Plexiform Schwannoma of the Oral Cavity: Report of Eight Cases and a Review of the Literature.

Plexiform schwannoma represents an unusual schwannoma variant, characterized by multinodular growth grossly and/or microscopically. A review of the English-language literature reveals only 28 previously reported cases involving the oral cavity, and herein we present 8 additional cases. Among these 36 patients, the average age at diagnosis was 28 years (range 5 to 62 years), with a female-to-male ratio of 1.4:1. The most frequently involved sites were the tongue (n = 13) and lip (n = 11). Lesion duration prior to presentation averaged 5.3 years (range, 6 weeks to 26 years). The average lesion size was 2.1 cm (range, 0.3 to 16 cm). The typical clinical presentation was a painless mass, although infrequent findings included pain/discomfort, paresthesia, difficulty chewing, and limited buccal mobility. All cases clinically appeared as a solitary mass or localized cluster of tumor nodules, with the exception of one patient who had neurofibromatosis 2 (NF2) and exhibited two distinct nodules on the tongue and buccal mucosa. In addition, extraoral neural neoplasms were evident in four patients, including three with NF2. Typical microscopic findings included multiple well-circumscribed tumor nodules, each surrounded by a perineurium-derived capsule with immunoreactivity for epithelial membrane antigen. The nodules contained characteristically bland and diffusely S-100-positive spindle cells arranged in Antoni A and B patterns; however, modest nuclear pleomorphism was evident in three cases. Most patients (n = 23) were treated by excision or enucleation and curettage, and three patients experienced recurrence. Unlike plexiform neurofibromas, plexiform schwannomas exhibit only a weak association with neurofibromatosis and have no known malignant potential.

(Not so) Great Expectations: Listening to Foreign-Accented Speech Reduces the Brain's Anticipatory Processes.

This study examines the effect of foreign-accented speech on the predictive ability of our brain. Listeners actively anticipate upcoming linguistic information in the speech signal so as to facilitate and reduce processing load. However, it is unclear whether or not listeners also do this when they are exposed to speech from non-native speakers. In the present study, we exposed native Dutch listeners to sentences produced by native and non-native speakers while measuring their brain activity using electroencephalography. We found that listeners' brain activity differed depending on whether they listened to native or non-native speech. However, participants' overall performance as measured by word recall rate was unaffected. We discussed the results in relation to previous findings as well as the automaticity of anticipation.

Food Effects on Oral Drug Absorption: Application of Physiologically-Based Pharmacokinetic Modeling as a Predictive Tool.

The bioavailability of an orally administered small molecule is often dictated by drug-specific physicochemical characteristics and is influenced by many biological processes. For example, in fed or fasted conditions, the transit time within the gastrointestinal tract can vary, confounding the ability to predict the oral absorption. As such, the effects of food on the pharmacokinetics of compounds in the various biopharmaceutics classification system (BCS) classes need to be assessed. The consumption of food leads to physiological changes, including fluctuations in the gastric and intestinal pH, a delay in gastric emptying, an increased bile secretion, and an increased splanchnic and hepatic blood flow. Despite the significant impact of a drug's absorption and dissolution, food effects have not been fully studied and are often overlooked. Physiologically-based pharmacokinetic (PBPK) models can be used to mechanistically simulate a compound's pharmacokinetics under fed or fasted conditions, while integrating drug properties such as solubility and permeability. This review discusses the PBPK models published in the literature predicting the food effects, the models' strengths and shortcomings, as well as future steps to mitigate the current knowledge gap. We observed gaps in knowledge which limits the ability of PBPK models to predict the negative food effects and food effects in the pediatric population. Overall, the further development of PBPK models to predict food effects will provide a mechanistic basis to understand a drug's behavior in fed and fasted conditions, and will help enable the drug development process.

Adverse effects of naphthenic acids on reproductive health: A focus on placental trophoblast cells.

There is considerable concern that naphthenic acids (NA) related to oil extraction can negatively impact reproduction in mammals yet the mechanisms are unknown. Since placental dysfunction is central to many adverse pregnancy outcomes, the goal of this study was to determine the effects of NA exposure on placental trophoblast cell function. Htr-8/SVneo cells were exposed to a commercial technical NA mixture (Sigma-Aldrich) for 24 h to assess steroid production, markers of inflammation and oxidative stress. NA treatment significantly altered steroid production; progesterone was decreased at all doses tested, whereas there was a significant increase in testosterone production (125 mg/L only). There were no effects on estradiol production. In addition, NA treatment resulted in increased markers of inflammation (interleukin 1ß and prostaglandin E2) and oxidative damage to lipids and nucleic acids. These findings suggest that it is biologically plausible that NA exposure may contribute to placental dysfunction.

