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BACKGROUND: The Expanded Disability Status Scale (EDSS) has wide scientific and regulatory precedent but limited ability to detect clinically relevant disability progression in secondary progressive multiple sclerosis (SPMS) patients, partly due to a lack of meaningful measurement of short-distance ambulatory and upper-extremity function. OBJECTIVE: To present a rationale for a composite endpoint adding the timed 25-foot walk (T25FW) and 9-Hole Peg Test (9HPT) to EDSS for SPMS disability progression assessment. METHODS: Using the International Multiple Sclerosis Secondary Progressive Avonex Clinical Trial (IMPACT) placebo arm ( n = 215) data, we analyzed disability progression using a novel progression endpoint, "EDSS-Plus," defined as progression on ⩾1 of 3 components (EDSS, T25FW, and/or 9HPT) confirmed ⩾24 weeks apart and with a ⩾20% minimum threshold change for T25FW and 9HPT. RESULTS: Over 2 years, subjects classified as T25FW, 9HPT (dominant hand), or 9HPT (non-dominant hand) progressors worsened on average by 103.4%, 69.0%, and 59.2%, respectively, while non-progressors' times remained largely unchanged. Using EDSS-Plus, 59.5% of the patients had 24-week confirmed disability progression versus 24.7% (EDSS), 41.9% (T25FW), and 34.4% (9HPT (either hand)) on each component alone. CONCLUSION: The 24-week confirmed minimum worsening of ⩾20% for T25FW and 9HPT clearly separates SPMS progressors from non-progressors. We propose that EDSS-Plus may represent an improved endpoint to identify SPMS disability progression.
- Klíčová slova
- Disability evaluation, disease progression, endpoint determination, secondary progressive multiple sclerosis,
- MeSH
- časové faktory MeSH
- chronicko-progresivní roztroušená skleróza diagnóza patofyziologie MeSH
- chůze fyziologie MeSH
- dospělí MeSH
- horní končetina patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- postižení rehabilitace MeSH
- posuzování pracovní neschopnosti MeSH
- progrese nemoci MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Gait impairment represents one of the most common and disabling symptom of multiple sclerosis. Quantification of the gait is an important aspect of clinical trials. In order to identify which temporal or spatial parameters of gait could be used as outcome measures in interventional studies of patients with different levels of disability, we evaluated characteristics of these parameters in MS patients across the whole spectrum of mobility from EDSS 0 to 6.5. METHODS: This is a cross-sectional study of spatial and temporal parameters of gait at self selected speed and at fast speed of walking in 284 patients with multiple sclerosis (108 men, mean age 38 years ± SD 10.8 years, range 18-64) divided into seven levels of disability (EDSS 0 to 1.5, EDSS 2.0 to 2.5, EDSS 3.0 to 3.5, EDSS 4.0 to 4.5, EDSS 5.0 to 5.5, EDSS 6.0, EDSS 6.5). RESULTS: The velocity of gait decreases with increasing EDSS levels. Hovewer, the spatio-temporal parameters of gait that are involved in this process differ across the EDSS levels. The step length is decreased at higher EDSS levels up to the EDSS 6.0, but was not different between EDSS 6.0 and 6.5. The step time is significantly longer at EDSS 6.0 and 6.5, while the step length remains the same at those levels. The increase in percentage of double support time becomes statistically significant at EDSS 3.0-3.5 and continues to increase until EDSS 6.5. Variability of step time, step length or step width did not show significant difference between studied EDSS levels. CONCLUSIONS: There is no single spatio-temporal parameter of gait (other than velocity of gait) that would show significant differences among all levels of EDSS. The step length reflects shortening of steps at lower EDSS levels (2.0 to 6.0), and percentage of double support time better reflects changes at higher EDSS levels 3.0 - 6.5. Gait variability is not associated with disability in MS and therefore would not be a suitable outcome measure. These observations have to be considered when designing gait experiments with temporal and spatial parameters of gait as outcomes.
