Effectiveness of antibiotics in treating cholera reviewed

Researchers from the Cochrane Infectious Diseases Group, co-ordinated through the editorial base in LSTM, conducted an independent review of the effects of treating cholera with antimicrobial drugs, published in The Cochrane Library today.

Cholera is an acute watery diarrhea caused by infection with the bacterium Vibrio cholerae, which can cause rapid dehydration and death. Effective treatment requires early diagnosis and rehydration using oral rehydration salts or intravenous fluids. This review looked at the effects of adding antimicrobial drugs to this treatment.

Thirty-nine randomized and quasi-randomized controlled clinical trials were included in the review, with a combined total of 4623 participants, both adults and children. Overall the researchers found that antimicrobial therapy shortened the average duration of diarrhea by about a day and a half when compared to placebo or no treatment. Antimicrobial therapy also reduced the total stool volume by 50% and reduced the amount of rehydration fluids required by 40%, and shortened the duration of fecal extraction of vibrios bacteria by almost three days.

There was substantial variation between trials in the size of these benefits, probably due to differences in the antibiotic used, the trial methods (particularly effective randomization), and the timing of outcome assessment. However the benefits of antibiotics were seen both in trials recruiting only patients with severe dehydration and in those recruiting patients with mixed levels of dehydration.

In direct head-to-head comparisons, researchers found that there were no obvious differences detected in diarrhea duration or stool volume for tetracycline compared to doxycycline or tetracycline compared to ciprofloxacin or norfloxacin. However, a higher number of studies looked at indirect comparisons and in those cases tetracycline appeared to have larger benefits than doxycycline, norfloxacin and trimethoprim-sulfamethoxazole, while single dose azithromycin shortened the duration of diarrhea by over a day compared to ciprofloxacin and by half a day compared to erythromycin. Tetracycline was not compared with azithromycin.

Ya'ara Leibovici-Weissman from Tel Aviv University said: "In treating cholera a quick and accurate diagnosis remains key, but it is clear from the results that antimicrobials result in substantial improvements in clinical and microbiological outcomes, with similar effects observed in severely and non-severely ill patients. Our results also point to the likelihood that azithromycin and tetracycline may have some advantages over other antibiotics."

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The above story is based on materials provided by Liverpool School of Tropical Medicine . Note: Materials may be edited for content and length.

No, not evolutionary biology, too! [Pharyngula]

We’ve heard so much about bad behavior at conferences, and how sexist attitudes can suppress the contributions of women. And it doesn’t seem to matter what the conference is about: tech, gaming, atheism, skepticism, philosophy, you name it. Now Prof-Like Substance describes the scene at evolutionary biology conferences, explaining how many women are hesitant to participate in important events because of the predatory behavior of some men. And she gives a little advice.

So dudes, pull this apart a little bit. First off, the frequency with which inappropriate advances occur is causing some women to avoid after hours social events. Not only does that have consequences, but that very fact in itself should bother you. Also consider that even consensual sexyfuntimes have very different career implications for men versus women. These communities are small and things get around. Finally, are you going to be That Guy who women are warned against being around alone? Do you want the dumb things you say when you’re out late to be the reason a woman leaves the field or is uncomfortable attending social events? Consider that maybe your work colleagues are not the best target audience for your affections.

Interesting. She isn’t appealing to the altruistic best side of men, who ought to care about what’s best for their colleagues, but their self-interest. Sounds like an evolutionary biologist.

Star Talk

Josh Valcarcel/WIRED

Blink a few times, and then a few more, and the world will be smothered in signal; ubiquitous Internet and voice service is coming. Balloons, miniature satellites, and aerial drones will get us there. But not yet, not today. Even here in the United States, there are plenty of spots where a cellular signal is impossible to come by. That’s where GlobalStar’s Sat-Fi comes in. It lets you make calls and use the Internet from anywhere there’s sky.

The Sat-Fi is a satellite antenna that’s connected by a cable to a Wi-Fi router. It has apps for iOS, Android, Mac OS, and Windows that let you make voice calls, send emails (or even update your Twitter and Facebook accounts). It’s designed for areas where there is no network to connect to—4G, 3G, Edge, you name it. It’s really geared towards industrial use, but preppers take note, it would make a great emergency kit addition as well.

And here’s the thing: it works. If you need to send an email or make a call from way boonie nowhere, the Sat-Fi will connect you. Once I had it properly set up (more on that below) and had a clear shot at the sky, there was never an instance where I absolutely couldn’t connect.

A pair of Sat-Fi apps—one for voice, another for data—serve as your comms center. They jack into your phone’s address book and suck up your contacts—which is nice because you don’t have to manually plug in phone numbers or email addresses to get in touch with people. The email function is pretty basic, and takes some getting used to, because, for example, the “send” button on Android isn’t right in front of you. You actually have to go into the options. But it’s also solid in a way that you want something in the field to be. When you send and receive email, you can see the server connections, and you get a confirmation message so you know you were able to communicate. One nice touch? You can attach photos to your messages. These are dropped way down in resolution so the files are small enough to reasonably transmit and end up looking about like the phone cam pictures you took a decade ago. But they’re enough to get the point across.

