Risk factors and management of biliary leakage after Endocystectomy for hepatic cystic echinococcosis.

BACKGROUND: Endocystectomy is a conservative surgical approach to managing cystic echinococcosis. Bile leakage is the main complication of this technique. The aim of this study was to evaluate the factors associated with bile leakage and to assess the outcomes and cost efficiency of strategies used to treat bile leakage. METHODOLOGY/PRINCIPAL FINDINGS: Patients who underwent endocystectomy between 2005 and 2020 were included. The preoperative characteristics, intra- and postoperative outcomes, hospital costs, and cost efficiency (the Diagnosis-Related Group reimbursement minus the overall cost) were evaluated prospectively. A total of eighty patients with 142 cysts were included. Postoperative complications occurred in 17 patients (21%), including 11 patients with bile leakage (type A: 1, type B: 6 and type C: 4 patients, total 13%). Bile leakage was more frequent in patients with preoperative MRI signs of cysto-biliary fistulas or intraoperative visible cysto-biliary fistulas (p = 0.03 and p = 0.04, respectively) and in patients with cysts larger than 8 cm (p = 0.03). Patients with bile leakage who underwent reoperation (type C) had significantly shorter hospital stays (9 vs. 16 days, p<0.01) and better cost efficiency than those who received radiologic or endocscopic interventions (€2,072 vs. -€2,097 p = 0.01). No mortality was observed, and recurrence was seen in two patients. CONCLUSIONS/SIGNIFICANCE: Endocystectomy is a safe and efficient technique. Preoperative and intraoperative cysto-biliary fistulas and a cyst diameter larger than 8 cm are correlated to postoperative bile leakage. Early operative management of bile leakage reduces hospital stay and improves cost efficiency compared with radiologic or endoscopic treatments.

A Novel Squirrel Respirovirus with Putative Zoonotic Potential.

In a globalized world, the threat of emerging pathogens plays an increasing role, especially if their zoonotic potential is unknown. In this study, a novel respirovirus, family Paramyxoviridae, was isolated from a Sri Lankan Giant squirrel (Ratufa macroura), which originated in Sri Lanka and deceased with severe pneumonia in a German zoo. The full-genome characterization of this novel virus, tentatively named Giant squirrel respirovirus (GSqRV), revealed similarities to murine (71%), as well as human respiroviruses (68%) with unique features, for example, a different genome length and a putative additional accessory protein. Congruently, phylogenetic analyses showed a solitary position of GSqRV between known murine and human respiroviruses, implicating a putative zoonotic potential. A tailored real-time reverse transcription-polymerase chain reaction (RT-qPCR) for specific detection of GSqRV confirmed a very high viral load in the lung, and, to a lesser extent, in the brain of the deceased animal. A pilot study on indigenous and exotic squirrels did not reveal additional cases in Germany. Therefore, further research is essential to assess the geographic distribution, host range, and zoonotic potential of this novel viral pathogen.

Detection of rotavirus species A, B and C in domestic mammalian animals with diarrhoea and genotyping of bovine species A rotavirus strains.

Rotaviruses (RVs) are a major cause of neonatal diarrhoea in humans and animals worldwide. In this study, 425 faecal samples were collected between 1999 and 2013 from diarrhoeic livestock and companion animals at different locations in Germany and tested for RVs. A previously published real-time RT-PCR assay was optimized for detection of a larger variety of RV species A (RVA) strains, and real-time RT-PCR assays for detection of RV species B (RVB) and C (RVC) were newly developed. The detection limits of the assays were 1.54×10(2), 3.95×10(2) and 3.60×10(3) genome copies for RVA, RVB and RVC, respectively. RVA was identified in 85.2% of bovine samples, 51.2% of porcine samples, 50.0% of feline samples, 43.2% of equine samples and 39.7% of canine samples. RVB was found in 3.0% of bovine samples, 2.7% of equine samples and 1.6% of porcine samples. RVC was detected in 31.0% of porcine samples, 21.7% of feline samples, 9.0% of canine samples and 6.0% of bovine samples. For genotyping, 101 RVA-positive bovine samples were further analysed by semi-nested RT-PCR. Genotype combination G6P[5] was most frequently detected (67.3% of samples), followed by G6P[11] (13.9%), G10P[5] (4.0%), G8P[11] (3.0%), G6P[1] (1.0%), and G10P[11] (1.0%). Mixed RVA infections were detected in 5.9% of samples; no or incomplete typing was possible in 4.0% of the samples. This first overview on RV species and RVA genotypes in diarrhoeic livestock and companion animals from Germany indicates a broad circulation of a large variety of RVs.

