CharonY

Antibiotics. Bacterial diseases were a major killer, where even small wounds could be fatal or lead to loss of limbs. Use of antibiotics made us mostly safe from bacteria (at least compared to what used to be the case). Now, we managed to throw it so much around that it may very likely not work in the relatively near future. Most of us had to use antibiotics sometime in their life and even if someone did not, the fact that other people around them were not chronically sick assisted in that (a bit like the herd effect for immunizations). Labeling seems to have no effect whatsoever considering that the amount of use has increased over the years. I do think it is likely that more regulations (and actual enforcement) may come up. But I am pretty sure that until public opinion changes (i.e. consumers vote with their wallet) the food industry will fight tooth and nail. I am not even blaming the farmers as on their end Ag is a cut-throat business. Not using any advantage they can get could sink them.

First, as StringJunky indicated, ABs do not create resistance, they select for it. Resistances emerge by mechanisms such as mutations and horizontal gene transfer. I.e. resistance has to be present in the population to begin with. However, without ABs they do not confer any fitness advantage and will stay in low amounts (which reduces the risk of multiple resistances, which is the real issue here) and do not spread further or may vanish over time again. At lethal doses the selection is strong, killing off all sensitive strains while only those with resistance survive (there are exceptions like persisters and biofilms, which I will ignore for now). However, at sub-lethal doses (what that level is may differ from strain to strain), it still creates a selective advantage for the already resistant, but gives the sensitive ones still the chance to gain resistance (e.g. by horizontal gene transfer) or to accumulate sufficient mutations that they spontaneously become resistant. So while the selection is weaker, it still exist. And considering that the pool is much larger, as the concentrations are found in wastewater, aquifers and soil, whereas lethal doses mostly at point of application, the overall impact is likely to be higher (as newer research starts to suggest). For example, the amount of resistance genes in soil increase significantly after applying manure. Also, it has been known for years that wastewater sludge is a massive pool of rseistance plasmids that are able to spread resistance rapidly. These plasmids have found to confer resistances to a wide range of ABs at the same time, which, again is the real issue here. The food improvement seems to be due to the actions of ABs on gut biota, therefore as long as they affect bacteria, they will affect resistance. The only way to stop it is to use something else (such as hormones, which is also not ideal). Also there are not good regulations in place that I know of. E.g. in Germany the use of ABs for livestock was banned, however the actual use has not decreased a bit. Farmers just declare it for therapeutic use and continue to use it to fatten up livestock. The amount of ABs in effluents has, increased in most countries rather than decreased. And yes, it has been used for years. And that is one of the reasons why we suddenly find multiple resistant strains popping up in many places and slowly and steadily run out of antibiotics to use. There are some last-line antibiotics that are only used if the patient does not react to any other treatment (such as vancomycin). But recently strains with resistances against those have been found, too. From a disease standpoint, this is nothing short of a disaster. About 10-20 years ago we were in good spirit and were talking about the arms race between chemists and bacteria to develop ever new ABs to combat resistances. The arrival of multiple resistant strains, coupled with high genetic mobility has show over the last few years that we are losing. Badly. In the 90s about 10% of infections were resistant to treatment. Today we are easily above 50% and last-line antibiotics have seen a rise in use (which means they are not last-line anymore). At the same time, the development and production of new antibiotics have been declining and there are many reasons for that. Although crucial, it has become harder and harder to develop antibiotics to which bacteria are sensitive but does not harm the patient too much. The Obama administration has initiated funding for development of new drugs (which is mostly claimed by small companies). But most working on this field know that it is just a band-aid. If we continue to do what we are doing we are promoting resistances at a vastly higher rate than we can hope to cope with. Alternatives to ABs are being developed, but there is nothing that is no killer treatment yet (and even then we do not know how resistances may evolve and how we may screw it up again. We had the means to overcome bacterial diseases in our hands and we manage to turn it into shit (almost literally). If that sounds gloom and doom to you, I feel like that because I have been following the lit for years. In contrast to things like ebola scares the numbers, unfortunately, add up. Almost all areas imply resistance increase and we see little incentives for us to reduce it to crucial (i.e. therapeutic uses). It is a sad fact that most likely people will only start thinking about it once we actually monitor deaths related to resistances in more detail. Current clinical practice does not always collect this data. But estimates in the US are on the order of 20k deaths (2013) associated with resistant strains, of which over half are Clostridium difficile. What is worse, however, is that in non-fatal diseases the number of reported multiple resistances are also increasing, not only locally, but globally (the WHO gave a report last year, I think). Unfortunately I think the time to react was about 15 years ago.

