Exmovere Brainfax Saliva Testing Concept by David Bychkov, PhD

BrainFax Marketing Strategy
Version 1.1
August 2011
Exmovere Holdings, Inc.
1650 Tysons Boulevard
Suite 1580
McLean, VA 22102
Tel: +1-703-663-4090
Fax: +1-703-663-7350

BrainFax – Market Report
August 29, 2011 P a g e | 2
BrainFax – Marketing Overview
Exmovere Holdings, Inc. has developed new models for use in detecting human emotions.
Based on a cheek swab of an individual’s saliva, biochemical markers can be measured and
compared to baseline metrics. Adrenaline, cortisol and pH are all present in saliva, and
recent studies have pointed out significant correlations of these chemicals with emotional
states and well-being. Exmovere’s emphasis on emotion detection and its proprietary
algorithms will be applied to this latest research in order to provide a new mechanism for
more clearly measuring and reporting a person’s emotional state. A laboratory-grade test
for each individual or patient who submits a cheek swab, BrainFax will be used to:
 Measure levels of adrenaline, cortisol and pH in the saliva sample
 Compare measured levels to baseline metrics associated with alternative emotions
 Report the individual’s most likely emotional state(s) at the time of the sample
 Provide a way for physicians, psychiatrists, psychologists, therapists and other
healthcare professionals to measure and document patient’s emotional states along
with their other diagnoses
Practitioners in healthcare have long studied and attempted to match the connections
between emotions and various health conditions. For example, feelings and emotions have
been studied and evaluated as predictors of a variety of health conditions, including but not
limited to depression, schizophrenia, bipolar disorder and others. And, emotions play a role
in signaling or being symptoms of Alzheimers, obesity, heart disease and a number of
immune and endocrine system ailments. These relationships are well documented through
the resources and research sponsored by the National Institute of Health, National Institute
of Mental Health, the Center for Disease Control, Department of Defense and a number of
academic and private industry studies.
There has also been recent evidence pointing to emotional histories, much like we all have
genetics. These emotional histories and our experiences are directly tied to manifestations
of both mental and physical health conditions that require treatment. However, despite all
of the research, study and documentation to date, there are no independent and objective
biophysical measurements that practitioners can use to document and report an individual’s
emotions.
BrainFax will change all that. The premise behind the new system is that all of the research
done to date combined with company’s proprietary algorithms provides a unique model and
measurement system. The system and its analytics deliver baseline metrics and associated
emotional states which are used to derive typical or standardized protocols for various
emotional states or moods. Similar to a meta analysis, BrainFax presents levels of salivary
chemical levels, statistical analysis of results, and projections of emotional states all in one
place based on thousands of existing, approved research studies and results.

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With access to BrainFax and its outputs, laboratory testing of an individual’s salivary
outputs can be compared to these baselines. Target emotional states and moods can be
objectively and precisely measured for the first time by the healthcare professionals
responsible for various treatments and cures.
The emotional state captured at a point in time can then be used by the practitioner in a
number of ways:
 Confirm diagnoses derived from office examinations and assessments
 Track emotional states over time to compare with mental and physical health or
disease states
 Provide objective verification of diagnoses for insurance and liability purposes
 Support additional research into identifying connections between emotions and
disease
There are thousands of scientific research studies from the medical archives that
demonstrate the connections between emotions and both mental and physical disease
states and illness. One of the largest in recent history was performed by the Department of
Preventive Medicine at Kaiser Permanente (KP) San Diego with the cooperation of 17,421
adult Health Plan members and with the ongoing collaboration of Dr Robert Anda at the
Centers for Disease Control and Prevention (CDC). The cooperating health plan members
and their emotions, disease diagnoses and treatments were tracked starting in 1990 over
the next 10+ years. One of the basic conclusions of the study reveals a powerful relation
between our emotional experiences as children and our adult mental health, physical
health, and major causes of mortality in the United States.
In addition to these proven connections between emotions and health, there have been
numerous studies that show strong correlations between biophysical indicators – such as
cortisol, adrenaline and pH level – with emotional states. Feelings like stress, for example,
trigger the adrenal glands to produce cortisol and adrenaline. Cortisol is very helpful in
small doses (as part of the fight or flight response) but sustained high cortisol levels (the
result of unremitting stress) have very destructive effects on the body and mind. Adrenalin,
also produced by stressful events, can have similar effects. And, for pH – one of the body’s
regulators – proper balance is required.

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Cortisol, adrenalin and pH have all been studied in connection with various emotional
states. For example, among key emotional states tied to these 3 biochemicals, the
following appear to be the most serious in their relation to mental and physical disease
states:
 anxiety
 depression
 fatigue/lethargy
 pain
 euphoria
 anger
By measuring cortisol, adrenalin and pH, medical practitioners can develop a picture of the
patient’s emotional state and how that may be contributing to related mental and physical
conditions. As both cortisol and adrenaline pass through the body’s biophysical system, the
last point of processing is the soft tissue in the mouth, which also affects the level of pH
(acidity). Hormones in saliva have already been processed into useable forms and pass
through the mouth on their way out of a person’s system.
How BrainFax Works
The building blocks of the new BrainFax service are the demonstrated and well-researched
connections between hormone and pH levels and emotional states based on existing and
ongoing research, field studies and Exmovere’s proprietary algorithms. Emotions detected
by the process can then be used as input into diagnoses and as predictors of mental and
physical health. Similar to the ranges used in blood serum testing, BrainFax presents a
level of precision in understanding and detecting human emotions to identify precise
moods.
•Cortisol
•Adrenaline
•pH
Biophysical
Metrics
•Correlations
•Baselines
•Algorithms
Emotion
Detection •Objective
Measurement
•Tracking and
Reporting
Mental and
Physical Health

