Untersuchungen zur linearen thiol-en-photopolymerisation

The photoinitiated free-radical polymerization of 3,6-dioxa-1,8-octanedithiol and bis(allyl) hydroquinone ether or ethylene glycol divinyl ether leads to poly(thioethers) having anti Markovnikov structure with number-average molar mass M?_n: 14000, 12000 g/mol, respectively. The chain propagation is limited by disulfide propagation is limited by disulfide production (nearly 3%) and cycle production (nearly 4 %). Differential scanning calorimetry (DSC) investigations showed that the rate of polymerization decreases in the series vinyl ether ? allyl ether > 1-alkene. The influence of the dithiol structure (β-mercapto ether, thioglycolate, aliphatic thiols) is not dominant.     

Fluorescence in situ hybridisation (FISH) accelerates identification of Gram-positive cocci in positive blood cultures

Sepsis is a life-threatening disease with a high mortality rate. Rapid identification of blood culture isolates plays a crucial role in adequate antimicrobial therapy in sepsis patients. To accelerate microbiological diagnosis, a comprehensive panel of oligonucleotide probes for fluorescence in situ hybridisation (FISH) targeting Gram-positive cocci was compiled and evaluated on 428 positive blood culture specimens. By combining genus-specific and species-specific probes, the assay allowed discrimination of staphylococci, streptococci and enterococci as well as differentiation of therapy-relevant pathogens such as Staphylococcus aureus and Enterococcus faecium/durans. Furthermore, the newly designed FISH probes STREP2, ENCO and GRANU targeted Streptococcus pneumoniae/mitis, Enterococcus spp. (except E. faecalis) and Granulicatella adiacens group, respectively. The FISH assay achieved an overall sensitivity of 98.65% and a specificity of 99.0% and therefore allowed rapid and reliable molecular identification of Gram-positive cocci in blood culture specimens.     

Soziodemografische und soziale Korrelate selbstberichteter Resilienz im Alter – Ergebnisse der populationsbasierten LIFE-Adult-Studie

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Resilienz bezeichnet eine gute Anpassung an Widrigkeiten und ist ein bedeutsamer Faktor für das Wohlbefinden im Alter. Erste...     

