The association between interleukin-21 (rs2055979G/T) gene polymorphism and the risk of hepatocellular carcinoma and metastasis in patients with hepatitis C virus

Cancer prevalence is critically increasing worldwide; accordingly, improved prediction and therapeutic tools are necessary. Interleukin (IL)-21 is a potent antitumor cytokine, and the relationship between its gene variations and cancer risk is well established. Nevertheless, so far no study has investigated its role in hepatocellular carcinoma (HCC) progression and metastasis in hepatitis C virus (HCV)-infected people. Therefore, the present investigation was led on 267 Egyptian participants, involving 177 patients with HCV of which 90 patients had HCC (HCC group), 87 patients without HCC (non-HCC group), and 90 unrelated healthy controls. The association between rs2221903A/G and rs2055979G/T of the IL-21 gene and the risk of HCC and metastasis, as well as the clinico-pathological features, were analyzed. While rs2221903A/G polymorphism was not polymorphic in our cohort, patients carrying the genotype TT and allele T of the rs2055979G/T polymorphism had a significantly lower risk of HCC when comparing with HCC group and healthy controls. Also, participants carrying the aforementioned genotype and allele had a significantly lower risk of metastasis when comparing metastatic group with both nonmetastatic group and control group. The rs2055979G/T polymorphism was not significantly associated with clinico-pathological features of HCC. This is the first study to report a relationship between an intronic polymorphism in IL-21 gene and HCC and metastasis risk in the Egyptian people, in addition to identifying a potential new marker for the early detection and treatment of HCC.     

Diel activity patterns of adult female mosquitoes (Diptera: Culicidae) determined by a novel rotated trap in northeastern Florida,U.S.A.

A novel rotator trap was evaluated to determine the diel activity patterns and physiological state of adult female mosquitoes in St. Augustine, FL, U.S.A. Culex nigripalpus were most active from 19:00‐21:00, followed by 1:00‐3:00, based on collections from the novel rotator trap. Furthermore, analysis of the physiological state of female mosquitoes collected by the novel rotator trap suggested that non‐parous (nulliparous) host‐seeking mosquitoes were more frequently active in the 21:00‐23:00 and 09:00‐19:00 time frames. Parous host‐seeking mosquitoes were more frequently collected from 19:00‐21:00 and 1:00‐3:00. A low abundance of gravid females was collected by the rotator trap, so analysis of their activity periods was inconclusive. These results indicate that the novel rotated trap could be used to detect the diel activity patterns of adult mosquitoes in mosquito control programs and more testing should be conducted in the future.     

Medical Student Research: An Integrated Mixed-Methods Systematic Review and Meta-Analysis

Importance

Despite the rapidly declining number of physician-investigators, there is no consistent structure within medical education so far for involving medical students in research.

Objective

To conduct an integrated mixed-methods systematic review and meta-analysis of published studies about medical students'' participation in research, and to evaluate the evidence in order to guide policy decision-making regarding this issue.

Evidence Review

We followed the PRISMA statement guidelines during the preparation of this review and meta-analysis. We searched various databases as well as the bibliographies of the included studies between March 2012 and September 2013. We identified all relevant quantitative and qualitative studies assessing the effect of medical student participation in research, without restrictions regarding study design or publication date. Prespecified outcome-specific quality criteria were used to judge the admission of each quantitative outcome into the meta-analysis. Initial screening of titles and abstracts resulted in the retrieval of 256 articles for full-text assessment. Eventually, 79 articles were included in our study, including eight qualitative studies. An integrated approach was used to combine quantitative and qualitative studies into a single synthesis. Once all included studies were identified, a data-driven thematic analysis was performed.

Findings and Conclusions

Medical student participation in research is associated with improved short- and long- term scientific productivity, more informed career choices and improved knowledge about-, interest in- and attitudes towards research. Financial worries, gender, having a higher degree (MSc or PhD) before matriculation and perceived competitiveness of the residency of choice are among the factors that affect the engagement of medical students in research and/or their scientific productivity. Intercalated BSc degrees, mandatory graduation theses and curricular research components may help in standardizing research education during medical school.     

