Discussion: RE: NURS_6630_Week2_Discussion_Rubric
I think you did a great job of providing insightful information on the discussion topic. You briefly touched
on the subject of epigenetics and I wanted to share with you some additional information I discovered that
you may find helpful. Epigenetics can be described as a story of the brain that can be affected by
inheriting certain genes and by the environment one is experiencing which can trigger genes to be
activated or silenced (Stahl, 2013). More specifically, genetically identical cells can experience changes
because epigenetics influences gene transcription by affecting changes in DNA and chromatin structure
and accessibility (Maity et al., 2021).
Epigenetics is important to mental health disorders because many of them are either inherited or
developed because of one’s environment. For example, schizophrenia is a condition that is known to be
correlated with genetics, but personality disorders seem to be triggered by experiences such as traumas.
With that being said, psychopharmacologic therapy can be utilized to treat these disorders but epigenetic
research needs to take place to determine which specific genes are the culprit behind these disorders to
develop and prescribe medications to actively target these disorders (Lisoway et al., 2021). It is
imperative for prescribers to have a knowledge base of genetics and how medicines can be utilized to
improve mental health disorders.
Lisoway, A. J., Chen, C. C., Zai, C. C., Tiwari, A. K., & Kennedy, J. L. (2021). Toward
personalized medicine in schizophrenia: Genetics and epigenetics of
antipsychotic treatment. Schizophrenia Research, 232, 112–124.
Maity, S., Farrell, K., Navabpour, S., Narayanan, S. N., & Jarome, T. J. (2021).
Epigenetic Mechanisms in Memory and Cognitive Decline Associated with
Aging and Alzheimer’s Disease. International Journal of Molecular
Sciences, 22(22), 12280. https://doi.org/10.3390/ijms222212280
Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and
practical application (4 th ed.) Cambridge University Press.
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1 month ago
Week two response # 2
Your post was educative and informative especially in the area of epigenetics
and pharmacology. Kular and Kular (2018) in their article, epigenetics applied
to psychiatry: clinical opportunities and future challenges studied epigenetics
and pharmacotherapy. The epigenetic system consists of various
DNA/histone modifications and non-coding RNAs (Furtado et al, 2019). Kular
and Kular (2018) classified epigenetic medicine into two:DNA
methyltransferase (DNMT) inhibitors that acts on DNA methylation (5-
aza(2’deoxy)cytidine or decitabine); and histone deacetylase (HDAC)
inhibitors (valproic acid (VPA) or trichostatin A) which targets the histone
The DNMT inhibitors have been effective in the treatment of cancer, but it is
still in the preliminary stage in the treatment of psychiatric disorders. The
DNMT inhibitors produce neurotoxic substances which limits their use in the
treatment of psychiatric disorders (Kular & Kular, 2018).
For quite some time, the HDAC inhibitor VPA has been used as (mood
stabilizer) in the treatment of patients with bipolar disorders and
(anticonvulsant) in epileptic patients. The use of DNMT or HDAC inhibitors are
limited because of their overall effect on regulating multiple genes which can
lead to numerous side effects such as teratogenicity (Kular & Kular, 2018).
Kular and Kular (2018) identified two systems that have been studied in the
area of reducing the global effect of DNMT or HDAC inhibitors. The CRISPR-
dCas9 system can lower the global effect of the DNMT and HDAC inhibitors
by targeting a particular genome and deactivating the endonuclease dCas9
fused to the catalytic domain of an epigenetic enzyme (Kular & Kular,
2018).This effect produces a lasting DNA methylation or histone PTM. Also
tissue specificity can reduce the global effect of DNMT and HDAC by using
natural or synthetic carrier nanoparticles which work as delivery tools to the
specific area of the central nervous system (Kular & Kular, 2018).
Furtado et al. (2019). Epidrugs: Targeting epigenetic marks in cancer
Kular, L., & Kular, S. (2018). Epigenetics applied to psychiatry: Clinical
opportunities and future challenges. Psychiatry and Clinical
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1 month ago
You have widened my understanding of how the antagonist medication works as it relates to
benzodiazepam and flumazenil. According to Razavizadeh, et al (2021), flumazenil is a
competitive benzodiazepine receptor antagonist that has proven to be an efficient antidote. Other
study has shown strong recommendation for the use of flumazenil as an antagonist. According
to Sivilotti, (2016), it has been a pharmacological ideal antidote.
