Speaking February 4 at the 69th Annual Meeting of the American Academy of

Dermatology (Academy), dermatologist Brett M. Coldiron, MD, FAAD, clinical

associate professor of dermatology at the University of Cincinnati in Cincinnati, Ohio,
presented new statistics pointing to an increase in non-melanoma skin cancer and why
young people are at an increased risk of developing this disease.

Dr. Coldiron reported that in a recent analysis of Medicare claims, data showed that
treatment performed for non-melanoma skin cancers in the United States nearly doubled
from 1994 to 2006. Specifically, the total number of new non-melanoma skin cancers in
2006 was estimated to be more than 3.5 million.

"While the American Cancer Society estimates more than 2 million new skin cancers will
be diagnosed this year, our research shows that the annual incidence in 2008 could
actually have been 3.7 million," said Dr. Coldiron. "This is especially troubling as our
estimate only includes Medicare patients, which means this could be even higher when
young people are included in the count."

While both basal cell and squamous cell carcinomas can be easily treated if detected
early, Dr. Coldiron noted that the long-established culture of tanning for the sake of
vanity often includes annual spring break vacations to sunny climates that glamorize
tanning. The fact is that ultraviolet (UV) light exposure (both natural and artificial) has
been proven to be the most preventable risk factor for skin cancer.

"As dermatologists, we know that it is hard to change behavior, even in the face of
proven scientific evidence," said Dr. Coldiron. "Attitudes about tanning are no different,
as studies have shown that even though people know that overexposure to ultraviolet
light can lead to skin cancer, they still tan. We need young people to realize that tanning
for cosmetic reasons now will ultimately negatively affect their appearance later and even
increase their risk for skin cancer."

To minimize your risk of skin cancer, the Academy recommends that everyone Be Sun
Smart®:

Generously apply a broad-spectrum water-resistant sunscreen with a Sun

Protection Factor (SPF) of at least 30 to all exposed skin. "Broad-spectrum" provides
protection from both ultraviolet A (UVA) and ultraviolet B (UVB) rays. Re-apply
every two hours, even on cloudy days, and after swimming or sweating.
Wear protective clothing, such as a long-sleeved shirt, pants, a wide-brimmed hat
and sunglasses, where possible.
Seek shade when appropriate, remembering that the sun's rays are strongest
between 10 a.m. and 4 p.m. If your shadow is shorter than you are, seek shade.
Protect children from sun exposure by playing in the shade, wearing protective
clothing, and applying sunscreen.
Use extra caution near water, snow and sand as they reflect the damaging rays of
the sun which can increase your chance of sunburn.
 Get vitamin D safely through a healthy diet that may include vitamin
supplements. Don't seek the sun.
Avoid tanning beds. Ultraviolet light from the sun and tanning beds can cause
skin cancer and wrinkling. If you want to look like you've been in the sun, consider
using a UV-free self-tanning product, but continue to use sunscreen with it.
Check your birthday suit on your birthday. If you notice anything changing,
growing, or bleeding on your skin, see a dermatologist. Skin cancer is very treatable
when caught early.

a. What questions does the paper address?

ANS: The paper addresses the following questions:

1.What are the current statistics and trends regarding non-melanoma skin cancer in the
United States?

2.Why are young people at an increased risk of developing non-melanoma skin cancer?

3.How does the culture of tanning contribute to the rise in skin cancer cases?

4.What preventive measures can individuals take to minimize their risk of developing
skin cancer?

b.What are the main conclusions of the paper? Are they important/relevant to the
society?

Ans: The incidence of non-melanoma skin cancer has been increasing, with a significant
rise in cases from 1994 to 2006.

Young people are particularly at risk of developing skin cancer due to tanning behaviors
influenced by the culture of vanity and spring break vacations to sunny destinations.

Preventive measures, such as using sunscreen, wearing protective clothing, seeking

shade, and avoiding tanning beds, are crucial in reducing the risk of skin cancer.

