Die Geschäftsfähigkeit Minderjähriger im Datenschutzrecht am Beispiel der Zustimmungserklärung gem. § 4 Z 14 DSG

Das Datenschutzgesetz (DSG) legt fest, unter welchen Voraussetzungen die Verwendung personenbezogener Daten zulässig ist. Eine der wichtigsten Grundlagen in der Praxis ist die Zustimmungserklärung des Betroffenen (§ 4 Z 14 DSG) definiert. Allerdings lässt sich dem DSG nicht entnehmen, ob auch Minderjährige rechtswirksam eine datenschutzrechtliche Zustimmungserklärung abgeben können. Einschlägige Rechtsprechung liegt – soweit ersichtlich – ebenfalls noch nicht vor. Die Auslegung des Begriffes der Zustimmung führt zu dem Ergebnis, dass eine Regelungslücke vorliegt. Diese ist mittels Analogie zu schließen. Eine passende Analogiebasis findet sich in § 146c ABGB. Diese Bestimmung stellt auf die Einsichts- und Urteilsfähigkeit des Minderjährigen und nicht auf die starre Rechtsgeschäfts-Fähigkeit, wie sie in den §§ 151, 865 ABGB geregelt ist, ab. Die vorliegende Arbeit weist nach, dass ein ausreichend einsichts- und urteilsfähiger Minderjähriger eine rechtswirksame datenschutzrechtliche Zustimmung zur Verwendung nicht sensibler personenbezogener Daten abgeben kann; ab Erreichen des vierzehnten Lebensjahres kann das Vorliegen der erforderlichen geistigen Fähigkeiten analog zu § 146c Abs 1 ABGB vermutet werden. Bei der Verwendung sensibler personenbezogener Daten ist – wie bei Heilbehandlungen, die mit schwerwiegenden oder nachhaltigen Auswirkungen verbunden sein können – zusätzlich die Genehmigung des gesetzlichen Vertreters erforderlich. Grundlage für eine rechtswirksame Zustimmungserklärung ist aber in jedem Fall eine vorangehende vollständige und verständliche Information (Aufklärung) des Minderjährigen sowie - im Falle der Verwendung sensibler Daten – des gesetzlichen Vertreters.The Austrian Data Protection Act (ADPA) defines the prerequisites for the processing of personal data. One of the most important legal bases in practice is the data subject's consent (sec. 4 cif. 14 ADPA). However, the ADPA does not clarify whether a data controller can obtain a minor's valid consent. Apparently, there is no case law on this matter so far. Interpretation of the term consent indicates a regulatory gap which has to be filled by analogy. In this context sect. 146c of the Austrian Civil Code (ACC) provides a suitable basis for comparison. Unlike sect. 151 and sect 865 ACC, which define a rigid system re a minor's capacity to contract, sect. 146c ACC focuses on the minor's ability to understand the reasons and implications of his/her decisions and to act accordingly. This paper aims to prove that a minor who is able to understand the reasons and the implications of his decision (which can be assumed when the minor is at least fourteen years old; sect. 146c par. 1 ACC per analogiam) can give a valid consent with respect to the processing of non sensitive personal data. If a minor wants to receive a medical treatment which may lead to serious adverse reactions or undesirable long-term effects or if he/she wants to consent to the processing of sensitive data the parent's additional approval is required. In any case the data controller is required to give the minor and – if sensitive data are to be processed – the parent prior complete and clear information

RADICAL SAM ENZYMES IN THIENAMYCIN BIOSYNTHESIS

Despite its broad anti-infective activity, the biosynthesis of the paradigm carbapenem antibiotic, thienamycin, remains largely unknown. Apart from the first two biosynthetic steps shared with a simple carbapenem, the pathway sharply diverges to the more structurally complex members of this class of beta-lactam antibiotics like thienamycin. Existing evidence points to three putative cobalamin-dependent, radical S- adenosylmethionine (RS) enzymes, ThnK, ThnL and ThnP, potentially being responsible for assembly of the ethyl side chain at C6, bridgehead epimerization at C5, installation of the C2-thioether side chain and C2/3-desaturation. The C2 substituent has been demonstrated to be derived from stepwise truncation of coenzyme A, but the timing of these events with respect to C2—S bond formation is not known. Using in vitro reactions with synthetically-accessed substrates, we show that ThnK of the three apparent cobalamin-dependent RS enzymes performs sequential methylations to build out the C6- ethyl side chain in a stereocontrolled manner. This enzymatic reaction produced the expected RS methylase coproducts S-adenosylhomocysteine (SAH) and 5’- deoxyadenosine (5’-dA) by LC-MS and was also found to require cobalamin. For double methylation to occur, the carbapenam substrate must bear a coenzyme A-derived C2- thioether side chain, implying the activity of a prior sulfur insertion by an unidentified enzyme. Heterologous expression of thienamycin biosynthetic enzymes in Streptomyces combined with a competition bioassay now implicates ThnL in attachment of the thioether. Additional substrate profiling with ThnK suggests that CoA itself is added to the bicyclic carbapenam nucleus. These insights allow refinements of the central steps in complex carbapenem biosynthesis

