Uromodulin is expressed in renal primary cilia and UMOD mutations result in decreased ciliary uromodulin expression

Uromodulin (UMOD) mutations are responsible for three autosomal dominant tubulo-interstitial nephropathies including medullary cystic kidney disease type 2 (MCKD2), familial juvenile hyperuricemic nephropathy and glomerulocystic kidney disease. Symptoms include renal salt wasting, hyperuricemia, gout, hypertension and end-stage renal disease. MCKD is part of the 'nephronophthisis-MCKD complex', a group of cystic kidney diseases. Both disorders have an indistinguishable histology and renal cysts are observed in either. For most genes mutated in cystic kidney disease, their proteins are expressed in the primary cilia/basal body complex. We identified seven novel UMOD mutations and were interested if UMOD protein was expressed in the primary renal cilia of human renal biopsies and if mutant UMOD would show a different expression pattern compared with that seen in control individuals. We demonstrate that UMOD is expressed in the primary cilia of renal tubules, using immunofluorescent studies in human kidney biopsy samples. The number of UMOD-positive primary cilia in UMOD patients is significantly decreased when compared with control samples. Additional immunofluorescence studies confirm ciliary expression of UMOD in cell culture. Ciliary expression of UMOD is also confirmed by electron microscopy. UMOD localization at the mitotic spindle poles and colocalization with other ciliary proteins such as nephrocystin-1 and kinesin family member 3A is demonstrated. Our data add UMOD to the group of proteins expressed in primary cilia, where mutations of the gene lead to cystic kidney disease.

EPITHET: Positive Result After Reanalysis Using Baseline Diffusion-Weighted Imaging/Perfusion-Weighted Imaging Co-Registration

the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) was a prospective, randomized, double-blinded, placebo-controlled, phase II trial of alteplase between 3 and 6 hours after stroke onset. The primary outcome of infarct growth attenuation on MRI with alteplase in mismatch patients was negative when mismatch volumes were assessed volumetrically, without coregistration, which underestimates mismatch volumes. We hypothesized that assessing the extent of mismatch by coregistration of perfusion and diffusion MRI maps may more accurately allow the effects of alteplase vs placebo to be evaluated.

Measuring attitudes, behaviours, and influences in inner city victims of interpersonal violence (VIVs) - a Swiss emergency room pilot study

Background Switzerland is confronted with the problem of interpersonal violence. Violence is in the increase and the potential for aggression seems to be rising. Observations by hospitals discern an appalling increase of the severity of the injuries. The aim of this study is to collect accurate information about the social environment, the motivation and possible reasons for violence. We also intend to investigate whether sociocultural, or ethnic differences among male victims exist. Materials and methods For the first time in Switzerland, this survey employed a validated questionnaire from the division of violence prevention, Atlanta, Georgia. The first part of the questionnaire addressed social and demographic factors which could influence the risk of violence: age, gender, duration of stay in Switzerland, nationality and educational level. Beside these social structural factors, the questionnaire included questions on experience of violent offences in the past, information about the most recent violent offence and intra and interpersonal facts. The questionnaire itself consists of 27 questions, translated into German and French. In a pilot study, the questionnaire was checked with adolescents for feasibility and comprehensibility. Results 69 male VIVs were interviewed at two hospitals in the Canton of Bern. Most of the adolescents emphasised that weapons were not used during their confrontations. It is astonishing that all of the young men considered themselves to be victims. Most of the brawls were incited after an exchange of verbal abuse and provocations with unfamiliar individuals. The rivals could neither be classified with the help of ethnic categories nor identifiable groups of the youth scenes. The incidents took place in scenes, where violence was more likely to happen. Interestingly and contrary to a general perception the offenders are well integrated into sport and leisure clubs. A further surprising result of our research is that the attitude towards religion differs between young men with experience of violence and non-violent men. Discussion Youth violence is a health issue, which concerns us globally. The human and economic toll of violence on victims and offenders, their families, and on society in general is high. The economic costs associated with violence-related illness and disability is estimated to be millions of Swiss francs each year. Physicians and psychologists are compelled to identify the factors, which cause young people to be violent, to find out which interventions prove to be successful, and to design effective prevention programs. The identification of effective programs depends on the availability of reliable and valid measures to assess changes in violence-related attitudes. In our efforts to create healthier communities, we need to investigate; document and do research on the causes and circumstances of youth violence.

How reliable are Hounsfield-unit measurements in forensic radiology?