Actually, that entry is rather bad in this regard as the source it cites is rather poorly sourced itself (not your fault, rather a general issue of encyclopedia). It is based on estimates that are themselves based on estimates within surveys. But that being said, it hints at a different problem, AB use almost worldwide is not regulated and monitored well enough (although countries, including China are starting to pick it up since the last couple of years). But obviously it would make a lot of sense since India are the most populated countries and are also areas where production is outsourced to. It is likely that the US would be roughly next on the list. But as John mentioned, stopping the use of AB for meat production would cut shit tons of ABs from the environment.

I am wondering why you are specifically naming India and China. This practice is common everywhere. Ca. 75-80% of antibiotics used in the US are used on livestock (as opposed to medical use). Or are you talking about production? In that case it should be noted that these are US or EU-owned. They just moved their manufacturing sites overseas. A few countries in the US are starting to ban the practice but from I have heard it is still in common use (I think either Denmark or Sweden being one of the exceptions). But blaming countries is just silly. Rather, blame our desire for cheap meat.

Also, at therapeutic concentrations it is actually harmful for growth. Also even if used only at lethal concentrations, manure and other effluents would still be a source of sub-lethal concentrations of antibiotics (as it is quite stable and will be released to the environment. I.e. there is no use of AB that would entirely prevent the rise and spread of resistances (though rate is, as pointed out, likely to be slower if minimized). Or to make it more specific, the largest (in terms of total volume) reservoir of resistance determinants is not in a treated person/animal or meat (even if applied at sub-lethal doses) but rather wastewater and similar effluents. In these matrices a massive amount of e.g. resistance plasmids and similar sources of mobile resistance elements have been found. In terms of impact the direct transmission in hospitals is of course the largest concern.

Well, now it is moving from the microbiota to infectious diseases. If that is of interest to you maybe start a new topic? While common it is as much a normal part of the human microbiota as, say Plasmodium palcifarum (causative agent of malaria).

Well, OP seems under the impression that therapeutic use of ABs are the reason for the rise of multiple-resistant strains whereas John highlighted that we actually throw massive amounts of ABs around for production reasons. Also jajrussel still seems to ignore that point and thinks it is about keeping cattle healthy. It is not as the amount used are too low dosed to have therapeutic effects. It just makes them fatten faster (the same way growth hormones were used before bans),

Absolutely, and there is more. Antibiotics are released as waste and manure into soil and aquifers and create selective situations there, and I think that these may even be larger pools of resistance determinants. Also, in many mass production facilities animals are culled rather than treated as it is cheaper that way.

Well Toxoplasma are parasites spread by cats (and also they are not bacteria). But the point is that as many other pathogens they infect host cells. This is what the normal flora is not able to do (provided the host does not have some severe condition, which would disrupt the flora). The same argument can be made for viruses (e.g. infected blood samples) etc. But again, it would be a topic separate from the normal microflora.

I think we start off on a point of agreement but the conclusions you draw and especially the extrapolations you make(people would die if they exchanged floras) are quite different. There are various degrees of what you may perceive as chaotic interactions and there are underlying mechanisms. For example, every birth incorporates transplantation of the gut biota, so to say. It is by far something drastic. Every time you take antibiotics you re-arrange your flora as another example. The process of establishment of biota is under investigation and it is not a total random process.