- MeSH
- chůze (způsob) MeSH
- chůze MeSH
- dospělí MeSH
- hodnocení výsledků zdravotní péče MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- neurologické poruchy chůze diagnóza etiologie MeSH
- postižení MeSH
- průřezové studie MeSH
- roztroušená skleróza komplikace MeSH
- stupeň závažnosti nemoci * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: A special care of MS women planning a pregnancy is highly demanding especially in the terms of disease modifying treatment (DMD) decisions and counselling regarding periods of conception, pregnancy and postpartum period. OBJECTIVE: To provide data about impact of pregnancy, delivery or miscarriage/artificial abortion on MS disease course in Czech women with MS based on analysis of retrospective data from the Czech national registry ReMuS. METHODS: The analysis focused on women with MS with at least one record of pregnancy in the registry. Clinical data (EDSS, relapses) were collected prior to conception, during pregnancy and after delivery or miscarriage/artificial abortion. These data were analysed according to baseline characteristics of DMD treatment prior to conception and according to breastfeeding status. RESULTS: A total of 1 533 pregnancies were analysed from the period of 2013 until 31st December 2019. The occurrence of relapses and worse EDSS was significantly related to the treatment with escalation therapy prior to conception. Relapses were significantly more frequent in women who breastfed less than 3 months than in women who breastfed more than 3 months or did not breastfeed at all. Patients treated with either fingolimod or natalizumab prior to pregnancy were significantly more likely to develop relapses during pregnancy. CONCLUSION: Pregnancy and postpartum period were generally safe for Czech women with MS. Better disease outcomes were observed in those who had been treated with first line injectable DMDs prior to conception and those who either breastfed more than 3 months or did not breastfeed at all. We confirmed the assumption of rebound phenomenon of MS after discontinuation of treatment due to planned pregnancy both for fingolimod and natalizumab.
- Klíčová slova
- Czech national registry ReMuS, EDSS, Multiple sclerosis, Pregnancy, Relapses,
- MeSH
- fingolimod hydrochlorid terapeutické užití MeSH
- lidé MeSH
- natalizumab terapeutické užití MeSH
- retrospektivní studie MeSH
- roztroušená skleróza * chemicky indukované farmakoterapie epidemiologie MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
- Názvy látek
- fingolimod hydrochlorid MeSH
- natalizumab MeSH
INTRODUCTION: The influence of breastfeeding and it´s duration on the course of multiple sclerosis (MS) is unclear. Here we analyzed a real-world data for breastfeeding women with MS and their disease course collected from a Czech national registry ReMuS. OBJECTIVES: To identify risk factors associated with not initiating breastfeeding after delivery, to analyze the impact of breastfeeding on the MS disease course, evaluate the assumption, that breastfeeding is not harmful in MS patients, and compare the disease course by breastfeeding status. MATERIALS AND METHODS: Using propensity score matching we compared Expanded Disability Status Scale (EDSS), confirmed disease worsening (CDW) and annual relapse rate (ARR) in breastfeeding and non-breastfeeding MS patients according to disease duration, disease modifying treatment (DMT) before pregnancy, last EDSS score before conception, age, and ARR during pregnancy. We also compared these parameters between breastfeeding patients not using a DMT and non-breastfeeding patients who resumed DMT within 3 months after delivery. EDSS, ARR, and CDW were collected at 12, 24, and 36 months after delivery. RESULTS: A total of 1681 pregnancies that ended in delivery were analyzed from 2013 through 2020. Change in ARR and EDSS values and 6-months CDW did not significantly differ between the analyzed groups. Compared with non-breastfeeding women who resumed DMT early after delivery, breastfeeding women with MS did not experience worse clinical outcomes even without initiating a DMT. DISCUSSION: Breastfeeding in Czech women with MS did not negatively affect the disease course and can be supported. Patients with MS can be treated with certain DMTs alongside breastfeeding and there is no need to stop breastfeeding, if the patient is clinically stable.