Razavizadeh, A. S., Zamani, N., Ziaeefar, P., Ebrahimi, S., & Hassanian-Moghaddam, H.
(2021). Protective effect of flumazenil infusion in severe acute benzodiazepine toxicity: a
pilot randomized trial. European Journal of Clinical Pharmacology, 77(4), 547–554.
Sivilotti, M. L. A. (2016). Flumazenil, naloxone and the “coma cocktail.” British Journal of Clinical
Pharmacology, 81(3), 428–436. https://doi.org/10.1111/bcp.12731
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1 month ago
I agreed with you that “Understanding how neurotransmitters and receptors work in the
brain and body is vital for nurse practitioners to understand when prescribing
medications to promote optimal health responses and outcomes.” Example of the above
statement can be seen in the following exampes: the understanding of dopamine and
glutamate assist psychiatry nurse practitioners in treating Schizophrenia; the
understanding of catecholamine depletion helps in the management of depression; also,
the understanding of dopaminergic models of attention-deficit/hyperactivity disorder and
substance abuse is vital when managing these patients (Stern et. al., 2016).
Stern, T. A., Fava, M., Wilens, T. E., & Rosenbaum, J. F. (2016). Massachusetts General Hospital
psychopharmacology and neurotherapeutics (pp. 1–19). Elsevier.
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1 month ago
RE: NURS_6630_Wee2 Responce #2
I am impressed by the way you have structured your response in brief paragraphs responding to each
question separately. For instance, the first paragraph brings
out a clear understanding of the agonist-to-antagonist spectrum of action of psychopharmacologic agents.
In the second part of your discussion, despite not
mentioning directly, a reader can be able to draw the differences between g protein-coupled receptors
and the ion gated channels. While G proteins are large
receptors of drugs that affect the physiological and pathological process, the ligand-gated ion channels
are an essential protein-membrane with a pore that allows
the flow of selected ions across plasma membranes (Yudin & Rohacs, 2019). Just as mentioned,
epigenetics has played a significant role in the innovation of new
pharmacological interventions for the management of chronic health complications such as brain
disorders, cancer, and cardiovascular diseases. Additionally,
studies show that the epigenetic regulation of the activity of certain genes has been very beneficial in
maintaining the normal phenotypic cell activity (Khan et al.,
2019). From the last part of your paper, a comprehensive understanding of the neuropathophysio
of mental disorders and mode of action of psychotropic
agents is crucial in promoting effective prescription practices. From the example that you have provided, it
is clear how a great understanding of the mode of
action of different drugs has led to synergistic combination therapy in the management of nordiazepam
ReferencesKhan , M. A., Tania, M., & Fu, J.
(2019). Epigenetic role of thymoquinone: impact on the cellular mechanism and cancer therapeutics.
Drug discovery today, 24(12), 2315-2322.
https://doi.org/10.1016/j.drudis.2019.09.007Yudin, Y., & Rohacs, T. (2019). The G‐protein‐biased
agents PZM21 and TRV130 are partial agonists of μ‐opioid receptor‐
mediated signaling to ion channels. British journal of pharmacology, 176(17), 3110-3125.
Psychiatric nurse practitioner needs to have a good knowledge of foundational
neuroscience and the impacts of psychopharmacology in the central nervous system. This is
essential in the diagnosis and treating patients with psychiatric disorders. This post will give a
response to the topics below to show how the concept of foundational neuroscience applies to the
role of psychiatric mental health nurse practitioners in prescribing patients’ medications.
The agonist-to-antagonist spectrum of action of psychopharmacologic
agents, including how partial and inverse agonist functionality may impact
the efficacy of psychopharmacologic treatments
Agonists are medications or molecules that bind to specific receptors and induce some
impulse transmission which leads to a biological response, while antagonists are medications or
agents that bind to specific receptors, and does not induce any actions or signal, but at the same
time prevent any other molecule from doing so, as long as it is bound to that receptor. Drugs like
barbiturates and morphine are agonists. (Abimbola, F. 2021).
