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Chapters 1-4 for PSYC62 midterm

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University of Toronto Scarborough
Zachariah Campbell

Chapter 1 Psychopharmacology • Study of how drugs affect mood, perception, thinking, or behavior • Psychoactive drugs – drugs that affect mood, perception, thinking, or behavior by acting in the nervous system • Attempts to relate actions and effects of drugs to issues in psychology • Behavioral pharmacology = study of how drugs affect behavior • Nueropsychopharmacology = study of how drugs affect the nervous system and how these nervous system changes alter behavior Drugs:Administered Substances ThatAlter Physiological Functions • Drug=an administered substance that alters physiological functioning • Limitations to this definition – administered= doesn’t include substances naturally made inside your body; naturally produced chemical important for making dopamine in the body is called levodopa – primary drug for Parkinson’s disease; emphasis on physiological functions also has limits – is food a drug – it does produce physiological changes in the body Psychoactive Drugs: Described by Manner of Use • Person uses a drug instrumentally towards addressing a specific purpose – often occurs with therapeutic drugs (those used for treating mental disorders such as depression) • Recreational use refers to using a drug entirely to experience its effects – drinking alcohol for the intoxicating effects – may lead to abuse or dependence • Misuse – when drugs that are intended for instrumental purpose are used recreationally • Abuse – drug use that causes harm to user or others • Dependence – can include features of drug abuse but a user also experiences a need or urge to continue using substance Generic Names, Trade Names, and Street Names for Drugs • Trade name – drug named developed for marketing the drug – sometimes developed to be memorable or emotion provoking • Generic name – names that show how drugs organization fits with other drugs • Scientific reports usually report the drug’s generic name and trade names are capitalized whereas generic names aren’t • Street names – develop by those who sell, use, or make recreational drugs Drug Effects: Determined by Dose • Dose – ratio of the amount of drug per organism’s body weight • Dose-effect curve – depicts the level of a drug effect by dose • ED50 value – dose at which 50% of an effect was observed – provides a mean to compare the potency of the drugs • Potency – amount of drug used to produce certain level of effect o Highly potent drug= low doses produce significant drug effects o Used to compare different drugs that produce similar effects • LD50 – lethal dose value; allows for the determination of a therapeutic index= ratio of a drug’s lethal dose-effect value relative to a therapeutic dose-effect value • One way to calculate it is to divideLD50 by ED50 value • Therapeutic index answers the questions – how dif is a dose that kills half of the subjects from a dose of the same drug that produces a full therapeutic effect in half of the subjects? • ID a lethal dose that only cause 1% of the subjects to die (LD1) and divide it by a dose that achieved a 99% therapeutic effect (ED99) describe very different therapeutic and lethal dose-effect curves Pharmacology: Pharmacodynamics, Pharmacokinetics, and Pharmacogenetics • Pharmacodynamics – study of how drugs affect biological actions • Pharmacokinetics – study of how drugs pass through the body – different ways to administer drugs, how long drugs stay in your body, and how the drug enters the brain and leaves the body • Pharmacogenetics – study of how genetic differences influence a drug’s pharmacokinetic and pharmacodynamic effects – sometimes knowing that a person may be a fast metabolizer and this enable the physician to alter treatment plans Psychoactive Drugs: Objective and Subjective Effects • Objective effects – pharmacological effects that can be directly observed by others – can independently measure a drug’s effect (ex. Psychostimulants increase heart rate – can measure person’s heart rate by taking a pulse) • Subjective effects – pharmacological effects that cannot be directly observed by others – ask people to describe the effects of the drug – the drug’s subjective effect may differ from person to person thus researcher must develop consensus about a drug’s effects among many individuals and assume this consensus accurately reflects the effects of the drug • Subjective effects more important to understand because they explain the purpose of recreational and addictive drug use • Also explain therapeutic value of antidepressants, anti-anxiety, and antipsychotic drugs  only the patients can truly say if the medication helped or not Study Designs and theAssessment of Psychoactive Drugs • Dependent variable – study variable measured by a researcher – usually consists of behavioral measures • Independent variables – study conditions or treatments that may affect a DV – whether the IV produces change in a DV • Correlational study – no alteration of study conditions; changes in study variables are observed and relationships inferred • Experiment – study’s IV is altered by the researcher and changes in the DV are measured/observed; can