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Part of the new model embedded in the BrainFax system relies on saliva as the primary
measurement substance. Since 1983, according to Dr. Richard Weinstein, there have been
over 2,500 research studies and papers published supporting the use of salivary hormone
testing. From most of these studies, it is clearly demonstrated that salivary tests are as
good as or more accurate than blood tests. Blood serum and the ways in which cortisol
and adrenalin, for example, are measured are not the same as in saliva. Chemicals in
blood serum are attached to proteins or other cell structures which means they are already
in use. Whereas, in saliva, these chemicals are refined, processed, and ready for use.
Basically, the saliva tests provide a much more sensitive and accurate reading on the
chemicals, hormones and indicators tied to alternative emotional states.
Furthermore, saliva testing is much less invasive and less stressful for most patients. In a
typical medical office, blood testing is the norm. Patients are asked to provide blood
samples further increasing some patient’s stress due to being in a doctor’s office, a blood
testing office, and having to deal with the pain of being punctured by a needle. The
increased hormone levels associated with the added stress can make the results unreliable.
By comparison, a cheek swab used to collect saliva is much less invasive and threatening.
Part of the improved accuracy demonstrated in saliva research is due to the low impact of
the technique on the patient.
Thus far, though, most of the understanding we have about salivary testing is confined to
the research laboratory. Practicing medical professionals are often left without a diagnostic
tool based on hormone levels and other bio-chemicals specifically tied to emotional states
and alternative mental or physical disease states. If during an office session a physician,
psychologist, psychiatrist, licensed social worker, or therapist determines a diagnosis of
physical or mental illness, the practitioner goes through a series of verbal or physical
testing and evaluation prior to recording the final patient condition. Salivary testing of
hormone levels – cortisol, adrenaline and pH – will provide the medical professional with an
objective tool that can be used to confirm their recorded diagnosis.
BrainFax brings salivary emotion detection to the mental and physical health professional
marketplace on a large scale for the first time. There have been small, niche laboratories
dedicated to salivary emotion detection serving small practitioner communities such as
Chiropractors and other health professionals. However, over the past 10 years, according
to a recent article scheduled for publication in Clinical Chemistry, “the use of saliva as a
diagnostic fluid has gained attention over time and has become a translational research
success story. Some of the current nanotechnologies have been demonstrated to have the
analytical sensitivity required for the use of saliva as a diagnostic medium to detect and
predict disease progression. However, these technologies have not yet been integrated into
current clinical practice and work flow.”

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Based on the abstract of the article, titled Diagnostic potential of saliva: current state and
future applications – currently available online at http://PubMed.gov – the authors state:
“As a diagnostic fluid, saliva offers advantages over serum because it can be collected
noninvasively by individuals with modest training, and it offers a cost-effective approach for
the screening of large populations. There is minimal risk of contracting infections during
saliva collection, and saliva can be used in clinically challenging situations, such as
obtaining samples from children or handicapped or anxious patients, in whom blood
sampling could be a difficult act to perform.” And, in summary, “Saliva has the potential to
become a first-line diagnostic sample of choice owing to the advancements in detection
technologies coupled with combinations of biomolecules with clinical relevance.”
The actual implementation of BrainFax will include suggested data collection protocols to
supplement models built from existing data and research. The purpose of the
recommended regular saliva collection will be to:
 develop an individualized baseline profile for the subject
 track daily changes between therapy sessions
 track specific events
With this additional detail, healthcare professionals will be able to refine or augment their
recommended treatment regimens – including related prescription drugs – for their patients
who use BrainFax. And, BrainFax will be continuously improved. As additional data and
detail is added to the predictive database and the company’s algorithms applied, the
tolerance around each metric will likely become smaller, improving the accuracy of test
results even further.
By using the research done on the connections between hormone levels and emotions, as
well as the connections between emotions and mental health states, Exmovere Holdings,
Inc. will be providing leading edge technology-based solutions in emotion detection
products for healthcare professionals worldwide. BrainFax represents a new offering
consistent with the company’s core competencies and product development strategies.
Initially, due to the greater need for an objective measurement tool, the new product
introduction and launch will focus on mental health professionals, specifically psychiatrists.
By doing so, these professionals will be able to clinically assess and objectively confirm a
patient’s emotional state at the time of or near their examination and diagnosis. The
company’s launch plans will open up BrainFax to psychologists and licensed social workers
next in order to provide additional support for practicing healthcare professionals who need
the testing available to help determine a patient’s emotional state over time.

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Physicians also have needs for BrainFax. Particular segments or specialties – such as
Pediatricians – can benefit from the depth and breadth of information available. In their
practices, physicians also may need to prescribe drugs with emotional and mental side-
effects. BrainFax can help ascertain the impact of these compounds on patients over time,
but tracking moods through daily or periodic saliva testing. This in turn benefits their
practice by helping generate additional revenues.
To market BrainFax to the large potential markets where it can do the most good,
Exmovere Holdings, Inc. will seek to partner several major laboratories in the U.S. –
including Quest Diagnostics, Salimetrics, Labrix and other experienced salivary testing labs.
Using these laboratories initially will ensure national coverage in the U.S. during the
BrainFax launch, top of the line nanotechnologies for use in testing, as well as consistent
standards and quality controls in salivary assays and reporting of emotion detection results.
Using national and ultimately worldwide testing partners, distribution and use of BrainFax
becomes cost-effective and almost a medical necessity. Cheek swabs are an economical
commodity and can be purchased and distributed throughout the world. Using the swabs
to collect saliva can be easily taught and self-administered. The potential to reach billions
with a new technology that can assist with their diagnosis and treatment is also part of the
Exmovere Holdings, Inc. company mission.
While the National Institutes of Health, the National Institute of Mental Health, the Center
for Disease Control and the World Health Organization have all sponsored studies and seen
results which recognize saliva testing as a cost-effective, non-invasive alternative to blood
tests, most of the prior tests have all been laboratory based. The results are both deep and
broad for babies, women, and men. No other company has launched a broad effort to
bring emotion detection tools to healthcare professionals worldwide.
BrainFax – the world’s first salivary emotion detection technology. Your
healthcare professional knows how you feel.

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The Market
By focusing first on psychiatrists, Exmovere will focus BrainFax on a large, underserved
market. According to the latest information available from the National Institute of Mental
Health (NIMH), approximately 13% of adults in the U.S. use or receive mental health
services every year. This includes care in inpatient or outpatient settings and/or use of
prescription medication for mental or emotional problems. This percentage has remained
stable over the last several years.

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Among different segments of the population, there are several key differences in the
incidence of mental health issues. Young adults – in the 18 to 25 age group – have the
highest rate among all age segments. And, women have higher incidence than men. Among
major racial groups, White, Hispanic and Native American have the highest rates. However,
the incidence among racial groups ranges from about 3% to about 6%, while in the
youngest adult age group, the occurrence of serious mental illness is closer to 8%.

