The Effect of Surgical Weight Loss on Cognition in Individuals with Class II/III Obesity.

BACKGROUND: Obesity is a global epidemic and is associated with cognitive impairment and dementia. It remains unknown whether weight loss interventions, such as bariatric surgery, can mitigate cognitive impairment. OBJECTIVES: We aimed to determine the effect of surgical weight loss on cognition in individuals with class II/III obesity. DESIGN: We performed a prospective cohort study of participants who underwent bariatric surgery. At baseline and two years following surgery, participants completed metabolic risk factor and neuropsychological assessments. SETTING: Participants were enrolled from an academic suburban bariatric surgery clinic. PARTICIPANTS: There were 113 participants who completed baseline assessments and 87 completed two-year follow-up assessments (66 in-person and 21 virtual) after bariatric surgery. The mean (SD) age was 46.8 (12.5) years and 64 (73.6%) were female. INTERVENTION: Bariatric surgery. There were 77 (88.5%) participants that underwent sleeve gastrectomy and 10 (11.5%) that underwent gastric bypass surgery. MEASUREMENTS: Cognition was assessed using the NIH toolbox cognitive battery (NIHTB-CB) and the Rey Auditory Verbal Learning Test (AVLT). The primary outcome was the change in NIHTB-CB fluid composite score before and after surgery. RESULTS: The primary outcome, NIHTB-CB composite score, was stable following bariatric surgery (-0.4 (13.9), p=0.81,n=66). Among secondary outcomes, the NIHTB-CB dimensional card sorting test (executive function assessment), improved (+6.5 (19.9),p=0.01,n=66) while the Rey AVLT delayed recall test (memory assessment) declined (-0.24 (0.83),p=0.01,n=87) following surgery. Improvements to metabolic risk factors and diabetes complications were not associated with improvements to NIHTB-CB composite score. The other 4 NIHTB-CB subtests and Rey AVLT assessments of auditory learning and recognition were stable at follow-up. CONCLUSIONS: Following bariatric surgery, the age-adjusted composite cognitive outcome did not change, but an executive subtest score improved. These results suggest that bariatric surgery may mitigate the natural history of cognitive decline in individuals with obesity, which is expected to be faster than normal aging, but confirmatory randomized controlled trials are needed. The decline in delayed recall also warrants further studies to determine potential differential effects on cognitive subtests.

The influence of persistent bleeding after supracervical hysterectomy on depressive and anxious symptoms: a prospective bicenter study.

PURPOSE: Postoperative spotting is a frequent adverse symptom after laparoscopic supracervical hysterectomy (LSH). The conical excision (eLSH) reduces the postoperative spotting rate, but data in a larger collective are still rare and inconsistent. The influence of persistent bleeding on the anxious and depressive symptoms has not been analyzed yet. METHODS: 311 patients, who underwent a laparoscopic supracervical hysterectomy with conical excision (n = 163), or with straight cervical resection (n = 148) were included. Anxious and depressive symptoms and postoperative spotting were recorded before operation, at 3 month follow-up and at 1 year follow-up in both operative groups using a validated questionnaire (German version of Hospital Anxiety and Depression Scale, HADS-D) and additional questions concerning the frequency and impact of bleeding. Statistical analysis included the impairment of bleeding as well as its impact on depressive and anxious symptoms for both groups. RESULTS: 11.5% after eLSH and 15.5% after LSH reported spotting after 1 year. Supracervical hysterectomy significantly improves depressive and anxious symptoms at 3 and at 12 month follow-up for both groups (p < 0.001) independent on residual spotting. Patients with a preoperative continuous bleeding showed a maximum benefit independent on operative method. CONCLUSION: Laparoscopic supracervical hysterectomy has a positive effect on anxious and depressive symptoms in the short-term and intermediate-term follow-up. The conical excision of the cervical stump reduces postoperative spotting rate, but has no explicit advantage on symptoms of depression or anxiety, irrespective of residual postoperative spotting.