identify causal relationships between an IV and a DV • Placebo – substance identical in appearance to drug by physiologically inert • Treatment arms – number of treatments and dose provided to patients described in a clinical study • Two-arm design= two patient experimental groups – one group receives an experimental drug and the other a placebo • Testing an experimental drug in comparison with a standard treatment and placebo provides a valuable assessment of drug efficacy compared to existing medication or no medications • Clinical study reports – detailed summaries of a clinical study’s design and results • Single-blind procedure – researcher’s do not inform the participants which treatment or placebo they received  Informed consent – study investigators provide study participants with a description of treatments that might be administered but do not say which one is given to them • Double-blind procedures – neither participants nor investigators know which treatments are assigned to whom  Prevent potential biased responses from participants and prevent biased judgments by study investigators • Open-label studies – assignment of study treatments without using blinded procedures • Used in situations where disguising study medications may have important ethical consequences or be impractical – ex. Cancer treatments Experimental Validity: Addressing the Quality and Impact of an Experiment • Experimental validity – addresses the logical design of effective quality experimental studies Internal validity – adequacy of controlling variables that may influence a DV External validity – ability to extend findings beyond experimental conditions Thalidomide – in humans, it is broken into teratogens – substances harmful to fetuses and results in deformities in children – had the researchers tested on rabbits (which convert it into teratogens, un like mice, this would not have been prescribed for morning sickness) Face validity – a model appears similar to a disorder Construct validity – how well a study’s model approximates a disorder Predictive validity – addresses how well a model predicts test results in a disorder • Confound variables – variables other than IV that cause change in he DV • Placebo groups control for many confound variables – such that if placebo-treated patients also exhibit reduced depression, then researchers will conclude that variables other than the study medication caused reductions in depression • Drug developers rely on models with high predictive validity when screening experimental drugs Animals and Advancing Medical Research • To develop drugs for human research, medical research relies heavily on animal testing – proof of extensive animal research is required before approving dugs for clinical testing • Medical advances rely on animal research because of three reasons o Alack of feasible alternatives – humans do not provide an alternative to animal models – invasive techniques that would be highly unethical to perform on humans; experimental drugs that have not been tested on animals carry severe risk and possibly irreversible adverse effects in humans o High predictive value for drug effects in humans – animal models do well to predict drug effects in humans – during drug development, animal models identify effective drugs from hundreds or thousands synthesized in a drug-development program o Assessing Drugs in carefully controlled lab environments – lab conditions for animal studies include housing, diet, age, weight, and a consistent experimental routine; the great variety in human differences may prevent researchers from identifying an effective drugs (confounding variables); carefully controlled animal lab conditions provide the ability to ID drugs with potential efficacy before evaluating them in complex environments  only the most likely effective drugs reach human participants The Regulation of Animal Research • All legitimate journals publishing scientific studies require high ethical standards of animal care and use in research • The FDAwill not approve any treatments resulting from animal studies that have not complied with the federal regulations and policies • IAUCUC oversees an institution’s entire animal care and use program, including quality of housing, veterinary practices and research practices – makes ethical judgments according to the three R’s – replacements, reduction, and refinement • Replacement – assesses the necessity of using animals for the purpose of the study; sometimes it is possible to work with cells and invertebrates and thus the proposal would be rejected • Reduction – using the minimum number of animals necessary to achieve the study objectives • Refinement – minimize any pain and distress experienced by research animals • Ethical cost – assessment that weighs the value of potential research discoveries against the potential pain and distress experienced by research subjects Animal Rights Activism Seeks to Minimize or EliminateAnimal Research • PETAand ALF actively seek the complete cessation of animal research, either seeing no value in the work or dismissing any value as unjustified • Legal animal rights activities may include information sessions, public protests, petitions, and advertising • Illegal animal rights activities include distributing false