midterm Flashcards
1
Q
biomedical model
A
doesn’t include psychological issues
2
Q
biopsychosocial model
A
- bidirectional
- whatever sickness you have can be subtle but will effect even your brain
3
Q
Galen
A
-realized that certain traits coincided with certain illnesses
4
Q
Phases of mind-body research
A
- 1st: case histories
- 2nd: documented assoc b/w stress and illness/death
- 3rd: documented assoc b/w stress and changes in physiology
- 4th: multivariate models linking stress and health, including risk factors; focus on mechanisms relevant for particular diseases
5
Q
Stress systems
A
- 2 key stress systems
1. Autonomic nervous system (ANS)
2. Neuroendocrine system (HPA axis)
6
Q
ANS
A
- involuntary, innervates internal organs
- regulates things like breathing, digestion, heart rate, temperature, etc.
- two branches: sympathetic (stress) parasympathetic (peace)
7
Q
Sympathetic nervous system
A
- fight or flight system
- key hormones: Norepinephrine (NE) and epinephrine (E)
8
Q
Parasympathetic Nervous System
A
- rest and digest system
- key hormone: acetylcholine
9
Q
measures of ANS functioning
A
- cardiovascular (BP/heart rate)
2. E and NE concentrations in urine/blood
10
Q
HPA axis
A
- activated by physical and psychological stress
2. end product: release of glucocorticoids (cortisol in humans) from adrenal glands
11
Q
what activates physical/psychological stress?
A
- physical injury
- hunger
- internal bleeding
- uncontrollability
- unpredictability
12
Q
what does cortisol do?
A
- helps to mobilize energy
2. modulates aspects of stress response
13
Q
CRF/CRH
A
corticotropin releasing factor/hormone
14
Q
ACTH
A
adrenocortico-tropic hormone
15
Q
Regulators of HPA axis
A
- CRF/CRH
- ACTH
- negative feedback (shuts itself off)
- diurnal rhythm (peaks in morning)
16
Q
cortisol collection
A
- blood
- urine
- saliva
17
Q
what to look at in collecting cortisol
A
- total output
- diurnal rhythm
18
Q
core of stress response
A
- mobilize energy to help muscles work (glucose metabolism)
- transport energy to where it is needed (inc heart rate, BP, breathing to transport glucose)
- turn off long-term projects (no digestion/reproduction)
19
Q
stress is adaptive if
A
dealing with short term physical stressors requiring energy mobilization
20
Q
allostatic load
A
wear and tear resulting from chronic overactivity or underactivity of stress system
21
Q
general stress def
A
environmental demands that tax or exceed the adaptive capacity of an organism
22
Q
how to conceptualize stress
A
- something that happens to you
- how you feel about something
- how your body responds to it
((or all three))
23
Q
event-based
A
- something that happens to you
- focus on objective, observable events that are normatively assoc with substantial demands
- measured by checklist or interview
24
Q
life events and difficulties schedule (LEDS)
A
- 2 hr structured interview asking about stressors in 10 domains of life
- presented to panel of raters who make a contextual rating of the event
25
pros of event list
1. cover major/minor events that might have impact on health
| 2. interviews can provide detailed information on stressor characteristics (i.e. timing, chronicity and domain)
26
cons of event lists
1. don't take into account context of event or meaning for individual
2. verty time intensive and costly
27
stress perceptions/ subjective experience
1. how you feel about it
2. perception that demands exceed one's ability to cope
3. perceived stress scale
28
pros of stress perceptions
gets closer to person's individual exp
29
cons of stress perceptions
colored by mood and personality, which may confound assoc with health
30
biological stress assessment
1. body's response to an event or experience
- > inc in SNS &/or HPA activity
2. GOLD STANDARD IN ANIMAL STUDIES
31
problems with studying stress
1. lack of agreement on what is stress and how to measure it causes big problems
2. studies typically use diff measure of stress, leading to diff outcomes
- > assoc may depend on type of stressor
32
experimental study
1. ideal
| 2. manipulate variable of interest, look at effect on outcome
33
randomly assign lab animal to stress vs no stress condition and look at effects on cancer development and progression
1. experimental
2. looking at x->z
3. to look at x->y look at biological mechanisms with this design
34
observational studies
1. no manipulation of study variables
| 2. these designs can provide evidence of links b/w stress and disease in humans (x->z pathway)
35
cross-sectional
- an observational study
| - predictor and outcome variables assessed at same time
36
longitudinal
- an observational study
| - predictor variable assessed first, outcome variable assessed at later time
37
experimental study
1. independent variable is manipulated
