Renal involvement in mitochondrial cytopathies

Mitochondrial cytopathies constitute a group of rare diseases that are characterized by their frequent multisystemic involvement, extreme variability of phenotype and complex genetics. In children, renal involvement is frequent and probably underestimated. The most frequent renal symptom is a tubular defect that, in most severe forms, corresponds to a complete De Toni-Debré-Fanconi syndrome. Incomplete proximal tubular defects and other tubular diseases have also been reported. In rare cases, patients present with chronic tubulo-interstitial nephritis or cystic renal diseases. Finally, a group of patients develop primarily a glomerular disease. These patients correspond to sporadic case reports or can be classified into two major defects, namely 3243 A>G tRNALEU mutations and coenzyme Q10 biosynthesis defects. The latter group is particularly important because it represents the only treatable renal mitochondrial defect. In this Educational Review, the principal characteristics of these diseases and the main diagnostic approaches are summarized

The role of 'filth flies' in the spread of antimicrobial resistance

'Filth flies' feed and develop in excrement and decaying matter and can transmit enteric pathogens to humans and animals, leading to colonization and infection. Considering these characteristics, 'filth flies' are potential vectors for the spread of antimicrobial resistance (AMR). This review defines the role of flies in the spread of AMR and identifies knowledge gaps. The literature search (original articles, reviews indexed for PubMed) was restricted to the English language. References of identified studies were screened for additional sources. 'Filth flies' are colonized with antimicrobial-resistant bacteria of clinical relevance. This includes extended spectrum beta-lactamase-, carbapenemase-producing and colistin-resistant (mcr-1 positive) bacteria. Resistant bacteria in flies often share the same genotypes with bacteria from humans and animals when their habitat overlap. The risk of transmission is most likely highest for enteric bacteria as they are shed in high concentration in excrements and are easily picked up by flies. 'Filth flies' can 'bio-enhance' the transmission of AMR as bacteria multiply in the digestive tract, mouthparts and regurgitation spots. To better understand the medical importance of AMR in flies, quantitative risk assessment models should be refined and fed with additional data (e.g. vectorial capacity, colonization dose). This requires targeted ecological, epidemiological and in vivo experimental studie

Die Abfuhr und Verwerthung der Dungstoffe in verschiedenen deutschen und ausserdeutschen Städten und darauf bezügliche Vorschläge für Berlin

DIE ABFUHR UND VERWERTHUNG DER DUNGSTOFFE IN VERSCHIEDENEN DEUTSCHEN UND AUSSERDEUTSCHEN STÄDTEN UND DARAUF BEZÜGLICHE VORSCHLÄGE FÜR BERLIN Die Abfuhr und Verwerthung der Dungstoffe in verschiedenen deutschen und ausserdeutschen Städten und darauf bezügliche Vorschläge für Berlin / Salviati, Carl von (Public Domain) ( - ) Title page ( - ) Vorbemerkung ( - ) Inhalt ([V]) Bericht ( - ) Hannover (1) Cöln (5) Gent (11) Ostende (18) Antwerpen (30) Metz (48) Karlsruhe (55) Strassburg (62) Basel (68) Lyon (70) Zürich (76) München (78) Nürnberg (82) Dresden (84) Leipzig (89) Ergebnisse der Reise und Vorschläge für Berlin ([93]) Tabelle: Kosten der Latrinen-Stoffe (104) Imprint (114) Tafel I: Reinigungs-Apparate in Ostende und Antwerpen; Die "Lanterne" des Ostender Apparates ( - ) Tafel II: Das Dépotoir (fosse voutée) zu Wyneghem bei Antwerpen am Verbindungs-Kanale der Maas mit der Schelde. Anwendung der Entleerungs-Pumpe in Metz ( - ) Tafel III: Kasernen-Abtritt in Karlsruhe; Kasten Wagen in Karlsruhe; Dépotoir bei Strassburg; Schiettinger's (New-Yorker) Schieber-Pumpe ( - ) Tafel IV: Gusseiserne Einfassung des Loches; Verschluss der Fässer in Dresden; Verschluss in Strassburg; Ansicht Diviseur in Lyon; Seitenansicht eines Eisenblechkessels in Leipzig; Tonnen (Kübel)-System in Leipzig; Einrichtung der Fosses mobiles in den Häusern ( -

Long-term investigations of extended-spectrum beta-lactamases (ESBL)/AmpC beta-lactamases-producing Escherichia coli in pig fattening farms and their surrounding areas