information, illegal entering animal facilities, releasing lab animals, and damaging equipment • Groups supporting animal research are providing public information on the medical advances derived through animal research Researchers Consider many Ethical Issues When Conducting Human Research • Informed consent – consists of a participants thorough understanding of a study procedure, possible gains, and potential risks – animals lack the capacity to provide this • The Nuremberg Principles – consist of some of the first written statements about the thical conduct of human research Therapeutic Drug Development • Pharmaceutical drug research and development generally occurs in several stages o Company usually decides for which disorder to develop a treatment – carefully considered opinions from scientists, outside consultants, and business executives; seek to develop a feasible treatment that yield a reasonable likelihood of making a significant profit  Likelihood of profit – depends on the disorders prevalence – to develop treatment for rare diseases, there must be a high potential of developing successful treatment  approach must be low risk  Companies seek to improve treatments for currently treatable disorders  Companies seek a high-risk high-reward approach where finding the cure for cancer would have great profit o Drug synthesis – develop experimental compounds  May develop variations of existing therapeutic drugs for a disorder or develop drugs based on established theories o Tested in biological experiments – prefer using high-througput screening – rapid testing process involving a large number of experimental drugs -> quick results, but low precision  Whether the experimental drugs are close to achieving the desired biological effect  The best drugs from the previous batch serve as the best direction for developing the next set of experimental drugs – the process goes on until the drug meets their goal for a biological effect o Refined screening measures – slower but with greater precision  Use models that have face, construct or predictive validity, often these methods include animal models o Safety pharmacology testing – screening process that identifies the adverse effects of the drug  mild to serious physiological effects, addiction risks, and change sin mental functioning  Also identify a drug’s lethal dose  Many drugs reveal a low therapeutic index  same doses that produce therapeutic results also show serious adverse effects  To get acceptance for clinical testing, it must be shown that a drug’s harmful doses far exceeds its therapeutic doses o Human drug testing – clinical trials = gov-approved experimental drug testing in humans; phase I – employ a low dose to a specific patient population for a short period of time; phase II – seek to measure a drug’s therapeutic efficacy (larger dose for longer periods); phase III – greater info about therapeutic effects and potential adverse effects – recruit more diverse participants ; Phase IV – further investigate a specific patient population or evaluate longer periods of drug treatment Chapter 2 Cells in the Nervous System • Neurons – cells in the NS that receive and transmit info to other neurons – 100 billion neurons • Glial cells – cells that support the function of neurons – 10X as many as neurons Neuron Communication in the NS • Neurons have 4 major components: o Soma – body; within the soma, support a neuron’s basic physiological processes o Nucleus – holds DNA o Dendrites – branch off soma and receive info from other neurons; membranes of dendrites and dendritic spines contain proteins called receptors that neurotransmitters can activate  Receptive area – overall coverage of dendrite for a neuron o Axon – send neurotransmitters to other neurons  Axon begins as a part of the soma called the axon hillock and ends with multiple branches containing axon terminals (axon collaterals) • Synapse = components that compromise a connection between two neurons that include the axon terminal, postsynaptic terminal, and synaptic cleft • Interneurons – neurons with the soma and axon found within the same structure • Afferent neuron – axon going to other structures • Sensory neurons – neurons that convey sensory information via axons to the CNS • Efferent – coming from other structures • Motor neurons – convey motor information via axons from the CNS (efferent neurons) Glial Cells: Facilitating Nervous System Functions • Three different types: o Oligodendrocytes – produce a material around the axons of neurons called myelin – functions like an insulating material to facilitate the movement of electrical impulses down an axon  Schwann cells – found in PNS  The motor dysregulation, paralysis and other symptoms that occur in MS result from the degeneration of myelin sheaths that surround axons in the nervous system o Astrocytes – play a role in the forming of the blood-brain barrier (by making the endothelial cells fit tightly together), facilitating neuronal function and responding to injury  Gliosis – process involving the swelling of glial cells in response to injury ; aka glial scar  Segregate damaged tissue from undamaged tissue  Severely limits the ability of regenerated axons to reach healthy tissue and then how well an individual can recover from brain injury o