120 research outputs found
Long-term follow-up of acute porphyria in female patients : Update of clinical outcome and life expectancy
Background: Acute hepatic porphyria includes four inherited disorders caused by partial deficiencies of enzymes related to the heme biosynthesis. Clinical manifestations include acute attacks, occurring mainly among female patients. This study describes the diversity of acute symptoms, changes in triggering factors and life expectancy among female patients during the past five decades. Methods: 107 Finnish female patients were enrolled into a retrospective, longitudinal study during 2015. Clinical, biochemical and genetic data was obtained from the medical reports, registry data and a questionnaire designed for the study. Causes of death were studied in additional 32 female patients. Results: Of the 43 patients with hospitalization, 33% had non-complicated, 35% prolonged and 28% severe attacks with no correlation with the disease-causing mutation. Of the deceased patients, 31% died of an acute attack during 1957-1979. Thereafter the incidence and severity of acute attacks have decreased substantially. 55% of the subjects reported acute symptoms (dysautonomia and mental symptoms) without hospitalization, 29% had porphyria symptoms >10 times, and 23% within the last year. Despite 22% of the female patients had died of primary liver cancer, the life expectancy increased more than 10 years during the follow-up, and did not differ from the normal population at present. Conclusions: The incidence of acute attacks requiring hospitalization has decreased, but more than half of the female patients reported acute symptoms affecting their well-being. Symptoms are currently triggered by hormonal changes and weight loss emphasizing the importance of early recognition and active management to avoid disease exacerbation. Death due to primary liver cancer is common and should be screened regularly.Peer reviewe
Wet chemical polishing for industrial type PERC solar cells
Industrial PERC cell process flows typically apply the polishing of the rear side after texturing as well as the edge isolation after POCl3 diffusion. In this paper, we present a novel single step polishing process which we apply post double sided texturing and diffusion in order to remove the rear emitter and to reduce the rear surface roughness. One challenge is to minimize the etch back of the front side emitter during rear side polishing due to the reactive gas phase of the polishing process. By optimizing the polishing process, we are able to limit the increase of the emitter sheet resistance below 5 Ω/sq. However, the wet cleaning post polishing contributes an additional 20 Ω/sq emitter sheet resistance increase which is subject to further optimization. We compensate the emitter sheet resistance increase due to wet cleaning by applying a 45 Ω/sq POCl3 diffusion instead of a 60 Ω/sq diffusion. The resulting PERC solar cells with polished rear surface post texture and diffusion show conversion efficiencies up to 19.6% which is comparable to the reference PERC cells which apply a rear protection layer instead of a polishing process.German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety/0325296Heraeus Precious MetalsRenaSingulus TechnologiesSolar Worl
Champacyclin, a New Cyclic Octapeptide from Streptomyces Strain C42 Isolated from the Baltic Sea
New isolates of Streptomyces champavatii were isolated from marine sediments of the Gotland Deep (Baltic Sea), from the Urania Basin (Eastern Mediterranean), and from the Kiel Bight (Baltic Sea). The isolates produced several oligopeptidic secondary metabolites, including the new octapeptide champacyclin (1a) present in all three strains. Herein, we report on the isolation, structure elucidation and determination of the absolute stereochemistry of this isoleucine/leucine (Ile/Leu = Xle) rich cyclic octapeptide champacyclin (1a). As 2D nuclear magnetic resonance (NMR) spectroscopy could not fully resolve the structure of (1a), additional information on sequence and configuration of stereocenters were obtained by a combination of multi stage mass spectrometry (MSn) studies, amino acid analysis, partial hydrolysis and subsequent enantiomer analytics with gas chromatography positive chmical ionization/electron impact mass spectrometry (GC-PCI/EI-MS) supported by comparison to reference dipeptides. Proof of the head-to-tail cyclization of (1a) was accomplished by solid phase peptide synthesis (SPPS) compared to an alternatively side chain cyclized derivative (2). Champacyclin (1a) is likely synthesized by a non-ribosomal peptide synthetase (NRPS), because of its high content of (d)-amino acids. The compound (1a) showed antimicrobial activity against the phytopathogen Erwinia amylovora causing the fire blight disease of certain plants
Tumour assessment in advanced melanoma: value of FDG-PET/CT in patients with elevated serum S-100B
