Main Risk Factors Association with Proto-Oncogene Mutations in Colorectal Cancer

Objective: Although several factors have been shown to have etiological roles in colorectal cancer, few investigationshave addressed how and to what extent these factors affect the genetics and pathology of the disease. Precise relationshipswith specific genetic mutations that could alter signaling pathways involved in colorectal cancer remain unknown.We therefore aimed to investigate possible links between lifestyle, dietary habits, and socioeconomic factors and specificmutations that are common in colorectal cancers. Methods: Data were retrieved from a baseline survey of lifestyle factors,dietary behavior, and SES, as well as anthropometric evaluations during a physical examination, for 100 confirmedprimary sporadic colorectal cancer patients from Northwest Iran. Results: High socioeconomic status was significantlyassociated with higher likelihood of a KRAS gene mutation (P < 0.05) (odds ratio: 3.01; 95% CI: 0.69–13.02). Consumingcarbohydrates and alcohol, working less, and having a sedentary lifestyle also increased the odds of having a KRASmutation. Conclusion: Although research has not yet described the exact relationships among genetic mutations withdifferent known risk factors in colorectal cancer, examples of the latter may have an impact on KRAS gene mutations.     

Air pollution and non-respiratory health hazards for children

Air pollution is a global health issue with serious public health implications, particularly for children. Usually respiratory effects of air pollutants are considered, but this review highlights the importance of non-respiratory health hazards. In addition to short-term effects, exposure to criteria air pollutants from early life might be associated with low birth weight, increase in oxidative stress and endothelial dysfunction, which in turn might have long-term effects on chronic non-communicable diseases. In view of the emerging epidemic of chronic disease in low- and middle- income countries, the vicious cycle of rapid urbanization and increasing levels of air pollution, public health and regulatory policies for air quality protection should be integrated into the main priorities of the primary health care system and into the educational curriculum of health professionals.     

Factor Analysis of Markers of Inflammation and Oxidation and Echocardiographic Findings in Children with a Positive Family History of Premature Coronary Heart Disease

The objective of this study was to determine the predictive factor of a combination of traditional and new risk factors for coronary heart diseases (CHDs) as well as the echocardiographic findings in children of parents suffering premature myocardial infarction in comparison with controls. Overall, 239 adolescents aged 12 to 18 years including 112 children of parents with premature CHD (<55 years) and 127 age- and sex-matched controls without such a family history. In addition to measuring anthropometric indexes and blood pressure, serum fasting blood sugar, lipid profile, C-reactive protein, Lpa, and oxidized LDL as well as carotid-intima media thickness and left ventricular mass were determined. Factor analysis showed that clusters of inflammatory factors and markers of oxidation as well as carotid-intima media thickness and left ventricular mass were correlated with each other and were associated with a positive parental history of premature CHD in youths. These findings complement the functional and structural changes in arteries of adults with a familial predisposition to CHD and underscore the importance of using a high-risk approach for primordial/primary prevention of CHD from early life and of considering the screening of children and siblings in the management of patients with premature CHD.     

Relation between stress and other life style factors

Objective: To describe and evaluate the relationship between stress and other lifestyle behaviors. Methods: A cross‐sectional study within the context of an Isfahan Healthy Heart Program (IHHP). Demographic details (age, gender, marital status and educational level) and lifestyle variables including diet (fruit and vegetable consumption), smoking status, daily physical activity and psychological distress were recorded. Data were analyzed by t‐test, χ² and logistic regression. Setting: Central Iranian country of Isfahan, Najaf‐Abad and Arak. Participants: Five thousand and eight hundred and ninety‐two adults over 19 years of age. Results: Mean age of all participants was 40.5 (15.4) years and 36 per cent of them had high stress levels. High stress levels were negatively associated with fruit and vegetable consumption, non‐smoking and marriage. Conversely, the female gender and less than 6 years of education were positively associated with stress levels. Physical activity was not found to be associated with stress. Conclusion: This study demonstrated an association between high stress levels and other unhealthy lifestyle factors. Hence, special attention must be paid to intervention programs aimed at modifying lifestyle and providing education on stress management techniques. Copyright © 2006 John Wiley & Sons, Ltd.     

