***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Multiple sclerosis ( MS ) presents with optic neuritis ( ON ) in 20 % of cases and 50 % of ON patients develop MS within 15 years . In this study , we evaluated the preventive effects of vitamin D3 administration on the conversion of ON to MS ( primary outcome ) and on the MRI lesions ( secondary outcome ) of ON patients with low serum 25 ( OH ) D levels . Thirty ON patients ( 15 in each of 2 groups , aged 20–40 years ) with serum 25 ( OH ) D levels of less than 30 ng/ml were enrolled in a double blind , r and omized , parallel-group trial . The treatment group ( cases ) received 50,000 IU of vitamin D3 weekly for 12 months and the control group ( controls ) received a placebo weekly for 12 months . Finally , the subsequent relapse rate and changes in MRI plaques were compared between the two groups . Risk reduction was 68.4 % for the primary outcome in the treatment group ( relative risk = 0.316 , p = 0.007 ) . After 12 months , patients in the treatment group had a significantly lower incidence rate of cortical , juxtacortical , corpus callosal , new T2 , new gadolinium-enhancing lesions and black holes . The mean number of total plaques showed a marginally significant decrease in the group receiving vitamin D3 supplementation as compared with the placebo group ( p = 0.092 ) . Administration of vitamin D3 supplements to ON patients with low serum vitamin 25 ( OH ) D levels may delay the onset of a second clinical attack and the subsequent conversion to MS Background : The prospect i ve Nurses ’ Health Study II ( NHS-II ) , which enrolled over 116,000 female nurses , provides a unique opportunity to test the hypothesis of whether migraine is associated with multiple sclerosis ( MS ) and to explore the temporal aspects of the interrelationship . Objectives : To calculate relative risk of MS among NHS-II participants with and without migraine and to estimate odds ratio ( OR ) of being diagnosed with migraine in women with and without pre-existing MS . Methods : Cox proportional hazards regression was used to estimate rate ratios and 95 % confidence intervals ( CIs ) of being diagnosed with MS in women with and without pre-existing migraine adjusted for potential confounders . Multivariate adjusted ORs of being diagnosed with migraine in women with and without pre-existing MS were estimated using logistic regression . Results : The prevalence of migraine in women  with MS at baseline ( 26 % , p = 0.11 ) and those diagnosed with MS after enrolment ( 29 % , p < 0.0001 ) was higher than in the non-MS cases ( 21 % ) . The relative risk of developing MS in migraineurs was 1.39 times higher than in non-migraineurs ( 95 % CI 1.10–1.77 , p = 0.008 ) . The absolute risk of developing MS in women migraineurs over a 15-year follow-up was 0.47 % and among non-migraineurs 0.32 % . The odds of being diagnosed with migraine was higher in women with pre-existing MS compared with those without MS , but did not reach statistical significance ( OR = 1.57 , 95 % CI 0.97–2.52 ; p = 0.06 ) . Conclusions : Using a large , cohort of women-nurses , history of migraine was associated with an increased risk of MS . However , the difference in absolute risk of MS in migraineurs and non-migraineurs was small A wide variety of potential risk factors for acute exacerbations in multiple sclerosis were evaluated in a one year case-control study . Eighty nine consecutive patients with clinical ly definite multiple sclerosis and relapsing remitting course presenting with a relapse between January and December 1992 were compared with patients matched for age , sex , and degree of disability , who did not experience clinical exacerbations during the same period . Only potential risk factors occurring in the three months preceding the interview were considered patients . Relapsing patients reported no significant increase in the frequency of any risk factor in the three month period before exacerbation compared with the control group . These results suggest that most relapses are not preceded by the conditions commonly considered as risk factors Objective : Low past sun exposure , fair skin type , and polymorphisms of the MC1R gene have been associated with multiple sclerosis ( MS ) risk . We aim ed to investigate the interplay between melanocortin 1 receptor gene variants , red hair/fair skin phenotype , and past environmental sun exposure in MS . Methods : Population -based case – control study in Tasmania , Australia , involving 136 cases with MS and 272 controls r and omly drawn from the community and matched on sex and year of birth . Measures included  past sun exposure by calendar and question naire , spectrophotometric skin type , and MC1R genotype , with any MC1R Arg151Cys , Arg160Trp , or Asp294His alleles present denoted as red hair color ( RHC ) variant . Results : The association between RHC variant genotype and MS was more evident for women ( odds ratio 2.02 [ 1.15–3.54 ] ) than for men ( odds ratio 0.65 [ 0.27–1.57 ] ) ( difference in effect , p = 0.03 ) . The RHC variant genotype was associated with behavioral sun avoidance . In addition , increasing summer sun exposure at ages 6 through 10 years was associated with reduced MS risk among those with no RHC variant ( p = 0.03 ) , but not among those with RHC variant genotype ( p = 0.15 ; difference in effect , p = 0.02 ) . Similar findings were evident for other past sun exposure measures and when the sample was restricted to women only . Conclusion : The interplay between red hair color variant genotype , red hair/fair skin phenotype , and multiple sclerosis ( MS ) is complex . The modification of past sun exposure by MC1R genotype provides further support that ultraviolet radiation or derivatives such as vitamin D may be causally related to a reduced MS risk CONTEXT Epidemiological studies suggest an association between infection with Epstein-Barr virus ( EBV ) and risk of multiple sclerosis ( MS ) . OBJECTIVE To determine whether elevation in serum antibody titers to EBV viral capsid antigen ( VCA ) , nuclear antigens ( EBNA , EBNA-1 , and EBNA-2 ) , and diffuse and restricted early antigen ( EA-D and EA-R ) as well as to cytomegalovirus ( CMV ) precede the occurrence of MS . DESIGN , SETTING , AND SUBJECTS Prospect i ve , nested case-control study . Of 62 439 women participating in the Nurses ' Health Study ( aged 30 - 55 years in 1976 ) and Nurses ' Health Study II ( aged 25 - 42 years in 1989 ) who gave blood sample s in 1989 - 1990 and 1996 - 1999 , respectively , and were followed up through 1999 , 144 women with definite or probable MS and 288 healthy age-matched controls were included in the analysis . MAIN OUTCOME MEASURE Serum antibody titers to the specific EBV and CMV antigens , compared between cases and controls . RESULTS We documented 18 cases of MS with blood collected before disease onset . Compared with their matched controls , these women had higher serum geometric mean titers ( GMTs ) of antibodies to EBV but not CMV . Elevations were significant for antibodies to EBNA-1 ( GMT , 515 vs 203 ; P = .03 ) , EBNA-2 ( GMT , 91 vs 40 ; P = .01 ) , and EA-D ( 15.9 vs 5.9 ; P = .04 ) . The strongest association was found for antibodies to EBNA-2 ; a 4-fold difference in titers was associated with a relative risk ( RR ) of MS of 3.9 ( 95 % confidence interval [ CI ] , 1.1 - 13.7 ) . The corresponding RRs were 1.6 ( 95 % CI , 0.7 - 3.7 ) for VCA , 2.5 ( 95 % CI , 1.0 - 6.3 ) for EBNA , 1.8 ( 95 % CI , 1.0 - 3.1 ) for EA-D , and 1.0 ( 95 % CI , 0.6 - 1.7 ) for CMV . Significant but generally weaker elevations in anti-EBV antibodies were also found in analyses of 126 cases of MS with blood collected after disease onset and their matched controls . CONCLUSIONS Our results support a role of EBV in the etiology of MS The possibility of a link between active smoking and incident multiple sclerosis ( MS ) has been raised . However , possible links between incidence of MS and passive smoking , particularly in children , have not been analysed . We conducted a population -based , case-control study . The cases were patients with incident MS occurring between 1994 and 2003 , before the age of 16 years , in France . Each case was matched for age , sex and geographic origin with 12 controls , r and omly selected from the French general population . Information about the smoking history of the parents of the cases and controls was collected with a st and ardized question naire . Conditional logistic regression was used to estimate the rate ratio ( RR ) of MS associated with parental smoking at home . The 129 cases of MS were matched with 1038 controls . Information about parental smoking was obtained for all these cases and controls . Exposure to parental smoking was noted in 62.0 % of cases and 45.1 % of controls . The adjusted RR of a first episode of MS associated with exposure to parental smoking at home was 2.12 ( 95 % confidence interval : 1.43 - 3.15 ) . Stratification for