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There are significant opportunities for BrainFax to assist with mental healthcare
professional’s diagnoses. According to NIMH, over 40% of services are provided on an
outpatient basis, and over 50% involve use of prescription medications. As psychiatrists
provide their professional services and expertise, the objective assessment and reporting
provided by BrainFax can provide significant substantiation, documentation and verification.
Faced with a choice of treatment regimens including both counseling or talk-based
therapies as well as prescription drugs, psychiatrists can now measure emotional state or
mood at the start of their doctor-patient relationship as well as track over time.

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Among all people in the U.S., there are over 36 million involved in some form of mental
health services. While that number is almost double over the 10 year period from 1996 –
2006, the proportion of the adult population has remained relatively stable. One of the
implications of these results is increased incidence and use of mental health services among
children, 18 and younger, in the overall population.
Average annual costs of mental health support on a per person basis had remained
between $1,500 and $1,600 per year since 2002.

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Prevalence among children aged 13 to 18 remains under half, but over 45%. And, the
highest rates occur in older teen years, among 17 and 18 year olds.
The statistics underscore the importance of having non-invasive testing procedures and
tools available for mental health professionals. As they examine and diagnose younger
patients in particular, the use of BrainFax swabs can provide a simple, painless way to
collect information and test for emotion detection. Rather than create additional tension
and stress in patients by requiring invasive blood testing, salivary testing is easier and less
invasive to administer.

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The Technology
Saliva testing has many advantages over blood testing. Saliva specimen collection does not
require a blood draw and there are no risks to patients. Saliva collections are convenient
and can be done at work or at home. When stored properly, saliva samples are stable for
several weeks. With an accuracy of 92-96%, saliva testing is more accurate than blood
testing. The ability to collect more than one specimen is another advantage of saliva testing
because this can give providers more information than a single collection.
There are several different ways of measuring the hormones in a person’s body. Most blood
and serum tests look only at the level of hormones that are present in a person’s tissues.
This is known as “bound hormone levels”. Saliva testing looks at the “unbound hormone
levels” also known as “free fraction hormone levels” which are the hormone levels that are
available to be used by the body’s tissues. This gives providers a better idea of the levels of
hormones that are actually influencing the tissues, rather than just the level of hormones
that are present in the tissues. Measuring free fraction hormone levels gives a provider
more information than measuring bound hormone levels.
To properly assess emotions through saliva testing, cortisol, adrenaline and pH must be
measured and compared. BrainFax has been designed to use the measurements of all
three in order to triangulate results and confirm the emotional assessment. Rationale for
the use of this design is provided below.
Cortisol
The human adrenal glands do not secrete steroid hormones at a constant level throughout
the day. The hormones – especially cortisol – are actually released in a cycle, with the
highest value in the morning and the lowest value at night when functioning properly. This
24-hour cycle is called the circadian rhythm and is depicted below. An abnormal adrenal
rhythm can influence many functions of the body including both mental and physical
disease states.

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Adrenaline
Adrenaline is the body's activator, and is released in response to anxiety, exercise, or fear.
This is the basis of the so-called 'fight-or-flight' reaction. When a person or animal is
threatened, the options are usually either to stand its ground and fight, or run away as fast
as possible. Both responses would require extra supplies of blood and oxygen in the
muscles. Fright causes the brain to send signals to the renal glands which start pumping
large amounts of adrenalin into the bloodstream. This increases the heart and breathing
rate in preparation for the ensuing action. Levels of adrenaline in the saliva are typically
most highly correlated with extreme emotions, such as rage, anger, fear or heightened
levels of anxiety.
pH
Emotions do not have to be strong to cause a physical response. Your body responds to all
of your mental activities and emotions. Worry, anxiety, hate, joy, elation, and so on. Every
emotion affects your body. And if you are clinging to some past stress, that same emotion
is played over and over again for weeks, months, and years; your body continues to be
affected the same way over and over.
Emotions affect the pH of your saliva. Salivary test design using pH levels requires a two-
stage test. The pH of your saliva dances from low to high depending on what you’ve put
into your mouth recently. The “normal” pH of saliva is considered to be around 6.8.
However, it can go much lower and much higher than that. Chew on an orange, and your
saliva pH can drop like a rock. Swish a solution of water and baking soda in your mouth
(although I’m not sure why you would want to do that) and your saliva pH shoots up like a
rocket. The point is that your saliva pH changes instantly to handle current conditions,
including your emotions.
In the two-stage test, patients take a pH reading (with the BrainFax swab and litmus
paper) once in the morning before they have eaten anything and record that level. Next,
the patient introduces an acidic stimulus – a slice of lemon or teaspoon of lemon juice –
and measures the pH level of the saliva a second time and again record pH numbers.
According to research from Dr. Clark Brooks, the results can be interpreted as follows:
Numbers Go Up
If your pH numbers go up, this indicates that your body can respond easily to strong stimuli
(acid of the lemon). No matter what color your first number was, this change to higher is
beneficial.

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Numbers Go Down
If your numbers don’t go up but instead go down, something is bothering you; stress or
anxiety is dominating your physiology. Take this as a sign that your life and health could be
improved with a few changes.
Numbers Don’t Change
When before and after numbers are virtually the same, this can be the strongest indication
that emotional distress is a key factor. It’s time to take action. Emotional habits and the
moods they create need to be re-examined and modified.
Based on these three tests – cortisol, adrenaline and pH – mental health professionals can
objectively determine a patient’s emotional state. The purpose of the testing will be to
provide the practitioner with a confirmation of their diagnosis and help them create a
record or basis for any related medication prescriptions.
BrainFax begins by taking all published and laboratory results from saliva testing over the
past 10 years. Archives of the NIH, NIMH, CDC, DOD as well as independent labs are used
to produce a set of baseline biometrics and the moods that go with them. Comparing an
individual patient’s lab results to these baselines provides the psychiatrist with an objective
assessment of the emotional state of the individual. Similar to many blood serum tests,
BrainFax provides a range of valences which correspond to the individual’s results.
For example, the following ranges apply to common blood test results:
A full list of reference ranges from common blood tests is available on Wikipedia at
http://en.wikipedia.org/wiki/Reference_ranges_for_common_blood_tests. These reference
ranges are a result of years of research, laboratory records and individual records which
help create a national database.
Test Arterial/Venous Lower limit Upper limit
pH Arterial 7.34 7.44
Venous 7.31 7.41
Test Patient type Lower limit Upper limit Unit
Cortisol 9:00 AM 140 700 nmol/L
5 25 μg/dL
Midnight 80 350 nmol/L
2.9 13 μg/dL

