Visual Dysfunction and Occupational Performance in Persons With Parkinson's Disease.

IMPORTANCE: Visual function is critical to support occupational performance for persons with Parkinson's disease (PwP), yet it can be adversely affected by the disease. OBJECTIVE: To evaluate the prevalence and general awareness of visual dysfunction and identify the association between visual dysfunction and occupational performance in PwP. DESIGN: Self-reported cross-sectional electronic survey. PARTICIPANTS: PwP, identified from a registered database at a neurological institute, were invited to complete the survey through emails and newsletters. OUTCOMES AND MEASURES: The survey contained items of self-reported visual difficulties, diagnosed eye conditions, and about general awareness about disease-related visual dysfunction. Ophthalmological symptoms and occupational performance were measured with the Visual Impairment Parkinson's disease Questionnaire and the Revised Self-Reported Functional Visual Performance Scale, respectively. RESULTS: Data from PwP (n = 92; Mage = 69 yr) were analyzed. Nearly half were unaware that their disease could affect vision. Awareness was not associated with disease duration. Individuals reporting awareness tended to report difficulties with vision. Functional activities requiring vision were mildly impaired, and the frequency of ophthalmologic symptoms (commonly related to ocular surface disorder) was low. Nevertheless, a higher frequency of ophthalmologic symptoms was positively associated with a higher degree of disability in activities of daily living (Spearman's ρ = .49, p < .01). CONCLUSIONS AND RELEVANCE: Visual dysfunction related to Parkinson's disease may affect occupational performance. Screening for changes in vision in these individuals may aid occupational therapists in addressing functional independence and activity engagement. What This Article Adds: People with Parkinson's disease may not have a general awareness that the disease can adversely affect visual function. Those individuals with awareness tend to notice changes in vision, and this disease-related visual dysfunction may limit engagement and participation in everyday activities. Active evaluation of visual function in people with Parkinson's disease is recommended. Occupational therapists could play a key role by screening for visual dysfunction and providing patient education in the clinic.

Practice Patterns and Responses to the Patient-Driven Groupings Model and Coronavirus Disease 2019 Pandemic in Home Health Occupational Therapy: A Pilot Survey Study.

The purpose of the pilot survey was to understand current practice patterns and responses to the Patient-Driven Groupings Model and the coronavirus disease 2019 (COVID-19) pandemic in home health occupational therapy care. Fifty home health occupational therapy practitioners from 27 states in the United States completed the survey. Descriptive analysis was used to organize and summarize survey responses. The survey items on practice patterns included assessment tools, treatment approaches, and care coordination with physical therapy colleagues. The most reported assessment of occupational performance was the Barthel Index. The common treatment approaches included activities of daily living retraining, energy conservation, and functional mobility and transfer. The majority of respondents (n = 44) communicated with their physical therapy colleagues at least once a week. The communications were often related to scheduling and changes in a patient's condition. Seventy percent of practitioners experienced a reduction in home visits during the recent Medicare payment reform and the pandemic. These practitioners perceived that some patients might have been discharged from home health care prematurely. Additional studies to investigate the impact of policy changes and the pandemic on therapy intensity and patients' functional outcomes are warranted.

Predicting the handgrip strength across the age span: Cross-validating reference equations from the 2011 NIH toolbox norming study.

