Non-invasive index of liver fibrosis induced by alcohol, thioacetamide and schistosomal infection in mice

<p>Abstract</p> <p>Background</p> <p>Non invasive approaches will likely be increasing utilized to assess liver fibrosis. This work provides a new non invasive index to predict liver fibrosis induced in mice.</p> <p>Methods</p> <p>Fibrosis was generated by thioacetamide (TAA), chronic intake of ethanol, or infection with <it>S. mansoni </it>in 240 mice. Both progression and regression of fibrosis (after treatment with silymarin and/or praziquantel) were monitored. The following methods were employed: (i) The METAVIR system was utilized to grade and stage liver inflammation and fibosis; (ii) Determination of hepatic hydroxyproline and collagen; and (iii) Derivation of a new hepatic fibrosis index from the induced changes, and its prospective validation in a group of 70 mice.</p> <p>Results</p> <p>The index is composed of 4 serum variable including total proteins, γ-GT, bilirubin and reduced glutathione (GSH), measured in diseased, treated and normal mice. These parameters were highly correlated with both the histological stage and the grade. They were combined in a logarithmic formula, which non-invasively scores the severity of liver fibrosis through a range (0 to 2), starting with healthy liver (corresponding to stage 0) to advanced fibrosis (corresponding stage 3).Receiver operating characteristic curves (ROC) for the accuracy of the index to predict the histological stages demonstrated that the areas under the curve (AUC) were 0.954, 0.979 and 0.99 for index values corresponding to histological stages 1, 2 and 3, respectively. Also, the index was correlated with stage and grade, (0.947 and 0.859, respectively). The cut off values that cover the range between stages 0-1, 1-2 and 2-3 are 0.4, 1.12 and 1.79, respectively. The results in the validation group confirmed the accuracy of the test. The AUROC was 0.869 and there was good correlation with the stage of fibrosis and grade of inflammation.</p> <p>Conclusion</p> <p>The index fulfils the basic criteria of non-invasive marker of liver fibrosis since it is liver-specific, easy to implement, reliable, and inexpensive. It proved to be accurate in discriminating precirrhotic stages.</p

Geological and geophysical investigation of Kamil crater, Egypt

We detail the Kamil crater (Egypt) structure and refine the impact scenario, based on the geological and geophysical data collected during our first expedition in February 2010. Kamil Crater is a model for terrestrial small-scale hypervelocity impact craters. It is an exceptionally well-preserved, simple crater with a diameter of 45 m, depth of 10 m, and rayed pattern of bright ejecta. It occurs in a simple geological context: flat, rocky desert surface, and target rocks comprising subhorizontally layered sandstones. The high depth-to-diameter ratio of the transient crater, its concave, yet asymmetric, bottom, and the fact that Kamil Crater is not part of a crater field confirm that it formed by the impact of a single iron mass (or a tight cluster of fragments) that fragmented upon hypervelocity impact with the ground. The circular crater shape and asymmetries in ejecta and shrapnel distributions coherently indicate a direction of incidence from the NW and an impact angle of approximately 30 to 45 . Newly identified asymmetries, including the off-center bottom of the transient crater floor downrange, maximum overturning of target rocks along the impact direction, and lower crater rim elevation downrange, may be diagnostic of oblique impacts in well-preserved craters. Geomagnetic data reveal no buried individual impactor masses >100 kg and suggest that the total mass of the buried shrapnel >100 g is approximately 1050–1700 kg. Based on this mass value plus that of shrapnel >10 g identified earlier on the surface during systematic search, the new estimate of the minimum projectile mass is approximately 5 t.Published1842–18683.8. Geofisica per l'ambienteJCR Journalrestricte

Outcomes of gonioscopy-assisted transluminal trabeculotomy in pseudoexfoliative glaucoma: 24-month follow-up

AimTo report on outcomes of gonioscopy-assisted transluminal trabeculotomy (GATT) in eyes with pseudoexfoliative glaucoma (PXG).MethodsProspective, interventional, non-comparative case series. A total of 103 eyes from 84 patients with PXG were enrolled to undergo a 360-degree ab interno trabeculotomy with gonioscopic assistance using either a 5.0 polypropylene suture or an illuminated microcatheter with up to 24 months of follow-up. Main outcome measures were intraocular pressure (IOP), number of antiglaucoma medications, success rate (IOP reduction ≥20% from baseline or IOP between 6 and 21 mm Hg, without further glaucoma surgery) and complication rate.ResultsMean preoperative IOP was 27.1 mm Hg (95% CI 25.5 to 28.7) using 2.9 (SD 1.1) glaucoma medications which decreased postoperatively to 13.0 mm Hg (95% CI 11.5 to 14.4) and 1.0 (SD 1.1) medications at 24 months (p&lt;0.001). Success rate was 89.2% at 24 months of follow-up, and complication rate was 2.9%.ConclusionAt 24 months of follow-up, our results for GATT in PXG demonstrate that this conjunctival sparing procedure effectively lowers IOP and reduces the medications with a low complication rate, in this relatively aggressive glaucoma subtype.</jats:sec

Do U.S. Environmental Protection Agency water quality guidelines for recreational waters prevent gastrointestinal illness? A systematic review and meta-analysis.

