Aminu Alibe

17 January 2019
G/T Intern Mentor
Annotated Source List

Chitwood, W. R., Jr. (n.d.). Disruptive Innovation in Cardiac Surgery. Phi Kappa Phi Forum, 4-
7.

This article is written by W. Randolph Chitwood Jr and discusses the recent innovations in
cardiac surgery -- which flurried after the heart-lung machine was first used in 1953. This
machine allowed more complex heart surgeries to take place by performing the heart and lungs’
functions. Cardiovascular surgery is moving away from open-chest, invasive procedures to
procedures completed with a small incision and a catheter. Even though these operations might
not be as effective as the traditional methods, patients preferred less invasive procedures. The
article goes through the major innovations in the 20th century and leading into the 21st century
and “disruptive innovation.” Disruptive innovation challenges cardiovascular surgeons to shift
their thinking and create more innovations. The intra-coronary stent and other procedures
lowered the usage of coronary surgery to 40 percent in 2007. Finally, cardiac surgeons utilized
lateral thinking and worked with other disciplines like engineering to innovate medical devices.
This article was useful because it provided a baseline insight into recent medical innovations
in the field of cardiac surgery. Further research can be completed based on the procedures and
concepts discussed in this article.

Coloigner, J., Kim, Y., Bush, A., Borzage, M., Rajagopalan, V., Lepore, N., & Wood, J. (n.d.).
Low-frequency fluctuation amplitude analysis of resting-state fMRI in sickle cell disease.
Proc SPIE Int Soc Opt Eng. https://doi.org/10.1117/12.2211383

This article was written by sickle cell researchers investigating the disease’s impact on the
brain. Patients with sickle cell anemia are more likely to have strokes as a result of a blood clot
forming and blocking off oxygen supply to the brain. This aspect of sickle cell anemia is one of
the contributing factors to higher mortality. The authors conducted a functional magnetic
resonance imaging to measure brain activity and observed spontaneous Blood Oxygenation
Level-Dependent signals during rest. The researchers found higher ALFF, which is the Altitude
of Low Frequency Fluctuations and used to measure BOLD signals, in regions such as the
posterior cingulate cortex, medial prefrontal cortex, and precuneus and posterior frontal cortex.
The fMRI of the anterior cingulate cortex (ACC) revealed higher connectivity in patients with
sickle cell. Other studies have observed a strong association with ACC and the emotional
response to pain.
This article was useful because it provided in-depth information about sickle cell disease’s
impact on the brain. Further research will be conducted on the potential problems associated with
abnormal brain activity as well as investigating the impact the activity has on people’s lives.

Coloigner, J., Kim, Y., Bush, A., Choi, S., Balderrama, M. C., Coates, T. D., . . . Wood, J. C.
(2017). Contrasting resting-state fMRI abnormalities from sickle and non-sickle anemia.
Plos One. https://doi.org/10.1371/journal.pone.0184860

This authors of this article compared functional magnetic resonance images (fMRIs) of
subjects with sickle cell disease and healthy subjects. The authors note that sickle cell anemia is
associated with increased cerebral blood flow and increased cerebral blood volume. The superior
frontal gyrus and precuneus brain regions are more vulnerable to drops in oxygen delivery
because they are located in between two major arteries. Some similarities of white matter loss
were seen among both the sickle cell disease subjects and healthy subjects that the authors
attributed to hypoxia. However, the right postcentral gyrus and left lingual gyrus was higher in
the healthy subjects than in the sickle cell disease subjects. Overall, the authors noticed that even
after controlling for anemia, there was decreased activity in sickle cell subjects in the frontal
pole, cerebellum, and mSFG.
This article was helpful to understand the pathophysiology of sickle cell anemia and how
sickle cell affects different areas of the brain. This article can be grouped with the other research
on silent strokes to hypothesize which areas of the brain sickle cell patients receive less oxygen
in and therefore the effects of sickle cell disease on a patient’s everyday life.

