[Qualification and classification of medical apps : What should be noted and what is BfArM's contribution?] / Abgrenzung und Klassifizierung von Medical Apps : Was ist zu beachten und welche Unterstützung bietet das BfArM?

Smartphones and tablets with their nearly unlimited number of different applications have become an integral part of everyday life. Thus, mobile devices and applications have also found their way into the healthcare sector.For developers, manufacturers, or users as well, it is often difficult to decide whether a mobile health application is a medical device.In this context, it is extremely important for manufacturers to decide at an early stage of the development whether the product is to be introduced into the market as a medical device and is therefore subject to the legislation on medical devices.This article first presents the regulatory framework and subsequently introduces the reader to the Federal Institute for Drugs and Medical Devices' (BfArM) view of the criteria for differentiating between apps as non-medical products and apps as medical apps as well as the classification thereof. Various examples are presented to demonstrate how these criteria are applied practically and options that support developers and manufacturers in their decision making are shown. The article concludes with a reference to current developments and offers a perspective on the new European medical device regulations MDR/IVDR (Medical Device Regulation/In-Vitro Diagnostic Regulation) as well as on future challenges regarding medical apps.

Marker genes for the metabolic adaptation of Pseudomonas aeruginosa to the hypoxic cystic fibrosis lung environment.

Pseudomonas aeruginosa is the leading pathogen of chronic cystic fibrosis (CF) lung infection. Life-long persistence in the inflamed and ever fluctuating CF lungs results in the selection of a variety of changes in P. aeruginosa physiology. Accumulating evidence suggests that especially metabolic changes support the survival and growth of P. aeruginosa within the hypoxic and nutritious CF mucus. To investigate if metabolic adaptations we described for hypermutable P. aeruginosa from late CF lung disease (Hoboth et al., 2009. J. Infect. Dis., pp. 118-130) may represent specific changes in response to the selective conditions within the oxygen-restricted CF mucus, we determined the expression of a set of genes during aerobic and hypoxic growth in LB and the artificial sputum medium ASM. We further focused on the regulation of the two isocitrate dehydrogenases Icd and Idh. Interestingly, both isoenzymes may replace each other under aerobic and hypoxic conditions. The NADPH- and RpoS-dependent Icd seems to be the leading isoenzyme under prolonged oxygen limitation and stationary growth phase. LacZ reporter analysis revealed that oxygen-restriction increased the expression levels of azu, cbb3-1, cbb3-2, ccpR, icd, idh and oprF gene, whereas himD and nuoA are increasingly expressed only during hypoxic growth in ASM. Overexpression of the anaerobic regulator Anr improved the expression of azu, ccpR, cbb3-2 and icd. In summary, expression of azu, cbb3-1, cbb3-2, ccpR, icd, idh, oprF, himD, and nuoA appeared to be beneficial for the growth of P. aeruginosa under hypoxic conditions indicating these genes may represent marker genes for the metabolic adaptation to the CF lung environment.

No ecological effect modification of the association between negative life experiences and later psychopathology in adolescence: A longitudinal community study in adolescents.

BACKGROUND: The aim of the study was to examine the potential contribution of exposure to bullying and adverse life events to the development of psychopathology in adolescents, and possible effect modification by neighbourhood social capital. METHODS: Two waves of routine, longitudinal, standard health examinations at local community paediatric health services, pertaining to 749 adolescents living in Maastricht (The Netherlands) who were attending second grade of secondary school (age 13/14 years) and approximately 2 years later going to the fourth grade (age 15/16 years), were analysed. A self-report questionnaire was used, including measures of psychopathology and two measures of negative life experiences, exposure to bullying and adverse life events, that were available for both age groups and subjected to (multilevel) regression analysis. RESULTS: Exposure to bullying in the past school-year as well as the experience of adverse life events over a 12 month period, at the age of 13/14 years, predicted an increase in psychopathology at follow-up. Exposure to bullying was associated with the development of hyperactivity and emotional problems, while the experience of adverse life events predicted the development of conduct problems. Family-related adverse events had greatest effect sizes. Effects of bullying and adverse life events were not moderated by neighbourhood social capital. CONCLUSION: Negative life experiences impact on liability to psychopathology in adolescents independent of the wider social environment.

Childhood victimisation and developmental expression of non-clinical delusional ideation and hallucinatory experiences: victimisation and non-clinical psychotic experiences.

BACKGROUND: Victimisation in childhood may be associated with adult psychosis. The current study examined this association in the crucial developmental period of early adolescence and investigated whether (1) unwanted sexual experiences, and (2) being bullied, were associated with non-clinical delusional ideation and hallucinatory experiences in a general population sample of 14 year olds. METHODS: Data were derived from standard health screenings of the Youth Health Care Divisions of the Municipal Health Services in Maastricht, the Netherlands. A self-report questionnaire was filled out by a total of 1290 adolescents to assess non-clinical psychotic experiences, as well as experiences of being bullied and sexual trauma. RESULTS: Non-clinical psychotic experiences were strongly and independently associated with both bullying (OR=2.9, 95% CI 1.8-4.8) and sexual trauma (OR=4.8, 95% CI 2.3-10.1). CONCLUSIONS: The results suggest that reported associations between childhood victimisation and adult psychosis can be understood in a developmental framework of onset of at-risk mental states in early adolescence. In addition, the data suggest that the traumatic experience of being bullied may also feed the cognitive and biological mechanisms underlying formation of psychotic ideation.

An enzyme module system for the synthesis of dTDP-activated deoxysugars from dTMP and sucrose.

A flexible enzyme module system is presented that allows preparative access to important dTDP-activated deoxyhexoses from dTMP and sucrose. The strategic combination of the recombinant enzymes dTMP-kinase and sucrose synthase (SuSy), and the enzymes RmlB (4,6-dehydratase), RmlC (3,5-epimerase) and RmlD (4-ketoreductase) from the biosynthetic pathway of dTDP-beta-L-rhamnose was optimized. The SuSy module (dTMP-kinase, SuSy, +/-RmlB) yielded the precursor dTDP-alpha-D-glucose (2) or the biosynthetic intermediate dTDP-6-deoxy-4-keto-alpha-D-glucose (3) on a 0.2-0.6 g scale with overall yields of 62 % and 72 %, respectively. A two-step strategy in which the SuSy module was followed by the deoxysugar module (RmlC and RmlD) resulted in the synthesis of dTDP-beta-L-rhamnose (4; 24.1 micromol, overall yield: 35.9 %). Substitution of RmlC by DnmU from the dTDP-beta-L-daunosamine pathway of Streptomyces peucetius in this module demonstrated that DnmU acts in vitro as a 3,5-epimerase with 3 as substrate to yield 4 (32.2 mumol, overall yield: 44.7 %). Chemical reduction of 3 with NaBH4 gave a mixture of the C-4 epimers dTDP-alpha-D-quinovose (6) and dTDP-alpha-D-fucose (7) in a ratio of 2:1. In summary, the modular character of the presented enzyme system provides valuable compounds for the biochemical characterization of deoxysugar pathways playing a major role in microbial producers of antibiotic and antitumour agents.