Identification of candidate cerebrospinal fluid biomarkers in parkinsonism using quantitative proteomics.

INTRODUCTION: Neurodegenerative parkinsonian syndromes have significant clinical and pathological overlap, making early diagnosis difficult. Cerebrospinal fluid (CSF) biomarkers may aid the differentiation of these disorders, but other than α-synuclein and neurofilament light chain protein, which have limited diagnostic power, specific protein biomarkers remain elusive. OBJECTIVES: To study disease mechanisms and identify possible CSF diagnostic biomarkers through discovery proteomics, which discriminate parkinsonian syndromes from healthy controls. METHODS: CSF was collected consecutively from 134 participants; Parkinson's disease (n = 26), atypical parkinsonian syndromes (n = 78, including progressive supranuclear palsy (n = 36), multiple system atrophy (n = 28), corticobasal syndrome (n = 14)), and elderly healthy controls (n = 30). Participants were divided into a discovery and a validation set for analysis. The samples were subjected to tryptic digestion, followed by liquid chromatography-mass spectrometry analysis for identification and relative quantification by isobaric labelling. Candidate protein biomarkers were identified based on the relative abundances of the identified tryptic peptides. Their predictive performance was evaluated by analysis of the validation set. RESULTS: 79 tryptic peptides, derived from 26 proteins were found to differ significantly between atypical parkinsonism patients and controls. They included acute phase/inflammatory markers and neuronal/synaptic markers, which were respectively increased or decreased in atypical parkinsonism, while their levels in PD subjects were intermediate between controls and atypical parkinsonism. CONCLUSION: Using an unbiased proteomic approach, proteins were identified that were able to differentiate atypical parkinsonian syndrome patients from healthy controls. Our study indicates that markers that may reflect neuronal function and/or plasticity, such as the amyloid precursor protein, and inflammatory markers may hold future promise as candidate biomarkers in parkinsonism.

Understanding clusters of risk factors across different environmental and social contexts for the prediction of injuries among Canadian youth.

BACKGROUND: Among Canadian youth, injury is the most common reason for presentation to the emergency department. Youth who commonly engage in multiple risk-taking behaviours are at greater risk for injury, but is it unknown if this phenomenon is more pronounced in different contexts. We aimed to study relationships between risk-taking behaviours and injury, and variations in such relationships between different environmental and social contexts, among youth in Canada. METHODS: Risk-taking behaviour and injury outcome data were collected from grade 9 to 10 students using the 2009-2010 (Cycle 6) of the Health Behaviour in School-Aged Children Survey (n=10,429). Principal components analysis was used to identify clusters of risk-taking behaviours. Within each identified cluster, the degree of risk-taking was categorized into quartiles from lowest to highest engagement in the behaviours. Risk ratios with 95% confidence intervals were calculated to determine the association between the risk of any injury and the degree of risk-taking behaviour specific to the cluster. Clusters were then examined across home, school, neighbourhood and sport contexts. RESULTS: Four clusters of risk-taking behaviour were identified which were labelled as "gateway substance use", "hard drugs and weapons", "overt risk-taking", and "physical activity". Each cluster was related to injury occurrence in a graded fashion. Clusters of risk behaviour were most strongly associated with injuries sustained in neighbourhood settings, and expectedly, increasing physical activity behaviours were associated with increased risk of sport injuries and injuries occurring at school. CONCLUSIONS: This study furthers understanding of clustered risk-taking phenomena that put youth at increasing levels of injury risk. Higher risks for injury and associated gradients were observed in less structured contexts such as neighbourhoods. In contrast, clustered physical activity behaviours were most related to school injury or sport injury and were more likely to be sustained in a supervised context. Understanding the clustered and cumulative nature of risk-behaviours, and how these vary by environmental and social context, helps to explain potential mechanisms of injury as well as modifiable factors that may be important avenues for intervention.

Developing injury indicators for First Nations and Inuit children and youth in Canada: a modified Delphi approach.

