydrochlorothiazide. Single-nucleotide polymorphisms with
P
<5×10
−
5
were prioritized according to their biological function, using RegulomeDB, haploreg, and Genome-Wide Annotation of Variants. The results from the prioritization approach revealed rs10995 as the most likely functional single-nucleotide polymorphism, among single-nucleotide polymorphisms tested, that has been associated with hydrochlorothiazide BP response. The rs10995
G
-allele was associated with better BP response to hydrochlorothiazide versus noncarriers (Δ systolic BP/Δ diastolic BP: −12.3/−8.2 versus −6.8/−3.5 mm Hg, respectively, Δ systolic BP
P
=3×10
−4
, Δ diastolic BP
P
=5×10
−5
). This association was replicated in independent participants treated with chlorthalidone. In addition, rs10995
G-allele
was associated with increased mRNA expression of
VASP
(vasodilator-stimulated phosphoprotein). Moreover, baseline expression of the VASP mRNA was significantly higher in 25 good responders to hydrochlorothiazide compared with 25 poor responders (
P
=0.01). This finding was replicated in independent participants treated with chlorthalidone (
P
=0.04). Last, allelic-specific expression analysis revealed a significant but modest imbalance with rs10995 and rs10156, a single-nucleotide polymorphism in high linkage disequilibrium (
r
2
=0.7) with rs10995, which both could contribute to the observed genetic effects by affecting VASP mRNA expression.

Conclusions—

This study highlights the strength of using different omics to identify novel biomarkers of drug response and suggests
VASP
as a potential determinant of thiazide diuretics BP response.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifiers: NCT00246519 and NCT01203852.
The Role of Lucius Vitellius in the Death of Messallina
Authors: Woods David 
Published: January 2017

AbstractThe role of Lucius Vitellius in the events leading to the death of Valeria Messallina, the third wife of the emperor Claudius, in autumn 48adis re-examined. It is argued that the freedman Narcissus delayed his action against Messallina for her dangerous affair with Gaius Silius until he could be sure of the tacit support of Vitellius, where Vitellius had been hoping for a practical opportunity to strike against Messallina ever since she had forced him to play a key part in the trial of his friend Valerius Asiaticus in late 47ad.
On the Leeuwin Current System and Its Linkage to Zonal Flows in the South Indian Ocean as Inferred from a Gridded Hydrography
Authors: Furue Ryo , Guerreiro Kévin , Phillips Helen E. , McCreary Julian P. , Bindoff Nathaniel L. 
Published: January 2017

AbstractThe Leeuwin Current System (LCS) along the coast of Western Australia consists of the poleward-flowing Leeuwin Current (LC), the equatorward-flowing Leeuwin Undercurrent (LUC), and neighboring flows in the south Indian Ocean (SIO). Using geostrophic currents obtained from a highly resolved (⅛°) hydrographic climatology [CSIRO Atlas of Regional Seas (CARS)], this study describes the spatial structure and annual variability of the LC, LUC, and SIO zonal currents, estimates their transports, and identifies linkages among them. In CARS, the LC is supplied partly by water from the tropics (an annual mean of 0.3 Sv; 1 Sv ≡ 106 m3 s−1) but mostly by shallow (200 m) eastward flows in the SIO (4.7 Sv), and it loses water by downwelling across the bottom of this layer (3.4 Sv). The downwelling is so strong that, despite the large SIO inflow, the horizontal transport of the LC does not much increase to the south (from 0.3 Sv at 22°S to 1.5 Sv at 34°S). This LC transport is significantly smaller than previously reported. The LUC is supplied by water from south of Australia (0.2 Sv), by eastward inflow from the SIO south of 28°S (1.6 Sv), and by the downwelling from the LC (1.6 Sv) and in response strengthens northward, reaching a maximum near 28°S (3.4 Sv). North of 28°S it loses water by outflow into subsurface westward flow (−3.6 Sv between 28° and 22°S) and despite an additional downwelling from the LC (1.9 Sv), it decreases to the north (1.7 Sv at 22°S). The seasonality of the LUC is described for the first time.
Severely impaired activity of lipoprotein lipase Arg243His is partially ameliorated by emulsifying phospholipids inin vitrotriolein hydrolysis analysis
Authors: Yamaguchi Takashi , Murano Takeyoshi , Tatsuno Ichiro , Hiruta Nobuyuki , Suzuki Toru , Sawada Shojiro , Katagiri Hideki , Shirai Kohji , Schneider Wolfgang J , Bujo Hideaki 
Published: January 2017