Clinical Implementation of Tangential Field Intensity Modulated Radiation Therapy (IMRT) Using Sliding Window Technique and Dosimetric Comparison with 3D Conformal Therapy (3DCRT) in Breast Cancer

The purpose of this study was to evaluate the clinical implementation of tangential field IMRT using sliding window technique and to compare dosimetric parameters with 3-dimensional conformal radiation therapy (3DCRT). Twenty breast cancer patients were randomly selected for comparison of intensity modulated radiation therapy (IMRT)-based treatment plan with 3DCRT. Inverse treatment was performed using the sliding window technique, employing the Eclipse^® Planning System (version 7.1.59, Varian, Palo Alto, CA). The dosimetric parameters compared were V₉₅ (the percentage of target volume getting ≥95% of prescribed dose), V₁₀₅, V₁₁₀, and dose homogeneity index, DHI (percentage of target volume getting between 95% and 110% of prescribed dose). The mean V₉₅, DHI, V₁₀₅, and V₁₁₀ for target volume for IMRT vs. 3D were 90.6% (standard deviation [SD]: 3.2) vs. 91% (SD: 3.0), 87.7 (SD: 6.0) vs. 82.6 (SD: 7.8), 27.3% (SD: 20.3) vs. 49.4% (SD: 14.3), and 2.8 (SD: 5.6) vs. 8.4% (SD: 7.4), respectively. DHI was increased by 6.3% with IMRT compared to 3DCRT (p < 0.05). The reductions of V₁₀₅ and V₁₁₀ for the IMRT compared to 3DCRT were 44.7% and 66.3%, respectively (p < 0.01). The mean dose and V₃₀ for heart with IMRT were 2.3 (SD: 1.1) and 1.05 (SD: 1.5) respectively, which was a reduction by 6.8% and 7.9%, respectively, in comparison with 3D. Similarly, the mean dose and V₂₀ for the ipsilateral lung and the percentage of volume of contralateral volume lung receiving > 5% of prescribed dose with IMRT were reduced by 9.9%, 2.2%, and 35%, respectively. The mean of total monitor units used for IMRT and 3DCRT was about the same (397 vs. 387). The tangential field IMRT for intact breast using sliding window technique was successfully implemented in the clinic. We have now treated more than 1000 breast cancer patients with this technique. The dosimetric data suggest improved dose homogeneity in the breast and reduction in the dose to lung and heart for IMRT treatments, which may be of clinical value in potentially contributing to improved cosmetic results and reduced late treatment-related toxicity.     

SIRT1 Gene SNP rs932658 Is Associated With Medication-Related Osteonecrosis of the Jaw

Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious adverse drug reaction. Our previous whole-exome sequencing study found SIRT1 intronic region single-nucleotide polymorphism (SNP) rs7896005 to be associated with MRONJ in cancer patients treated with intravenous (iv) bisphosphonates (BPs). This study aimed to identify causal variants for this association. In silico analyses identified three SNPs (rs3758391, rs932658, and rs2394443) in the SIRT1 promoter region that are in high linkage disequilibrium (r² > 0.8) with rs7896005. To validate the association between these SNPs and MRONJ, we genotyped these three SNPs on the germline DNA from 104 cancer patients of European ancestry treated with iv BPs (46 cases and 58 controls). Multivariable logistic regression analysis showed the minor alleles of these three SNPs were associated with lower odds for MRONJ. The odds ratios (95% confidence interval) and p values were 0.351 (0.164–0.751; p = 0.007) for rs3758391, 0.351 (0.164–0.751; p = 0.007) for rs932658, and 0.331 (0.157–0.697; p = 0.0036) for rs2394443, respectively. In the reporter gene assays, constructs containing rs932658 with variant allele A had higher luciferase activity than the reference allele, whereas constructs containing SNP rs3758391 and/or rs2394443 did not significantly affect activity. These results indicate that the promoter SNP rs932658 regulates the expression of SIRT1 and presumably lowers the risk of MRONJ by increasing SIRT1 expression. © 2020 American Society for Bone and Mineral Research (ASBMR).     

Nosocomial infection due to rotavirus in infants in Alzahra Hospital, Isfahan, Iran

Rotavirus is one of the most common causes of acute diarrhoea during infancy, and the spread of this infection due to rotavirus in paediatric wards can cause acute diarrhoea during hospitalization, and, in turn, prolong hospitalization or rehospitalization. It is, therefore, important to evaluate the problem and to find an appropriate approach to decrease the rate of infection. The incidence of nosocomial infection due to rotavirus was studied in 80 children aged 3-24 months from November 2003 to April 2004 in the Alzahra Hospital, Isfahan, Iran. Rotavirus antigen was detected by latex aggulutation in stool samples obtained during hospitalization and up to 72 hours after discharge from the hospital. The prevalence of nosocomial infection due to rotavirus was 26.25%, which is a considerable prevalence compared to similar studies which reported a prevalence of 27.7%, 19.4%, and 14.6%. Overall, 15% of the 21 children with positive rotavirus antigen in their stools had acute diarrhoea during hospitalization and up to 72 hours after discharge (symptomatic nosocomial infection), and 11.25% of all children (n=80) studied had asymptomatic nosocomial infection. Regarding the low frequency of nosocomial infection due to rotavirus in other studies which have only studied symptomatic cases during hospitalization and reported a prevalence of 3.3 and 9%, it is suggested that the real estimation of nosocomial infection due to rotavirus in asymptomatic cases that might become symptomatic after discharge from hospital should also be considered. Due to the relatively high frequency of nosocomial infection in the Alzahra Hospital, it is necessary to follow stricter health issues, e.g. isolation of patients with diarrhoea and hand-washing before and after the examination of every patient.     