Nonlocal Reaction-Diffusion Equations in Biomedical Applications.

Nonlocal reaction-diffusion equations describe various biological and biomedical applications. Their mathematical properties are essentially different in comparison with the local equations, and this difference can lead to important biological implications. This review will present the state of the art in the investigation of nonlocal reaction-diffusion models in biomedical applications. We will consider various models arising in mathematical immunology, neuroscience, cancer modelling, and we will discuss their mathematical properties, nonlinear dynamics, resulting spatiotemporal patterns and biological significance.

The influence of conventional and extended supracervical hysterectomy on sexuality and quality of life parameters: a prospective bi-center study with a special focus on postoperative spotting.

PURPOSE: Supracervical as well as total hysterectomy are considered to improve postoperative sexuality as well as quality of life, but the benefit of supracervical hysterectomy (LSH) is impaired in up to 20 percent by postoperative spotting. The aim of this study was to analyze the influence of a conical excision of the cervical stump during supracervical hysterectomy on the postoperative spotting rate and its influence on sexuality and in turn quality of life. METHODS: 321 Patients who underwent a laparoscopic supracervical hysterectomy with conical excision (extended laparoscopic supracervical hysterectomy, eLSH, n = 166, Dormagen hospital) or with straight cervical resection (laparoscopic supracervical hysterectomy, LSH, n = 133, MIC Clinics Berlin) were included. Sexual matters, quality of life parameters and additional questions were recorded before operation, at three months of follow up, and at one year of follow up in both groups using a validated questionnaire (German version of International Consultation on Incontinence Questionnaire Vaginal Symptoms Module, ICIQ_VS). Statistical analysis included the impact and impairment of bleeding on sexuality, quality of life in both groups and co-factors such as vaginal symptoms. RESULTS: 11.3% after eLSH and 15.5% after LSH reported spotting after 1 year. Supracervical hysterectomy significantly improves quality of life and sexuality and a conical excision of the remaining stump is associated with a lower but insignificantly reduced spotting rates. Postoperative spotting has no negative influence on sexual matter score of ICIQ_VS, but reduces the postoperative quality of life focusing on vaginal symptoms in a significant way. CONCLUSION: The improvement of ICIQ_VS scores after supracervical hysterectomy is independent of postoperative spotting, but the quality-of-life score is positively influenced by a reduction in the postoperative spotting rate.

Assessment of DNA Methylation in p15, p16 and E-Cadherin Genes as a Screening Tool for Early Carcinoma Cervix.

Cancer cervix is diagnosed late in women due to anatomical inaccessibility of the area. Hence, a robust screening strategy will help detect carcinoma cervix early which will significantly decrease the mortality and morbidity due to this disease. We evaluated DNA methylation of three tumour suppressor genes p15, p16 and E-Cadherin on cervical smears to assess DNA methylation as a screening tool for detection of early cervical cancer in comparison to PAP smears. DNA was extracted from cervical smears of 20 cases and 30 controls. The DNA was bisulphite modified. Methylation specific PCR (MSP) was performed to assess the methylation status of the promoter region of each of the genes. MSP results were compared with PAP smears to assess the utility of DNA methylation of these genes in screening for cervical cancer. DNA methylation was detected in 55% subjects in p15 gene, 45% in p16 gene and 40% in E-Cadherin gene. This was statistically significant when compared to the controls. DNA methylation of E-Cadherin, and p15 genes as a panel has a sensitivity and specificity of 80% and 90% respectively, which is better than the sensitivity of PAP smear for detection of early cancer cervix. Increased DNA methylation is seen in p15, p16 and E-Cadherin genes in early cancer cervix. p15 and E-Cadherin in combination can be used as a screening tool for detection of early cancer cervix.

Cytokine gene variants and treatment outcome of cisplatin-based concomitant chemoradiotherapy in cervical cancer.

