Jennifer L. Zamanian
May 2, 2012; 32:6391-6410
Neurobiology of Disease

Pediatric osteoarticular infections can be treated with successful microbiologic and clinical outcomes with a transition from parenteral to oral therapy. The best way to determine the timing of this transition is neither well studied nor standardized.

A total of 193 (99.5%) of 194 pediatric patients with acute bacterial osteoarticular infections were successfully transitioned to oral therapy, determined by using a combination of clinical findings and C-reactive protein levels, representing the largest single-center data set analyzed. (Read the full article)

Biomarkers such as C-reactive protein (CRP) and procalcitonin are elevated in children with severe bacterial infections. Children with severe malnutrition are at increased risk of bacterial infections and early markers for the diagnosis of infection in these children are needed.

Despite elevated values in severely malnourished children with invasive bacterial infection or infectious diarrhea, CRP and procalcitonin have limited diagnostic value. CRP could predict death in these children with a good negative predictive value. (Read the full article)

ABSTRACT

The obligatory intracellular pathogen Ehrlichia chaffeensis lacks most factors that could respond to oxidative stress (a host cell defense mechanism). We previously found that the C terminus of Ehrlichia surface invasin, entry-triggering protein of Ehrlichia (EtpE; EtpE-C) directly binds mammalian DNase X, a glycosylphosphatidylinositol-anchored cell surface receptor and that binding is required to induce bacterial entry and simultaneously to block the generation of reactive oxygen species (ROS) by host monocytes and macrophages. However, how the EtpE-C–DNase X complex mediates the ROS blockade was unknown. A mammalian transmembrane glycoprotein CD147 (basigin) binds to the EtpE-DNase X complex and is required for Ehrlichia entry and infection of host cells. Here, we found that bone marrow-derived macrophages (BMDM) from myeloid cell lineage-selective CD147-null mice had significantly reduced Ehrlichia-induced or EtpE-C-induced blockade of ROS generation in response to phorbol myristate acetate. In BMDM from CD147-null mice, nucleofection with CD147 partially restored the Ehrlichia-mediated inhibition of ROS generation. Indeed, CD147-null mice as well as their BMDM were resistant to Ehrlichia infection. Moreover, in human monocytes, anti-CD147 partially abrogated EtpE-C-induced blockade of ROS generation. Both Ehrlichia and EtpE-C could block activation of the small GTPase Rac1 (which in turn activates phagocyte NADPH oxidase) and suppress activation of Vav1, a hematopoietic-specific Rho/Rac guanine nucleotide exchange factor by phorbol myristate acetate. Vav1 suppression by Ehrlichia was CD147 dependent. E. chaffeensis is the first example of pathogens that block Rac1 activation to colonize macrophages. Furthermore, Ehrlichia uses EtpE to hijack the unique host DNase X-CD147-Vav1 signaling to block Rac1 activation.

IMPORTANCE Ehrlichia chaffeensis is an obligatory intracellular bacterium with the capability of causing an emerging infectious disease called human monocytic ehrlichiosis. E. chaffeensis preferentially infects monocytes and macrophages, professional phagocytes, equipped with an arsenal of antimicrobial mechanisms, including rapid reactive oxygen species (ROS) generation upon encountering bacteria. As Ehrlichia isolated from host cells are readily killed upon exposure to ROS, Ehrlichia must have evolved a unique mechanism to safely enter phagocytes. We discovered that binding of the Ehrlichia surface invasin to the host cell surface receptor not only triggers Ehrlichia entry but also blocks ROS generation by the host cells by mobilizing a novel intracellular signaling pathway. Knowledge of the mechanisms by which ROS production is inhibited may lead to the development of therapeutics for ehrlichiosis as well as other ROS-related pathologies.