STUDY DESIGN: This is a cross-sectional observational study. BACKGROUND: Reference equations for describing hand-grip strength across the age span were derived from the 2011 NIH Toolbox norming study. PURPOSE: The purpose of this study was to cross-validate reference equations by evaluating its predicting power on a separate, independent data set from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) study METHODS: Observed hand-grip strength data from 13,676 noninstitutionalized participants were obtained from the NHANES study. Best values (best from 3 trials) and the mean values (averaged from 3 trials) were determined for each hand. Using the age (yr), height (m), and weight (kg), we computed predicted grip strength values for dominant and nondominant hands using the reference equations. For validation, three predictability measures: the correlation coefficient, residuals, and accuracy, were used along with the Bland-Altman plot. RESULTS: The predicted values highly correlated with observed values (r = 0.90, ICC = 0.89). In predicting best values, means (SD) of residuals were 1.41 (5.57) and 1.03 (5.44) kg for dominant and nondominant hands, respectively. In predicting mean values, means (SD) of residuals were -0.23 (5.42) and -0.54 (5.31) kg for dominant and nondominant hands, respectively. Root mean square error ranged from 4.10 (female's nondominant mean values) to 6.74 (male's dominant best values). About 5.56% fell outside of the 95% confidence interval of the prediction. CONCLUSIONS: We acknowledged that the two studies' hand-grip protocols (NIH Toolbox, NHANES) were different. Results provided the preliminary predicting performance of the reference equations derived from the NIH Toolbox study.

The Nexus of Sensory Loss, Cognitive Impairment, and Functional Decline in Older Adults: A Scoping Review.

BACKGROUND AND OBJECTIVES: The prevalence of cognitive impairment and sensory loss in hearing or vision increases with age. Based on the Information Processing Model, cognitive impairment coupled with sensory loss may exacerbate disability in late life. Yet this issue has not been systematically studied. The purpose of this scoping review was to examine the literature that studied the relationship between cognitive impairment, sensory loss, and activities of daily living in older adults. RESEARCH DESIGN AND METHODS: Two reviewers independently screened 1,410 studies identified from 5 electronic databases (Medline, EMBASE, PsycINFO, CINHAL, and Web of Science). The search was completed in June 2020. A study was eligible if it included measurements of cognitive function, vision or hearing, and activities of daily living. Additionally, the data analyses must address how cognitive impairment and sensory loss are related to the performance of activities of daily living. RESULTS: The final review included 15 studies. Findings show an additive effect of cognitive impairment and sensory loss on the activities of daily living. Cognitive impairment or vision loss independently relates to the decline in activities of daily living. Hearing loss relates to the decline only when the loss is severe, or if the daily task is hearing - specific. DISCUSSION AND IMPLICATIONS: Older adults with coexisting sensory loss and cognitive impairment have the highest risk or prevalence of disability, comparing to cognitive impairment or sensory loss alone. This finding highlights the importance of developing interventions to reduce the risk of disability for older adults experiencing multiple impairments.

Loneliness and Activity Engagement Among Rural Homebound Older Adults With and Without Self-Reported Depression.

IMPORTANCE: Rural homebound older adults are a vulnerable population at risk for depression, loneliness, and limited participation, but studies that examine these factors in this population are scarce. OBJECTIVE: To describe the degree of depression, loneliness, and activity engagement among rural homebound older adults and determine differences in loneliness and activity engagement between those with and those without self-reported depression. DESIGN: Cross-sectional survey. SETTING: Two rural counties in south central Indiana. PARTICIPANTS: Homebound adults ages 60 yr and older who received nutritional or companionship services from a local Area Agency on Aging. Outcomes and Measures: Depression was measured with an item on the self-report questionnaire and the Geriatric Depression Scale-15. Loneliness was measured with an item on the self-report questionnaire and the UCLA Loneliness Scale. Activity engagement was measured with the Engagement in Meaningful Activities Survey and the Meaningful Activity Participation Assessment. RESULTS: Ninety-one participants returned surveys, of which 78 were analyzed. Regarding depression, 40% of participants reported having it, but results for the Geriatric Depression Scale-15 showed that 63% were in the indicative or suggestive range for depression. Participants in general reported moderate loneliness and low to moderate engagement in meaningful activities. Those with self-reported depression had significantly higher loneliness and lower activity engagement, particularly in self-care, leisure, and socializing activities. CONCLUSIONS AND RELEVANCE: A high proportion of this sample of rural homebound older adults had depression. Those who did tended to have a higher degree of loneliness and lower engagement in meaningful activities. What This Article Adds: Depression was associated with greater loneliness and lower activity engagement in rural homebound older adults. Occupational therapy practitioners serving rural homebound older adults with depression should consider providing interventions to address loneliness and facilitate activity engagement.

