You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
Trace elements in serum from patients with Parkinson's disease — a prospective case-control study: The Nord-Trøndelag Health Study (HUNT)
Abstract 1:
To assess whether trace elements are involved in Parkinson 's disease ( PD ) we have conducted a prospect i ve study where 19 trace elements have been determined in serum collected from 33 patients before they were diagnosed with the disease , and 99 controls . As a follow-up , serum from 19 of the same patients collected 4 - 12 years after they were diagnosed with PD has been analysed . In the prospect i ve part of the study , the only significant difference was a slightly lower content of Hg in the patient group than in the controls . In the follow-up , significantly higher levels of Hg , Ni , and Y , and lower levels of Ca , Fe , Mg , Mn , Rb and Se were found in the serum sample s collected after the patients were diagnosed with PD compared with pre-diagnostic levels


Title 2:
Smoking and Parkinson disease
Abstract 2:
Objective To investigate whether cigarette smoking interacts with genes involved in individual susceptibility to xenobiotics for the risk of Parkinson disease ( PD ) . Methods Two French population -based case-control studies ( 513 patients , 1,147 controls ) were included as a discovery sample to examine gene-smoking interactions based on 3,179 single nucleotide polymorphisms ( SNPs ) in 289 genes involved in individual susceptibility to xenobiotics . SNP – by – cigarette smoking interactions were tested in the discovery sample through an empirical Bayes ( EB ) approach . Nine SNPs were selected for replication in a population -based case-control study from California ( 410 patients , 845 controls ) with st and ard logistic regression and the EB approach . For SNPs that replicated , we performed pooled analyses including the discovery and replication data sets and computed pooled odds ratios and confidence intervals ( CIs ) using r and om-effects meta- analysis . Results Nine SNPs interacted with smoking in the discovery data set and were selected for replication . Interactions of smoking with rs4240705 in the RXRA gene and rs1900586 in the SLC17A6 gene were replicated . In pooled analyses ( logistic regression ) , the interactions between smoking and rs4240705-G and rs1900586-G were 1.66 ( 95 % CI 1.28–2.14 , p = 1.1 × 10−4 , p for heterogeneity = 0.366 ) and 1.61 ( 95 % CI 1.17–2.21 , p = 0.003 , p for heterogeneity = 0.616 ) , respectively . For both SNPs , while smoking was significantly less frequent in patients than controls in AA homozygotes , this inverse association disappeared in G allele carriers . Conclusions We identified and replicated suggestive gene-by-smoking interactions in PD . The inverse association of smoking with PD was less pronounced in carriers of minor alleles of both RXRA-rs4240705 and SLC17A6-rs1900586 . These findings may help identify biological pathways involved in the inverse association between smoking and PD


Title 3:
Elemental fingerprint as a cerebrospinal fluid biomarker for the diagnosis of Parkinson's disease
Abstract 3:
The diagnosis of Parkinson 's disease ( PD ) still lacks objective diagnostic markers independent of clinical criteria . Cerebrospinal fluid ( CSF ) sample s from 36 PD and 42 age-matched control patients were subjected to inductively coupled plasma-sector field mass spectrometry and a total of 28 different elements were quantified . Different machine learning algorithms were applied to the data set to identify a discriminating set of elements yielding a novel biomarker signature . Using 19 stably detected elements , the extreme gradient tree boosting model showed the best performance in the discrimination of PD and control patients with high specificity and sensitivity ( 78.6 % and 83.3 % , respectively ) , re-classifying the training data to 100 % . The 10 times 10-fold cross-validation yielded a good area under the receiver operating characteristic curve of 0.83 . Arsenic , magnesium , and selenium all showed significantly higher mean CSF levels in the PD group compared to the control group ( p = 0.01 , p = 0.04 , and p = 0.03 ) . Reducing the number of elements to a discriminating minimum , we identified an elemental cluster ( Se , Fe , As , Ni , Mg , Sr ) , which most importantly contributed to the sample discrimination . Selenium was identified as the element with the highest impact within this cluster directly followed by iron . After prospect i ve validation , this elemental fingerprint in the CSF could have the potential to be used as independent biomarker for the diagnosis of PD . Next to their value as a biomarker , these data also argue for a prominent role of these highly discriminating six elements in the pathogenesis of PD