2. can provide evidence that stress causes diseases in animal models (x->z)
3. can be used to examine links b/w stress and physiological changes relevant for disease in human studies (x->y)
38
atherosclerosis
1. caused by inflammation of the lining of the blood vessels (endothelium)
2. endothelial cells are irritated or damaged by high BP
39
inflammation
the basic way the body responds to damage, injury or infection
40
initial stages of atherosclerosis
1. inflammatory response in the inner layer of blood vessels
2. monocytes recruited to area
3. fibrous cap forms on top of area
4. tissues are plaques which thicken the arterial wall and can obstruct the flow
41
acute events
1. if plaques rupture this can be bad: heart attack/stroke
42
heart attack
if plaques block blood flow to heart
43
stroke
if plaques block blood flow to brain
44
timing CVD
- starts in childhood and continues throughout adult life
| - >fatty steaks and clinically significant lesions inc dramatically during ages 15-34
45
risk factors for CVD
1. high cholesterol
2. high BP
3. smoking
4. diabetes
5. high fat diet
6. lack of exercise
7. stress?
46
stress and CVD
1. conduct large scale study, see whether those who report more stress have more CVD related events
47
stressors of interest for CVD
1. work stress
2. bereavement
3. social isoltation
4. childhood stress
48
MRFIT study
12,236 men without evidence of CVD but with elevated risk
- assessed 7 types of work related stressors over 6 yr period
- also assessed seperation/divorce
- followed for nine years
49
MRFIT study results
1. men with 3+ work stressors had elevated risk of CVD-related mortality
2. men who seperated/divored also had elevated risk of CVD related mortality
50
vacations and CVD
1. vacations reduced it
51
job strain and cvd
1. job strain is the most common type of work-related stress studied
2. combination of high demand and low control
52
combining across studies of job strain and CVD
1. many studise examined job strain and CVD
| 2. meta-analysis yields an ave effect size measure
53
metaanalysis CVD 1
1. effect is 1.2 significant effect of job strain (20% inc risk)
2. effect remains sig controlling for health behaviors
54
updated review of stress and CVD
1. hazard ratio of 1.2-1.4 for job strain
| 2. can compare that to HR of 2+ for other risk factors like high bp, smoking and high BMI
55
other stressors linked to CVD
1. childhood stress
| 2. social isolation
56
BP as a Y for CVD
1. well BP is a risk factor b/c of its relevance to atherosclerosis
2. stress also leads to heightened BP
57
stress reactivity and CVD evidence
1. 756 finnish men
2. CV stress response assessed using lab stress tasks
3. memory, rxn time, tracing and stroop color-word tasks
4. atherosclerosis assessed at 4 yr and 11 yr visits
5. results
a. cross sectional: larger BP response, higher carotid IMT -> more artherosclerosis
b. longitudinal: larger BP response -> more rapid inc IMT over time
58
non invasively measuring atherosclerosis
carotid intima-media thickness (IMT)
59
pittsburgh healthy heart project
1. 340 older adults
2. electronic diaries every 45 mins for 3 days
3. asked about task demands and decisional control
-also assessed IMT
4. more demands were assoc with higher bp daily life
5. more demands were also assoc with greater IMT
THEREFORE INC BP, INC IMT
60
does stress trigger heart attacks in ppl with underlying cvd?
- acute stressors are strongly assoc with cardiac events in high risk pops and those with CVD
- may involve diff mechanisms
61
Control Groups
used to rule out or weaken rival hypotheses or alt explanations
62
alt explanations
1. ruled out by control groups
2. history/ maturation: improvement over time
3. improvement as a result of completing assessments
4. improvement as a result of receiving some kind of treatment, doesn't depend on actual treatment received
63
placebo
substance or procedure a subject accepts as medicine or therapy but that has not specific therapeutic activity
64
placebo controls for:
1. patient expectancies
2. therapeutic alliance
3. spontaneous remission
4. deterioration of symptoms
65
placebo for control groups
1. gold standard for drug trials
| 2. hard to achieve with behavior research
66
usual care for control groups
1. compare new treatment to one that is provided in setting
| 2. may not be comparable in terms of time, attention or other factors
67
contact/attention control groups
1. controls for "nonspecific" aspects of your intervention
e. g. attending treatment sessions, attention to symptoms, contact with therapist, provision of info
2. credible but not "active"- closest to placebo controlled trial
68
ENRICHD trial
1. Intervention: CBT both individual and group (depressed patients), added SSRI at 5 weeks for patients showing no improvement