[Utilization and utility of psycho-oncologic support of patients with mamma-carcinoma]. / Nutzung und Nutzen psychoonkologischer Versorgung bei Patientinnen mit Mamma-Karzinom.

OBJECTIVES: This study explores patients' utilization of psycho-oncologic support and the effectiveness thereof. METHODS: At the hospital in Munich-Harlaching, 51 patients were recruited following their first admission to the breast centre, 27 of whom utilized the psycho-oncologic service. They were compared to 24 decliners of the service. All patients completed self-rating questionnaires (Distress-Thermometer and Patient Health Questionnaire) at admission and at release. Group differences were calculated statistically by chi-square- and t-tests. RESULTS: We found no significant differences between users and decliners concerning socio-demographic and somatic data, but there were significant group differences in mental health. Users reported more mental distress and more depressive and anxiety symptoms. Psycho-oncologic interventions showed small to large effect sizes. CONCLUSIONS: Although this study corresponded more to external than to internal validity standards, it did yield provisional empirical evidence that psycho-oncologic interventions are effective in the treatment of the mental symptoms of breast cancer patients.

Dermatan 4-O-sulfotransferase1 ablation accelerates peripheral nerve regeneration.

Chondroitin sulfate (CS) and dermatan sulfate (DS) proteoglycans are major components of the extracellular matrix implicated in neural development, plasticity and regeneration. While it is accepted that CS are major inhibitors of neural regeneration, the contributions of DS to regeneration have not been assessed. To enable a novel approach in studies on DS versus CS roles during development and regeneration, we generated a mouse deficient in the dermatan 4-O-sulfotransferase1 (Chst14(-/-)), a key enzyme in the synthesis of iduronic acid-containing modules found in DS but not CS. In wild-type mice, Chst14 is expressed at high levels in the skin and in the nervous system, and is enriched in astrocytes and Schwann cells. Ablation of Chst14, and the assumed failure to produce DS, resulted in smaller body mass, reduced fertility, kinked tail and increased skin fragility compared with wild-type (Chst14(+/+)) littermates, but brain weight and gross anatomy were unaffected. Neurons and Schwann cells from Chst14(-/-) mice formed longer processes in vitro, and Chst14(-/-) Schwann cells proliferated more than Chst14(+/+) Schwann cells. After femoral nerve transection/suture, functional recovery and axonal regrowth in Chst14(-/-) mice were initially accelerated but the final outcome 3months after injury was not better than that in Chst14(+/+) littermates. These results suggest that while Chst14 and its enzymatic products might be of limited importance for neural development, they may contribute to the regeneration-restricting environment in the adult mammalian nervous system.

The N-terminal sequences of four major hydrogenosomal proteins are not essential for import into hydrogenosomes of Trichomonas vaginalis.