Title 4:
A selenium species in cerebrospinal fluid predicts conversion to Alzheimer’s dementia in persons with mild cognitive impairment
Abstract 4:
Background Little is known about factors influencing progression from mild cognitive impairment to Alzheimer ’s dementia . A potential role of environmental chemicals and specifically of selenium , a trace element of nutritional and toxicological relevance , has been suggested . Epidemiologic studies of selenium are lacking , however , with the exception of a recent r and omized trial based on an organic selenium form . Methods We determined concentrations of selenium species in cerebrospinal fluid sample d at diagnosis in 56 participants with mild cognitive impairment of nonvascular origin . We then investigated the relation of these concentrations to subsequent conversion from mild cognitive impairment to Alzheimer ’s dementia . Results Twenty-one out of the 56 subjects developed Alzheimer ’s dementia during a median follow-up of 42 months ; four subjects developed frontotemporal dementia and two patients Lewy body dementia . In a Cox proportional hazards model adjusting for age , sex , duration of sample storage , and education , an inorganic selenium form , selenate , showed a strong association with Alzheimer ’s dementia risk , with an adjusted hazard ratio of 3.1 ( 95 % confidence interval 1.0–9.5 ) in subjects having a cerebrospinal fluid content above the median level , compared with those with lower concentration . The hazard ratio of Alzheimer ’s dementia showed little departure from unity for all other inorganic and organic selenium species . These associations were similar in analyses that measured exposure on a continuous scale , and also after excluding individuals who converted to Alzheimer ’s dementia at the beginning of the follow-up . Conclusions These results indicate that higher amounts of a potentially toxic inorganic selenium form in cerebrospinal fluid may predict conversion from mild cognitive impairment to Alzheimer ’s dementia


Title 5:
Serum copper, zinc and selenium levels in Tunisian patients with Parkinson's disease.
Abstract 5:
BACKGROUND Parkinson 's disease ( PD ) is a progressive neurodegenerative disorder . The etiology of this disease is still not fully clear , but free radicals have been proposed to cause neuronal injury . Metals play a key role in the intracellular oxidative balance . However their implication in the degeneration process remains unknown . AIM To assess Cu , Zn and Se concentrations in serum of a group of PD patients in order to determinate , in comparison with age-matched controls , whether alteration in their levels could be involved in PD . METHODS A serum level of 3 trace elements ( Cu , Zn and Se )  was investigated in 48 patients with PD and 36 matched controls using plasma atomic absorption spectrometry .  We compared these parameters in PD patients with controls , and we also compared the variations within the PD group according to age , illness duration , stage of the disease and levodopa intake . RESULTS Patients with PD had significantly lower Cu levels compared to controls . The mean Zn and Se levels in PD patients did not differ significantly from those of controls . Levodopa therapy , age , stage , and illness duration did not significantly influence the measured parameters . CONCLUSION These results suggest that a disturbance of the plasmatic rate of Cu could be a marker of PD or at least , a risk factor for the development of this disease . Although zinc participates to the reduction of oxidative stress and the antioxidant role of the selenium , their implication in the onset of PD is not clearly established . Perspectives for the future could include antioxidant therapy . For this reason , other prospect i ve studies should be conducted on this subject to eluci date the implication of trace elements in PD


