Coronary artery calcifications and diastolic dysfunction versus visceral fat area in type 1 diabetes: VISCERA study

Aims

Type 1 diabetic patients (T1DM) experience a higher cardiovascular disease and mortality risk than controls. We investigated whether visceral adipose tissue (VAT) contributes to coronary artery calcifications (CAC) and cardiac dysfunction in T1DM.

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.     

Patients with Lynch Syndrome Mismatch Repair Gene Mutations Are at Higher Risk for Not Only Upper Tract Urothelial Cancer but Also Bladder Cancer

Background

Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer, is caused by mutations in mismatch repair (MMR) genes. An increased risk for upper tract urothelial carcinoma (UTUC) has been described in this population; however, data regarding the risk for bladder cancer (BCa) are sparse.

Objective

To assess the risk of BCa in MMR mutation carriers and suggest screening and management recommendations.

Design, setting, and participants

Cancer data from 1980 to 2007 were obtained from the Familial Gastrointestinal Cancer Registry in Toronto for 321 persons with known MMR mutations: mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli) (MLH1); mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli) (MSH2); mutS homolog 6 (E. coli) (MSH6); and PMS2 postmeiotic segregation increased 2 (S. cerevisiae) (PMS2).

Outcome measurements and statistical analysis

Standardized incidence ratios from the Ontario Cancer Registry, using the Surveillance Epidemiology and End Results public database, were used to compare cancer risk in patients with MMR mutations with the Canadian population. Microsatellite instability analysis and immunohistochemistry (IHC) of the MMR proteins were also performed and the results compared with matched sporadic bladder tumors.

Results and limitations

Eleven of 177 patients with MSH2 mutations (6.21%, p < 0.001 compared with the Canadian population) were found to have BCa, compared with 3 of 129 patients with MLH1 mutations (2.32%, p > 0.05). Of these 11 tumors, 81.8% lacked expression of MSH2 on IHC, compared with the matched sporadic cases, which all displayed normal expression of MSH2 and MLH1. The incidence of UTUC among MSH2 carriers was 3.95% (p < 0.001), and all tumors were found to be deficient in MSH2 expression on IHC. Mutations in the intron 5 splice site and exon 7 of the MSH2 gene increased the risk of urothelial cancer. Limitations include possible inflated risk estimates due to ascertainment bias.

Conclusions

LS patients with MSH2 mutations are at an increased risk for not only UTUC but also BCa and could be offered appropriate screening.     

Role of individual and household level factors on stunting: a comparative study in three Indian states

BACKGROUND: Status of growth especially in early childhood is not only the most important determinant of health of a child but also a reflection of the well-being of the entire society. The extent of malnutrition in India is very high, but the exact magnitude varies considerably depending on which indicator is used. Child health in this paper is measured through chronic malnutrition (termed as stunting). Three states were selected, namely Bihar, West Bengal and Kerala. These three states represent the three stages of development. Bihar is one of the least and Kerala is one of the most developed states in India. AIM: The present paper aims to investigate the degree of chronic malnutrition in the context of socio-economic, demographic and other characteristics of the children and their households in the three selected states in India. SUBJECTS AND METHODS: The data for this study were taken from the National Family Health Survey (NFHS-2) conducted by the International Institute for Population Sciences (IIPS), Mumbai, in 1998-1999. The NFHS-2 sample covers ever-married women in the age group 15-49 years from 26 states in India. Besides collecting information on health, the survey collects data on socio-economic and demographic characteristics at individual and household level. RESULTS: The percentage of stunting of children in Bihar, West Bengal and Kerala was found to be 54, 39 and 23%, respectively. Regression analysis showed that the major factors that significantly influenced the status of health in the children in all three states were women's education and the household condition index. Months of breastfeeding and birth interval also had some association with health status. The effect of the above-mentioned variables was most prominent in Bihar and least in Kerala in terms of statistical significance. CONCLUSION: There is a close positive link between the nutritional status of pre-school children and the stages of development of the states. Mothers' education and household condition are important influences on children's health status irrespective of the stage of development.     

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.     

Unraveling the cytotoxic potential of Temozolomide loaded into PLGA nanoparticles

Background

Nanotechnology has received great attention since a decade for the treatment of different varieties of cancer. However, there is a limited data available on the cytotoxic potential of Temozolomide (TMZ) formulations. In the current research work, an attempt has been made to understand the anti-metastatic effect of the drug after loading into PLGA nanoparticles against C6 glioma cells.Nanoparticles were prepared using solvent diffusion method and were characterized for size and morphology. Diffusion of the drug from the nanoparticles was studied by dialysis method. The designed nanoparticles were also assessed for cellular uptake using confocal microscopy and flow cytometry.

Results

PLGA nanoparticles caused a sustained release of the drug and showed a higher cellular uptake. The drug formulations also affected the cellular proliferation and motility.

Conclusion

PLGA coated nanoparticles prolong the activity of the loaded drug while retaining the anti-metastatic activity.