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Exmovere Holdings, Inc. as part of the BrainFax service will create a similar database of
research, ranges and test results using records and studies from NIH, NIMH, CDC and other
publicly available records. To the extent that cooperation from national and international
agencies or laboratories can be used as inputs as well – without violating current HIPAA
rules and regulations – those results will be used as well. A small sample of the types of
studies and key results is below.
Recommended Reading
To further understand the connections between cortisol, adrenaline and pH as well as how
they are used in salivary assays to detect emotional states, the following research, reports
and studies will be useful.
Salimetrics, one of the leading salivary assay labs in the U.S. has compiled archives of the
latest uses and results of saliva testing. These listings represent the most important
findings from 2011. Additional archives that summarize results from 2008 - 2010 are
available at the company’s website in the Archives page.
08.11.11 - Psychological distress and salivary cortisol covary within persons during pregnancy.
Giesbrecht, G.F., et al. (2011). Psychoneuroendocrinology.
This study examined the possibility of a link between altered cortisol levels due to maternal psychological
distress during pregnancy and changes in fetal development. A robust association was found between
negative mood and salivary cortisol in mothers, suggesting that cortisol may plausibly transfer the effects of
maternal stress to the developing fetus. Abstract
08.11.11 - Allostasis and allostatic load in the context of poverty in early childhood.
Blair, C., et al. (2011). Dev Psychopathol.
The effect of early environmental adversity on children’s basal salivary cortisol levels was followed in this
longitudinal study of children from the age of 7 to 48 months. Elevated cortisol levels were found to be
related to poor housing quality, African-American ethnicity, low positive caregiving behavior, adult exits from
the home, and perceived economic insufficiency. Abstract
08.04.11 - Salimetrics Spit Camper wins research award!
Bridget Hatfield, Ph.D., a research associate working with the Center for Advanced Study of Teaching and Learning,
is among five researchers nationally receiving an Early Career Educational Psychology Research Award from the
Education Psychology Division (15) of the American Psychological Association. News Release

August 29, 2011 P a g e | 17
07.26.11 - Assessing stress reactivity indexed via salivary cortisol in preschool-aged children.
Kryski, K.R., et al. (2011). Psychoneuroendocrinology.
To fulfill the need for a stressor paradigm that evokes mean increases in salivary cortisol in young children,
this study examines the ability of a standardized task (adapted from Lewis and Ramsay, 2002) to assess
cortisol reactivity in a group of preschool-aged children, with positive results. Abstract
07.26.11 - Direct and moderating links of salivary alpha-amylase and cortisol stress-reactivity to youth
behavioral and emotional adjustment.
Allwood, M.A., et al. (2011) Biol Psychol.
This study explores basal levels and stress responses of salivary alpha-amylase and cortisol as measures of
activity in the autonomic nervous system and HPA axis, respectively, in relation to behavioral and emotional
adjustment in children aged 7-16 years. Alpha-amylase was positively related to anxiety and also moderated
associations between cortisol reactivity and problem behavior. Abstract
07.12.11 - 2D:4D ratios in the first 2 years of life: Stability and relation to testosterone exposure and
sensitivity.
Knickmeyer, R.C., (2011). Horm Behav.
In this study on the development of 2D:4D ratios in infancy, salivary testosterone levels were measured and
DNA samples were genotyped for the CAG repeat polymorphism in the androgen receptor. Substantial
variability across age in the 2D:4D ratios and small sex differences compared to adults suggest that 2D:4D
may not function well as a proxy measure of prenatal testosterone exposure in infancy. The interaction of
salivary testosterone and CAG repeat length predicted digit ratios and change in digit rations in males.
2D:4D ratios in adults may reflect, in part, neonatal testosterone exposure. Abstract
07.12.11 - Influences of menstrual cycle position and sex hormone levels on spontaneous intrusive
recollections following emotional stimuli.
Ferree, N.K., et al. (2011). Conscious Cogn.
Salivary sex hormone levels were analyzed in women to investigate the relationship between the menstrual
cycle and the higher rates of spontaneous intrusive recollections (SIR) in women following emotional events
compared to men. Women in the luteal phase reported significantly more SIRs than did women in the
follicular phase, and SIR frequency significantly correlated with salivary progesterone levels. Implications for
disorders such as PTSD are discussed. Abstract
06.15.11 - Increased serum androstenedione in adults with autism spectrum conditions.
Ruta, L., et al. (2011). Psychoneuroendocrinology.
Current research in neurodevelopment is exploring possible associations between sex-steroid hormones,
autism spectrum conditions (ASC), and autistic traits. This study examined serum levels of the sex steroids
testosterone and estradiol, and their precusors, DHEA-S and androstenedione. ASC diagnosis strongly
predicted androstenedione levels, and serum androstenedione levels were significantly elevated in the ASC
individuals, adding support to the proposed relationship between sex hormones and brain development.
Abstract

