Genetic Characterization of Goutanap Virus,a Novel Virus Related to Negeviruses,Cileviruses and Higreviruses

Pools of mosquitoes collected in Côte d’Ivoire and Mexico were tested for cytopathic effects on the mosquito cell line C6/36. Seven pools induced strong cytopathic effects after one to five days post infection and were further investigated by deep sequencing. The genomes of six virus isolates from Côte d’Ivoire showed pairwise nucleotide identities of ~99% among each other and of 56%–60% to Dezidougou virus and Wallerfield virus, two insect-specific viruses belonging to the proposed new taxon Negevirus. The novel virus was tentatively named Goutanap virus. The isolate derived from the Mexican mosquitoes showed 95% pairwise identity to Piura virus and was suggested to be a strain of Piura virus, named C6.7-MX-2008. Phylogenetic inferences based on a concatenated alignment of the methyltransferase, helicase, and RNA-dependent RNA polymerase domains showed that the new taxon Negevirus formed two monophyletic clades, named Nelorpivirus and Sandewavirus after the viruses grouping in these clades. Branch lengths separating these clades were equivalent to those of the related genera Cilevirus, Higrevirus and Blunervirus, as well as to those within the family Virgaviridae. Genetic distances and phylogenetic analyses suggest that Nelorpivirus and Sandewavirus might form taxonomic groups on genus level that may define alone or together with Cilevirus, Higrevirus and Blunervirus a viral family.     

Evidence-based, interdisciplinary guidelines for anti-inflammatory treatment of uveitis associated with juvenile idiopathic arthritis

Uveitis in juvenile idiopathic arthritis (JIA) is frequently associated with the development of complications and visual loss. Topical corticosteroids are the first-choice therapy, and immunosuppression is commonly used. However, treatment has not been standardized. Representatives from the German Ophthalmological Society, Society for Childhood and Adolescent Rheumatology, and the German Society for Rheumatology reached consensus on a standardized treatment strategy according to disease severity in the individual patient. The recommendations were based on a systematic literature analysis in MEDLINE and consensus expert meetings. Evidence and recommendations were graded, and an algorithm for anti-inflammatory treatment and final statements confirmed in a Delphi method. An interdisciplinary, evidence-based treatment guideline for JIA uveitis is presented.     

Long-term follow-up of early treatment of unilateral forced posterior crossbite with regard to temporomandibular disorders and associated symptoms

Forty-four subjects, who at the age of 4 years had been treated for unilateral forced cross-bite by grinding or by maxillary arch expansion, were 16-19 years later followed-up by means of a questionnaire about their present condition with regard to temporomandibular disorders (TMD). Twenty-two of them had received only early treatment (early questionnaire group) and 22 had received late treatment (late questionnaire group). Fourteen of the subjects who received late treatment also received early treatment. Twenty-nine of the subjects were also examined clinically. Eighteen of these had only received early treatment at 4 years of age (early clinical group), whereas 11 of them also received later treatment in the mixed or permanent dentition because of relapse (late clinical group). No significant differences were found between the early and late groups with regard to signs and symptoms of TMD. Most of the young adults who had undergone orthodontic treatment had well-functioning masticatory systems, and severe TMD signs and symptoms were rare. The results of this study suggest that relapse of early orthodontic treatment and further need of treatment does not influence the later status of subjective symptoms or clinical signs of TMD in young adults.     

Kontrastmittelsonographie nach EVAR

Contrast-enhanced ultrasound is an established method for surveillance after endovascular abdominal aortic aneurysm repair (EVAR). According to study data, it is at least equivalent to CT angiography (CTA). The time requirements for the vascular surgeon should not be underestimated. The new technology is now available from well-known manufacturers and high-end devices. However, it has not been implemented yet due to cost and time requirements, despite significant advantages for the patient: no nephrotoxicity, no iodine-containing contrast media, and no radiation exposure.     

Cerebral monitors versus regional anesthesia to detect cerebral ischemia in patients undergoing carotid endarterectomy: a meta-analysis

Purpose

The aim of this meta-analysis is to compare the ability of different types of brain monitoring systems vs clinical monitoring of the brain function to detect cerebral ischemia during cross-clamping of the carotid artery under regional anesthesia.

Methods

In May 2012, a search was conducted in PubMed, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Ovid MEDLINE^® for prospective trials with 20 patients or more where a cerebral monitoring system was compared with clinical brain monitoring during a carotid endarterectomy performed under regional anesthesia. The quality of the study was evaluated with the Cochrane Collaboration’s tool. Data were extracted independently by the two investigators.