Despite numerous studies, uncertainty remains about how water quality indicators can best be used in the regulation of recreational water. We conducted a systematic review of this topic with the goal of quantifying the association between microbial indicators of recreational water quality and gastrointestinal (GI) illness. A secondary goal was to evaluate the potential for GI illness below current guidelines. We screened 976 potentially relevant studies and from these identified 27 studies. From the latter, we determined summary relative risks for GI illness in relation to water quality indicator density. Our results support the use of enterococci in marine water at U.S. Environmental Protection Agency guideline levels. In fresh water, (Italic)Escherichia(/Italic) coli was a more consistent predictor of GI illness than are enterococci and other bacterial indicators. A log (base 10) unit increase in enterococci was associated with a 1.34 [95% confidence intervals (CI), 1.00-1.75] increase in relative risk in marine waters, and a log (base 10) unit increase in E. coli was associated with a 2.12 (95% CI, 0.925-4.85) increase in relative risk in fresh water. Indicators of viral contamination were strong predictors of GI illness in both fresh and marine environments. Significant heterogeneity was noted among the studies. In our analysis of heterogeneity, studies that used a nonswimming control group, studies that focused on children, and studies of athletic or other recreational events found elevated relative risks. Future studies should focus on the ability of new, more rapid and specific microbial methods to predict health effects, and estimating the risks of recreational water exposure among susceptible persons

Effect of surgical experience and spine subspecialty on the reliability of the AO Spine Upper Cervical Injury Classification System.

OBJECTIVE The objective of this paper was to determine the interobserver reliability and intraobserver reproducibility of the AO Spine Upper Cervical Injury Classification System based on surgeon experience ( 20 years) and surgical subspecialty (orthopedic spine surgery, neurosurgery, and "other" surgery). METHODS A total of 11,601 assessments of upper cervical spine injuries were evaluated based on the AO Spine Upper Cervical Injury Classification System. Reliability and reproducibility scores were obtained twice, with a 3-week time interval. Descriptive statistics were utilized to examine the percentage of accurately classified injuries, and Pearson's chi-square or Fisher's exact test was used to screen for potentially relevant differences between study participants. Kappa coefficients (κ) determined the interobserver reliability and intraobserver reproducibility. RESULTS The intraobserver reproducibility was substantial for surgeon experience level ( 20 years: 0.70) and surgical subspecialty (orthopedic spine: 0.71 vs neurosurgery: 0.69 vs other: 0.68). Furthermore, the interobserver reliability was substantial for all surgical experience groups on assessment 1 ( 20 years: 0.62), and only surgeons with > 20 years of experience did not have substantial reliability on assessment 2 ( 20 years: 0.59). Orthopedic spine surgeons and neurosurgeons had substantial intraobserver reproducibility on both assessment 1 (0.64 vs 0.63) and assessment 2 (0.62 vs 0.63), while other surgeons had moderate reliability on assessment 1 (0.43) and fair reliability on assessment 2 (0.36). CONCLUSIONS The international reliability and reproducibility scores for the AO Spine Upper Cervical Injury Classification System demonstrated substantial intraobserver reproducibility and interobserver reliability regardless of surgical experience and spine subspecialty. These results support the global application of this classification system

The AO spine upper cervical injury classification system: Do work setting or trauma center affiliation affect classification accuracy or reliability?

PURPOSE To assess the accuracy and reliability of the AO Spine Upper Cervical Injury Classification System based on a surgeons' work setting and trauma center affiliation. METHODS A total of 275 AO Spine members participated in a validation of 25 upper cervical spine injuries, which were evaluated by computed tomography (CT) scans. Each participant was grouped based on their work setting (academic, hospital-employed, or private practice) and their trauma center affiliation (Level I, Level II or III, and Level IV or no trauma center). The classification accuracy was calculated as percent of correct classifications, while interobserver reliability, and intraobserver reproducibility were evaluated based on Fleiss' Kappa coefficient. RESULTS The overall classification accuracy for surgeons affiliated with a level I trauma center was significantly greater than participants affiliated with a level II/III center or a level IV/no trauma center on assessment one (p1<0.0001) and two (p2 = 0.0003). On both assessments, surgeons affiliated with a level I or a level II/III trauma center were significantly more accurate at identifying IIIB injury types (p1 = 0.0007; p2 = 0.0064). Academic surgeons and hospital employed surgeons were significantly more likely to correctly classify type IIIB injuries on assessment one (p1 = 0.0146) and two (p2 = 0.0015). When evaluating classification reliability, the largest differences between work settings and trauma center affiliations was identified in type IIIB injuries. CONCLUSION Type B injuries are the most difficult injury type to correctly classify. They are classified with greater reliability and classification accuracy when evaluated by academic surgeons, hospital-employed surgeons, and surgeons associated with higher-level trauma centers (I or II/III)

Asc-Dependent and Independent Mechanisms Contribute to Restriction of Legionella Pneumophila Infection in Murine Macrophages

The apoptosis-associated speck-like protein containing a caspase recruitment domain (Asc) is an adaptor molecule that mediates inflammatory and apoptotic signals. Legionella pneumophila is an intracellular bacterium and the causative agent of Legionnaire's pneumonia. L. pneumophila is able to cause pneumonia in immuno-compromised humans but not in most inbred mice. Murine macrophages that lack the ability to activate caspase-1, such as caspase-1−/− and Nlrc4−/− allow L. pneumophila infection. This permissiveness is attributed mainly to the lack of active caspase-1 and the absence of its down stream substrates such as caspase-7. However, the role of Asc in control of L. pneumophila infection in mice is unclear. Here we show that caspase-1 is moderately activated in Asc−/− macrophages and that this limited activation is required and sufficient to restrict L. pneumophila growth. Moreover, Asc-independent activation of caspase-1 requires bacterial flagellin and is mainly detected in cellular extracts but not in culture supernatants. We also demonstrate that the depletion of Asc from permissive macrophages enhances bacterial growth by promoting L. pneumophila-mediated activation of the NF-κB pathway and decreasing caspase-3 activation. Taken together, our data demonstrate that L. pneumophila infection in murine macrophages is controlled by several mechanisms: Asc-independent activation of caspase-1 and Asc-dependent regulation of NF-κB and caspase-3 activation