A Reflection of My Neurochemistry Experience

The experience I had in my neurochemistry capstone incorporated more of the goals for liberal learning than any other class I have taken at Concordia. Although I am biased, as I have always had a passion for neuroscience and believe that is has so many answers to questions that are raised in today’s society, I do not doubt that my classmates would similarly agree.
Each week of class we were given a scientific literature review to read and ask questions about. The beginning of the week started with a general discussion about the paper and questions that we had about the paper. As a class, we accumulated a list of topics we did not quite understand in the paper and/or wanted to know more about. At the end of class, we divided this list amongst us so that we would each be responsible for investigating a specific topic for the following class. Then, at the next class, each of us would teach our classmates about the topic we had researched more about. This information helped us to grasp the concepts of the paper far better than we had on the first day. Finally, at the end of the week, the class divided into two large groups to discuss the paper. There were not any rules to the conversation; in fact, we often strayed from the topic of the paper (eventually finding our way back).
The topics that we covered throughout the semester ranged from concussions, to autism, Alzheimer’s disease, to marijuana use, obesity, to alcoholism. The neuroscientific literature that exists in correspondence to these topics is incredible, and immensely important to progressing forward in learning about these issues. Until we learn how the body’s most important organ (again, biased), the brain, is involved in these diseases or addictions, we cannot make advancements towards treatments, or therapies, or prevention strategies that address these national and worldly issues.
The class encouraged me to pull information from so many areas of my liberal arts education as well as my own experiences. I was inspired to use my prior education as well as my new knowledge of the topics to contribute to our fascinating discussions. Actually, this was my last class on Fridays, and I always left class with our discussion still buzzing in my head hours (or sometimes even days) later. I felt that our in-class discussions stimulated within me a sense of responsibility I had to society to address these issues, even if that was simply through spreading the word about the information I had obtained.
In my opinion, neuroscience has so many answers and can contribute to putting society on a path where we are consistently “bettering” ourselves. I view neuroscience as a way to discover treatments for neurological disease and raise community awareness about neurological disorders so that we are more accepting of others, ultimately leading to a more cohesive and tolerant country.

Autism and Xenobiotics

“Methylation and redox buffering activities are equally supported by the methionine cycle and transsulfuration during normal redox conditions. [However], during oxidative stress multiple adaptive mechanisms shift the flux of sulfur resources toward GSH synthesis, including reduced activity of methionine synthase, increased activity of cystathionine-b-synthase (CBS) and decreased activity of cysteine dioxygenase (CDO). Lower methionine synthase activity reduces methylation, including dopamine-stimulated phospholipid methylation and its role in attention.”
For some readers, this paragraph might be slightly overwhelming. However, the phrases that are most important to pay attention to for the rest of this blog are italicized; normal redox conditions, oxidative stress, reduces methylation, role in attention. What do these phrases have in common? They are all important pieces in the story of autism.
Autism is a developmental disorder that affects the brain’s normal development of social and communication skills. The exact number of children with autism is unknown, but the number of diagnoses seems to be increasing. However, it is also unknown whether this is because the disorder is becoming more prevalent in the population or because there is an increased ability to diagnose the disorder.
There is little known about what causes autism, but scientists speculate that xenobiotics, or chemicals found in the body that are not normally produced by it, play a role in the development of the disorder. Researchers speculate that environmental insults (chemicals) promote oxidative stress and reduce methylation that leads to developmental delays and attention deficits as well as a lack of synchronization of neurons that is characteristic in autism.
This raises a concern for the chemicals that we encounter throughout our daily life, especially when these chemicals have such adverse effects on our bodies. It makes you wonder what other diseases these chemicals can induce in our bodies. Out of my own curiosity, I did the inevitable, and Googled it. What I found was slightly disheartening. The Agency for Toxic Substances and Disease Registry divides the bodies systems into categories and lists possible contaminants that might affect that particular system and where these contaminants might be found. For example, lead had negative effects on the renal system and can be found in old paint and outdate plumbing and nickel may adversely affect the skin and can be found in cement. The list was already quite extensive and it did not even include all the chemicals that we can be exposed to in our lifetime.
I sometimes wonder if society is so concerned with making life “easier” and more “efficient” that we forget that those things that might make life easier or more efficient for us also contain contaminants, contaminants that can harm our families and us. Or, for example, induce a disorder in children that negatively affects their social development and attention abilities.
If further research accumulates evidence pointing to certain chemicals that induce autism in children, will efforts be taken to take these chemicals off of the market? Due to the economics, I sometimes wonder if the necessary steps would be taken to do so, but ethically, it must be done.