2. X: depression and LPSS (low social support)
3. Y: No Y!
4. Z: Recurrent myocardial infarction (heart attack or all cause mortality- death)
5. Plausible Y based on lecture: systemic inflammation (atherosclerosis), blood pressure
6. Results:
- >Intervention influenced X
- >No effect on Z (maybe because there’s no Y)
69
Dean Ornish Lifestyle Medicine Program
1. intervention: 18 group sessions, 4 hrs/ session
2. x: lack of activity, nutrition, fitness and support
3. y: ?
4. z: stenosis (narrowing of arteries) and cardiac events
5. results: at 5 yr follow-up intervention group had less narrowing of arteries and fewer cardiac events
70
immune system
1. collection of cells and organs in the body
2. designed to detect and protect body against foreign substances
3. must also ignore self, but it sucks at this one
71
4 classes of pathogens (that immune system attacks)
1. extracellular bacteria, parasites, fungi
2. intracellular bacteria, parasites
3. viruses (intracellular)
4. parasitic worms (extracellular)
72
two arms of immune system:
1. innate immune system
| 2. adaptive immune system
73
innate immune system
1. first line of defense
2. rapid response
3. key cells:
a. neutrophils
b. macrophages
c. natural killer (NK) cells
74
neutrophils
secrete factors that kill and digest pathogens
75
macrophages
1. big eaters
2. engult and digest pathogens
3. release PROINFLAMMATORY CYTOKINES to signal other cells
76
NK cells
attack virally infected cells
77
inflammation features
1. heat
2. pain
3. redness
4. swelling
78
inflammation
1. reflects the effects of cytokines and other inflammatory mediators on local blood vessels
2. key cytokines:
1. IL-1beta
2. TNF-alpha
3. IL-6
79
key cytokines
1. IL-1beta
2. TNF-alpha
3. IL-6
80
adaptive immune system
1. second line of defense
2. responds slowly and specific to pathogens you've seen before
3. key cells
a. t cells
b. b cells
81
t cells
1. CD4 "helper": direct other immune cells to attack pathogens
2. CD8 "cytotoxic" t cells: provide protection against pathogens that live inside of cells; find infected cells and kill
82
CD4 helper
1. t cell
2. adaptive immune system
3. instruction to attack
83
CD8 cytotoxic
1. t cell
2. adaptive immune system
3. kill them all!
84
B cells
1. protect against pathogens that live outside of cells
2. release antibody that disables pathogens and helps to get rid of them
ANTIBODY MEDIATED IMMUNITY
85
pathways b/w brain and IS
1. brain communicates with IS through ANS and NE system
2. ANS sends fibers into immune organs, releases neurotransmitters that influence immune cells
3. hormones from NE system also influence immune processes
- > cortisol ahs profound effects on immune cell dev
86
acute stress:
1. parachute jumping, public speaking with evaluation (trier social stress task)
3. enhancement of certain components of immune system, particularly innate branch: inflammation/NK cells
87
chronic stress:
1. bereavement, divorce, care taking
2. suppression of certain aspects of the immune system, particularly the adaptive branch
3. inc in inflammation
88
suppression of adaptive branch of immune system
decrease in ability of adaptive immune cells to do their jobs (i.e. make antibodies and replicate themselves)
89
common cold
1. infection of upper respiratory tract
2. rhinovirus
3. symptoms: cough, runny nose, nasal congestion, sore throat
90
stress and common cold
studies suggest that stress inc risk of geting a cold
91
Salisbury Common Cold Unity (CCU)
1. more stress = more cold?
