Pittsburg secondary problem prompt: OK to talk about an intellectual problem?

[OdysseanUnderdog]

You are being thick-headed. Reread Goro’s post about being unteachable...
Stop. Putting. Your. “Hypotheses”. In. Secondary. Answers.
The question does not ask what your hypotheses were, it just asks for a time when you demonstrated lifelong learning. A (revised) version of the first paragraph you wrote about conducting your research would suffice.

Sigh...Ok. I will expand on that first paragraph as best as I can. Thank you for the reality check.

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[JustAUser]

Does this Kaiser secondary prompt offer any opportunity to talk about what I learned or hypothesized in addition to everything else it asks about? It instructs specifically to "Tell us about an area of intellectual exploration you are passionate about and have sustained over time." That sounds like it's asking applicants to describe the area of intellectual exploration a little, no? And maybe to give a flavor for why you're so passionate about it and have sustained it over time? Below is the full prompt, and then how I've begun my second attempt, attempting to integrate everyone's excellent feedback:

"Lifelong learning is an essential process for continued professional development in physicians that includes reflection and being open and responsive to constructive feedback. Tell us about an area of intellectual exploration you are passionate about and have sustained over time. What means have you used to explore this area? (250 Words)"

"I’ve read, written, and integrated findings and feedback from researchers about Alzheimer’s disease (AD) for >2,000 hours. I wrote a thesis, and then a paper. Reviewers requested revisions. I found the feedback helpful and used it to revise that paper and write a new one. Both await peer review. As evidence of my passion and sustained exploration, here’s what I’ve learned or found:...."


I feel like I've already answered all the other parts of the prompt with this opening. Could I use the rest to summarize some novel hypotheses I've developed based on other people's empirical findings, as evidence of passion and sustained exploration like the prompt asks about? Here's an updated version of what I could write for the rest, integrating feedback from @differentiating and others. Sorry if I'm being thick-headed! Just double checking, since I think this prompt is quite a bit different than the Pitt one and therefore worth asking about.


"As evidence of my passion and sustained exploration, here’s what I’ve learned/found: AD’s distal drivers are pathogens and oxidative stress. Viruses, bacteria, fungi accumulate in AD brains via immunosuppression. Amyloid-beta is antimicrobial. Innate immunity cannot distinguish between oxidized biomolecules and pathogens: interferons respond to viral DNA and cytoplasmic oxoDNA via cGAS. p53-deficient neurons secrete trans-synaptic exosomes bearing amyloid-beta, phospho-tau, and likely oxoDNA, sterile pseudo-viruses destroying synapses.

Oxidative stress is contributed to by diseases, stress, unhealthy lifestyle, pollutants, including combustion-derived nanoparticles, iron, aluminum. Activated by oxidative DNA damage, PARP1/PARG/TRPM2-produced AMP blocks ANTs, starving mitochondria of ADP—inhibiting ATP synthase. To survive, remaining AD neurons catabolize amino acids liberated from proteins via autophagy. Upregulated ALT1/2 convert L-Alanine to pyruvate and glutamate, fueling the Krebs cycle but promoting excitotoxicity, killing neurons and synapses.

Reflecting on this, it makes sense decades’ phase III clinical trials of amyloid-targeting therapies have failed. Only multicomponent treatment protocols will prevent, arrest, and reverse AD. A minimum viable set of likely indicated approaches includes antioxidant hydrogen, iron/aluminum chelators, DNase, PARP inhibitors, ADP, ALT-inhibiting hesperidin, extracellular vesicle uptake inhibitors (EVUIs), anti-retrovirals, anti-herpes drugs, anti-fungals, biofilm disruptors, gingipain inhibitors, lipopolysaccharide-targeting agents, interferon lambda, etc. administered intranasally to reach the brain."

Where possible, for those who are curious, I've added links to papers that give you one of many reasons why each approach might be indicated. 🙂

You still haven't answered the prompt and you need to get over your research.

I don't think you're understanding the feedback everyone has been telling you.
1) Read the prompt carefully and answer it.
2) Stop trying to shove your "findings" into every secondary. We get it that you spent a lot of time researching, but only include IF they ask you what you found. If they ask you what you learned, that's a totally different essay/response.
3) You really need to do a lot of introspection over this.


So AD is your intellectual pursuit. What have you reflected about it? Have you received constructive feedback? How did you handle it? How did you use it? How are you exploring your interests?
Nowhere does it ask you, "Please tell us your research findings?" Because that doesn't tell adcoms anything about YOU.

But don't change your essay because of us. It will help let the adcoms know that you can't read the prompt, introspect, and answer it accordingly. Despite all the constructive feedback you've received on here, you haven't applied any of it.

 

[OdysseanUnderdog]

You are being thick-headed. Reread Goro’s post about being unteachable...
Stop. Putting. Your. “Hypotheses”. In. Secondary. Answers.
The question does not ask what your hypotheses were, it just asks for a time when you demonstrated lifelong learning. A (revised) version of the first paragraph you wrote about conducting your research would suffice.

