Video on optogenetic neural stimulation in experimental neuroscience

As I have mentioned before, my field of research focus and interest is neuroscience. One of the most interesting and exciting areas of investigation, in my opinion, is the use of optogenetics to identify neuronal function, effects of neural excitability on regeneration and other cool aspects of neuronal circuitry and anatomical/functional integration. This is not my area of expertise, but generally, the concept is simple in that mice are generated with genetic modifications that allow neurons in the nervous system to express light-sensitive channels (channelrhodopsin) on the neurons that all them to be turned on and off with application of light wavelengths. These channels allow neurons to respond to light as they would normally to neurochemical signals, sort of how the neurons in your retina are activated by light. There is more to it than that of course, but it is one of those things that is difficult to explain in words. Well, there is a journal online known as the Journal of Visualized Experiments (JOVE) that provides videos of many experimental procedures, models, and other topics and methods that really are better comprehended when described visually. A recent JOVE video article was published by Sidor et al. entitled, In vivo Optogenetic Stimulation of the Rodent Central Nervous System that really does a good job of describing how optogenetic rodent models are made and how they are utilized in research. For anyone who thinks this topic sounds interesting, this video is a treat. It is open access, which means it is free to watch and requires no subscription, so I recommend it to anyone who is interested as most JOVE videos are not open access. JOVE is a great resource for scientists and non-scientists alike, so if you like this educational resource, I recommend searching for other open access video articles on topics of interest. This really pulls back the curtains on science to some degree, which provides perspectives you just cannot get from written articles.

In vivo Optogenetic Stimulation of the Rodent Central Nervous System

Michelle M. Sidor1, Thomas J. Davidson2, Kay M. Tye3, Melissa R. Warden4, Karl Diesseroth2,5, Colleen A. McClung1

1Department of Psychiatry, University of Pittsburgh Medical Center, 2Department of Bioengineering, Stanford University, 3Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, 4Department of Neurobiology and Behavior, Cornell University, 5Department of Psychiatry and Behavioral Sciences, Stanford University

Getting your fix: Formaldehyde released from E-cigarettes

As smokers huddle in the winter cold outside of work, home, or pretty much anywhere these days to get their nicotine fix, the current availability and popularity in E-cigarettes has reduced some of the shame and self-consciousness associated with satisfying a nicotine habit. It is the toxic effects of burning tobacco and the other compounds in traditional cigarettes that are the primary offenders and emphasis of anti-smoking campaigns. E-cigarettes appeared on the scene within the past several years, and have gained popularity and increased use as an alternative by many smokers looking to try and kick the habit altogether or those just wanting a safer way to get nicotine than traditional cigarettes. Many in medical practice suggest these cigarettes are likely safer than old-fashioned tobacco cigarettes, and may serve as a useful alternative to help smokers quit cigarette smoking. Others withhold comment and recommend Food and Drug Administration (FDA)-approved nicotine replacement products (NRTs) such as Nicotrol inhalers, Nicorette gum or similar products (though E-cigs and NRTs were recently compared to assess what types of smokers choose one or there other as cessation tools).

It would seem that E-cigarettes, that come in a variety of styles and flavors, might be safer than cigarettes as they do not actually involve inhaling smoke but rather vapor from heating nicotine-containing liquids. However, with all non-FDA approved products, the buyer or user beware, as the actual contents of the products, and thus any potential hazards, do not have to be displayed on the products’ packaging. This has shielded general understanding of the both the benefits and risks of using E-cigarettes. Even so, the days of deregulated E-cigarette sales and use may be numbered.

A recent editorial article by Jensen and colleagues in the prestigious New England Journal of Medicine reported preliminary evidence that E-cigarettes actually pose a risk of producing toxic formaldehyde. This article is one of the first providing scientific documentation of clear risks associated with E-cigarettes. The formaldehyde results from the heating of the liquid which generally contains glycerol, propylene glycol, and nicotine as primary components. The super-heating of this liquid to produce vapor that is inhaled causes a chemical byproduct of a change in propylene glycol to fomaldehyde. Thus, when inhaling the vaporized liquid, intake of formaldehyde occurs.