Promotion of Bone Morphogenetic Protein Signaling by Tetraspanins and Glycosphingolipids

Bone morphogenetic proteins (BMPs) belong to the transforming growth factor β (TGFβ) superfamily of secreted molecules. BMPs play essential roles in multiple developmental and homeostatic processes in metazoans. Malfunction of the BMP pathway can cause a variety of diseases in humans, including cancer, skeletal disorders and cardiovascular diseases. Identification of factors that ensure proper spatiotemporal control of BMP signaling is critical for understanding how this pathway is regulated. We have used a unique and sensitive genetic screen to identify the plasma membrane-localized tetraspanin TSP-21 as a key new factor in the C. elegans BMP-like “Sma/Mab” signaling pathway that controls body size and postembryonic M lineage development. We showed that TSP-21 acts in the signal-receiving cells and genetically functions at the ligand-receptor level. We further showed that TSP-21 can associate with itself and with two additional tetraspanins, TSP-12 and TSP-14, which also promote Sma/Mab signaling. TSP-12 and TSP-14 can also associate with SMA-6, the type I receptor of the Sma/Mab pathway. Finally, we found that glycosphingolipids, major components of the tetraspanin-enriched microdomains, are required for Sma/Mab signaling. Our findings suggest that the tetraspanin-enriched membrane microdomains are important for proper BMP signaling. As tetraspanins have emerged as diagnostic and prognostic markers for tumor progression, and TSP-21, TSP-12 and TSP-14 are all conserved in humans, we speculate that abnormal BMP signaling due to altered expression or function of certain tetraspanins may be a contributing factor to cancer development.     

Usefulness of Anthropometry and DXA in Predicting Intra‐abdominal Fat in Obese Men and Women

Objective: To investigate the usefulness of anthropometry and DXA in predicting intra‐abdominal fat (IAF) in obese men and women. Research Methods and Procedures: Observational, cross sectional study of 22 women and 18 men with a body mass index of 30 or above. IAF from 20 cm above and 10 cm below the L4 to L5 intervertebral disc was measured by magnetic resonance imaging (MRI) as a reference method. Central abdominal fat was measured from the upper border of L2 to the lower border of L4 by DXA. Waist and hip circumferences were also measured. Results: In obese women DXA, waist circumference and waist‐hip ratio were equally well correlated with IAF (r = 0.74, 0.75, and 0.70, respectively). In obese men DXA was moderately correlated with IAF measured by MRI (r = 0.46), whereas waist circumference and waist‐hip ratio were not significantly correlated with IAF. Discussion: The prediction of IAF in obese subjects was highly dependent on sex more than in non‐obese persons. Anthropometry and DXA were equally useful in obese women, whereas anthropometry had no predictive power and DXA was the only acceptable predictor of IAF in obese men.     

Synthetic peptide sequence from the C-terminus of the insulin-like growth factor-I receptor that induces apoptosis and inhibition of tumor growth

Although the type 1 insulin-like growth factor receptor (IGF-IR) is a potent inhibitor of apoptosis, its C-terminus sequence sends contradictory signals, including a clearly proapoptotic signal. We have synthesized a peptide, peptide 2, having the sequence of the IGF-IR from residue 1282 to residue 1298 (C-terminus of the β subunit). To favor its uptake into cells, we linked it to a stearic acid moiety at its NH-terminus. Peptide 2 is taken up by the cells, where it inhibits DNA synthesis and causes apoptosis, while a scrambled peptide (with stearic acid) and peptide 2 without stearic acid are completely ineffective. Peptide 2 is more effective when cells are in anchorage-independent conditions than when they grow in monolayer cultures. Accordingly, we find that peptide 2 can inhibit the growth of a human prostatic cell line in nude mice. The proapoptotic effect of peptide 2 is inhibited by the expression of Bcl-2 or by a dominant negative mutant of caspase 9. These and other data indicate that peptide 2 does not seem to be competing directly with the IGF-IR for common substrates, but that its proapoptotic effect is related to its ability to activate the caspase cascade. J. Cell. Physiol. 181:124–135, 1999. © 1999 Wiley-Liss, Inc.     

Mammalian cell death proteases: A family of highly conserved aspartate specific cysteine proteases

So far nine human aspartate-specific cysteine proteases (ASCPs) have been identified and cloned in our lab and others. Their sequence and structural homology to the nematode Ced-3 implicated them in the cell death pathway of mammalian cells. Recent evidence suggests that ASCPs initiate apoptosis by acting at or near the cell death effector level. However, it is not clear whether the activity of one or several of these enzymes is necessary for execution of apoptosis. In addition, it is not yet clear how the proenzymes of ASCPs are activated or what triggers their activation. Execution of apoptosis in higher eukaryotes is apparently more complicated than in nematodes. It is most likely that in mammalian cells this process involves the coordinated action of multiple ASCPs and multiple redundant proteolytic pathways. J. Cell Biochem. 64:33–42. © 1997 Wiley-Liss, Inc.