564 research outputs found
MorbiditÀt und MortalitÀt der HIV-Infektion
Zusammenfassung: MorbiditĂ€t und MortalitĂ€t von HIV-infizierten Menschen haben seit 1996 aufgrund der antiretroviralen Kombinationstherapie (cART) dramatisch abgenommen. Die HIV-Infektion wurde somit zu einer chronischen, ambulant behandelbaren und meist asymptomatischen Krankheit mit praktisch normaler Lebenserwartung. Ein Hauptgrund der verbleibenden MorbiditĂ€t und Sterblichkeit ist, dass die HIV-Infektion in etwa 20% der FĂ€lle spĂ€t diagnostiziert bzw. therapiert wird. Oft liegt zu diesem Zeitpunkt die CD4-Zellzahl bereits unter der Schwelle von 200Zellen/”l und/oder AIDS-definierende Krankheiten haben sich manifestiert. Weitere GrĂŒnde fĂŒr die verbleibende MorbiditĂ€t und MortalitĂ€t sind KomorbiditĂ€ten, insbesondere die Koinfektion mit einer viralen Hepatitis und Tumoren bei Ă€lteren Patienten. Durch die verbesserte Prognose nimmt das Alter HIV-infizierter Menschen zu. Dies bedeutet aufgrund von KomorbiditĂ€ten und sozioökonomischen Kosten eine erhebliche Herausforderung fĂŒr die Zukunf
The metastatic potential of seminomatous germ cell tumours is associated with a specific microRNA pattern
Background
Seminomatous germ cell tumours (SGCT) are the most frequent malignancy in young men. Reliable prognostic biomarkers for the prediction of metastasis at diagnosis and the risk of relapse in clinical stage I (CSI) are lacking. Adjuvant therapies carry a risk of overtreatment, whereas salvage therapies have a risk of high toxicities. Thus, the identification of reliable prognostic biomarkers is highly desirable to identify patients who will benefit from early adjuvant treatment. MicroRNAs (miRNAs) regulate tumour development and progression, and their potential as biomarkers has already been proven in a variety of malignancies.
Objectives
The aim of our study was to define a specific miRNA expression pattern that discriminates metastatic from nonâmetastatic primary SGCT.
Materials and methods
Total RNA was isolated from 24 formalinâfixed paraffinâembedded (FFPE) primary SGCT tumours (10 nonâmetastatic, five metachronously and nine synchronously metastatic) and from 10 normal testicular tissue samples. Microarray analysis was performed for global miRNA expression profiling. The results were validated by quantitative realâtime polymerase chain reaction (qRTâPCR). Statistical analysis was performed using SPSS.
Results
Microarray analyses revealed a specific miRNA pattern that distinguishes metastatic from nonâmetastatic SGCT. Sixtyâthree miRNAs were differentially expressed in metastatic compared to nonâmetastatic tumours (P < .01). Microarray results were confirmed by qRTâPCR for three out of five selected miRNAs (miRâ29câ5p, miRâ506â3p and miRâ371aâ5p; P < .05). All five miRNAs (miRâ29câ5p, miRâ506â3p, miRâ1307â5p, miRâ371aâ5p and miRâ371aâ3p) showed differential expression between tumour and normal tissues (P < .05).
Conclusion
Metastatic primary SGCTs are characterized by a specific miRNA expression pattern. Therefore, specific miRNAs could represent a new tool to predict the metastatic potential in SGCT patients
Microtubule-based perception of mechanical conflicts controls plant organ morphogenesis.
Precise coordination between cells and tissues is essential for differential growth in plants. During lateral root formation in Arabidopsis thaliana, the endodermis is actively remodeled to allow outgrowth of the new organ. Here, we show that microtubule arrays facing lateral root founder cells display a higher order compared to arrays on the opposite side of the same cell, and this asymmetry is required for endodermal remodeling and lateral root initiation. We identify that MICROTUBULE ASSOCIATED PROTEIN 70-5 (MAP70-5) is necessary for the establishment of this spatially defined microtubule organization and endodermis remodeling and thus contributes to lateral root morphogenesis. We propose that MAP70-5 and cortical microtubule arrays in the endodermis integrate the mechanical signals generated by lateral root outgrowth, facilitating the channeling of organogenesis
miRNA Expression Characterizes Histological Subtypes and Metastasis in Penile Squamous Cell Carcinoma
Although microRNAs are described as promising biomarkers in many tumor types, little
is known about their role in PSCC. Thus, we attempted to identify miRNAs involved in tumor
development and metastasis in distinct histological subtypes considering the impact of HPV infection.
In a first step, microarray analyses were performed on RNA from formalin-fixed, paraffin-embedded
tumor (22), and normal (8) tissue samples. Microarray data were validated for selected miRNAs by
qRT-PCR on an enlarged cohort, including 27 tumor and 18 normal tissues. We found 876 significantly
differentially expressed miRNAs (p †0.01) between HPV-positive and HPV-negative tumor samples
by microarray analysis. Although no significant differences were detected between normal and tumor
tissue in the whole cohort, specific expression patterns occurred in distinct histological subtypes,
such as HPV-negative usual PSCC (95 differentially expressed miRNAs, p †0.05) and HPV-positive
basaloid/warty subtypes (247 differentially expressed miRNAs, p †0.05). Selected miRNAs were
confirmed by qRT-PCR. Furthermore, microarray data revealed 118 miRNAs (p †0.01) that were
significantly differentially expressed in metastatic versus non-metastatic usual PSCC. The lower
expression levels for miR-137 and miR-328-3p in metastatic usual PSCC were validated by qRT-PCR.