Extended-spectrum beta-lactamases (ESBL)/AmpC beta-lactamases-producing Enterobacteriaceae, especially Escherichia coli (E. coli), are dramatically limiting the therapeutic options in today’s medicine. The development and potential spread of these resistant microorganisms amongst farm animals and the potential emission from livestock to the environment are discussed critically. However, there is only little information available on the occurrence of ESBL/AmpC-producing E. coli in German pig farms and their vicinity, especially with regard to their detection over the course of a fattening period and potential paths of transmission. Therefore, the main objectives of this long-term study were to determine the potential sources of emission, the prevalence dynamics and the quantities of ESBL/AmpC-producing E. coli in seven German conventional pig fattening farms over the course of one fattening period, and to simultaneously investigate the surroundings of the pig farms for these resistant bacteria to determine faecal, airborne and other potential emission routes. Samples tested were taken at three different times within one finishing fattening period and included 20 individual faeces samples as well as various samples from the animals’ housing environment inside the barn such as pooled faeces, boot swabs, dust, environmental swabs, barn air, flies and mice faeces. Samples from the surroundings of the pig barns were taken simultaneously to the samples inside and included ground surfaces and ambient air on the up- and downwind side of the barn as well as slurry and digestate from biogas plants. One suspected E. coli colony was randomly selected for each sample, confirmed using the MALDI-TOF method and tested for antimicrobial susceptibility by the disk diffusion method. In addition, PCR and sequencing of resistance genes were performed to determine the presence and type of ESBL/AmpC beta-lactamases genes in these isolates. Moreover, selected E. coli isolates from samples from inside and outside the pig barns were typed by pulsed-field gel electrophoresis (PFGE) analysis to identify the clonal relationship of the isolates. Different detection levels of ESBL/AmpC-producing E. coli were observed at different times of investigation during the fattening period. In individual faeces average detection levels of 45% (63/140), 29% (41/140) and 36% (51/140) at the three sampling times were accompanied by decreasing faecal counts from 2.97 x 104 cfu/g at the first to 2.17 x 103 cfu/g at the third visit (p = 0.000). Moreover, detection frequencies of ESBL/AmpC-producing E. coli in individual faeces samples differed amongst the different pig farms: There were two farms with a continuous high prevalence, three farms with a low prevalence and two farms with prevalences in between. In the animals’ housing environment inside the barn pooled faeces and boot swab samples each showed a detection rate of 47.6% (10/21). 5.9% (4/68) of environmental swabs, 9.5% (6/63) of barn air samples, as well as 25% (3/12) of flies and 33% (1/3) of mice faeces samples, but none of the dust samples tested positive for ESBL/AmpC-producing E. coli. In the vicinity of the pig barns ESBL/AmpC-producing E. coli were detected in 16.1% (14/87) of the examined boot swab samples taken from various ground surfaces and in 6% (2/36) of ambient air samples. The majority of slurry samples (82.4%; 14/17) and three of four samples of digestate from biogas plants were also tested positive for these resistant bacteria. In total 274 E. coli isolates were further analysed by phenotypical and genotypical methods. Using antimicrobial susceptibility testing, 32 E. coli isolates were AmpC- and 224 E. coli isolates were ESBL-positive. By PCR analyses and subsequent sequencing, ESBL or AmpC beta-lactamases genes were detected in 215 of the 274 E. coli isolates. The dominant ESBL gene family detected was blaCTX-M with 97.2% (209/215) blaCTX-M-positive isolates. In addition, a new beta-lactamase encoding gene, blaTEM-206, was found during this study. PFGE analyses proved faecal emission of resistant E. coli as well as a possible distribution via flies. The present study provides novel information about amounts and dynamics of ESBL/AmpC-producing E. coli in the German pig production. Moreover, this is the first systematic study on a potential emission and transmission of ESBL /AmpC-producing bacteria between pig fattening farms and their surroundings. Contaminated slurry presented the major emission source for ESBL/AmpC- producing E. coli in the pig fattening farms. A spread via the airborne route or via different vectors also seems possible, but appears to play a minor role. A potential risk of colonisation for exposed animals or humans cannot be estimated at the moment and needs to be further investigated.Extended-Spektrum-Beta-Laktamase (ESBL)/AmpC Beta-Laktamase-bildende Enterobacteriaceae, insbesondere Escherichia coli (E. coli), schränken die Therapieoptionen