August 29, 2011 P a g e | 18
06.15.11 - Hair cortisol levels as a retrospective marker of hypothalamic-pituitary axis activity
throughout pregnancy: Comparison to salivary cortisol.
D’Anna-Hernandez, K.L. et al. (2011). Physiol Behav.
Cortisol levels in hair of women were evaluated and compared to diurnal salivary cortisol levels throughout
the course of pregnancy. Salivary and hair cortisol levels rose during pregnancy, and the areas under the
curve with respect to ground (AUCg) were also correlated for both measures throughout pregnancy. Hair
cortisol levels are a useful measure of long-term cortisol activity. Abstract
06.09.11 - No effect of social exclusion on salivary cortisol secretion in women in a randomized
controlled study.
Zöller, C., et al. (2010). Psychoneuroendocrinology.
The effects of social exclusion on mood and HPA-axis response (salivary cortisol) were examined in this
study using a standardized Cyberball paradigm. The social exclusion paradigm was not observed to affect
HPA-axis function, although significant effects on mood were observed. Abstract
06.09.11 - Neural pathways link social support to attenuated neuroendocrine stress responses.
Eisenberger, N.I., et al. (2007). NeuroImage.
This study examined relationships between levels of social support and assessments of neurocognitive
reactivity to a social rejection task (fMRI imaging during a Cyberball paradigm) and neuroendocrine
reactivity to a social stressor (salivary cortisol responses to the TSST procedure). Individuals who had
regular social support showed reduced neurocognitive reactivity to social stressors in two brain regions,
which in turn was associated with reduced cortisol reactivity. The hypothalamus mediated the relationship
between the two brain regions and cortisol responses, suggesting a link between activity in the two regions
and activation of the HPA axis. Abstract
06.09.11 - Effects of an early family intervention on children’s memory: The mediating effects of
cortisol levels.
Bugental, D., et al. (2010). Mind Brain Educ.
This study examined the effects of a home visitation intervention program on salivary cortisol levels and
memory abilities of at-risk pre-term children. Maternal participation in the program led to lowered basal
cortisol levels in the infants and higher verbal short-term memory at age 3. Abstract
05.27.11 - State, not trait, neuroendocrine function predicts costly reactive aggression in men after
social exclusion and inclusion.
Geniole, S.N., et al. (2011). Biol Psychol.
Aggression was measured in men randomly assigned to a social exclusion or social inclusion condition
during a computer ball-toss game. Salivary cortisol and testosterone were measured at three points.
Increases in cortisol and testosterone were found to predict aggressive behavior, while baseline cortisol and
testosterone did not. Abstract
05.27.11 - Diet and the evolution of human amylase gene copy number variation.
Perry, G.H., et al. (2011). Nature Genetics.
Copy number of the salivary amylase gene (AMY1) is correlated positively with salivary amylase protein
level, and individuals from populations with high-starch diets have, on average, more AMY1 copies than
those with traditionally low-starch diets. Abstract

August 29, 2011 P a g e | 19
05.27.11 - The cortisol awakening response in context.
Clow, A., et al. (2010). Int Rev Neurobiol.
This discussion examines the initiation and control of the CAR, with a consideration of its relationship to
other awakening-induced processes, changes in hormones and the immune system, and mobilization of the
motor system. Abstract
05.27.11 - Diagnostic potential of Saliva: Current state and future applications.
Pfaffe, T., et al. (2011). Clin Chem.
This review examines the production and secretion of saliva, the salivary proteome, transportation of
biomolecules from blood into saliva, and the diagnostic potential of saliva for use in detection of
cardiovascular disease and oral and breast cancers. Abstract
05.18.11 - Predictors and patterns of participant adherence to a cortisol collection protocol.
Hall, D.L., et al. (2011). Psychoneuroendocrinology.
This study examined participant adherence to a multi-point salivary cortisol sampling protocol with respect
to various demographic factors and fatigue. Abstract
05.18.11 - Current developments in salivary diagnostics.
Miller, C.S., et al. (2010). Biomark Med.
Recent developments in the diagnostic use of salivary biomarkers are examined in this paper, with particular
emphasis on panels of markers that could potentially help with the identification and treatment of
periodontal disease and cardiovascular disease. Abstract
05.18.11 - Self-esteem moderates neuroendocrine and psychological responses to interpersonal
rejection.
Ford, M.B. & Collins, N.L. (2010). J Pers Soc Psychol.
Salivary cortisol was used in this study that explores interactions between interpersonal rejection,
physiological stress pathways, and defensive social action. Self-blame attributions were found to mediated
the link between low self-esteem and increased cortisol reactivity; cortisol reactivity, in turn, was found to
mediate the link between low self-esteem and increased partner derogation. Abstract
05.18.11 - Individual differences in biological stress responses moderate the contribution of early peer
victimization to subsequent depressive symptoms.
Rudolph, K.D., et al. (2011). Psychopharmacology (Berl).
Salivary cortisol and alpha-amylase were used to study possible relationships between individual differences
in biological stress responses, peer victimization, and the development of depressive symptoms in children.
Victimization was found to interact with high levels of cortisol measured in anticipation of a laboratory stress
task to predict rumination and depressive symptoms one year later. Victimization also predicted subsequent
depressive symptoms in girls with high sAA reactivity across the task. Abstract

August 29, 2011 P a g e | 20
05.12.11 - Are salivary gonadal steroid concentrations influenced by acute psychosocial stress? A study
using the Trier Social Stress Test (TSST).
Schoofs, D., & Wolf, O.T. (2011). Int J Psychophysiol.
The effects of the TSST on the HPA axis, sympathetic nervous system, and HPG axis were studied using
salivary analytes. As expected the stress condition led to increased salivary concentrations of cortisol and
alpha-amylase. Levels of testosterone, progesterone, and estradiol were not affected, however, indicating
that acute psychosocial laboratory stress had no strong rapid effects on salivary gonadal steroids. Abstract
05.12.11 - Cross-sectional and 35-year longitudinal assessment of salivary cortisol and cognitive
function: The Vietnam Era Twin Study of Aging.
Franz, C.E., et al. (2011). Psychoneuroendocrinology.
This study examined the effects of cortisol levels on executive function abilities related to the prefrontal
cortex in humans. Higher average salivary cortisol output across three days in a sample of middle-aged
male twins was found to be associated with poorer performance in three domains: executive measures,
processing speed, and visual-spatial memory. Abstract
05.05.11 - Stress in migrant farmworkers during premigration.
Clingerman, E.M., & Brown, A. (2011). Biol Res Nurs.
Salivary cortisol was used in this study of the effects of stress on migrant farmworkers. Results indicated
that migrant workers experienced significant levels of stress prior to migration and that cortisol responses
varied significantly by the levels of perceived stress. Abstract
05.05.11 - Neurobiological and behavioral stress reactivity in children prenatally exposed to tobacco.
Huijbregts, S.C., et al. (2011). Psychoneuroendocrinology.
Salivary cortisol and salivary alpha-amylase levels were measured throughout a stressful neuropsychological
test session in three groups of children: those exposed prenatally to tobacco, those with disruptive behavior
problems, and normal controls. No significant differences in cortisol responses were found for the three
groups. sAA levels , sAA reactivity, and behavioral reactivity patterns, however, were found to be similar in
prenatally exposed children and those with behavior problems, compared to the normal controls. Abstract
04.29.11 - Salivary alpha-amylase levels as a biomarker of experienced fear.
Buchanan, T.W., et al. (2011). Commun Integr Biol.
Salivary cortisol and salivary alpha-amylase were studied as indices of emotional arousal before and after
participants went through a fear-challenge course. Alpha-Amylase, but not cortisol, showed a highly specific
increase for participants with both emotional arousal and negative valence. Participants who had high
arousal and positive valence exhibited no increase in alpha-amylase. Abstract
04.29.11 - Asymmetry of salivary cortisol and alpha-amylase responses to psychosocial stress in
anorexia nervosa but not in bulimia nervosa.
Monteleone, P., et al. (2011). Psychol Med.
Salivary cortisol and salivary alpha-amylase responses to the Trier Social Stress Test (TSST) were studied in
individuals with anorexia nervosa or bulimia nervosa, and in healthy controls. Anorexia patients showed a
normal cortisol response to the TSST (at significantly increase hormone levels), but almost no response of
alpha-amylase. In contrast, bulemia patients showed a normal response of both alpha-amylase and cortisol
to the TSST (with elevated pre-stress levels of alpha-amylase). Abstract