Title 6:
Coenzyme Q10 deficiency in patients with Parkinson's disease
Abstract 6:
UNLABELLED Reactive oxygen species ( ROS ) are well known to contribute to the pathophysiology of Parkinson 's disease ( PD ) . Clinical trials of antioxidants are currently underway in PD patients , however , antioxidant research has been hindered by a lack of peripheral biomarkers . METHODS Twenty-two patients with PD elected to have a novel antioxidant assessment ( Functional Intracellular Assay ( FIA ) , SpectraCell Lab , Houston , TX ) performed between 2004 and 2008 . Each PD case was compared to four age- and gender-matched controls ( n=88 ) in four separate , r and om iterations using laboratory data su bmi tted during the same time period . Logistic regression was used to determine the odds of functional deficiency in antioxidant nutrients ( i.e. , glutathione , coenzyme Q10 , selenium , vitamin E and alpha-lipoic acid ) by case-control status . The proportion of cases with functional deficiency was also compared to that for controls by chi(2 ) test . RESULTS Compared to cases , PD patients had a significantly greater odds of deficiency in coenzyme Q10 status ( OR : 4.7 - 5.4 ; 95 % CI : 1.5 - 17.7 ; P=0.003 - 0.009 ) based on FIA results , but not of vitamin E , selenium , lipoic acid , or glutathione ( all P>0.05 ) . The proportion of cases with coenzyme Q10 deficiency was also significantly greater in cases than in controls ( 32 - 36 % vs. 8 - 9 % ; P=0.0012 - 0.006 ) . CONCLUSIONS Deficiency of coenzyme Q10 assessed via FIA should be explored as a potential peripheral biomarker of antioxidant status in PD


Title 7:
Effect of Zinc Supplementation on Antioxidant Activity in Young Wrestlers
Abstract 7:
This study aims to examine the effect of zinc supplementation on free-radical formation and antioxidant system in individuals who are actively engaged in wrestling as a sport . The study registered a total of 40 male subjects , of whom 20 were wrestlers and 20 were sedentary individuals . The subjects were equally allocated to four groups : group 1 , zinc-supplemented sportsmen group ; group 2 , sportsmen group without supplementation ; group 3 , zinc-supplemented sedentary group ; group 4 , sedentary group without supplementation . Blood sample s were collected from all subjects twice , once at the beginning of the study and once again at the end of 8-week procedures . The blood sample s collected were analyzed to determine the levels of malondialdehyde ( MDA ) , serum glutathione ( GSH ) , serum glutathione peroxidase ( GPx ) activity , serum superoxide dismutase ( SOD ) activity ( ELISA colorimetric method ) and zinc ( colorimetric method ) . No difference was found between MDA levels of the study groups in the beginning of the study . The highest MDA value at the end of the study was obtained in group 4 ( p < 0.01 ) . MDA levels in group 2 were established to be significantly higher than those in groups 1 and 3 ( p < 0.01 ) . GSH level , GPx , and SOD activities and zinc level measured in the beginning of the study were not different between groups . Measurements performed at the end of the study showed that groups 1 and 3 ( zinc-supplemented groups ) had the highest GSH level , GPx , and SOD activities and zinc level ( p < 0.01 ) . These parameters were not different in the groups without supplementation ( groups 2 and 4 ) . Results obtained at the end of the study indicate that zinc supplementation prevents production of free radicals by activating the antioxidant system . In conclusion , physiologic doses of zinc supplementation to athletes may beneficially contribute to their health and performance


Title 8:
Plasma selenium is positively related to performance in neurological tasks assessing coordination and motor speed.
Abstract 8:
Parkinson 's disease ( PD ) is a degenerative process affecting the striato nigral system ( SN ) . Its etiology , although obscure , may involve oxidative damage . Selenium , an antioxidant , was shown to protect the SN in animal models . In the current study , we investigate the association between plasma selenium concentrations and the presence of " soft " neurological signs related to the SN .  Plasma selenium concentration was assessed in participants of age ≥65 years in the InCHIANTI study , a population -based cohort study in Tuscany , Italy . PD was defined based on st and ard criteria . " Soft " neurological signs were ascertained by physical examination . A total of 1,012 participants were included . No association was found between the presence of PD and plasma selenium . There was , however , a strong association between plasma selenium and timed performance-based assessment s. Lower levels of selenium were significantly associated withdecreased performance in neurological tests of coordination among older adults . Prospect i ve studies are needed to further investigate the effects of selenium on SN dysfunction
A longer duration of the disease tends to be associated with overall lower trace element levels in either CSF or blood .
Conclusions : Due to the study findings and the greater relevance of the CSF compartment compared with the circulating peripheral ones , this meta- analysis suggests that overexposure in the central nervous system to selenium , and possibly to copper and iron , may be a risk factor of the disease , while zinc might have a protective effect