What about this?

I have read, written, and integrated findings and feedback from doctors and scientists about Alzheimer’s disease (AD) for >2,000 hours. I wrote a thesis, and then a paper, the latter of which I submitted to a journal. Peer reviewers requested revisions. I found their feedback extremely helpful and used it to revise the paper. I also write a whole new paper, integrating their feedback from the first draft. For example, they suggested focusing each paper on only one question at a time. Doing that significantly clarified and shortened my next drafts. Both the revised paper and the new one are awaiting peer review. If they are accepted, good; if not, I will continue integrating feedback and revising them, and making them better in the process. As I continue to write, I will continue to read and learn as well, as this project is an ongoing part of my overall practice of life-life learning.

 

[ThrowawayShmoaway]

I guess you’re on the right track now, but it could use some improvements and editing. I suggest rereading and really thinking about the below suggestions form JustAUser, because you still need to dig a little deeper

So AD is your intellectual pursuit. What have you reflected about it? Have you received constructive feedback? How did you handle it? How did you use it? How are you exploring your interests?

For example, did you ever face struggles in researching AD since it was DIY and not part of a structured program? Did that ever make you feel discouraged? How did you feel when you received feedback about your research and/or the writing? Did/do you feel like an underdog when submitting your paper(s) to a peer-reviewed journal (again, since it’s DIY and presumably not co-authored by an established researcher in the field)? If so, what have you learned about yourself and/or your passion for learning in the process?

 

[JustAUser]

That's much better. In addition to what ThrowawayShmoaway said,

You can expand more on what you wrote.
What caused you to be interested in AD? Do you know someone affected by it that sparked your interest?

How did you go about doing your research? Do you have a mentor on this project? Perhaps, you found one journal and did all your readings about AD from there and then someone guided you to another article/journal? What caused you to start trying to compile all the information you read and publish it, etc.

You probably get the point. You have a lot more space in your essay so take the reader through why you're interested in AD, what caused you to do further research and write about it, how you went about researching it, the constructive criticism you've received along the way and how you've incorporated it, reflections you've had, etc.

 

[TelemarketingEnigma]

What you're really missing right now, as others have mentioned, is the WHY. Why are you interested in AD? what drives you to research AD? It's totally okay if that answer is just "we learned about it in biology class and I thought it was interesting." Give us context for your research!

For additional context, you should talk about anything you've done related to AD outside of your personal research. Have you taken neuroscience classes? visited/volunteered at a nursing facility for patients with AD? shadowed a physician in the field? Attended a conference on the subject?

You should also talk about how your understanding of the subject has evolved over time. This does NOT mean listing out findings you've read about. Did you come into your research with a basic understanding of AD, or none at all? is the subject more complex than you first appreciated? has your research changed the way you view aging/memory/the human condition overall?

 

[ciestar]

OP, I just get the feeling you’re trying to show how smart you are in these responses. Once again, you’re failing to answer the questions. You’re hiding behind technical terms. This isn’t the place for that. Answer the question.. it asked about lifelong learning. You answer just that, don’t go into an abstract of research that nobody will read.

 

[Goro]

Does this Kaiser secondary prompt offer any opportunity to talk about what I learned or hypothesized in addition to everything else it asks about? It instructs specifically to "Tell us about an area of intellectual exploration you are passionate about and have sustained over time." That sounds like it's asking applicants to describe the area of intellectual exploration a little, no? And maybe to give a flavor for why you're so passionate about it and have sustained it over time? Below is the full prompt, and then how I've begun my second attempt, attempting to integrate everyone's excellent feedback:

"Lifelong learning is an essential process for continued professional development in physicians that includes reflection and being open and responsive to constructive feedback. Tell us about an area of intellectual exploration you are passionate about and have sustained over time. What means have you used to explore this area? (250 Words)"

"I’ve read, written, and integrated findings and feedback from researchers about Alzheimer’s disease (AD) for >2,000 hours. I wrote a thesis, and then a paper. Reviewers requested revisions. I found the feedback helpful and used it to revise that paper and write a new one. Both await peer review. As evidence of my passion and sustained exploration, here’s what I’ve learned or found:...."


I feel like I've already answered all the other parts of the prompt with this opening. Could I use the rest to summarize some novel hypotheses I've developed based on other people's empirical findings, as evidence of passion and sustained exploration like the prompt asks about? Here's an updated version of what I could write for the rest, integrating feedback from @differentiating and others. Sorry if I'm being thick-headed! Just double checking, since I think this prompt is quite a bit different than the Pitt one and therefore worth asking about.


"As evidence of my passion and sustained exploration, here’s what I’ve learned/found: AD’s distal drivers are pathogens and oxidative stress. Viruses, bacteria, fungi accumulate in AD brains via immunosuppression. Amyloid-beta is antimicrobial. Innate immunity cannot distinguish between oxidized biomolecules and pathogens: interferons respond to viral DNA and cytoplasmic oxoDNA via cGAS. p53-deficient neurons secrete trans-synaptic exosomes bearing amyloid-beta, phospho-tau, and likely oxoDNA, sterile pseudo-viruses destroying synapses.