BackgroundWe investigated the in vitro effects of various phospholipids as emulsifiers on the hydrolysing activities of lipoprotein lipase (LPL) Arg243His against triolein as substrate. LPL Arg243His, identified in a patient with hyperchylomicronaemia, displays severely diminished activity for triolein when emulsified with Triton X-100.MethodsLipolytic activities of plasma obtained by heparin injection from a homozygous patient with LPL Arg243His were analysed using triolein emulsified with phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), lysophosphatidylcholine (LPC), or Triton X-100 as substrates.ResultsThe hydrolysing activities of the patient’s plasma for triolein emulsified with PC, PE, PS, PI, LPC and Triton X-100 were 9.22 ± 1.06  μmol/ml/h/ngLPL, 2.94 ± 1.60  μmol/ml/h/ng LPL, 3.72 ± 1.63  μmol/ml/h/ng LPL, 3.40 ± 1.20  μmol/ml/h/ngLPL, 3.72 ± 1.96  μmol/ml/h/ngLPL and 7.80 ± 4.48  μmol/ml/h/ng LPL, respectively. Thus, the specific activities of the patient’s LPL determined with triolein emulsified with PC were significantly higher than those with PE, PS, PI or LPC as emulsifiers. Relative to the activities of normal plasma measured with PC, PE, PS, PI and LPC as emulsifiers, the mutant’s activities were 49.1 ± 5.2%, 44.1 ± 5.7%, 31.7 ± 12.6%, 19.2 ± 6.9% and 23.8 ± 11.3%, respectively. Using PC, PE, PS, PI and LPC as emulsifiers, the mutant’s activities for triolein-lipolysis relative to normal were significantly increased in comparison to the relative activity measured with the classical emulsifier, Triton X-100 (12.9 ± 6.7%).ConclusionsImpaired triolein hydrolysis by LPL Arg243His was partially ameliorated by triolein emulsification with phospholipids. The in vitro analysis of triolein hydrolysis using various phospholipid emulsifiers may be useful for the further understanding of impaired LPL function.
Expression of Lysyl Oxidase Predictive of Distant Metastasis of Laryngeal Cancer
Authors: Lee Yoon Se , Park Yangsoon , Kwon Minsu , Roh Jong‐Lyel , Choi Seung‐Ho , Nam Soon Yuhl , Kim Sang Yoon 
Published: January 2017

ObjectiveTo investigate the prognostic significance of lysyl oxidase (LOX) expression in laryngeal cancer.Study DesignRetrospective chart review and histologic analysis.SettingTertiary referral academic center.Subjects and MethodsPatients (N = 100) underwent surgical treatment for laryngeal cancer and had tissue specimens available. Immunohistochemical staining for LOX was performed on laryngeal cancer tissue microarrays, and the proportion and intensity of staining were evaluated. Patients with LOX scores ≤6 were classified into the low LOX group, while those with scores >6 were classified into the high LOX group. We analyzed the correlation between LOX expression and clinical factors as well as prognosis.ResultsLOX was predominantly expressed in the cytoplasm and nuclei of tumor cells. Kaplan‐Meier analysis revealed that the high LOX group had worse overall survival and recurrence‐free survival rates than the low LOX group (P <. 05). LOX expression exhibited marginally significant correlation with lymph node metastasis. In the Cox regression analysis, LOX expression and lymph node metastasis were significant factors correlated with overall survival rate (odds ratio [OR] = 3.92, 95% confidence interval [95% CI]: 1.35‐11.37, P =. 012; OR = 1.96, 95% CI: 0.93‐1.43, P =. 024, respectively). LOX expression was related to distant metastasis free survival rate (OR = 7.72, 95% CI: 1.02‐19.18, P =. 048).ConclusionA high expression level of LOX is associated with lymph node and distant metastasis as well as poor prognosis among patients with laryngeal cancer.
Clinical Evidence Supporting US Food and Drug Administration Approval of Otolaryngologic Prescription Drug Indications, 2005‐2014
Authors: Rathi Vinay K. , Wang Bo , Ross Joseph S. , Downing Nicholas S. , Kesselheim Aaron S. , Gray Stacey T. 
Published: January 2017