Background: Cervical cancer is the second most common cancer among women after breast cancer. Its standard treatment is cisplatin-based concomitant chemoradiotherapy. Chronic inflammation in uterine cervix triggers both pro- and anti-inflammatory pathways. The unpredictability in toxicity and efficacy of treatment is a major challenge. We hypothesized a link between IL-1, IL-6 and TNF gene variants and treatment response.Material & Methods: We genotyped 246 cervical cancer cases and 246 controls by PCR, PCR-RFLP and ARMS-PCR. Treatment and response were evaluated by RECIST criteria. Chemotherapy and radiation doses were same for all patients, whilst 48 were followed-up for 36 months after treatment.Results: SNPs in IL-1RN, IL-1ß, IL-6 and TNFα were linked with cervical cancer. Cases with certain allele combinations in IL-1RN, IL-1ß, IL-6(-597A/G) and TNF-α showed odds ratios (95% CI) of up to 17.54 (2.7-24.08) for the presence of cervical cancer. Variant IL-1ß (-511T/C) was linked to vital status but none were linked to overall survival.Conclusion: Certain cytokine gene variants may help detect susceptibility to cervical cancer and predict response to chemoradiotherapy.

Genotypic analysis of XRCC4 and susceptibility to cervical cancer.

Background: XRCC4 encodes a DNA repair protein which maintains genome stability by repairing double-strand breaks by the error-prone method. Defects in the protein-encoding gene lead to impairment of DNA repair process and accumulation of DNA damage, a hallmark of cancer development. We hypothesised that variants in XRCC4 are linked to cervical cancer.Material and methods: Genotyping of XRCC4 variants viz. intron3 DIP (rs28360071), intron7 DIP (rs28360017), G-1394T(rs6869366) and G-652T (rs2075685) was carried out in 246 women with cervical cancer cases and 246 control women.Results: There were several links to cervical cancer: intron3 DIP (rs28360071) II genotype (p = 0.002) and I allele (odds ratio is 0.54-0.89) (p = 0.004), intron7 DIP (rs28360017) II genotype (p = 0.003) and I allele (odds ratio 0.68 [0.53-0.88]) (p = 0.004), and G-652T (rs2075685) genotype (p = 0.044) and the T allele (odds ratio 1.35 [1.03-1.77]) (p = 0.032). In combining data into haploviews, the DDGG allele combination had an odds ratio of 0.12 (0.04-0.39) (p= 0.029) and the IIGT combination an odds ratio of 3.08 (1.25-7.55) (p = 0.01) for cervical cancer.Conclusion: Our results suggested that homozygous 'I' and 'T' genotypes in certain XRCC4 sequences may be associated with the development of cervical cancer and so may be a useful biomarker to predict cervical cancer susceptibility.

Genetic polymorphisms in DNA repair genes and their association with cervical cancer.

Background and objective: Carcinoma of cervix is the second most common cancer among women worldwide. The DNA repair network plays an important role in the maintenance of genetic stability, protection against DNA damage and carcinogenesis. Alterations in repair genes XRCC1, XRCC2 and XRCC3 and been reported in certain cancers. We hypothesised an association between XRCC1+399A/G, XRCC2+31467G/A and XRCC3+18067C/T polymorphisms and the risk of cervical cancer. Subjects and methods: This study included 525 subjects (265 controls and 260 cervical cancer cases). Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: Women with GA and AA genotypes of XRCC1+399A/G showed 2.4-3.8 fold higher risk of cervical cancer (P = 0.001). The +399A* allele was significantly linked with cervical cancer (P = 0.002). However, XRCC2+31479G/A and XRCC3+18067C/T polymorphisms did not show any statistically significant associations. Conclusion: The XRCC1+399A/G SNP is linked with cervical cancer. We suggest that this variant can be utilized as a prognostic marker for determination of cervical cancer susceptibility.

