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(Image caption: The orbitofrontal cortex (blue) and medial temporal cortex (red) were more similar in terms of thickness in youths with Conduct Disorder than in typically-developing youths, suggesting that the normal pattern of brain development is disrupted. Credit: Nicola Toschi)

‘Map’ of teenage brain provides strong evidence of link between serious antisocial behaviour and brain development

The brains of teenagers with serious antisocial behaviour problems differ significantly in structure to those of their peers, providing the clearest evidence to date that their behaviour stems from changes in brain development in early life, according to new research led by the University of Cambridge and the University of Southampton, in collaboration with the University of Rome “Tor Vergata” in Italy.

In a study published in the Journal of Child Psychology and Psychiatry, researchers used magnetic resonance imaging (MRI) methods to look at the brain structure of male adolescents and young adults who had been diagnosed with conduct disorder – persistent behavioural problems including aggressive and destructive behaviour, lying and stealing, and for older children, weapon use or staying out all night.

In particular, the researchers looked at the coordinated development of different brain regions by studying whether they were similar or different in terms of thickness. Regions that develop at similar rates would be expected to show similar patterns of cortical thickness, for example.

“There’s evidence already of differences in the brains of individuals with serious behavioural problems, but this is often simplistic and only focused on regions such as the amygdala, which we know is important for emotional behaviour,” explains Dr Luca Passamonti from the Department of Clinical Neurosciences at the University of Cambridge. “But conduct disorder is a complex behavioural disorder, so likewise we would expect the changes to be more complex in nature and to potentially involve other brain regions.”

In a study funded by the Wellcome Trust and the Medical Research Council, researchers at the University of Cambridge recruited 58 male adolescents and young adults with conduct disorder and 25 typically-developing controls, all aged between 16 and 21 years. The researchers divided the individuals with conduct disorder according to whether they displayed childhood-onset conduct disorder or adolescent-onset conduct disorder.

The team found that youths with childhood-onset conduct disorder (sometimes termed ‘early-starters’) showed a strikingly higher number of significant correlations in thickness between regions relative to the controls. They believe this may reflect disruptions in the normal pattern of brain development in childhood or adolescence.

On the other hand, youths with adolescent-onset conduct disorder (‘late starters’) displayed fewer such correlations than the healthy individuals. The researchers believe this may reflect specific disruptions in the development of the brain during adolescence, for example to the ‘pruning’ of nerve cells or the connections (synapses) between them.

As the findings were particularly striking, the researchers sought to replicate their findings in an independent sample of 37 individuals with conduct disorder and 32 healthy controls, all male and aged 13-18 years, recruited at the University of Southampton; they were able to confirm their findings, adding to the robustness of the study.

“The differences that we see between healthy teenagers and those with both forms of conduct disorders show that most of the brain is involved, but particularly the frontal and temporal regions of the brain,” says Dr Graeme Fairchild, who is an Associate Professor in the Department of Psychology at the University of Southampton. “This provides extremely compelling evidence that conduct disorder is a real psychiatric disorder and not, as some experts maintain, just an exaggerated form of teenage rebellion.

“These findings also show that there are important differences in the brain between those who develop problems early in childhood compared with those who only show behavioural problems in their teenage years. More research is now needed to investigate how to use these results to help these young people clinically and to examine the factors leading to this abnormal pattern of brain development, such as exposure to early adversity.”

“There’s never been any doubt that conditions such as Alzheimer’s disease are diseases of the brain because imaging allows us to see clearly how it eats away at the brain,” adds Professor Nicola Toschi from the University “Tor Vergata” of Rome, “but until now we haven’t been able to see the clear – and widespread – structural differences in the brains of youths with conduct disorder.”

Although the findings point to the importance of the brain in explaining the development of conduct disorder, it is not clear how the structural differences arise and whether, for example, it is a mixture of an individual’s genetic make-up and the environment in which they are raised that causes the changes. However, the researchers say their findings may make it possible to monitor objectively the effectiveness of interventions.