Oxidative stress is contributed to by diseases, stress, unhealthy lifestyle, pollutants, including combustion-derived nanoparticles, iron, aluminum. Activated by oxidative DNA damage, PARP1/PARG/TRPM2-produced AMP blocks ANTs, starving mitochondria of ADP—inhibiting ATP synthase. To survive, remaining AD neurons catabolize amino acids liberated from proteins via autophagy. Upregulated ALT1/2 convert L-Alanine to pyruvate and glutamate, fueling the Krebs cycle but promoting excitotoxicity, killing neurons and synapses.

Reflecting on this, it makes sense decades’ phase III clinical trials of amyloid-targeting therapies have failed. Only multicomponent treatment protocols will prevent, arrest, and reverse AD. A minimum viable set of likely indicated approaches includes antioxidant hydrogen, iron/aluminum chelators, DNase, PARP inhibitors, ADP, ALT-inhibiting hesperidin, extracellular vesicle uptake inhibitors (EVUIs), anti-retrovirals, anti-herpes drugs, anti-fungals, biofilm disruptors, gingipain inhibitors, lipopolysaccharide-targeting agents, interferon lambda, etc. administered intranasally to reach the brain."

Where possible, for those who are curious, I've added links to papers that give you one of many reasons why each approach might be indicated. 🙂

I've encountered only one other SDNer like you, who was dying, just DYING to write about his research notions in his med school app. This person, like you, also did 100% library work and never set foot in a lab.

That person never got into med school.

You are still not understanding the prompts (both Kaiser's and Pitt's) and and appear to be obsessed with vomiting up your laundry list of every trial that tested some intervention with AD.

Just go to grad school already.

 

[Bonne Nuit]

OP, it seems like you're really struggling with drafting these secondaries. You're a capable scientific writer, no doubt, but you need to be able to "code switch" and adopt a different voice for secondaries.

Do you have access to a writing center or tutoring service, perhaps through your university? The tutors there can sit down with you and the secondary prompts and help you brainstorm appropriate topics. They can also help you outline, draft, and polish your final product. I think you might benefit from more intensive writing assistance, and that's beyond the scope of what SDN can help you with.

 

[deleted938090]

Only rationally-designed up-to-date multicomponent treatment protocols will ever prevent, arrest, and reverse AD. A minimum viable set of likely indicated approaches would include antioxidant molecular hydrogen, I-CAM1-catalase fusion peptide, nucleus-penetrating iron/aluminum chelators, TRPM2 antagonists, DNase, PARP inhibitors, ADP, potassium, hesperidin, extracellular vesicle uptake inhibitors (EVUIs), anti-amyloid-beta-oligomers, anti-retrovirals, anti-herpes drugs, anti-fungals, biofilm disruptors, gingipain inhibitors, lipopolysaccharide-targeting agents, interferon lambda, etc. all administered intranasally to reach the brain directly, plus whole-body hyperthermia or sauna and Mediterranean diet.

BREAKING NEW RESEARCH CONFIRMS PATHOGENIC ORIGINS FOR ALZHEIMERS. FIRST IMAGES BELOW

Spoiler

 

[OdysseanUnderdog]

I guess you’re on the right track now, but it could use some improvements and editing. I suggest rereading and really thinking about the below suggestions form JustAUser, because you still need to dig a little deeper

For example, did you ever face struggles in researching AD since it was DIY and not part of a structured program? Did that ever make you feel discouraged? How did you feel when you received feedback about your research and/or the writing? Did/do you feel like an underdog when submitting your paper(s) to a peer-reviewed journal (again, since it’s DIY and presumably not co-authored by an established researcher in the field)? If so, what have you learned about yourself and/or your passion for learning in the process?

That's much better. In addition to what ThrowawayShmoaway said,

You can expand more on what you wrote.
What caused you to be interested in AD? Do you know someone affected by it that sparked your interest?

How did you go about doing your research? Do you have a mentor on this project? Perhaps, you found one journal and did all your readings about AD from there and then someone guided you to another article/journal? What caused you to start trying to compile all the information you read and publish it, etc.

You probably get the point. You have a lot more space in your essay so take the reader through why you're interested in AD, what caused you to do further research and write about it, how you went about researching it, the constructive criticism you've received along the way and how you've incorporated it, reflections you've had, etc.

What you're really missing right now, as others have mentioned, is the WHY. Why are you interested in AD? what drives you to research AD? It's totally okay if that answer is just "we learned about it in biology class and I thought it was interesting." Give us context for your research!

For additional context, you should talk about anything you've done related to AD outside of your personal research. Have you taken neuroscience classes? visited/volunteered at a nursing facility for patients with AD? shadowed a physician in the field? Attended a conference on the subject?