Endoscopic surgery: talent or training?

PURPOSE: There are two groups of undergraduate students involved in endoscopic surgery with different degrees of experience: average and more experience. This study proves whether the subjective impression of the laparoscopic trainer is verifiable and which factors influence extreme talent. METHODS: 21 medical students of the eighth term of the University of Witten-Herdecke participated in the study. On their first course day, students got instructed in suturing and knot technique. They were then required to tie a maximum of five knots within 2 h. After a week, students repeated this procedure. Time used for tying knots was stopped. RESULTS: Regarding the time students used for their first knots, great differences were provable (7-8 min, average 23 min). However, an adaption of the knotting time was noticed at the end of the first course day. This was confirmed during the second course day. Neither acquired factors (music, sport, etc.) nor individual factors (visual acuity, handedness, etc.) had any impact on the time used for knotting. Merely, one advantage was seen with the first knots with the factors of playing the guitar and having a more than 10-h surgical previous experience. Knotting times leveled off at 95% to less than 10 min, though. DISCUSSION: Neither normally talented nor extremely talented junior surgeons could be noticed, and so could not the co-factors providing an advantage or disadvantage for surgery, respectively. All prospective surgeons can learn defined tasks (knots) by short interval training, and thus show similarly good results after a few repetitions.

Impact of GSTM1, GSTT1 and GSTP1 genes polymorphisms on clinical toxicities and response to concomitant chemoradiotherapy in cervical cancer.

BACKGROUND: Certain forms of chemoradiotherapy generate toxic reactive oxygen species, which may be ameliorated by antioxidant enzymes such as glutathione S-transferase (GST). Genetic polymorphisms of GST may predict treatment outcomes and can be used as genetic marker to screen patients before treatment. We hypothesised an effect of GST polymorphisms on the response and toxicities produced by chemoradiation therapy. MATERIALS AND METHODS: GST polymorphisms were determined by multiplex polymerase chain reaction and PCR-restriction fragment length polymorphism (PCR-RFLP) in 227 women with cervical cancer receiving cisplatin based chemoradiotherapy. Treatment response and toxicities were evaluated by standard internationally recognised criteria (RECIST and RTOG). RESULTS: Severe (grade 3-4) gastrointestinal and haematological toxicities were present in 22 (9.4%) and 16 (7.0%) patients, respectively. GSTM1 null, GSTT1 null and GSTP1 AG genotypes brought marginally better non-significant associations. In single locus analysis GSTP1 AG and GG was linked to greatest risk of severe (grade 3-4) gastrointestinal toxicity (OR = 3.12, P = 0.035 and OR = 6.99, P = 0.01, respectively). In gene-gene interaction analysis, GSTM1 null-GSTP1 GG showed 4.2-fold higher risk of severe gastrointestinal toxicity (P = 0.014). GSTT1 null-GSTP1 AG reached statistical significance with a 3.9-fold higher risk of high grade gastrointestinal toxicity (P = 0.038). CONCLUSIONS: Although no significant links were found between GST polymorphism and treatment response, null genotypes of GSTM1, GSTT1 and 'G' allele of GSTP1 bring a higher risk of severe gastrointestinal toxicity due to chemoradiation therapy in cervical cancer.

Role of pRIFLE Criteria in Early Diagnosis of Severity Staging of Neonatal AKI and its Impact on Management.