Psychometric evaluation of the disabilities of the arm, shoulder and hand (DASH) in patients with orthopedic shoulder impairments seeking outpatient rehabilitation.

STUDY DESIGN: This is a cross-sectional, observational study. INTRODUCTION: The disability of the arm, shoulder and hand (DASH) questionnaire is an upper-extremity specific outcome measure commonly used in routine clinical care and clinical trials. PURPOSE OF THE STUDY: Our purposes were to: (1) examine the psychometric properties of the DASH questionnaire using factor analysis, one- and two-parameter item response theory models, and (2) develop a functional staging map illustrating the relationships between the item difficulty hierarchy of the DASH items and the patient's DASH total score. METHODS: Data from 2724 patients with orthopedic shoulder impairments seeking outpatient physical therapy in 79 clinics in the US were analyzed. RESULTS: Factor analysis supported a general factor, explaining 62.2% of the total variance. The coverage of DASH items was suitable for patients with shoulder impairments with no ceiling or floor effect. Endorsed items representing the most difficult items were related to feeling less capable, executing recreational activities with force or impact, and performing recreational activities in which you move your arm freely. Items with higher discriminating abilities were those related to do heavy household chores, garden/yard work, and change a light bulb overhead. With a separation index equaled to 4.94, the DASH can differentiate persons into at least 6 statistically distinct person strata. None of the DASH items exhibited differential item functioning by gender or symptom acuity, except two items by age group. DISCUSSION: Besides a total (summed) final score obtained from a specific measure, the keyform and functional staging plots/maps can be used to assist clinicians in clinical interpretation of the scores. CONCLUSIONS: Results supported the clinical usage of the DASH questionnaire in patients with orthopedic shoulder impairments seeking outpatient rehabilitation.

Interventions Within the Scope of Occupational Therapy Practice to Improve Performance of Daily Activities for Older Adults With Low Vision: A Systematic Review.

IMPORTANCE: The prevalence of low vision increases with age. Low vision has detrimental effects on older adults' independence. OBJECTIVE: To identify the effectiveness of interventions within the scope of occupational therapy practice to maintain, restore, and improve performance in daily activities for older adults with low vision. DATA SOURCES: Literature published between 2010 and 2017 was searched in CINAHL, Cochrane Databases, MEDLINE, OTseeker, and PsycINFO. STUDY SELECTION AND DATA COLLECTION: The authors screened and appraised studies following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. Studies were eligible if the participants' mean age was 55 yr or older, the level of evidence was Level III or higher, the intervention was within the scope of occupational therapy practice, and the outcome measures assessed the performance of daily activities. FINDINGS: Fourteen studies met the review criteria. Three intervention themes were identified: low vision rehabilitation services (n = 6), self-management approach (n = 6), and tango (n = 2). Moderate evidence was found for low vision rehabilitation services. Low evidence was found for using the self-management approach or adding the self-management approach to existing low vision rehabilitation services. Low evidence was found for tango. CONCLUSION AND RELEVANCE: This systematic review supports the use of low vision rehabilitation services as an effective approach. Occupational therapy practitioners are encouraged to be part of multidisciplinary teams that offer comprehensive low vision evaluations and multicomponent services. WHAT THIS ARTICLE ADDS: Low vision rehabilitation that offers multidisciplinary services, including occupational therapy, is effective in promoting independence among older adults with low vision.

Feasibility of staff-led 3-Step Workout for Life to reduce late-life activities of daily living disability: a community-based translational study.