I am not so sure about the rigid part. It depends on how you are able to carry them and how strong you are. But assuming you try to move a body of roughly your own size and are not terribly strong it is easier to have some muscle tone to assist. Unconscious people for example are very floppy and it is hard to get a good grip on them.

The thing is that most companies often do not care too much about the content of your degree, provided you fulfill their basic requirements. Some positions require technical skills that you should demonstrate but other than that just layering degrees does not necessarily make you a more attractive candidate. Rather, you should check what they want (go to job fairs, read job postings, get into contact with companies, network) and position yourself accordingly. A degree is just a badge, that alone will not sell your person.

There is also a spray but it is diluted with inert substances are added to make it more stable. It is recommended not to shake it but but it is not because it may explode. Rather, air bubbles can form that mess up the dosing. In short, it is provided in low concentrations, and stabilized with other substances to render it completely non-explosive.

Typically urine has a pH range of about 4.4-8. Low pH can have a lot of various sources, and if only for a short time not unusual. But aside from measurement errors drinking too much alcohol, or water loss (not drinking enough, diarrhea, sweating or other forms of dehydration), starvation and a umber of medical conditions can result in low urine pH.

You are missing the point that there are constant interactions between host and the bacteria. There are constant changes occuring at any minute. You use soap, you change the properties of your hand massively. You eat something, your gut sees a massive change in nutrient levels. Yet there is a kind of an equilibrium happening (which can change). The difference between biological systems and an engine is that it is very sturdy and can react very well to distortions. A transplant is generally used when the patients has some conditions that put their biota out of whack leading to rise of unfavorable communities that e.g. may promote further inflammatory actions. In the best case the new biota eventually settles to a new system that hopefully gets rid of most the harmful ones that initiated. So regardless of your feelings about it, it actually works and does not kill the host. Also note that if your biota changes during your own development and what settles on you is based on what you are exposed to. If there is only one specific community that is safe for you, it would mean your chances of dying from infection just after birth would be massive. The fact is that we can accommodate a wide range of communities although there are certain groups that tend to settle stably in the various niches of our body. And it is far from total chaos, or at least, about as chaotic as other ecological studies. Or look at it that way, your skin is so similar to mine that exchanging our bacteria would have little effect (they will in either case be various compositions of Staphylococcus, Propionibacterium, Streptococcus, Pseudomonas, Corynebacterium (and a few others that I forgot) as the major candidates. Unless you have a certain genetic condition of your skin for example, the composition may shift once it is exchanged but that is about it.

Nope, as already pointed out, fecal transplants are in medical use and our human physiology is so similar that the overall properties of microflora are not drastically different (though the composition does vary a bit). If we were that sensitive to bacterial load, any amount outside of a sterile room would kill us.

Morphologically you cannot distinguish the metabolic capacities of the bacteria. There is also no correlation with size. Also, cell size can vary signficantly within a species, depending on nutritional status (especially in those with marked length growth).

Why is a 1 in 10 dilution 0.01?

I think I see the reason for the confusion on side effects. You have added in the list a few drugs that affect blood clotting in a very different (and sometimes global) way. Those may have side effects. However, those similar in function (i.e. polymer applied to wound to promote sealing and/or clotting) to the one in the article are generally known to be safe. And since the mechanism is very similar any side effects are likely also to happen to the one proposed. So I guess we can agree that we are not talking about something new or revolutionary but a new application that may (or may not) show improvement over existing products. The impact will have to be shown in future (as it may have yet unknown issues that make it less or not more effective than what we have today).