2. 3 stress measures
a. life events checklist
b. perceived stress scale
c. negative affect scale
3. possible y: ANS (e/ne) or HPA (cortisol)
4. not the y they thought
92
HIV/AIDS
1. HIV: human immunodeficiency virus
2. AIDS: acquired immune deficiency syndrome
- > chronic illness that occurs after HIV infection attacks your immune system
93
pathogenesis of HIV/AIDS
1. HIV infects and kills CD4 T cells
2. rapid depletion of CD4 T cells until immune system mounts a response
3. body establishes "set pt" with balance b/w virus and immune system
94
unique stressors of HIV
1. stigmatized diease
2. homo sex
3. IV drug use
4. infection occurs early in life -> not "age appropriate"
5. social networks also effected
95
HIV: stress / disease progression in animal studies
1. infect animals with HIV
2. exposure to stress v no stress conditions
3. eval effects on disease
4. monkey model: social stress led to reduced survival
5. studies generally support assoc b/w stress and HIV progress
- > most robust when capture severity and chronicity of stress events
96
Leserman et al, 2000 (HIV)
1. intervention: n/a
2. x: stress based on life events checklist
3. y: dec immune response, SNS act inc
4. z: AIDS onset
5. results: AIDS risk doubled for every inc of one severe stressor
97
stress and aids mortality
1. intervention: n/a
2. x: stress assessed using interview and questionnaire
3. y: dec immune response, SNS act inc
4. z: death
5. results: risk of death inc by 17% for every trauma
98
CBSM trial
1. intervention: 10 wk group based stress management/relaxation component
2. X: perceived stress, anxiety, and anger
3. Y: SNS activity
4. Z: T-cell sub-populations
5. Results:
- >Declines in anxiety (X) were associated with decreases in NE (Y)
- >Decreases in norepinephrine (Y) were associated with changes in CD8+ T cells (Z)
99
appraisals
our interpretation of events, not necessarily accurate can be modified
e.g. threat v challenge
100
coping
cognitive, emotional and behavioral response to stressors
101
approach oriented strategies
designed to deal with problem and/or thoughts/ feelings about it
102
avoidance oriented strategies
designed to avoid problems and/or thoughts and feelings about it
103
improving interpersonal communication and relationships
1. anger management and assertiveness training
| 2. social support building
104
anger management and assertiveness training
teaches ppl to communicate their feelings and desires in a more productive/less confrontational manner
105
social support building
promotes awareness of resources in social network and strategies for improving sources of support
106
progressive muscle relaxation
trains participants to relax by tensing and then relaxing each of 16 mucle groups
107
limitations of CBSM trial
1. relatively small homogeneous group
| 2. no control for attention, nonspecific aspects of intervention
108
CBSM for HIV positive women
1. intervention: CBSM
2. x: HIV+
3. y: not in notes
4. z: depression and immune status
5. results: depression inc in control group, CD4 and NK cells dec in control group
109
2 meta analyses for CBT/stress management and HIV+ individuals
1. overall saw small - moderate reduction in depression, anxiety, anger and stress
2. limited evidence for effects on CD4 t cells, viral load, or NE measures
110
why did CBSM trial lead to biological effects while other interventions don't?
1. more effective intervention leads to sig reduction in distress
2. longer-term followup allows time for immune effects to emerge
(possibilities only)
111
cancer
1. a term for diseases in which abnormal cells divide without control and can invade other tissues
2. cancer always begins with mutations in DNA that interfere with normal cell growth
- > cells can't die when they should and new cells are formed when they shouldn't be
- > not always inherited
112
benign
1. not yet cancer
2. tumor cells grow only locally and can't spread by invasion or metastasis
3. caused by incorrect cell growth
113
malignant
1. cancer
| 2. cells invade neighboring tissues, enter blood vessels, and metastasize to different sites
114
invasion and metastasis
1. cancer cells invade surrounding tissues and blood vessels
2. cancer cells are transported by teh circulatory system to distant sites
3. cancer cells reinvade and grow at new location
115
why cancer is potentialy dangerous
1. b/c it gets into other organs that can't handle large masses
a. brain
b. liver
c. melanoma (initial tumor)
d. melanoma cells travel through blood stream
116
many types of cancer
1. over 100 types
2. arise from diff prts of body
3. triggered by diff factors
a. inherited genes
b. viruses (15% of all cancers)
c. environment
d. behavioral
117
stress and breast cancer
1. prospective study
2. x: occurrence of 21 life events in last 5 yrs + stress of daily living
a. covariates: BMI, alcohol, tobacco, physical activity, daily stress, neuroticism
3. y=?