Purpose: To evaluate the usefulness of PET/CT in melanoma patients with an elevated serum S-100B tumour marker level. Methods: Out of 165 consecutive high-risk melanoma patients referred for PET/CT imaging, 47 had elevated (>0.2μg/l) S-100B serum levels and a contemporaneous 18F-FDG PET/CT scan. PET/CT scans were evaluated for the presence of metastases. To produce a composite reference standard, we used cytological, histological, MRI and PET/CT follow-up findings as well as clinical and S-100B follow-up. Results: Among the 47 patients with increased S-100B levels, PET/CT correctly identified metastases in 38 (30 distant metastases and eight lymph node metastases). In one patient with cervical lymph node metastases, PET/CT was negative. Eight patients had no metastases and PET/CT correctly excluded metastases in all of them. Overall sensitivity for metastases was 97% (38/39), specificity 100% (8/8) and accuracy 98% (46/47). S-100B was significantly higher in patients with distant metastases (mean 1.93μg/l, range 0.3-14.3μg/l) than in patients with lymph node metastases (mean 0.49μg/l, range 0.3-1.6μg/l, p = 0.003) or patients without metastases (mean 0.625μg/l, range 0.3-2.6μg/l, p = 0.007). However, 6 of 14 patients with a tumour marker level of 0.3μg/l had no metastases. Conclusion: In melanoma patients with elevated S-100B tumour marker levels, FDG-PET/CT accurately identifies lymph node or distant metastases and reliably excludes metastases. Because of the significant number of false positive S-100B tumour marker determinations (17%), we recommend repetition of tumour marker measurements if elevated S-100B levels occur before extensive imaging is use
Interventional Pneumology in Pulmonary Bleeding; A Review: From the Bronchus to the Vessel
Interventional pneumology includes both bronchological and vascular methods of diagnosis
and therapy, especially in emergency situations such as pulmonary hemorrhage. In
massive pulmonary hemorrhage bronchological diagnosis is required to determine the site
and extent of bleeding, as well as angiography of bronchial arteries, and of pulmonary
arteries. Bronchus occlusion by aid of balloon catheter or double lumen tube are holding
measures until definitive surgery or embolization of bronchial or pulmonary arteries can
be performed. The paper suggests a close relationship between bronchoscopic and angiographic
diagnosis and therapy in case of severe pulmonary bleeding
An epigenetic reprogramming strategy to re-sensitize radioresistant prostate cancer cells
Radiotherapy is a mainstay of curative prostate cancer treatment, but risks of recurrence after treatment remain significant in locally advanced disease. Given that tumor relapse can be attributed to a population of cancer stem cells (CSC) that survives radiotherapy, analysis of this cell population might illuminate tactics to personalize treatment. However, this direction remains challenging given the plastic nature of prostate cancers following treatment. We show here that irradiating prostate cancer cells stimulates a durable upregulation of stem cell markers that epigenetically reprogram these cells. In both tumorigenic and radioresistant cell populations, a phenotypic switch occurred during a course of radiotherapy that was associated with stable genetic and epigenetic changes. Specifically, we found that irradiation triggered histone H3 methylation at the promoter of the CSC marker aldehyde dehydrogenase 1A1 (ALDH1A1), stimulating its gene transcription. Inhibiting this methylation event triggered apoptosis, promoted radiosensitization, and hindered tumorigenicity of radioresistant prostate cancer cells. Overall, our results suggest that epigenetic therapies may restore the cytotoxic effects of irradiation in radioresistant CSC populations
Children’s first experience of taking anabolic-androgenic steroids can occur before their 10th birthday: a systematic review identifying 9 factors that predict doping among young people
Taking performance-enhancing drugs (PEDs) can cause serious and irreversible health consequences, which can ultimately lead to premature death. Some young people may take PEDs without fully understanding the ramifications of their actions or based on the advice from others. The purpose of this systematic review was to identify the main factors that predicted doping among young people. The literature was systematically reviewed using search engines, manually searching specialist journals, and pearl growing. Fifty-two studies, which included 187,288 young people aged between 10 and 21 years of age, 883 parents of adolescent athletes, and 11 adult coaches, who were interviewed regarding young athletes, were included in this review. Nine factors predicted doping among young people: gender; age; sports participation; sport type; psychological variables; entourage; ethnicity; nutritional supplements’ and health harming behaviors. In regards to psychological variables, 22 different constructs were associated with doping among young people. Some psychological constructs were negatively associated with doping (e.g., self-esteem, resisting social pressure, and perfectionist strivings), whereas other were positively associated with doping (e.g., suicide risk, anticipated regret, and aggression). Policy makers and National Anti-Doping Organisations could use these findings to help identify athletes who are more at risk of doping and then expose these individuals to anti-doping education. Based on the current findings, it also appears that education programs should commence at the onset of adolescence or even late childhood, due to the young age in which some individuals start doping
DNA-Methylome based Tumor Hypoxia Classifier Identifies HPV-negative Head & Neck Cancer Patients at Risk for Locoregional Recurrence After Primary Radiochemotherapy
BACKGROUND
Tumor hypoxia is a paradigmatic negative prognosticator of treatment resistance in Head and Neck Squamous Cell Carcinoma (HNSCC). The lack of robust and reliable hypoxia classifiers limits the adaptation of stratified therapies. We hypothesized that the tumor DNA methylation landscape might indicate epigenetic reprogramming induced by chronic intratumoral hypoxia.