Could a silent stroke erode your memory?: Without any warning, your mind could be at risk.
(2012). Harvard Women's Health Watch, 19(10). Retrieved from EBSCOhost database.
(Accession No. 75914859)

This article was written in Harvard Women’s Health Watch and provides background
information about silent strokes and the risk they pose to a person. A stroke occurs when a part
of the brain is deprived of oxygen and the cells in that area of the brain die. Depending on the
area of the brain impacted, a person’s speech, memory, and motor skills may be altered. In a
traditional stroke, a clot blocks a blood vessel that supplies oxygen and nutrients to the brain,
damaging vital functions. A subtler type of stroke is a silent stroke, which creates smaller areas
of damage in the brain that a traditional stroke. However, silent strokes can still leave lasting
damage on the brain’s functioning. Silent strokes leave damage to areas of the brain that do not
control any vital functions -- meaning a person might not know they are suffering from a silent
stroke. An accumulation of silent strokes can have a significant impact on a person’s memory.
The article notes that silent strokes are more prevalent than traditional strokes: for every one
person that has a traditional stroke, 14 people have silent strokes.
This article was helpful because it provides a baseline understanding about silent strokes for
the research. Other sources describe the danger of traditional and silent strokes on patients
suffering from Sickle Cell Anemia. Further research on silent strokes will be conducted as
another facet of dealing with Sickle Cell Anemia.

DeBaun, M. R. (2014). Perspective: Thinking beyond survival. Nature Publishing Group,

515(7526). https://doi.org/10.1038/515S16a

This article was written for the Nature Journal and concerns the major advances in
Sickle Cell Anemia research that have happened in the last two decades. These advances have
improved the life expectancy of people suffering from the disease; From 1983 to 2002, children
younger than 4 living in the U.S. have seen a decrease in mortality rate by 68 percent. Similarly,
the overall life expectancy has increased to 50 years. The author notes that with this great
improvement comes increasing problems, including a higher chance of stroke and incurable
organ damage. The author further differentiates between outward and inward strokes, noting that
inward strokes are almost exclusive to people suffering from sickle cell anemia-- they do not
include the traditional symptoms associated with outward strokes, but can still negatively affect a
child’s performance in a job and classroom and intelligence. Another long-term concern with
managing sickle cell anemia is the rigorous annual visits to a hospital that should be adhered to.
They include at least 3-4 visits to monitor blood toxicity attributable to the drug hydroxyurea, a
transcranial doppler scan (TCD) to monitor for overt strokes, a visit to an opthamologist, and
biannual oral hygiene checkups.
This article was helpful to the research because it provided more information on the state of
Sickle Cell Anemia research today compared with the late 1900s and early 2000s. More research
will be conducted on silent strokes and the impacts and dangers they have on sickle cell patients.

Estcourt, L. J., Fortin, P. M., Hopewell, S., Trivella, M., Doree, C., & Abboud, M. R. (n.d.).
Interventions for preventing silent cerebral infarcts in people with sickle cell disease.
Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD012389.pub2

This article is about preventing silent cerebral infarcts in people suffering from sickle cell
anemia. A silent cerebral infarct (or SCI) is an abnormality on an MRI without a history or
physical examination abnormalities. Silent strokes affect a person’s physical health as well as a
person’s cognitive abilities, which could result in poorer academic performance and a lower
intelligence quotient. 5 different trials containing 660 children or adolescents were analyzed for
methods to prevent silent cerebral infarcts. A method the authors identified for reducing silent
cerebral infarcts was long term blood transfusions in individuals with a higher risk of stroke.
This method increases the amount of red blood cells in a patient with sickle cell disease’s blood.
Long-term blood transfusions reduced the frequency of acute chest syndrome and vaso-occlusive
crisis. However, no difference was noted in children or adolescents with previous silent cerebral
infarcts. The risks of transfusions can include the possibility of infection and iron overload.
This article was useful to gain more information about silent cerebral infarcts in patients with
Sickle Cell Anemia, as well as to learn about long-term blood transfusion as a potential method
to reduce the incidence of it. Further research can be conducted with the articles referenced in
this article.

