Gallbladder Ejection Fraction is Unrelated to Gallbladder Pathology in Children and Adolescents

Objectives: Biliary dyskinesia is a common diagnosis that frequently results in cholecystectomy. In adults, most clinicians use a cut off value for the gallbladder ejection fraction (GBEF) of <35% to define the disease. This disorder is not well characterized in children. Our aim was to determine the relation between GBEF and gallbladder pathology using a large statewide medical record repository. Methods: We obtained records from all patients of 21 years and younger who underwent hepatic iminodiacetic acid (HIDA) testing within the Indiana Network for Patient Care from 2004 to 2013. GBEF results were obtained from radiology reports using data mining techniques. Age, sex, race, and insurance status were obtained for each patient. Any gallbladder pathology obtained subsequent to an HIDA scan was also obtained and parsed for mention of cholecystitis, cholelithiasis, or cholesterolosis. We performed mixed effects logistic regression analysis to determine the influence of age, sex, race, insurance status, pathologist, and GBEF on the presence of these histologic findings. Results: Two thousand eight hundred forty-one HIDA scans on 2558 patients were found. Of these, 310 patients had a full-text gallbladder pathology report paired with the HIDA scan. GBEF did not correlate with the presence of gallbladder pathology (cholecystitis, cholelithiasis, or cholesterolosis) when controlling for age, sex, race, insurance status, and pathologist using a mixed effects model. Conclusions: Hypokinetic gallbladders are no more likely to have gallbladder pathology than normal or hyperkinetic gallbladders in the setting of a patient with both a HIDA scan and a cholecystectomy. Care should be used when interpreting the results of HIDA scans in children and adolescents

Antiparasitic and Antiproliferative Effects of Indoleamine 2,3-dioxygenase Enzyme Expression in Human Fibroblasts.

Studies were carried out to evaluate the proposed role of indoleamine 2,3-dioxygenase (INDO) induction in the antimicrobial and antiproliferative effects of gamma interferon (IFN-gamma) in human fibroblasts. The INDO cDNA coding region was cloned in the pMEP4 expression vector, containing the metallothionein (MTII) promoter in the sense (+ve) or the antisense (-ve) orientation. Human fibroblasts (GM637) stably transfected with the sense construct expressed INDO activity after treatment with CdCl2 or ZnSO4, but cells transfected with the antisense construct did not. The growth of Chlamydia psittaci was strongly inhibited in INDO +ve cells but not in INDO -ve cells after treatment with Cd2+ or Zn2+. The inhibition correlated with the level of INDO activity induced and could be reversed by the addition of excess tryptophan to the medium. The growth of Toxoplasma gondii was also strongly inhibited in INDO +ve cells but not in INDO -ve cells after treatment with Cd2+. Expression of Cd(2+)-induced INDO activity also inhibited thymidine incorporation and led to cytotoxicity in INDO +ve cells but not in INDO -ve cells. Thus, the induction of INDO activity by IFN-gamma may be an important factor in the antimicrobial and antiproliferative effects of IFN-gamma in human fibroblasts

Kynurenine pathway inhibition reduces central nervous system inflammation in a model of human African trypanosomiasis

Human African trypanosomiasis, or sleeping sickness, is caused by the protozoan parasites &lt;i&gt;Trypanosoma brucei rhodesiense&lt;/i&gt; or &lt;i&gt;Trypanosoma brucei gambiense&lt;/i&gt;, and is a major cause of systemic and neurological disability throughout sub-Saharan Africa. Following early-stage disease, the trypanosomes cross the blood-brain barrier to invade the central nervous system leading to the encephalitic, or late stage, infection. Treatment of human African trypanosomiasis currently relies on a limited number of highly toxic drugs, but untreated, is invariably fatal. Melarsoprol, a trivalent arsenical, is the only drug that can be used to cure both forms of the infection once the central nervous system has become involved, but unfortunately, this drug induces an extremely severe post-treatment reactive encephalopathy (PTRE) in up to 10% of treated patients, half of whom die from this complication. Since it is unlikely that any new and less toxic drug will be developed for treatment of human African trypanosomiasis in the near future, increasing attention is now being focussed on the potential use of existing compounds, either alone or in combination chemotherapy, for improved efficacy and safety. The kynurenine pathway is the major pathway in the metabolism of tryptophan. A number of the catabolites produced along this pathway show neurotoxic or neuroprotective activities, and their role in the generation of central nervous system inflammation is well documented. In the current study, Ro-61-8048, a high affinity kynurenine-3-monooxygenase inhibitor, was used to determine the effect of manipulating the kynurenine pathway in a highly reproducible mouse model of human African trypanosomiasis. It was found that Ro-61-8048 treatment had no significant effect (P = 0.4445) on the severity of the neuroinflammatory pathology in mice during the early central nervous system stage of the disease when only a low level of inflammation was present. However, a significant (P = 0.0284) reduction in the severity of the neuroinflammatory response was detected when the inhibitor was administered in animals exhibiting the more severe, late central nervous system stage, of the infection. &lt;i&gt;In vitro&lt;/i&gt; assays showed that Ro-61-8048 had no direct effect on trypanosome proliferation suggesting that the anti-inflammatory action is due to a direct effect of the inhibitor on the host cells and not a secondary response to parasite destruction. These findings demonstrate that kynurenine pathway catabolites are involved in the generation of the more severe inflammatory reaction associated with the late central nervous system stages of the disease and suggest that Ro-61-8048 or a similar drug may prove to be beneficial in preventing or ameliorating the PTRE when administered as an adjunct to conventional trypanocidal chemotherap

Extent of hypoattenuation on CT angiography source images in Basilar Artery occlusion: prognostic value in the Basilar Artery International Cooperation Study