August 29, 2011 P a g e | 21
04.18.11 - The SIS release date is here!
The Salimetrics Infant’s Swab is set to be released in June, 2011. See product details here.
04.13.11 - ‘Immunogenetics of Aging’: Report on the activities of the 15th International HLA and
Immunogenetics Working Group and 15th International HLA and Immunogenetics Workshop.
Naumova, E., et al. (2011). Tissue Antigens.
This report presents information from studies that have examined human leukocyte antigen (HLA) genes,
cytokine genes, and some innate immunity genes in relation to successful aging and longevity. Abstract
04.13.11 - Children’s internalizing symptoms: The role of interactions between cortisol and respiratory
sinus arrhythmia.
El-Sheikh, M., et al. (2011). Physiol Behav.
The interactions of the HPA axis and the parasympathetic nervous system were examined using salivary
cortisol and respiratory sinus arrhythmia (RSA), respectively, as measures of activity in the two systems.
Children with higher cortisol levels in conjunction with higher RSA levels tended to exhibit the lowest levels
of depression and anxiety symptoms. Abstract
03.28.11 - Genome-wide association studies of sleep disorders.
Byrd-Craven, J., et al. (2010). J Social Personal Relationships.
This study used salivary cortisol and salivary alpha-amylase as measures of activity in the hypothalamic-
pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS), respectively, in order to explore the
reactivity of the two systems to co-rumination in same-sex friendships among young women. At low levels
of negative affect the SNS system was more responsive than the HPA axis, but higher levels of negative
affect from excessive problem discussion was found to influence both systems. These results suggest that
examination of both stress systems may be important in order to understand the social dynamics of coping.
Abstract
03.28.11 - Genome-wide association studies of sleep disorders.
Raizen, D.M. & Wu, M.N. (2011). Chest.
This review examines recent advances in the study of sleep disorders through genome-wide association
studies. In particular, the identification of gene variants associated with restless legs syndrome and
narcolepsy have opened new areas of research that may lead to a better understanding of these disorders.
Abstract
03.17.11 - Biosocial influences on the family: A decade review.
D’Onofrio, B.M., & Lahey, B.B. (2010). J Marriage Family.
This review examines recent advances in biosocial family research, with a discussion of the need to
integrate measurement of biological factors. Abstract
03.17.11 - Effects of an early family intervention on children’s memory: The mediating effects of
cortisol levels.
Bugental, D.B., et al. (2010). Mind Brain Educ.
This study examines the use of an early family intervention program to reduce cortisol levels in at-risk
preterm infants, with subsequent improvements in short-term memory at age 3. Abstract

August 29, 2011 P a g e | 22
03.02.11 - a-Amylase as a reliable and convenient measure of sympathetic activity: Don’t start
salivating just yet!
Bosch, J.A., et al. (2011). Psychoneuroendocrinology.
In this invited mini-review, the authors address the use of a-amylase as a non-invasive measure of
sympathetic nervous activity. They summarize research that has shown that parasympathetic nerves also
contribute to a-amylase release, as well as regulating saliva flow from the saliva glands. Failure to consider
differences in the structure and innervation of the various saliva glands and the resultant effects on salivary
levels of a-amylase may result in data that is hard to interpret and that does not represent a reliable
measure of SNS activity. Unstimulated whole saliva collected by the passive drool technique is
recommended for a-amylase determinations. Abstract
02.25.11 - Conference on Stress and the Brain to be held at Johns Hopkins University, April 28th-29th,
2011.
The Johns Hopkins University is sponsoring an interactive summit conference on Stress and the Brain –
Implications for Health, Development, and Learning, to be held April 28th-29th, 2011. The keynote speaker
will be Sir Michael Rutter. Read More
02.23.11 - Correlated genotypes in friendship networks
Fowler, J.H., et al. (2011). Proc. Natl. Acad. Sci.
Using information about respondents’ genes and friendship ties from two large independent studies–the
National Longitudinal Study of Adolescent Health, and the Framingham Heart Study Social Network– this
paper examines the question of whether any correlation exists among genotypes of people in
nonreproductive, friendship unions. Correlations for two genes were found, one positive and one negative,
suggesting that genotypic clustering does occur in social networks. Abstract
02.16.11 - Dr. Douglas A. Granger to give seminar on Salivary Analytes
The Pediatric Topics in Growth and Development Seminar Series at the University of Maryland
School of Medicine will feature Dr. Douglas A. Granger in a talk titled “Integration of Salivary Analytes into
Behavioral and Developmental Science,” March 1, 2011. Dr. Granger serves as director of the Center for
Interdisciplinary Salivary Bioscience Research at the Johns Hopkins University School of Nursing, as well as
Founder and Chief Scientific and Strategy Advisor at Salimetrics. Read More
02.10.11 - Oral Fluid Reveals More Heroin Use Than Previously Believed, According to Quest
Diagnostics Drug Testing Index.
Quest Diagnostics (Jan. 25, 2011). News Release.
Testing more than 320,000 oral fluid samples collected from the general U.S. workforce in 2010 has found a
higher user rate for the heroin marker 6-acetylmorphine (6-AM) when compared to the results from urine
testing. News Release