Galvin, G. (n.d.). The State of Health Care in Rural America. Retrieved September 16, 2018,
from U.S. News website:
http://search.ebscohost.com/login.aspx?direct=true&db=f5h&AN=127479507&site=ehos
t-live

Written by Gabby Galvin from U.S. News, this article details the challenges in providing
healthcare to rural areas in the United States. First and foremost, rural states face different
medical challenges than their more populated counterparts, such as personnel shortages, an
increase in disease rates, and transportation problems. The Bipartisan Policy Center conducted
research of seven rural states (Iowa, Minnesota, Montana, Nebraska, North Dakota, South
Dakota, and Wyoming) and found isolation and an aging population are specific issues that hit
rural areas hard. A senator from a rural state, Heidi Heitkamp (ND), mentions that problems
facing rural healthcare are also linked to economic problems facing those same communities. At
the end of the article, the author proposes some potential avenues to solve this problem, such as
having doctors conduct residencies in rural areas and holding spaces in health programs from
those living in rural areas.
This article was helpful to analyze different problems facing rural America, and learn how
they might be different from the problems that face more populated states. More research can be
conducted about potential solutions to many of these problems and an avenue of further research
could go into the disease rates of rural areas.

Galvin, G., & Cline, S. (n.d.). America's 'Guerilla' Medics. Retrieved September 16, 2018, from
U.S. News & World Report website:
http://search.ebscohost.com/login.aspx?direct=true&db=f5h&AN=130305724&site=ehos
t-live

Published in U.S. News & World Report, this article explores new forms of medical treatment
throughout communities in the United States. The author discusses the effort communities have
taken to change how medical emergency responses work. In North Carolina, some patients may
be able to have paramedics come to their houses weekly or biweekly after being released from
the hospital to perform essential health monitoring functions, such as checking a patient’s blood
pressure. This innovation means that if a patient has a specific, non life-threatening concern after
a complicated procedure or hospitalization, they can call paramedics instead of 911.
The assigned paramedics would arrive to the patient’s home within 30 minutes and be able to
provide assistance. This program is particularly beneficial to senior citizens living in their homes
or in assisted living facilities. Another benefit of this program is to help people released from
rehabilitation treatment for opioid use. Officials say paramedics might be able to gain opioid use
patients trust and be able to help them more effectively.
This article is helpful to lay a foundation for my research because it discusses new strategies
communities are testing to combat serious medical problems in the United States today. Further
research can be conducted about the ways medical professionals and healthcare communities
across the country are adapting the traditional model to medicine in favor of utilizing technology
and new approaches.

Gammon, K. (n.d.). Gene therapy: Editorial control. Nature, 11-13.

https://doi.org/10.1038/515S11a

This article is written by Katharine Gammon and is about gene therapy and its potential
impact on sickle cell disease. This disease is a candidate for gene therapy because it would only
involve manipulating one amino acid in the “β-globin” gene of DNA. There are two forms of
gene therapy that researchers are about to begin early-testing: conventional gene therapy that
involves inserting additional genes and gene editing, which involves cutting out faulty DNA
sequences and inserting laboratory-created DNA. The author notes that further research about
gene editing in sickle cell must be research further to prevent any adverse factors. Complications
arise from harvesting stem cells from a patient because stem cells cannot be enticed to enter the
bloodstream because it increases the risk for a sickle cell crisis, so researchers must obtain them
from the bone marrow.
This article was helpful because it discusses the possibility of curing sickle cell anemia as well
as the potential complications with using gene therapy to do so. This article provided more ideas
for further research that can be investigated in the future.