Microglia – removes normal cellular waste from neurons and glia cells and also contribute to gliosis The Nervous System: Control of Behavior and Physiological Functions The Peripheral nervous System: Controlling and Responding to Physiological Processes in the Body The Somatic NS • Responsible for delivering voluntary motor signals from the CNS to the muscles throughout the body and for conveying sensory information from the body to the CNS • Sensory neurons send information to the dorsal part of the spinal cord (dorsal root/horn); motor signals send to muscles from the ventral part of the spinal cord (ventral horn/root) • Neuromuscular junction = point where motor neuron meets a muscle fiber TheAutonomic Nervous System • Controls involuntary movements for vital functions such as heartbeat, breathing, and swallowing • Sympathetic nervous system – prepares body for rigorous activity by increasing the heartbeat, inhibiting digestion, and opening airways • Parasympathetic NS – dominant during relaxed states, including decreased heartbeat, stimulation of the digestive system, and closing of airways The Central Nervous System • Hindbrain – lower part of the brainstem and it begins where the spinal cord meets the brain stem at the medulla • Midbrain – includes inferior colliculus (auditory processing), superior colliculus (eye movement) • Forebrain – cerebral cortex and structures beneath such as corpus callosum, basal ganglia, thalamus, and the hypothalamus The Medulla and Hypothalamus: Controlling Unlearned Behaviors • ANS is controlled by the medulla – which rests where spinal cord meets the hindbrain • Controls basic functions such as breathing, heart rate and vomiting • Cranial nerves that come from the medulla are devoted to the movement and sensation of the head • Vagus nerve – controls and receives sensory information from various internal organs in the body, including the heart, liver, and intestines • Narcotics and central nervous system depressants suppress medullary functions, which can be fatal at high dosages • Mixing two or more CNS depressants at safe amounts can produce combined suppressant effects on the medullary functions • Hypothalamus – found in the forebrain; maintains many physiological processes through motivating an organism’s behavior; also facilitates the motivation for sexual activity which maintains the survival of the species • Also controls the pituitary gland which secretes several hormones into the bloodstream , affecting organ function in the body • Water absorption into the kidneys, growth, thyroid function, and reproduction functions • Also controls the pineal gland (releases melatonin – sleep-regulating hormone. The Limbic System: Controlling Emotional Behaviors • Forms a ring around the thalamus and the hypothalamus • Series of structures – cingulate gyrus, hippocampus, amygdala, nucleus accumbens, and olfactory bulb • Many systems control emotional behaviors o Amygdala  facilitates fear and aggression; many drugs aimed at reducing anxiety, reduce activity in the amygdala o Nucleus accumbens  facilitates reinforcing effects; brain’s reward center The Cerebral Cortex: Processing Information, Controlling Cognitive Functions, and Eliciting Movement • Occipital lobe – processing visual information • Temporal lobe – processing auditory info and supporting language comprehension and production; also processes certain aspects of vision (shape and colour analysis) • Parietal lobe – processing touch information from the body and analyzes visual information that contains movement • Frontal lobe – decision making and movement; prefrontal cortex – integrated in all sorts of sensory input and where the signal to produce movement also occurs; also supports STM and attention; sensory information is integrated in the prefrontal cortex • Thalamus – routes sensory information from the body to the appropriate lobes The Frontal Lobe and the Basal Ganglia: Controlling Voluntary Movement • Primary motor cortex - sends movement signals to the body through the pyramidal system (lateral corticospinal tract & medial corticospinal tract) • Lateral tract – sends motor info to the limbs, hands, and feet • Medial tract – sends info from each hemisphere to the same side of the body – functions for middle parts of the body – provides posture and balance • Basal ganglia – aka striatum, has three major structures  caudate nucleus, putamen, and the globus pallidus • Substantia nigra – aids in regulating the activity in the basal ganglia • Parkinson’s  destruction of the substantia nigra neurons that go into the basal ganglia  muscle rigidity, tremor, and resistance to voluntary movement • First drugs used to treat schizophrenia (antipsychotic drugs) disrupt those neurons and lead to Parkinson-like symptoms= extrapyramidal side effects • Pons – elicits startle reflexes • Cerebellum – facilitates balance and timing of movement Learning and Memory Processes in the Brain • Working memory consists of short-term verbal or non-verbal memories employed to carry out a task ; prefrontal cortex • LTM is stored verbal and nonverbal information • LTM formation and retrieval requires the hippocampus, which then sends info to the prefrontal cortex • Damage to the hippocampus Alzheimer’s disease  impairments in LTM • Long term procedural