ObjectiveThe US Food and Drug Administration (FDA) approves indications for prescription drugs based on premarket pivotal clinical studies designed to demonstrate safety and efficacy. We characterized the pivotal studies supporting FDA approval of otolaryngologic prescription drug indications.Study DesignRetrospective cross‐sectional analysis.SettingPublicly available FDA documents.SubjectsRecently approved (2005‐2014) prescription drug indications for conditions treated by otolaryngologists or their multidisciplinary teams. Drugs could be authorized for treatment of otolaryngologic disease upon initial approval (original indications) or thereafter via supplemental applications (supplemental indications).MethodsPivotal studies were categorized by enrollment, randomization, blinding, comparator type, and primary endpoint.ResultsBetween 2005 and 2014, the FDA approved 48 otolaryngologic prescription drug indications based on 64 pivotal studies, including 21 original indications (19 drugs, 31 studies) and 27 supplemental indications (18 drugs, 33 studies). Median enrollment was 299 patients (interquartile range, 198‐613) for original indications and 197 patients (interquartile range, 64‐442) for supplemental indications. Most indications were supported by ≥1 randomized study (original: 20/21 [95%], supplemental: 21/27 [78%]) and ≥1 double‐blinded study (original: 14/21 [67%], supplemental: 17/27 [63%]). About half of original indications (9/21 [43%]) and one‐quarter of supplemental indications (7/27 [26%]) were supported by ≥1 active‐controlled study. Nearly half (original: 8/21 [38%], supplemental: 14/27 [52%]) of all indications were approved based exclusively on studies using surrogate markers as primary endpoints.ConclusionThe quality of clinical evidence supporting FDA approval of otolaryngologic prescription drug indications varied widely. Otolaryngologists should consider limitations in premarket evidence when helping patients make informed treatment decisions about newly approved drugs.
Change of coagulation after NovoSeven® use for bleeding during cardiac surgery
Authors: Tomita Emi , Takase Hajime , Tajima Keiichi , Suematsu Yoshihiro 
Published: January 2017

Objectives Recombinant activated factor VII has been used for the treatment of hemophilia, factor VII deficiency, and Glanzmann’s thrombasthenia. Off-label uses have recently been increasing, and there are reports that recombinant activated factor VII is effective for the treatment of excessive bleeding during or after cardiovascular surgery. We retrospectively reviewed the effectiveness of recombinant activated factor VII and its influence on the coagulation system as a treatment for uncontrollable bleeding during cardiovascular surgery. Methods Between April 2009 and May 2015, recombinant activated factor VII was used to treat uncontrollable bleeding during cardiovascular surgery in 17 patients at our hospital. The indications for recombinant activated factor VII administration were critical uncontrollable bleeding during surgery and normal platelet and fibrinogen levels. Results Blood loss significantly decreased in every case after recombinant activated factor VII administration ( p < 0.05). No adverse thromboembolic events were encountered. The prothrombin time-international normalized ratio, activated partial thromboplastin time, fibrin degradation product and D-dimer levels decreased significantly after recombinant activated factor VII administration. One day later, all blood coagulation test values were almost within the normal ranges. Conclusions Recombinant activated factor VII has a strong hemostatic action, but it is necessary to exclude surgical bleeding to exhibit the hemostatic effect. Administration that does not comply with the indications for recombinant activated factor VII may lead to serious complications such as thromboembolism. In properly selected patients, recombinant activated factor VII is an effective agent for the treatment of uncontrollable bleeding during cardiovascular surgery.
Infratrochlear neuralgia: A prospective series of seven patients treated with infratrochlear nerve blocks
Authors: Villar-Quiles Rocío-Nur , García-Moreno Héctor , Mayo Diego , Gutiérrez-Viedma Álvaro , Ramos María-Isabel , Casas-Limón Javier , Cuadrado María-Luz 
Published: January 2017