- Klíčová slova
- Breastfeeding, Czech national multiple sclerosis patient registry ReMuS, EDSS, Multiple sclerosis, Relapses,
- MeSH
- kojení MeSH
- lidé MeSH
- progrese nemoci MeSH
- recidiva MeSH
- relabující-remitující roztroušená skleróza * farmakoterapie MeSH
- roztroušená skleróza * farmakoterapie epidemiologie MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
The identification of prognostic markers in early multiple sclerosis (MS) is challenging and requires reliable measures that robustly predict future disease trajectories. Ideally, such measures should make inferences at the individual level to inform clinical decisions. This study investigated the prognostic value of longitudinal structural networks to predict 5-year Expanded Disability Status Scale (EDSS) progression in patients with relapsing-remitting MS (RRMS). We hypothesized that network measures, derived from MRI, outperform conventional MRI measurements at identifying patients at risk of developing disability progression. This longitudinal, multicentre study within the Magnetic Resonance Imaging in MS (MAGNIMS) network included 406 patients with RRMS (mean age = 35.7 ± 9.1 years) followed up for 5 years (mean follow-up = 5.0 ± 0.6 years). EDSS was determined to track disability accumulation. A group of 153 healthy subjects (mean age = 35.0 ± 10.1 years) with longitudinal MRI served as controls. All subjects underwent MRI at baseline and again 1 year after baseline. Grey matter atrophy over 1 year and white matter lesion load were determined. A single-subject brain network was reconstructed from T1-weighted scans based on grey matter atrophy measures derived from a statistical parameter mapping-based segmentation pipeline. Key topological measures, including network degree, global efficiency and transitivity, were calculated at single-subject level to quantify network properties related to EDSS progression. Areas under receiver operator characteristic (ROC) curves were constructed for grey matter atrophy and white matter lesion load, and the network measures and comparisons between ROC curves were conducted. The applied network analyses differentiated patients with RRMS who experience EDSS progression over 5 years through lower values for network degree [H(2) = 30.0, P < 0.001] and global efficiency [H(2) = 31.3, P < 0.001] from healthy controls but also from patients without progression. For transitivity, the comparisons showed no difference between the groups [H(2) = 1.5, P = 0.474]. Most notably, changes in network degree and global efficiency were detected independent of disease activity in the first year. The described network reorganization in patients experiencing EDSS progression was evident in the absence of grey matter atrophy. Network degree and global efficiency measurements demonstrated superiority of network measures in the ROC analyses over grey matter atrophy and white matter lesion load in predicting EDSS worsening (all P-values < 0.05). Our findings provide evidence that grey matter network reorganization over 1 year discloses relevant information about subsequent clinical worsening in RRMS. Early grey matter restructuring towards lower network efficiency predicts disability accumulation and outperforms conventional MRI predictors.
- Klíčová slova
- EDSS progression in MS, brain network measures, graph theory, relapsing-remitting multiple sclerosis, structural covariance,
- MeSH
- atrofie patologie MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- mladý dospělý MeSH
- mozek diagnostické zobrazování patologie MeSH
- prognóza MeSH
- progrese nemoci MeSH
- relabující-remitující roztroušená skleróza * diagnostické zobrazování patologie MeSH
- roztroušená skleróza * diagnostické zobrazování patologie MeSH
- šedá hmota diagnostické zobrazování patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
BACKGROUND: Short-term outcomes of optic neuritis (ON) have been well characterized. Limited data exists on longer-term visual outcomes in patients who present with ON. The large MSBase registry allows for characterization of long-term visual outcomes after ON. METHODS: Via the MSBase Registry, data on patients from 41 centers was collected during routine clinical and research visits. Physical and visual disability were measured using the expanded disability status scale (EDSS) and the visual function score (VFS). Inclusion criteria for this analysis included age ≥ 18 years, clinically isolated syndrome (CIS), ON-onset, baseline visit within 6 months of onset, and at least one follow-up visit. Survival analysis was used to evaluate the association of disease-modifying treatment with time to conversion to clinically definite MS or sustained EDSS/VFS progression. RESULTS: Data from 60,933 patients were obtained from the MSBase registry in July 2019. Of these, 1317 patients met inclusion criteria; 935 were treated at some point in disease course, while 382 were never treated. At baseline, mean age was 32.3 ± 8.8 years, 74% were female, median EDSS was 2 (IQR 1-2), and median VFS was 1 (IQR 0-2). Median follow-up time was 5.2 years (IQR 2.4-9.3). Treatment was associated with reduced risk and delayed conversion to clinically definite MS (HR = 0.70, p < 0.001), sustained EDSS progression (HR = 0.46, p < 0.0001) and sustained VFS (HR = 0.41, p < 0.001) progression. CONCLUSIONS: In the MSBase cohort, treatment after ON was associated with better visual and neurological outcomes compared to no treatment. These results support early treatment for patients presenting with ON as the first manifestation of MS.