You should also talk about how your understanding of the subject has evolved over time. This does NOT mean listing out findings you've read about. Did you come into your research with a basic understanding of AD, or none at all? is the subject more complex than you first appreciated? has your research changed the way you view aging/memory/the human condition overall?

Thank you all so much for the excellent feedback! 😍 I wrote this new version in large part based on @ThrowawayShmoaway's suggestions, since they got at aspects of the project that were very true that I hadn't already talked about in my primary. I also got in a non-redundant why statement and info about my advising situation as per @TelemarketingEnigma and @JustAUser. Other suggestions were also excellent, but I already talked about those topics in my primary to some extent. What do you think?

"I’ve read, written, and integrated findings and feedback from researchers about Alzheimer’s disease (AD) for >2,000 hours. This has been a challenging process because AD is infinitely complex and I didn’t do this as part of a structured program, so I had to be self-directed. To establish contact with experts, I emailed them without technically being one of their students; luckily, most graciously responded. I wrote a thesis, and then a paper, which I submitted, even though I felt like an underdog because I did not have an established co-author. Peer reviewers requested revisions. First, I felt disappointed. Then, though, I realized their feedback was helpful and used it to revise the paper. I also wrote a new paper, integrating their feedback from the beginning. For example, they suggested focusing each paper on only one question. Doing that clarified and shortened my drafts. Both the revised paper and the new one await peer review. If they are accepted, good; if not, I will continue integrating feedback and revising and improving them. Sometimes I’ve found the many setbacks I’ve encountered throughout this process discouraging, but every time, I’ve coped in a variety of ways to rejuvenate myself, and I’ve reminded myself of my hope that the ideas we’ve been working on will one day contribute to improving the prognosis or quality of life for patients with AD. That possibility has been enough to keep me learning through every obstacle."



To @ThrowawayShmoaway's questions, the answers are pretty much all yes, definitely. Thank you.

Here are excerpts from my primary that I think cover all suggestions I didn't address here, but please tell me if you think I could go more in depth, or could provide a better answer here! I've got 8 words left, and I could probably free up more if I needed to.



@JustAUser: "What caused you to be interested in AD? Do you know someone affected by it that sparked your interest?"

@Telemarketing: "What you're really missing right now, as others have mentioned, is the WHY. Why are you interested in AD? what drives you to research AD? It's totally okay if that answer is just "we learned about it in biology class and I thought it was interesting." Give us context for your research!"

From my PS: "I became interested in the biology underlying medicine seeing my grandfather suffer from Parkinson’s, which naturally made me want to understand neurodegeneration and do something about it….When I did not get accepted into medical school, in addition to improving my application in multiple ways, I responded by making concrete progress towards the goal of addressing the suffering of patients with neurodegenerative diseases by reading papers and writing a DIY thesis about the most prevalent neurodegenerative disorder: Alzheimer’s disease."

Like I said, it's basically that I saw my grandfather losing his mind to neurodegeneration, and I said to myself, "woah, this is terrifyingly evil, I feel the need to do something about this, but I don't know how". I focused on AD when I got the chance to instead of Parkinson's disease because AD is more prevalent. It's the bigger threat. It just seemed like the place to start, even though I realize it's so complicated that I might never get further than that beginning. But it's the frontline.



@JustAUser: "How did you go about doing your research?"

This is a good question, but I don't really know how to answer it beyond I read, I wrote, and I tried to figure out this disease and how to fix it. From my activities description of this though: "As I learned more and more though, I began to connect the dots between recent mechanistic findings and decades of neuropathology and imaging results, forming novel hypotheses of increasing sophistication….It was like seeing a ghost hiding in plain sight. Due to the possible implications for patients, I pursued this idea. I attempted multiple times to write about it, but it was more complex than anything I had attempted so far. Doctors and researchers gave me pieces of the puzzle I was missing, which allowed me to finally do it."



@TelemarketingEnigma: "For additional context, you should talk about anything you've done related to AD outside of your personal research. Have you taken neuroscience classes? visited/volunteered at a nursing facility for patients with AD? shadowed a physician in the field? Attended a conference on the subject?"

I used to visit my grandfather and uncle in facilities and interact with them and the other residents, for what it's worth. My wiley anatomy and physologicaly professor (who's also my independent study adviser) taught me how to conduct an action potential. An awesome doctor gave my grandfather glutathione, slowing the progression, which I was and still am very impressed by. And I was just on a layover in LAX while the Alzheimer's Disease Conference was going on there, lol. (That's what lit the fire under me to write another paper while travelling I think, lol.) 🤣



@TelemarketingEnigma: "You should also talk about how your understanding of the subject has evolved over time. This does NOT mean listing out findings you've read about. Did you come into your research with a basic understanding of AD, or none at all? is the subject more complex than you first appreciated? has your research changed the way you view aging/memory/the human condition overall?"

Yes! From my activities description: "…In retrospect, when I started, my knowledge of human biology was primitive. As I learned more and more though, I began to connect the dots between recent mechanistic findings and decades of neuropathology and imaging results, forming novel hypotheses of increasing sophistication…."

