TGF-ß specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf.

T follicular helper (TFH) cells are essential for effective antibody responses, but deciphering the intrinsic wiring of mouse TFH cells has long been hampered by the lack of a reliable protocol for their generation in vitro. We report that transforming growth factor-ß (TGF-ß) induces robust expression of TFH hallmark molecules CXCR5 and Bcl6 in activated mouse CD4+ T cells in vitro. TGF-ß-induced mouse CXCR5+ TFH cells are phenotypically, transcriptionally, and functionally similar to in vivo-generated TFH cells and provide critical help to B cells. The study further reveals that TGF-ß-induced CXCR5 expression is independent of Bcl6 but requires the transcription factor c-Maf. Classical TGF-ß-containing T helper 17 (TH17)-inducing conditions also yield separate CXCR5+ and IL-17A-producing cells, highlighting shared and distinct cell fate trajectories of TFH and TH17 cells. We demonstrate that excess IL-2 in high-density T cell cultures interferes with the TGF-ß-induced TFH cell program, that TFH and TH17 cells share a common developmental stage, and that c-Maf acts as a switch factor for TFH versus TH17 cell fates in TGF-ß-rich environments in vitro and in vivo.

New insights of Nb2O5-based coatings on the 316L SS surfaces: enhanced biological responses.

This communication aims to propose new insights of Nb2O5-based coatings on the 316L SS surface with great prospects to be used in the dentistry field as brackets. The Nb2O5 thin film was incorporated into the 316L SS by using PVD method. For this purpose, the studied system was characterized structurally and morphologically by using AFM, FTIR-IRRAS, Raman spectroscopy and X-ray photoelectron spectroscopy (XPS). Biological assays were performed using human gingival fibroblast cell-line HGF-1. In agreement with FTIR and Raman results, the XPS technique indicates that Nb is present in an oxidation state assigned to Nb2O5. Furthermore, the coatings produced by PVD technique are less toxic and induces less inflammation in gingival cells (cell-line HGF-1), suggesting the strategy of use Nb2O5 thin film to cover the 316L SS promoted since its protection of the physiological environment to its biocompatibility improvement.

Reliability and Minimal Detectable Change for Sit-to-Stand Tests and the Functional Gait Assessment for Individuals With Parkinson Disease.

BACKGROUND AND PURPOSE: This study examined test-retest relative (intraclass correlation coefficient [ICC]) and absolute (minimum detectable change [MDC]) reliabilities for the 5 times sit-to-stand (5×STS), 30-second sit-to-stand (30sSTS), and the functional gait assessment (FGA) tests in people with Parkinson disease (PD). In addition, correlation of these functional tests with a history of falls was examined over a 6-month period, and the internal consistency of the FGA was established. METHODS: Twenty-two patients with PD (Hoehn and Yahr stages 1-3) completed 3 functional tests over 2 test-retest periods of 6 to 8 days. Falls were self-reported for the prior 6 months. RESULTS AND DISCUSSION: Moderate-to-excellent test-retest ICC(2,2) and MDC95 values were found for the 30sSTS (0.94, 3 times) and ICC(2,1) and MDC95 values were found for the FGA (0.86, 4 points). The 5×STS demonstrated a lower ICC(2,2) and a high MDC95 value (0.74, 10 seconds). A significant correlation was only found between past falls and the FGA test (r =-0.48, P < .05) during session 1. Cronbach α values for the 10-item FGA during session 1 and session 2 were 0.75 and 0.85, respectively. CONCLUSIONS: To assess for change over time, we found the 30sSTS and the FGA tests can be used reliably in patients with PD. A lower FGA score was associated with a higher chance of falls, and good internal consistency of the FGA was found.

Long-term exercise training for an individual with mixed corticobasal degeneration and progressive supranuclear palsy features: 10-year case report follow-up.

