Gute Lücken, schlechte Lücken?: Zur objektiv-rechtlichen Dimension des IT-Grundrechts

Staatliches Hacking von Computern und Smartphones hat Konjunktur. Durch das Gesetz zur effektiveren und praxistauglicheren Ausgestaltung des Strafverfahrens vom 17. August 2017 (BGBl. I S. 3202) wurden Online-Durchsuchung und Quellen-TKÜ mittels "Staatstrojanern" zu Standardmaßnahmen im strafrechtlichen Ermittlungsverfahren. Die StPO erlaubt seither den Einsatz von Staatstrojanern in mehreren zehntausend Fällen im Jahr: Sie sind nun immer dann zulässig, wenn bisher eine klassische Telekommunikationsüberwachung gem. § 100a Abs. 1 StPO unter Einbindung der jeweiligen Provider (vgl. § 100b StPO a.F.) vorgenommen wurde

Nonsteroidal Antiinflammatory Drug Administration and Postpartum Blood Pressure in Women With Hypertensive Disorders of Pregnancy

OBJECTIVE: To evaluate whether postpartum nonsteroidal antiinflammatory drug (NSAID) administration is associated with increased blood pressure in women with hypertensive disorders of pregnancy and to estimate the association between NSAID administration and use of opioid medication. METHODS: We conducted a retrospective cohort study of women with hypertensive disorders of pregnancy. Patients were analyzed in two groups according to whether they received NSAIDs postpartum. Study participants were women delivered at a tertiary care center from 2008 to 2015. The primary outcome was change in mean arterial pressure during the postpartum period. Secondary outcomes were postpartum pain scores, cumulative postpartum opioid requirement, initiation or dose escalation of antihypertensive agents, and adverse postpartum outcomes including acute renal failure, change in hematocrit, and maternal readmission for hypertensive disorder. RESULTS: Two hundred seventy-six women with hypertensive disorders of pregnancy were included (129 NSAID-unexposed and 147 NSAID-exposed). Postpartum NSAID administration was not associated with a statistically significant change in mean arterial pressure compared with no NSAID administration (-0.7 vs -1.8; mean difference 1.10, 95% CI -1.44 to 3.64). Similarly, no difference was observed between the cohorts in terms of need for initiation or escalation in dose of antihypertensive agents or maternal readmission for hypertensive disorder. The study was underpowered to determine whether NSAID administration was associated with any difference in less frequent secondary outcomes (eg, incidence of acute renal insufficiency, need for postpartum transfusion) or cumulative opioid use. CONCLUSION: Nonsteroidal antiinflammatory drug administration to postpartum patients with hypertensive disorders of pregnancy is not associated with a change in blood pressure or requirement for antihypertensive medication

Requirement for PCNA in DNA Mismatch Repair at a Step Preceding DNA Resynthesis

Abstractid system was used to screen yeast and human expression libraries for proteins that interact with mismatch repair proteins. PCNA was recovered from both libraries and shown in the case of yeast to interact with both MLH1 and MSH2. A yeast strain containing a mutation in the PCNA gene had a strongly elevated mutation rate in a dinucleotide repeat, and the rate was not further elevated in a strain also containing a mutation in MLH1. Mismatch repair activity was examined in human cell extracts using an assay that does not require DNA repair synthesis. Activity was inhibited by p21 WAF1 or a p21 peptide, both of which bind to PCNA, and activity was restored to inhibited reactions by addition of PCNA. The data suggest a PCNA requirement in mismatch repair at a step preceding DNA resynthesis. The ability of PCNA to bind to MLH1 and MSH2 may reflect linkage between mismatch repair and replication and may be relevant to the roles of mismatch repair proteins in other DNA transactions

Emotional expression during attention-deficit/hyperactivity disorders treatment: initial assessment of treatment effects.