These conclusions are important and relevant to society because they highlight the
increasing prevalence of skin cancer and the need for awareness and preventive
measures, especially among young people.

c. What evidence supports those conclusions?

Supporting evidences to the conclusions are as follow:

1.Analysis of Medicare claims showing a nearly doubled rate of treatment for non-
melanoma skin cancer between 1994 and 2006.

2.Observations of the culture of tanning for vanity purposes and spring break vacations to
sunny locations.

3.Scientific evidence linking UV light exposure, both natural and artificial, to the
development of skin cancer.

4.Studies demonstrating that despite awareness of the risks, people still engage in tanning
behaviors.

d. Do the data actually support the conclusions?

Ans: The data presented in the article support the conclusions to some extent. The
analysis of Medicare claims provides quantitative evidence of the increase in non-
melanoma skin cancer treatment. The observations on tanning culture and the association
of UV light with skin cancer are supported by existing scientific knowledge. However,
the article does not provide specific data on the link between tanning behaviors among
young people and the rise in skin cancer cases

e. What is the quality of the evidence?

Ans: The quality of evidence is reasonably strong, considering the reliance on Medicare
claims analysis and scientific knowledge regarding the association between UV light and
skin cancer. However, it would be beneficial to have more comprehensive data and
studies specifically focusing on the impact of tanning behaviors among young people on
skin cancer rates to further strengthen the conclusions.
(UCSD The research provides evidence that inhibition of this particular brain region --
the lateral habenula -- using implanted electrodes can reverse certain behaviors associated
with depression, and also provides a mechanism to explain this effect. These findings
lend support to the use of deep brain stimulation as a clinical treatment for people with
long-standing, treatment-resistant depression.
"This research identifies a new anatomical circuit in the brain that mediates depression,
and shows how it interacts with the brain's reward system to trigger a constant
disappointment signal -- which certainly would be depressing," said Fritz Henn, a
neurobiologist and psychiatrist at Brookhaven and Cold Spring Harbor laboratories and a
co-investigator on the research. "But," he added, optimistically, "identifying this circuit
and how it works may open new doors to reversing these effects."
For example, said co-investigator Roberto Malinow, a professor of neurosciences at the
UCSD School of Medicine, "it's possible that the genes specifically expressed in these
neurons could be targeted genetically or pharmacologically in order to manipulate them
and reduce depression."
Scientists have known that cells in the lateral habenula are activated by negative or
unpleasant events, including punishment and disappointment, such as when you don't get
an expected reward. It may seem intuitive that such negative stimuli can lead to
depression, but not everyone who experiences disappointment collapses into a state of
helplessness. To explore this connection, the scientists wanted to take a closer look at the
brain circuits.
They examined the sensitivity of lateral habenula brain cells -- particularly those that
connect and send signals to the brain's reward centers -- in two animal models of "learned
helplessness," a form of depression, as well as in control animals that weren't helpless.
Overall, the scientists found that these lateral habenula nerve cells were hyperactive in
the depressed animals but not in the controls. Furthermore, the degree of hyperactivity
coincided with the degree of helplessness.
"The activation of the lateral habenula is known to influence the release of serotonin and
norepinepherine, two targets of current antidepressant medications," said Henn. "The
current study looked at the role of the lateral habenula in terms of the dopamine system,
the system involved in reward signaling. We found that hyperactivity in the lateral
habenula due to stress-induced helplessness shuts off the brain's reward system."
To explore whether electrical stimulation could potentially reverse this reward-
dampening effect, the researchers placed a stimulating electrode in the lateral habenula
and measured the effects on the brain cells leading to the reward center. This was a study
of rat brain cells that simulated the effects of deep brain stimulation, a technique that is
currently being explored as a treatment for clinical depression, which has shown
promising results. The scientists found that electrical stimulation of hyperactive habenula
brain cells markedly decreased excitatory activity leading to the reward center.
Next the scientists tested to see if deep brain stimulation in living rats that exhibited
helplessness would affect their behavior. The result was a marked reduction in helpless
behavior that was dependent on both placement of the electrode in the lateral habenula
(not adjacent brain regions), and the intensity of the stimulation.
"Our results clearly show that suppression of synaptic transmission at the lateral habenula
through deep brain stimulation can acutely reverse helpless behavior in rats," said Henn.
"It's very likely that this beneficial effect was mediated by a suppression of excitatory
nerve cells leading to the brain's reward system, as we observed in the cellular studies."
"Our study provides a cellular mechanism that may explain the hyperactivity of lateral
habenula nerve cells observed in depressed humans and animal models of depression, as
well as why 'silencing' these circuits, whether surgically or pharmacologically, can reduce
depression-like symptoms in animals," Henn said.
Identifying these specific brain circuits and their dysfunction in depression may open the
door to new effective treatments, including, potentially, lateral-habenula-targeted deep
brain stimulation.
This research was supported through Laboratory Directed Research and Development
funding at Brookhaven Lab, and by the Simons Foundation, the Dana Foundation, the
National Institute of Mental Health, and a Shiley-Marcos endowment at UCSD.
In addition to Henn and Malinow, co-authors include: Bo Li (UCSD and Cold Spring
Harbor), Joaquin Piriz (UCSD), Martine Mirrione (Cold Spring Harbor and Brookhaven),
Chihye Chung (UCSD), Christophe Proulx), and Daniela Schulz (Brookhaven).

