An Innovative and Simple Approach to Functional Salivary Reservoir Fabrication

Saliva is a valuable oral fluid that is often taken for granted. Impaired salivary function is a major and a debilitating sequela of radiation treatment for patients with head and neck cancer. It can persist for years and thereby increases the risk of oral infection significantly. Moreover, it has a notably negative impact on the quality of life of such patients. To help overcome this problem, a number of techniques have been proposed for incorporating a reservoir containing salivary substitute into a removable prosthesis. A new design for a functional salivary reservoir is presented here. This design is simple to construct and easily maintained by the wearer. Details of its design, construction, and other potential advantages are presented.     

An Anatomic Study on Whether the Patella is Centered in an Ideal Anteroposterior Radiograph of the Knee

BackgroundCurrently, an anteroposterior radiograph of the knee is judged based on a centered position of the patella between the femoral condyles. We are not aware of any anatomic literature supporting this recommendation.Questions/PurposesOrthogonal images are required for accurate assessment of knee deformity. Although an image with the patella centered at the distal femur is generally accepted as a true anteroposterior (AP) radiograph of the knee, there is minimal anatomic data to support that this view is orthogonal to a true lateral view of the knee where the condyles are overlapped. We designed an anatomical study to test the relationship between these two radiographic views.MethodsWe studied 428 well-preserved cadaveric skeletons ranging from 40 to 79 years of age at death. Centering of the patella was calculated based on distal femoral and patellar widths. Multiple regression analysis was then performed to determine the relationship between patellar centering and age, gender, ethnicity, mechanical lateral distal femoral angle (mLDFA), medial proximal tibial angle (MPTA), femoral anteversion, and contralateral centering.ResultsAverage patellar centering was 0.13 ± 0.04, indicating that the average patella was laterally positioned in the distal femur. Only mLDFA and contralateral centering showed statistically significant independent correlations with patellar centering with modest standardized beta coefficients of 0.10 and 0.23, respectively.ConclusionsIn the average specimen, the patella is laterally deviated by 13% of the condylar width. Clinicians should be aware that a lateral view with the femoral condyles overlapped is not always orthogonal to a patella-centered AP view when planning and implementing deformity correction.

Electronic supplementary material

The online version of this article (doi:10.1007/s11420-014-9419-3) contains supplementary material, which is available to authorized users.     

Does Acetaldehyde Mediate Ethanol Action in the Central Nervous System?

BACKGROUND: Some of the effects of ethanol in the central nervous system are due to changes in function of ligand-gated ion channels. Production of detectable amounts of acetaldehyde, a primary metabolite of ethanol, has been demonstrated in brain homogenates. The aim of this study was to determine whether central actions that are often attributed to ethanol may actually be mediated by acetaldehyde. METHODS: The effects of acetaldehyde (1-1000 microM) were tested by two-electrode voltage-clamp electrophysiology in Xenopus laevis oocytes expressing 10 different ligand-gated ion channel receptors [alpha1 glycine; alpha1beta2gamma2Sgamma-aminobutyric acid (GABA)A; rho1 GABAc; 5-hydroxytryptamine-3A; NR1a/NR2A NMDA; GluR1/GluR2 AMPA; GluR6/KA2 kainate; and alpha4beta2, alpha4beta4, and alpha2beta4 nicotinic-acetylcholine] and the G-protein-coupled inward rectifying potassium channel GIRK2. We also investigated the effect of acetaldehyde on the dopamine transporter (DAT), performing dopamine uptake assays in oocytes expressing DAT. RESULTS: Acetaldehyde (1 and 10 microM) significantly enhanced alpha1 glycine receptor-mediated currents. Acetaldehyde did not affect the function of any of the other receptors tested or the potassium currents measured in GIRK2 channels. Moreover, acetaldehyde did not alter the DAT-mediated dopamine uptake. CONCLUSIONS: Our results suggest a potential minor role for acetaldehyde in the glycine receptor-mediated effects of ethanol. Otherwise, acetaldehyde does not modulate function of the neuronal receptors tested in this study, in GIRK channels or DAT, when expressed recombinantly in Xenopus laevis oocytes.     

An Observational Study of Social and Emotional Support in Smoking Cessation Twitter Accounts: Content Analysis of Tweets

Background

Smoking continues to be the number one preventable cause of premature death in the United States. While evidence for the effectiveness of smoking cessation interventions has increased rapidly, questions remain on how to effectively disseminate these findings. Twitter, the second largest online social network, provides a natural way of disseminating information. Health communicators can use Twitter to inform smokers, provide social support, and attract them to other interventions. A key challenge for health researchers is how to frame their communications to maximize the engagement of smokers.

Objective

Our aim was to examine current Twitter activity for smoking cessation.

Methods

Active smoking cessation related Twitter accounts (N=18) were identified. Their 50 most recent tweets were content coded using a schema adapted from the Roter Interaction Analysis System (RIAS), a theory-based, validated coding method. Using negative binomial regression, the association of number of followers and frequency of individual tweet content at baseline was assessed. The difference in followership at 6 months (compared to baseline) to the frequency of tweet content was compared using linear regression. Both analyses were adjusted by account type (organizational or not organizational).

