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Dresden, Germany

Dartell M.,Danish Cancer Society | Rasch V.,University of Southern Denmark | Munk C.,Danish Cancer Society | Kahesa C.,Ocean Road Cancer Institute | And 4 more authors.
Sexually Transmitted Diseases | Year: 2013

BACKGROUND: Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. The prevalence is dependent on several known factors notably sexual behavior and age, and factors still under scrutiny. OBJECTIVE: This study aimed to examine risk factors for high-risk (HR) HPV infection among HIV-positive and HIV-negative women from the general population of Tanzania and to assess whether specific risk factors could contribute to the high prevalence of HR HPV infection in older age found in some populations including Tanzanian women. METHODS: A cross-sectional study of 3699 women from Tanzania was conducted. We obtained information on sociodemographic and lifestyle factors through personal interview. Cervical swabs were collected for detection of HR HPV (Hybrid Capture 2; Qiagen, Hildesheim, Germany) and genotyping (LiPaExtra; Innogenetics, Gent, Belgium). Finally, we obtained a blood sample for HIV testing. RESULTS: HIV positivity was the strongest risk factor for HR HPV (odds ratio, 4.1; 95% confidence interval, 3.3-5.3). Young age, shorter duration of present relationship, and increasing number of sex partners were also associated with higher risk for HR HPV. Among women 20 to 29 years old, especially number of partners (P = 0.005) and HIV positivity (P < 0.0001) determined the risk. In underweight women 50 years or older (P = 0.004) and HIV positivity (P = 0.0009) increased the risk, whereas increasing number of partners was not related to the risk of HR HPV (P = 0.46). CONCLUSIONS: Human papillomavirus risk factors among HIV-positive and HIV-negative women were similar, but the strength of association was greater among HIV-positive women, notably for lifetime number of sex partners, time in present relationship, genital warts, and body mass index. We were not able to identify a clear explanation for the high HPV prevalence among older women. However, in the age-stratified analysis, potential indicators of decreased immunity increased the risk for HPV infection among older women, whereas in younger women, risk was particularly associated with sexual activity. Copyright © 2013 American Sexually Transmitted Diseases Association. All rights reserved. Source


Craddock C.,Center for Clinical Haematology | Labopin M.,EBMT ALWP Office | Pillai S.,Center for Clinical Haematology | Finke J.,Albert Ludwigs University of Freiburg | And 15 more authors.
Leukemia | Year: 2011

Treatment options for adults with primary refractory acute myeloid leukaemia (PREF AML) are extremely limited. Although sibling allogeneic stem cell transplantation can result in long-term survival, most patients lack a matched family donor and are destined to die of refractory disease. Greater availability of unrelated donors and improvements in supportive care have increased the proportion of patients with PREF AML in whom allografting is technically feasible, but the outcome of unrelated donor transplantation in this population has not been studied. We therefore analysed overall survival in 168 patients with PREF AML, who underwent unrelated donor transplantation between 1994 and 2006. The 5-year overall survival for the whole group was 22%. In multivariate analysis, fewer than three courses of induction chemotherapy, a lower percentage of bone marrow blasts at transplant and patient cytomegalovirus seropositivity were associated with improved survival. This allowed the development of a scoring system that identified four groups with survival rates between 4411% and 0%. This study demonstrates an important role for unrelated donor transplantation in the management of selected patients with PREF AML and confirms the importance of initiating an urgent unrelated donor search in patients with no matched sibling donor, who fail to respond to induction chemotherapy. © 2011 Macmillan Publishers Limited All rights reserved. Source


Huang L.,Genetics and Molecular Pathology | Huang L.,Central South University | Jolly L.A.,Genetics and Molecular Pathology | Willis-Owen S.,Genetics and Molecular Pathology | And 20 more authors.
American Journal of Human Genetics | Year: 2012

The discovery of mutations causing human disease has so far been biased toward protein-coding regions. Having excluded all annotated coding regions, we performed targeted massively parallel resequencing of the nonrepetitive genomic linkage interval at Xq28 of family MRX3. We identified in the binding site of transcription factor YY1 a regulatory mutation that leads to overexpression of the chromatin-associated transcriptional regulator HCFC1. When tested on embryonic murine neural stem cells and embryonic hippocampal neurons, HCFC1 overexpression led to a significant increase of the production of astrocytes and a considerable reduction in neurite growth. Two other nonsynonymous, potentially deleterious changes have been identified by X-exome sequencing in individuals with intellectual disability, implicating HCFC1 in normal brain function. © 2012 The American Society of Human Genetics. Source