in der heutigen Medizin dramatisch ein. Die Entwicklung und potenzielle Verbreitung dieser resistenten Mikroorganismen bei Nutztieren und der mögliche Austrag aus der Tierhaltung in die Umwelt werden kritisch diskutiert. Allerdings gibt es nur wenig detaillierte Daten zum Vorkommen von ESBL/AmpC-produzierenden E. coli in deutschen Schweinehaltungen und deren Umgebung, insbesondere zu potenziellen Verbreitungswegen und Nachweisraten im Mastverlauf. Daher waren Hauptziele dieser Langzeitstudie zum einen die Untersuchung potenzieller Emissionsquellen und der Prävalenzdynamik sowie auch die quantitative Analyse ESBL/AmpC-bildender Escherichia coli in sieben deutschen konventionellen Schweinemastbetrieben im Mastverlauf. Zum anderen wurde parallel die Umgebung der Betriebe auf diese resistenten Bakterien hin untersucht, um fäkale, aerogene und andere potenzielle Ausbreitungswege von ESBL/AmpC-produzierenden E. coli zu analysieren. Die Probenahmen erfolgten dabei zu drei verschiedenen Zeitpunkten innerhalb einer Endmastperiode und umfassten 20 Einzeltierkotproben sowie verschiedene Proben der Tierumgebung im Stall wie Sammelkot, Sockentupfer, Staub, Umgebungstupfer, Stallluft, Fliegen und Mäusekot. Proben von der Umgebung der Schweineställe wurden zeitgleich genommen und beinhalteten Bodenoberflächen und Außenluft von der windzugewandten und der windabgewandten Seite des Stalls sowie Gülle und Gärrest von Biogasanlagen. Für jede Probe wurde eine verdächtige E. coli- Kolonie zufällig ausgewählt, mittels MALDI-TOF-Untersuchung bestätigt und anhand der Agardiffusionsmethode auf antimikrobielle Empfindlichkeit getestet. Zusätzlich wurden PCR und Sequenzierungen der Resistenzgene durchgeführt, um das Vorhandensein und den Typ von ESBL/AmpC Beta-Laktamase-Genen in diesen Isolaten zu ermitteln. Darüber hinaus wurden ausgewählte E. coli-Isolate von Proben von innerhalb und außerhalb der Schweineställe mittels Pulsfeldgelelektrophorese (PFGE)-Analyse typisiert, um eine klonale Verwandtschaft der Isolate herauszufinden. Unterschiedliche Nachweishäufigkeiten von ESBL/AmpC-bildenden E. coli wurden zu verschiedenen Untersuchungszeitpunkten im Mastverlauf nachgewiesen. In den Einzeltierkotproben lagen die durchschnittlichen Nachweishäufigkeiten von ESBL/AmpC-E. coli zu den drei Probenahmezeitpunkten bei 45% (63/140), 29% (41/140) und 36% (51/140), wobei eine signifikante Abnahme der Konzentration von 2,97 x 104 KbE/g zum ersten Zeitpunkt zu 2,17 x 103 KbE/g zum dritten Zeitpunkt zu verzeichnen war (p = 0.000). Zudem unterschieden sich die Nachweishäufigkeiten von ESBL/AmpC-bildenden E. coli in den Einzeltierkotproben zwischen den verschiedenen Schweinebetrieben: Es gab zwei Betriebe mit einer kontinuierlich hohen Prävalenz, drei Betriebe mit einer niedrigen Prävalenz und zwei Betriebe mit Prävalenzen dazwischen. In der Tierumgebung im Stall wurden bei Sammelkot- und Sockentupferproben jeweils 47,6% (10/21) der Proben positiv getestet. 5,9% (4/68) der Umgebungstupferproben, 9,5% (6/63) der Stallluftproben sowie 25% (3/12) der Fliegen- und 33% (1/3) der Mäusekotproben, jedoch keine der Staubproben war ESBL/AmpC-positiv. In der Umgebung der Schweineställe wurden ESBL/AmpC- bildende E. coli in 16,1% (14/87) der untersuchten Sockentupferproben von verschiedenen Bodenoberflächen nachgewiesen. Des Weiteren wurden in 6% (2/36) der Außenluftproben diese resistenten Keime gefunden. Die Mehrzahl der Gülleproben (82,4%; 14/17) und drei von vier Gärrestproben von Biogasanlagen waren ebenfalls positiv. Insgesamt 274 E. coli-Isolate wurden durch phänotypische und genotypische Methoden weiter analysiert. Davon waren bei der antimikrobiellen Empfindlichkeitstestung 32 E. coli-Isolate AmpC- und 224 Isolate ESBL-positiv. Mittels PCR-Analysen und nachfolgender Sequenzierung wurden in 215 von 274 E. coli-Isolaten ESBL- oder AmpC Beta-Laktamase-Gene detektiert. Dabei war blaCTX-M die dominante ESBL-Genfamilie mit 97,2% (209/215) blaCTX-M-positiven Isolaten. Darüber hinaus wurde während dieser Studie ein neues Gen blaTEM-206, welches für eine Beta-Laktamase kodiert, gefunden. PFGE-Analysen bewiesen einen fäkalen Austrag von resistenten E. coli sowie eine mögliche Verbreitung über Fliegen. Die vorliegende Studie liefert neue Informationen zum Vorkommen und der Prävalenzdynamik von ESBL/AmpC- bildenden E. coli in der deutschen Schweineproduktion. Darüber hinaus ist dies die erste systematische Studie über eine potenzielle Emission und Übertragung von ESBL/AmpC-produzierenden Bakterien zwischen Schweinemastbetrieben und ihrer Umgebung. Kontaminierte Gülle stellte die Hauptemissionsquelle für ESBL /AmpC-bildende E. coli in den Schweinemastbetrieben dar. Eine Verbreitung über die Luft oder über verschiedene Vektoren scheint ebenfalls möglich, jedoch eine geringere Rolle zu spielen. Eine mögliche Gefahr der Besiedlung von exponierten Tieren oder Menschen kann im Augenblick nicht abgeschätzt werden und muss weiter untersucht werden