Mortality is high among sick neonates who have concomitant acute kidney injury (AKI). This observational study was done at Special Care Baby Unit (SCABU) of Dhaka Medical College Hospital (DMCH), Bangladesh from October 2013 to March 2014 to find out the role of pRIFLE criteria in prediction of severity stages of AKI in neonate and early intervention to see the immediate outcome. A total of 44 neonates with AKI were included, all were treated conservatively and with intermittent peritoneal dialysis (IPD) as needed. The neonate of ≤7 days old comprised the main bulk (n=28) and M: F = 21: 23. The diagnosis was based on eCCL criteria of pRIFLE showed that 40.9% neonates were at risk of AKI, 20.5% have had already injured. Higher proportions of neonates were classified as failure (38.6%). The distribution of biochemical parameters among three stages of AKI showed serum potassium was significantly higher in failure group (p<0.001). The serum creatinine both at baseline and at next evaluations were significantly raised in the failure group (p<0.001). However, failure group had a significantly longer hospital stay compared to risk and injury group (p<0.001). Multiorgan failure was found to be lower in the risk group compared to other two groups (p=0.026). Majority of the failure group needed dialysis as compared to the risk and injury group (p<0.001). The mortality was progressively higher from risk to failure groups (p=0.106). Overall 27% of the neonates diagnosed AKI by pRIFLE were died of the disease. The study concluded that pRIFLE staging in AKI is useful and sensitive in the diagnosis and management of AKI in neonates.

Inter- and intraobserver reliability of the Rockwood classification in acute acromioclavicular joint dislocations.

PURPOSE: The reliability of the Rockwood classification, the gold standard for acute acromioclavicular (AC) joint separations, has not yet been tested. The purpose of this study was to investigate the reliability of visual and measured AC joint lesion grades according to the Rockwood classification. METHODS: Four investigators (two shoulder specialists and two second-year residents) examined radiographs (bilateral panoramic stress and axial views) in 58 patients and graded the injury according to the Rockwood classification using the following sequence: (1) visual classification of the AC joint lesion, (2) digital measurement of the coracoclavicular distance (CCD) and the horizontal dislocation (HD) with Osirix Dicom Viewer (Pixmeo, Switzerland), (3) classification of the AC joint lesion according to the measurements and (4) repetition of (1) and (2) after repeated anonymization by an independent physician. Visual and measured Rockwood grades as well as the CCD and HD of every patient were documented, and a CC index was calculated (CCD injured/CCD healthy). All records were then used to evaluate intra- and interobserver reliability. RESULTS: The disagreement between visual and measured diagnosis ranged from 6.9 to 27.6 %. Interobserver reliability for visual diagnosis was good (0.72-0.74) and excellent (0.85-0.93) for measured Rockwood grades. Intraobserver reliability was good to excellent (0.67-0.93) for visual diagnosis and excellent for measured diagnosis (0.90-0.97). The correlations between measurements of the axial view varied from 0.68 to 0.98 (good to excellent) for interobserver reliability and from 0.90 to 0.97 (excellent) for intraobserver reliability. CONCLUSION: Bilateral panoramic stress and axial radiographs are reliable examinations for grading AC joint injuries according to Rockwood's classification. Clinicians of all experience levels can precisely classify AC joint lesions according to the Rockwood classification. We recommend to grade acute ACG lesions by performing a digital measurement instead of a sole visual diagnosis because of the higher intra- and interobserver reliability. LEVEL OF EVIDENCE: Case series, Level IV.

Patterns of early resuscitation associated with mortality after penetrating injuries.

BACKGROUND: Penetrating injuries are rare in European populations so their management represents a particular challenge. The aim was to assess early therapeutic aspects that are associated with favourable outcomes in patients with penetrating trauma. METHODS: Patients with penetrating injuries documented from 2009 to 2013 in the TraumaRegister DGU® were analysed. Patients with a primary admission and an Injury Severity Score (ISS) of at least 9 were included. The Revised Injury Severity Classification (RISC) II score was used for mortality prediction, and a standardized mortality ratio (SMR) calculated per hospital. Hospitals with favourable outcome (SMR below 1) were compared with those with poor outcome (SMR 1 or more). RESULTS: A total of 50 centres had favourable outcome (1242 patients; observed mortality rate 15.7 per cent) and 34 centres had poor outcome (918 patients; observed mortality rate 24.4 per cent). Predicted mortality rates according to RISC-II were 20.4 and 20.5 per cent respectively. Mean(s.d.) ISS values were 22(14) versus 21(14) (P = 0.121). Patients in the favourable outcome group had a significantly shorter time before admission to hospital and a lower intubation rate. They received smaller quantities of intravenous fluids on admission to the emergency room, but larger amounts of fresh frozen plasma, and were more likely to receive haemostatic agents. A higher proportion of patients in the favourable outcome group were treated in a level I trauma centre. Independent risk factors for hospital death following penetrating trauma identified by multivariable analysis included gunshot injury mechanism and treatment in non-level I centres. CONCLUSION: Among penetrating traumas, gunshot injuries pose an independent risk of death. Treatment of penetrating trauma in a level I trauma centre was significantly and independently associated with lower hospital mortality.