Fraccarollo D.,Klinik fuer Kardiologie und Angiologie | Fraccarollo D.,Universitatsklinikum | Berger S.,German Cancer Research Center | Galuppo P.,Klinik fuer Kardiologie und Angiologie | And 7 more authors.
Circulation | Year: 2011

Background- Mineralocorticoid receptor (MR) blockade improves morbidity and mortality among patients with heart failure; however, the underlying mechanisms are still under investigation. We studied left ventricular remodeling after myocardial infarction in mice with cardiomyocyte-specific inactivation of the MR gene (MR) that were generated with a conditional MR allele (MR) in combination with a transgene expressing Cre recombinase under control of the myosin light-chain (MLC2a) gene promoter. Methods and Results- Control (MR, MR) and MR mice underwent coronary artery ligation. MR ablation had no detectable baseline effect on cardiac morphology and function. The progressive left ventricular chamber enlargement and functional deterioration in infarcted control mice, detected by echocardiography and conductance catheter analysis during the 8-week observation period, were substantially attenuated in MR mice. Chronically infarcted MR mice displayed attenuated pulmonary edema, reduced cardiac hypertrophy, increased capillary density, and reduced accumulation of extracellular matrix proteins in the surviving left ventricular myocardium. Moreover, cardiomyocyte-specific MR ablation prevented the increases in myocardial and mitochondrial O2 production and upregulation of the NADPH oxidase subunits Nox2 and Nox4. At 7 days, MR mice exhibited enhanced infarct neovessel formation and collagen structural organization associated with reduced infarct expansion. Mechanistically, cardiomyocytes lacking MR displayed accelerated stress-induced activation and subsequent suppression of nuclear factor-κB and reduced apoptosis early after myocardial infarction. Conclusion- Cardiomyocyte-specific MR deficiency improved infarct healing and prevented progressive adverse cardiac remodeling, contractile dysfunction, and molecular alterations in ischemic heart failure, highlighting the importance of cardiomyocyte MR for heart failure development and progression. Copyright © 2011 American Heart Association. All rights reserved. Source


Kahesa C.,Copenhagen University | Kahesa C.,Ocean Road Cancer Institute | Kjaer S.K.,Danish Cancer Society | Kjaer S.K.,Copenhagen University | And 7 more authors.
BMC Public Health | Year: 2012

Background: Tanzania is among the countries in the world where the cervical cancer incidence is estimated to be highest. Acknowledging an increase in the burden of cervical cancer, VIA was implemented as a regional cervical cancer screening strategy in Tanzania in 2002. With the aim of describing risk factors for VIA positivity and determinants of screening attendances in Tanzania, this paper present the results from a comparative analysis performed among women who are reached and not reached by the screening program". Methods. 14 107 women aged 25-59 enrolled in a cervical cancer screening program in Dar es Salaam in the period 2002 - 2008. The women underwent VIA examination and took part in a structured questionnaire interview. Socioeconomic characteristics, sexual behavior, HIV status and high-risk (HR) HPV infection were determined in a subpopulation of 890 who participated and 845 who did not participate in the screening. Results: Being widowed/separated OR=1.41 (95% CI: 1.17-1.66), of high parity OR=3.19 (95% CI: 1.84-5.48) of low education OR= 4.30 (95% CI: 3.50-5.31) and married at a young age OR=2.17 (95% CI: 1.37-3.07) were associated with being VIA positive. Women who participated in the screening were more likely to be HIV positive OR= 1.59 (95% CI. 1.14-2.25) in comparison with women who had never attended screening, while no difference was found in the prevalence of HR-HPV infection among women who had attended screening and women who had not attended screening. Conclusion: Women who are widowed/separated, of high parity, of low education and married at a young age are more likely to be VIA positive and thus at risk of developing cervical cancer. The study further documents that a referral linkage between the HIV care and treatment program and the cervical cancer screening program is in place in the setting studied, where HIV positive were more likely to participate in the cervical cancer screening program than HIV negative women. © 2012 Kahesa et al.; licensee BioMed Central Ltd. Source

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