(Image caption: GLT-1, a glutamate transporter, soaks up glutamate (a neurotransmitter) released by neurons and converts it back into a safer substance. Credit: Wilson lab, UC Riverside)

Researchers Unpack How Toxoplasma Infection Is Linked to Neurodegenerative Disease

Toxoplasma gondii, a protozoan parasite about five microns long, infects a third of the world’s population. Ingested via undercooked meat or unwashed vegetables, the parasite infects 15-30 percent of the US population. In France and Brazil, up to 80 percent of the population has the infection.

Particularly dangerous during pregnancy – infection in pregnant women can cause serious congenital defects and even death of the fetus – this chronic infection has two components: the unicellular parasite, and inflammation of tissues it causes.

Working on mice (like all mammals, a natural host for this parasite), a University of California, Riverside team of biomedical scientists reports in the journal PLOS Pathogens that Toxoplasma infection leads to a disruption of neurotransmitters in the brain and postulates that it triggers neurological disease in those already predisposed to such a disease.

They note that Toxoplasma infection leads to a significant increase in glutamate – the primary and most important neurotransmitter in the brain, which transmits excitatory signals between neurons. This glutamate increase is “extracellular,” meaning outside the cell, and is strictly controlled by specialized cells in the central nervous system (brain and spinal cord), called astrocytes. Glutamate buildup is seen in traumatic brain injury as well as highly pathological and neurodegenerating diseases such as epilepsy, multiple sclerosis and amyotrophic lateral sclerosis (ALS).

One role astrocytes play is to remove extracellular glutamate, lest it increase to pathological levels that could damage neurons. This is primarily achieved using a glutamate transporter, called GLT-1, tasked with regulating extracellular glutamate. GLT-1 soaks up glutamate released by neurons and converts it back into the safer substance glutamine, which can then be used by cells for energy.

“When a neuron fires it releases glutamate into the space between itself and a nearby neuron,” explained lead researcher Emma H. Wilson, an associate professor in the Division of Biomedical Sciences in the School of Medicine, who has worked on toxoplasmosis for more than 15 years. “The nearby neuron detects this glutamate which triggers a firing of the neuron. If the glutamate isn’t cleared by GLT-1 then the neurons can’t fire properly the next time and they start to die.”

Wilson and her team found that during toxoplasma infection, astrocytes swell and are not able to regulate extracellular glutamate concentrations. Further, GLT-1 is not expressed properly. This leads to a buildup of the glutamate released from neurons and the neurons misfire.

“These results suggest that in contrast to assuming chronic Toxoplasma infection as quiescent and benign, we should be aware of the potential risk to normal neurological pathways and changes in brain chemistry,” Wilson said.

When the researchers treated the infected mice with ceftriaxone, an antibiotic known to produce beneficial results in mouse models of ALS as well as neuroprotection in a variety of central nervous system injuries, they found that GLT-1 was upregulated. This restoration of GLT-1 expression significantly reduced extracellular glutamate from pathological to normal concentrations, returning neuronal function to a normal state.

“We have shown for the first time the direct disruption of a major neurotransmitter in the brain resulting from this infection,” Wilson said. “More direct and mechanistic research needs to be performed to understand the realities of this very common pathogen.”

Next, Wilson and her colleagues will research what initiates the downregulation of GLT-1 during chronic Toxoplasma infection.

“Despite the importance of this transporter to maintaining glutamate homeostasis, there is little understanding of the mechanism that governs its expression,” Wilson said. “We’d like to know how cells, including peripheral immune cells, control the parasite in the brain. Toxoplasma infection results in the lifelong presence of parasitic cysts within the neurons in the brain. We’d like to further develop a project focused on killing the cysts, which is where the parasite hides from the immune response for the rest of the infected person’s life. Getting rid of the cyst removes the threat of reactivation of the parasite and the risk of encephalitis while also allowing us to minimize chronic inflammation in the brain.”

Mysteriously, the parasite that causes toxoplasmosis can sexually reproduce only in cats. Asexually, it can replicate and live in any mammalian cell that has a nucleus. Indeed, the parasite has been found in every mammal ever tested.