Gravitz, L., & Pincock, S. (2014). Sickle-cell disease. Nature, 515(7526).

https://doi.org/10.1038/515S1a

This article is published in the Journal Nature and discusses some of the complications that
arise as a result of Sickle Cell Anemia. There is a contrast drawn between people with Sickle
Cell Anemia born in developed and developing countries. The life expectancy for people born in
developed countries can go beyond 60 years old while 90% of those born in developing countries
die before their fifth birthday. This is largely a result of medical treatments that people in
developed countries can afford. However, the authors note that the medical treatments do not
prevent sickle cell crises from occurring. Serious manifestations of this disease can affect
emotional and physical well-being, especially strokes. Progress is being made towards
developing additional therapies for sickle cell disease, but the authors caution that they are at an
early stage.
This article is helpful because it provides a lot of useful information about Sickle Cell Disease.
Information the authors reference can be used for further research about the hardships of sickle
cell disease and any medications that are being used to treat it.

Healed in the womb. (n.d.). New Scientist, 216(2895). Retrieved from EBSCOhost database.
(Accession No. 84339292)

This article is written by Meera Senthilingam and concerns the potential implications
regarding gene therapy in the womb. This would be considered a daring and bold move that
could potentially be a cure for sickle cell anemia. Like other gene therapy procedures, there is a
need to have a suitable donor. The author identifies the ideal donor as the mother. The positives
for attempting a bone marrow transplant in a baby is that its immune system has not yet
developed. Even if a minority of all the cells in the bloodstream were donated, it would be
enough to alleviate pain from sickle cell. Researchers who have conducted studies have had
success in dogs with the canine equivalent of sickle cell anemia. The risks of this procedure still
need to be considered. The author discusses how injections into the womb has a risk of
miscarriage between 1 and 5 percent.
This article is helpful because it further discusses the potential use of gene therapy in the
treatment of sickle cell anemia. Furthermore, more research can be conducted on transplants
conducted in the womb.

Issar, P., Nehra, M., Singh, G., & Issar, S. (n.d.). Conventional and advanced brain MR imaging
in patients with sickle cell anemia. Indian Journal of Radiology and Imaging.
https://doi.org/10.4103/ijri.IJRI_166_17

The authors discuss how sickle cell disease causes vaso-occlusive crisis, ischemia, and
infarction. One of the body organs sickle cell disease most impacts is the brain as it can lead to
mortality and morbidity. Stroke, silent cerebral ischemia, brain atrophy, and transient ischemic
attack are some complications as a result of sickle cell disease that can occur in the brain. Often,
the impact of sickle cell disease is underestimated through conventional neuroimaging. One of
the reasons the authors attribute to this is that conventional magnetic resonance imaging cannot
adequately tell microstructural changes in the brain’s white matter. A new technique, called
diffusion tensor imaging, or DTI, can show white matter fibers and living cells. The authors used
tested this technique in patients with sickle cell. They concluded that brain regions in patients
with sickle cell had potential axonal damage as a result of the disease.
This article was helpful because it provided added a new perspective towards this research by
providing information about how sickle cell disease impacts the brain in microstructural ways
that sometimes might not be clearly visible through a normal MRI. The article provided other
resources that can be explores to learn more about this topic and will contributed towards
narrowing down the research.
Mallapaty, S. (2014). Q&A: Healthy progress. Nature Publishing Group, 515(7526).
https://doi.org/10.1038/515S6a

This article is a question and answer with Graham Serjeant, a physician living in Jamaica that
works to help the local population by providing free-screening for people with sickle cell
anemia. He initially worked at the Medical Research Council Laboratories in Kingston, the
capital and largest city in Jamaica. He has also worked in Brazil, Saudi Arabia, India, and other
countries in Africa. He and his charity were able to provide information for the people screened
who had Sickle Cell Anemia, including resources they could use. He discusses the importance of
sickle cell anemia to the global society, noting that the problem has become more prevalent as
the years progress. One problem with the current response to sickle cell anemia is the lack of
political will to dedicate resources to fighting this disease.Three Indian states have developed
sickle cell programs to assist their citizens who have Sickle Cell Anemia.
This article is helpful because it provides information about people dealing with sickle cell
anemia. Other sources referenced in this article can be used for further research. Finally, research
on Dr. Serjeant’s work can be conducted to examine efforts people and governments across the
world have taken to mitigate sickle-cell-anemia.

