Progression of Treated versus Untreated Liver Imaging Reporting and Data System Category 4 Masses after Transcatheter Arterial Embolization Therapy

Purpose

To compare outcomes of treated vs untreated Liver Imaging Reporting and Data System category 4 (LR-4) masses after transcatheter arterial embolization.

Mitochondria a key role in microcystin-LR kidney intoxication

Microcystins (MCs) are a group of closely related cyclic heptapeptides produced by a variety of common cyanobacteria. These toxins have been implicated in both human and livestock mortality. Microcystin-LR could affect renal physiology by altering vascular, glomerular and urinary parameters, indicating that MC-LR could act directly on the kidney. The aim of the current work was to examine the effect of MC-LR on mitochondrial oxidative phosphorylation of rat kidney isolated mitochondria.Furthermore, microcystin-LR decreased both state 3 and carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP)-uncoupled respiration. The transmembrane potential was strongly depressed by MC-LR in a concentration dependent manner, pointing to an uncoupling effect; however, microcystin-LR did not increase the permeability of the inner mitochondria membrane to protons. Therefore, the transmembrane decrease was a consequence of a strong inhibitory effect on redox complexes. The addition of uncoupling concentrations of MC-LR to Ca(2+)-loaded mitochondria treated with ruthenium red resulted in mitochondrial permeability transition pore (MPTP) opening, as evidenced by mitochondrial swelling in isosmotic sucrose medium. Mitochondrial swelling in the presence of Ca(2+) was prevented by cyclosporin A and was drastically inhibited by catalase and dithiothreitol, indicating the participation of mitochondrial generated reactive oxygen species in this process. From this study it can be concluded that the bioenergetic lesion promoted by microcystin-LR seems to be sufficient to explain renal injury.     

A single mild fluid percussion injury induces short-term behavioral and neuropathological changes in the Long-Evans rat: support for an animal model of concussion

Brain concussion is a serious public health concern and is associated with short-term cognitive impairments and behavioral disturbances that typically occur in the absence of significant brain damage. The current study addresses the need to better understand the effects of a mild lateral fluid percussion injury on rat behavior and neuropathology in an animal model of concussion. Male Long-Evans rats received either a single mild fluid percussion injury or a sham-injury, and either a short (24 h) or long (4 weeks) post-injury recovery period. After recovery, rats underwent a detailed behavioral analysis consisting of tests for rodent anxiety, cognition, social behavior, sensorimotor function, and depression-like behavior. After testing all rats were sacrificed and brains were examined immunohistochemically with markers for microglia/macrophage activation, reactive astrocytosis, and axonal injury. Injured rats (mean injury force: 1.20 ± .03 atm) displayed significant short-term cognitive impairments in the water maze and significantly more anxiolytic-like behavior in the elevated-plus maze compared to sham controls. Neuropathological analysis of the brains of injured rats showed an acute increase in reactive astrogliosis and activated microglia in cortex and evidence of axonal injury in the corpus callosum. There were no significant long-term effects on any behavioral or neuropathological measure 4 weeks after injury. These short-term behavioral and neuropathological changes are consistent with findings in human patients suffering a brain concussion, and provide further evidence for the use of a single mild lateral fluid percussion injury to study concussion in the rat.     

Value of clinical assessment in the diagnostic evaluation of Global Developmental Delay (GDD) using a Likelihood Ratio Model

Objective

A selective approach is recommended for investigating children with GDD. Our objective is to identify clinical markers to improve the diagnostic yield of evaluation of children with GDD.

Method

Children with GDD (delay > 2 S.D. in > 1 domain) followed up in our centre were reviewed retrospectively. We selected nine clinical markers (sex, severity of GDD, parental consanguinity, family history, behavioral problems, head size, facial dysmorphism, non-facial anomalies and neurological deficits) and looked into the likelihood of finding an underlying etiology during follow-up.

Results

There were 577 children with 63%, 33% and 4% having mild, moderate and severe grade GDD. An identifiable etiology is detected in 53%. Genetic disease (25%) was the commonest cause identified. We have found that severity of GDD (severe and moderate versus mild grade [LR+ = 1.92 (95% C.I. = 1.49-2.48); LR− = 0.72(0.64-0.81)], behavioral problems [LR+ = 0.24 (95% C.I. = 0.17-0.34); LR− = 1.67 (1.48-1.88)], facial dysmorphism [LR+ = 2.66 (95% C.I. = 1.10-3.54); LR− = 0.65 (0.58-0.73)] and neurological deficits [LR+ = 2.85 (95% C.I. = 2.32-3.50); LR− = 0.31(0.25-0.39)] were clinical markers associated with increased chance of identifying an underlying etiology by multivariate analysis.

Conclusion

These four clinical markers are useful in selecting patients with GDD for further diagnostic tests. Using the LR model, clinical markers in the first clinical evaluation of any child with GDD can potentially improve the etiological yield using targeted investigations.