OBJECTIVE: To assess the reliability of computed tomography (CT) numbers, also known as Hounsfield-units (HU) in the differentiation and identification of forensically relevant materials and to provide instructions to improve the reproducibility of HU measurements in daily forensic practice. MATERIALS AND METHODS: We scanned a phantom containing non-organic materials (glass, rocks and metals) on three different CT scanners with standardized parameters. The t-test was used to assess the influence of the scanner, the size and shape of different types of regions-of-interest (ROI), the composition and shape of the object, and the reader performance on HU measurements. Intra-class correlation coefficient was used to assess intra- and inter-reader reliability. RESULTS: HU values did not change significantly as a function of ROI-shape or -size (p>0.05). Intra-reader reliability reached ICC values >0.929 (p<0.001). Inter-reader reliability was also excellent with an ICC of 0.994 (p<0.001). Four of seven objects yielded significantly different CT numbers at different levels within the object (p<0.05). In 6/7 objects the HU changed significantly from CT scanner to CT scanner (p<0.05). CONCLUSION: Reproducible CT number measurements can be achieved through correct ROI-placement and repeat measurements within the object of interest. However, HU may differ from CT-scanner to CT-scanner. In order to obtain comparable CT numbers we suggest that a dedicated Forensic Reference Phantom be developed.

Radiologic identification of disaster victims: a simple and reliable method using CT of the paranasal sinuses

To assess the reliability of radiologic identification using visual comparison of ante and post mortem paranasal sinus computed tomography (CT).

[Adhesions and abdominal pain]

Adhesions occur with a high incidence after intra-abdominal surgery but can also develop due to infections, radiation or for idiopathic reasons. The formation of adhesions is initiated by tissue damage and is the result of peritoneal tissue repair involving the activation of the inflammatory system and the coagulation cascade. Acute small bowel obstruction is one of the most common complications and should be diagnosed rapidly using clinical examination and radiological imaging. A complete obstruction is life threatening and in a high percentage of patients requires rapid surgical intervention by laparotomy or laparoscopy depending on the clinical situation and the patients history. Despite numerous investigations, there is no reliable, commonly used method to prevent intra-abdominal adhesions. Minimizing tissue damage and foreign body exposure, avoiding spillage of intestinal and biliary contents as well as a laparoscopic approach seem to have a beneficial effect on the formation of intra-abdominal adhesions.

Deglaciation records of 17O-excess in East Antarctica: reliable reconstruction of oceanic relative humidity from coastal sites

We measured δ17O and δ18O in two Antarctic ice cores at EPICA Dome C (EDC) and TALDICE (TD), respectively and computed 17O-excess with respect to VSMOW. The comparison of our 17O-excess data with the previous record obtained at Vostok (Landais et al., 2008) revealed differences up to 35 ppm in 17O-excess mean level and evolution for the three sites. Our data showed that the large increase depicted at Vostok (20 ppm) during the last deglaciation, is a regional and not a general pattern in the temporal distribution of 17O-excess in East Antarctica. The EDC data display an increase of 13 ppm, whereas the TD data show no significant variation from the Last Glacial Maximum (LGM) to the Early Holocene (EH). Lagrangian moisture source diagnostic revealed very different source regions for Vostok and EDC compared to TD. These findings combined with the results of a sensitivity analysis, using a Rayleigh-type isotopic model, suggest that relative humidity (RH) at the oceanic source region (OSR) are a determining factor for the spatial differences of 17O-excess in East Antarctica. However, 17O-excess in remote sites of continental Antarctica (e.g. Vostok) may be highly sensitive to local effects. Hence, we consider 17O-excess in coastal East Antarctic ice cores (TD) to be more reliable as a proxy for RH at the OSR.

Are endodontically treated incisors reliable abutments for zirconia-based fixed partial dentures in the esthetic zone?

This ex vivo pilot study tested the influence of defect extension and quartz-fiber post placement (QFP) on the ex vivo survival rate and fracture resistance of root-treated upper central incisors served as abutments for zirconia 2-unit cantilever fixed partial dentures (2U-FPDs) exposed to 10 years of simulated clinical function.

How reliable is Ki-67 immunohistochemistry in grade 2 breast carcinomas? A QA study of the Swiss Working Group of Breast- and Gynecopathologists