Partial agonists are molecules or medications that bind to the receptor and exerts a partial
or mild effect on the receptor, causing it to act weakly and not to full potential, while inverse
agonists are molecules or agents that bind to the receptor, inhibits the action or normal activity,
and applies an opposite action.
So, when certain medications are given concurrently, their different spectrums of actions
can affect the efficacy of psychopharmacologic treatments. Antagonists, partial and inverse
agonists occupy a certain space, inhibiting agonists from binding and acting. While an antagonist
will produce no biological effect, a partial agonist will exert a less than normal action and an
inverse agonist will give an opposite activity to the action it stops when bound to receptor.
Comparing and contrasting the actions of g couple proteins and ion gated
Ligands are molecules that bind to receptors. These receptors have existing sites which
are specific for binding of particular ligands, both of which match each other just like a key
matches a particular lock. G protein-coupled receptors (GPCRs) and ion channels are types of
physiologic and drug-receptor proteins. Both receptors are on the cell surface and
transmembrane and have ligand-binding domains and effector domains. Ion flux through ion
channels is rapid and they rapidly alter neuronal activity and membrane potential, while GPCRs
transmission is through slower second messenger systems (Stern et al., 2016). Examples of ion
channels are acetylcholine binding to nicotinic receptors where sodium enters the cell causing an
electrochemical gradient to be created which results in depolarization. Other examples are
GABA, Glutamate, Glycerin, while examples of GPCR are acetylcholine (muscarinic), alpha and
beta-adrenergic receptor proteins, and eicosanoids (Abimbola, 2021).
Ion channels are transmitter-activated channels, they are divided into ligand-gated and
voltage-gated ion channels. Ligand-gated ion channels (LGIC) require specific ligand-gated
channels on their cell membrane to enable hydrophilic molecules to move through it and into the
cell. Once the ligands link and bind to the receptors, the ligand-binding domain recognizes the
specific ligand and causes the channel gate to open and enable movement of small ions like
sodium ion (Na+), calcium ion (Ca2+), potassium ion (K+), and chloride ions (Cl−). The effector
domain produces this downstream effect, and inside the cells are located hydrophobic molecules
receptors. Also, LGICs are called ionotropic receptors with the same molecules acting as the
receptor as well as the channel.
G protein-coupled receptors (GPCRs) are a large family of cell surface receptors. They
are integral membrane proteins that act through G proteins and regulate the function of the wide
range of enzymes and ion channels. These membrane proteins enable cells to convert
extracellular signals into intracellular responses. Once the ligand binds to the receptor, it causes
structural changes in the receptor, thereby changing the shape of the G protein by reducing
guanosine triphosphate (GTP) to guanosine diphosphate (GDP) and causing the subunits to
divide into alpha on one side and beta and gamma units on the other side. This process then leads
to the activation of other enzymes and effector proteins (Wang et al., 2018), producing responses
to neurotransmitters, hormone signals, taste, olfaction, and vision signals. As mentioned above,
GPCRs act by second messenger systems, they “convert receptor signals into a coordinated set of
cellular effects by altering the function of multiple target proteins. These targets include ion
channels that control neuronal firing, synaptic proteins that regulate synaptic efficacy, and
cytoskeletal elements that determine cellular morphology” (Stern et al., 2016. P. 10).
How the role of epigenetics may contribute to pharmacologic
Current drug discovery efforts are targeting epigenetic dysregulations; pharmacological
actions are directed towards acting on the enzymes that distort or alter the epigenetic codes.
Thereby will redesign the chromatin material and largely change the global gene regulation.
Moreso, by using epigenetic marks, a particular gene responsible for a disorder or disease is
identified and some medications are designed to target that specific abnormally regulated gene
How this information may impact the way medications are prescribed to
This means that practitioners must do comprehensive history taking to get to know their
patients well and also possess a sound knowledge of the medications' possible effect on the
individual patient factors before medications are prescribed. Also, the psychiatric mental health
nurse practitioner must also be aware of the medication’s action, for example, in cases like
Alzheimer’s where there is degeneration, or in other mental disorders, the change or loss in the
identity of the cell are defined, and drugs are developed to target the proteins used in reading,
erasing, or writing the epigenetic marks (Lansdowne, 2018). In bipolar disorder, second
messenger pathway which involves glycogen synthase kinase is being targeted to mediate some
therapeutic efficacy of lithium salts (Stren et al. 2018). Knowing this will better direct her choice
of drugs, thus prolonging the patient’s sanity and quality of life.