Herpes Zoster in Breast Cancer Patients after Radiotherapy

Background: We have studied the incidence of herpes zoster in patients with adjuvant radiotherapy for breast cancer with special emphasis on possible correlations with other prognostic factors or survival. Patients and Methods: From 1/1985 through 12/1993, 1 155 breast cancer patients received postoperative radiotherapy with curative interent in our department. After mastectomy 961 patients were irradiated and after breast-preserving treatment 194 patients. The age ranged from 34 to 79 years, the median follow-up was 3.1 years (range: 0.3 to 12.4 years). There were 443 women (38%) pre- and 712 (62%) postmenopausal. 21% had T3- to T4-tumors, 55% had axillary lymph node involvement, and 65% received additional systemic hormonal and/or cytotoxic therapy. In case of postmastectomy radiotherapy, the lateral chest wall and lymphatics (axilla, parasternal and supraclavicular nodes) were irradiated with an anterior photon field to 50 Gy (axilla 44 Gy) and most of the chest wall with an electron field to 44 Gy in 2-Gy fractions. After breast-preservation, the breast was irradiated via tangential fields with 6- to 8-MV photons up to 50 Gy plus 8 Gy electron boost to the tumor bed. Most of the patients were followed routinely in the department for 2 to 5 years. The frequency of zoster was determined retrospectively by reviewing the patients' records. Results: A zoster after radiotherapy occurred in 41/1 155 patients (3.7%), mostly within the first 2 years after completion of radiotherapy. All infections remained localized and there was no evidence for systemic infections. Type of treatment (mastectomy vs breast-preservation) had no impact on the frequency of herpes zoster (36/961 patients after mastectomy and 5/194 patients after breast-preservation). There was also no correlation with other prognostic factors such as age, menopausal status, stage of disease or the use of adjuvant chemotherapy, nor was the occurrence of zoster linked to the degree of acute skin reaction in the radiation field. Moreover, patients with zoster had the same prognosis as compared to patients without zoster with regard to local control and survival. Conclusions: The observed frequency of zoster (about 4% of patients after postoperative radiotherapy) in this retrospective study suggests that the risk of developing zoster in this patient group may be 3- to 5-fold higher as compared to the incidence in the general population. However, the occurrence of zoster was not linked to prognosis and treatment response. Hintergrund: Wir haben in einer retrospektiven Analyse die Häufigkeit eines Herpes zoster bei Patientinnen mit Mammakarzinom und postoperativer Radiotherapie untersucht. Patientinnen und Methode: Von Januar 1985 bis Dezember 1993 erhielten 1 155 Patientinnen an unserer Klinik eine postoperative Bestrahlung nach Mastektomie (n = 961) oder brusterhaltende Operation (n = 194) in kurativer Intention. Das Alter betrug 34 bis 79 Jahre. 443 (38%) waren prä- und 712 (62%) postmenopausal, 21% hatten T3- bis T4-Tumoren, und 55% wiesen einen axillären Lymphknotenbefall auf. Alle Patientinnen erhielten eine Bestrahlung der Restbrust bzw. Thoraxwand bis 50 Gy, bei mastektomierten Patientinnen wurden zusätzlich die regionären Lymphknoten mit 44 Gy bestrahlt. 65% der Patientinnen erhielten eine zusätzliche Systemtherapie. Die Nachbeobachtungszeit betrug drei Monate bis 12,5 Jahre (Median 3,1 Jahre). Ergebnisse: 41/1 155 Patientinnen (3,7%) entwickelten im Nachbeobachtungszeitraum einen Herpes zoster. Alle Infektionen waren lokalisiert, eine generalisierte Hautinfektion oder systemische Infektionen traten nicht auf. Alter, Menopausenstatus, Erkrankungsstadium oder Art der Therapie (Brusterhaltung vs. Mastektomie, zusätzliche Chemotherapie) hatten keinen Einfluss auf die Frequenz von Zoster. Patientinnen mit starker akuter Hautreaktion waren ebenfalls nicht signifikant stärker betroffen als Patientinnen mit geringer Hautreaktion im Bestrahlungsfeld (5% vs. 2%). Das Auftreten eines Zosters nach Therapie hatte keinen Einfluss auf die Prognose hinsichtlich lokaler Kontrolle oder Überleben. Schlussfolgerungen: Die beobachtete Häufigkeit von Herpes zoster (etwa 4% nach drei Jahren Follow-up) lässt vermuten, dass ein Herpes zoster im untersuchten Kollektiv etwa drei- bis fünffach häufiger auftritt als anhand der Inzidenzen in der Normalbevölkerung erwartet. Dies ist nicht mit einer schlechteren Prognose assoziiert. Ob die erhöhte Frequenz auf die Radiotherapie zurückzuführen ist oder in Zusammenhang mit der Krebserkrankung steht, kann nich beurteilt werden.     

Associations and correlates of general versus specific successful ageing components

The heterogeneity in the operationalisation of successful ageing (SA) hinders a straightforward examination of SA associations and correlates, and in turn, the identification of potentially modifiable predictors of SA. It is unclear which SA associations and correlates influence all facets of the SA construct, and whether psychosocial reserve models developed in neuropathological ageing research can also be linked to SA. It was therefore the aim of this study to disentangle the effect of various previously identified SA associations and correlates on (1) a general SA factor, which represents the shared underpinnings of three SA facets, and (2) more confined, specific factors, using bifactor modelling. The associations and correlates of three recently validated SA operationalisations were compared in 2478 participants from the German AgeCoDe study, aged 75 years and above. Based on participants’ main occupation, cognitive reserve (CR) and motivational reserve (MR) models were built. Younger age, male gender, more education, higher socio-economic status, being married or widowed, as well as more physical exercise and cognitive activities in old age were found to correlate positively with the general SA factor, indicating a simultaneous effect on all aspects of SA. Smoking and ApoE-ε4 were related only to the physiological facet of SA. CR models were significantly related to the general SA factor. Among all SA associations and correlates, proxy indicators of lifelong cognitive activity and physical exercise showed the strongest effects on SA. Future intervention studies should assess the influence of the preservation of active lifestyle across the life span on SA.Electronic supplementary materialThe online version of this article (10.1007/s10433-020-00593-4) contains supplementary material, which is available to authorised users.     