Commentary: In retrospect, I feel like I knew essentially NOTHING about AD or human biology when I started, to be blunt lol. Now I know dramatically more--just enough to know how little I really know compared to the overall picture. But I've felt up this whole elephant pretty good by now, so I've made some progress. 🙂

 

[OdysseanUnderdog]

I've encountered only one other SDNer like you, who was dying, just DYING to write about his research notions in his med school app. This person, like you, also did 100% library work and never set foot in a lab.

That person never got into med school.

You are still not understanding the prompts (both Kaiser's and Pitt's) and and appear to be obsessed with vomiting up your laundry list of every trial that tested some intervention with AD.

Just go to grad school already.

I will try to learn from their experience then. Sir, thank you, but I am a physician scientist but nature. It's med school or bust for me. 🙂

 

[OdysseanUnderdog]

OP, I just get the feeling you’re trying to show how smart you are in these responses. Once again, you’re failing to answer the questions. You’re hiding behind technical terms. This isn’t the place for that. Answer the question.. it asked about lifelong learning. You answer just that, don’t go into an abstract of research that nobody will read.

Fair enough, will do. Just FYI though, I am of average intelligence, and showing that off isn't my intention at all. Did Paul Revere going riding around because he wanted to show how smart he was? No, he did it because he felt like had to warn people the British were coming. Likewise, I feel the desire to warn the medical community that hordes of pathogens and oxidative stress-induced "undead/zombie" damaged biomolecules are coming to rot our patients' brains.

 

[ciestar]

Fair enough, will do. Just FYI though, I am of average intelligence, and showing that off isn't my intention at all. Did Paul Revere going riding around because he wanted to show how smart he was? No, he did it because he felt like had to warn people the British were coming. Likewise, I feel the desire to warn the medical community that hordes of pathogens and oxidative stress-induced "undead/zombie" damaged biomolecules are coming to rot our patients' brains.

That’s fine but a secondary isn’t the place to do that, which i believe you’re starting to realize. You’ve shown a passion for this research. You can really get this warning out by getting into med school and into a lab that does AD research and testing your hypotheses. If you were applying to phd programs, this would be different. You’re applying to be a physician.

 

[LizzyM]

The real prompt is "what means have you used to explore this area?"

We don't need to know that you spent 2,000 hours. We need to know if you've been in the lab, what techniques you used in the lab, if you've been in the library, if you've had challenges in finding materials or making use of papers published in foreign languages, if you've attended talks or conferences or poster sessions and had an opportunity to learn from other investigators, That is the sort of thing that they are going for. I think that the idea is that the means you use now to explore your area of interest will be the means you use going forward to learn about new areas of medicine as things will change during the decades that you practice.

 

[OdysseanUnderdog]

The real prompt is "what means have you used to explore this area?"

We don't need to know that you spent 2,000 hours. We need to know if you've been in the lab, what techniques you used in the lab, if you've been in the library, if you've had challenges in finding materials or making use of papers published in foreign languages, if you've attended talks or conferences or poster sessions and had an opportunity to learn from other investigators, That is the sort of thing that they are going for. I think that the idea is that the means you use now to explore your area of interest will be the means you use going forward to learn about new areas of medicine as things will change during the decades that you practice.

I’m working on getting into a lab, ma’am. Thank you for this feedback. I’ll think about and add in what I’ve got so far out of this very helpful list of experiences.

 

[Goro]

Did Paul Revere going riding around because he wanted to show how smart he was? No, he did it because he felt like had to warn people the British were coming. Likewise, I feel the desire to warn the medical community that hordes of pathogens and oxidative stress-induced "undead/zombie" damaged biomolecules are coming to rot our patients' brains.

I'm trying to say this in the nicest possible way:

It's not like neurologists aren't already aware of this, they just want some solid proof. I have good friends working in this area. We already know that there are multiple dementias, with multiple causes and confounders.

The idea that some pre-med who hasn't ever set foot in a lab is thinking that he is going "to warn the medical community " screams multiple pathologies and will lead to instant rejection if screeners and Adcoms get a whiff of this mindset.

You're not a neurologist
You're not a scientist
You're not a clinician
You've never tested a hypothesis
You don't understand simple prompt questions

You're somebody who has just collected a lot of library work, but can't apply what you have learned.

So here's a warning: get over yourself.

 

[TelemarketingEnigma]

"I’ve read, written, and integrated findings and feedback from researchers about Alzheimer’s disease (AD) for >2,000 hours. This has been a challenging process because AD is infinitely complex and I didn’t do this as part of a structured program, so I had to be self-directed. To establish contact with experts, I emailed them without technically being one of their students; luckily, most graciously responded. I wrote a thesis, and then a paper, which I submitted, even though I felt like an underdog because I did not have an established co-author. Peer reviewers requested revisions. First, I felt disappointed. Then, though, I realized their feedback was helpful and used it to revise the paper. I also wrote a new paper, integrating their feedback from the beginning. For example, they suggested focusing each paper on only one question. Doing that clarified and shortened my drafts. Both the revised paper and the new one await peer review. If they are accepted, good; if not, I will continue integrating feedback and revising and improving them. Sometimes I’ve found the many setbacks I’ve encountered throughout this process discouraging, but every time, I’ve coped in a variety of ways to rejuvenate myself, and I’ve reminded myself of my hope that the ideas we’ve been working on will one day contribute to improving the prognosis or quality of life for patients with AD. That possibility has been enough to keep me learning through every obstacle."