The human pathogen Trichomonas vaginalis harbors hydrogenosomes, organelles of mitochondrial origin that generate ATP through hydrogen-producing fermentations. They contain neither genome nor translation machinery, but approximately 500 proteins that are imported from the cytosol. In contrast to well-studied organelles like Saccharomyces mitochondria, very little is known about how proteins are transported across the two membranes enclosing the hydrogenosomal matrix. Recent studies indicate that-in addition to N-terminal transit peptides-internal targeting signals might be more common in hydrogenosomes than in mitochondria. To further characterize the extent to which N-terminal and internal motifs mediate hydrogenosomal protein targeting, we transfected Trichomonas with 24 hemagglutinin (HA) tag fusion constructs, encompassing 13 different hydrogenosomal and cytosolic proteins of the parasite. Hydrogenosomal targeting of these proteins was analyzed by subcellular fractionation and independently by immunofluorescent localization. The investigated proteins include some of the most abundant hydrogenosomal proteins, such as pyruvate ferredoxin oxidoreductase (PFO), which possesses an amino-terminal targeting signal that is processed on import into hydrogenosomes, but is shown here not to be required for import into hydrogenosomes. Our results demonstrate that the deletion of N-terminal signals of hydrogenosomal precursors generally has little, if any, influence upon import into hydrogenosomes. Although the necessary and sufficient signals for hydrogenosomal import recognition appear complex, targeting to the organelle is still highly specific, as demonstrated by the finding that six HA-tagged glycolytic enzymes, highly expressed under the same promoter as other constructs studied here, localized exclusively to the cytosol and did not associate with hydrogenosomes.

Discovery and genetic characterization of novel caliciviruses in German and Dutch poultry.

Caliciviruses (CV) were identified in the intestinal contents of five chickens and one turkey from various regions in Germany between 2009 and 2011 by degenerate reverse transcription PCR. The full 7,656-nt-long genomic sequence of the turkey CV L11043 was determined. Partial nucleotide sequences were determined for nine chicken strains. Phylogenetic analysis based on partial deduced amino acid sequences of the protease and RNA polymerase and the complete VP1 capsid sequence identified two distinct clusters of avian CVs, the first of which contained chicken CVs that were closely related to strains found in German chickens in Bavaria and that had been proposed to form a novel CV genus (proposed name: Bavovirus). In contrast, the turkey CV strain L11043 and three chicken CV strains formed a genetically distinct second cluster. Distance analysis suggested that the strains of the second cluster may represent members of two distinct genogroups of another novel CV genus (proposed name: Nacovirus). Based on the newly obtained sequence information, two real-time RT-PCR assays were developed and used to identify bavovirus and nacovirus in pooled intestinal contents from 24 chicken farms in Germany and the Netherlands. Of these, 20 (83 %) were positive for bavovirus, 11 (46 %) were positive for nacovirus, and nine (38 %) were positive for both bavovirus and nacovirus. Attempts were made to propagate chicken and turkey CVs from both the bavovirus and nacovirus clusters in primary chicken cecal cells, embryonal liver cells and fibroblast cells, but these attempts were not successful.

Central hepatectomy: the golden mean for treating central liver tumors?

The treatment of patients with central liver tumors involving segments 4, 5 and 8 is a difficult clinical problem. These tumors often straddle Cantlie's line and involve parts of both lobes of the liver. The traditional management of such tumors is to perform either an extended right or an extended left hepatectomy. However, extended hepatectomies are associated with greater morbidity and mortality, mainly due to increased risk of postoperative liver failure. Central hepatectomy (or mesohepatectomy) may be superior to extended hepatectomy, because it conserves more liver parenchyma. However, the operation can be tedious and may result in increased blood loss, and was therefore infrequently used. Recommendations for its application for centrally located tumors are not clear. The aim of our study is to evaluate the evidence supporting central hepatectomy as a safe procedure for the management of central hepatic tumors, and to describe the effectiveness of central hepatectomy compared to extended hepatectomy. We present herein two patients who underwent central hepatectomy and systematically review the English literature until December 2006. We found 13 studies of multisegmental (> or = 2 segments) central liver resection that included at least four patients. Only three retrospective non-randomized studies have looked at central hepatectomy in comparison to lobar or extended hepatectomy, and no clear consensus emerges. To date, there is insufficient evidence to categorically state that central hepatectomy is superior to extended hepatectomy, thus the use of all approaches can be justified. However, if central hepatectomy can be performed without excessive blood loss, then it should be preferred, as it is less extensive and results in greater functional remnant liver. Additionally, it would clearly be superior in patients with cirrhosis.