4. z: breast cancer
5. results: risk for breast cancer inc w/ more life events, effects sig controlling for confounds
STRESS OF DAILY LIVING NOT ASSOC WITH CANCER RISK
118
daily living stress
1. feelings of tension/nervousness
2. stress
3. demand assoc with daily activities
4. daily mental and physical exhaustion
119
stress and breast cancer 2: Kvikstad et al, 1994, 96
1. prospective study
2. x: divorce/ loss of hubby, death of child
a. covariates: age, # of children
3. y:?
4. Z:?
5. results: they got nada
- > divorce assoc with slightly lower risk of breast cancer
120
stress and breast cancer 3: kroenke et al, 2004
1. prospective study
2. x: hours/ wk caregiving (chronic stress)
3. y: dec immune system
4. z: breast cancer progression
5. results: found nada
121
meta analyses of stress and cancer incidence
1. results suggested a pos but weak assoc b/w stress and cancer
2. conclusion limited by heterogeneity of studies considered
122
meta analysis of work stress and cancer incidence
1. examined link between work stress and cancer incidence
2. used males and females from 12 european cohort studies
3. no evidence that job strain is assoc with cancer
123
stress of social isolation and breast cancer
1. social isolation is most influence viarable
| 2. socially isolated women had higher risk of recurrence, breast cancer- related mortality and total mortality
124
stress of social isolation and ovarian cancer
1. competed measure of social isolation/attachment
| 2. high social attachment -?> more likely to be alive at the end
125
immunity and cancer
1. NK cells good, help kill tumor cells
- > can ID them and kill them
2. Cytotoxic t cells good, help kill tumor cells
- > good for killing tumor cells but not at IDing them
3. Macrophages: try to be good but are bad; help tumor grow and spread b/c it gives it blood
126
immunosurveillance
the immune system patrols the body looking for evidence of developing tumors
127
Y variable for immune change and cancer
1. suppression of cellular immunity?
a. immunosurveillance
b. studies show assoc b/w stress and immune suppression in cancer patients mirror those seen in other groups-> stress makes NK cells less effective and slows replication of t and b lymphocytes
128
breast cancer animal models
1. inject rats with tumor in lung
2. expose to stress: forced swimming
3. results: dec in NK act and more tumor spread
129
stress, immunosuppression and skin cancer: animal models
1. expose mice to UVB rad, which induces skin cancer
2. expose to chronic restraint stress (can't move)
3. results:
- > stressed mice faster tumor dev and prog
- > stress reduce t cell infiltration of ttumor; not able to destroy cell possibly
130
stress, immunosuppression and skin cancer: human models
1. prospective
2. x: depression makes it worse
3. y: (additional pathways depression in general leads to death?)
4. z: cancer of liver, gall bladder and pancreas
5. results: inc depress sympt -> shorter survival, mediated by lower NK cells
131
y variables in the x-y-z model: inflammation
1. inflammation plays a key role in cancer growth, progression and metastasis
2. mediated by proinflam cytokines
a. enhance cancer cell proliferation
b. stimulate and sustain angiogensis
c. facilitate tissue invasion
d. support tumor spread
132
relevance of animal studies with renal cancer in humans?
1. depressive symptoms linked to:
a. inc inflam in circulating immune cells
b. inc macrophaage infiltration into tumors
c. shorter survival
133
relevance of animal studies with breast cancer in humans?
1. we see inc in lymphatic vessel density in breast tumors from women who are HIGH IN SOCIAL ISOLATION
a. looking to see # of macrophages in tumors
b. looking at inc in lymph ves
c. looked at stressors
2. only thing that really effected it was amt of social support
134
cole et al., 2015
1. showed that NE influences the kinds of cells that go to tumor and what they do in tumor.
2. if target NE then effects don't show (use beta blockers)
3. x: stress
4. y1: NE
5. y2: inflammation
6. z: cancer progression
135
spiegel and coyne
1. Psychosocial interventions and cancer survival
2. interpret the same body of literature differently (about half have shown positive effects on survival**) Note: this doesn’t mean that psychosocial interventions don’t have positive effects on mood, well-being, etc.