Finding cancer in primary care outpatients with low back pain

OBJECTIVE: To compare strategies for diagnosing cancer in primary care patients with low back pain. Strategies differed in their use of clinical findings, erythrocyte sedimentation rate (ESR), and plain x-rays prior to imaging and biopsy. DESIGN: Decision analysis and cost effectiveness analysis with sensitivity analyses. Strategies were compared in terms of sensitivity, specificity, and diagnostic cost effectiveness ratios. SETTING: Hypothetical MEASUREMENTS: Estimates of disease prevalence and test characteristics were taken from the literature. Costs were represented by the Medicare reimbursement for the tests and procedures employed. MAIN RESULTS: In the baseline analysis, using magnetic resonance imaging (MRI) as the imaging procedure prior to a single biopsy, strategies ranged in sensitivity from 0.40 to 0.73, with corresponding diagnostic costs of $14 to $241 per patient and average cost effectiveness ratios of $5,283 to $49,814 per case of cancer found. Incremental cost effectiveness ratios varied from $8,397 to $624,781; 5 strategies were dominant in the baseline analysis. Use of a higher ESR cutoff point (50 mm/hr) improved specificity and cost effectiveness for certain strategies. Imaging with MRI, or bone scan followed in series by MRI, resulted in a fewer unnecessary biopsies than imaging with bone scan alone. Cancer prevalence was an important determinant of cost effectiveness. CONCLUSIONS: We recommend a strategy of imaging patients who have a clinical finding (history of cancer, age > or = 50 years, weight loss, or failure to improve with conservative therapy) in combination with either an elevated ESR (> 50 mm/hr) or a positive x-ray, or using the same approach but imaging directly those patients with a history of cancer.     

Retrospective study of the renal effects of amphotericin B lipid complex when used at higher-than-recommended dosages and longer durations compared with lower dosages and shorter durations in patients with systemic fungal infections

BACKGROUND: Patients with fungal infections who are treated with amphotericin B lipid complex (ABLC) often receive dosages less than that recommended in the product information (5 mg/kg.d). This occurs despite the described safety and increased efficacy in select patients treated with higher ABLC dosages. OBJECTIVE: The purpose of this study was to compare the renal effects of high-dosage/long-duration (HDos/LDur) ABLC therapy (>5 mg/kg.d for >12 days) with those of low-dosage/short-duration (LDos/SDur) ABLC therapy (or=4 ABLC doses according to a large, multicenter patient database, the Collaborative Exchange of Antifungal Research (CLEAR) registry. The safety profile of each dosage was evaluated using serum creatinine concentration (S-Cr) and calculated creatinine clearance (CCcr). RESULTS: A total of 1726 patients were studied. The HDos/LDur group included 309 patients and theLDos/SDur group included 1417 patients. The median ages of the HDos/LDur and LDos/SDur groups were 42 and 48 years, respectively (ranges, <1 to 83 and <1 to 95 years; P < 0.001); females comprised 51% and 42% of the 2 populations (P = 0.004); and 6% and 12% had solid tumors (P = 0.002). The HDos/LDur group was more likely than the LDos/SDur group to have been treated for multiple systemic fungal pathogen infections (16% and 9%, respectively) and for mold infections (28% and 12%, respectively) (both, P < 0.001). The median change in S-Cr from baseline was 0.1 mg/dL in both groups (range, -4.9 to 5 mg/dL in the HDos/LDur group and -3.96 to 4.7 mg/dL in the LDos/SDur group). No increased risk for renal dysfunction, as reflected in the median change from baseline in CCcr, was observed in either cohort (-3 mL/min [range, -118.65 to 69.03 mL/min] in the HDos/LDur group; -2.17 mL/min [range, -107.48 to 104.45 mL/min] in the LDos/SDur group). CONCLUSION: These data suggest that higher ABLC dosages appear to be as well tolerated as lower dosages, warranting further study of ABLC dosages >5 mg/kg.d for >12 days in the treatment of systemic fungal infections.