- Klíčová slova
- Clinically isolated syndrome, Expanded disability status scale (EDSS), MSBase registry, Optic neuritis, Vision,
- MeSH
- demyelinizační nemoci * MeSH
- dospělí MeSH
- kohortové studie MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- posuzování pracovní neschopnosti MeSH
- progrese nemoci MeSH
- registrace MeSH
- roztroušená skleróza * komplikace diagnóza epidemiologie MeSH
- zánět zrakového nervu * diagnóza epidemiologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND PURPOSE: This study assessed the effect of patient characteristics on the response to disease-modifying therapy (DMT) in multiple sclerosis (MS). METHODS: We extracted data from 61,810 patients from 135 centers across 35 countries from the MSBase registry. The selection criteria were: clinically isolated syndrome or definite MS, follow-up ≥ 1 year, and Expanded Disability Status Scale (EDSS) score ≥ 3, with ≥1 score recorded per year. Marginal structural models with interaction terms were used to compare the hazards of 12-month confirmed worsening and improvement of disability, and the incidence of relapses between treated and untreated patients stratified by their characteristics. RESULTS: Among 24,344 patients with relapsing MS, those on DMTs experienced 48% reduction in relapse incidence (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.45-0.60), 46% lower risk of disability worsening (HR = 0.54, 95% CI = 0.41-0.71), and 32% greater chance of disability improvement (HR = 1.32, 95% CI = 1.09-1.59). The effect of DMTs on EDSS worsening and improvement and the risk of relapses was attenuated with more severe disability. The magnitude of the effect of DMT on suppressing relapses declined with higher prior relapse rate and prior cerebral magnetic resonance imaging activity. We did not find any evidence for the effect of age on the effectiveness of DMT. After inclusion of 1985 participants with progressive MS, the effect of DMT on disability mostly depended on MS phenotype, whereas its effect on relapses was driven mainly by prior relapse activity. CONCLUSIONS: DMT is generally most effective among patients with lower disability and in relapsing MS phenotypes. There is no evidence of attenuation of the effect of DMT with age.
- Klíčová slova
- EDSS, immunotherapy, marginal structural model, multiple sclerosis, relapse,
- MeSH
- chronicko-progresivní roztroušená skleróza * MeSH
- imunoterapie MeSH
- lidé MeSH
- proporcionální rizikové modely MeSH
- recidiva MeSH
- relabující-remitující roztroušená skleróza * MeSH
- roztroušená skleróza * terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Fingolimod, an oral sphingosine 1-phosphate receptor immunomodulator, is approved in Europe for people with multiple sclerosis (pwMS) with highly active disease despite a full and adequate course of treatment with ≥ 1 disease-modifying therapy or patients with rapidly evolving severe relapsing-remitting MS. GOLEMS, a national, multicenter, non-interventional, single-arm, real-world study showed a favorable benefit-risk profile of 12-month treatment with fingolimod in pwMS in the Czech Republic. Here, we evaluated the long-term effectiveness and safety of fingolimod and its impact on disability progression and work capability for up to 48 months in pwMS. METHODS: The endpoints assessed were the incidence and severity of MS relapses in fingolimod-treated patients and the proportion of relapse-free patients up to 48 months of fingolimod treatment, change from baseline in the Expanded Disability Status Scale (EDSS) score, and change from baseline in work capability assessment. Efficacy outcomes were analyzed in the completed and efficacy sets, and safety was evaluated in all the enrolled patients. RESULTS: Of 240 enrolled patients, 237 were included into efficacy set. Patients with a minimum of a 12-month observation period in the core study who continued fingolimod treatment, were eligible to participate in the extension phase. Of 211 patients enrolled in extension study, 155 were evaluated in the completed set. Based on analysis of 48-month period of fingolimod treatment, 95/237 patients (40.1%) in the efficacy set, 54/155 (34.8%) in the completed set were free of relapses. The majority of relapses reported were moderate in intensity. Mean EDSS score remained stable throughout 48-month study period (Baseline, 3.4; Month 48, 3.6). No trend was observed in changes in work capability assessment or number of missed days of work. Of 240 enrolled patients, 147 (61.3%) had ≥ 1 treatment-emergent adverse event (AE) and 20 (8.3%) reported serious AEs. In total, 45 patients (18.8%) permanently discontinued treatment because of AEs related to study drug; two patients reported pregnancy after treatment initiation and subsequently discontinued the treatment; no deaths were reported. CONCLUSION: GOLEMS study demonstrated the sustained effectiveness and manageable safety profile of fingolimod under real-world conditions over 48 months in patients with MS. TRIAL REGISTRATION: Not applicable.