For those unfamiliar with the uses of formaldehyde, it is used as a fixative for preserving animal tissue or cells for microscopy in scientific research. It is also used as a preservative in resins added to wood and wood-based products used in construction. Formaldehyde is also a known human carcinogen as recorded by the International Agency for Research on Cancer. The researchers of the published study in the New England Journal stated that, based on their evidence, a person vaping 3 ml of liquid per day would inhale approximately 14 mg of formaldehyde each day in formaldehyde-releasing agents. The amount of formaldehyde suggested to be in one pack of cigarettes is about 3 mg. The authors of the paper indicate that, all things considered equal between traditional cigarettes and E-cigarettes, the risk of cancer due to formaldehyde intake from E-cigarettes could be from 5 to 15 times higher than the risk from traditional cigarettes. Things are not equal between these two products, however, so much research is still needed to fully understand the risks of formaldehyde intake from E-cigarettes. Importantly, this study will likely push efforts to regulate E-cigarettes further faster which will likely be a good thing overall.

Potential treatment for problems associated with chronic kidney disease

Chronic kidney disease can be highly debilitating and even life-threatening. It is often linked to onset of other diseases including diabetes and cardiovascular disease. An interesting and promising new study by Park and colleagues in AJP: Regulatory, Integrative and Comparative Physiology (DOI: 10.1152/ajpregu.00409.2014) suggests a compound called tetrahydrobiopterin (BH4) may have possible action in reducing cardiovascular risk factors for those with chronic kidney disease. The study was covered nicely in Science Daily yesterday, so if you get the chance to take a look at the study and the coverage. Though the study was relatively small and further research is needed, it is a nice first step.

Vitamins reduce gastric cancer risk, but don’t forget your fruits and veggies!

I have a friend that once ate nearly half a bottle of adult gummy multivitamins because they were essentially gummy bears, and how could gummy bears hurt anyone? Thankfully, all was ok, but this highlights an overarching debate over the risks and benefits of multivitamins and vitamin or other over the counter supplement. One problem with any over the counter vitamin or supplement is the lack of Food and Drug Association (FDA) evaluation and approval of the contents or statements made on the label of such products. You think you could be getting high-quality Vitamin D3, but be getting powdered pencil shavings stuffed in a capsule. Seriously. Though there are obviously more reliable commercial sources of vitamins and supplements than others, this lack of protective oversight has limited research and the overall medical community’s enthusiasm for endorsing certain products for patient use. This is not to say research on vitamin intake has not been performed, as many studies on specific vitamin effects in various human diseases and conditions exist in the scientific literature. In fact, some researchers consider certain vitamins and supplements, should be considered pharmaceuticals and be labeled accordingly due to potential toxicity and overdose side effects. Again, this requires FDA oversight

With this said, there is evidence for therapeutic benefits for regular intake of over-the-counter vitamins, and one recent study by Kong et al. (Dec. 2014, Vitamin Intake Reduce the Risk of Gastric Cancer: Meta-Analysis and Systematic Review of Randomized and Observational Studies. PLoS ONE 9(12): e116060) showed that intake of vitamins reduced risk of developing gastric cancer. The study was a retrospective systematic review and analysis of published clinical studies including a wide variation of patients of different ethnic backgrounds, ages, and times they were followed. Ultimately, 47 studies and over 1,000,000 subjects were included in the analysis. Data assessed from the studies included study design, location, subject age, gender, study period, control subjects in case-control studies, sample size, types of vitamins assessed and intake method used in the study. Other factors such as whether studies were blinded (keeping doctors and patients in the dark about treatments to reduce bias) quality of the methods, and other concerning sources of bias were taken into consideration in this study. You have to pay attention to all of these factors, as patients and researchers have a good way of convincing themselves of things they may believe to be true, whether they are or not.

As an aside: For your benefit, when reading a study look to see if the analyses (or at least some) were blinded, there are good controls (placebo treatments) or other control which should have no effect (negative control) and sometimes positive controls (where a desired effect is expected for comparison) are used. These can help you interpret the validity of the study, the data collected, and discussion and statements made about the data from the study. Sometimes even the statistical tests used may be inappropriate, but even scientists do not know which stats should be used in all scenarios. Bottom line, be aware and be educated. This work is to help the people, in principle, and we are the people.
At any rate, this study seems to be solidly constructed, but has some limitations as almost all studies do. Interestingly, 29 of the 47 studies should an inverse association between the amount of vitamins (general) and the risk of developing gastric cancer. In other words, taking vitamins = less gastric cancer. For dose-response of independent vitamins, 1.5 mg/day Vitamin A, 100 mg/day Vitamin C, and 10 mg/day Vitamin E were linked to a significantly reduced risk of gastric cancer development (36% reduction for Vitamin A, 35% for Vitamin C, and 32% reduction for Vitamin E). These are not super-high amounts, in fact they are relatively low, but still the reduced gastric cancer risk is there.