Nogrady, B. (n.d.). Neurobiology: Life beyond the pain. Nature, 8-9.

https://doi.org/10.1038/515S8a

This article, written by Bianca Nogrady, discusses pain levels in people with sickle cell
anemia. People with sickle cell suffer from debilitating crises that happen without a moment’s
notice. It is thought that this pain is a result of oxygen-deprived tissues as blood vessels carrying
oxygen are clogged and damaged. In 2010, researchers asked people with sickle cell to describe
their pain using the McGill Pain Questionnaire and found that people described the pain with
words such as “aching” or “stabbing” rather than words like “pounding,” which is typically
associated with vaso-occlusive crises (crises in which blood vessels are blocked). After further
investigation, researchers discovered that people with sickle cell have a heightened sensitivity to
temperature and pain because of the CaMKIIα enzyme. Researchers tried using a drug that
inhibits CaMKIIα in a trial of 18 patients and found that 8 felt 50% less pain.
This article is helpful because it provides a more in-depth view of sickle cell disease’s impact
on the body’s functioning. Further research can be conducted based on the information learned in
this article and the other sources that were referenced.
Pleasants, S. (n.d.). Epidemiology: A moving target. Nature, 515(7526).
https://doi.org/10.1038/515S2a

This article was written by Simon Pleasants and is about the movement of the sickle cell
disease from areas of high concentration such as Africa and India to those of low concentration,
such as Europe, North America, and the eastern coast of South America. Sickle cell naturally
occurs in areas with a high prevalence of malaria. Limited migration out of Africa restricted the
spread of the disease until recently when migration has spread the disease. Researchers found out
that the sickled-shape of the cells helps prevent malaria from spreading in a person’s body.
According to the author, the Sickle Cell Disease Association of America estimates an average of
100,000 people living in the United States with the disorder. Advanced medical treatments and
longer life expectancy in developed countries leads to an increased prevalence.
This article was helpful because it provides background information for the spread of sickle
cell anemia to other continents. This contributes to the research because it helps to build a more
detailed profile of a potential cure to sickle cell disease. Further research can be conducted on the
impact this has on the progression of the research.

Reduce your risk of silent strokes. (2015). Harvard Heath Letter, 40(5), 3. Retrieved from
EBSCOhost database. (Accession No. 101101451)

This article was written by Harvard Health Letter and provides information about ways to
reduce the risk of silent strokes. The author begins by acknowledging the common notion of a
stroke as something that causes numbness and tingling, causes part of a person’s face to droop,
and makes talking difficult. However, another type of stroke is subtle and referred to as a silent
stroke, which occurs without any symptoms. The author notes that both share common causes of
high blood pressure and cardiovascular disease. Silent strokes are usually caused by a clot
formed in a small artery supplying blood to a ‘silent’ part of the brain -- one that does not control
vital functions such as speech of walking. A person can accumulate silent strokes, which could
potentially impact memory and a person’s mood. To reduce the risk of a silent stroke, a person
can work on reducing his or her blood pressure and cholesterol, but importantly working with a
doctor to maintain a healthy lifestyle.
This article was helpful to the research because it provides more background information on
silent strokes and how they impact a person’s brain. This will be helpful in Sickle Cell research
as patients suffering from this disease have a higher risk of having traditional and silent strokes.
Further in-depth research will be conducted on silent strokes to learn the ways Sickle Cell
patients might be able to lower the risk.

Richmond, C. (n.d.). Why Do So Many People Have High Blood Pressure. Time Inc. Lifestyle
Group, 98-104.

This article addresses the increase in people with high blood pressure, or hypertension. High
blood pressure’s definition has been reclassified as a blood pressure over 130/80 mm Hg --
meaning ½ of all U.S. adults now have high blood pressure. High blood pressure can contribute
to different medical problems, such as heart attack or stroke. Factors that contribute to
hypertension include race, gender, and family history. Hypertension can be managed in a variety
of different methods, from medications to lifestyle changes. Those with more severe medical
problems are prescribed medications to prevent other serious medical problems, like a heart
attack or stroke from happening.
This article was helpful to understand background information on hypertension and provided a
base-level understanding of some demographic factors that contribute to high blood pressure,
what people with high blood pressure can do, and the importance of management. Further
specific and in-depth research on hypertension as it relates to other cardiovascular problems can
be conducted.