INTRODUCTION: The purpose of this research was to take the initial step in developing valid indicators that reflect the injury issues facing First Nations and Inuit children and youth in Canada. METHODS: Using a modified-Delphi process, relevant expert and community stakeholders rated each indicator on its perceived usefulness and ability to prompt action to reduce injury among children and youth in indigenous communities. The Delphi process included 5 phases and resulted in a refined set of 27 indicators. RESULTS: Indicators related to motorized vehicle collisions, mortality and hospitalization rates were rated the most useful and most likely to prompt action. These were followed by indicators for community injury prevention training and response systems, violent and inflicted injury, burns and falls, and suicide. CONCLUSION: The results suggest that a broad-based modified-Delphi process is a practical and appropriate method, within the OCAP™ (Ownership, Control, Access and Possession) principles, for developing a proposed set of indicators for injury prevention activity focused on First Nations and Inuit children and youth. Following additional work to validate and populate the indicators, it is anticipated that communities will utilize them to monitor injury and prompt decisions and action to reduce injuries among children and youth.

TITRE: Élaboration d'indicateurs de blessures chez les enfants et les jeunes des Premières nations et inuits au Canada grâce à une méthode de Delphes modifiée. INTRODUCTION: Le but de cette recherche était de franchir la première étape de l'élaboration d'indicateurs valides et représentatifs des blessures chez les enfants et les jeunes des Premières nations et Inuits du Canada. MÉTHODOLOGIE: À l'aide d'une méthode de Delphes modifiée, des intervenants des collectivités et des experts ont évalué chaque indicateur en fonction de son utilité perçue et de sa capacité à inciter à l'action dans le but de réduire les blessures chez les enfants et les jeunes des collectivités autochtones. Le processus s'est déroulé en 5 étapes et a permis d'obtenir un ensemble de 27 indicateurs. RÉSULTATS: Les indicateurs évalués comme étant les plus utiles et les plus susceptibles d'inciter à l'action ont été ceux liés au taux de collision de véhicules à moteur, au taux de mortalité et au taux d'hospitalisation. Ont été sélectionnés ensuite les indicateurs de la formation en prévention des blessures et programmes communautaires d'intervention, ceux des blessures intentionnelles, ceux des brûlures et des chutes et enfin ceux du suicide. CONCLUSION: Les résultats indiquent qu'utiliser une méthode de Delphes modifiée avec participation élargie est efficace et pertinent pour élaborer un ensemble d'indicateurs visant à guider les activités de prévention des blessures chez les enfants et les jeunes des Premières nations et Inuits, tout en respectant les principes PCAP™ (propriété, contrôle, accès et possession). Une fois achevés les travaux complémentaires de validation des indicateurs et la collecte des données associées, ces indicateurs vont pouvoir servir aux collectivités pour la surveillance des blessures et pour la prise de décisions et de mesures efficaces de réduction des blessures chez les enfants et les jeunes.

Do light truck vehicles (LTV) impose greater risk of pedestrian injury than passenger cars? A meta-analysis and systematic review.

OBJECTIVE: Pedestrian crashes present a growing challenge for public health trauma and road safety researchers around the world. They are associated with substantial morbidity, mortality, and cost, yet there is an international lack of published work on the topic, especially when compared with vehicle occupant safety studies. Our review attempts to quantify the risk of fatal injury among vulnerable road users. The specific objective of this systematic review and meta-analysis is to quantify and compare the impact of light truck vehicles (LTVs) versus conventional cars on pedestrian fatal injury. METHODS: A protocol was developed using methods of the Cochrane Collaboration. We conducted a search for the studies in bibliographic databases that included ATI (Australian Transport Index); Cochrane Injuries Group Specialized Register; EMBASE; ERIC; MEDLINE; National Research Register; PsycINFO; Road Res (ARRB); SIGLE; Science (and Social Science) Citation Index; TRANSPORT (NTIS, TRIS, TRANSDOC, IRRD). Web sites of traffic and road accident research bodies, government agencies, and injury prevention organizations were searched for grey literature. Reference lists from selected papers or topic reviews were scanned for potentially relevant papers. RESULTS: Our initial search identified 878 potentially eligible studies. After thorough review by three of the researchers a total of 12 studies were included in the systematic review, 11 of which were included in the meta-analysis. The overall pooled odds ratio for the risk of fatal injury in pedestrian collisions with LTVs compared to conventional cars was odds ratio 1.54, 95 percent confidence interval 1.15-1.93, p = 0.001. Thus, the risk for pedestrians of sustaining fatal injury is 50 percent greater in collisions with LTVs than in collisions with conventional cars. CONCLUSIONS: Our systematic review and meta-analysis suggests that LTVs pose a greater risk of pedestrian injury death compared to conventional cars. These findings have important implications for the automotive industry and the safety of vulnerable road users.