Results

The 18 accounts had 60,609 followers at baseline and 68,167 at 6 months. A total of 24% of tweets were socioemotional support (mean 11.8, SD 9.8), 14% (mean 7, SD 8.4) were encouraging/engagement, and 62% (mean 31.2, SD 15.2) were informational. At baseline, higher frequency of socioemotional support and encouraging/engaging tweets was significantly associated with higher number of followers (socioemotional: incident rate ratio [IRR] 1.09, 95% CI 1.02-1.20; encouraging/engaging: IRR 1.06, 95% CI 1.00-1.12). Conversely, higher frequency of informational tweets was significantly associated with lower number of followers (IRR 0.95, 95% CI 0.92-0.98). At 6 months, for every increase by 1 in socioemotional tweets, the change in followership significantly increased by 43.94 (P=.027); the association was slightly attenuated after adjusting by account type and was not significant (P=.064).

Conclusions

Smoking cessation activity does exist on Twitter. Preliminary findings suggest that certain content strategies can be used to encourage followership, and this needs to be further investigated.     

Increased thrombin generation in splanchnic vein thrombosis is related to the presence of liver cirrhosis and not to the thrombotic event

Introduction

In recent years there have been increasing evidence associating liver disease with hypercoagulability, rather than bleeding. The aim of the study was to evaluate the haemostatic potential in patients with liver disease.

Patients and methods

We measured thrombin generation in the presence and absence of thrombomodulin in patients with portal vein thrombosis (PVT, n = 47), Budd-Chiari syndrome (BCS, n = 15) and cirrhosis (n = 24) and compared the results to those obtained from healthy controls (n = 21). Fifteen patients with PVT and 10 patients with BCS were treated with warfarin and were compared to an equal number of patients with atrial fibrillation matched for prothrombin time-international normalized ratio. We assessed resistance to thrombomodulin by using ratios [marker measured in the presence/absence of thrombomodulin].

Results

There were no differences in thrombin generation between patients on warfarin treatment and their controls. Cirrhotic patients generated more thrombin in the presence of thrombomodulin and exhibited thrombomodulin resistance compared to controls [p = 0.006 for endogenous thrombin potential (ETP) and p < 0.001 for peak thrombin and both ratios ETP and peak] and patients with non-cirrhotic PVT (p = 0.001, p = 0.006, p < 0.001, p < 0.001 for ETP, peak, ratio ETP, ratio peak, respectively). The patients with cirrhotic PVT exhibited higher ETP (p = 0.044) and peak (p = 0.02) in the presence of thrombomodulin than controls, as well as thrombomodulin resistance (ETP and peak ratios: p = 0.001).

Conclusions

Hypercoagulability and thrombomodulin resistance in patients with cirrhosis were independent of the presence of splanchnic vein thrombosis. The hypercoagulability in patients with cirrhotic PVT could have implications for considering longer or more intensive treatment with anticoagulants in this group.     

Investigation of the urge-to-cough sensation in healthy volunteers

Background and objective: Recently, there has been interest in the sensation of irritation that precedes the motor act of coughing, which has been termed the urge‐to‐cough (UTC). The aim of this study was to perform the largest evaluation to date of the UTC threshold (C_u) in a healthy population. The specific aims were to investigate the relationship between C_u and cough reflex sensitivity, to evaluate gender differences in the UTC and to assess the reproducibility of measurements of C_u. Methods: Standard capsaicin cough challenge methodology was employed to measure cough reflex sensitivity in 100 healthy adult non‐smokers (50 females) with the additional measurement of C_u. A subgroup of 40 subjects (20 males) underwent repeat cough challenges after 1 week to examine the reproducibility of the measurements. Results: All 100 subjects demonstrated motor cough in response to capsaicin. Twenty‐one subjects (10 females) did not show a discernible C_u, as the motor cough event preceded a UTC sensation unaccompanied by cough. Although cough reflex sensitivity, as measured by the concentration of capsaicin inducing five or more coughs (C₅), was enhanced in women, there was no gender difference in C_u. Similar to standard cough reflex sensitivity measurements, the measurement of C_u was highly reproducible. Conclusions: These results demonstrate that the UTC threshold can be effectively and reproducibly measured using a modification of standard cough challenge methodology. Given its clinical significance as a prevalent symptom, UTC, as measured by C_u, represents an additional relevant end point for studies investigating the effects of pharmacological and other interventions in cough and cough reflex sensitivity.     

Structural requirements for imidazo[1,2-a]pyrazine derivatives as Aurora A kinase inhibitors and validation of the model

Aurora kinases belong to the family of serine/threonine kinases. They are divided into three subclasses, Aurora A kinase, Aurora B kinase, and Aurora C kinase and are reported to be vital for cell proliferation. Abnormal expression of these enzymes leads to cancer. Predictive CoMFA and CoMSIA based quantitative structure activity relationship models have been developed on 51 imidazo[1,2-a]pyrazine derivatives reported previously by Merck Research Laboratories. AutoDock was used for docking of the most active compound (34) and the conformation thus obtained was used for the alignment of 3D structures. The developed (CoMSIA-SEHD) model showed good predictive ability with predictive squared correlation coefficient (r ²) value of 0.752. The best model was validated systematically using different validation parameters. The CoMSIA model gave useful information to understand features required to modify and develop new potential Aurora kinase inhibitors.