August 29, 2011 P a g e | 23
01.27.11 - The effects of maltreatment and neuroendocrine regulation on memory performance.
Cicchetti, D., et al. (2010). Child Dev.
In the setting of a week-long camp for maltreated children, memory performance, behavioral symptoms,
and morning salivary cortisol levels were evaluated. The results of the study illustrate the effects of
maltreatment and hypocortisolism on children’s recognition memory errors. Abstract
01.27.11 - Genetic and environmental influences on cortisol regulation across days and contexts in
middle-aged men.
Franz, C.E., et al. (2010). Behav Genet.
The heritability of salivary cortisol concentrations was examined as part of the Vietnam Era Twin Study of
Aging. Significant cortisol heritability estimates for identical twins were found for laboratory measures, but
not when samples were collected independently while the subjects were at home. The authors suggest that
cortisol results were correlated in identical twins only when they were both exposed to the same mild
challenge of the unfamiliar laboratory experience. Abstract
01.14.11 - Salimetrics Introduces New Saliva Collection Device for Infants
In response to requests from researchers for a safe, effective, and easy-to-use saliva collection device for
use with infants, Salimetrics has now introduced the Salimetrics Infant’s Swab (SIS). This new swab has the
following features:
 Small size appropriate for the mouths of infants (5 x 90 mm).
 No choking hazard. The extra length allows one end of the swab to be held by an adult while the
other end is placed in the infant’s mouth.
 The taste and texture of the durable polymer used in the SIS are acceptable to infants.
 Better recovery of sample volumes (typically in range of 200-1000 µL). Samples may be recovered by
centrifugation, or by compression in a needle-less syringe while in the field, so that the actual volume
collected can be determined, followed by repetition if necessary. Reports from researchers indicate
the SIS helps them avoid the problem of samples with insufficient volume for testing.
 Excellent analyte recovery characteristics (>95% for cortisol).
 No assay interference for a broader range of analytes. The SIS may used to collect saliva for
determination of the following analytes: alpha-amylase, chromogranin A, cortisol, cotinine, C-reactive
protein, SIgA, and testosterone.
 The SIS is made of the same synthetic polymer used in our regular Salimetrics Oral Swab (SOS) and
in the Salimetrics Children’s Swab (SCS), making possible consistency in collection method over the
course of longitudinal studies.
These results are only a partial list of the most recent results from over 2,500 studies.
They do, though, show the dramatic potential of BrainFax to offer psychiatrists and
opportunity to objectively measure and track key indicators of emotional states or moods in
their patients. The body of research does also point to the longer term potential of
BrainFax to bring new technologies and testing to not only hormones and pH, but most of
the same types of indicators currently used in blood testing. BrainFax promises to
significantly advance psychiatry and other medical disciplines with its ability to tie emotional
states and disease states (both mental and physical) together through saliva testing.

August 29, 2011 P a g e | 24
BrainFax Design
Based on the combined metrics from all NIH, NIMH, CDC and other professional outcomes,
BrainFax will make distinct connections between the laboratory-level readings and
respondents emotional state and moods. Exmovere’s proprietary algorithms are applied
against the available data to provide precise interpretations. The following diagram explains
more about how BrainFax works.
Key elements of the BrainFax system include in-home administration of saliva sample
collection, expert panel validation of baselines and methodology, and creation of standards
for determining emotional states. Medical professionals and healthcare experts will have
access to lab reports from BrainFax that is similar to what they receive today from blood
serum testing. All parts of the system will remain in compliance with HIPAA laws. Each of
these design elements and system attributes is described in more detail below.
Saliva
Sample
Collection
Ship to Lab
Lab
Testing
Stat
Modeling
Compare
to baseline
Metrics
Exmovere
Algorithms
Mood ID
Online
Reporting
Patient, in office
or at home
Expert Panel
Validation
and
Standards
HIPAA
Compliant
Access for
Healthcare
Professional

August 29, 2011 P a g e | 25
In-home administration of sample collection is an important part of BrainFax application
and use. One of the more important reasons for this part of the design is based on the
need for multiple samples throughout the day. Because an individual’s cortisol levels vary
throughout the day, a single reading will not be adequate. Rather than have patients
provide samples at the practitioner’s office, it will be easier and more cost-effective to
administer at home. The collection devices – cheek swabs – are easy to distribute and use.
Similarly, samples need to be taken twice to accurately capture pH readings. And, finally
adrenaline readings can be monitored with the multiple readings as well.
One of the benefits of in-home sample collection will be the psychiatrist’s ability to compare
mood states when the patient is at home and compare those to readings taken when the
patient is in the office. With the wealth of information becoming available on younger
segments of the population, including infant, adolescent, and pre-teen, the opportunity to
monitor mood states in different settings can potentially have a dramatic impact on
behavior modification and prescribed therapies. Rather than depend only on what a patient
says or does while in the office, by using BrainFax, mental health professionals can capture
substantially more information and data to help the patient.
Perhaps the most important aspect of in-home sample collection, though, is the ease of use
and non-invasive BrainFax protocol. Based on the types of swabs manufactured, parents of
younger patients can administer the sample collection procedures at home. Pre-teens,
teens, and adults as well can take saliva samples with the BrainFax swabs in the comfort of
their own homes. If these patients were to provide samples in the psychologist, psychiatrist
or therapist office, their stress levels could be elevated resulting in higher levels of cortisol
and adrenaline as well as affecting pH balance. These elevated readings would cause
analytics and emotion detection to present false readings. To capture true and accurate
readings of cortisol, adrenaline and pH levels, as well as promote ease of use, BrainFax is
best administered at home by the patients themselves.
The following represent different types of swabs and collection vials, designed for
alternative population and demographic segments, which can easily be used to collect
saliva samples at home. These are typical of what’s available on the market today.