Effectiveness of cataract surgery in reducing driving-related difficulties: a systematic review and meta-analysis.

OBJECTIVES: To assess the effects of cataract surgery in improving vision and driving performance while reducing driving-related difficulties. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Twelve electronic databases were searched from the date of inception of each database to May 2007. Other sources of potentially relevant information were also identified and examined. REVIEW METHODS: Eligible study designs included randomized controlled trials (RCT), non-RCT, quasi-experimental, case-control, controlled-before-and-after, and cohort studies that examined driving-related indicators in patients undergoing cataract surgery. MAIN OUTCOME MEASURES: The outcome measures included any type of driving-related indicator. A secondary outcome measure was motor vehicle (MV) crash involvement. RESULTS: Seven studies were included in the review and five in the meta-analysis. The overall pooled odds ratio (OR) was 0.12 (95% CI 0.10 to 0.16). Results suggest that the risk of driving-related difficulties was reduced by 88% following cataract surgery. CONCLUSIONS: Cataract surgery is associated with an 88% reduction in the risk of driving-related difficulties. This supports the efficacy of cataract surgery to improve driving in older people, as well as positive implications for a reduction in MV crashes, overall traffic safety, and individual well-being.

Compulsory child restraint seat law and motor vehicle child occupant deaths and injuries in Japan 1994-2005.

The purpose of child restraint seats (CRS) is to reduce the number of individuals killed or injured in motor vehicle (MV) crashes. Japanese Road Traffic Law 17-3-4 (April 2000) specifies a requirement that CRS be used for all children aged 0-5 years. The objective of this evaluation was to determine the legislative impact on fatalities in Japan for the period 1994-2005. Data were obtained from the Institute for Traffic Accident Research and Data Analysis. A time-series Poisson regression model was used to analyse the change (6 years pre/post) in incidence rate ratios of fatality and injury in MV crashes among children ages 0-5 years. Despite increases in CRS use, fatalities failed to decrease significantly after enactment of the law (incidence rate ratio: 0.80; 95% CI: 0.49-1.31). In 2005, 67% of children aged 0-5 years, who were killed as MV occupants were not seated in CRS. Between 2000 and 2005, the lack of CRS led to 43% of front seat passenger deaths, 54% of rear seat deaths, 143 children died in total and 500 + children were seriously injured. It was found that the compulsory CRS law enacted in April 2000 did not result in a statistically significant reduction in child MV occupant fatalities and injuries in Japan.

Impact of lowering the legal blood alcohol concentration limit to 0.03 on male, female and teenage drivers involved alcohol-related crashes in Japan.

In June of 2002, a revision to part of the Road Traffic Act drastically increased the penalties for drinking and driving offences in Japan. Most notably, the legal blood alcohol concentration (BAC) limit for driving was lowered from 0.05 mg/ml to 0.03 mg/ml. The rationale for the new lower BAC limit was predicated on the assumption that drinking drivers will comply with the new, lower limit by reducing the amount of alcohol they consume prior to driving, thereby lowering their risk of crash involvement. This, in turn, would lead to fewer alcohol-related crashes. A key limitation of previous lower BAC evaluation research in determining the effectiveness of lower legal BAC limit policies is the assumption of population homogeneity in responding to the laws. The present analysis is unique in this perspective and focuses on the evaluation of the impact of BAC limit reduction on different segments of the population. The chief objective of this research is to quantify the extent to which lowering the legal limit of BAC has reduced male, female and teenager involvement in motor vehicle crashes in Japan since 2002. Most notably, the introduction of reduced BAC limit legislation resulted in a statistically significant decrease in the number of alcohol-impaired drivers on the road in Japan, indicating responsiveness to the legal change among adults and teenagers. In addition, this preliminary assessment appears to indicate that the implementation of 0.03 BAC laws and other associated activities are associated with statistically significant reductions in alcohol-involved motor vehicle crashes. In comparison, the rates of total crashes showed no statistically significant decline nor increase in the period following the introduction of the BAC law, indicating that the lower BAC limit only had an effect on alcohol-related crashes in Japan. The evidence suggests that the lower BAC legal limit and perceived risk of detection are the two most important factors resulting in a sustained change in drinking and driving behaviour in Japan. It is recommended that future research and resources in other countries be focused on these factors as determinants to reduced alcohol-related crashes.

Severity of alcohol-related motor vehicle crashes in British Columbia: case - control study.