Translating and implementing research exercise programs that fit into the context of community service provisions could become part of the effort to reduce late-life disability. The purpose of this study was to examine the feasibility of a staff-led 3-Step Workout for Life program by applying a logic model in a local senior living community. The academic investigator and community fitness staff worked together to modify and implement the program protocol following the logic model. The community staff recruited residents and delivered the program. Residents were eligible if they were sedentary, showed muscle weakness, and experienced difficulty in performing activities of daily living. Feasibility was evaluated with program completion and attendance rates, adverse events, physical performance, and activities of daily living. Seventeen residents (mean age = 80 years) enrolled and 13 completed the program with an average attendance rate of 95%. No severe adverse events were reported. After program completion, participants' muscle strength and gross motor coordination of the upper extremity, as well as performance and satisfaction of activities of daily living were improved. This study supported the feasibility of the staff-led 3-Step Workout for Life program to promote independence for residents at risk of late-life disability in a senior living community.

Redesigning care for older people to preserve physical and mental capacity: WHO guidelines on community-level interventions in integrated care.

Islene Araujo de Carvalho and coauthors discuss the WHO guidelines on integrated care for older people.

Occupational Therapy Interventions to Improve Activities of Daily Living for Community-Dwelling Older Adults: A Systematic Review.

OBJECTIVE: This systematic review aimed to synthesize the effects of interventions within the scope of occupational therapy to improve performance of activities of daily living (ADLs) in community-dwelling older adults. METHOD: Searches were conducted in CINAHL, the Cochrane Database of Systematic Reviews, MEDLINE, PsycINFO, and OTseeker. Empirical studies published between 1995 and 2015 were individually screened and appraised by two reviewers. RESULTS: Forty-three studies met the review inclusion and exclusion criteria. Physical exercise was the most common intervention approach. Physical exercise interventions for frail older adults showed a moderate benefit, but no benefits were found for older adults without noticeable difficulty in ADLs. For older adults with difficulty in ADLs, there was a high benefit of using home-based intervention. CONCLUSION: The findings of this systematic review highlight the importance of addressing older adults' living environment in intervention to promote independence in ADLs.

Functional Ability in the Changing Demographic Landscape: Evidence and Opportunities for Occupational Therapy.

The growing number of older adults is changing the demographic landscape. Occupational therapy can better serve the older adult population by helping them maintain their functional ability, which is the ability to engage in occupations. This special issue includes both studies of interventions to evaluate and support functional ability in community-dwelling older adults and systematic reviews of such studies. This editorial highlights the six systematic reviews, which were completed in collaboration with the American Occupational Therapy Association's Evidence-Based Practice Project. These reviews compile evidence for the effectiveness of interventions within the scope of occupational therapy practice to promote occupational performance in community-dwelling older adults. The distinct value of occupational therapy in supporting the functional ability of community-dwelling older adults with stable or declining health is discussed using the World Health Organization's framework for healthy aging.

Exergame Grading Scheme: Concept Development and Preliminary Psychometric Evaluations in Cancer Survivors.

The challenge of using exergames to promote physical activity among cancer survivors lies in the selection of the exergames that match their fitness level. There is a need for a standardized grading scheme by which to judge an exergame's capacity to address specific physical fitness attributes with different levels of physical engagement. The study aimed to develop an Exergame Grading Scheme and preliminarily evaluate its psychometric properties. Fourteen (14) items were created from the human movement and exergame literature. The content validity index (CVI) was rated by content experts with two consecutive rounds (N = 5 and N = 3 independently). The interrater reliability (IRR) was determined by two raters who used the Exergame Grading Scheme to determine the grading score of the five exergames performed by two cancer survivors (N = 10). Each item had a score of 1 for item-level CVI and 1 for k. For IRR, 9 items had rho values of 1, 1 item had 0.93, and 4 items had between 0.80 and 0.89. This valid and reliable Exergame Grading Scheme makes it possible to develop a personalized physical activity program using any type of exergame or fitness mobile application in rehabilitation practice to meet the needs of cancer survivors.