Pathophysiology of myocardial remodeling in survivors of ST-elevation myocardial infarction revealed by native T1 mapping: inflammation, remote myocardium and prognostic significance

Background: The pathophysiology and prognostic significance of remote myocardium in the natural history of STEMI is uncertain. Cardiac magnetic resonance (CMR) provides a non-invasive assessment of myocardial pathology that is spatially and temporally coordinated. Native T1 quantified by CMR (T1 relaxation time, milliseconds) is a fundamental tissue property determined by water content and cellularity. We aimed to investigate the clinical significance of remote myocardium in survivors of acute ST-elevation myocardial infarction (STEMI) using native T1 mapping. Methods: We performed a prospective single center cohort study in reperfused STEMI patients who underwent CMR 2 days and 6 months post-MI and long term follow-up (18 months minimum). Native T1 CMR (MOLLI investigational prototype sequence: 3 (3) 3 (3) 5) was measured in regions-of-interest in remote and injured myocardium. Infarction was depicted on late gadolinium contrast enhancement imaging. Adverse remodeling was defined as an increase in left ventricular end-diastolic volume ≥ 20% at 6 months. Major adverse cardiac events (MACE) were defined as cardiac death or hospitalization for non-fatal MI or heart failure. Results are mean±SD unless specified. Results: 300 STEMI patients (mean age 59 years, 74% male) gave informed consent (14 July 2011 - 21 November 2012). Of these, 288 STEMI patients had evaluable native T1 CMR and follow-up data (median duration 845 days). Infarct size was 18±14% of left ventricular mass. Two days post-STEMI, native T1 in remote myocardium was lower than native T1 in the infarct zone (961±25 ms vs. 1097±52 ms; p<0.01). In multivariable linear regression, remote zone native T1 was independently associated with incomplete ST-segment resolution (9.42 (2.37 to 16.47); p=0.009), the log of the initial CRP concentration (regression coefficient 3.01 (95% CI 0.016 to 5.55); p=0.038) and the peak monocyte count within 2 days of admission (10.20 (0.74, 19.67); p=0.035). At 6 months, left ventricular end-diastolic volume increased by 5 (25) ml (n=262 patients with evaluable data) overall, and adverse remodeling occurred in 30 (12%) patients. Remote zone native T1 was a multivariable predictor of the change in left ventricular end-diastolic volume from baseline (0.13 (0.01, 0.24); p=0.035). 39 (13.5%) patients experienced a MACE including 20 (6.9%) patients with a post-discharge MACE. Remote zone native T1 was an independent predictor of post-discharge MACE (hazard ratio 1.016, 95% CI 1.000, 1.032; p=0.048) including after adjustment for changes in LVEF (p=0.032), LV end-diastolic volume (p=0.053), and monocyte count (p=0.036). Conclusions: Remote zone tissue characteristics early post-MI are temporally linked with reperfusion injury and inflammation and independently predict left ventricular remodeling and MACE in STEMI survivors

Prognostic significance of infarct core pathology in ST-elevation myocardial infarction survivors revealed by non-contrast T1 mapping cardiac magnetic resonance

Background: Myocardial longitudinal relaxation time (T1, ms) is a fundamental magnetic property of tissue that is related to water content and mobility. The pathophysiological and prognostic importance of native myocardial T1 values in acute ST-elevation myocardial infarction (STEMI) patients is unknown. We aimed to assess the clinical significance of infarct core native T1. Methods: We performed a prospective single center cohort study in reperfused STEMI patients who underwent CMR 2 days and 6 months post-MI. Native T1 CMR (MOLLI investigational prototype sequence: 3 (3) 3 (3) 5) was measured in myocardial regions-of-interest. The infarct territory and microvascular obstruction (MVO) were depicted with late gadolinium enhancement CMR. Adverse remodeling was defined as an increase in LV end-diastolic volume (LVEDV) ≥ 20% at 6 months. All-cause death or heart failure hospitalization was a pre-specified outcome that was assessed during follow-up. Results: 300 STEMI patients (mean±SD age 59±12 years, 74% male, 114 with anterior STEMI) gave informed consent and had CMR (14 July 2011 - 22 November 2012). Of these, 288 STEMI patients had evaluable T1 maps. Infarct size was 18 ±14% of LV mass. One hundred and forty five (50%) of 288 patients had late MVO, whereas 160 (56%) patients had infarct core pathology revealed by native T1. Native T1 within the infarct core (996.9±57.3; p<0.01) was higher than in the remote zone (961±25 ms; p<0.01) but lower than in the area-at-risk (1097 ±52 ms). In multivariable linear regression, native T1 in the infarct core was negatively associated with age, initial systolic blood pressure, TIMI coronary flow grade at initial angiography, Killip class at presentation and neutrophil count (all p<0.05), independent of LVEF, LVEDV or infarct size. At 6 months, LVEDV increased by 5 (25) ml (n=262 patients with evaluable data). Adverse remodeling occurred in 30 (12%) patients and 23 (76.7%) of these patients MVO at baseline. T1 in the infarct core was a multivariable predictor of adverse remodeling (-0.01 (-0.02, -0.00); p=0.048). 288 (100%) patients were followed-up for a median of 845 days. Thirty (10.4%) patients died or experienced a heart failure event and 13 (4.5%) of these patients experienced the event post-discharge. Infarct core native T1 predicted all-cause death or heart failure post-discharge (hazard ratio 0.969, 95% CI 0.953, 0.985; p<0.001) including after adjustment for LVEF (p<0.001) and LVEDV at baseline (p<0.001), and was comparable with MVO