Key Points

Key Points

The plasmas of diabetic or uremic patients and of those receiving peritoneal dialysis treatment have increased levels of the glucose-derived dicarbonyl metabolites like methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG). The elevated dicarbonyl levels can contribute to the development of painful neuropathies. Here, we used stimulated immunoreactive Calcitonin Gene–Related Peptide (iCGRP) release as a measure of nociceptor activation, and we found that each dicarbonyl metabolite induces a concentration-, TRPA1-, and Ca2+-dependent iCGRP release. MGO, GO, and 3-DG were about equally potent in the millimolar range. We hypothesized that another dicarbonyl, 3,4-dideoxyglucosone-3-ene (3,4-DGE), which is present in peritoneal dialysis (PD) solutions after heat sterilization, activates nociceptors. We also showed that at body temperatures 3,4-DGE is formed from 3-DG and that concentrations of 3,4-DGE in the micromolar range effectively induced iCGRP release from isolated murine skin. In a novel preparation of the isolated parietal peritoneum PD fluid or 3,4-DGE alone, at concentrations found in PD solutions, stimulated iCGRP release. We also tested whether inflammatory tissue conditions synergize with dicarbonyls to induce iCGRP release from isolated skin. Application of MGO together with bradykinin or prostaglandin E2 resulted in an overadditive effect on iCGRP release, whereas MGO applied at a pH of 5.2 resulted in reduced release, probably due to an MGO-mediated inhibition of transient receptor potential (TRP) V1 receptors. These results indicate that several reactive dicarbonyls activate nociceptors and potentiate inflammatory mediators. Our findings underline the roles of dicarbonyls and TRPA1 receptors in causing pain during diabetes or renal disease.

The reactive suspension system pioneered by Lotus for the 2012 system has been banned for the new season, according to reports

Premature babies have the risk of reactive attachment disorder which can impair a child's ability to function in normal situations and their social interactions,

Amarís, Hortensia, author

Panel Juha Paananen (twitter github blog) Joe Fiorini (twitter github blog) AJ O’Neal (twitter github blog) Jamison Dance (twitter github blog) Joe Eames (twitter github blog) Merrick Christensen (twitter github) Charles Max Wood (twitter github Teach Me To Code Rails Ramp Up) Discussion 01:20 - Joe Fiorini Introduction Interaction Developer at Designing Interactive in Cleveland, OH 01:42 - Juha Paananen Introduction Software Developer at Reaktor in Helsinki, Finland 02:30 - Functional Reactive Programming (FRP) vs Functional Programming 057 JSJ Functional Programming with Zach Kessin 04:25 - Declarative Programming 05:55 - Map and Filter 07:05 - bacon.js Flapjax 09:10 - Mapping and filtering event streams 10:40 - Asynchronicity and Promises 14:28 - Using FRP ReactiveCocoa Complex UIs TodoMVC with Bacon.js, Backbone.js and Transparency.js by pyykiss 20:02 - Ember.js and FRP 22:04 - MVC frameworks and FRP Juha Paananen: FRP, Bacon.js and stuff: Chicken, Egg and Bacon.js 24:35 - Learning FRP 25:49 - Where did FRP come from? What is (functional) reactive programming? - Stack Overflow Conal Elliott: Composing Reactive Animations Haskell Reactive-banana - HaskellWiki 29:07 - Going beyond visual media substack/stream-handbook 32:18 - Wrappers 33:31 - How to build things with FRP libraries Juha Paananen @ MLOC.JS: Functional Reactive Programming in JavaScript using Bacon.js Picks SlideShare: Functional Reactive Programming in JavaScript (AJ) Valve: The AI Systems of Left 4 Dead by Michael Booth (Jamison) programming is terrible (Jamison) Simple Made Easy: Rich Hickey (Jamison) AngularJS Fundamentals (Joe's Pluralsight Course) (Joe) Open Source Bridge (Joe) That Conference (Joe) Star Trek: Into Darkness (Joe) ServerBear (AJ) rainwave (AJ) rwbackend (AJ) Mesa Boogie Lone Star Guitar Amplifier (Merrick) backburner.js (Merrick) messageformat.js (Merrick) Digital Ocean (Chuck) Emacs (Chuck) emacs_libs (Chuck) Tmux (Chuck) GitLab (Chuck) Flight by Twitter (Joe F.) Ember.js (Joe F.) CodeMash (Joe F.) fantasy-land (Juha) The Bacon.js postings featuring Phil Roberts (Juha) Iron Sky (Juha) Reaktor Dev Day (Juha) Next Week Dojo with Dylan Schiemann Transcript MERRICK:  How come nobody acknowledges when I talk? What about that? JAMISON:  That’s a deeper problem than a microphone. [Hosting and bandwidth provided by the Blue Box Group. Check them out at Bluebox.net.]  [This episode is sponsored by Component One, makers of Wijmo. If you need stunning UI elements or awesome graphs and charts, then go to Wijmo.com and check them out.]  CHUCK:  Hey everybody, and welcome to Episode 61 of the JavaScript Jabber Show. This week on our panel, we have AJ O’Neal. AJ:  Yo, yo, yo. Coming at you live from Iowa. CHUCK:  Again? AJ:  Oh, I guess I was there last time, huh? It’ll be New York soon. CHUCK:  We have Jamison Dance. JAMISON:  Howdy, guys. CHUCK:  Joe Eames. JOE E:  Hey there. CHUCK:  Merrick Christensen. MERRICK:  What’s up? CHUCK:  I’m Charles Max Wood from DevChat.tv. This week, we have two special guests. We have Joe Fiorini. JOE F:  Hello everyone. CHUCK:  And Juha Paananen. JUHA:  Yeah. Hi everybody. Juha Paananen. CHUCK:  Thank you for straightening that up for me. We’re going to have you guys introduce yourself real quick, since you haven’t been on the show before. Joe, why don’t you start us off? JOE F:  Sure. My name is Joe Fiorini and I am an Interaction Developer at Designing Interactive in Cleveland, Ohio. I do a decent amount of JavaScript development every week. I’ve discovered Functional Reactive Programming three or four months ago and it’s changed my world. CHUCK:  Awesome. And Juha, do you want to introduce yourself as well? JUHA:  Yeah, why not? I’m Juha. I’m from Finland. Helsinki.