Serine hydrolases activate/inactivate trisubstituted nitrosoureas in dependence on intra- and extracellular enzyme location: an SCE study in Chinese hamster V79-E cells

Trisubstituted nitrosoureas are very stable in aqueous systems.But they are potent genotoxins in Chinese hamster V79-E cells,if no exogenous metabolizing system is added, and the mechanismof their genotoxic and carcinogenic activity has been largelyunknown. This investigation shows that the sister-chromatid-exchange(SCE)-inducing capacity of 1,3-dimethyl-3-phenyl-1-nitrosourea(DMPNU) is eliminated by adding dlisopropylfluorophospbate (DFP)or porcine liver carboxylesterase to the incubation system.These effects are caused by two different mechanisms: (i) DFPinhibits endogenous amidases existing in V79-E cells, thus preventingthe intracellular decomposition, which means an activation;and (ii) exogenous carboxylesterase cleaves DMPNU extra cellularly,and the genotoxic decomposition product is obviously too short-livedto reach a critical intracellular target. A second trisubstitutednitrosourea, 3,3-diethyl-1-methyl-1-nitrosourea (DEMNU), whichis mainly activated by monooxygenases, but in the absence ofan exogenous metabolizing system also induces SCEs in V79-Ecells, was studied in the same way. It was found that the ‘direct’genotoxicity of DEMNU may be inhibited by DFP as well, but carboxylesterasedecomposes this trialklynitrosourea with a much lower efficiencythan DMPNU suggesting a low substrate affinity. The SCE-inducingcapacity of both compounds is strongly influenced by the presenceof calf serum in the culture medium. The nature of the serumfactor is still unknown. Pathways for the amidase catalysisof DMPNU and for the activation of DEMNU by monooxygenases andamidases are proposed and discussed with respect to the topicalor systemic carcinogenicity of these agents.     

Early identification of language delay by direct language assessment or parent report?

OBJECTIVE: The goal of the study was to compare the accuracy and diagnostic power of a parent report measure and direct language assessment for early identification of children with language delay. METHOD: The parent language report and direct language measures were compared for 47 typically developing toddlers and 70 late-talking toddlers aged 24 to 26 months. One year later, language abilities of 102 of the 117 children were reassessed. RESULTS: The concurrent validity of the parent report was high both for judging language skills and for identifying language delay. No evidence was found of differences in the rating accuracy of mothers with different educational levels. Language abilities 1 year later were predicted better with direct language measurement than with the parent report. However, there were no differences between the accuracy of the parent report and individual language assessment concerning the prediction of language delay at age 3. CONCLUSION: The results suggest that the parent language report is a valid and efficient tool for assessing productive language abilities and judging expressive language delay in 2-year-old toddlers. The measurement characteristics of the parent report are comparable with those of direct language measures.     

Imaging Characteristics and First Experience of [<Superscript>68</Superscript>Ga]THP-PSMA,a Novel Probe for Rapid Kit-Based Ga-68 Labeling and PET Imaging: Comparative Analysis with [<Superscript>68</Superscript>Ga]PSMA I&amp;T

Purpose

[⁶⁸Ga]Trishydroxypyridinone (THP)–prostate-specific membrane antigen (PSMA) is a novel tracer that can be labeled in one step by cold reconstitution of a kit with unprocessed generator eluate, targeting PSMA via the lysine-urea-glutamate (KuE) motif. The aim of this study was to evaluate the human imaging characteristics of [⁶⁸Ga]THP-PSMA.

Procedures

[⁶⁸Ga]THP-PSMA positron emission tomography (PET)/x-ray computed tomography (CT) was performed in 25 patients with biochemical recurrence after radical prostatectomy for prostate cancer. Urinary and biliary excretion and tumor lesion uptake were quantified using standardized uptake values (SUVs). Imaging characteristics were assessed in terms of non-target organ uptake, background activity, target-to-background ratios (TBRs) of tumor lesions, and frequency of bladder halo artifacts. Findings were compared to a matched cohort of 25 patients undergoing PET/CT with the established agent [⁶⁸Ga]PSMA I&T.

Results

Physiologic uptake of [⁶⁸Ga]THP-PSMA was significantly lower in salivary glands (P?<?0.0001), liver (P?<?0.0001), spleen (P?<?0.0001), and kidneys (P?<?0.0001) than with [⁶⁸Ga]PSMA I&T. While biliary tracer excretion of [⁶⁸Ga]THP-PSMA was negligible, urinary tracer excretion of [⁶⁸Ga]THP-PSMA was fast, and significantly higher than for [⁶⁸Ga]PSMA I&T, contributing to a higher frequency of bladder artifacts. Malignant lesion uptake of [⁶⁸Ga]THP-PSMA assessed as either SUV or TBR was significantly lower than with [⁶⁸Ga]PSMA I&T.

Conclusion

[⁶⁸Ga]THP-PSMA yields suitable in vivo uptake characteristics. The simplified synthesis method for [⁶⁸Ga]THP-PSMA may facilitate wider application and higher patient throughput with PSMA imaging. However, direct intraindividual comparison studies are needed to assess the relative performance of [⁶⁸Ga]THP-PSMA vs other PSMA ligands in terms of clinical detection rate and image quality.