Cissus quadrangularis Linn exerts dose-dependent biphasic effects: osteogenic and anti-proliferative, through modulating ROS, cell cycle and Runx2 gene expression in primary rat osteoblasts.

OBJECTIVES: This report highlights phytoconstituents present in Cissus quadrangularis (CQ) extract and examines biphasic (proliferative and anti-proliferative) effects of its extract on bone cell proliferation, differentiation, mineralization, ROS generation, cell cycle progression and Runx2 gene expression in primary rat osteoblasts. MATERIALS AND METHODS: Phytoconstituents were identified using gas chromatography-mass spectroscopy (GC-MS). Osteoblasts were exposed to different concentrations (10-100 µg/ml) of CQ extract and cell proliferation and cell differentiation were investigated at different periods of time. Subsequently, intracellular ROS intensity, apoptosis and matrix mineralization of osteoblasts were evaluated. We performed flow cytometry for DNA content and real-time PCR for Runx2 gene expression analysis. RESULTS: CQ extract's approximately 40 bioactive compounds of fatty acids, hydrocarbons, vitamins and steroidal derivatives were identified. Osteoblasts exposed to varying concentrations of extract exhibited biphasic variation in cell proliferation and differentiation as a function of dose and time. Moreover, lower concentrations (10-50 µg/ml) of extract slightly reduced ROS intensity, although they enhanced matrix mineralization, DNA content in S phase of the cell cycle, and levels of Runx2 expression. However, higher concentrations (75-100 µg/ml) considerably induced the ROS intensity and nuclear condensation in osteoblasts, while it reduced mineralization level, proportion of cells in S phase and Runx2 level of the osteogenic gene. CONCLUSIONS: These findings suggest that CQ extract revealed concentration-dependent biphasic effects, which would contribute notably to future assessment of pre-clinical efficacy and safety studies.

Predictors of recovery of ovarian function during aromatase inhibitor therapy.

BACKGROUND: Aromatase inhibitors (AIs) may cause a rise in estrogen levels due to ovarian function recovery in women with clinical chemotherapy-induced ovarian failure (CIOF). We carried out a prospective registry trial to identify predictors of ovarian function recovery during AI therapy. PATIENTS AND METHODS: Women with hormone receptor (HR)-positive breast cancer who remained amenorrheic and had hormonal levels consistent with ovarian failure after adjuvant chemotherapy were enrolled in a multi-institutional clinical trial of anastrozole. Subjects underwent frequent assessment using an ultrasensitive estradiol assay. Multivariable analysis was used to evaluate clinical and biochemical predictors of ovarian function recovery within 48 weeks. RESULTS: Recovery of ovarian function during AI therapy was observed in 13 of 45 (28.9%) assessable subjects after a median 2.1 months (range 0.6-11.9). Median age at chemotherapy initiation was statistically significantly different between those who regained ovarian function (43 years, range 40-51) and those who remained postmenopausal (49 years, range 44-52; P < 0.0001). CONCLUSIONS: A significant proportion of women with CIOF recover ovarian function during AI therapy, including a woman over age 50 at initiation of chemotherapy. Tamoxifen remains the standard of care for women with CIOF. If an AI is used, patients should be monitored frequently with high-quality estradiol assays. CLINICALTRIALS.GOV: NCT00555477.