Background Infratrochlear neuralgia is a recently described painful cranial neuropathy that causes pain in the internal angle of the orbit and the medial upper eyelid, the upper bridge of the nose and/or the lacrimal caruncle. We aim to present seven new cases of infratrochlear neuralgia treated with anaesthetic nerve blocks. Methods Over an 18-month period, we prospectively identified seven cases of infratrochlear neuralgia among the patients attending the Headache Unit in a tertiary hospital. Anaesthetic blocks were performed by injecting 0.5 cc of bupivacaine 0.5% at the emergence of the nerve above the internal canthus. Results All patients were women, and the mean age was 49.1 years (standard deviation, 17.9). The pain appeared at the internal angle of the orbit and/or the medial upper eyelid in six cases, and the whole territory of the infratrochlear nerve in one case. Six patients had continuous pain and one had episodes lasting 8–24 hours. All patients showed sensory disturbances within the painful area and tenderness upon palpation of the infratrochlear nerve. Nerve blocks resulted in complete and long-lasting relief in four patients and short-lasting relief in the other three patients. Conclusions Infratrochlear neuralgia should be considered among the neuralgic causes of orbital and periorbital pain. Anaesthetic blocks may assist clinicians in the diagnosis and may also be an effective therapy.
Endoscopic Versus Open Excision of Os Trigonum for the Treatment of Posterior Ankle Impingement Syndrome in an Athletic Population: A Randomized Controlled Study With 5-Year Follow-up
Authors: Georgiannos Dimitrios , Bisbinas Ilias 
Published: January 2017

Background: Open surgical excision of the os trigonum has been the traditional treatment for posterior ankle impingement syndrome (PAIS). However, the endoscopic excision has recently become quite popular. Purpose/Hypothesis: The purpose of our study was to compare the results of endoscopic versus open excision of a symptomatic os trigonum for the treatment of PAIS in an athletic population. It was hypothesized that the endoscopic technique would be superior to the open technique regarding functional outcomes, pain, and time to return to training and the previous sports level. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: From 2008 to 2011, 52 athletes underwent a symptomatic os trigonum excision; 26 athletes had an open procedure (group A) and 26 had an endoscopic procedure (group B). The American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score and the Visual Analog Score–Foot and Ankle (VAS-FA) were obtained, and the time to return to training and to previous sports level was recorded. Results: Patients in group B appeared to have significant improvement of AOFAS hindfoot score compared with those in group A ( P < .05), whereas no statistical significance was found for the postoperative VAS-FA scores between the 2 groups. The mean ± SD time to return to training was 9.58 ± 3.98 weeks for group A and 4.58 ± 1.47 weeks for group B ( P < .001). The time to return to previous sports level was 11.54 ± 3.89 weeks for group A and 7.12 ± 2.25 weeks for group B ( P < .001). The overall complication rate was 23% for group A (6 cases) and 3.8% for group B (1 case). Conclusion: Both the open procedure and the endoscopic approach yielded acceptable outcomes in terms of function and pain. However, complication rates were remarkably lower with endoscopic treatment, and the time to return to full activities was much shorter. Endoscopic excision of the os trigonum is a safe and effective treatment option for athletes who require early return to their previous sports level.
Between the patient and the next of kin in end-of-life care: A critical study based on feminist theory
Authors: Ramvi Ellen , Ueland Venke Irene 
Published: January 2017

Background: For the experience of end-of-life care to be ‘good’ many ethical challenges in various relationships have to be resolved. In this article, we focus on challenges in the nurse–next of kin relationship. Little is known about difficulties in this relationship, when the next of kin are seen as separate from the patient. Research problem: From the perspective of nurses: What are the ethical challenges in relation to next of kin in end-of-life care? Research design: A critical qualitative approach was used, based on four focus group interviews. Participants: A total of 22 registered nurses enrolled on an Oncology nursing specialisation programme with experience from end-of-life care from various practice areas participated. Ethical considerations: The study was approved by the Norwegian Social Science Data Service, Bergen, Norway, project number 41109, and signed informed consent obtained from the participants before the focus groups began. Findings and discussion: Two descriptive themes emerged from the inductive analysis: ‘A feeling of mistrust, control and rejection’ and ‘Being between hope and denial of next of kin and the desire of the patient to die when the time is up’. Deductive reinterpretation of data (in the light of moral distress from a Feminist ethics perspective) has made visible the constraints that certain relations with next of kin in end-of-life care lay upon the nurses’ moral identity, the relationship and their responsibility. We discuss how these constraints have political and societal dimensions, as well as personal and relational ones. Conclusion: There is complex moral distress related to the nurse–next of kin relationship which calls for ethical reflections regarding these relationships within end-of-life care.