Psychiatric nurse practitioners need to have a good knowledge of foundational
neuroscience and the impacts of psychopharmacology in the central nervous system. This is
essential in the diagnosis and treating patients with psychiatric disorders, thereby bringing about
global sanity and improving the quality of life.
Abimbola, F. (2021) Drug–Receptor
Lansdowne, L. E. (2018). Epigenetics and drug discovery. Technology
Stern, T. A., Favo, M., Wilens, T. E., & Rosenbaum, J. F. (2016). Massachusetts general
hospital psychopharmacology and neurotherapeutics. Elsevier.
Wang W, Qiao Y, Li Z. (2018). New insights into modes of GPCR activation. Trends
Pharmacological Science. 39(4):367-386. https://doi.org/10.1016/j.tips.2018.01.001
Week 2 Discussion
Providers must understand the functioning of the brain and the CNS to optimally provide
psychopharmacological therapy to their patients. To begin with, agonists are drugs with both
affinity (they bind to the target receptor) and intrinsic efficacy (they change receptor
activity to produce a response) while antagonists have affinity but zero intrinsic efficacy
meaning they bind to the target receptor but do not produce a response (Berg, & Clarke,
2018). The antagonistic agents affect the efficacy of agonists by occupying space that
could be used by agonists to provide therapeutic effect; this can be remedied by
increasing the concentration of the agonist the probability of its receptor occupancy
increases resulting in overcoming or reducing the inhibitory/ blocking effect of the
antagonist. Agonists can be full or partial based on functionality and efficacy defined by
drug structure with full agonist producing maximal response a system is capable of and
partial agonist producing a submaximal response. Drugs with inverse agonist properties
may act as an inverse agonist in some tissues and as a competitive antagonist in others
depending on the degree of constitutive receptor activity and the activity of an
endogenous agonist (Berg, & Clarke, 2018). In a nutshell, when there is a constitutive
receptor activity present, inverse agonists and antagonists will have different maximal
effects and when there is an inverse agonist effect, an antagonist should reduce the
inverse agonist component.
Ion gated channels are the mechanisms that control the movement of ions across the
membrane in neurons. The ligand-gated ion channels are either open or closed for substances to
allow for substances to move across the membranes; the opening and closing mechanism is
controlled by the agonist in most cases which can be a drug (Philips, et al., 2020). The G-
coupled proteins (GPCRs) are the largest embedded proteins that activate the intracellular
signaling pathways and modulate ion channel activity. The GPCRs modulate channel activity
through to distinct ways of either: an indirect pathway that involves a common second messenger
leading to phosphorylation or a direct pathway of binding of a GBy directly to the channel which
is commonly known as membrane delimitation (Philips, et al., 2020). The second messenger
systems usually involve multi enzyme cascades.
Epigenetics is how cells control gene activity without changing the DNA sequence.
These changes are modifications to the DNA and determine whether genes are turned on or off,
but not change the sequence of DNA building block. In epigenetics the environment and
lifestyles can change gene expression with factors such as diet, obesity, low physical activity,
smoking, alcohol, pollution, and stress leading the way (Marinova, 2020). Understanding
epigenetics in terms of how gene expression affects drug metabolism, transport, and receptors
which leads to drug efficacy and safety. Epigenetic variations may for example influence the
expression of drug transporters which leading to changes in the intracellular and extracellular
concentration of drugs and drug response like in the epigenetic modifications of the multidrug
resistance 1 (MDR1/ABCB1) gene that encodes the P-glycoprotein (P-gp).
Understanding the pharmacology of drugs and how they affect psychiatric patients is
important for nurse practitioners. This information is important to ensure the safety and efficacy
of prescribed medications. Understanding how different medications work and how different
psychiatric diagnoses are affected by neurotransmitters enables the psychiatric mental
practitioner selects the right treatment regimen for patient. It is important to note that every
patient is unique, and they need they need to be treated as such when making medication
prescriptive decisions. For example, the reduced inter-neuron input may disrupt synchronized
neural activity which in turn affects the working memory deficits in schizophrenia (Stern, et al.,
2016). Mental health nurse practitioners should consider prescribing medications that improve
memory or the use of innovative GABAergic therapies (Kwakowsky, et al., 2018).