This is getting much closer to the type of thing you want to be writing, although I would keep working for a while on it before you submit anything. I don't mean to be harsh, but right now you come across as very naive about the research and publishing process, in this case in the way you're writing about peer review - I'm going to guess that pretty much any person who reads your application has been through the peer review process (except maybe if it's a school that lets med students read applications, and even then it's probably still true). everyone knows peer review can be harsh and disappointing, but it's also absolutely necessary (not just "helpful"). If I were you, I would focus less on describing the peer review process and more on the other things you mentioned in your post, such as the parts about your grandfather and other physicians you met with. Even if it's already mentioned in your personal statement or elsewhere, it doesn't hurt to reiterate it in this answer.

I've encountered only one other SDNer like you, who was dying, just DYING to write about his research notions in his med school app. This person, like you, also did 100% library work and never set foot in a lab.

Between the mythological username, saint bernard avatar, and interesting essay ideas, there's either some serious coincidences happening or OP may not be as new to SDN as they appear...

 

[OdysseanUnderdog]

I'm trying to say this in the nicest possible way:

It's not like neurologists aren't already aware of this, they just want some solid proof. I have good friends working in this area. We already know that there are multiple dementias, with multiple causes and confounders.

The idea that some pre-med who hasn't ever set foot in a lab is thinking that he is going "to warn the medical community " screams multiple pathologies and will lead to instant rejection if screeners and Adcoms get a whiff of this mindset.

You're not a neurologist
You're not a scientist
You're not a clinician
You've never tested a hypothesis
You don't understand simple prompt questions

You're somebody who has just collected a lot of library work, but can't apply what you have learned.

So here's a warning: get over yourself.

Thank you for the difficult feedback, Goro.

I apologize if I sounded like I needed to get over myself. Apprenticing to a long line of "messengers" is a humbling role, for me. But I appreciate being made aware that what I said could be interpreted that way, and I hear what you're saying that a lot of neurologists already know about the fungi, bacteria, and viruses more accumulated in AD patients' brains than in controls.

Nothing can ever be technically proven definitively according to philosophy of science--there's always room for doubt, no? But at what point is there enough evidence that action becomes indicated on a compassionate usage basis? People have been finding that AD patients have brain infections associated with the plaques since Dr. Oskar Fischer, the co-discoverer of AD.

Specific viruses and bacteria have been shown to increase amyloid-beta generation experimentally, and amyloid-beta oligomers propagate almost all aspects of AD, including tau phosphorylation and neurotoxicity, in animal models. This is strong evidence that pathogens are central mediators of sporadic AD etiopathogenesis. However, the question remains, why do these pathogens accumulate in AD patients' brains more so than in controls? Is it purely because of exposure? The other possibility is that AD patients' brains may be immunocompromised.

In response to your excellent point that I haven't yet tested a hypothesis (just formulated them) and your point about the lack of proof that AD brain infections play an etiological role in AD, I wrote (in between writing secondaries, etc.) and submitted a paper investigating these questions and tested this hypothesis: if AD brains are immunosuppressed, then there might be more genes related to immunosuppression that are upregulated than downregulated in AD patients' brains.

To test this hypothesis, I cross-referenced the 955 genes in the Human Immunosuppression Gene Atlas (biokb.ncpsb.org/HisgAtlas/) and the pooled meta-analysis of AD patients' brains genome-wide mRNA expression data available at AlzData.org. Sure enough, 161/958 immunosuppression-related genes were downregulated, whereas 381 genes were significantly upregulated, a statistically significant difference (p < 0.0001).

Then, I manually curated the upregulated immunosuppression-related genes. I found many potential upregulated mediators of immunosuppression, including the T-cell-inhibiting immune checkpoint proteins of cancer immunotherapy fame CTLA-4, LAG-3, Tim-3, and the PD-1 ligand PD-L2. Curious what could be underlying these changes, I analyzed the transcription factors binding to the promoters of these genes using the bioinformatics databases curated at Harmonizome. Comparing this transcription factor-promoter interaction data to changes in transcription factors observed in AD patients' brains to check for plausibility, I learned that STAT3 appears to be activated in the AD hippocampus and could promote 39/44 of the immunosuppressive genes examined.