The objective of the present study was to compare the injury severity and vehicle damage severity rates of alcohol-related crashes with rates of non-alcohol-related crashes in British Columbia (BC). Injury severity rates and vehicle damage severity rates were taken from 2002 Insurance Corporation of British Columbia traffic collision data. The data were computed in order to compare the differences in injury severity and vehicle damage severity rates of alcohol-related vs. non-alcohol-related motor vehicle crashes. Case - control methods were used in this study to analyse the risk of alcohol-related crashes compared to non-alcohol-related crashes in BC. Odds ratios (OR) and 95% CI were calculated to estimate relative risks. In the case - control analysis, the risk of fatal collision was increased for those drinking and driving compared with those driving sober (OR 4.70; 95% CI 3.15 - 7.01). Risk of injury collision was increased for those drinking and driving compared with those driving sober (OR 1.32; 95% CI 1.19 - 1.37). Importantly, the risk of vehicle damage severity was increased for those drinking and driving compared with those driving sober (write-off vehicle OR 4.24; 95% CI 3.70 - 4.86, severely damaged vehicles OR 1.98; 95% CI 1.77 - 2.21). The study reinforces existing literature to suggest that current evidence is sufficient to show an increased risk of injury and fatality to drivers and occupants in alcohol-related crashes. This paper not only emphasizes this well-known relationship, but also such consequences as increased vehicle damage severity. The connection between drinking and severity of motor vehicle crashes is popularly believed and has now received substantial scientific support. There is strong justification for injury prevention experts and policy-makers to step up motor vehicle crash injury prevention advocacy by implementing evidence-based policies to reduce rates of alcohol-impaired driving in the province of BC. Most unintentional injuries in BC are related to motor vehicle crashes. Significant improvements can be made in these statistics by: increasing the use of occupant protection (safety belt and child restraint seats); reducing alcohol-related injuries through multiple strategies including corrections in the physical environment, extensive enforcement of drinking and driving laws and health promotion/education.

Pregnancy outcome for nomadic Turkana pastoralists of Kenya.

The outcome of an individual pregnancy is a key component of overall reproductive success and is strongly influenced by environmental, behavioral, and biological variation within populations. This prospective study examined the outcomes of 68 pregnancies among nomadic Turkana of Kenya from July 1993 to July 1994. A total of 12 women experienced pregnancy losses, and 3 women experienced live births with a subsequent perinatal death. The following characteristics are associated with increased risk for experiencing a fetal or perinatal death: severe morbidity episodes, shorter nonpregnant intervals, lower third-trimester weight, higher third-trimester summed skinfolds but limited third-trimester reduction in summed skinfolds, and higher activity levels late in gestation. Turkana newborns measured within 48 hr of birth (n = 19) weighed an average of 2,860 +/- 640 g and had a mean ponderal index of 2.72 +/- 0.46. Variation in birth weight was predicted by preterm delivery, delivery during the wet season, and maternal morbidity levels. Birth length averaged 50.8 +/- 6.8 cm and was positively influenced by full term delivery, better maternal health, and birth during the dry season. These results suggest complicated pathways linking the physical environment, subsistence requirements, heterogeneity in maternal fitness, behavior, and pregnancy outcome. The results augment the larger picture of reproductive success for Turkana nomads who live in a highly variable savanna environment.

The nutritional consequences of pregnancy sickness : A critique of a hypothesis.

The purpose of this paper is to assess Profet's (1992) and others' hypothesis that nausea and vomiting in pregnancy (NVP) is adaptive. A number of studies have found an association between NVP and a decreased risk for early fetal loss (<20 weeks). It is assumed that the adaptive benefits of improved survivorship associated with NVP outweigh the minimal nutritional consequences. However, in populations that experience marginal levels of nutrition, NVP may have important nutritional consequences. To test these potential consequences, a study on NVP, nutritional status, and pregnancy outcome was conducted among Turkana pastoralists, who experience seasonal and chronic nutritional stress. Interviews and anthropometric assessments were conducted on 68 pregnant Turkana women of Kenya during a 1993-1994 field season. The results from the case study suggest that women who experience NVP do encounter nutritional consequences in the later stages of pregnancy and are more likely to experience poor pregnancy outcomes. These results suggest that NVP may not be adaptive in all environmental settings, particularly among marginally nourished populations.

Characterization of anti-hepatitis C virus-positive sera not genotyped by restriction fragment length polymorphism or serology.

