Mutant p53–associated myosin-X upregulation promotes breast cancer invasion and metastasis

Mutations of the tumor suppressor TP53 are present in many forms of human cancer and are associated with increased tumor cell invasion and metastasis. Several mechanisms have been identified for promoting dissemination of cancer cells with TP53 mutations, including increased targeting of integrins to the plasma membrane. Here, we demonstrate a role for the filopodia-inducing motor protein Myosin-X (Myo10) in mutant p53–driven cancer invasion. Analysis of gene expression profiles from 2 breast cancer data sets revealed that MYO10 was highly expressed in aggressive cancer subtypes. Myo10 was required for breast cancer cell invasion and dissemination in multiple cancer cell lines and murine models of cancer metastasis. Evaluation of a Myo10 mutant without the integrin-binding domain revealed that the ability of Myo10 to transport β₁ integrins to the filopodia tip is required for invasion. Introduction of mutant p53 promoted Myo10 expression in cancer cells and pancreatic ductal adenocarcinoma in mice, whereas suppression of endogenous mutant p53 attenuated Myo10 levels and cell invasion. In clinical breast carcinomas, Myo10 was predominantly expressed at the invasive edges and correlated with the presence of TP53 mutations and poor prognosis. These data indicate that Myo10 upregulation in mutant p53–driven cancers is necessary for invasion and that plasma-membrane protrusions, such as filopodia, may serve as specialized metastatic engines.     

Adverse events following immunization with pentavalent vaccine: experiences of newly introduced vaccine in Iran

Background

The most important factors that affect the incidence of vaccine-related complications are the constituent biological components of the vaccine, injection site reactions, age and sex. The aim of this study is to determine the incidence rate of adverse events following immunization with pentavalent vaccine (DTPw-Hep B-Hib (PRP-T) vaccine (pentavac) (adsorbed) is manufactured by Serum Institute of India ltd), which was introduced in Iran in November 2014. It is important to monitor vaccine-related adverse events because of the role of vaccine safety in immunization program success.

Methods

This study was a mixed cohort study that included 1119 children less than 1 year of age. In 2015, the children were referred to Hamadan health centers to receive pentavalent vaccine at 2, 4 and 6 months of age. The data were collected from the parents of the children using a questionnaire that was administered either face-to-face or by telephone. The cumulative incidence of side effects and risk ratio was reported with 95% confidence intervals (CI). Chi-squared tests and logistic regressions were used to investigate the association between the variables.

Results

The cumulative incidence rate of pentavalent-related adverse events during 48 h following immunization was estimated to be 15.8% for swelling, 10.9% for redness, 44.2% for pain, 12.6% for mild fever, 0.1% for high fever, 20.0% for drowsiness, 15.0% for loss of appetite, 32.9% for irritability, 4.6% for vomiting and 5.5% for persistent crying. There is no evidence for the occurrence of convulsion and encephalopathy among children who receive pentavalent vaccines.

Conclusion

Further large studies with long time follow up are required to address rare events include convulsions, encephalopathy or persistent crying. However, Findings urge immunization programs to use pentavalent vaccinations and to continue implementing the current immunization program in children under 1 year of age.

     

The More Publication,the Higher Impact Factor: Citation Analysis of Top Nine Gastroenterology and Hepatology Journals

Background

The impact factor (IF), as the most important criterion for journal’s quality measurement, is affected by the self-citation and number of publications in each journal.

Objectives

To find out the relationship between the number of publications and self-citations in a journal, and their correlations with IF.

Materials and Methods

Self-citations and impact factors of nine top gastroenterology and hepatology journals were assessed during the seven recent years (2005-2011) through Journal Citation Reports (JCR, ISI Thomson Reuters).

Results

Although impact factors of all journals increased during the study, five out of nine journals increased the number of publications from 2005 to 2011. There was an increase in self-citation only in the journal of HEPATOLOGY (499 in 2005 vs. 707 in 2011). Impact factors of journals (6.5 ± 3.5) were positively correlated with total number of publications (248.6 ± 91.7) (R: 0.688, P < 0.001). Besides, the self-citation rate (238.73 ± 195.317) was highly correlated with total number of publications in each journal (248.6 ± 91.7) (R: 0.861, P < 0.001). On the other hand, impact factor without self-citation (6.08 ± 3.3) had a correlation (R: 0.672, P < 0.001) with the number of published items (248.6 ± 91.7).