BACKGROUND AND PURPOSE: This case report describes the effects of long-term (10-year) participation in a community exercise program for a client with mixed features of corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). The effects of exercise participation on both functional status and brain volume are described. CASE DESCRIPTION: A 60-year-old male dentist initially reported changes in gait and limb coordination. He received a diagnosis of atypical CBD at age 66 years; PSP was added at age 72 years. At age 70 years, the client began a therapist-led community group exercise program for people with Parkinson disease (PD). The program included trunk and lower extremity stretching and strengthening, upright balance and strengthening, and both forward and backward treadmill walking. The client participated twice weekly for 1 hour for 10 years and was reassessed in years 9 to 10. OUTCOMES: Falls (self-reported weekly over the 10-year period of the study by the client and his wife) decreased from 1.9 falls per month in year 1 to 0.3 falls per month in year 10. Balance, walking endurance, and general mobility declined slightly. Gait speed (both comfortable and fast) declined; the client was unable to vary gait speed. Quantitative brain measurements indicated a slow rate of whole brain volume loss and ventricular expansion compared with clients with autopsy-proven CBD or PSP. DISCUSSION: This client has participated consistently in a regular group exercise program for 10 years. He has reduced fall frequency, maintained balance and endurance, and retained community ambulation using a walker. Combined with the slow rate of brain volume loss, this evidence supports the efficacy of a regular exercise program to prolong longevity and maintain function in people with CBD or PSP.

The Effect of Parkinson Drug Timing on Cardiovascular Response during Treadmill Exercise in a Person with Parkinson Disease and Freezing of Gait.

PURPOSE: To examine the response of cerebral oxygenation during treadmill walking in a person with Parkinson disease (PD) who experiences freezing of gait (FOG) and to determine whether the oxygen response was related to the timing of his PD medication. Client Description: A 61-year-old man with PD performed two bouts of treadmill testing on the same day, during the on- and off-phases of his PD medication. Measures and Outcome: The client experienced two FOG episodes during the first testing session (on-phase with hypokinetic movement session). Cerebral oxygen response (measured by near-infrared spectroscopy) was stable until the FOG episodes occurred, at which point it decreased until the FOG episode was over. No electrocardiogram (ECG) changes or lightheadedness were noted; blood pressure (BP) remained stable. During the second exercise testing session (off-phase with dyskinetic movement session), the client did not experience any FOG episodes, and his cerebral oxygen response remained stable. Toward the end of the second testing session, he experienced lightheadedness and a drop in BP of approximately 30 mmHg, along with significant ST segment depression on his ECG. IMPLICATIONS: Haemodynamic and cerebral oxygen changes occurred that were specific to the timing of the client's PD medication and to his FOG episodes. This case study shows a person with PD demonstrating decreased cerebral oxygenation during FOG, which may be based on his variable response to levodopa medication or may be attributable to as yet unidentified physiologic mechanisms.

Objectif : Analyser la réaction de l'oxygénation cérébrale au cours de la marche sur tapis roulant chez une personne souffrant de la maladie de Parkinson (MP) aux prises avec un blocage de la marche (freezing of gait, FOG), puis déterminer si la réaction de l'oxygène cérébral est liée à l'horaire selon lequel ses médicaments pour la MP sont administrés. Description du client : Un homme de 61 ans souffrant de la MP. Il a accompli deux tests sur tapis roulant la même journée, lorsque ses médicaments pour la MP étaient en phase et lorsqu'ils étaient hors-phase. Mesures et résultat : Le client a vécu deux épisodes de FOG au cours de la première séance de tests (en phase, avec séance de mouvements hypocinétiques). La réaction de l'oxygène cérébral (mesurée par spectroscopie proche infrarouge) était stable jusqu'à ce que le trouble de la démarche se manifeste; elle a alors décru et est demeurée telle jusqu'à la fin de l'épisode de FOG. Aucun changement à l'électrocardiogramme (ECG) ni aucun étourdissement n'ont été observés et la tension artérielle (TA) est demeurée stable. Au cours de la deuxième séance de tests avec exercice (hors phase, avec séance de mouvements dyscinétiques), le client n'a pas subi d'épisodes de FOG et la réaction de l'oxygène cérébral est demeurée stable. À la fin de la deuxième séance, il a ressenti des étourdissements et sa tension artérielle a chuté d'environ 30 mmHg, et on a aussi constaté un fléchissement appréciable du segment ST de son ECG. Conséquences : Les changements survenus à l'oxygène hémodynamique et à l'oxygène cérébral étaient directement liés au moment de la prise des médicaments pour la MP par le patient et à ses épisodes de FOG. Cette étude de cas démontre que la baisse de l'oxygénation cérébrale au cours des épisodes de FOG chez une personne souffrant de MP peut s'expliquer par sa réaction variable à la lévodopa, ou peut être attribuable à des mécanismes physiologiques non encore identifiés.

Community-based exercise and wellness program for people diagnosed with Parkinson disease: experiences from a 10-month trial.