BACKGROUND: The hepatitis C virus genome is extremely heterogeneous and has been classified into six major genotypes. Genotyping of hepatitis C has been achieved through both direct molecular approach and indirect detection of host genotype-specific antibodies by serological methods. The purpose of this study was to characterize anti-hepatitis C positive sera samples that were not genotyped either by restriction fragment length polymorphism or by serology. METHODS: Two hundred and two patients from northern California with established chronic hepatitis C virus infection were studied by restriction fragment length polymorphism analysis of the 5'-untranslated region amplicon. A serological genotyping assay, based on synthetic peptides derived from non-structural region 4 of the hepatitis C virus genome, was used to determine serological genotype. RESULTS: Of the 202 patients studied, 187 (93%) were polymerase chain reaction-positive. One hundred and eighty-six patients were able to be genotyped by restriction fragment length polymorphism, compared with 144/202 (71%) of patients genotyped by serology (P < 0.0001). Only two of 202 samples showed discordant genotyping results. The distribution of hepatitis C virus genotypes in northern California was found to be type 1a, 41%; 1b, 35%; 2a, 3%; 2b, 10%; 3a, 11%; and 4, < 1%. There was no association between hepatitis C genotypes and age, gender distribution, ethnic origin, presumptive mode of transmission, serum alanine aminotransferase levels and the proportion of patients with cirrhosis. Of the 15 patients who were not genotypable by the molecular assay, four patients were genotyped by serology, with hepatitis C virus genotypes 1, 2 and 3 represented. Of the 58 samples that were not genotyped by serology, 47 were genotyped based on the molecular assay, and the distribution of hepatitis C virus genotypes was similar to that of the overall study population. CONCLUSIONS: These data showed that: (i) molecular genotyping assay based on 5'-untranslated region is more sensitive than serologic genotyping based on the non-structural-4 region but the results were highly concordant; (ii) hepatitis C virus genotypes 1-4 are present in northern California, with genotype 1 being the most prevalent; and (iii) the failure to determine hepatitis C virus genotype based on molecular or serological genotyping assay does not appear to be related to specific hepatitis C genotypes.

An alternative method for assessing early mortality in contemporary populations.

Biological anthropologists are interested in a population's early mortality rates for a variety of reasons. Early mortality (infant or juvenile) is of obvious importance to those interested in demography, but early mortality statistics are useful for life history analysis, paleodemography, and human adaptability studies, among others. In general, the form of mortality statistics is derived from demography, where chronological age is the gold standard for statistical calculation and comparison. However, there are numerous problems associated with the collection, analysis, and interpretation of early mortality statistics based on age, particularly for anthropological research, which is often conducted in small or non-calendrical-age numerate populations. The infant mortality rate (IMR), for example, is notoriously difficult to determine in populations where accurate accounting of age is not routine, and yet it is widely used in demography, public health, medicine, and social science research. Here we offer an alternative to age-based early mortality statistics that makes use of human biologists' interest in, and skill at, assessing human growth and development. Our proposal is to use developmental stages of juveniles instead of relying exclusively on age as the basis for mortality statistics. Death or survival according to a developmental stage (such as crawling or weaning) may provide more accurate data that are also more closely related to the cause of death. Developmental stages have the added advantage of putting infants and children back at the center of the discussion of early mortality by focusing on their activities in relation to their environment. A case study from the Turkana population of Kenya illustrates the use of developmental stages in describing early mortality.

Hemochromatosis and male infertility.

BACKGROUND: The clinical association of hemochromatosis and infertility is rare. Hemochromatosis may affect fertility through a variety of mechanisms. CASE: A 44-year-old man and his 36-year-old wife presented with primary infertility of 7 years' duration. The husband was diagnosed as having idiopathic hemochromatosis, abnormal glucose tolerance, and hypogonadism accompanied by impotence, retrograde ejaculation, and azoospermia. Treatment consisted of phlebotomies followed by gonadotropins, which corrected retrograde ejaculation and improved semen characteristics. Concomitant pelvic factors in the woman were corrected endoscopically. After failure of pregnancy with ovulation stimulation and intrauterine inseminations, a singleton pregnancy was achieved by in vitro fertilization, augmented with intracytoplasmic sperm injection. CONCLUSION: This case underscores the need to consider advanced reproductive technologies after the failure of specific, first-line therapeutic options in infertile couples.