Biocatalytic production of bicyclic β-lactams with three contiguous chiral centres using engineered crotonases

YesThere is a need to develop asymmetric routes to functionalised β-lactams, which remain the most important group of antibacterials. Here we describe biocatalytic and protein engineering studies concerning carbapenem biosynthesis enzymes, aiming to enable stereoselective production of functionalised carbapenams with three contiguous chiral centres. Structurallyguided substitutions of wildtype carboxymethylproline synthases enable tuning of their C-N and C-C bond forming capacity to produce 5-carboxymethylproline derivatives substituted at C-4 and C-6, from amino acid aldehyde and malonyl-CoA derivatives. Use of tandem enzyme incubations comprising an engineered carboxymethylproline synthase and an alkylmalonylCoA forming enzyme (i.e. malonyl-CoA synthetase or crotonyl-CoA carboxylase reductase) can improve stereocontrol and expand the product range. Some of the prepared 4,6-disubstituted-5-carboxymethylproline derivatives are converted to bicyclic β-lactams by carbapenam synthetase catalysis. The results illustrate the utility of tandem enzyme systems involving engineered crotonases for asymmetric bicyclic β-lactam synthesis

Enhancement of cutaneous wound healing by Dsg2 augmentation of uPAR secretion

In addition to playing a role in adhesion, desmoglein 2 (Dsg2) is an important regulator of growth and survival signaling pathways, cell proliferation, migration and invasion, and oncogenesis. While low-level Dsg2 expression is observed in basal keratinocytes and is downregulated in non-healing venous ulcers, overexpression has been observed in both melanomas and non-melanoma malignancies. Here, we show that transgenic mice overexpressing Dsg2 in basal keratinocytes primed the activation of mitogenic pathways, but did not induce dramatic epidermal changes or susceptibility to chemical-induced tumor development. Interestingly, acceleration of full-thickness wound closure and increased wound-adjacent keratinocyte proliferation was observed in these mice. As epidermal cytokines and their receptors play critical roles in wound healing, Dsg2-induced secretome alterations were assessed with an antibody profiler array and revealed increased release and proteolytic processing of the urokinase-type plasminogen activator receptor (uPAR). Dsg2 induced uPAR expression in the skin of transgenic compared to wild-type mice. Wound healing further enhanced uPAR in both epidermis and dermis with concomitant increase in the pro-healing laminin-332, a major component of the basement membrane zone, in transgenic mice. This study demonstrates that Dsg2 induces epidermal activation of various signaling cascades and accelerates cutaneous wound healing, in part, through uPAR-related signaling cascades

Accurate prediction of response to endocrine therapy in breast cancer patients: current and future biomarkers

WOS: 000390900700001PubMed ID: 27903276Approximately 70% of patients have breast cancers that are oestrogen receptor alpha positive (ER+) and are therefore candidates for endocrine treatment. Many of these patients relapse in the years during or following completion of adjuvant endocrine therapy. Thus, many ER+ cancers have primary resistance or develop resistance to endocrine therapy during treatment. Recent improvements in our understanding of how tumours evolve during treatment with endocrine agents have identified both changes in gene expression and mutational profiles, in the primary cancer as well as in circulating tumour cells. Analysing these changes has the potential to improve the prediction of which specific patients will respond to endocrine treatment. Serially profiled biopsies during treatment in the neoadjuvant setting offer promise for accurate and early prediction of response to both current and novel drugs and allow investigation of mechanisms of resistance. In addition, recent advances in monitoring tumour evolution through non-invasive (liquid) sampling of circulating tumour cells and cell-free tumour DNA may provide a method to detect resistant clones and allow implementation of personalized treatments for metastatic breast cancer patients. This review summarises current and future biomarkers and signatures for predicting response to endocrine treatment, and discusses the potential for using approved drugs and novel agents to improve outcomes. Increased prediction accuracy is likely to require sequential sampling, utilising preoperative or neoadjuvant treatment and/or liquid biopsies and an improved understanding of both the dynamics and heterogeneity of breast cancer.European CommissionEuropean Commission Joint Research Centre [658170]This work was funded by the European Commission H2020 Marie Sklodowska Curie Action Individual Fellowship (H2020-MSCA-IF, 658170) to CS and Breast Cancer Now to JMD and AHS