OBJECTIVE: This study considered whether a therapy community could create an infrastructure for developing and maintaining a service delivery model grounded in a clinic-based physiotherapy model. A longitudinal clinical study was conducted to assess the abilities of participants with Parkinson disease in a 10-month community exercise program. METHODS: Fifteen individuals averaging stage 3 on the Hoehn and Yahr scale, 6 years since Parkinson disease diagnosis, and 72 years old, participated. RESULTS: Graphical analysis of ambulation endurance demonstrated the strongest improvement over time (11%). Walking speeds, balance, and mobility showed a maintenance effect over the 10 months. The total unified Parkinson disease rating scale, activities of daily living subscale, and motor subscale remained statistically unchanged in the study. Scores on the unified Parkinson disease rating scale mentation, behavior, and mood subscale improved by 38%. None of the scores met or exceeded the minimal detectable change, MDC95 but two scores demonstrated more than 10% change. CONCLUSION: This clinical study implemented previous short-term research findings into an ongoing community wellness program for individuals with Parkinson disease. No community-based studies have demonstrated an ability to maintain a group for an extended time frame. Group exercise including forward and backward treadmill training, designed and monitored by a physical therapist, may improve or maintain functional outcomes.

Test-retest reliability and minimal detectable change on balance and ambulation tests, the 36-item short-form health survey, and the unified Parkinson disease rating scale in people with parkinsonism.

BACKGROUND AND PURPOSE: Distinguishing between a clinically significant change and change due to measurement error can be difficult. The purpose of this study was to determine test-retest reliability and minimal detectable change for the Berg Balance Scale (BBS), forward and backward functional reach, the Romberg Test and the Sharpened Romberg Test (SRT) with eyes open and closed, the Activities-specific Balance Confidence (ABC) Scale, the Six-Minute Walk Test (6MWT), comfortable and fast gait speed, the Timed "Up & Go" Test (TUG), the Medical OUTCOMES: Study 36-Item Short-Form Health Survey (SF-36), and the Unified Parkinson Disease Rating Scale (UPDRS) in people with parkinsonism. SUBJECTS: Thirty-seven community-dwelling adults with parkinsonism (mean age=71 years) participated. The Hoehn and Yahr Scale median score of 2 was on the lower end of the scale; however, the scores ranged from 1 to 4. METHODS: Subjects were tested twice by the same raters, with 1 week between tests. Test-retest reliability was calculated using intraclass correlation coefficients (ICCs). Minimal detectable change was calculated using a 95% confidence interval (MDC(95)). RESULTS: The ICCs for test-retest reliability were above .90 for the BBS, ABC Scale, SRT with eyes closed, 6MWT, and comfortable and fast gait speeds. The MDC(95) values for those functional tests were: BBS=5/56, ABC Scale=13%, SRT with eyes closed=19 seconds, 6MWT=82 m, comfortable gait speed=0.18 m/s, and fast gait speed=0.25 m/s. The ICCs for test-retest reliability of SF-36 scores were above .80, with the exception of the social functioning subscale. The MDC(95) values for the SF-36 ranged between 19% and 45%. The MDC(95) values for the UPDRS Activities of Daily Living section, Motor Examination section, and total scores were 4/52, 11/108, and 13/176, respectively. DISCUSSION AND CONCLUSION: Minimal detectable change values are useful to therapists in rehabilitation and wellness programs in determining whether change during or after intervention is clinically significant. High test-retest reliability of scores for the BBS, ABC Scale, SRT with eyes closed, 6MWT, and gait speed make them trustworthy functional assessments in people with parkinsonism. The SF-36 and UPDRS provide quality-of-life and disease severity rating values in the ongoing assessment of people with parkinsonism.

Long-term locomotor training for gait and balance in a patient with mixed progressive supranuclear palsy and corticobasal degeneration.