Why do you think that the other products have more severe side effects? Metastudies indicate no negative effects on a variety of sealents and hemostatics (at least for polymer based ones). Also it is very similar to claims from other polymers used to promote the coagulation cascade. Again, the description does not highlight uniqueness to me. I am not saying there isn't but from the tidbits so far I do not see it. Maybe it is faster? But then I would need clinically performance data as in vitro tests are for these types of reactions usually not very conclusive. From what I understand they are still in the pre-trial phase. Not surprisingly, they do not disclose actual relevant data at this point (which is normal procedure). To me, revolutionary would require some unique and novel function. It seems to have both benefits of sealants and heomstatics, but again, detailed performance data would be required to see whether it is any better than what you can get. At least none of the functions are new by itself. On top of it there are a large range of hemostatics under trial (or just coming out of) so it certainly is not a product that exists in isolation. And some older ones have more clinical data to indicate utility (or lack thereof), which, from my understanding, is not available yet for this product. From what I can see the most unique aspect is the age of the CEO. To summarize, from the short sales pitches there is little in term of uniqueness. You cannot even claim that it has less side effects as those have not been tested yet. That would be the role of trials. A thing that is also lacking in the pitch is to separate them from their competitors. At least I would have expected a statement that it acts much faster than other polymers or something to that effect. In order to show impact, they would need to demonstrate the clinical utility, which, based on the article, has not been established yet. Edit: note that the article itself even highlights another, similar product. Also, rubbing it into the wound does no good. It requires to be injected into the wound. Hemostatics that work on the surface and are part of trauma bandages (such as cellulose based systems) already exist. So if you think that part is revolutionary, then you are about 10 years late to the party (could be off, but by 2008 there was already a lot of data from already commercialized product, so quite some time before that I guess).

I am not sure about the precise properties but considering that there are other hemostatics I do not see it as revolutionary per se. Maybe it has some added benefits (ease of use maybe?) that would make it an improvement over existing products. The article itself is a bit light on the science to be certain.

We had this discussion already. We also discussed the massive outbreak expected to swamp US and Europe it is easy to extrapolate the scariness of it. The reality is different, of course. All recent cases that were not controlled were (as expected) in Guinea, Liberia and Sierra Leone while being contained or gone everywhere else. And there is a slow down in new infections. Those outside of the countries were mostly health workers in contact with patients and the most recent case was in Italy who is now confirmed to be healed. Certainly, the situation in the outbreak countries is bad and as others have noted for a number of reasons. But let's look at numbers again (cases/deaths), data from June: Mali 8/6 Nigeria: 20/8 Senegal: 1/0 Guinea: 3674/2444 Liberia 10666/4806 Sierra Leone 12965/3919 So despite the fact that the disease is raging in three countries, it is well contained. As others have said, ebola is so characteristic and only infectious when symptomatic, it is much easier to stop than other diseases (say avian or swine flu variants or even HIV or hepatitis). Let us look at the developed worlds: Italy: 1/0 Spain: 1/0 United Kingdom: 1/0 United States of America:4/1 Same picture, even if in contact with many people (as in at least one US case) none of the people living with the patient contracted the disease. In almost all cases the afflicted persons were involved in handling late-stage persons (e.g. family members). Note that even without quarantine there is no global threat of ebola. While much harder to contract, and being on the decline Hiv has lead to 1,500,000 deaths worldwide in 2013, for example (do not have 2014 numbers). Contrast this with a total of 11,184 ebola deaths from the outbreak 2014 to June this year. Of course the burden is massive on these countries and they need every help they can get, which IMO is the part we should concentrate one (as opposed to the panicky non data-driven part).

Hrrrnnngggh. I am not sure what is worse. The joke or the fact that I tried to zoom in to check whether there are no errors.

Actually I would not be that sure. I have seen ligation of oligonucleotides referred to as polymerization. The most common example being in vitro use, such as joining of various templates or creation of functionalized polymers. The wording is tricky but I would probably allow both answers as, (to my knowledge) the term is typically not used in an extremely narrow sense.

Also the case overseas from what I see and hear. Having a direct contact goes a long way toward getting a job. And I agree, it hard work to get a job.