Microvascular retinopathy and angiographically-demonstrated coronary artery disease: A cross-sectional, observational study.

Epidemiological studies suggest retinal microvascular abnormalities predict cardiac events. This study examined microvascular features associated with coronary artery abnormalities. This was a single-centre, cross-sectional, observational study of 144 consecutive subjects undergoing coronary angiography for clinical indications. Their angiograms were deidentified and graded for disease (Leaman score, LAD stenosis ≥ 70%, number of vessels stenosed ≥ 70%), and Thrombolysis in Myocardial Infarction (TIMI) blush score. Subjects also underwent retinal photography (KOWA non-mydriatic camera, Japan), and their deidentified retinal images were graded for hypertensive microvascular retinopathy (Wong and Mitchell classification), vessel calibre using a computer-assisted method (IVAN, U Wisconsin), and diabetic retinopathy (modified Airlie House scheme) independently by a trained grader and an ophthalmologist. Retinal abnormalities were compared between subjects with high and low angiography scores using one way ANOVA, Chi squared and logistic regression analysis (StataCorp, Texas). Subjects had a mean age of 61 years (range 32-88), and included 101 males (70%). Seventeen (12%) had Leaman scores > 10.5, 46 (32%) had LAD stenosis, 13 (9%) had ≥ 3 arteries stenosed, and 20 (14%) had TIMI blush scores < 1. Twenty-six subjects (18%) had a retinal hemorrhage, and 115 (74%) a mild or moderate hypertensive retinopathy. Fifty-five (38%) had diabetes, and 24 (17%) a background (n = 20) or proliferative (n = 4) diabetic retinopathy. A retinal hemorrhage (p = 0.046), moderate microvascular retinopathy (p = 0.08) and proliferative diabetic retinopathy (p = 0.04) were all associated with a higher Leaman score. Venular calibre was increased with triple vessel disease (205.7 ± 21.6 µm, and 193.7 ± 22.3 µm in normals, p = 0.03). Diabetic retinopathy correlated with an increased TIMI blush score (p = 0.01). Retinal microvascular imaging warrants further evaluation in identifying the presence, extent and nature of coronary artery disease.

Backward Dependencies and in-Situ wh-Questions as Test Cases on How to Approach Experimental Linguistics Research That Pursues Theoretical Linguistics Questions.

The empirical study of language is a young field in contemporary linguistics. This being the case, and following a natural development process, the field is currently at a stage where different research methods and experimental approaches are being put into question in terms of their validity. Without pretending to provide an answer with respect to the best way to conduct linguistics related experimental research, in this article we aim at examining the process that researchers follow in the design and implementation of experimental linguistics research with a goal to validate specific theoretical linguistic analyses. First, we discuss the general challenges that experimental work faces in finding a compromise between addressing theoretically relevant questions and being able to implement these questions in a specific controlled experimental paradigm. We discuss the Granularity Mismatch Problem (Poeppel and Embick, 2005) which addresses the challenges that research that is trying to bridge the representations and computations of language and their psycholinguistic/neurolinguistic evidence faces, and the basic assumptions that interdisciplinary research needs to consider due to the different conceptual granularity of the objects under study. To illustrate the practical implications of the points addressed, we compare two approaches to perform linguistic experimental research by reviewing a number of our own studies strongly grounded on theoretically informed questions. First, we show how linguistic phenomena similar at a conceptual level can be tested within the same language using measurement of event-related potentials (ERP) by discussing results from two ERP experiments on the processing of long-distance backward dependencies that involve coreference and negative polarity items respectively in Dutch. Second, we examine how the same linguistic phenomenon can be tested in different languages using reading time measures by discussing the outcome of four self-paced reading experiments on the processing of in-situ wh-questions in Mandarin Chinese and French. Finally, we review the implications that our findings have for the specific theoretical linguistics questions that we originally aimed to address. We conclude with an overview of the general insights that can be gained from the role of structural hierarchy and grammatical constraints in processing and the existing limitations on the generalization of results.

Active search for antecedents in cataphoric pronoun resolution.