OBJECTIVE: The purpose of this research was to provide an initial examination of the effects of atomoxetine and stimulants on emotional expression using a newly developed scale for assessing emotional expression in children with attention-deficit/hyperactivity disorder (ADHD). METHOD: The parent-rated Expression and Emotion Scale for Children (EESC) was collected during two studies. During a cross-sectional validation study, the EESC was completed to assess the child\u27s current treatment and retrospectively for previous medication. In a randomized, placebo-controlled trial of atomoxetine, the EESC was collected at baseline and endpoint. RESULTS: In the validation study, no statistically significant differences in EESC scores were found between groups taking atomoxetine (n = 74) and stimulants (n = 105). Patients who switched from a stimulant to atomoxetine (n = 40) had greater improvement in emotional expression than those switched to another stimulant (n = 21) (p = 0.008). In the clinical trial, no difference in rates of worsening of emotional expression were observed (atomoxetine 8.8%, placebo 12.3%; p = 0.440). CONCLUSION: No treatment differences in emotional expression were observed based on current medications. However, stimulant patients needing to switch medications may have greater improvements in emotional expression by switching to atomoxetine

Association of common variants in mismatch repair genes and breast cancer susceptibility: a multigene study

<p>Abstract</p> <p>Background</p> <p>MMR is responsible for the repair of base-base mismatches and insertion/deletion loops. Besides this, MMR is also associated with an anti-recombination function, suppressing homologous recombination. Losses of heterozygosity and/or microsatellite instability have been detected in a large number of skin samples from breast cancer patients, suggesting a potential role of MMR in breast cancer susceptibility.</p> <p>Methods</p> <p>We carried out a hospital-based case-control study in a Caucasian Portuguese population (287 cases and 547 controls) to estimate the susceptibility to non-familial breast cancer associated with some polymorphisms in mismatch repair genes (<it>MSH3</it>, <it>MSH4</it>, <it>MSH6</it>, <it>MLH1</it>, <it>MLH3</it>, <it>PMS1 </it>and <it>MUTYH</it>).</p> <p>Results</p> <p>Using unconditional logistic regression we found that <it>MLH3 </it>(L844P, G>A) polymorphism GA (Leu/Pro) and AA (Pro/Pro) genotypes were associated with a decreased risk: OR = 0.65 (0.45-0.95) (p = 0.03) and OR = 0.62 (0.41-0.94) (p = 0.03), respectively.</p> <p>Analysis of two-way SNP interaction effects on breast cancer revealed two potential associations to breast cancer susceptibility: <it>MSH3 </it>Ala1045Thr/<it>MSH6 </it>Gly39Glu - AA/TC [OR = 0.43 (0.21-0.83), p = 0.01] associated with a decreased risk; and <it>MSH4 </it>Ala97Thr/<it>MLH3 </it>Leu844Pro - AG/AA [OR = 2.35 (1.23-4.49), p = 0.01], GG/AA [OR = 2.11 (1.12-3,98), p = 0.02], and GG/AG [adjusted OR = 1.88 (1.12-3.15), p = 0.02] all associated with an increased risk for breast cancer.</p> <p>Conclusion</p> <p>It is possible that some of these common variants in MMR genes contribute significantly to breast cancer susceptibility. However, further studies with a large sample size will be needed to support our results.</p

Selective recognition of pyrimidine–pyrimidine DNA mismatches by distance-constrained macrocyclic bis-intercalators

Binding of three macrocyclic bis-intercalators, derivatives of acridine and naphthalene, and two acyclic model compounds to mismatch-containing and matched duplex oligodeoxynucleotides was analyzed by thermal denaturation experiments, electrospray ionization mass spectrometry studies (ESI-MS) and fluorescent intercalator displacement (FID) titrations. The macrocyclic bis-intercalators bind to duplexes containing mismatched thymine bases with high selectivity over the fully matched ones, whereas the acyclic model compounds are much less selective and strongly bind to the matched DNA. Moreover, the results from thermal denaturation experiments are in very good agreement with the binding affinities obtained by ESI-MS and FID measurements. The FID results also demonstrate that the macrocyclic naphthalene derivative BisNP preferentially binds to pyrimidine–pyrimidine mismatches compared to all other possible base mismatches. This ligand also efficiently competes with a DNA enzyme (M.TaqI) for binding to a duplex with a TT-mismatch, as shown by competitive fluorescence titrations. Altogether, our results demonstrate that macrocyclic distance-constrained bis-intercalators are efficient and selective mismatch-binding ligands that can interfere with mismatch-binding enzymes