I documented about a dozen upstream activators converging on chronic STAT3 phosphorylation that are upregulated along with pTyr705-STAT3 in AD brains, including LPS, IL-6 and IL-10. By integrating findings from neuropathology and mechanistic studies, I traced the increased IL-6 and IL-10 signaling in AD patients back to LPS and ectopic oxidatively damaged DNA. LPS accumulates in AD patients' brains, and Gram-negative bacteria have been found even in the hippocampi of normal controls. One of the primary drivers of the chronically elevated oxidatively damaged DNA in AD patients' brains is the iron and aluminum that has been found significantly accumulated in their hippocampal neural chromatin. Therefore, iron, aluminum, and Gram-negative bacteria exposure might be upstream distal drivers of immunosuppression in AD patients' brains, permitting downstream poly-pathogen infections and brain amyloidosis.

Future investigations should try to determine which comes first, the immunosuppression, or the pathogens. If AD immunosuppression driven by all-cause brain oxidative stress and LPS precedes the amyloidogenic poly-pathogen infections, which it could and arguably appears to do, then treating the infections will likely turn out to be necessary but not sufficient to prevent, arrest, or reverse AD. So if you happen to know anyone who can figure out how to make exosomally-delivered, small, hydrophobic nucleus-penetrating aluminum and iron chelators, please introduce us.

 

[PA_dud3]

Man, this thread is just too much, lmao.

 

[sm96]

 

[Lawpy]

 

[JustAUser]

Man, this thread is just too much, lmao.

You might as well lock the thread. Everything that has had to be said has been said and OP is just not getting the point

 

[differentiating]

Thank you for the difficult feedback, Goro.

I apologize if I sounded like I needed to get over myself. Apprenticing to a long line of "messengers" is a humbling role, for me. But I appreciate being made aware that what I said could be interpreted that way, and I hear what you're saying that a lot of neurologists already know about the fungi, bacteria, and viruses more accumulated in AD patients' brains than in controls.

Nothing can ever be technically proven definitively according to philosophy of science--there's always room for doubt, no? But at what point is there enough evidence that action becomes indicated on a compassionate usage basis? People have been finding that AD patients have brain infections associated with the plaques since Dr. Oskar Fischer, the co-discoverer of AD.

Specific viruses and bacteria have been shown to increase amyloid-beta generation experimentally, and amyloid-beta oligomers propagate almost all aspects of AD, including tau phosphorylation and neurotoxicity, in animal models. This is strong evidence that pathogens are central mediators of sporadic AD etiopathogenesis. However, the question remains, why do these pathogens accumulate in AD patients' brains more so than in controls? Is it purely because of exposure? The other possibility is that AD patients' brains may be immunocompromised.

In response to your excellent point that I haven't yet tested a hypothesis (just formulated them) and your point about the lack of proof that AD brain infections play an etiological role in AD, I wrote (in between writing secondaries, etc.) and submitted a paper investigating these questions and tested this hypothesis: if AD brains are immunosuppressed, then there might be more genes related to immunosuppression that are upregulated than downregulated in AD patients' brains.

To test this hypothesis, I cross-referenced the 955 genes in the Human Immunosuppression Gene Atlas (biokb.ncpsb.org/HisgAtlas/) and the pooled meta-analysis of AD patients' brains genome-wide mRNA expression data available at AlzData.org. Sure enough, 161/958 immunosuppression-related genes were downregulated, whereas 381 genes were significantly upregulated, a statistically significant difference (p < 0.0001).

Then, I manually curated the upregulated immunosuppression-related genes. I found many potential upregulated mediators of immunosuppression, including the T-cell-inhibiting immune checkpoint proteins of cancer immunotherapy fame CTLA-4, LAG-3, Tim-3, and the PD-1 ligand PD-L2. Curious what could be underlying these changes, I analyzed the transcription factors binding to the promoters of these genes using the bioinformatics databases curated at Harmonizome. Comparing this transcription factor-promoter interaction data to changes in transcription factors observed in AD patients' brains to check for plausibility, I learned that STAT3 appears to be activated in the AD hippocampus and could promote 39/44 of the immunosuppressive genes examined.

I documented about a dozen upstream activators converging on chronic STAT3 phosphorylation that are upregulated along with pTyr705-STAT3 in AD brains, including LPS, IL-6 and IL-10. By integrating findings from neuropathology and mechanistic studies, I traced the increased IL-6 and IL-10 signaling in AD patients back to LPS and ectopic oxidatively damaged DNA. LPS accumulates in AD patients' brains, and Gram-negative bacteria have been found even in the hippocampi of normal controls. One of the primary drivers of the chronically elevated oxidatively damaged DNA in AD patients' brains is the iron and aluminum that has been found significantly accumulated in their hippocampal neural chromatin. Therefore, iron, aluminum, and Gram-negative bacteria exposure might be upstream distal drivers of immunosuppression in AD patients' brains, permitting downstream poly-pathogen infections and brain amyloidosis.

Future investigations should try to determine which comes first, the immunosuppression, or the pathogens. If AD immunosuppression driven by all-cause brain oxidative stress and LPS precedes the amyloidogenic poly-pathogen infections, which it could and arguably appears to do, then treating the infections will likely turn out to be necessary but not sufficient to prevent, arrest, or reverse AD. So if you happen to know anyone who can figure out how to make exosomally-delivered, small, hydrophobic nucleus-penetrating aluminum and iron chelators, please introduce us.