Die Abfuhr und Verwerthung der Dungstoffe in verschiedenen deutschen und ausserdeutschen Städten und darauf bezügliche Vorschläge für Berlin : Bericht der ... Kommission

C. von Salviati ; O. Roeder u. H. Eichhor

Off-pump versus on-pump coronary artery bypass grafting: A systematic review and meta-analysis of propensity score analyses

ObjectiveDespite numerous randomized and nonrandomized trials on off- and on-pump coronary artery bypass grafting, it remains open which method is superior. Patient selection and small sample sizes limit the evidence from randomized trials; lack of randomization limits the evidence from nonrandomized trials. Propensity score analyses are expected to improve on at least some of these problems. We aimed to systematically review all propensity score analyses comparing off- and on-pump coronary artery bypass grafting.MethodsPropensity score analyses comparing off- and on-pump surgery were identified from 8 bibliographic databases, citation tracking, and a free web search. Two independent reviewers abstracted data on 11 binary short-term outcomes.ResultsA total of 35 of 58 initially retrieved propensity score analyses were included, accounting for a total of 123,137 patients. The estimated overall odds ratio was less than 1 for all outcomes, favoring off-pump surgery. This benefit was statistically significant for mortality (odds ratio, 0.69; 95% confidence interval, 0.60–0.75), stroke, renal failure, red blood cell transfusion (P < .0001), wound infection (P < .001), prolonged ventilation (P < .01), inotropic support (P = .02), and intraaortic balloon pump support (P = .05). The odds ratios for myocardial infarction, atrial fibrillation, and reoperation for bleeding were not significant.ConclusionsOur systematic review and meta-analysis of propensity score analyses finds off-pump surgery superior to on-pump surgery in all of the assessed short-term outcomes. This advantage was statistically significant and clinically relevant for most outcomes, especially for mortality, the most valid criterion. These results agree with previous systematic reviews of randomized and nonrandomized trials

Respiratory chain dysfunction and oxidative stress correlate with severity of primary CoQ10 deficiency.

Coenzyme Q(10) (CoQ(10)) is essential for electron transport in the mitochondrial respiratory chain and antioxidant defense. Last year, we reported the first mutations in CoQ(10) biosynthetic genes, COQ2, which encodes 4-parahydroxybenzoate: polyprenyl transferase; and PDSS2, which encodes subunit 2 of decaprenyl diphosphate synthase. However, the pathogenic mechanisms of primary CoQ(10) deficiency have not been well characterized. In this study, we investigated the consequence of severe CoQ(10) deficiency on bioenergetics, oxidative stress, and antioxidant defenses in cultured skin fibroblasts harboring COQ2 and PDSS2 mutations. Defects in the first two committed steps of the CoQ(10) biosynthetic pathway produce different biochemical alterations. PDSS2 mutant fibroblasts have 12% CoQ(10) relative to control cells and markedly reduced ATP synthesis, but do not show increased reactive oxygen species (ROS) production, signs of oxidative stress, or increased antioxidant defense markers. In contrast, COQ2 mutant fibroblasts have 30% CoQ(10) with partial defect in ATP synthesis, as well as significantly increased ROS production and oxidation of lipids and proteins. On the basis of a small number of cell lines, our results suggest that primary CoQ(10) deficiencies cause variable defects of ATP synthesis and oxidative stress, which may explain the different clinical features and may lead to more rational therapeutic strategies