BACKGROUND AND PURPOSE: Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are slowly progressive tauopathies characterized by impaired balance, disturbances in gait, and frequent falls, among other features. Wheelchair dependence is an inevitable outcome in people with these disorders. Insufficient evidence exists regarding the effectiveness of exercise in the management of people with these disorders. This case report describes a program of exercise and long-term locomotor training, using a treadmill (both with and without body-weight support), to reduce falls and improve the balance and walking ability of a patient with mixed PSP and CBD features. CASE DESCRIPTION: Six years after diagnosis with mixed PSP and CBD features, the client, a 72-year-old dentist, was seen for physical therapy for asymmetric limb apraxia, markedly impaired balance, and frequent falls during transitional movements. INTERVENTION: Over a 2.5-year period, intervention included routine participation in an exercise group for people with Parkinson disease (mat exercise and treadmill training) and intermittent participation in individual locomotor training on a treadmill. The exercise group met for 1 hour, twice weekly. The individual treadmill sessions lasted 1 hour, once weekly, for two 14-week periods during the follow-up period. OUTCOMES: Over the 2.5-year period, fall frequency decreased, and tests of functional balance showed improved limits of stability (functional reach tests) and maintained balance function (Berg Balance Scale). Tests of walking performance showed only slight declines. A 4-wheeled walker was introduced and accepted by the client early in the intervention period. The client, with supervision, remained ambulatory with this wheeled walker in the community. DISCUSSION: In this case report of a person with mixed PSP and CBD features, a physical therapy intervention, which included locomotor training using a treadmill and a long-term exercise program of stretching and strengthening, appears to have improved some dimensions of balance, slowed the rate of gait decline, prevented progression to wheelchair dependence, and decreased falls. Contrary to the expected decline in function, this client maintained independent mobility over a 2.5-year period. An ongoing, intensive program of exercise and locomotor training may help people with PSP and CBD maintain upright balance, decrease falls, and decrease the rate of decline of ambulation.

Testing functional performance in people with Parkinson disease.

BACKGROUND AND PURPOSE: Although the Unified Parkinson's Disease Rating Scale (UPDRS) is the most common performance measure for people with Parkinson disease (PD), the Berg Balance Scale (BBS), Forward Functional Reach Test (FFR), Backward Functional Reach Test (BFR), Timed "Up & Go" Test (TUG), and gait speed may be used to quantify some aspects of functional performance not measured by the UPDRS. The purpose of this study was to describe the relationship among a set of tests of balance, walking performance, and mobility in people with PD. SUBJECTS: Twenty-five community-dwelling adults (11 female, 14 male) with a diagnosis of PD were recruited from PD support groups in southeastern Wisconsin and consented to participate in the study. The mean age of the participants was 76 years (SD=7). The average Hoehn and Yahr Stage Scale score was 2. METHODS: Functional abilities of each subject were assessed with the UPDRS, BBS, FFR, BFR, TUG, and gait speed. Spearman and Pearson correlations were performed. RESULTS: The UPDRS total score was correlated with the BBS (r=-.64, P<.001), FFR (r=-.52, P<.05), and TUG (r=.50, P<.05) measurements. The BBS is the only test of functional performance where scores correlate with all other functional tests and the UPDRS. DISCUSSION AND CONCLUSIONS: The UPDRS total score may not reflect a comprehensive measure of mobility in people with PD. Because the BBS scores correlate both with UPDRS scores and with scores of all other tests of functional performance, the BBS appears to be a good overall measure of function in this population.

Age- and gender-related test performance in community-dwelling elderly people: Six-Minute Walk Test, Berg Balance Scale, Timed Up & Go Test, and gait speeds.

BACKGROUND AND PURPOSE: The interpretation of patient scores on clinical tests of physical mobility is limited by a lack of data describing the range of performance among people without disabilities. The purpose of this study was to provide data for 4 common clinical tests in a sample of community-dwelling older adults. SUBJECTS: Ninety-six community-dwelling elderly people (61-89 years of age) with independent functioning performed 4 clinical tests. METHODS: Data were collected on the Six-Minute Walk Test (6MW), Berg Balance Scale (BBS), and Timed Up & Go Test (TUG) and during comfortable- and fast-speed walking (CGS and FGS). Intraclass correlation coefficients (ICCs) were used to determine the test-retest reliability for the 6MW, TUG, CGS, and FGS measurements. Data were analyzed by gender and age (60-69, 70-79, and 80-89 years) cohorts, similar to previous studies. Means, standard deviations, and 95% confidence intervals for each measurement were calculated for each cohort. RESULTS: The 6MW, TUG, CGS, and FGS measurements showed high test-retest reliability (ICC [2,1]=.95-.97). Mean test scores showed a trend of age-related declines for the 6MW, BBS, TUG, CGS, and FGS for both male and female subjects. DISCUSSION AND CONCLUSION: Preliminary descriptive data suggest that physical therapists should use age-related data when interpreting patient data obtained for the 6MW, BBS, TUG, CGS and FGS. Further data on these clinical tests with larger sample sizes are needed to serve as a reference for patient comparisons.