Genetic polymorphisms in NQO1 and SOD2: Interactions with smoking,schistosoma infection,and bladder cancer risk in Egypt

BackgroundBladder cancer is the most prevalent form of cancer in men among Egyptians, for whom tobacco smoke exposure and Schistosoma haematobium (SH) infection are the major risk factors. We hypothesized that functional polymorphisms in NAD(P)H:quinone oxidoreductase 1 (NQO1) and superoxide dismutase 2 (SOD2), modulators of the effects of reactive oxidative species, can influence an individual's susceptibility to these carcinogenic exposures and hence the risk of bladder cancer.MethodsWe assessed the effects of potential interactions between functional polymorphisms in the NQO1 and SOD2 genes and exposure to smoking and SH infection on bladder cancer risk among 902 cases and 804 population-based controls in Egypt. We used unconditional logistic regression to estimate the odds ratios (OR) and confidence intervals (CI) 95%.ResultsWater pipe and cigarette smoking were more strongly associated with cancer risk among individuals with the TT genotype for SOD2 (OR [CI 95%] = 4.41 [1.86–10.42]) as compared with those with the CC genotype (OR [CI 95%] = 2.26 [0.97–6.74]). Conversely, the risk associated with SH infection was higher among the latter (OR [CI 95%] = 3.59 [2.21–5.84]) than among the former (OR [CI 95%] = 1.86 [1.33–2.60]). Polymorphisms in NQO1 genotype showed a similar pattern, but to a much lesser extent. The highest odds for having bladder cancer following SH infection were observed among individuals with the CC genotypes for both NQO1 and SOD2 (OR [CI 95%] = 4.41 [2.32–8.38]).ConclusionOur findings suggest that genetic polymorphisms in NQO1 and SOD2 play important roles in the etiology of bladder cancer by modulating the effects of known contributing factors such as smoking and SH infection.     

Review of side-effect profile of combination ezetimibe and statin therapy in randomized clinical trials

Effective treatment to achieve target lipid parameters in high-risk patients may require combination drug therapies. Concerns regarding risks associated with such combination therapies may limit their use. A systematic overview of randomized controlled trials to assess risks associated with combination statin and ezetimibe therapy was performed. Eighteen trials were identified, including 14,471 patients. Follow-up ranged from 6 to 48 weeks. Compared with statin monotherapy, combination therapy did not result in significant absolute increases in risks of myalgias (risk difference -0.033, 95% confidence interval [CI] -0.06 to -0.01), creatine kinase increases (risk difference 0.011, 95% CI -0.02 to 0.04), rhabdomyolysis (risk difference -0.003, 95% CI -0.01 to 0.004), transaminase increases (risk difference -0.003, 95% CI -0.01 to 0.005), gastrointestinal adverse events (risk difference 0.005, 95% CI -0.03 to 0.04), or discontinuations because of an adverse event (risk difference -0.005, 95% CI -0.03 to 0.02). In conclusion, based on available randomized trials, the addition of ezetimibe to statin therapy did not increase the risk of myalgias, creatine kinase increases, rhabdomyolysis, transaminase increases, gastrointestinal adverse events, or discontinuations because of an adverse event. Additional trials are necessary to ensure that results of clinical trials are consistent with routine clinical practice, particularly in older patients with more co-morbid conditions and patients on higher statin doses.     

Development of the Arabic Version of Dysphagia Handicap Index (DHI)

The Dysphagia Handicap Index (DHI) is a 25-item self-administered questionnaire. It is a noninvasive tool for measuring the handicapping effect of dysphagia on the physical, functional, and emotional aspects of people’s lives. The purposes of the present study were to develop an Arabic version of the DHI and to evaluate its validity, consistency, and reliability in the normal Arabic population with oropharyngeal dysphagia. This was a prospective study that was carried out at the Communication and Swallowing Disorders Unit, King Saud University. The generated Arabic DHI was administered to 94 patients with oropharyngeal dysphagia and 98 control subjects. Internal consistency and test-retest reliability were evaluated. The results of the patients and the control group were compared. The Arabic DHI showed excellent internal consistency (Cronbach’s α = 0.95). Also, good test–retest reliability was found for the total scores of the Arabic DHI (r = 0.9, p = 0.001). There was a significant difference between the DHI scores of the control group and those of the oropharyngeal dysphagia group (p < 0.001). This study demonstrated that the Arabic DHI is a valid tool for self-assessment of the handicapping effect of dysphagia on the physical, functional, and emotional aspects of patients and can be used by Arabic language speakers.     