I also thought it was kind of neat to be able to link up with Facebook and Twitter. While that may seem twee (hey, I’m tweeting from space!), when you consider one of Twitter’s best use cases is as a form of emergency communication—to tell the world about a fire or a flood or some other disaster when there are no other ways of getting the word out—it makes perfect sense that Sat-Fi included it. Similarly, it’s easy to see how the Facebook connection could be very handy to send updates to your friends and families when doing so would normally be impossible.

When everything is set up right, and conditions are good (meaning you’ve got a clear sky setup) it worked perfectly. Voice calls don’t exhibit noticeable lag. The internet connection just rolls data out and reels it back in again. At night under a wide open starry sky by the side of a lake, I had stellar voice quality that sounded about like a normal cell phone call. Yet on a heavily overcast day when I had the antenna in the shadow of a house, there was a noticeable lag of several seconds between the time I would say something and when it came through to the other caller.

The downside to everything running through the Sat Fi apps is that those apps are, frankly, ugly and a little confusing to set up and use. You’re going to have to RTFM. If you set everything up correctly, it works nearly flawlessly. But there are a lot of set up steps, and if you mess something up, it’s hard to tell what went wrong. My one hiccup, for example, was due to not selecting the right option in a drop down menu, and it kept me from making a data connection. It was an easy fix, but I couldn’t diagnose it myself because the interface just isn’t very intuitive. It all feels a bit industrial. And if someone is using this in an emergency type of situation, perhaps for the very first time, you want it to be easy.

But overall this is a really impressive product. It connects you with the rest of the world, where you previously could not. It’s a remarkable feat.

Come for the Oz-kicking, stay for the information [Pharyngula]

This is an excellent piece on that quack, Dr Oz, by John Oliver. The first 5 minutes is spent mocking the fraud, but then, the last ten minutes are all about the real problem: the evisceration of the FDA’s regulatory power over supplements, thanks to Senators Hatch and Harkin.

OK, there is a silly bit at the end where they show that you can pander to your audience without lying to them about the health benefits of magic beans, but still — let’s beef up the FDA, all right?

Molecule regulates production of antibacterial agent used by immune cells

Researchers have discovered how a protein molecule in immune cells promotes the production of nitric oxide, a potent weapon in the cells' arsenal to defend the body from bacterial attack. The protein may offer a target for reining in the inflammatory response, which must be able to fight infection without damaging tissue.

The study was published in the Journal of Innate Immunity.

NFATc3 is one of several related protein molecules known to play a role in regulating genes in the T and B cells of the immune system. Ravi Ranjan, research scientist at the University of Illinois at Chicago College of Medicine, who is first author on the paper, said he and his collaborators wanted to know if NFATc3 also had any function in macrophages -- specialized killer cells that hunt down, engulf and destroy marauding bacteria.

Macrophages kill using chemicals, including nitric oxide, that they synthesize in response to infection. Macrophages are also important in reducing the inflammation in sepsis, an out-of-control reaction to infection that can cause organ failure and death.

When the researchers exposed macrophages to chemicals that signal a bacterial infection, they found that NFATc3 increasingly bound to genes that boost the production of nitric oxide synthase -- the enzyme that makes nitric oxide. The binding of NFATc3 suggests the molecule is turning on those genes and upping the production of nitric oxide. Macrophages deficient in NFATc3 produced much less nitric oxide synthase under the same conditions.

"Without the ability to synthesize inducible nitric oxide synthase, a macrophage would be missing a key element of its chemical weaponry," Ranjan said. "We would expect these cells to be much less effective at killing bacteria and attenuating sepsis."

To test this hypothesis, the researchers then induced sepsis in mice that lacked the ability to make NFATc3. As expected, lung tissue from these mice had a much higher bacterial load than the lung tissue of septic mice that could produce NFATc3.

"Our study demonstrates that NFATc3 is required for macrophages to effectively fight infection, because without it, they can't make their primary bactericidal agent -- nitric oxide," Ranjan said.

The immune system must strike a balance between fighting infection and going overboard as it does in sepsis and actually causing harm, Ranjan said.

"An overproduction of nitric oxide can actually contribute to lung injury even as it helps clear bacterial infections," he said.

"An NFATc3 inhibitor, given as a drug to people in septic shock, may be a way to attenuate the harmful effects that come with an overproduction of nitric oxide."

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The above story is based on materials provided by University of Illinois at Chicago . The original article was written by Sharon Parmet. Note: Materials may be edited for content and length.