3. Spiegel’s proposed Y: immune system (this relates to what we know about stress and the immune system)
4. Coyne: The psychotherapy may not be the “active ingredient” or the most important
136
results of other trials after spiegel
1. 10 other trials examined
2. 5 trials with benefits, 5 null
3. but they disagree
4. to decide: look at replication of studies and other mechanisms
137
Goodwin Replication Study
1. breast cancer study
2. intervention: 90 min session/ wk for a yr
3. x: social isolation/ mood disturbance?
4. y: ?
5. z: survival/ mood disturbance
6. result: no diff
138
second spiegel study
1. breast cancer
2. intervention: 90 min sess/ wk for 1 yr
3. x: social isolation
4. y: potentially: behavioral/ neuroimmune pathways
5. z: survival, mood disturbance
6. results: dec mood disturbance/pain, no gr diff in survival, intervention effect among women with particular type of tumor (ER neg)
139
4 mon follow up of stress and immunity study
1. breast cancer study
2. intervention: met wkly 4 mons, then monthly 8 mons
3. x: mood disturbance/ immunity
4. y: quality of life, health behavior, adherence to treatment
5. z: recurrence/ survival, mood dist/QOL, Immune
6. results:
a. reduced anxiety
b. inc soc support
c. inc diet habits
d. reduce smoking
e. better adherence to chemo
f. improvement in cellular immunity
140
proliferation
1. a measure of how good immune cells are at making more of themselves (making an army)
2. higher is better!
141
11 yr follow up of stress and immunity study
1. stress management intervention assoc with low risk of recurrence and death
2. immune changes not examined as mediators
3. possible mediation by health behavior/immproved diet habits or chemo adherence
142
PNI pathway
x: reduced stress
y: immune enhancement or inflammation dec
z: cancer survival
143
Fetal Programming
changes in the fetal environment during sensitive periods of dev can cause long-lasting changes in brain/body structure and fn
2. state of mom's exp provides a "weather forecast" to fetus about world outside
3. demonstrated with maternal nutrition (e.g. thrifty phenotype with malnourished mom)
144
prenatal stress
1. maternal stress results in:
a. alt in brain and gut (animals)
b. alt in learning and behavior (inc in ADHD/anxiety, lower cog perform)
c. alt in HPA axis and immune system
145
postnatal stress and health
1. early rearing environ => long term effects on physical health
2. crit dev period: 1st-5th yr of life
146
ACES
1. questionnaire on adverse childhood experiences
2. looked for assoc with presence of adult diseases
3. 50% reported some kind of adversity
4. 4 or more categories of childhood exposure had higher rates of:
a. heart disease
b. cancer
c. stroke
d. bronchitis/emphysema
e. diabetes
147
meta analysis of childhood abuse and physical health
1. all retrospective
| 2. small-medium assoc
148
childhood abuse and mortality
1. ages 25-74 yrs at baseline
2. assessed emotional abuse, moderate physical abuse, severe physical abuse
3. followed for 20 yrs
4. abuse assoc w/ inc risk of mortality in women
5. problems/ confounds: many other stressors co-occur with such exposure:
a. low ses
b. high exp to environ toxins
c. poor health behav
149
Ys of childhood stress
1. children in orphanages
| 2. documented abuse
150
what effect would childhood stress have on HPA axis act/ cortisol?
1. inc HPA response to stress
151
rat study on stress in childhood
1. groomed v not groomed
2. not groomed=
a. inc hpa response
b. dec expression of glucocorticoid receptors
c. reduced sensitivity of glucocorticoid receptors
152
human research on cortisol response with early life stressors
1. women with early life stress (ELS) + major dep (MDD) show elevated cortisol response to acute stress
153
ELS intervention trial
Purpose: to enhance cortisol regulation among at-risk children
ABC intervention used (nurturing parenting)
It worked- kids in the intervention had steeper diurnal cortisol slope
154
adversity
| and human research on diurnal cortisol
1. PI kids and post foster care kids
| 2. adversity exposed kids show lower morning cortisol -> flatter slopes -> not healthy
155
dunedine longitudinal study
1. looked at ECE stress exp as it occured
2. longitudinal
3. diff measures:
a. age 3: exposure to maternal reject
b. age 7,9: exposure to harsh discipline
c. age 11: exposure to disruptive caregiver changes
d. age 26: exposure to physical and sexual abuse
4. looked at CRP and white blood cells
5. results: assoc of childhood maltreatment with biomarkers of inflammation