Reflecting on A Cobber's Capstone Experience

When I first registered to take Neurochemistry I was nervous to say the least. At the same time as taking Neurochemistry I was also enrolled for Biochemistry. I felt at a real disadvantage since I had no prior Biochemistry background and my experience with biology and anatomy was on par with a 7th grade health class (or at least it felt like it to me). My adviser and professor of the class assured me that the class would turn out fine for me. Skeptical, I entered the class with expectations that the course would entail heavy lectures and horrendous assignments. I was meet with a completely different experience. The class turned out to be a lot more low-key and individualized than a regular class.
Lecture was not the main focus of the course. The idea behind the class was all about becoming an independent learner, someone who is capable of reading a scientific research article and critically analyzing the aspects of the research. The class was very much discussion based and I must say it was one of the best discussion based courses I have participated in. It was hard not to find something to talk about. Our topics, such as: obesity, alzheimer’s disease, alcohol, autism, opioid addiction, and concussions, allowed us to extend our discussions to the realms of sociology, psychology, chemistry, and personal experience.
Because I was taking Biochemistry at the same time of this course, the two complimented each other well. Often in Neurochemistry we would discuss a topic looking at specific pathways, enzymes, neurotransmitters, and proteins which I would later hear about in Biochemistry (mainly because Biochemistry progressed kind of slowly). I was able to take what I learned in Neurochemistry and use that to help me understand the basics, which I received in Biochemistry. It sounds a little odd that studying such in-depth topics would actually help me understand the fundamentals of Biochemistry, but because I was able to connect the basics with an application I could see the importance of what I was learning. This application of Neurochemistry to other areas of science and life was one of the major reasons I enjoyed the class.
Compared to the all the classes I have taken up to this point, Neurochemistry wasn’t the hardest class but it did demand and push me the most. Blogging was in part one of the reasons that Neurochemistry pushed me. I have to say I wasn’t the most comfortable with having blogging as an assignment. The one thing blogging did do for me which I appreciated was cause me to reflect on the topics discussed in Neurochemistry. If you didn’t know Concordia College is all about reflecting on one’s personal experiences and this capstone class definitely encompassed this mentality. This class allowed me to apply chemistry outside of chemistry. I was able to broaden my view outside of a simple restricted tunnel. Neurochemistry in a way revitalized my love of chemistry, because I was able to make connections with chemistry to areas I would have never thought could be related. Overall, I enjoyed my capstone experience and will take with me that science, specifically chemistry, has far more application in society that may be apparent at first glance.

It's More Than Just a "Choice"