METHODS
A DNA methylome-based tumor hypoxia classifier (Hypoxia-M) was trained in the TCGA-HNSCC cohort based on matched assignments using gene expression-based signatures of hypoxia (Hypoxia-GES). Hypoxia-M was validated in a multicenter DKTK-ROG trial consisting of Human Papilloma Virus (HPV)-negative HNSCC patients treated with primary radiochemotherapy (RCHT).
RESULTS
While hypoxia-GSEs failed to stratify patients in the DKTK-ROG, Hypoxia-M was independently prognostic for local recurrence (LR, HR=4.3, p=0.001) and overall survival (OS, HR=2.34, p=0.03) but not distant metastasis (DM) after RCHT in the both cohorts. Hypoxia-M status was inversely associated with CD8 T-cells infiltration in both cohorts. Hypoxia-M was further prognostic in the TCGA-PanCancer cohort (HR=1.83, p=0.04), underscoring the breadth of this classifier for predicting tumor hypoxia status.
CONCLUSIONS
Our findings highlight an unexplored avenue for DNA Methylation-based classifiers as biomarkers of tumoral hypoxia for identifying high-risk features in patients with HNSCC tumors.
TRIAL REGISTRATION
Retrospective observational study from the German Cancer Consortium (DKTK-ROG), not interventional
DIMA - Annotation Guidelines for German Intonation
KĂĽgler F, Smolibocki B, Arnold D, et al. DIMA - Annotation Guidelines for German Intonation. In: Proceedings of the 18th International Congress of Phonetic Sciences. Glasgow, Scotland; 2015: 317.This paper presents newly developed guidelines for
prosodic annotation of German as a consensus
system agreed upon by German intonologists. The
DIMA system is rooted in the framework of
autosegmental-metrical phonology. One important
goal of the consensus is to make exchanging data
between groups easier since German intonation is
currently annotated according to different models.
To this end, we aim to provide guidelines that are
easy to learn. The guidelines were evaluated running
an inter-annotator reliability study on three different
speech styles (read speech, monologue and
dialogue). The overall high Îş between 0.76 and 0.89
(depending on the speech style) shows that the
DIMA conventions can be applied successfully
DIMA - Annotation Guidelines for German Intonation
KĂĽgler F, Smolibocki B, Arnold D, et al. DIMA - Annotation Guidelines for German Intonation. In: Proceedings of the 18th International Congress of Phonetic Sciences. Glasgow, Scotland; 2015: 317.This paper presents newly developed guidelines for
prosodic annotation of German as a consensus
system agreed upon by German intonologists. The
DIMA system is rooted in the framework of
autosegmental-metrical phonology. One important
goal of the consensus is to make exchanging data
between groups easier since German intonation is
currently annotated according to different models.
To this end, we aim to provide guidelines that are
easy to learn. The guidelines were evaluated running
an inter-annotator reliability study on three different
speech styles (read speech, monologue and
dialogue). The overall high Îş between 0.76 and 0.89
(depending on the speech style) shows that the
DIMA conventions can be applied successfully
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