a. What questions does the paper address?

The paper addresses the following questions:

- What is the role of the lateral habenula, a brain region, in depression?

- How does the lateral habenula interact with the brain's reward system to trigger
depressive symptoms?

- Can deep brain stimulation of the lateral habenula reverse the behavioral symptoms
associated with depression?

- What is the cellular mechanism underlying the hyperactivity of lateral habenula cells in
depression?

- Can targeting the lateral habenula with deep brain stimulation provide a potential
treatment for depression?

b. What are the main conclusions of the paper?

The main conclusions of the paper are:

 - Hyperactivity of cells in the lateral habenula is associated with depressive
symptoms and a dampening of the brain's reward system.

- Deep brain stimulation of the lateral habenula can reduce the hyperactivity of
these cells and reverse behavioral symptoms associated with depression.

c. What evidence supports those conclusions?

The evidence supporting these conclusions includes:

- The identification of hyperactivity in lateral habenula cells in animal models of

depression.

- Observations of the correlation between the degree of hyperactivity and the degree of
helplessness in animals.

- Cellular studies showing that deep brain stimulation of hyperactive lateral habenula
cells reduces excitatory activity leading to the brain's reward system.

- Behavioral experiments in live rats demonstrating a marked reduction in helpless

behavior following deep brain stimulation of the lateral habenula.

d. Do the data actually support the conclusions?

Based on the information provided, the data seem to support the conclusions drawn in the
paper. The findings show a correlation between hyperactivity of lateral habenula cells
and depressive symptoms, and the use of deep brain stimulation to reverse these
symptoms in animal models. However, it is important to note that the study was
conducted in animal models, and further research is needed to determine the effectiveness
and safety of these findings in human patients.

e.What is the quality of the evidence?

The quality of the evidence appears to be good, as the study involved cellular studies,
behavioral experiments in animal models, and the use of deep brain stimulation to
investigate the effects on depressive symptoms. However, it is always important to
consider the limitations of animal models and the need for further research in human
subjects.

f. Why are the conclusions important

The conclusions of the paper are important because they contribute to our understanding
of the neural circuits involved in depression and provide insights into potential
therapeutic interventions. Identifying the role of the lateral habenula and its interaction
with the brain's reward system in depression opens up new possibilities for targeted
treatments, such as deep brain stimulation. This research may pave the way for
developing more effective therapies for individuals with long-standing, treatment-
resistant depression.