Approaching a stoplight, you see a homeless man standing on the corner where you are about to make a left turn. He is holding a piece of cardboard that says, “Homeless. No food. No money. Anything helps.” You cannot help it, your mind instantly goes to the assumption that the five dollars you could give him sitting in your wallet will go straight to the liquor store because the man MUST be an alcoholic. Although it’s understandable why some people might assume this, the effects of such assumptions are completely unfair. The stigmas that arise from these assumptions are unfair to the person and do nothing to help them get back on their feet.
I have often wondered why diseases that involve, for example, the heart or the lungs seem to be “socially acceptable”. Is this because, historically, there has been a more biological, medical explanation for such diseases? Sometimes, I feel that this is the case. It seems that when society has a scientific explanation for a disease or disorder, we are more willing to accept and understand what the person is going through. For example, society is more willing to accept someone who has coronary artery disease or emphysema because we recognize that these diseases are out of the person’s control, that it is not their CHOICE to have intense chest pains or a chronic cough. More recently in our history, disorders of the brain are also becoming more accepted and understood by the public, such as bipolar disorder or schizophrenia. Instead of believing that the person is simply “moody”, or “crazy”, we understand that their brains do not function as the “normal” person’s does. This means that society is more willing to understand their condition and exerts effort to help the person maintain a normal lifestyle through therapies and/or medications.
Unfortunately, this is not yet the case for addictive disorders such as alcoholism. Society places a great stigma on those who are addicted to drugs and/or alcohol, which does nothing to help the person or the country as a whole. We are quick to associate alcoholism with bad choices and irresponsibility. “Why can’t they control their drinking? I can..” are questions that may often be raised when encountering someone who has a history of alcoholism. What society does not understand is that, just as coronary artery disease and bipolar are diseases that can be “explained” scientifically  (although much is still unknown about the diseases), so too are addictive disorders. Genetics and environment have an affect on the body and on a person’s susceptibility to become addicted to drugs and/or alcohol. Too often we assume that it is simply a matter of choice for a person to quit abusing drugs or alcohol, but we forget that far more is occurring within that person than we could ever understand without experiencing the addiction ourselves.
Not only does science explain why addicts experience an almost unbearable withdrawal from substances when they try to quit or refrain from using, but science can also point to childhood experiences and environments that increase a person’s likelihood of experiencing addictive substances and their susceptibility to addiction. When we understand that addiction is more than just a “bad choice”, we are more willing to understand and be empathetic towards a person’s state of wellbeing rather than climbing aboard our high horse and passing judgments on them.
This week in class we reviewed a scholarly literature review that looked into the chemical and biological mechanisms that played a role in a person’s susceptibility to alcoholism as well as the dysfunctional mechanisms that exist in the disorder. Alcoholism is so much more than simply a “bad choice”. Yes, it IS a person’s choice to take a sip of alcohol, but it is naïve to believe that this is the only piece of the story. Just as we accept those with other diseases, we must also accept those who have addictions, as neither the person or the country move forward until we do.

Capstone Culmination

As I look back on my capstone in chemistry experience, I am glad that I was able to take part in this class.  Capstone courses are meant to tie several disciplines together while encouraging engagement in the world, and I think we achieved these goals throughout the course of the semester.  This blog is one way in which we have been able to express our thoughts about the topics covered in our class discussions.  Writing about science in this style has been a unique experience.  As a chemistry major, I have been accustomed to writing in a style that is usually a little more formal and quite a bit more structured.  Being able to communicate scientific knowledge with others is one of the hallmarks of being an effective scientist.  If one possesses knowledge but cannot express it in a way that is meaningful to others, one may just as well not possess this knowledge at all.  After reading an article each week, discovering more about the contents of the paper on my own and with the help of my classmates, and discussing the topic at the end of the week, this blog was another way to capture my thoughts. The things I enjoyed most were the class discussions that we had each week and how we, as students, were responsible for a large portion of the class.
To me, the role that we, as students, took in this class made it a class that could only be undertaken by students that are ready for a capstone experience.  This class most likely would not have been as successful if taken by a group of underclassmen.  From the beginning of the semester, we were responsible for discovering things on our own, using resources of our choosing.  Not only were we responsible for finding this information, we then were charged with explaining this information and teaching it to our classmates.  Once we started discussing academic articles each week, we had a large amount of input as to which topics needed further investigation, each person reported to the class on these topics, and took turns drafting questions that would serve as a guide for an engaging discussion with our classmates.
Class discussions can be very helpful and productive when done in the right way.  As a student, and in life in general, it is easy to think of discussions that are neither helpful nor productive.  Many students dislike group activities in classes, for a variety of reasons.  Some of the chief complaints are that their fellow students don’t participate, participate to the point of dominating the discussion, are unwilling or unable to listen to or validate their classmates’ thoughts and ideas, aren’t prepared, or take comments made by others too personally.  None of these complaints seemed, to me, to be an issue during this class.  Each of us took turns acting as discussion leaders, so we had a mutual appreciation for the amount of extra work put into preparing for class.  After spending time researching and learning about the deeply scientific, academic facets of each topic, it was nice to have time in which we could explore the effects that recent developments and further research might have on society.  We were able to engage in dynamic conversations each week, because we entered the discussions with similar intentions.
 