On today's episode, Charles Max Wood, Joe Eames, and Tracy Lee discuss Reactive Programming and RxJS with Ben Lesh. Ben works at Netflix and also has a side job for Rx Workshop with Tracy. He is the lead author of RxJS 5. Tune in to learn more about RxJS!

Dean is a developer from Chicago and was previously on React Round Up 083. Today he has come over to JavaScript Jabber to talk about reactive programming and Storybook. Reactive programming is the opposite of imperative programming, where it will change exactly when needed instead of change only when told to. Reactivity existed long before React, and Dean talks about his history with reactive programming. He illustrates this difference by talking about Trello and Jira. In Trello, as you move cards from swimlane to another swimlane, everyone on the board sees those changes right away. In Jira,  if you have 11 tabs open, and you update data in one tab, probably 10 of your tabs are stale now and you might have to refresh. Reactive programming is the difference between Trello and Jira.

The panel discusses why reactive JavaScript is not more widely used. People now tend to look for more focused tools to solve a particular part of the problem than an all in one tool like Meteor.js. Dean talks about the problems that Storybook solves. Storybook has hot reloading environments in frontend components, so you don’t need the backend to run. Storybook also allows you to create a catalogue of UI states. JC and Dean talk about how Storybook could create opportunities for collaboration between engineers and designers. They discuss some causes of breakage that automation could help solve, such as styles not being applied properly and internationalization issues. Dean shares how to solve some network issues, such as having operators in RxJs. RxJs is useful for overlapping calls because it was built with cancelability from the beginning. 

Dean talks about his tool Storybook Animate, which allows you to see what the user sees. Storybook is an actively updated product, and Dean talks about how to get started with it. The show concludes with Dean talking about some things coming down the pipe and how he is actively involved in looking for good general solutions to help people write bulletproof code. 

Panelists

• JC Hiatt

With special guest: Dean Radcliffe

Sponsors

• Hasura, Inc.

• Sentry use the code “devchat” for 2 months free on Sentry’s small plan

• Adventures in Angular

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"The MaxCoders Guide to Finding Your Dream Developer Job" by Charles Max Wood will be out on November 20th on Amazon.  Get your copy on that date only for $1.

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Links

• RRU 083

• Knockout.js 

• Node.js

• Meteor.js

• RXJS

• Storybook Animate

• RX Helper library

Follow DevChatTV on Facebook and Twitter

Picks

JC Hiatt:

• Joker

• DevLifts

Dean Radcliffe: 

• Twitter @deaniusol and Github @deanius

• The Keyframers

• Action for Healthy Kids

Publisher Amsterdam : Elsevier, 1982-©1988.

Location World Wide Web

Call No. TP156.P6