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Background: Multidrug-resistant Gram-negative bacteria (MRGN) and the infections they cause are a serious threat and a challenge to the healthcare system. This particularly applies to carbapenem-resistant Gram-negative bacteria (CRGN). Currently, the introduction of a nationwide mandatory notification system for CRGN in Germany is under consideration. Against this background, this paper presents an analysis of the mandatory reporting system for CRGN in effect since November 2011 in the federal state of Hesse (Germany). Materials and methods: All carbapenem-resistant Gram-negative bacteria and the detected carbapenemases reported to the public health department of the city of Frankfurt am Main, Hesse, Germany, on the basis of the mandatory notification system were analyzed. Results: 827 CRGN cases were reported to the public health department of Frankfurt/Main between April 2012 and December 2015. The following bacterial species were reported: Pseudomonas spp. (n=268), Acinetobacter spp. (n=183), Klebsiella spp. (n=195), Enterobacter spp. (n=77), Escherichia coli (n=75) and others (n=29). Between 2012 and 2015, a reduction of the CRGN reports was noticed, mainly due to changes in the reporting of Pseudomonas spp. Between 2012 and 2015, the total number of notifications decreased slightly, although the number of reported CRGN in screening samples increased, thus giving no indication of a decreased testing frequency. For 10.5% of the patients, the place of residence was not Germany, 18.0% of the patients had previously stayed in hospitals abroad, often in countries with a high CRGN prevalence. CRGN bacteria were reported from all of Frankfurt’s hospitals, and 3.9% were reported from out-patient care facilities. Carbapenemases were detected and reported in 251 CRGN bacteria, including 73 OXA-48, 76 OXA-23, 56 NDM subtypes, and 21 KPC subtypes. There have been no major epidemiological signs of outbreak scenarios. Discussion: CRGN bacteria are already widespread in patien, Hintergrund: Multiresistente gramnegative Stäbchenbakterien (MRGN) und dadurch verursachte Infektionen sind eine Bedrohung und große Herausforderung für das Gesundheitswesen. Das betrifft insbesondere Carbapenem-resistente gramnegative Bakterien (CRGN). Derzeit wird überlegt, eine bundesweite Meldepflicht für CRGN in Deutschland einzuführen. Vor diesem Hintergrund wird eine Analyse der seit Ende 2011 in Hessen geltenden Meldepflicht für CRGN vorgelegt. Material und Methode: Alle dem Gesundheitsamt Frankfurt auf der Grundlage der Hessischen Meldepflicht gemeldeten Erreger mit Resistenz gegen Carbapeneme (4MRGN nach KRINKO) und der nachgewiesenen Carbapenemasen werden vorgestellt. Ergebnisse: Von April 2012 bis Dezember 2015 erreichten das Gesundheitsamt 827 Nachweise von CRGN, darunter 268 Nachweise von Pseudomonas spp., 183 Nachweise von Acinetobacter spp., 195 Klebsiella spp., 77 Enterobacter spp., 75 Escherichia coli und 29 andere. Von 2012 bis 2015 ist insgesamt ein leichter Rückgang der Meldungen erkennbar, bedingt im Wesentlichen durch eine Änderung der Meldepflicht für P. aeruginosa. Über die Jahre hat der Anteil der gemeldeten Nachweise aus Screeningproben zugenommen, d.h. es liegt kein Hinweis auf eine abnehmende Untersuchungsfrequenz vor. Fast 10,5% der Patienten hatten ihren Wohnsitz im Ausland, 18% hatten einen vorangegangenen Klinikaufenthalt im Ausland angegeben, häufig in Ländern mit bekannt hohem CRGN-Risiko. CRGN wurden aus allen Frankfurter Kliniken gemeldet, 3,9% auch aus ambulanten Einrichtungen. Bei 251 CRGN-Bakterien wurden Carbapenemasen nachgewiesen und gemeldet, darunter u.a. 73 OXA-48-, 76 OXA-23-, 56 NDM-, 21 KPC-Subtypen. Hinweise auf größere Ausbrüche ergaben sich nicht. Diskussion: Der Nachweis von CRGN bei Patienten in allen Kliniken und auch in ambulanten Praxen zeigt, dass diese Erreger schon weit verbreitet sind. Nicht nur in der Klinik, sondern auch im ambulanten Bereich muss mit dieser Problematik sachgerecht umgegangen werden. Ein