Saey, T. H. (2011). Sickle-cell trait blunts malaria. Science News, 179(12). Retrieved from
EBSCOhost database. (Accession No. 61036445)

This article was written by Tina Hesman Saey for Science News and is about research into the
relationship between the Sickle Cell trait and malaria. The conventional thought behind why
people with the sickle cell trait cannot get malaria is that it was blocked from entering the blood
cell. The mutation responsible for sickle cell also increases heme oxygenase-1 production, a
protein found in carbon monoxide gas. In mice infected with malaria, the gas reduced
inflammation and protected them from death. Furthermore, the mutation helped the mice’s body
protect against the malaria parasite, which shreds red blood cells because of the extra carbon
monoxide production in the mice with sickle cell. Mice infected with malaria that were kept in a
chamber with low amounts of carbon monoxide did better than their counterparts in a chamber
with regular air. Although malaria can still infect the cells of a person with sickle cell mutation,
he or she will not get as sick, which allows the immune system to respond.
This article was interesting because it examined the link between malaria and sickle cell
anemia and presented some alternate solutions to why people with sickle cell anemia do not get
as sick from malaria. This furthers the research by giving a more detailed background to how
sickle cell mutated in the regions it did.

Weintraub, A. (n.d.). Rewriting the Faulty Code. U.S. News & World Report, 20-24. Retrieved
from MasterFILE Premier database. (Accession No. 132062624)

This article is written by Arlene Weintraub and concerns gene editing and how it can be a
potential cure to many diseases. This article was read specifically for gene editing’s implications
to sickle cell disease research. The author describes how researchers are attempting to cure sickle
cell with this treatment by inserting a new gene that makes normal hemoglobin. This would be
done by taking stem cells from a patient’s body, editing them, and reintroducing them to the
body. A specific form of gene editing that the author looks at is CRISPR-Cas9, which involves
the Cas9 enzyme ‘cutting out’ portions of the DNA, allowing them to be replaced. If successful
in the future, this cure would provide a cure for those living in the wealthier countries who suffer
from sickle cell disease. The current cure, involving bone marrow transplant, is only viable for
10% of people that have Sickle Cell Anemia because it involves having a donor.
This article was helpful to learn more about the gene editing process as it relates to Sickle Cell
Anemia and the potential implications it could have for curing the disease. Further research can
be conducted about the status of these research trials.

Weintraub, K. (2016). A surprising fix for Sickle Cell. Scientific American, 314(5). Retrieved
from MasterFILE Premier database.

This article was written by Karen Weintraub and is about a case study of a nine year old girl
from Boston, Ceniya Harris, who was born with sickle cell but does not suffer from its
complications because of a second mutation in her genes. This case study, coupled with new
gene-editing therapies have given researchers a model of what could be done to help those
dealing with sickle cell in the developed world. The fetus has a different form of hemoglobin,
referred to as fetal hemoglobin, that binds tightly to oxygen. After a baby is born, the body’s
production of fetal hemoglobin dwindles. In Ceniya Harris’ case, her body continued producing
it so that 20% of her hemoglobin remains fetal. This allows her organs to receive the oxygen
they need. The article notes that the body doesn’t completely shut off fetal hemoglobin
production since about 1% of the body’s hemoglobin production remains fetal. Researchers have
begun trials to develop a drug that would further mutate a person’s genes in order to keep fetal
hemoglobin production up. So far, the trials present a stark tradeoff for parents. In order for the
drug to work, it would require strong chemotherapy that presents problems for the patient, such
as a risk of cancer in the future.
This article was useful to research potential avenues for treating sickle cell anemia. Further
research will be conducted into gene therapies that the author referenced for more information
about the progress of such treatments.