Localization of histamine (H1, H2, H3 and H4) receptors in mouse inner ear

Conclusion The present findings show that all four types of histamine receptors (H1R, H2R, H3R, and H4R) are present in the inner ear, thus supporting the hypothesis that histamine plays a physiological role in the inner ear. Objective To analyse the presence of histamine receptors in the normal mouse inner ear. Methods CBA/J mice were used in this study. The localization of H1R, H2R, H3R, and H4R in the inner ear, i.e. cochlea, vestibular end organs, vestibular ganglion, and endolymphatic sac, was studied by real-time PCR and immunohistochemistry. Results The mRNA for each receptor sub-type was detected in the inner ear. In the immunohistochemical study, the organ of Corti, spiral ganglion, vestibular ganglion, vestibular sensory epithelium, and endolymphatic sac cells showed an immunofluorescent reaction to all histamine receptors.     

High stromal versican expression predicts unfavourable outcome in oral squamous cell carcinoma

BACKGROUND: Versican, an extracellular matrix proteoglycan, has been noted to be expressed in several malignant tumours and has been suggested to play an important role in cancer development and tumour growth. AIMS: To investigate whether the versican expression level in the peritumoural stromal tissue of primary oral squamous cell carcinoma (OSCC) predicts relapse-free or disease-specific survival. Also, to study the associations between versican expression and several other clinicopathological variables, as well as tumour cell proliferation. METHODS: Immunohistochemistry was used to study the expression of versican and tumour cell proliferative activity in 139 OSCCs. All pertinent clinical data were collected retrospectively from the hospital records. RESULTS: In this cohort, versican expression did not correlate with the clinicopathological factors or tumour cell proliferation. In univariate analyses, higher risk for disease recurrence was associated with higher stromal versican expression score (p = 0.02), positive neck node status (p = 0.02), lower Karnofsky performance status (p = 0.03) and higher tumour cell proliferation index (p = 0.04). Increased disease-specific risk of death was associated with high stromal versican expression score (p = 0.005) higher T class (p = 0.002), positive neck node status (p<0.001), higher stage (p<0.001), poorer histological differentiation (p = 0.005), worse general condition of the patient (p = 0.049) and increased tumour cell proliferative index (p = 0.02). In multivariate disease-specific survival analysis, high stromal versican expression score (p = 0.048), poorer histological differentiation (p = 0.047) and higher stage (p = 0.002) independently predicted poorer disease outcome. CONCLUSIONS: In this cohort, increased stromal versican expression correlated with both increased risk for disease recurrence and shortened survival. High stromal versican expression may thus be considered an independent and adverse prognostic marker in OSCC.     

Evaluation of current care effectiveness: a survey of hypertension guideline implementation in Finnish health centres

OBJECTIVE: To assess the extent and style of implementation of the Hypertension Guideline (HT Guideline) in Finnish primary health centres, and to identify a scale of contrasting implementation styles in the health centres (with the two ends of the scale being referred to as information implementers or disseminators respectively). DESIGN: A cross-sectional study. Development of a questionnaire and criteria for assessing the extent and style of implementation of the HT Guideline. SETTING: Primary healthcare. SUBJECTS: All head physicians and senior nursing officers in Finnish health centres (n =290). MAIN OUTCOME MEASURES: The extent of adoption of the HT Guideline in health centres and the characteristics associated with the implementation style. RESULTS: Responses were received from 410 senior medical staff (246 senior nursing officers and 164 head physicians) representing altogether 264 health centres (91%) in Finland. The HT Guideline had been introduced into clinical practice in most health centres (89%). The style of implementation varied widely between health centres: at opposite ends of the implementation scale were 21 implementer health centres, which used multiple implementation channels, and 23 disseminator health centres, which used few or no implementation channels. The implementers had typically larger population bases and had organized services around the family doctor system, while the disseminators were smaller and had organized services according to a traditional model (appointments could be with any doctor in the surgery). CONCLUSION: The Finnish HT Guideline has become well known in most health centres since being introduced into clinical practice. However, the style of implementation varies markedly between health centres.     

Quantification of alkylresorcinol metabolites in urine by HPLC with coulometric electrode array detection

BACKGROUND: Whole-grain rye and wheat cereals contain high amounts of alkylresorcinols (ARs), phenolic lipids. ARs can be quantified in plasma. Two recently identified urinary AR metabolites, 3,5-dihydroxyphenylbenzoic acid (DHBA) and 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), may be useful as biomarkers of intake of whole-grain rye and wheat. METHODS: We evaluated 4 pretreatment protocols for quantifying urinary DHBA and DHPPA using HPLC coupled with a coulometric electrode array detector. Syringic acid was used as the internal calibrator. RESULTS: Measured urinary concentrations of DHBA and DHPPA were 0.8-115 micromol/L. The mean recoveries of all added concentrations were 85%-104% for DHBA and 86%-99% for DHPPA, depending on the degree of the purification. The protocol versions with less purification correlated well with the protocol including highest purification. The correlation coefficients (r(2)) were 0.9699-0.8153 for DHBA and 0.9854-0.8371 for DHPPA. CONCLUSION: Although the protocol with the most purification steps was most specific, all protocols were suitable for measuring DHBA and DHPPA in urine. The rapid protocol with simple hydrolysis could be used in large-scale clinical studies. Additional investigation is needed to clarify whether these metabolites are useful biomarkers of whole-grain intake and helpful in the exploration of its association with human diseases.     