New stable isotope dilution assays were developed for the simultaneous quantitation of [13C5]-labelled and unlabelled intact folate vitamers and folate catabolites. The application of the [2H4]-labelled isotopologues as internal standards required the synthesis of the [2H4]-labelled catabolites, [2H4]-p-aminobenzoyl glutamate and [2H4]-p-acetamidobenzoyl glutamate. The new assays were applied successfully in a novel human “area under the curve/ileostomy” model to investigate folate bioavailability from wholemeal bread. Additionally, in a separate study, folate concentration and pattern in raw and heat treated breast milk were investigated by simulation of generally used heating processes., Es wurden Stabilisotopenverdünnungsassays für die gleichzeitige Quantifizierung von [13C5]-markierten und unmarkierten intakten Folatvitameren und Folatmetaboliten in Humanproben entwickelt. Die Anwendung der [2H4]-markierten Isotopologen als interne Standards erforderte die Synthese der [2H4]-markierten Metaboliten, [2H4]-p- Aminobenzoyl glutamat und [2H4]-p-Acetamidobenzoyl glutamat. Die entwickelten Assays wurden in einer neuartigen „Area under the curve/ileostomy“-Humanstudie zur Untersuchung der Bioverfügbarkeit von Folat aus Vollkornbrot erfolgreich eingesetzt. Daneben wurden in einer gesonderten Studie die Folatkonzentration und die Vitamerenverteilung in unbehandelter und erhitzter Muttermilch mittels der Simulation gebräuchlicher Wärmebehandlungsverfahren untersucht.

"Internetforen als moderne Kommunikationsformen bieten ein neues, interessantes Untersuchungsgebiet für qualitativ explorierende Forschungsverfahren. Gerade direkte Interaktionen zwischen Ratsuchenden und Ratgebenden bei einem sensiblen Thema wie kriminellem Verhalten sind meist nur schwer zugänglich. Die anonyme Kommunikationsform bietet der Forschung einen um soziale Erwünschtheit weitestgehend bereinigten Gegenstand. Anhand des Internetforenthreads 'Ausbildung trotz Eintrag im Führungszeugnis' auf der Seite des Pflegenetzwerks für Auszubildende in Pflegeberufen werden die Reaktionen der Forenteilnehmer_innen auf die Frage einer anderen Forenteilnehmerin nach dem Umgang mit einer Vorstrafe im Bewerbungsprozess untersucht. Ausgehend von der Annahme eines aufgrund der anonymen Internetsituation ausgeprägten Sanktionsverhaltens werden verschiedene kriminalsoziologische Ansätze vorgestellt, anhand derer im Anschluss die unterschiedlichen Reaktionsmuster der Forenteilnehmer_innen herausgearbeitet werden. Die Ergebnisse zeigen eine differenzierende Argumentationsdynamik, die insgesamt aber einen eher verständnisvollen Tenor in den Antwortreaktionen deutlich macht." (Autorenreferat)

New stable isotope dilution assays were developed for the simultaneous quantitation of [13C5]-labelled and unlabelled intact folate vitamers and folate catabolites. The application of the [2H4]-labelled isotopologues as internal standards required the synthesis of the [2H4]-labelled catabolites, [2H4]-p-aminobenzoyl glutamate and [2H4]-p-acetamidobenzoyl glutamate. The new assays were applied successfully in a novel human “area under the curve/ileostomy” model to investigate folate bioavailability from wholemeal bread. Additionally, in a separate study, folate concentration and pattern in raw and heat treated breast milk were investigated by simulation of generally used heating processes., Es wurden Stabilisotopenverdünnungsassays für die gleichzeitige Quantifizierung von [13C5]-markierten und unmarkierten intakten Folatvitameren und Folatmetaboliten in Humanproben entwickelt. Die Anwendung der [2H4]-markierten Isotopologen als interne Standards erforderte die Synthese der [2H4]-markierten Metaboliten, [2H4]-p- Aminobenzoyl glutamat und [2H4]-p-Acetamidobenzoyl glutamat. Die entwickelten Assays wurden in einer neuartigen „Area under the curve/ileostomy“-Humanstudie zur Untersuchung der Bioverfügbarkeit von Folat aus Vollkornbrot erfolgreich eingesetzt. Daneben wurden in einer gesonderten Studie die Folatkonzentration und die Vitamerenverteilung in unbehandelter und erhitzter Muttermilch mittels der Simulation gebräuchlicher Wärmebehandlungsverfahren untersucht.

BACKGROUND: Breastmilk is the recommended aliment for preterm infants. Milk banks provide donated breastmilk for the neonatal care of preterm infants when mother's own milk is not is available. To avoid pathogen transmission, donated breastmilk is heat-treated according to different procedures before administration. There is varying information on the effect of heat treatment on folate in breastmilk. Sufficient folate intake, however, is essential for normal growth and brain development. This study determined and compared the effects of different heat treatments on breastmilk folate content and pattern of individual folate forms. MATERIALS AND METHODS: Donated Swedish breastmilk samples were heat-treated according to three procedures: two low temperature treatments (57°C, 23 minutes; 62.5°C, 12 minutes) and a rapid high temperature treatment (heating to 73°C in boiling water). The folate content and pattern were determined before and after treatment by high-performance liquid chromatography. RESULTS: The folate content in 38 untreated Swedish breastmilk samples was 150±46 nmol/L. Two different folate vitamers were detected: 5-methyltetrahydrofolate (78±7%) and tetrahydrofolate (22±7%). Heat treatment affected only tetrahydrofolate stability and decreased folate content by 15-24%; however, the effects on folate content did not differ among the investigated heat treatment procedures. CONCLUSIONS: Folate losses during heat treatment of human milk were considered acceptable. Yet, native folate content of heat-treated, non-fortified breastmilk supplied only 25% of the recommended daily intake for preterm infants.