&lt;p&gt;&lt;b&gt;Background and Purpose:&lt;/b&gt; The posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) quantifies the extent of early ischemic changes in the posterior circulation with a 10-point grading system. We hypothesized that pc-ASPECTS applied to CT angiography source images predicts functional outcome of patients in the Basilar Artery International Cooperation Study (BASICS).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; BASICS was a prospective, observational registry of consecutive patients with acute symptomatic basilar artery occlusion. Functional outcome was assessed at 1 month. We applied pc-ASPECTS to CT angiography source images of patients with CT angiography for confirmation of basilar artery occlusion. We calculated unadjusted and adjusted risk ratios (RRs) of pc-ASPECTS dichotomized at &#8805;8 versus &#60;8. Primary outcome measure was favorable outcome (modified Rankin Scale scores 0–3). Secondary outcome measures were mortality and functional independence (modified Rankin Scale scores 0–2).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Of 158 patients included, 78 patients had a CT angiography source images pc-ASPECTS ≥8. Patients with a pc-ASPECTS ≥8 more often had a favorable outcome than patients with a pc-ASPECTS &#60;8 (crude RR, 1.7; 95% CI, 0.98–3.0). After adjustment for age, baseline National Institutes of Health Stroke Scale score, and thrombolysis, pc-ASPECTS &#8805;8 was not related to favorable outcome (RR, 1.3; 95% CI, 0.8–2.2), but it was related to reduced mortality (RR, 0.7; 95% CI, 0.5–0.98) and functional independence (RR, 2.0; 95% CI, 1.1–3.8). In post hoc analysis, pc-ASPECTS dichotomized at &#8805;6 versus &#60;6 predicted a favorable outcome (adjusted RR, 3.1; 95% CI, 1.2–7.5).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; pc-ASPECTS on CT angiography source images independently predicted death and functional independence at 1 month in the CT angiography subgroup of patients in the BASICS registry.&lt;/p&gt

Individual Response to Risk As a Function of Normative Social Pressure: A Pilot Study of Seat Belt Use

The authors attempt to clarify some of the variables that influence whether people act appropriately when a Risk is substantial and subject to individual control. They do so by reporting results of a pilot study of seat belt use. Also, the authors believe their approach to be generalizable to problems such as encouraging people to test for radon, to use condoms to prevent AIDS or to quit smoking

Carboniferous plant physiology breaks the mold

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155970/1/nph16460-sup-0001-SupInfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155970/2/nph16460_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155970/3/nph16460.pd

Dynamic Carboniferous tropical forests: new views of plant function and potential for physiological forcing of climate

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138385/1/nph14700_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138385/2/nph14700.pd

Serum hepatitis B virus RNA predicts response to peginterferon treatment in HBeAg-positive chronic hepatitis B

Hepatitis B virus (HBV) RNA in serum is a novel biomarker that reflects cccDNA activity. We investigated whether HBV RNA can predict serological response to peginterferon (PEG-IFN) treatment. Serum HBV RNA levels were retrospectively measured at weeks 0, 12, 24 and 52 of therapy and after treatment discontinuation (week 78) in 266 HBeAg-positive chronic HBV patients who had participated in a global randomized controlled trial (HBV99-01 study). Patients received 52 weeks PEG-IFN monotherapy (n = 136) or PEG-IFN and lamivudine (n = 130). The primary end point was HBeAg loss 24 weeks after PEG-IFN discontinuation. At baseline, the mean serum level of HBV RNA was 6.8 (SD 1.2) log c/mL. HBV RNA levels declined to 4.7 (1.7) log c/mL after one year of PEG-IFN therapy alone and to 3.3 (1.2)log c/mL after combination therapy. From week 12 onward, HBV RNA level was significantly lower in patients who achieved HBeAg loss at the end of follow-up as compared to those who did not, regardless of treatment allocation (week 12:4.4 vs 5.1 log c/mL, P =.01; week 24:3.7 vs 4.9 log c/mL, P <.001). The performance of a multivariable model based on HBV RNA level was comparable at week 12 (AUC 0.68) and 24 (AUC 0.72) of therapy. HBV RNA level above 5.5 log c/mL at week 12 showed negative predictive values of 93/67/90/64% for HBV genotypes A/B/C/D for the prediction of HBeAg loss. In conclusion, HBV RNA in serum declines profoundly during PEG-IFN treatment. Early on-treatment HBV RNA level may be used to predict nonresponse

Composite genome map and recombination parameters derived from three archetypal lineages of Toxoplasma gondii

Toxoplasma gondii is a highly successful protozoan parasite in the phylum Apicomplexa, which contains numerous animal and human pathogens. T.gondii is amenable to cellular, biochemical, molecular and genetic studies, making it a model for the biology of this important group of parasites. To facilitate forward genetic analysis, we have developed a high-resolution genetic linkage map for T.gondii. The genetic map was used to assemble the scaffolds from a 10X shotgun whole genome sequence, thus defining 14 chromosomes with markers spaced at ∼300 kb intervals across the genome. Fourteen chromosomes were identified comprising a total genetic size of ∼592 cM and an average map unit of ∼104 kb/cM. Analysis of the genetic parameters in T.gondii revealed a high frequency of closely adjacent, apparent double crossover events that may represent gene conversions. In addition, we detected large regions of genetic homogeneity among the archetypal clonal lineages, reflecting the relatively few genetic outbreeding events that have occurred since their recent origin. Despite these unusual features, linkage analysis proved to be effective in mapping the loci determining several drug resistances. The resulting genome map provides a framework for analysis of complex traits such as virulence and transmission, and for comparative population genetic studies