- Klíčová slova
- EDSS score, Fingolimod, GOLEMS extension study, Multiple sclerosis, Relapse,
- MeSH
- fingolimod hydrochlorid * škodlivé účinky terapeutické užití MeSH
- imunosupresiva * škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- recidiva MeSH
- relabující-remitující roztroušená skleróza farmakoterapie epidemiologie MeSH
- roztroušená skleróza * farmakoterapie epidemiologie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
- Názvy látek
- fingolimod hydrochlorid * MeSH
- imunosupresiva * MeSH
BACKGROUND: In severe conditions of limited motor abilities, frequent position changes for work or passive and active rest are essential bedside activities to prevent further health complications. We aimed to develop a system using eye movements for bed positioning and to verify its functionality in a control group and a group of patients with significant motor limitation caused by multiple sclerosis. METHODS: The eye-tracking system utilized an innovative digital-to-analog converter module to control the positioning bed via a novel graphical user interface. We verified the ergonomics and usability of the system by performing a fixed sequence of positioning tasks, in which the leg and head support was repeatedly raised and then lowered. Fifteen women and eleven men aged 42.7 ± 15.9 years in the control group and nine women and eight men aged 60.3 ± 9.14 years in the patient group participated in the experiment. The degree of disability, according to the Expanded Disability Status Scale (EDSS), ranged from 7 to 9.5 points in the patients. We assessed the speed and efficiency of the bed control and the improvement during testing. In a questionnaire, we evaluated satisfaction with the system. RESULTS: The control group mastered the task in 40.2 s (median) with an interquartile interval from 34.5 to 45.5 s, and patients mastered the task in in 56.5 (median) with an interquartile interval from 46.5 to 64.9 s. The efficiency of solving the task (100% corresponds to an optimal performance) was 86.3 (81.6; 91.0) % for the control group and 72.1 (63.0; 75.2) % for the patient group. Throughout testing, the patients learned to communicate with the system, and their efficiency and task time improved. A correlation analysis showed a negative relationship (rho = - 0.587) between efficiency improvement and the degree of impairment (EDSS). In the control group, the learning was not significant. On the questionnaire survey, sixteen patients reported gaining confidence in bed control. Seven patients preferred the offered form of bed control, and in six cases, they would choose another form of interface. CONCLUSIONS: The proposed system and communication through eye movements are reliable for positioning the bed in people affected by advanced multiple sclerosis. Seven of 17 patients indicated that they would choose this system for bed control and wished to extend it for another application.
- Klíčová slova
- Assistive technologies, BCI, EDSS, Eye-tracking, Fully adjustable electric bed, Multiple sclerosis,
- MeSH
- lidé MeSH
- pohyby očí MeSH
- postižení * MeSH
- průzkumy a dotazníky MeSH
- roztroušená skleróza * MeSH
- technologie sledování pohybu očí MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Vitamin D receptor polymorphisms have been the target of many studies focusing on multiple sclerosis. However, previously reported results have been inconclusive. The objective of this study was to investigate the association between five vitamin D receptor polymorphisms (EcoRV, FokI, ApaI, TaqI, and BsmI) and multiple sclerosis susceptibility and its course. The study was carried out as a case-control and genotype-phenotype study, consisted of 296 Czech multiple sclerosis patients and 135 healthy controls. Genotyping was carried out using polymerase chain reaction and restriction analysis. In multiple sclerosis men, allele and/or genotype distributions differed in EcoRV, TaqI, BsmI, and ApaI polymorphisms as compared to controls (EcoRV, pa = 0.02; Taq, pg = 0.02, pa = 0.02; BsmI, pg = 0.02, pa = 0.04; ApaI, pg = 0.008, pa = 0.005). In multiple sclerosis women, differences in the frequency of alleles and genotypes were found to be significant in ApaI (controls vs multiple sclerosis women: pg = 0.01, pa = 0.05). Conclusive results were observed between multiple sclerosis women in the case of EcoRV [differences in Expanded Disability Status Scale (p = 0.05); CT genotype was found to increase the risk of primary progressive multiple sclerosis 5.5 times (CT vs CC+TT pcorr = 0.01, sensitivity 0.833, specificity 0.525, power test 0.823)] and FokI [borderline difference in Multiple Sclerosis Severity Score (p = 0.05)]. Our results indicate that the distribution of investigated vitamin D receptor polymorphisms is a risk factor for multiple sclerosis susceptibility and progression in the Czech population. The association between disease risk and polymorphisms was found to be stronger in men. The association of disease progression with polymorphisms was observed only in women.
- Klíčová slova
- EDSS, MSSS, Multiple sclerosis, Single-nucleotide polymorphism, Vitamin D receptor,
- MeSH
- dospělí MeSH
- genetická predispozice k nemoci MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- receptory kalcitriolu genetika MeSH
- roztroušená skleróza genetika patologie MeSH
- senioři MeSH
- sexuální faktory MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- receptory kalcitriolu MeSH
- VDR protein, human MeSH Prohlížeč