Post-infection, a competent immune system is needed to prevent parasite reactivation and encephalitis. Infected people with compromised immune systems need to be on prophylactic drugs for life. Otherwise they are at risk of cyst reactivation and death. The parasite lives in areas of the brain that have the potential to disrupt certain behaviors such as risk-seeking (infected mice will run toward cat urine instead of away from it).

The parasite is not as latent or dormant as researchers once thought. Cases of congenital infection and retinal toxoplasmosis are on the rise (the brain and retina are closely linked). People who have schizophrenia are more likely to be infected with Toxoplasma. Infection shows some correlation with Alzheimer’s disease, Parkinson’s disease and epilepsy.

Nevertheless, Wilson notes that infection is no cause for major worry.

“In this column, I hope to explore various qualities of a physician that we learn through medical school experiences — whether it be through class, shadowing, research or even interacting with peers — but also to introduce a patient’s perspective in each case. Midway through my junior year of college, I was diagnosed with Cushing’s disease, a rare endocrine disorder that affected every aspect of my life. Throughout the next year and a half, I lived as a patient of my disease, while simultaneously trying to hold onto my plans and aspirations of becoming a physician.”

Earlier in the week family had decided it was time to withdraw care on their son. He had held on longer than expected, but his oxygen saturations had been decreasing throughout the day, and now were sitting in the 30’s.

“What do you think,” asked his mom, tears brimming in her eyes, “is it time to call in the family?”

“Yes, I think it’s time.”

“Do you know when he’ll go?”

“I’m not sure.”

“But if you had to guess?” Several other family members had gathered by this point and were looking at me expectantly.

“Within a couple of hours I expect. But it could be more or it could be less” This seemed to please them. Since staring residency I’ve found that more and more people are asking me for time lines for things. I think it gives a sense that someone is in control…

The next hour seemed like an eternity as I stood in the hallway watching his heart beat do the dance of death on the monitor along with a small collection of nurses. As it slowed towards its final beat one of the nurses turned to me.

“The attending says you can pronounce; do you feel comfortable with that?”

“I guess.”

About 10 family members stared at me as I walked into the room.

“His heart has stopped, I just need to listen to confirm, okay?”

Listening to a chest without a heartbeat is awful. It’s so quiet. I don’t think anyone in the room took a single breath, including myself.

“Time of death…”

I couldn’t even hear myself over the heart wrenching sobs of his mother.

“I’m so sorry for your loss.”

A small round of hugs from a few family members, calling the organ donation line, filling out paperwork with the Chaplin, and like that it was over. Down the hall another patient wakes up and starts playing the Lion King. I walk over and close the door as “The Circle of Life” starts echoing down the hall. I turn and sigh as my phone rings.

“Room 12 is in SVT.”

Brain structure that tracks negative events backfires in depression

A region of the brain that responds to bad experiences has the opposite reaction to expectations of aversive events in people with depression compared to healthy adults, finds a new UCL study funded by the Medical Research Council.

The study, published in Molecular Psychiatry, found that the habenula, a pea-sized region of the brain, functions abnormally in depression. The same team previously showed that the habenula was activated in healthy volunteers when they expected to receive an electric shock.

“A prominent theory has suggested that a hyperactive habenula drives symptoms in people with depression: we set out to test that hypothesis” says senior author Professor Jonathan Roiser (UCL Institute of Cognitive Neuroscience). “Surprisingly, we saw the exact opposite of what we predicted. In people with depression, habenula activity actually decreased when they thought they would get a shock. This shows that in depressed people the habenula reacts in a fundamentally different way. Although we still don’t know how or why this happens, it’s clear that the theory needs a rethink.”

The researchers scanned the brains of 25 people with depression and 25 never-depressed individuals using high-resolution functional magnetic resonance imaging (fMRI). The participants were shown a sequence of abstract pictures while they lay inside the scanner. Over time they learned that different pictures were associated with a chance of different outcomes – either good or bad. Images predicting electric shocks were found to cause increased habenula activation in healthy volunteers, but decreased activation in depressed people.