age showed that this increase in risk was significantly associated with the longer duration of exposure in older cases ( over 10 years of age at the time of the index episode)-RR 2.49 (1.53 - 4.08)-than in younger cases . Children exposed to parent smoking have a higher MS risk . The duration of exposure also affects the level of risk Abstract . Several studies indicate that patients with multiple sclerosis ( MS ) have low serum levels of the endogenous antioxidant uric acid ( UA ) , although it has not been established whether UA is primarily deficient or secondarily reduced due to its peroxynitrite scavenging activity . We measured  serum urate levels  in 124 MS patients and 124 age- and sex-matched controls with other neurological diseases . In addition , we compared UA levels when MS patients were stratified according to disease activity ( by means of clinical examination and MRI ) , duration , disability and course . MS patients had significantly lower serum urate levels than controls ( p= 0.001 ) . However , UA levels did not significantly correlate with disease activity , duration , disability or course . Our study favors the view that reduced UA in MS is a primary , constitutive loss of protection against oxidative agents , which deserves further pathogenetic elucidation aim ed at future therapeutic strategies Background : Antioxidant nutrients may reduce the risk of MS . In a recent case-control study , vitamin C intake was significantly inversely associated with  MS risk among women . However , no prospect i ve data are available . Objective : To examine prospect ively the associations of intakes of carotenoids , vitamin C , and vitamin E with the  risk of MS among women . Methods : The authors documented the occurrence of definite and probable MS within two large cohorts of women who completed detailed and vali date d semiquantitative food frequency question naires . One cohort ( Nurses ’ Health Study ) comprised 81,683 women aged 38 to 63 years in 1984 , who were followed for 12 years ; the other ( Nurses ’ Health Study II ) comprised 95,056 women aged 27 to 44 years in 1991 , who were followed for 6 years . Results : The authors documented a total of 214 cases of MS . After adjustments for age , latitude of birthplace , pack-years of smoking , and total energy intake , the pooled multivariate relative risks ( 95 % CIs ) comparing women in the highest quintile with those in the lowest quintile were 1.1 ( 0.7 to 1.7 ) for α-carotene , 1.1 ( 0.7 to 1.6 ) for β-carotene , 1.4 ( 0.8 to 2.2 ) for β-cryptoxanthin , 1.0 ( 0.6 to 1.5 ) for lycopene , 1.0 ( 0.7 to 1.6 ) for lutein/zeaxanthin , 1.4 ( 0.9 to 2.1 ) for total vitamin C , 1.3 ( 0.9 to 2.0 ) for dietary vitamin C , 0.8 ( 0.6 to 1.3 ) for total vitamin E , and 0.9 ( 0.6 to 1.4 ) for dietary vitamin E. The authors found no associations between intakes of fruits and vegetables and risk of MS . Use of vitamin C , vitamin E , and multivitamin supplements was also unrelated to risk of MS . Conclusions : These findings do not support hypotheses relating higher intakes of dietary carotenoids , vitamin C , and vitamin E to reduced risk of MS in women CONTEXT Epidemiological and experimental evidence suggests that high levels of vitamin D , a potent immunomodulator , may decrease the risk of  multiple sclerosis .  There are no prospect i ve studies addressing this hypothesis . OBJECTIVE To examine whether levels of 25- 
    Output:
    
Best evidence , which included one or more prospect i ve studies , suggested that lower exposure to sunlight and /or lower serum vitamin D levels were associated with an increased risk of developing MS onset and subsequent relapses , but a similar quality of evidence was lacking for disease progression .
Prospect i ve studies indicated that cigarette smoking may increase the risk of MS as well as accelerate disease progression , but whether smoking altered the risk of a relapse was largely unknown .
Infections were implicated in both risk of developing MS and relapses , but data for progression were lacking .
Specifically , exposure to the Epstein‐Barr virus , particularly if this manifested as infectious mononucleosis during adolescence , was associated with increased MS risk .
Upper respiratory tract infections were most commonly associated with an increase in relapses .
Relapse rates typically dropped during pregnancy , but there was no strong evidence to suggest that pregnancy itself altered the risk of MS or affected long‐term progression .