Cataphoric dependencies where a pronoun precedes its antecedent appear to call on different mechanisms in language comprehension from forward dependencies where the antecedent precedes the pronoun. Previous research has shown that the resolution of cataphoric dependencies involves predictive processes such as the active search mechanism, which hypothesizes the automatic search for an antecedent immediately after encountering a cataphoric pronoun. The current study employs gender mismatch to investigate whether the active search for an antecedent of a cataphoric pronoun is restricted only to grammatically licit positions. We present results from an event-related potential experiment on the reading comprehension of cataphoric dependencies in Dutch. Results show that gender mismatch gives rise to an anterior negativity at grammatically licit antecedent positions only. We hypothesize that this negativity reflects the prediction failure for an antecedent after encountering a pronoun, rather than a gender mismatch. We discuss the timing, topography and functionality of this negativity with respect to previous studies and how this relates to the ERPs elicited in the processing of structural constraints on pronoun resolution.

A high pH based reversed-phase high performance liquid chromatographic method for the analysis of aminoglycoside plazomicin and its impurities.

A reversed-phase high performance liquid chromatographic (RP-HPLC) method has been developed for the aminoglycoside (AG) plazomicin (ACHN-490). This method employed a high pH mobile phase (pH>11) with a gradient of 0.25 M ammonium hydroxide in water and acetonitrile, an XBridge C(18) column and UV detection at 210 nm. Although the molar UV absorption of plazomicin is weak, the high pH conditions of this method allow for higher loadings, which compensates for the inherent low UV sensitivity. Under these high pH conditions, impurities and degradants were base line separated from plazomicin. The mobile phases used for this method allowed for on-line mass detection for the impurities and degradants. The RP-HPLC method has been validated in terms of specificity, linearity and range, accuracy, and precision. The analytical method met specificity requirements of a homogenous peak with no interferences from the blank or from the known impurities in plazomicin. The linearity of the method for the plazomicin impurity determination was excellent, with a coefficient of determination (r(2)) of 0.9993, over the freebase (FB) concentration range of 0.0025-3.0 mg/mL. The method is capable of detecting impurities down to 0.1% of the peak area of plazomicin. A single point standard at a concentration of 1.0 mg/mL FB was validated over the range of 50-150% for quantitation of the freebase content (the assay) in bulk drug substance. The mean recoveries of FB are in the range 98.6-102.0% with a mean RSD (relative standard deviation) <1.0%. The study also examined the method precision for purity, impurities and the assay with two instruments on two different days. The method showed adequate accuracy and precision for the intended use. This high pH method was successfully used to determine the impurity and measure the drug content in the final plazomicin drug substance. In addition, the method with an on-line mass spectrometry detector has been used to characterize the structures of the impurities in plazomicin.

Improving Compliance with NICE Guidelines on Parkinson's isease: A Quality Improvement Study.

Parkinson's disease can progressively affect daily function and multidisciplinary teamwork is essential to provide high quality care. The National Institute of Health and Clinical Excellence (NICE) issued guidelines regarding diagnosis, follow-up, and multidisciplinary care. This quality improvement project sought to measure and improve the compliance of service provision against the guidelines. In total, 3 audit cycles were completed. Each audit involved reviewing notes of patients attending a Parkinson's disease outpatient clinic against the PD NICE guidelines audit criteria. The first and second audits showed compliance was high for the criteria relating to initial diagnosis and referral but poor for those criteria relating to multidisciplinary referral. A pro forma stamp was recommended to be placed in the notes at each regular Parkinson's outpatient review by a specified date (October 2009), with re-audit occurring in June 2011 as part of the official hospital audit plan. Compliance to the NICE criteria improved to 100% on all criteria measured. However, it was evident from the notes that the pro forma that had been recommended by the previous audit had been in use but was not at present. In fact the pro forma had been so successful that the clinicians had made each of the criteria a routine part of their consultations and so did not need to rely on it. Use of a checklist can have a lasting improvement on compliance with NICE guidelines, even if the intervention itself is transient.