Berg, K. A., & Clarke, W. P. (2018). Making Sense of Pharmacology: Inverse Agonism and
Functional Selectivity. The international journal of neuropsychopharmacology, 21(10),
Kwakowsky, A., Calvo-Flores Guzmán, B., Govindpani, K., Waldvogel, H. J., & Faull, R. L.
(2018). Gamma-aminobutyric acid A receptors in Alzheimer's disease: highly localized
remodeling of a complex and diverse signaling pathway. Neural regeneration
research, 13(8), 1362–1363. https://doi.org/10.4103/1673-5374.235240
Marinova, P. (2020). Why ‘epidrugs’ will be the next major focus for precision medicine. Retrieved
Phillips, M. B., Nigam, A., & Johnson, J. W. (2020). Interplay between Gating and Block of
Ligand-Gated Ion Channels. Brain sciences, 10(12),
Stern, T. A., Fava, M., Wilens, T. E., & Rosenbaum, J. F. (2016). Massachusetts General
Hospital Psychopharmacology and Neurotherapeutics. 1 st Ed. Elsevier.
Main Discussion Post
Agonist-to-Antagonist Spectrum of Action
Psychotropic drugs bind to specific receptors to produce a pharmacological effect.
Agonist is a drug that binds to a receptor, producing appropriate response to the intended
chemical and receptor. Full agonist produces the maximal response of 100% upon binding to
sufficient number of receptors compared to partial agonist which cannot produce maximal
response that the tissue is capable of. As a result, partial agonist may prevent the action of other
agonists Inverse agonist is a drug that binds to a receptor as an agonist but produces a
pharmacological response that is opposite to that of the agonist, thereby reducing the mediated
activity of the receptor. Antagonist is a drug that binds to a receptor without activating it but
blocks the receptor from being activated by another agonist (Rosenthal & Burchum, 2021).
G Couple Proteins and Ion Gated Channels
G-protein coupled receptors (GPCRs) also referred to as metabotropic receptors binds to
a ligand and activates a membrane called the G-protein. The G-protein disconnects from the
receptor and interacts directly with either an ion channel or an enzyme in the membrane. Cell
signaling using these receptors occur as a cyclic series of events. Ligand gated ion channels are
transmembrane protein complexes that form a pore through the plasma membrane that opens up
when the signaling molecules binds. The pore that forms allow ions such as sodium, calcium,
magnesium and hydrogen to flow into or out the cell (Stahl, 2013).
The DNA code that determines what a cell can transcribe is genetics. Epigenetics
mechanism determines if a gene is transcribed into a specific RNA and protein, be modified or
be silenced completely. Neurotransmission, genes, drugs, lifestyle and the environment regulate
which genes are made or switched off. These factors can affect the functioning of the brain,
resulting psychiatric disorders. Epigenetics have also modified how drugs are used in the
treatment of diseases. Treatment is no longer focused on the conventional drug- receptor sense
but is involved in a more global response approach (Stefanska & MacEwan, 2015). Drugs
may not be designed to a specific gene or protein but are able to be more broad-acting over a
range of epigenetic large-scale events.
An example of a case with a patient in which the psychiatric mental health nurse
practitioner must be aware of the medication’s action is case of a patient with a diagnosis of
Generalized Anxiety Disorder (GAD). Buspirone which is an anxiolytic first-line FDA
approved drug for the treatment of GAD was prescribed for the patient. Buspirone is as effective
as benzodiazepine but without the sedating effect and the potential for abuse. It has a delayed
therapeutic effect as initial response takes a week to appear and several more weeks before
responses peak (Rosenthal & Burchum, 2021). However, the patient complained of lack of relief
less than a week after initiating treatment. As a Psychiatric Mental Health Nurse Practitioner, it
is necessary to ensure that patients understand the indications, the actions as well as the
therapeutic effects of the prescribed medications. It is also important to provide education
regarding medication adverse effects and the importance of notifying the provider about the
occurrence of these adverse effects. For some patients, genetic testing might be necessary since
human genetic variations can influence the way receptors interact with the certain drugs,
resulting in either the effectiveness of the drug or possible adverse events.