The results of this study confirmed that specific miRNAs could serve as potential diagnostic and
prognostic markers in single PSCC subtypes and are associated with HPV-dependent pathways
Evaluation of Prognostic Parameters to Identify Aggressive Penile Carcinomas
Background: Advanced penile carcinoma is characterized by poor prognosis. Most data on
prognostic factors are based on small study cohorts, and even meta-analyses are limited in patient
numbers. Therefore, there is still a lack of evidence for clinical decisions. In addition, the most recent
TNM classification is questionable; in line with previous studies, we found that it has not improved
prognosis estimation. Methods: We evaluated 297 patients from Germany, Russia, and Portugal.
Tissue samples from 233 patients were re-analyzed by two experienced pathologists. HPV status, p16,
and histopathological parameters were evaluated for all patients. Results: Advanced lymph node
metastases (N2, N3) were highly significantly associated with reductions in metastasis-free (MFS),
cancer-specific (CS), and overall survival (OS) rates (p = <0.001), while lymphovascular invasion was
a significant parameter for reduced CS and OS (p = 0.005; p = 0.007). Concerning the primary tumor
stage, a significant difference in MFS was found only between pT1b and pT1a (p = 0.017), whereas CS
and OS did not significantly differ between T categories. In patients without lymph node metastasis
at the time of primary diagnosis, lymphovascular invasion was a significant prognostic parameter
for lower MFS (p = 0.032). Histological subtypes differed in prognosis, with the worst outcome
in basaloid carcinomas, but without statistical significance. HPV status was not associated with
prognosis, either in the total cohort or in the usual type alone. Conclusion: Lymphatic involvement
has the highest impact on prognosis in penile cancer, whereas HPV status alone is not suitable
as a prognostic parameter. The pT1b stage, which includes grading, as well as lymphovascular
and perineural invasion in the T stage, seems questionable; a revision of the TNM classification is
therefore required
Assessing the danger of self-sustained HIV epidemics in heterosexuals by population based phylogenetic cluster analysis.
Assessing the danger of transition of HIV transmission from a concentrated to a generalized epidemic is of major importance for public health. In this study, we develop a phylogeny-based statistical approach to address this question. As a case study, we use this to investigate the trends and determinants of HIV transmission among Swiss heterosexuals. We extract the corresponding transmission clusters from a phylogenetic tree. To capture the incomplete sampling, the delayed introduction of imported infections to Switzerland, and potential factors associated with basic reproductive number R0, we extend the branching process model to infer transmission parameters. Overall, the R0 is estimated to be 0.44 (95%-confidence interval 0.42-0.46) and it is decreasing by 11% per 10 years (4%-17%). Our findings indicate rather diminishing HIV transmission among Swiss heterosexuals far below the epidemic threshold. Generally, our approach allows to assess the danger of self-sustained epidemics from any viral sequence data
Incident Hepatitis C Virus Infections in the Swiss HIV Cohort Study : changes in treatment uptake and outcomes between 1991 and 2013
Background: The hepatitis C virus (HCV) epidemic is evolving rapidly in patients infected with human immunodeficiency virus (HIV). We aimed to describe changes in treatment uptake and outcomes of incident HCV infections before and after 2006, the time-point at which major changes in HCV epidemic became apparent. Methods. âWe included all adults with an incident HCV infection before June 2012 in the Swiss HIV Cohort Study, a prospective nationwide representative cohort of individuals infected with HIV. We assessed the following outcomes by time period: the proportion of patients starting an HCV therapy, the proportion of treated patients achieving a sustained virological response (SVR), and the proportion of patients with persistent HCV infection during follow-up. Results. âOf 193 patients with an HCV seroconversion, 106 were diagnosed before and 87 after January 2006. The proportion of men who have sex with men increased from 24% before to 85% after 2006 (P < .001). Hepatitis C virus treatment uptake increased from 33% before 2006 to 77% after 2006 (P < .001). Treatment was started during early infection in 22% of patients before and 91% after 2006 (P < .001). An SVR was achieved in 78% and 29% (P = .01) of patients treated during early and chronic HCV infection. The probability of having a detectable viral load 5 years after diagnosis was 0.67 (95% confidence interval [CI], 0.58-0.77) in the group diagnosed before 2006 and 0.24 (95% CI, 0.16-0.35) in the other group (P < .001). Conclusions. In recent years, increased uptake and earlier initiation of HCV therapy among patients with incident infections significantly reduced the proportion of patients with replicating HCV
A Generic Bio-Economic Farm Model for Environmental and Economic Assessment of Agricultural Systems
Bio-economic farm models are tools to evaluate ex-post or to assess ex-ante the impact of policy and technology change on agriculture, economics and environment. Recently, various BEFMs have been developed, often for one purpose or location, but hardly any of these models are re-used later for other purposes or locations. The Farm System Simulator (FSSIM) provides a generic framework enabling the application of BEFMs under various situations and for different purposes (generating supply response functions and detailed regional or farm type assessments). FSSIM is set up as a component-based framework with components representing farmer objectives, risk, calibration, policies, current activities, alternative activities and different types of activities (e.g., annual and perennial cropping and livestock). The generic nature of FSSIM is evaluated using five criteria by examining its applications. FSSIM has been applied for different climate zones and soil types (criterion 1) and to a range of different farm types (criterion 2) with different specializations, intensities and sizes. In most applications FSSIM has been used to assess the effects of policy changes and in two applications to assess the impact of technological innovations (criterion 3). In the various applications, different data sources, level of detail (e.g., criterion 4) and model configurations have been used. FSSIM has been linked to an economic and several biophysical models (criterion 5). The model is available for applications to other conditions and research issues, and it is open to be further tested and to be extended with new components, indicators or linkages to other models
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