Acupuncture for polycystic ovarian syndrome.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is characterised by the clinical signs of oligo-amenorrhoea (infrequent or very light menstruation), infertility (failure to conceive), and hirsutism (excessive hair growth). Whilst Aleem 1987 revealed the presence of beta-endorphin in the follicular fluid of both normal and polycystic ovaries, Petraglia 1987 demonstrated that the beta-endorphin levels in ovarian follicular fluid of otherwise healthy women who were undergoing ovulation were much higher than the levels measured in plasma. Given that acupuncture has an impact on beta-endorphin production, which may affect gonadotropin-releasing hormone (GnRH) secretion, it is postulated that acupuncture may have a role in ovulation induction and fertility. OBJECTIVES: To assess the efficacy and safety of acupuncture treatment for women with polycystic ovarian syndrome (PCOS). SEARCH STRATEGY: Relevant studies were identified from the Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), Ovid MEDLINE® In-Process and other non-indexed citations, Ovid MEDLINE® Daily and Ovid MEDLINE(R), EMBASE, PsycINFO, AMED, Chinese National Knowledge Infrastructure (CNKI) (including the Chinese journal full-text database (CJFD)), Chinese BioMedical Literature Database (CBM), VIP database for Chinese Technical Periodicals, China's important Conference Papers Database, and the China dissertation database. SELECTION CRITERIA: Truly randomised controlled trials (RCTs) that studied the efficacy of acupuncture treatment for infertility in women with PCOS. We excluded quasi- or pseudo-RCTs. DATA COLLECTION AND ANALYSIS: We aimed to extract data independently by three authors using a piloted data extraction form. Data on study characteristics including methods, participants, interventions, and outcomes would be extracted. Crossover trials were not included unless there were first-phase data provided. Non-randomised controlled studies have been excluded. MAIN RESULTS: No truly randomised controlled trials of acupuncture for PCOS were found . AUTHORS' CONCLUSIONS: The current conventional medical treatments for women with PCOS are prescription medications, surgery, and lifestyle changes. Associated problems with current western therapies are the cost, risk of multiple pregnancies, undesirable side effects, and inconsistent effectiveness. Non-randomised acupuncture studies in PCOS have suggested a low associated adverse events rate, no increased risk of multiple pregnancies, and that it is inexpensive. However, there no RCTs have been performed in this area thus far. Therefore, properly designed RCTs are required before a conclusive statement can be drawn to support the use of acupuncture in the management of PCOS.

Could it be Henoch-Schonlein purpura?

BACKGROUND: Henoch-Schönlein purpura is the most common form of systemic vasculitis in the paediatric setting with 90% of cases occuring in childhood. Although diagnosis in the primary care setting may be difficult, it is vital in order to avoid significant complications. OBJECTIVE: This article outlines the pathogenesis, clinical manifestations and classification of Henoch-Schönlein purpura and details evidence based investigations and management. DISCUSSION: Henoch-Schönlein purpura is a self limiting disease characterised by a tetrad of clinical manifestations that vary in occurrence and order of presentation. There is no single diagnostic test to confirm Henoch- Schönlein purpura; diagnosis depends on recognition of clinical manifestations. Management usually occurs in the ambulatory setting and is mainly supportive. Priorities include symptom relief and preventive therapy to reduce the risk of complications. Further trials to clarify the role of glucocorticosteroids are needed before a definitive role for steroids in the management of Henoch-Schönlein purpura can be established.

A swine model of pseudo-pulseless electrical activity induced by partial asphyxiation.

BACKGROUND: The incidence of pulseless electrical activity (PEA) as a presenting rhythm during cardiac arrest is increasing. The current animal models of PEA arrest, post-countershock or total asphyxiation, unreliably generate PEA for a specific time period. Neither of these models predictably generate pseudo-PEA. The purpose of this study was to create an animal model of pseudo-PEA that will allow for a prolonged time period in this arrest state for future research. METHODS: In a laboratory setting, five ventilated swine on inhaled anesthesia and 100% oxygen with continuous EKG recordings were instrumented with central aortic and venous pressure-transducing catheters. Animals were then switched to intravenous anesthesia while being ventilated with a 16% oxygen/84% nitrogen mix. Continuous EKG, aortic and venous pressures were recorded to a computerized data collection program. Arterial blood gas samples were taken every 10min. Time until onset of pseudo-PEA, duration of pseudo-PEA, and cardiac rhythm during pseudo-PEA were recorded. RESULTS: Mean time to onset of pseudo-PEA was 80.6+/-47.3min. Mean duration of pseudo-PEA was 18.6+/-6.2min. Mean arterial pH at pseudo-PEA onset was 7.20+/-0.05 with a mean associated base excess of -11.4+/--5.94. No significant differences were noted in other recorded variables. CONCLUSIONS: Partial asphyxiation using a 16% oxygen/84% nitrogen mix is a reliable laboratory method to create a prolonged state of pseudo-PEA in a swine model. The mechanism generating pseudo-PEA is hypoxemia-induced systemic acidosis. This model will allow sufficient time in this low-flow cardiac state for future research to be conducted.