Disease severity and radioactive iodine use for thyroid cancer.

CONTEXT: Although variation in radioactive iodine (RAI) use for thyroid cancer has been demonstrated, the role of region and nonclinical correlates of use within risk groups has not been investigated. OBJECTIVE: The objective of the study was to determine the correlates of RAI use within risk groups. DESIGN/SETTING/PATIENTS: Use of RAI was evaluated across 9 US regions in 85 948 patients with well-differentiated thyroid cancer diagnosed between 2004 and 2008 at 986 hospitals associated with the US National Cancer Database. Cancers were then categorized as low risk (tumor size ≤ 1 cm and American Joint Committee on Cancer stage I disease), medium risk (neither low nor high-risk), and high risk (American Joint Committee on Cancer stage III or IV). Within each risk stratum, the role of region and nonclinical correlates of RAI use were evaluated using hierarchical logistic regression. MAIN OUTCOME MEASURE: Use of RAI was measured. RESULTS: Rates of RAI use varied across geographic regions from 49% to 66%. Regional differences persisted after controlling for patient and hospital characteristics and evaluating less vs more intensive regions within low-risk [odds ratio (OR) 0.36 (95% confidence interval [CI] 0.25-0.53)], medium-risk [OR 0.23 (95% CI 0.16-0.34)], and high-risk cancers [OR 0.30 (95% CI 0.19-0.49)]. Patterns of RAI use were similar in medium- and high-risk patients. The most nonclinical correlates of use were in low-risk patients. CONCLUSION: Similar treatment patterns for the heterogeneous medium-risk thyroid cancer patients compared with the high-risk patients suggest more intensive management in patients with medium-risk disease. The large number of nonclinical correlates of RAI use, including region, imply controversy over indications for RAI.

Hepatitis C virus and other risk factors in hepatocellular carcinoma.

UNLABELLED: Hepatocellular carcinoma (HCC) increased in Egypt in the past years, becoming the most common cancer among men. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the known primary risk factors for HCC. This study describes the viral profile of HCC in a predominantly rural area in Egypt. We included 148 HCC cases and 148 controls from the Tanta Cancer Center and the Gharbiah Cancer Society in the Nile delta region. Serological (ELISA) and molecular (PCR) analysis for HBV and HCV infection were performed on plasma samples from each subject. Epidemiologic, environmental, and medical histories were collected by interviewing of subjects. Around 90.5% of cases and controls were from rural areas. HCV infection was high in both cases and controls (89.2% and 49.3%, for cases and controls respectively by serology). HCV was the most important HCC risk factor [OR 9.7 (95% CI: 3.3-28.0, P <0.01)], and HBV infection showed marginal tendency of increased risk [OR 5.4 (95% CI: 0.9-31.8, P <0.06)]. Ever worked in farming [OR 2.8 (95% CI: 1.1-7.2, P <0.03)] and history of cirrhosis [OR 3.6 (95% CI: 1.6-8.1, P <0.01)] or blood transfusion [OR 4.2 (95% CI: 0.99-17.8, P <0.05)] were also associated with increased HCC risk. This study in a predominantly rural area in Egypt supports previous reports from other parts of Egypt that HCV infection is the primary HCC risk factor in Egypt. Further understanding of the relationship between infection and other risk factors in the development of HCC could lead to targeted interventions for at-risk individuals. KEYWORDS: hepatocellular carcinoma; hepatitis; rural; risk factors; Egypt.

Bayesian piecewise mixture model for racial disparity in prostate cancer progression.