Effects of physical exercise in older adults with reduced physical capacity: meta-analysis of resistance exercise and multimodal exercise.

Older adults with reduced physical capacity are at greater risk of progression to care dependency. Progressive resistance strength exercise and multimodal exercise have been studied to restore reduced physical capacity. To summarize the best evidence of the two exercise regimes, this meta-analysis study appraised randomized-controlled trials from published systematic reviews. Medline, Embase, and the Cochrane Database of Systematic Review and Cochrane Central Register of Controlled Clinical Trials were searched for relevant systematic reviews. Two reviewers independently screened the relevant systematic reviews to identify eligible trials, assessed trial methodological quality, and extracted data. RevMan 5.3 software was used to analyze data on muscle strength, physical functioning, activities of daily living, and falls. Twenty-three eligible trials were identified from 22 systematic reviews. The mean age of the trial participants was 75 years or older. Almost all multimodal exercise trials included muscle strengthening exercise and balance exercise. Progressive resistance exercise is effective in improving muscle strength of the lower extremity and static standing balance. Multimodal exercise is effective in improving muscle strength of the lower extremity, dynamic standing balance, gait speed, and chair stand. In addition, multimodal exercise is effective in reducing falls. Neither type of exercise was effective in improving activities of daily living. For older adults with reduced physical capacity, multimodal exercise appears to have a broad effect on improving muscle strength, balance, and physical functioning of the lower extremity, and reducing falls relative to progressive resistance exercise alone.

Promoting ADL independence in vulnerable, community-dwelling older adults: a pilot RCT comparing 3-Step Workout for Life versus resistance exercise.

BACKGROUND: Resistance exercise is effective to increase muscle strength for older adults; however, its effect on the outcome of activities of daily living is often limited. The purpose of this study was to examine whether 3-Step Workout for Life (which combines resistance exercise, functional exercise, and activities of daily living exercise) would be more beneficial than resistance exercise alone. METHODS: A single-blind randomized controlled trial was conducted. Fifty-two inactive, community-dwelling older adults (mean age =73 years) with muscle weakness and difficulty in activities of daily living were randomized to receive 3-Step Workout for Life or resistance exercise only. Participants in the 3-Step Workout for Life Group performed functional movements and selected activities of daily living at home in addition to resistance exercise. Participants in the Resistance Exercise Only Group performed resistance exercise only. Both groups were comparable in exercise intensity (moderate), duration (50-60 minutes each time for 10 weeks), and frequency (three times a week). Assessment of Motor and Process Skills, a standard performance test on activities of daily living, was administered at baseline, postintervention, and 6 months after intervention completion. RESULTS: At postintervention, the 3-Step Workout for Life Group showed improvement on the outcome measure (mean change from baseline =0.29, P=0.02), but the improvement was not greater than the Resistance Exercise Only Group (group mean difference =0.24, P=0.13). However, the Resistance Exercise Only Group showed a significant decline (mean change from baseline =-0.25, P=0.01) 6 months after the intervention completion. Meanwhile, the superior effect of 3-Step Workout for Life was observed (group mean difference =0.37, P<0.01). CONCLUSION: Compared to resistance exercise alone, 3-Step Workout for Life improves the performance of activities of daily living and attenuates the disablement process in older adults.

Predicting hand function in older adults: evaluations of grip strength, arm curl strength, and manual dexterity.