Colors of the Rainbow – A Look at Autism

Autism is more common today than ever before.  According to the Autism Science Foundation, prevalence of autism was reported as 1 in 10,000.  During the nineties, it decreased to 1 in 2,500 and eventually 1 in 1,000.  In 2012, the Centers for Disease Control and Prevention cited the occurrence at 1 in 88 (see http://autismsciencefoundation.org/ for more information about autism).  These rates have increased for several different reasons.  Classification criteria have changed, technology in diagnosis methods have become more sensitive, awareness of the disease has increased, and parents have become more engaged in their children’s diagnosis process. Autism is diagnosed and treated along a spectrum.  The causes, symptoms, diagnosis, and treatments for individual cases of autism can be quite varied, thus autism is often referred to as a spectrum disease.  Recently, Asperger’s syndrome was repositioned underneath the umbrella of autism.  An individual with this form of autism would experience life quite differently than an individual with autism in which development delays in areas such as cognition and language are key characteristics.

Photo courtesy of http://www.cornwall.gov.uk/default.aspx?page=27969

With the increased visibility of autism, many people have become more understanding of individual behaviors.  Society today is putting more emphasis on awareness about numerous diseases, autism included.  Increased awareness corresponds with an increased sensitivity to the issues individuals have and the needs associated with these issues.  Inappropriate behavior in class or other socials situations would normally garner a matching social consequence.  Usually, disciplinary action or another negative reaction would be the typical result.  Special provisions and protocols may be put into place for those with social and neurological disorders.  This sets the precedent for different social behaviors in response to irregular behavior that is due to a condition such as autism.
Like many other disorders, autism is thought to have both a genetic and environmental component that predisposes someone to be at risk for developing the disorder.  In the article we read on autism, it was hypothesized that a variety of environmental factors can cause oxidative stress at the cellular level.  These environmental factors, however, do not affect all individuals the same.  Oxidative stress results only for those who are genetically vulnerable.  This is a relatively small set of individuals compared with the population as a whole.  Oxidative stress results in problems with methylation which affects genetic expression, resulting in delayed development and, in some cases, autism as well as dopamine receptor action that results in decreased neuronal synchronicity impairing attention and cognition, a hallmark of autism.
As diagnosis methods become more precise, more knowledge about the individual at the molecular level is gained, and helicopter parents become more perceptive to the medical needs of their children, increases of neurological disorders are being observed across the board.  The question is ever more becoming, How will we define normal?  Will each individual that has even the slightest deviation from the genotypic norm be classified as having a disorder?  With so many variants and possibility for differentiation within our species, it seems that at one point or another, each of us must surely be abnormal once we look hard enough and to the most specific degree.  I believe that what counts the most is how our idiosyncrasies affect the quality of our daily life and functioning.  When a biological abnormality results in an inability to function as one desires, many believe this is what legitimates taking an action to reverse these effects through medication, therapy, or other means.

More Than Just Social Drinking?

Culture plays a role in the use of alcohol.  Alcohol serves as a social lubricant, as it has across different cultures and time periods.  Although alcohol appears as a common thread in the tapestry of varying societies, its expression may differ from place to place and time to time.  This social practice has the profound ability to affect one’s health, either for the better or the worse.  While some drink alcohol for its immediate effects, prolonged usage can affect the neurological wiring of the brain.  The driving force for drinking changes, and metabolic processes can become affected.  While genetic predispositions and personal behaviors certainly play a large role, the role of society and culture should not be ignored.
In class conversation, we discussed the role of alcohol in our own community.  Fargo-Moorhead is a community that supports alcohol and enables those that are especially susceptible to alcoholism.  As a college community, the bar industry definitely appeals to the college demographic.  This community has specials unlike any community I have ever heard of.  On any given night, one could find a bar selling drinks for $2.50 and much less.  Friday nights at the Old Broadway: 2 hours of 10 ounce draft beers for the same cost in pennies as the date.  Bucks and The Bar give away 40 and 48 ounces, respectively, of almost any beverage (beer, mixed drinks) for free, weekly during the month of one’s birth.  Many bars have set up text clubs to inform their patrons when their specials are.  Bars give away free shots at the door when special texts are shown, advertise trips to Vegas, 70” TVs, and other events to lure individuals to their establishment.  Big D’s advertises 2-4-1 and for an extra dollar, a third drink.  Mug nights, dollar-you-call-its, and the list goes on.  Not only does our society support drinking, it supports binge drinking.  With an age limit of 21, drinking in America has turned into something that is done irresponsibly in secret until they are legal and something one does in great excess once they become legal.