memories may depends on the basal ganglia (ex. Riding a bike) • Reticular activating system = system of structures that supports arousal in the cerebral cortex ; includes reticular formation, tegmentum, thalamus, and hypothalamus • Drugs that increase the cortical arousal include psychostimulants; drugs that depress cortical activity = benzodiazepines, barbiturates, and alcohol • Neurons require a constant supply of glucose and oxygen particularly when engaging in highly demanding tasks Blood Flow in the Brain • Highly active brain regions require increased blood flow • Blood flow changes throughout the brain when blood capillaries dilate and contract • Highly active cells release a chemical called nitric oxide that dilates blood capillaries  more oxygen • fMRI – oxygen uptake in the brain can be pictured – high amounts of oxygen uptake imply higher levels of activity • Ischemia – too little cerebral blood flow • Stroke – occurs from the blockage of brain vessels – serious type of ischemia • Hyperemia – too much cerebral blood flow which may increase intracranial pressure and damage brain tissue • Angiograms – provides pictures of part of the circulatory system by taking X-ray images of blood vessels that contain an X-ray absorbing agent • Carotid artery – runs up the front of the neck and is the one we commonly press down to measure our heart rate • Vertebral artery – flows into a collection of arteries in the brain stem called the Circle of Willis Cerebrospinal Fluid • CSF – clear fluid that surrounds cells in the brain; provides a medium through which nutrients, glucose, hormones, and other chemicals can access the brain • Periaqueductal gray – small layer of tissue that surrounds the cerebral aqueduct 9small canal- like structure in the brain) th • Ventricles – CSF-filled cavities in the brain; 4 ventricle is found adjacent to the cerebellum in the brain stem; 3 ventricle surrounds much of the thalamus, and the lateral ventricles are found lateral to the 3 ventricle and have a large cavity at the midline • Also found in the meninges – form a layer in the subarachnoid space  form a protective cushion around the brain , protecting it from injury The Blood-Brain Barrier • Blood-brain barrier = barrier that surrounds the blood capillaries and vessels in the brain and prevents blood from assessing brain cells • Molecules must possess three properties to passively diffuse through o Chemical should be lipid soluble – can pass through cell membranes o Chemical should be uncharged – neurochemicals must be made within the brain o Chemical should be relatively small • Many nutrients lack the necessary properties and thus must use active-transport mechanisms – channels that penetrate endothelial cell membranes • Ex. Glucose passes through a channel in the blood-brain barrier in order to access wells within the brain Nervous System: Rapid DevelopmentAfter Fertilization • Teratogenic effects – harmful and potentially lethal effects for a fetus due to drugs • Alcohol consumption can lead to fetal alcohol syndrome, thalidomine, and isotretinoin (Accutane) which is effective at treating acne but is associated with high abortion risk and birth defects • First trimester begins at conception and ends at 12 weeks; second semester begins at week 13 and ends at week 27, and the third trimester begins at week 28 and continues till the birth • Primary features of the central nervous system are produced during the first trimester • Zygote becomes an embryo once it implants within the wall of the uterus, embryo quickly develops multiple layers of cells and within 4 weeks , exhibits the basic divisions of the CNS • Adiscernible brain, with a prominent forebrain, develops between 8 and 10 weeks; after 10 weeks = fetus • Gyri and sulci become most apparent between 24 and 30 weeks • Proliferation – stem cells near the neural tube develop into brain cells • Migration – moving of newly generated brain cells to parts of the nervous system • differentiation phase – when brain cells reach the appropriate part of the nervous system, they differentiate to become either neurons or glial cells • Synaptogenesis – development of connections with other neurons through forming axons and dendrites • Neurotrophins – chemicals released by neurons that promote survival; many neurons die during this stage because they do not get enough neurotrophins (cell death – apoptosis) • Synaptic rearrangement – rearrangement of synaptic connections during neurodevelopment Genes and the Development and Physiological Processes of Cells • Each chromosome contains DNAwhich contains the specific coding instructions for the basic functions of the cells called genes • Genes contain information to build and maintain cells • Polymorphism – differences in the gene that encodes for a trait within a species ; common, and determining what type of polymorphism an individual has can aid greatly in understanding a person’s response to drug effects • Transcription factor – activating genes leads to the release of genetic information (gene transcription); consists of a substance that increases or decreases gene transcription • Coding sequence of a gene copies onto RNA; type of RNAuse to trigger protein synthesis is called messenger RNA– it leaves the nucleus and binds to ribosomes