BACKGROUND: Hand function is critical for independence in activities of daily living for older adults. AIMS: The purpose of this study was to examine how grip strength, arm curl strength, and manual dexterous coordination contributed to time-based versus self-report assessment of hand function in community-dwelling older adults. METHODS: Adults aged ≥60 years without low vision or neurological disorders were recruited. Purdue Pegboard Test, Jamar hand dynamometer, 30-second arm curl test, Jebsen-Taylor Hand Function Test, and the Late-Life Function and Disability Instrument were administered to assess manual dexterous coordination, grip strength, arm curl strength, time-based hand function, and self-report of hand function, respectively. RESULTS: Eighty-four adults (mean age = 72 years) completed the study. Hierarchical multiple regressions show that older adults with better arm curl strength (ß = -.25, p < .01) and manual dexterous coordination (ß = -.52, p < .01) performed better on the time-based hand function test. In comparison, older adults with better grip strength (ß = .40, p < .01), arm curl strength (ß = .23, p < .05), and manual dexterous coordination (ß = .23, p < .05) were associated with better self-report of upper extremity function. CONCLUSIONS: The relationship between grip strength and hand function may be test-specific. Grip strength becomes a significant factor when the test requires grip strength to successfully complete the test tasks. Arm curl strength independently contributed to hand function in both time-based and self-report assessments, indicating that strength of extrinsic muscles of the hand are essential for hand function.

Age Differences in the Association Between Body Mass Index Class and Annualized Medicare Expenditures.

OBJECTIVE: The aim of the study is to assess the relationship between body mass index (BMI) class and Medicare claims among young-old (65-69), old (70-74), and old-old (75+) adults over a 10-year period. METHOD: We assessed costs by BMI class and age group among 9,300 respondents to the 1998 Health and Retirement Study (HRS) with linked 1998-2008 Medicare claims data. BMI was classified as normal (18.5-24.9), overweight (25-29.9), mild obesity (30-34.9), or severe obesity (35 or above). RESULTS: Annualized total Medicare claims adjusted for age, gender, ethnicity, education, and smoking history were 109% greater for severely obese young-old adults in comparison with normal weight young-old adults (US$9,751 vs. US$4,663). Total annualized claim differences between the normal weight and severely obese in the old and old-old groups were not statistically significant. DISCUSSION: Excess Medicare expenditures related to obesity may be concentrated among severely obese young-old adults. Preventing severe obesity among middle and older aged adults may have large cost implications for society.

Task-Oriented Exercise to Reduce Activities of Daily Living Disability in Vulnerable Older Adults: A Feasibility Study of the 3-Step Workout for Life.

The purpose of this feasibility study was to evaluate the 3-Step Workout for Life program, a 10-week exercise program that included moderate-intensity muscle strength training followed by task-oriented training. Fourteen participants completed the program (mean age = 73 years; SD = 6.83). The Box and Block test (Z = -2.24, p = .03) and the 30-s chair stand test (Z = -2.21, p = .03) indicate improved physical functioning of the upper and lower extremities. More importantly, results of the function component from the Late-Life Function and Disability Instrument (Z = -2.04, p = .04) and motor skills scale from the Assessment of Motor and Process Skills (Z = -2.97, p = .003) indicate subjective and objective improvements on performing activities of daily living. Supplementing moderate-intensity muscle strength exercise with task-oriented training components is feasible. Preliminary data support the effectiveness of 3-Step Workout for Life in reducing late-life disability.

What factors are related to understanding a stereoscopic 3D diabetes educational video in seniors?

The rise of three-dimensional imaging technology and products offers a new avenue for patient education to older adults. This study investigated older adults' perception of a three-dimensional health education video on diabetes, and factors associated with understanding the video. Twenty-one older adults without a history of diabetes watched a short diabetes educational video on a stereoscopic display. They perceived the video as helpful, valuable, and exciting, but too fast. Better understanding of the video is associated with having higher background knowledge of diabetes and greater vocabulary. Ethnicity is also a potential factor. Older adults may choose narrative information over graphic information to process a three-dimensional multimedia presentation.

C-Src/Jak2/PDGFR/PKCδ-dependent MMP-9 induction is required for thrombin-stimulated rat brain astrocytes migration.