Recent Advances in Polymer Nanocomposites Based on Polyethylene and Polyvinylchloride for Power Cables

Polymer nanocomposites used in underground cables have been of great interest to researchers over the past 10 years. Their preparation and the dispersion of the nanoparticles through the polymer host matrix are the key factors leading to their enhanced dielectric properties. Their important dielectric properties are breakdown strength, permittivity, conductivity, dielectric loss, space charge accumulation, tracking, and erosion, and partial discharge. An overview of recent advances in polymer nanocomposites based on LDPE, HDPE, XLPE, and PVC is presented, focusing on their preparation and electrical properties.     

A function of the hepatitis B virus precore protein is to regulate the immune response to the core antigen

A unique characteristic of the hepatitis B virus is the production of a secreted form (precore or HBeAg) of the structural nucleocapsid (core or HBcAg). By using T cell receptor (TCR) transgenic (Tg) and TCR x HBc/HBeAg double- and triple-Tg pairs, we demonstrate that HBeAg elicits T cell tolerance, whereas HBcAg is nontolerogenic in this system. In fact, TCR x HBc double-Tg mice spontaneously seroconvert to IgG anti-HBc positivity at an early age. However, the presence of HBeAg in the serum of TCR x HBc x HBe triple-Tg mice prevents anti-HBc seroconversion. HBeAg mediates its immunoregulatory effect by eliciting tolerance in HBc/HBeAg-specific T cells. The results suggest that hepadnaviruses have retained a secretory form of the nucleoprotein because it functions as a T cell tolerogen and regulates the immune response to the intracellular nucleocapsid. This HBeAg-mediated immune regulation may predispose to chronicity during perinatal infections and prevent severe liver injury during adult infections.     

Outcomes of transoral laser microsurgery and transoral robotic surgery in oropharyngeal squamous cell carcinoma

ObjectiveTransoral robotic surgery (TORS) has evolved to a standard therapy modality for oropharyngeal carcinoma, especially in T1/ T2 tumors involving the base of the tongue due to its advantages compared with open surgery. However, knowledge about its benefits compared with transoral laser microsurgery (TLM) are scarce. This study compares oncological and functional results of TLM or TORS in the treatment of oropharyngeal squamous cell carcinoma (OPSCC).MethodsThis retrospective analysis comprises all patients with OPSCC treated with TLM (n = 30) or TORS (n = 24) between April 2003 and May 2018 (follow-up 43 ± 38.3 months). Both treatment groups (TLM and TORS) were comparable in terms of the stage of the disease, prognosis-determining factors, and adjuvant therapy modalities.ResultsThere were no significant differences regarding to the resection status (p = 0.272), the rate of local- (p = 0.834) and distant- recurrence (p = 0.416), with a disease-free survival of 86.7 % and 87.5 %, respectively (p = 0.892). In addition, we could not confirm any differences regarding to operating time (p = 0.860), intraoperative blood loss (p = 0.660), inpatient stay (p = 0.585) and postoperative bleeding rate (p = 0.245). The frequency of tracheostomy and percutaneous endoscopic gastrostomy between both groups is comparable, with a longer duration of tube feeding in patients who have received TLM (p = 0.030).ConclusionIn conclusion, TORS allows for similar oncological outcomes compared with TLM at comparable perioperative risks. The postoperative swallowing function may benefit from TORS.     

Cerebellar Inhibitory Output Shapes the Temporal Dynamics of Its Somatosensory Inferior Olivary Input

The cerebellum is necessary and sufficient for the acquisition and execution of adaptively timed conditioned motor responses following repeated paired presentations of a conditioned stimulus and an unconditioned stimulus. The underlying plasticity depends on the convergence of conditioned and unconditioned stimuli signals relayed to the cerebellum by the pontine nucleus and the inferior olive (IO), respectively. Adaptive timing of conditioned responses relies on the correctly predicted onset of the unconditioned stimulus, usually a noxious somatosensory stimulus. We addressed two questions: First, does the IO relay information regarding the duration of somatosensory stimuli to the cerebellum? Multiple-unit recordings from the IO of anesthetized rats that received periorbital airpuffs of various durations revealed that sustained somatosensory stimuli are invariably transformed into phasic IO outputs. The phasic response was followed by a post-peak depression in IO activity as compared to baseline, providing the cerebellum with a highly synchronous signal, time-locked to the stimulus’ onset. Second, we sought to examine the involvement of olivocerebellar interactions in this signal transformation. Cerebello-olivary inhibition was interrupted using temporary pharmacological inactivation of cerebellar output nuclei, resulting in more sustained (i.e., less synchronous) IO responses to sustained somatosensory stimuli, in which the post-peak depression was substituted with elevated activity as compared to baseline. We discuss the possible roles of olivocerebellar negative-feedback loops and baseline cerebello-olivary inhibition levels in shaping the temporal dynamics of the IO’s response to somatosensory stimuli and the consequences of this shaping for cerebellar plasticity and its ability to adapt to varying contexts.