Stefanska, B., & MacEwan, D. J. (2015). Epigenetics and pharmacology. British journal of
pharmacology, 172(11), 2701–2704. https://doi.org/10.1111/bph.13136
Rosenthal, L.D., & Burchum, J.R. (2021). Lehner’s pharmacotherapeutics for advanced
Practice Nurses and physician assistants (2ned.).
Stahl, S. M. (2013). Stahl's essential psychopharmacology: Neuroscientific basis and practical
applications (4th ed.). New York, NY: Cambridge University Press
Week 2 Discussion
Explain the agonist-to-antagonist spectrum of action of psychopharmacologic agents,
including how partial and inverse agonist functionality may impact the efficacy
of psychopharmacologic treatments.
The difference between agonist and antagonists in psychoactive drugs is determined by
the level of activity that is happening at the synapse. Specifically, an agonist will
increase the level of activity at the synapse to its maximum capacity while the
antagonist decreases the level of activity occurring at the synapse (Barron, 2018). One
example of this would be fentanyl is an agonist while naloxone (Narcan) is an
antagonist on opioid receptors. When thinking of psychopharmacologic treatments, it is
important to be aware of there are not only agonists and antagonists, but also
partial agonists and inverse agonists. Partial agonists are agonists that bind at the
active receptor site but do not produce the maximum response potential that could be
produced by an agonist. An example of a partial agonist on the opioid receptors would
be Buprenorphine as it activates the receptors but to a lesser degree. An
inverse agonist binds to the active site, closes the site, and makes it inactive. It is
imperative to be aware of these pharmacological properties of the drugs you are
prescribing so that you can treat each condition appropriately and achieve the most
Compare and contrast the actions of g couple proteins and ion gated channels.
The G-protein is a specific membrane protein that is activated when a g-protein linked
receptor binds to a ligand. G-coupled proteins receptors (GCPR’s) work with second
messenger systems and involve multi-enzyme cascades (Camprodon & Roffman,
2016). These protein receptors interact with a variety of proteins to achieve a cellular
response. On the other hand, an ion gated channel binds a ligand and an open channel
to allow specific ions to flow through the membrane.
Explain how the role of epigenetics may contribute to pharmacologic action.
Epigenetics is the study of changes in a phenotype without there being a change in
DNA sequencing. Since there is no change in the primary DNA sequence, epigenetic
changes can be reversible. There are certain pharmacological agents that aid
in epigenetic regulation to maintain normal phenotypic activity, making these important
medications to be used in certain diseases such as cancer (Stefanska & MacEwan,
Explain how this information may impact the way you prescribe medications to patients.
Include a specific example of a situation or case with a patient in which the psychiatric
mental health nurse practitioner must be aware of the medication’s action.
It is important for a nurse practitioner to understand the mechanism of action of the
medications being prescribed to a patient in order to achieve the most successful
patient outcome. A specific example is of a nurse practitioner who may encounter a
patient who has been using opiates but is now going through withdrawal with the urge to
begin using again. If this patient is looking to quit using these opiates, knowing the
effects of prescribing Buprenorphine (Suboxone) would be beneficial.
Since Suboxone is a partial agonist, it is still stimulating the opiate receptors but not to
the maximum effect that heroin or fentanyl may produce. The use of the Suboxone will
help aid in treating the opiate dependence that the patient is experiencing and can be
less harmful to the patient if taken as prescribed.
Barron, S. (2018). Psychopharmacology. Nobia textbook series: Psychology. Retrieved
Camprodon, J. A., & Roffman, J. L. (2016). Psychiatric neuroscience: Incorporating pathophysiology into
clinical case formulation. In T. A. Stern, M. Favo, T. E. Wilens, & J. F. Rosenbaum. (Eds.), Massachusetts
General Hospital psychopharmacology and neurotherapeutics (pp. 1–19). Elsevier.
Stefanska, B., & MacEwan, D. J. (2015). Epigenetics and pharmacology. British journal
of pharmacology, 172(11), 2701–2704. https://doi.org/10.1111/bph.13136
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