Conclusions

The number of articles and self-citation have definite effects on IF of a journal and because IF is the most prominent criterion for journal’s quality measurement, it would be a good idea to consider factors affecting on IF such as self-citation.     

Emotion unfolded by motion: a role for parietal lobe in decoding dynamic facial expressions

Facial expressions convey important emotional and social information and are frequently applied in investigations of human affective processing. Dynamic faces may provide higher ecological validity to examine perceptual and cognitive processing of facial expressions. Higher order processing of emotional faces was addressed by varying the task and virtual face models systematically. Blood oxygenation level-dependent activation was assessed using functional magnetic resonance imaging in 20 healthy volunteers while viewing and evaluating either emotion or gender intensity of dynamic face stimuli. A general linear model analysis revealed that high valence activated a network of motion-responsive areas, indicating that visual motion areas support perceptual coding for the motion-based intensity of facial expressions. The comparison of emotion with gender discrimination task revealed increased activation of inferior parietal lobule, which highlights the involvement of parietal areas in processing of high level features of faces. Dynamic emotional stimuli may help to emphasize functions of the hypothesized ‘extended’ over the ‘core’ system for face processing.     

Distribution of hepatitis C virus genotype in Iranian multiply transfused patients with thalassemia

BACKGROUND: Hepatitis C virus (HCV) infection is the most common transfusion-transmitted disease in multiply transfused patients worldwide. In this study, the aim was to investigate distribution of HCV genotypes in Iranian patients with thalassemia.
STUDY DESIGN AND METHODS: Blood samples were received from 280 multiply transfused patients with thalassemia with chronic hepatitis C who were referred to us to start pegylated interferon-α plus ribavirin for duration of 48 weeks. HCV RNA viral load was detected using Amplicor test (Version 2, Roche Molecular Systems). Genotyping was performed by genotype-specific primers.
RESULTS: HCV genotype distribution was 1 in 57%, 3 in 35%, 2 in 1%, and mixed in 4% (1 + 3 in 2.8%, 3 + 4 in 0.4%, mixed subtypes in 0.8%) cases. A total of 2.5% of isolates were nontypable. Genotype 1 was associated with higher rate of splenectomy and greater serum ferritin.
CONCLUSION: Genotype 1 is the most frequently detected HCV genotype in Iranian patients with thalassemia and might cause more need for splenectomy and more severe iron overloading. Higher HCV viral load could be regarded as another risk factor for greater iron overloading.     

Plasma Zinc Level in Hepatitis C Patients With or Without Beta Thalassemia Major; Is There Any Difference?

Background

Zinc deficiency has been reported frequently in hepatitis C patients in the literature. Furthermore, a decrease in zinc level has been shown in beta thalassemia major as well. Iranians consume a large amount of phytate in their regimens which can bind with zinc and decrease its gastrointestinal absorption.

Objectives

This study was designed to determine plasma zinc level in an Iranian sample with the diagnosis of hepatitis C with or without concomitant beta thalassemia major.

Patients and Methods

Between April 2011 and April 2012, plasma zinc level was determined via atomic absorption method, in 130 hepatitis C patients with or without beta thalassemia major in a known referral center of hepatic diseases in Tehran, Iran.

Results

Mean ± standard deviation (SD) of plasma zinc levels was determined as 0.78 ± 0.22 mg/L. Also zinc level was 0.76 ± 0.19 mg/L and 0.80 ± 0.24 mg/L in thalassemic and non thalassemic patients, respectively. T-test analysis showed that there is no significant difference between these two groups regarding plasma zinc level (P = 0.235).

Conclusions

It is concluded that zinc level of studied patients is less than which is reported in normal Iranian population. Moreover, there is not a significant difference in plasma zinc levels between thalassemic and non thalassemic patients and it seems to be a common problem in both ones. Addition of zinc supplement may be recommended in both groups in order to optimize the nutritional support and probably improve the treatment response.