Results

Data could be extracted for 4,664 measurements taken from 29 studies: transcranial Doppler (TCD) = 739; cerebral saturation = 320; stump pressure = 2,549; electroencephalography (EEG) = 742; evoked potentials = 187; jugular venous saturation = 79; and jugular venous lactate = 48. The pooled diagnostic odds ratios (DOR) and 95% confidence intervals (CI) were obtained for EEG, TCD, stump pressure, evoked potentials, and cerebral saturation: (DOR 65.3; 95% CI 20.5 to 207.7; I² [56.8%]); (DOR 58.1; 95% CI 23.0 to 146.3; I² [24.9%]); (DOR 27.8; 95% CI 13.4 to 57.9; I² [59.9]); (DOR 17.2; 95% CI 2.4 to 123.9 I² [69.1]); and (DOR 12.1; 95% CI 3.5 to 41.2; I² [30.8]), respectively. Sequential testing with stump pressure 25 mmHg followed by either TCD or EEG delivered the best post-test probabilities. For EEG, the DOR increases with the number of channels used (P = 0.03).

Conclusion

A combination of stump pressure and either TCD or EEG appears to deliver the best results for detecting brain ischemia during carotid artery cross-clamping. Electroencephalography should be used with a high number of channels.     

Recent Progress in the Pathophysiology and Treatment of FSGS Recurrence

Focal segmental glomerulosclerosis (FSGS) is a glomerular disease characterized by proteinuria, frequent progression to end‐stage renal disease, and recurrence after kidney transplantation in ～25% of patients, which negatively impacts long‐term allograft survival. Experimental studies suggest that abnormalities in T and, possibly, B cells may represent one initial pathogenic trigger, leading to podocyte injury and progressive loss. New data also support the existence of circulating permeability factors able to damage the podocytes, but no single molecule has been consistently identified as the causal pathogenic element in FSGS recurrence. Unfortunately, major progress from mechanistic studies has not translated into substantial advancements in patient treatment, with plasmapheresis (PP) and high doses of cyclosporine (CsA) remaining the mainstays of therapy. Despite consistent experimental and clinical evidence that treatment of proteinuria slows renal function decline in proteinuric nephropathies, maximal use of antiproteinuric agents such as renin angiotensin system antagonists is not routine in the management of FSGS recurrence. More recently, encouraging results have been reported with anti‐CD20 depleting antibody rituximab, but further studies are needed to establish its safety/efficacy profile.     

Automatic Control of Veno‐Venous Extracorporeal Lung Assist

Veno‐venous extracorporeal lung assist (ECLA) can provide sufficient gas exchange even in most severe cases of acute respiratory distress syndrome. Commercially available systems are manually controlled, although an automatically controlled ECLA could allow individualized and continuous adaption to clinical requirements. Therefore, we developed a demonstrator with an integrated control algorithm to keep continuously measured peripheral oxygen saturation and partial pressure of carbon dioxide constant by automatically adjusting extracorporeal blood and gas flow. The “SmartECLA” system was tested in six animal experiments with increasing pulmonary hypoventilation and hypoxic inspiratory gas mixture to simulate progressive acute respiratory failure. During a cumulative evaluation time of 32 h for all experiments, automatic ECLA control resulted in a peripheral oxygen saturation ≥90% for 98% of the time with the lowest value of 82% for 15 s. Partial pressure of venous carbon dioxide was between 40 and 49 mm Hg for 97% of the time with no value <35 mm Hg or >49 mm Hg. With decreasing inspiratory oxygen concentration, extracorporeal oxygen uptake increased from 68 ± 25 to 154 ± 34 mL/min (P < 0.05), and reducing respiratory rate resulted in increasing extracorporeal carbon dioxide elimination from 71 ± 37 to 92 ± 37 mL/min (P < 0.05). The “SmartECLA” demonstrator allowed reliable automatic control of the extracorporeal circuit. Proof of concept could be demonstrated for this novel automatically controlled veno‐venous ECLA circuit.     

Opa proteins of pathogenic neisseriae initiate Src kinase-dependent or lipid raft-mediated uptake via distinct human carcinoembryonic antigen-related cell adhesion molecule isoforms

Several pathogenic bacteria exploit human carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) for adhesion to and invasion into their host cells. CEACAM isoforms have characteristic expression patterns on epithelial, endothelial, or hematopoietic cells, providing bacteria with distinct sets of receptors on particular tissues. For example, while CEACAM1 and CEACAM6 have a wide tissue distribution, CEACAM3, CEACAM4, and CEACAM8 are uniquely expressed on primary human granulocytes, whereas CEA and CEACAM7 are limited to epithelia. By reconstitution of a CEACAM-deficient cell line with individual CEACAMs, we have analyzed the requirements for CEACAM-mediated internalization of Neisseria gonorrhoeae. Our results point to two mechanistically different uptake pathways triggered by either epithelial CEACAMs (CEACAM1, CEA, and CEACAM6) or the granulocyte-specific CEACAM3. In particular, CEACAM3-mediated uptake critically depends on Src family protein tyrosine kinase (PTK) activity, and CEACAM3 associates with the SH2 domains of several Src PTKs. In contrast, epithelial CEACAMs require the integrity of cholesterol-rich membrane microdomains and are affected by cholesterol depletion, whereas CEACAM3-mediated uptake by transfected cells or the opsonin-independent phagocytosis by human granulocytes is not altered in the presence of cholesterol chelators. These results allow the subdivision of all human CEACAMs known to be utilized as pathogen receptors into functional groups and point to important consequences for bacterial engagement of distinct CEACAM isoforms.