A key finding from the analysis was that Vitamins FROM FOOD (veggies and animal sources) reduce the risk better than synthetic supplemental vitamins. I think this is quite logical, and matches well with the dosing from the studies that seemed to lower risk. The authors refer to suggestions from others that bioavailability is different between food sources and supplemental sources, which might account for this finding. Vitamins A, B, C, and E all seemed to lower risk of gastric cancer, but not Vitamin D. The study only included 5 case controlled studies for analysis, so the information may have been limited for a firm conclusion.

The authors state the strengths of the study are its large analyzed patient population and this is the first study like this to find a dose-dependent relationship between these vitamins and gastric cancer risk. Limitations highlighted are the variable study populations and time periods and flawed design of some of the studies analyzed. In this sort of analysis, it is hard to control for everything, and I think the strengths outweigh the weaknesses presented in this study.

So what are the take-aways from this article? Low doses of vitamins can lower risk of gastric cancer, and that food sources of these vitamins may be better at this than dietary supplements like multivitamins. The dosing emphasized from the analysis is consistent with what you might get from food items, so this is reasonable. Also, fruits and vegetable intake has been linked to reduced gastric cancer risk, so this strengthens the case.The FDA has approved food intake, assuming from the need to eat to survive, which is a plus based on the findings of this study. Basically, no need to worry about whether you getting the right vitamins (or vitamins at all) from supplements if you want to reduce gastric cancer risk. So go out and buy a bunch of colorful fruits and veggies, balance your diet well to reduce risk of other health issues, exercise, and you will be on your way to a you with lowered risk of gastric cancer and perhaps other types of cancer. Hats off to Kong and colleagues for this interesting and well-done study.

Writing is to science as...

You could plug in multiple analogies to finish this blog title, as long as your choice represents one part as an integral and undeniable requirement for the other. Writing, whether it is for disseminating one's research results to others or for securing research funding through grant proposals, is a large part of any researcher's career. It may come as a surprise how little training in effective scientific writing is provided to graduate students, post-doctoral scientists and other career researchers. Most of my training came from "trial by fire" experience submitting papers and proposals for peer review. I can say, to the credit of this approach, is that you learn quickly where your faults and weaknesses are in your writing. On the downside, your critics are often quite harsh and a thick skin is required. Although to forge a successful career in academic research you will ultimately need this outer shell, a safer and perhaps more consistently constructive mechanism should exist for training.

An article on a New York University course taught by Professor Stephen Hall of the Arthur L. Carter Journalism Institute was brought to my attention and it seems this course is quite popular and useful. It is a series of workshops geared toward teaching effective writing skills for reporting in fields of science and technology. Though it appears the course is quite intense and the instructor can be quite critical (and expects his students to do the same), this is still a good place to learn with less at stake among a small peer group. Also, the students in the course can be from quite different disciplines, which forces everyone to try and write in ways that can be understood by a wide audience while still getting key points across. This is the ultimate goal in scientific writing, especially for grant writing where much of the review panel may not have expertise in your particular field of research. Making the topic relevant to non-experts is a valuable skill, but one that is difficult to master.

As it turns out, analogies are one of the most effective ways for scientists and researchers to explain their concepts and findings in written publications and reports. When you think about how scientists acquire writing skills, pay attention to how clear and concise the next science article you read seems to be. If you cannot figure out heads from tails based on what the author has written, it may not be your fault. The author may have never had the proper training to easily get the point across to a wide audience. However, that doesn't mean they are off the hook. It seems more and more courses like the one at NYU are popping up, so maybe training in scientific and technical writing will improve for researchers and you may not have to primarily take scientists at their word. I believe this will improve transparency of scientists' work for the public, and help readers independently interpret findings while appreciating the reasoning and interpretation put forth by the researchers. For now, keep training yourself to discern great scientific writers from poor ones and scientists will hopefully keep doing the same.