There were no differences in average habenula size between people with depression and healthy volunteers. However, people with smaller habenulae, in both groups, were found to have more symptoms of anhedonia, a loss of interest or pleasure in life.

Researchers Find Potential Key to Preventing Heart Attacks, Strokes in Older Adults

Researchers at the University of Missouri have found that Insulin-like Growth Factor-1 (IGF-1), a protein that is naturally found in high levels among adolescents, can help prevent arteries from clogging, potentially limiting the chances for coronary heart disease. Coronary heart disease chances increase with age and the disease can lead to heart attacks, stroke, or death. 

Increases in IGF-1 could reduce the amount of plaque buildup in arteries, lowering their risk of heart disease.

“The body already works to remove plaque from arteries through certain types of white blood cells called macrophages,” said Yusuke Higashi, PhD, assistant research professor in the Division of Cardiovascular Medicine at the MU School of Medicine and lead author of the study. “However, as we age, macrophages are not able to remove plaque from the arteries as easily. Our findings suggest that increasing IGF-1 in macrophages could be the basis for new approaches to reduce clogged arteries and promote plaque stability in aging populations.”

“Our current study is one of the first ever to examine a link between IGF-1 and macrophages in relation to vascular disease,” Patrice Delafontaine, MD, the Hugh E. and Sarah D. Stephenson Dean of the MU School of Medicine said. “We examined mice whose macrophages were unresponsive to IGF-1 and found that their arteries have more plaque buildup than normal mice. These results are consistent with the growing body of evidence that IGF-1 helps prevent plaque formation in the arteries.”

Read more

Funding: Funding for the study was provided by the National Institutes of Health (R01HL070241), (R01HL080682), (R21HL113705), (R01HL59976), (P01HL095486), (R01AA221081), and the American Heart Association (13GRNT17230069).

Read more: http://bit.ly/2alCUPa

Pokémon Go Update: Local Man Walks Into an OR to Catch Abra

http://gomerblog.com/wp-content/uploads/2016/07/pokemonfb2.jpg

Charlotte, NC - Local man, Danny Nyguen, wandered into St. Elizabeth Hospital’s operating room chasing down a rare Pokémon: Abra. “I had no idea where I was,” stated Danny. “I knew Abra was nearby and I had to be extra sneaky. Last time I was even close he teleported before I could throw a …

Read more on http://gomerblog.com/2016/07/pokemon-go-update-man-walks-catch-abra/?utm_source=TR&utm_campaign=DIRECT

 Researchers might finally have an explanation for awful, heavy periods

Scientists think they might have finally found an explanation for why more than one-third of women experience heavy periods each month.

Rather than being related to hormones, a new small study suggests that low levels of a specific protein in the uterus might be to blame.

While most women lose up to 40 millilitres of blood each period, around 30 percent of women will lose as much as 80 millilitres - or more than a quarter of a cup - at least one cycle throughout their life.

That might not sound like a whole lot, but, trust me, it’s definitely noticeable when you’re running around trying to get on with work, school, and generally live life.

Sometimes this heavy bleeding is caused by a physical problem - such as fibroids or endometriosis - but around half the time, doctors have no idea what’s going on, or how to stop it.

“Heavy menstrual bleeding is one of the most common reasons for referral to a gynaecologist,” lead researcher Jackie Maybin, from the University of Edinburgh in the UK, told Jessica Hamzelou from New Scientist. “It can have a big impact on a person’s quality of life.”

Tracking Disease

When you’re sick, there’s nothing you want more than to be well again (unless you’re just angling for a day on the sofa). In fact, this could be seen as the goal of modern medicine – getting people back to normal life and health again following illness or infection. But in the early stages of a disease it’s hard to predict who is more resilient and likely to spring back to wellness and who will have lingering severe symptoms, perhaps needing more powerful treatment to fight the disease or never fully regaining their health. By tracking the presence of immune cells and parasites in humans and mice with malaria as they go through cycles of responding to the disease and recovering, scientists have created these colourful disease ‘maps’. Each one traces how the infection moves through individuals – mice on top, humans along the bottom – revealing crucial differences in recovery between them.