August 29, 2011 P a g e | 26
To aid labs with sample storage and compliance with HIPAA regulations, most have storage
boxes like the ones below.
Joint venture and laboratory partners with Exmovere Holdings, Inc. in the launch and
introduction of BrainFax will provide all needed saliva collection swabs and storage
collection boxes. Rather than wait for psychiatry practice offices to request swabs initially,
Exmovere and its partners plan to distribute swabs to known or interested offices
throughout the United States. In addition, early baselines – validated by the company’s
expert panel – will be provided along with reference to all of the research studies and
professional resources used to construct BrainFax. Exmovere and its partners will also
provide 2 or 3 lab results tests to each interested psychiatrist, free of charge, at the
beginning of the national launch of the new service. This will expose most psychiatry
offices and practitioners to BrainFax, allow them to read actual results for their patients and
compare what they get back from the lab results to their own exam results and diagnoses.
To facilitate the verification and validation of baseline results, developed from a complete
dataset gathered from existing research, an expert panel will be recruited by Exmovere
Holdings, Inc. as part of the BrainFax launch and service development. The panel will
consist of recognized experts from psychology, psychiatry and therapy fields, as well as the
broader medical community. Experience with or research pertaining to the use of saliva
testing will be a key attribute for panel members. The purpose of the panel will be to
testify to the quality of the database and to provide BrainFax usage protocols for the
system to ensure that the readings are as meaningful as possible. The experts have the
task of evaluating and validating results across a wide spectrum of segments, including but
not limited to age, gender, race, geography, lifestyle and other factors which may be
relevant to interpretation of future test result.
Members will be recruited from current leading hospitals and institutions as well as private
practice. For example, the following experts were recently identified as leading edge
experts in salivary assays and diagnostics.
Eric Anslyn, PhD, at the University of Texas (UT) at Austin has developed a sensor array platform
suited for point-of-care diagnostics; it is based on a micromachined bead-based platform that is
amenable to multianalyte detection and quantitation. The UT research group teamed with experts in
salivary diagnostics at the University of Kentucky, Lexington, for the collection and analysis of
clinical samples.

August 29, 2011 P a g e | 27
Daniel Malamud, PhD, MA, and his research team at New York University, New York City, are involved
in the identification and characterization of antibacterial and antiviral molecules, as well as assay
development, using oral fluid as a noninvasive diagnostic method. This research team is involved in
designing a point-of-care detection system for the identification of bacterial and viral pathogens.
Anup Singh, PhD, Sandia National Laboratories, Livermore, Calif., is developing microfluidic systems
for the analysis of biological molecules. His research group is developing an integrated microfluidic
system for simultaneous detection of multiple analytes in saliva and in other oral fluids.
David Stahl, PhD, University of Washington, Seattle, is involved in studies of microbial community
structure and function in many habitats, including the human mouth. Dr. Stahl’s group is developing
DNA microarray-based technology for the rapid and unambiguous detection of microbial biomarkers
in oral fluids.
David Walt, PhD, Tufts University, Medford, Mass., is using a bead-based fiber-optic–based detection
platform to investigate salivary diagnostics in the context of end-stage renal disease, asthma and
opportunistic infections
Many of these experts have been focused on oral-related health issues, dental practices
and more general physical health uses of salivary diagnostics research. For example, the
Wrigley Oral Healthcare Program sponsors Salivary Research Awards each year. The 2011
award winners can be reviewed at the company’s website.
Similar experts from psychiatry, psychology and therapy will be sought out and recruited to
be part of the BrainFax panel. The purpose of the panel will be to review testing and
results, assist Exmovere Holdings, Inc. with establishing baselines, and prepare support for
creating BrainFax standards for emotion detection using salivary assays for key emotional
states, including euphoria, anger, stress, fear and other emotions. Based on the company’s
algorithms and the BrainFax system, these will be used as predictors for many of the
emotional and mood states found in the Clinical Syndromes of the DSM IV, the key
diagnostic reference for mental health professionals.
Market Potential
According to the U.S. Bureau of Labor Statistics, there are over 325,000 practicing
psychologists, psychiatrists and therapists in the U.S. market today. Slightly more than half
of these (54%) are in private practice and another 10-15% work primarily in hospital and
in-patient care facilities. The remaining 25-30% are employed in government institutions,
research facilities, universities and government-sponsored agencies. For the initial BrainFax
launch, the relevant target is the combination of private practice and in-patient care
psychiatrists – roughly 22,500 working professionals in the United States.

August 29, 2011 P a g e | 28
The World Health Organization recently estimated there are on average 10 psychiatrists per
100,000 of the worlds population. The range of service varies considerably from a high of
about 15 in the U.S. to a low of 1 in many third world countries and lesser developed
economies. At this rate, based on current estimates of the world population, the
implication is that there are well over 500,000 practicing psychiatrists worldwide.
For these professionals, with normal office hours, their schedules permit working with 6-8
patients per day. During one week, for the total target of 22,500 professionals in the U.S.
that amounts to just under 1 million patients, or close to 30 million each month. If each
patient requires 2 or 3 swabs per day to capture the right information at the right time for
each patient, BrainFax could be responsible for as many as 90 million tests each month.
Worldwide, once BrainFax goes global based on reliable international labs and testing
results, the potential grows by a factor of at least 20 times based on the relationship of the
number of U.S. psychiatrists to the number worldwide. Based on international practice,
though, it may be more realistic to assume that not all patients will be considered for
BrainFax because payments for lab results may be prohibitive in some countries and
economies. Even with a factor of 10x, BrainFax could be responsible for over 900 million
tests per month.
Expansion to other practitioners of mental health care – including licensed social workers,
psychologists and therapists brings the total number of professionals in the U.S. to close to
225,000 based on the latest BLS statistics. Worldwide this number is even larger. As
BrainFax expands, the number of tests each month will begin to grow into a several billion.
As Exmovere Holdings, Inc. creates awareness and usage of BrainFax in the psychiatry
field, sales can be expected to grow rapidly and significantly. Assuming a $10 net revenue
contribution from each unit – after paying lab, testing and reporting fees to its joint venture
and lab testing partners – generates company contribution of about $900 million per month
or over $1.8 billion per year once the new service reaches a full-scale level of penetration
and usage in the U.S. marketplace.
In Years 1 – 5, the company can expect growth to increase rapidly. With marketing and
advertising support, creation of BrainFax standards, use and application of the saliva-based
emotion detection services, additional demand will be created. And, internationally, the
World Health Organization already supports the basis for BrainFax based on the
organization’s most recent research and findings. With the additional resources of the
WHO behind creating awareness and use around the world, the company expects to build a
multi-billion dollar service as the BrainFax offering matures.

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