Adjuvant chemotherapy decisions in breast cancer are increasingly based on the pathologist's assessment of tumor proliferation. The Swiss Working Group of Gyneco- and Breast Pathologists has surveyed inter- and intraobserver consistency of Ki-67-based proliferative fraction in breast carcinomas. Methods Five pathologists evaluated MIB-1-labeling index (LI) in ten breast carcinomas (G1, G2, G3) by counting and eyeballing. In the same way, 15 pathologists all over Switzerland then assessed MIB-1-LI on three G2 carcinomas, in self-selected or pre-defined areas of the tumors, comparing centrally immunostained slides with slides immunostained in the different laboratoires. To study intra-observer variability, the same tumors were re-examined 4 months later. Results The Kappa values for the first series of ten carcinomas of various degrees of differentiation showed good to very good agreement for MIB-1-LI (Kappa 0.56–0.72). However, we found very high inter-observer variabilities (Kappa 0.04–0.14) in the read-outs of the G2 carcinomas. It was not possible to explain the inconsistencies exclusively by any of the following factors: (i) pathologists' divergent definitions of what counts as a positive nucleus (ii) the mode of assessment (counting vs. eyeballing), (iii) immunostaining technique, and (iv) the selection of the tumor area in which to count. Despite intensive confrontation of all participating pathologists with the problem, inter-observer agreement did not improve when the same slides were re-examined 4 months later (Kappa 0.01–0.04) and intra-observer agreement was likewise poor (Kappa 0.00–0.35). Conclusion Assessment of mid-range Ki-67-LI suffers from high inter- and intra-observer variability. Oncologists should be aware of this caveat when using Ki-67-LI as a basis for treatment decisions in moderately differentiated breast carcinomas.

How reliable and safe is full-body low-dose radiography (LODOX Statscan) in detecting foreign bodies ingested by adults?

OBJECTIVE: Foreign body ingestion is common and potentially lethal. This study evaluates the use of low-dose Statscans (LODOX) in emergency departments. DESIGN: This comparative cross-sectional study retrospectively assessed 28 289 digital chest x-rays and 2301 LODOX scans performed between 2006 and 2010 at a tertiary emergency centre. The radiographic appearance, image quality and location of ingested foreign bodies were evaluated in standard digital chest and LODOX radiography. The mean irradiation (μSv) and cumulative mean radiation dose per patient with the ingested foreign body were calculated according to literature-based data, together with the sensitivity and specificity for each modality. RESULTS: A total of 62 foreign bodies were detected in 39 patients, of whom 19 were investigated with LODOX and 20 with conventional digital chest radiography. Thirty-three foreign bodies were located in the two upper abdominal quadrants, 21 in the lower quadrants-which are not visible on conventional digital chest radiography-seven in the oesophagus and one in the bronchial system. The sensitivity and specificity of digital chest radiography were 44.4% and 94.1%, respectively, and for the LODOX Statscan 90% and 100%, respectively. The calculated mean radiation dose for LODOX investigations was 184 μS, compared with 524 μS for digital chest radiography. CONCLUSIONS: LODOX Statscan is superior to digital chest radiography in the diagnostic work-up of ingested foreign bodies because it makes it possible to enlarge the field of view to the entire body, has higher sensitivity and specificity, and reduces the radiation dose by 65%.

Pulmonary artery thrombosis in experimental Angiostrongylus vasorum infection does not result in pulmonary hypertension and echocardiographic right ventricular changes

BACKGROUND: Dogs experimentally inoculated with Angiostrongylus vasorum develop severe pulmonary parenchymal lesions and arterial thrombosis at the time of patency. HYPOTHESIS: A. vasorum-induced thrombosis results in arterial hypoxemia, pulmonary hypertension (PH), and altered cardiac morphology and function. ANIMALS: Six healthy Beagles experimentally inoculated with A. vasorum. METHODS: Thoracic radiographs and arterial blood gas analyses were performed 8 and 13 weeks postinoculation (wpi) and 9 weeks posttherapy (wpt). Echocardiography was done before and 2, 5, 8, 13 wpi and 9 wpt. Invasive pulmonary artery pressure (PAP) measurements were obtained 8 wpi. Two untreated dogs were necropsied 13 wpi and 4 treated dogs 9 wpt. RESULTS: All dogs had patent infections at 7 wpi and clinical respiratory signs at 8 wpi. Moderate hypoxemia (median PaO2 of 73 and 74 mmHg) present at 8 and 13 wpi had resolved by 9 wpt. Echocardiographically, no evidence of PH and no abnormalities in cardiac size and function were discernible at any time point. PAP invasively measured at 8 wpi was not different from that of control dogs. Severe radiographic pulmonary parenchymal and suspected thrombotic lesions at 13 wpi were corroborated by necropsy. Most histopathologic changes had resolved at 9 wpt, but focal inflammatory, thrombotic, and fibrotic changes still were present in all dogs. CONCLUSION: In experimentally infected Beagles, pulmonary and vascular changes induced by A. vasorum are reflected by marked radiographic changes and arterial hypoxemia. These did not result in PH and echocardiographic changes in cardiac size and function.

Microsurgery and liver research: Lumbricus terrestris, a reliable animal model for training?

Experiments using animal models are the most common way to learn microsurgery. This expertise is necessary for liver research, microsurgical reconstruction of the esophagus by free jejunum or reconstruction of the hepatic artery during reimplantation from living donors. The goal of this prospective study is to assess the reliability of an invertebrate model for microsurgical training.