in the cell – ribosomes produce the type of protein specified in the message Box 2.1 Genetically Modified Organisms • Transgenetic mice - mouse with either altered genes or additional genetic information • Knock-out mice – mice that fail to express a particular gene • Wildtype – “+/+” – unaffected genes on both chromosomes – nongenetically modified animal • Animals with homozygous genotype for a certain trait are “--/--“ – deactivated gene on each chromosome • - / - describes the deactivation of the serotonin transporter gene on both chromosomes (ex.)  mice completely lack serotonin transporters • Phenotype – physiological or behavioral changes caused by a genetic alteration • Genetic alterations may cause unexpected changes during neurodevelopment • Conditional knock-out mice – have normally functioning genes until a researcher administers a type of enzyme that deactivates a gene – mice develop normally but still allow researcher to asses the effects of gene deactivation on some physiological or behavior characteristic Glial Scars and Recovery from Brain Injury • Aglial scar consists of a reactive astrocyte – astrocyte that swells in response to injury • Segregates damaged tissue from healthy tissue • Serves to repair the blood-brain barrier but by doing so, glial scars prevent neurons in damages tissue from regaining connections to other structures in the nervous system • The glial scars cause the regenerating axon terminals to divert from the damaged tissue  misaligned patterns of growth, including retractions into balls called dystrophic end bulbs • Inhibitory extracellular matrix – consists of chemicals that inhibit axon growth; each molecule prevents the growth or penetration of axons into the damaged tissue • Experimental treatments – ways to improve axon regeneration into damaged brain areas • One approach uses the enzyme chrondroitinase to break down proteoglycans • Other treatments focus on improving the availability of growth material for axons – involve neural growth factors that promotes the growth of axons in the damaged tissue Combining both the strategies to reduce inhibitory extracellular matrix components while promoting growth of axons – far greater growth when using both approaches than just one Chapter3 • Neurotransmission – transmission of information between neurons Electrical Events Within a Neuron and the Release of Neurotransmitters • Electrical transmission – series of electrical events that begin at an axon hillock and proceed down the length of the axon • Electrical potential – difference between the electrical charge within a neuron and the charge of the environment immediately outside the neuron o Negative inside compared to outside – leaves it polarized • Depolarization – reduced difference between the positive and negative charges on each side of the membrane • Hyperpolarization – described an increased difference between the positive and negative charges on each side of the membrane • Local potential – electrical potential on a specific part of a neuron ; change as charged particles called ions move in and out of the neuron through pores (ion channels) • Excitatory postsynaptic potential – depolarizes a local potential • Inhibitory postsynaptic potential – hyperpolarizes a local potential Box 3.1 – Electrophysiology and Micro Dialysis • Electrophysiology – uses electrodes to measure potentials on neuronal membranes • Macroelectrodes= record the activity of thousands of neurons within a structure can also be used to activate neurons • Microelectrodes= precise assessment of either just a few a few or single neurons, can be used to measure potentials within a single neuron called intracellular recording (to measure action potentials) • Cannot determine how much of a neurotransmitter a neuron releases • Microdialysis procedures can be used to sample neurotransmitter levels – a probes membrane allows some of the CSF to pass through  analyze it for certain chemicals as neurotransmitters – limits detection to an entire structure vs specific neuron • Lack the precision that electrophysiology can achieve; both complement each other • Ishida et al. (2005) – effects of B-phenylethylamine on dopamine neuron firing rates and dopamine release was assessed in rats o Mocrodialysis techniques revealed increased dopamine release – the increase was caused by B- phenylethylamine acting on dopamine D2 autoreceptors Nerve Impulses: Electrical Potential Changes in Neurons • Nerve impulses are compromised of changes from resting potential to action potentials • Resting potential – negatively charged local potential that precedes an action potential ; it exists because of negatively charged proteins within the neuron and closed ion channels that prevent the influx of positively charged sodium ions • K+ ions enter the neuron because they are attracted to the negative charge (called electrostatic attraction) • The balance between the electrostatic attraction and concentration-gradient repulsion facilitates a resting potential • Sodium-potassium pump – prevents excess Na+ ions from changing the resting potential – neuronal membrane that bring two K+ ions into the neuron while removing 3 Na+ ions - this results in a net negative effect • Voltage-gated ion c
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