Photo courtesy of http://www.123rf.com/photo_10217817_italian-salami-parmesan-cheese-bread-and-wine.html

We also discussed countries where the legal drinking age was lower and alcohol was integrated into culture more than in the United States.  In Italy, it is common to have an alcoholic beverage with dinner nightly.  When used in moderation, such as in this instance, alcohol can actually be healthful for an individual, including reduced risks of coronary heart disease, type 2 diabetes, and some types of cancer.  In Ireland, the institution of the pub is a pit-stop between home and work for many.  This practice is somewhere between the Italian and American examples.  While college American culture exhibits occasional to frequent binge drinking and Italian culture exhibits a single frequent, if not daily, drink, the Irish example appeared, to us, to be an example of frequent, if not daily, moderate drinking.
Photo courtesty http://www.123rf.com/photo_10217817_italian-salami-parmesan-cheese-bread-and-wine.html

Even at the level of minimal drinking, the brain is affected.  Receptors associated with reward are stimulated, so the individual feels the effects of ethanol to be positive ones.  The body’s inhibition system is compromised, and the feeling can be quite liberating.  Ethanol literally enables a different state of mind for those consuming alcoholic beverages.  Prolonged use and abuse of alcohol, however, can damage the body.  By stimulating the same parts of the brain with great repetition, one begins to develop a tolerance to ethanol.  Higher levels are needed to attain the same level of reward in pleasure centers of the brain.  Acetaldehyde, a product of breaking down ethanol for use by the body, alters the cell at the molecular level and can change which genes are turned “on” and “off” by transcription factors.
In addition to the problems alcoholism itself can cause, the number of diseases that exist in comorbidity with it is cause for great pause.  Although used as self-medication by many, alcohol use can actually aggravate other mental health problems.  Socialization and cultural norms are important in the decisions individuals make and the impact those decisions can have on one’s health.  Alcohol is a drug that has the capacity to affect and change the way the mind and body function.  When it comes to consuming alcohol, moderation is key, no matter what the cultural norm tells you.

Capstone? What's a capstone?

At the start of the semester, other than knowing I had to take a capstone course in order to get my degree, I had absolutely no idea what I was getting myself into.  Little did I know, the neurochemistry capstone that I had signed up for would become one of my favorite courses I’ve taken in my college career.  Not only was the material very interesting, but the style of the course was entirely different from any other course that I had previously taken at Concordia and was in fact very favorable for learning.
 
Prior to taking this class the normal class structure that I had participated in consisted of lecture style teaching with around four tests and some quizzes thrown in the mix.  Neurochemistry was an entirely different class, as it prompted discussion and problem solving from the students as we explored a vast array of neurochemistry related topics ranging from neurodegenerative diseases to alcoholism.  We started the course by exploring a different neurochemistry topic each class period and submitting information that we found onto an online page so we could learn the material cooperatively as a class.  Once we learned the basics of neurochem we started diving into scientific papers that dealt with different disorders and used problem-solving skills to dissect the papers and obtain a common understanding of the topic.  We finished each week with a class discussion about each paper that engaged everyone’s thoughts and opinions as we discussed each paper.  I thought this was a very nice change as it prompted us to learn the material because we wanted to learn it rather than learning material that we weren’t as interested in.  It was also very nice to be in a relatively small class that was very comfortable with each other so we could easily share our opinions and present new material that we had learned with the class.
 
My favorite part of the course was the fact that we tied each topic into our society.  This made the topics much more interesting because we could relate to each different point and talk about how we thought each disorder affected our society as a whole.  Simply due to this fact we were definitely practicing Concordia’s liberal learning concept known as BREW, or becoming responsibly engaged in the world.  Throughout the whole class we looked at different disorders that affect the lives of many individuals in our society in an attempt to understand just what neurochemical processes were flawed and if there would be any way to cure the disorder.
 
Overall I thought this was a great course for so many reasons.  It is one that will definitely be helpful in the future as we go out into the world and engage in society and are forced to use our problem solving skills in order to make the world a better place.  This class definitely developed my problem solving skills, as well as my ability to be able to communicate very complex information in an understandable manner.  All in all the capstone experience was a great one!!

Is the complex world we live in a possible cause of the rising cases of autism?

Our final neurochemistry topic of the semester focused on the developmental disorder known as autism.  Autism is a very interesting topic because its cause can be due to so many different events and it is relatively hard to get a concrete diagnosis.  The general definition of autism states that it is a disorder of neural development characterized by impaired social interaction and communication.  The paper that we explored outlined two particular hypotheses for the cause of autism, looking at both the genetic factors as well as the possibility of different environmental factors present in the causing of autism.
 