Dual-label stable isotope dilution assays for the simultaneous quantification of isotopologic folates in clinical samples offer the perspective for differentiating between unlabeled folates from endogenous body pools and administered [13C5]-labeled folates from a test dose when performing bioavailability trials. In contrast to intact folates, this methodology could hitherto not be applied to the quantification of the folate catabolites, p-aminobenzoyl glutamate and p-acetamidobenzoyl glutamate. In this study, [2H4]-p-aminobenzoyl glutamate, [2H4]-p-acetamidobenzoyl glutamate, and unlabeled p-acetamidobenzoyl glutamate were synthesized. The synthesis of the [2H4]-labeled compounds started at unlabeled p-aminobenzoic acid. For the formation of p-acetamidobenzoyl glutamate, p-aminobenzoyl glutamate was acetylated. The new substances were applied successfully in stable isotope dilution assays for the simultaneous quantification of the [13C5]-labeled and unlabeled folate catabolites, p-aminobenzoyl glutamate and p-acetamidobenzoyl glutamate, along with the predominant folate vitamers in urine. The assays were based on clean-up by strong anion exchange followed by liquid chromatography-tandem mass spectrometry detection. Assay sensitivity was sufficient to detect the folate catabolites in physiologic concentrations. The limit of detection was below 0.4 and 0.3 nmol/100 g for p-aminobenzoyl glutamate isotopologues and p-acetamidobenzoyl glutamate isotopologues in urine, respectively. The successful synthesis of [2H4]-p-aminobenzoyl glutamate, [2H4]-p-acetamidobenzoyl glutamate, and unlabeled p-acetamidobenzoyl glutamate and the implementation of these substances in stable isotope dilution assays allows dual-label designs that provide a more detailed insight into human folate metabolism.

New stable isotope dilution assays were developed for the simultaneous quantitation of [(13)C(5)]-labelled and unlabelled 5-methyltetrahydrofolic acid, 5-formyltetrahydrofolic acid, folic acid along with unlabelled tetrahydrofolic acid and 10-formylfolic acid in clinical samples deriving from human bioavailability studies, i.e. plasma, ileostomy samples, and food. The methods were based on clean-up by strong anion exchange followed by LC-MS/MS detection. Deuterated analogues of the folates were applied as the internal standards in the stable isotope dilution assays. Assay sensitivity was sufficient to detect all relevant folates in the respective samples as their limits of detection were below 0.62 nmol/L in plasma and below 0.73 μg/100 g in food or ileostomy samples. Quantification of the [(13)C(5)]-label in clinical samples offers the possibility to differentiate between folate from endogenous body pools and the administered dose when executing bioavailability trials.

Our data confirm differences in plasma absorption kinetics for reduced folates and synthetic folic acid administered with the test foods. Stomal folate contents indicated almost complete bioavailability of labeled folate from the breads or breakfast meal.

BACKGROUND: Recent data revealed differences in human absorption kinetics and metabolism between food folates and folic acid supplements and fortificant. OBJECTIVE: The objective was to determine folate bioavailability after ingestion of breads or a breakfast meal fortified with either 5-CH(3)-H(4) folate or folic acid by using a stable-isotope area under the curve (AUC) and ileostomy model. DESIGN: In a randomized crossover trial, healthy ileostomists (n = 8) ingested single doses of whole-meal bread that contained ap 450 nmol (200 micro g) of either (6S)-[(13)C(5)]5-CH(3)-H(4) folate or [(13)C(5)]folic acid or a breakfast meal that contained ap 450 nmol (200 micro g) [(13)C(5)]folic acid. We collected blood from the subjects during 12 h postdose for assessment of plasma kinetics. Nonabsorbed folate was assessed from labeled folate contents in stomal effluent 12 and 24 h postdose. RESULTS: The median (range) plasma AUC(0 rarr 12) (AUC from 0 to 12 h after ingested dose) of 66 nmol sdot h/L (34-84 nmol sdot h/L) after ingestion of bread that contained (6S)-[(13)C(5)]5-CH(3)-H(4) folate was significantly greater (P lt 0.001) than that after ingestion of [(13)C(5)]folic acid in fortified bread [28 nmol sdot h/L (15-38 nmol sdot h/L)] and a fortified breakfast meal [26 nmol sdot h/L (15-60 nmol sdot h/L)]. Both labeled doses resulted in increases of plasma [(13)C(5)]5-CH(3)-H(4) folate. However, the kinetic variables C(max) (maximum plasma concentration) and T(max) [time (min) of maximum plasma concentration] varied after ingestion of the different folate forms. The stomal folate content was lt 10% of the ingested dose and did not vary significantly after ingestion of test foods that contained (6S)-[(13)C(5)]5-CH(3)-H(4) folate [median (range): 13 nmol (10-31 nmol)] or [(13)C(5)]folic acid [median (range): 25 nmol (8-42 nmol)] (P = 0.33). CONCLUSIONS: Our data confirm differences in plasma absorption kinetics for reduced folates and synthetic folic acid administered wi