Among matrix metalloproteinases (MMPs), MMP-9 has been observed in patients with brain inflammatory diseases and may contribute to the pathology of brain diseases. Thrombin has been known as a regulator of MMP-9 expression and cells migration. However, the mechanisms underlying thrombin-induced MMP-9 expression in rat brain astrocytes (RBA-1 cells) were not completely understood. Here, we demonstrated that thrombin induced the expression of pro-form MMP-9 in RBA-1 cells and cells migration which were attenuated by pretreatment with the inhibitor of receptor tyrosine kinase (Genistein), c-Src (PP1), Jak2 (AG490), PDGFR (AG1296), PI3K (LY294002), Akt (SH-5), PKCs (Ro318220), PKCδ (Rottlerin), or NF-κB (Bay11-7082) and transfection with siRNA of c-Src, PDGFR, Akt, PKCδ, ATF2, p65, IKKα, or IKKß. In addition, thrombin-stimulated c-Src, Jak2, or PDGFR phosphorylation was inhibited by a thrombin inhibitor (PPACK), PP1, AG490, or AG1296. Thrombin further stimulated c-Src and PDGFR complex formation in RBA-1 cells. Thrombin also stimulated Akt and PKCδ phosphorylation and PKCδ translocation which were reduced by PPACK, PP1, AG490, AG1296, or LY294002. We further observed that thrombin markedly stimulated ATF2 or IκBα phosphorylation and NF-κB p65 translocation which were inhibited by Rottlerin or LY294002. Finally, thrombin stimulated in vivo binding of p65 to the MMP-9 promoter, which was reduced by pretreatment with Rottlerin or LY294002. These results concluded that in RBA-1 cells, thrombin activated a c-Src/Jak2/PDGFR/PI3K/Akt/PKCδ pathway, which in turn triggered ATF2 and NF-κB activation and ultimately induced MMP-9 expression associated with cell migration.

Thrombin mediates migration of rat brain astrocytes via PLC, Ca²âº, CaMKII, PKCα, and AP-1-dependent matrix metalloproteinase-9 expression.

Matrix metalloproteinase-9 (MMP-9) plays a crucial role in pathological processes of brain inflammation, injury, and neurodegeneration. Thrombin has been known as a regulator of MMP-9 expression and cells migration. However, the mechanisms underlying thrombin-induced MMP-9 expression in rat brain astrocytes (RBA-1 cells) remain unclear. Here, we demonstrated that thrombin induced the expression of pro-form MMP-9 and migration of RBA-1 cells, which were inhibited by pretreatment with the inhibitor of Gq-coupled receptor (GPAnt2A), Gi/o-coupled receptor (GPAnt2), PC-PLC (D609), PI-PLC (U73122), Ca(2+)-ATPase (thapsigargin, TG), calmodulin (CaMI), CaMKII (KN62), PKC (Gö6976 or GF109203X), MEK1/2 (PD98059), p38 MAPK (SB202190), JNK1/2 (SP600125), or AP-1 (Tanshinone IIA) or the intracellular calcium chelator (BAPTA/AM) and transfection with siRNA of PKCα, Erk2, JNK1, p38 MAPK, c-Jun, or c-Fos. In addition, thrombin-induced elevation of intracellular Ca(2+) concentration was attenuated by PPACK (a thrombin inhibitor). Thrombin further induced CaMKII phosphorylation and PKCα translocation, which were inhibited by U73122, D609, KN62, TG, or BAPTA/AM. Thrombin also induced PKCα-dependent p42/p44 MAPK and JNK1/2, but not p38 MAPK activation. Finally, we showed that thrombin enhanced c-Fos expression and c-Jun phosphorylation. c-Fos mRNA levels induced by thrombin were reduced by PD98059, SP600125, and Gö6976, but not SB202190. Thrombin stimulated in vivo binding of c-Fos to the MMP-9 promoter, which was reduced by pretreatment with SP600125 or PD98059, but not SB202190. These results concluded that thrombin activated a PLC/Ca(2+)/CaMKII/PKCα/p42/p44 MAPK and JNK1/2 pathway, which in turn triggered AP-1 activation and ultimately induced MMP-9 expression in RBA-1 cells.