The world that we live in is becoming increasingly complex as science develops new ways to build different products with new materials that often contain both heavy metals and xenobiotics.  Xenobiotics are simply chemicals that people can come in contact with and the main heavy metals that our paper focused on were arsenic, lead, and mercury. Combining these heavy metals and xenobiotics with genetic predisposition there is an extreme risk for the development of autism.  I will start out by briefly describing the science behind the hypotheses outlining the development of autism.  The development of autism starts out with either genetic factors or the exposure to heavy metals and xenobiotics causing impaired sulfur metabolism.  This impaired sulfur metabolism then inhibits the activity of methionine synthase causing decreased methylation of DNA, ultimately resulting in developmental delay and autism.
 
One of the main topics that we talked about in our discussion dealt with diagnosing autism and what this does to the social status of a child.  Diagnosing autism can be very difficult because the symptoms can cover a very broad spectrum ranging from very severe to very minor.  It is very hard for parents to know when to take their children into the doctor to get examined because it’s hard to know for sure if your child is simply in an awkward stage of development or is in fact suffering from the developmental disorder known as autism.
 
I personally have a family friend who was diagnosed with Asperger syndrome, which is an autism spectrum disorder that is very similar to autism but can be less severe.  In my friend’s case, he had a very awkward childhood and struggled socially prompting his parents to take him to the doctor, ultimately to be diagnosed with Asperger’s.  He now has grown up substantially and if you didn’t know that he had been diagnosed it would be impossible to tell that he has an autism spectrum disorder but he will forever have the title of having Asperger’s.  This is just one example showing the difficulties of diagnosing autism spectrum disorders and how hard it must be to label a child with autism.
 
It will be very interesting to see whether or not the number of cases of autism will continue to increase at the rate it is today now that scientists are uncovering more and more information on the causes of autism and whether or not they will be able to come up with a way to either prevent autism or treat individuals that are already suffering form the developmental disorder.

Liberal learning at its finest: Concordia College Neurochemistry

In a typical class for a core requirement at Concordia College there is usually a new perspective, a new skill, a new set of knowledge, or even a new language is learned. In my studies in chemistry I would not expect to learn the theologies of Islam, ancient Greek myth, or the development of the medieval castle in Europe but I was surprised to find great interest in these subjects and many others. The liberal arts learning have instilled in me a love for learning as is the first goal of liberal learning at Concordia. To top off the liberal arts major we must take a capstone class in a topic of our choice. I chose to take Neurochemistry as it related to my major field of study. This class has been stimulating and challenging and I am grateful for the opportunity to take it.
The class does something that most others do not, we stick our heads out into the scientific community and grasp onto multiple subjects trying our best to understand them. This is a skill that I will need for my career as I will be reading and writing the same type of scientific publications we tackle. Not many classes are able to provide this type of experience as they rarely peek out of the textbooks and assigned book readings mostly because the other core classes are at the 100 to 200 level, basic classes. Neurochem throws us into a world without a textbook causing us to learn for ourselves, be resourceful, and depend on each other as a team to understand the complex publications that we read. We cannot simply refer to the textbook to solve a problem or solidify a concept we cannot understand because these papers are often illustrating cutting-edge research that has yet to be recorded in texts mostly because even the researchers are not 100% confident their conclusions are the correct answer to the problem. This allows us to also form opinions when we can look at multiple hypotheses relating to one subject. This helps me for my career in chemistry as I will have to form my own hypotheses about new projects that I will undertake as a graduate student and beyond.
What I really enjoyed about my capstone experience is the component of learning from my peers. Every week we dissect a paper and assign different sections that the class is struggling to understand to each person in the class. Then we come back in a few days and present what we learned after researching the topics assigned to us. Through this technique we are learning from each other’s interpretation of the material and therefore it has been simplified and summarized so we may understand it better. This will be something that is very helpful to multiple careers as it will most likely come up that we will have to present some information, reports, etc. to our colleagues and peers.
Overall, the class has been a great experience in teaching me new material in a new way, broadening my learning abilities, perspectives, and knowledge base. I have come away with greater analytical skills and the ability to dissect complex topics into simpler terms in order to understand them and move forward.

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