Safe water for the people in Tanzania

Hydraulic engineer Andrea Schäfer and photovoltaics expert Bryce Richards have developed a solar filtration system to produce high-quality drinking water from polluted brackish water and tested it successfully in Tanzania. The test results are currently being analyzed at the KIT. The filter effectively separates undesired substances, bacteria, and viruses. Fluoride concentration that often is extremely high in Tanzania is reduced below the limit given by the World Health Organization (WHO). The system combines two membrane techniques for the separation of smallest particles and dissolved contaminants. As it is robust and autonomously mobile, it is suited well for water supply in poor and rural areas.

Outside of the rainy season, the area of Mdori which is located in the north of Tanzania in the region of Manyara is extremely hot and dry. Water is scarce, the lake located nearby has an extremely high salt concentration. A well drilled to extract water from a natural spring supplies water with a high salt concentration and 60 µg of fluoride per liter -- 40 times the concentration limit given by the WHO -. This water is not potable. At this spring, Professor Andrea Schäfer and Professor Bryce Richards, who are now working at the KIT, tested their water filtration system ROSI (Reverse Osmosis Solar Installation).

The system can be operated with solar and/or wind power. It combines ultrafiltration membranes of about 50 nm in pore size to retain macromolecular substances, particles, bacteria, and viruses with membranes for nanofiltration and reverse osmosis with pore sizes below 1 nm to remove dissolved molecules from the water. Andrea Schäfer and Bryce Richards conceived ROSI in Australia and developed it further in Scotland before they started to plan their field tests at the Nelson Mandela African Institution of Science and Technology in Tanzania. In February and March this year, they tested the system at places like Mdori. Presently, Schäfer and Richards are evaluating the test results at the KIT. In the next phase, the systems will be installed at the locations selected.

As the system is run directly by solar power without batteries, the behavior of the filter changes as a function of the light conditions: Under full solar irradiation, the filtration system reduces the fluoride concentration of the water below the WHO limit of 1.5 mg/l. As a result of the change between day and night and strong temporary cloud formation in the region of Mdori, however, energy supply varies considerably. It is interrupted, if solar irradiation is insufficient. Influence of such fluctuations on water quality was one of the aspects covered by the tests of the researchers. "If less power is available, pressure decreases. As a result, less water passes the membranes. The fluoride concentration increases for a short term," Professor Andrea Schäfer explains. She heads the Membrane Technology Division of the Institute of Functional Interfaces (IFG) of KIT. "The concentration of fluoride and other pollutants, however, is balanced as soon as more water passes the filter again. Hence, the water is completely safe."

Andrea Schäfer and Bryce Richards, Professor of Nanophotonics for Energy at the KIT, are now looking for companies to support system manufacture and installation and operation in rural regions of Tanzania. One system can supply about 50 people with high-quality drinking water and water for household use. "At the moment, no other system removes pollutants, such as fluoride, as reliably and sustainably as ours," Schäfer says. High fluoride concentrations may cause tooth discolorations and severe skeletal deformities in children. It is also important to remove bacteria and viruses from the water. In many areas of Africa, diseases that actually can be treated well, such as diarrheal diseases, are often fatal especially for children due to malnutrition and lacking medical care. Supply with safe drinking water will play a key role for the future of the people in Africa.

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The above story is based on materials provided by Karlsruhe Institute of Technology . Note: Materials may be edited for content and length.

How botulism-causing toxin enters bloodstream

UC Irvine School of Medicine researchers have discovered the mechanism by which bacterial toxins that cause food-borne botulism are absorbed through the intestinal lining and into the bloodstream. Their study, which appears in the June 20 issue of Science, points to new approaches to blocking this poisonous substance.

Botulism is a rare and often fatal paralytic illness due to a neurotoxin produced by Clostridium botulinum bacteria, which can appear in rotted, uncooked foods and in soil. Listed as a Tier 1 agent by the Centers for Disease Control & Prevention, the botulinum toxin is also a potential biological weapon.

Using a crystal structure of a complex protein compound of botulinum neurotoxin, Rongsheng Jin, associate professor of physiology & biophysics at UC Irvine, and collaborators found that these compounds -- called clostridial hemagglutinin (HA) -- bind with epithelial cell proteins in the intestines of patients, which initiates a process that disrupts the close intercellular seals so that the complex toxin molecules can slip through the epithelial barrier.

"Normally, botulinum neurotoxin molecules are too large to break through this tight junction of epithelial cells," Jin said. "By identifying this novel process by which the toxin compound manages to open the door from inside, we can better understand how to seek new methods to prevent these deadly toxins from entering the bloodstream."

In further tests, he and his colleagues designed a mutated version of the botulism compound, based on the novel crystal structure, in which HA would not bind with the epithelial cell protein E-cadherin.

Remarkably, even though this lab-made toxin compound contains the fully active live toxin molecule, it was not orally toxic when tested on mice because the mutated HA cannot break up the intercellular seals and, therefore, the toxin compound cannot be absorbed through the epithelial layer.

Jin said this approach could lead to the identification of small molecules able to stop HA from binding with epithelial cell proteins, thus preventing the toxin invasion.

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The above story is based on materials provided by University of California - Irvine . Note: Materials may be edited for content and length.