Written by Kat Arney

Image adapted from work by Brenda Y. Torres and Jose Henrique M. Oliveira, and colleagues

Program in Immunology, Stanford University, Stanford, CA, USA

Image originally published under a Creative Commons Licence (BY 4.0)

Published in PLOS Biology, April 2016

Not surprisingly, there aren’t many posts about surviving organic chemistry so I thought I might give my two cents + resources I’ve racked up over the two semesters for this gawdawful class (it’s not that bad once you get past the fear that it’s OCHEM!!)

General Tips

Always count your carbons!

When in doubt, build a model…actually, always build a model. Types of models you should have pre-made: functional groups, R & S conformers, cyclohexanes

Mechanisms are hard; and yes, you do have to memorize them (as in, know the basic format and how they may interact with different molecules). Use different colored pens for reactions. Different colors for different actions of electrophile/nucleophile. Draw the right kinds of arrows.

Please memorize your functional groups. Learn their properties and reactions because molecules with same functional groups have similar reactions.

Flashcards! Flashcards! Flashcards!

Like math, practice makes perfect. Practice all sorts of problems from the end of the chapter, online, etc.

Read the textbook before going to class. 

Focus on key concepts & examples during class, especially reaction mechanisms.

Review your notes after class; continual exposure to the material is the best way to retain and understand it.

Go to your professor’s/TA’s office hours - they are there to help you! If you’re not sure and you are struggling, please don’t sit there and keep struggling. Ask for help (use campus tutoring resources or online resources!!)

Review using old exams. The questions and question type are the same; the test is not scary when you are exposed to the format of the test and the question types; the professors recycle questions, and only change up the molecules.

Start early, and don’t fall behind. Organic chemistry is a fast paced class that you must be on top of at every moment; you must dedicate at least 1-2 hour every day outside of class in order to master this subject.

Connect labs and lecture. There’s a reason you are taking those two classes together. 

Specific Stuff

Nomenclature: know common names & IUPAC; know your priority groups; remember your prefixes; don’t forget your dashes, commas & parenthesis; always circle your parent chain; number your carbons!

Curved arrow points from the electron donor to the electron acceptor. 1) Drawn from a lone pair on the base to the proton on the acid [first arrow] /  2) Drawn from the electrons that the protons share to the atom on which they are left behind [second arrow]

pKa: know the pKa values of functional groups; the lower pKa acts as the acid; the higher pKa acts as the base

Degrees of unsaturation = 1 + #C - (#H/2) - (#X/2) + (#N/2) where X are halogens

Know the basic characteristics and identifiers of functional groups for IR spectra, HNMR, CNMR, and mass spec. 

Drawing resonance structures: lone pair to double bond; double bond to lone pair (and negative(-) charge); draw dashed lines wherever lone pair traveled (and ∂- signs); if double bond to single bond, positive (+) charge on previous double bond atom

Newman projections & chair conformers: know the types of strains, which one is more stable (less strain - more stable = less energy), cis/trans conformers of chairs, etc. For chair conformers: axial up = equatorial up and vice versa

Resources + Links

Survival 101 in: Organic Chemistry by @chemistrynerd2020

Mechanism printables by @colllegeruled​

Surviving Organic Chem by @colllegeruled​

Khan Academy: Organic Chemistry (lifesaver for sure) 

Leah4Sci Youtube Channel (great organic chemistry tutorials)

Six Pillars of Organic Chemistry

Master Organic Chemistry (great resources and study guides)

Organic Chemistry As a Second Language by David Klein (an amazing small book to reinforce concepts learnt in class)

Fundamental of organic chemistry doodle by @sciencescribbles

Functional Groups by @compoundchem (I would totally print this out if I were you)

Chemistry Resources by @study-well (great organic chemistry section)

Virtual Textbook of Organic Chemistry

Interactive organic mechanisms