Racial differences in prostate cancer incidence and mortality have been reported. Several authors hypothesize that African Americans have a more rapid growth rate of prostate cancer compared to Caucasians, that manifests in higher recurrence and lower survival rates in the former group. In this paper we propose a Bayesian piecewise mixture model to characterize PSA progression over time in African Americans and Caucasians, using follow-up serial PSA measurements after surgery. Each individual's PSA trajectory is hypothesized to have a latent phase immediately following surgery followed by a rapid increase in PSA indicating regrowth of the tumor. The true time of transition from the latent phase to the rapid growth phase is unknown, and can vary across individuals, suggesting a random change point across individuals. Furthermore, some patients may not experience the latent phase due to the cancer having already spread outside the prostate before undergoing surgery. We propose a two-component mixture model to accommodate patients both with and without a latent phase. Within the framework of this mixture model, patients who do not have a latent phase are allowed to have different rates of PSA rise; patients who have a latent phase are allowed to have different PSA trajectories, represented by subject-specific change points and rates of PSA rise before and after the change point. The proposed Bayesian methodology is implemented using Markov Chain Monte Carlo techniques. Model selection is performed using deviance information criteria based on the observed and complete likelihoods. Finally, we illustrate the methods using a prostate cancer dataset.

Urban-rural differences of gynaecological malignancies in Egypt (1999-2002).

OBJECTIVE: In previous studies, we have shown a three to four times higher urban incidence of breast cancer and estrogen receptor-positive breast cancers in the Gharbiah Province of Egypt. We investigated the urban-rural incidence differences of gynaecologic malignancies (uterine, ovarian and cervical cancers) to explore if they show the same trend that we found for breast cancer. DESIGN: Cancer registry-based incidence comparison. SETTING: Gharbiah population-based cancer registry (GPCR), Tanta, Egypt. SAMPLE: All patients with uterine, ovarian and cervical cancer in GPCR from 1999 to 2002. METHODS: We calculated uterine, ovarian and cervical cancer incidence from 1999 to 2002. For each of the three cancers, we calculated the overall and age-specific rates for the province as a whole, and by urban-rural status, as well as for the eight districts of the province. RESULTS: Incidence of all three cancer sites was higher in urban than in rural areas. Uterine cancer showed the highest urban-rural incidence rate ratio (IRR = 6.07, 95% CI = 4.17, 8.85). Uterine cancer also showed the highest urban incidence in the oldest age group (70+ age category, IRR = 14.39, 95% CI = 4.24, 48.87) and in developed districts (Tanta, IRR = 4.14, 95% CI = 0.41, 42.04). Incidence rates by groups of cancer sites showed an increasing gradient of urban incidence for cancers related to hormonal aetiology, mainly of the breast and uterus (IRR = 4.96, 95% CI = 2.86, 8.61). CONCLUSIONS: The higher urban incidence of uterine cancer, coupled with our previous findings of higher incidence of breast cancer and estrogen receptor positive breast cancer in urban areas in this region, may be suggestive of possible higher exposure to environmental estrogenic compounds, such as xenoestrogens, in urban areas.

Mutation analysis in Indian children with achondroplasia - utility of molecular diagnosis.

OBJECTIVE: Mutation analysis in Indian children with achondroplasia. METHODS: We studied 11 sporadic cases of achondroplasia. Mutation analysis was done by PCR/RFLP (Polymerase chain reaction/Restriction fragment length polymorphism) method. RESULTS: Nine of the 11 cases had mutation G-->A at 1138 nucleotide position in transmembrane domain of fibroblast growth-factor receptor 3 (FGFR3) gene. Substitution G-->A is a common recurrent mutation reported worldwide. In two cases we could not detect any common mutation and also in entire region of transmembrane domain sequenced. There is possibility of mutation in the other regions of FGFR3 gene in these two cases. CONCLUSION: Further study of these two cases is needed in order to define other genotypes resulting in achondroplasia. Postnatal diagnosis of achondroplasia depends on clinical and radiological features. Mutation detection is mainly useful for prenatal diagnosis.