I highly recommend you do some shadowing of physicians, because yes - neurologists, especially dementia experts, do more than just prescribe memantine and do neuropsych tests. Their notes & visits are infamously long because they do a holistic evaluation- they cover everything from diet to sleep (so many pts on citalopram) to mood, because they’re aware that it contributes.

It seems like you’re now changing your argument to infectious risk rather than oxidative stress, but regardless... to your point of how much science we need - we need evidence that benefit outweighs the risks. Antibiotic therapy has side effects, and if we don’t even know if it will actually help our patients, it’s not worth that risk. We took an oath to do no harm, and most of us practice evidence-based medicine because we’re not crazy homeopaths.

 

[Goro]

Thank you for the difficult feedback, Goro.

I apologize if I sounded like I needed to get over myself. Apprenticing to a long line of "messengers" is a humbling role, for me. But I appreciate being made aware that what I said could be interpreted that way, and I hear what you're saying that a lot of neurologists already know about the fungi, bacteria, and viruses more accumulated in AD patients' brains than in controls.

Nothing can ever be technically proven definitively according to philosophy of science--there's always room for doubt, no? But at what point is there enough evidence that action becomes indicated on a compassionate usage basis? People have been finding that AD patients have brain infections associated with the plaques since Dr. Oskar Fischer, the co-discoverer of AD.

Specific viruses and bacteria have been shown to increase amyloid-beta generation experimentally, and amyloid-beta oligomers propagate almost all aspects of AD, including tau phosphorylation and neurotoxicity, in animal models. This is strong evidence that pathogens are central mediators of sporadic AD etiopathogenesis. However, the question remains, why do these pathogens accumulate in AD patients' brains more so than in controls? Is it purely because of exposure? The other possibility is that AD patients' brains may be immunocompromised.

In response to your excellent point that I haven't yet tested a hypothesis (just formulated them) and your point about the lack of proof that AD brain infections play an etiological role in AD, I wrote (in between writing secondaries, etc.) and submitted a paper investigating these questions and tested this hypothesis: if AD brains are immunosuppressed, then there might be more genes related to immunosuppression that are upregulated than downregulated in AD patients' brains.

To test this hypothesis, I cross-referenced the 955 genes in the Human Immunosuppression Gene Atlas (biokb.ncpsb.org/HisgAtlas/) and the pooled meta-analysis of AD patients' brains genome-wide mRNA expression data available at AlzData.org. Sure enough, 161/958 immunosuppression-related genes were downregulated, whereas 381 genes were significantly upregulated, a statistically significant difference (p < 0.0001).

Then, I manually curated the upregulated immunosuppression-related genes. I found many potential upregulated mediators of immunosuppression, including the T-cell-inhibiting immune checkpoint proteins of cancer immunotherapy fame CTLA-4, LAG-3, Tim-3, and the PD-1 ligand PD-L2. Curious what could be underlying these changes, I analyzed the transcription factors binding to the promoters of these genes using the bioinformatics databases curated at Harmonizome. Comparing this transcription factor-promoter interaction data to changes in transcription factors observed in AD patients' brains to check for plausibility, I learned that STAT3 appears to be activated in the AD hippocampus and could promote 39/44 of the immunosuppressive genes examined.

I documented about a dozen upstream activators converging on chronic STAT3 phosphorylation that are upregulated along with pTyr705-STAT3 in AD brains, including LPS, IL-6 and IL-10. By integrating findings from neuropathology and mechanistic studies, I traced the increased IL-6 and IL-10 signaling in AD patients back to LPS and ectopic oxidatively damaged DNA. LPS accumulates in AD patients' brains, and Gram-negative bacteria have been found even in the hippocampi of normal controls. One of the primary drivers of the chronically elevated oxidatively damaged DNA in AD patients' brains is the iron and aluminum that has been found significantly accumulated in their hippocampal neural chromatin. Therefore, iron, aluminum, and Gram-negative bacteria exposure might be upstream distal drivers of immunosuppression in AD patients' brains, permitting downstream poly-pathogen infections and brain amyloidosis.

Future investigations should try to determine which comes first, the immunosuppression, or the pathogens. If AD immunosuppression driven by all-cause brain oxidative stress and LPS precedes the amyloidogenic poly-pathogen infections, which it could and arguably appears to do, then treating the infections will likely turn out to be necessary but not sufficient to prevent, arrest, or reverse AD. So if you happen to know anyone who can figure out how to make exosomally-delivered, small, hydrophobic nucleus-penetrating aluminum and iron chelators, please introduce us.

Wow, you just can't help yourself. You just had to present your thesis here...just had to.

Since you are indeed unteachable, putting on Ignore. You'll feel some slight pressure in the hippocampus.

 

[PA_dud3]

Alrighty, I feel like this thread has run its course. OP I wish you luck in your cycle/secondaries/manuscripts. Thanks to everyone for your input.