[Detection of DNA of the finch polyomavirus in diseases of various types of birds in the order Passeriformes]. / Nachweis von DNA des Finken-polyomavirus bei Erkrankungen verschiedener Vogelarten der Ordnung Passeriformes.

Between 2000 and 2004 a disease occurred in an aviary in Germany affecting various bird species belonging to the order Passeriformes including Collared Grosbeaks (Mycerobas affinis), Eurasian Bullfinches (Pyrrhula pyrrhula griseiventris), Brown Bullfinches (Pyrrhula nipalensis), Grey-headed bullfinches (Pyrrhula erythaca) and Yellow-bellied Tits (Periparus venustulus). The major clinical signs included increased mortality of fledglings and young birds, as well as feather disorders and feather loss in adult birds. In addition, adult Eurasian Bullfinches showed in one year a disease course, in which the major symptom was inflammation of the skin beginning on the basis of the beak and spreading over the head occurring a few days before death. Bacteriological and parasitological investigations did not reveal any consistent findings. Using a newly developed polymerase chain reaction protocol, DNA of the recently discovered finch polyomavirus (FPyV) was demonstrated in several affected birds. Because of the consistent detection of FPyV-DNA and the similarity of the symptoms with those observed during infection with the closely related avian polyomavirus in other bird species, an etiological role of FPyV in the observed disease is assumed.

Substrate specificity and mechanism of the intestinal clonidine uptake by Caco-2 cells.

PURPOSE: This study was performed to characterize the substrate specificity and mechanism of the intestinal clonidine transport. METHODS: Uptake of [3H]clonidine into Caco-2 cells was investigated. Interaction with drugs was studied in competition assays. RESULTS: Uptake of [3H]clonidine was linear for up to 2 min, Na+-independent, and insensitive to changes in membrane potential, but strongly H+-dependent. The uptake rate of clonidine was saturable with kinetic parameters of 0.5+/-0.1 mM (Kt) and 16.6+/-1.8 nmol/2 min per mg of protein (Vmax) at an outside pH of 7.5. Many drugs such as clonidine, guanabenz, methamphetamine, imipramine, clomipramine, nortriptyline, quinine, xylazine, ephedrine, and diphenhydramine strongly inhibited the [3H]clonidine uptake with Ki values between 0.15 and 1 mM. CONCLUSIONS: Clonidine is transported by a carrier-mediated process. Substrate specificity and mechanism are very similar to the transport described in blood-brain barrier endothelial cells. The transport characteristics do not correspond to carriers for organic cations of the SLC22 family or the choline transporters CHT1 and CLT1. The system might be identical to the H+/tertiary amine antiporter. It interacts with a large number of both hydrophilic and lipophilic cationic drugs, and also, interestingly, with opiates.

Functional characterization of a high-affinity choline transport system in human keratinocytes.

This study was performed to characterize the mechanism of choline transport into human keratinocytes. Uptake of [3H]choline was measured both in the HaCaT cell line and in native keratinocytes. Uptake in HaCaT cells was linear with time at least up to 10 min. There was little dependence of choline transport on sodium. Choline uptake was slightly stimulated by extracellular H+ with the pH optimum being 7.5. The uptake rate was saturable and indicated participation of a single transport system (Kt = 14.8 +/- 1.0 micro M, Vmax = 1.0 +/- 0.01 nmol per 10 min per mg protein). The choline uptake into HaCaT cells was inhibited by unlabeled choline, hemicholinium-3, and acetylcholine. The prototypical organic cation tetraethylammonium showed very little affinity for the choline uptake system in these cells. Several cationic drugs such as diphenhydramine, clonidine, and atropine also interacted with the transport system. Choline uptake in normal keratinocytes was very similar to that in HaCaT cells with respect to substrate specificity and affinity. We conclude that keratinocytes express a Na+ independent, high-affinity choline transport system. This system accepts many pharmacologically important organic cations as substrates. It is similar or identical to the choline carrier described in intestinal epithelial cells and in endothelial cells of the blood-brain barrier. The choline carrier seems to have relevance not only for the uptake of cationic drugs into the keratinocytes but also for the biosynthesis of skin lipids.