Multiparametric MRI with diffusion-weighted imaging in predicting response to chemotherapy in cases of osteosarcoma and Ewing’s sarcoma

Objective:To evaluate the multiparametric MRI in predicting chemotherapy response in pathologically proven cases of osteosarcoma and Ewing’s sarcoma. Correlation between the tumor size changes and internal breakdown using RECIST 1.1, modified RECIST, quantitative apparent diffusion coefficient (ADC) and tumor volume as well as dynamic contrast-enhanced MRI (DCE-MRI).Methods:The study included 104 patients pathologically proved osteosarcoma (53) and Ewing`s sarcoma (51) underwent MRI examinations; before and after chemotherapy. All patients were assessed using the RECIST 1.1 criteria, m-RECIST, quantitative ADC, and tumor volume evaluation. 21 patients underwent DCE-MRI curve type with quantitative parameters. Correlation between the different evaluations was carried out. Results were correlated with the post-operative pathology in 42 patients who underwent surgery and for statistical evaluation, Those patients were classified into responders (≥90% necrosis) and non-responders (<90% necrosis).Results:The initial mean ADC of 104 patients of osteosarcoma and Ewing’s sarcoma (0.90 ± 0.29) and (0.71 ± 0.16) respectively, differed significantly from that after treatment (1.62 ± 0.46) and (1.6 ± 0.39) respectively with (p<0.001).ADC variations (ADC%) in the non-progressive group were higher than those of the progressive group (128.3 ± 63.49 vs 36.34 ± 78.7) % with (p<0.001).ADC values and ADC variations were inversely correlated with morphologic changes, regardless of the effectiveness of chemotherapy expressed as changes in tumor size based on (RECIST 1.1, RECIST, and 3D volume). Linear regression analysis revealed a Pearson correlation coefficient of r=-0.427, -0.498 and -0.408, respectively with (p<0.001).An increase in the ADC value was not always associated with a reduction in tumor volume. The disease control rate (defined as the percentage of CR+PR+SD patients) was 89.4% and 93.9% according to RECIST 1.1 and m-RECIST respectively.42 out of the 104 patients had postsurgical histological evaluation as regards the chemotherapeutic response divided into two groups. ADC values showed a statistically significant difference between Group A and Group B being more evident with minimum ADC% (p<0.001).Conclusion:Quantitative diffusion-weighted imaging with ADC mapping and ADC % after chemotherapy allows a detailed analysis of the treatment response in osteosarcoma and Ewing’s sarcoma. The therapeutic response can be underestimated using RECIST 1.1, so the modified RECIST should be also considered.Advances in knowledge:Quantitative ADC especially ADC% provided an accurate non-invasive tool in the assessment of post-therapeutic cases of osteosarcoma and Ewing''s sarcoma     

Vitamin D receptor gene polymorphism as possible risk factor in rheumatoid arthritis and rheumatoid related osteoporosis

Objective

To study the role of VDR polymorphisms as risk factor for RA and osteoporosis, and whether osteoporosis complicating RA is due to RA or VDR polymorphisms.

Methods

VDR gene polymorphisms ApaI, TaqI, BsmI and FokI were typed by RFLP for 128 RA patients, 30 postmenopausal osteoporotic females and 150 healthy controls.

Results

Significant differences were found between patients and healthy controls in the frequency of BsmI and TaqI (Pc < 0.05) but no significant associations were found for FokI and ApaI polymorphisms except for aa genotype (Pc < 0.001). Titers of RF were higher with aa and bb genotypes. Anti-CCP and CRP levels were higher with aa genotype and more bone loss was associated with Bb genotype. Ff genotype frequency was higher in RA patients with osteoporosis than those without osteoporosis.

Conclusions

The ApaI, BsmI and TaqI polymorphisms may be a susceptibility risk factors for RA and the Ff genotype may be responsible for development of osteoporosis in RA Egyptian patients. However, the present study needs to be replicated in a large number of patients from allover the Egypt and also in multi-ethnic populations.     

Effects of vitamin K in postmenopausal women: Mini review

Possible benefits of vitamin K on bone health, fracture risk, markers of bone formation and resorption, cardiovascular health, and cancer risk in postmenopausal women have been investigated for over three decades; yet there is no clear evidence-based universal recommendation for its use.     

Scientific principles of regenerative medicine and their application in the female reproductive system

The goal of regenerative medicine is to repair, replace, or regenerate diseased tissues/organs in order to restore normal function. In this paper we will first discuss the general principle of regenerative medicine and the various techniques and approaches that have been used to replace or regenerate cells in diseased tissues and organs. Then, we will review different regenerative medicine approaches that have been used to treat specific diseased tissues and organs of the reproductive system in both animal and human experiments. It is clear from this article that regenerative medicine holds significant promise, and we hope that the review will serve as a platform for further development of regenerative medicine technologies for the treatment of inadequacies of the reproductive system.     

EMAS position statement: Individualized breast cancer screening versus population-based mammography screening programmes

Introduction

Breast cancer is the most prevalent cancer in women, with slightly more than ten percent developing the disease in Western countries. Mammography screening is a well established method to detect breast cancer.

Aims

The aim of the position statement is to review critically the advantages and shortcomings of population based mammography screening.

Materials and methods

Literature review and consensus of expert opinion.

Results and conclusion

Mammography screening programmes vary worldwide. Thus there are differences in the age at which screening is started and stopped and in the screening interval. Furthermore differences in screening quality (such as equipment, technique, resolution, single or double reading, recall rates) result in a sensitivity varying from 70% to 94% between studies. Reporting results of screening is subject to different types of bias such as overdiagnosis. Thus because of the limitations of population-based mammography screening programmes an algorithm for individualized screening is proposed.